Input: Claim: Owls can see in complete darkness due to their magical abilities. [SEP] Text: self breathing after breathing support in ICU study is a single centre, parallel group, randomised controlled trial with economic scoping, nested exploratory physiology study and nested qualitative study. The study protocol has been developed by the CI, associated research team and patient advisory group with extensive peer review from the funding body. The study aims to find out if it is possible to complete a large study to see whether using a cough device in ICU can help remove breathing support in ICU patients. There are 2 stages to the study:1. Feasibility intervention trial2. Semi structured interviewsRandomisation: Following informed consent/advice for study participation, participants will be randomized into a study arm to either A-control arm (standard care) or B-intervention arm (cough device plus standard care). Randomisation will occur using an online system called ‘Sealed envelopes’. Baseline data collection: Pre-designed data collection forms will be used during the course of the study. Baseline demographic data recoded for all participants includes age, gender, predicted body weight, history of chronic lung disease, smoking history, reason for intubation, date of hospital and ICU admission, date of intubation, score, baseline ventilator settings and airway type and size. Trial treatments:A-(standard care)- Patients will receive standard care including ventilation, weaning, standard physiotherapy techniques such as positioning, manual techniques, manual/ventilator hyperinflation, suctioning, and nebulisers. Respiratory physiotherapy treatments will vary across patients as treatments will be delivered at the discretion of the treating physiotherapist based on individual assessment and not be protocolised. Decisions to remove breathing support (extubate) and re-intubate will be made by the attending physician with reason(s) documented. Clinical data collection will occur during physiotherapy intervention sessions in the 24hours preceding extubation and up to 48 hours post extubation. B-(Cough device plus standard care). The cough device (MI-E) works by blowing air into the patients lungs followed by quickly sucking it out. This device can be used before and after extubation. The device is reusable between patients with single patient use circuits, filters and interface (mouthpiece, facemask and flexible catheter mount).

Output: pass


Input: Claim: Stem cell research holds potential for regenerating damaged tissues and organs. [SEP] Text: Anyway, recent findings investigate the safety and tolerability of SBSC in dental implantation for patients with severe bone defects. Nine patients received different doses of SB cells, and evaluations were conducted through computed tomography (CT) scans and comprehensive chemistry panel testing. The trial, spanning six months, revealed no severe adverse effects, with observed improvements in bone mineral density (BMD) and stress levels. Elevations in specific cytokines and chemokines indicated SBSC-triggered responses for local tissue repair [46]. The findings support the well-tolerated use of SB cells in dental implantation, suggesting their potential for accelerating osseointegration in high-risk patients. Coordinating embryonic, hematopoietic, and mesenchymal markers, along with the presence of various stem cell-related factors, accentuates the intriguing nature of SBSCs, warranting further investigation in the realm of stem cell research. Markers and methodologies used for isolationAnalyzing the surface markers of the five considered stem cell populations and isolation methods, SSEA-3 emerges as a key marker extensively used in the isolation process. SSEA-3 plays a pivotal role in identifying and purifying these stem cell populations [16]. The chemokine receptor CXCR4 has been identified as a relevant marker associated with VSELs. CXCR4, also known as C-X-C chemokine receptor type 4, plays a role in the migration and homing of stem cells. CXCR4 is expressed on the surface of VSELs, and its interaction with its ligand, SDF-1 (stromal cell-derived factor 1), is considered crucial for the mobilization and homing of VSELs in various tissues [32]. This interaction is implicated in the trafficking of VSELs to areas of tissue damage or injury, where they may contribute to regenerative processes. The presence of CXCR4 on VSELs is a notable characteristic and contributes to the understanding of the homing and migration mechanisms that these stem cells employ. CD133, also known as prominin-1, is a surface marker associated with VSELs. CD133 is a glycoprotein and is often utilized as one of the distinctive markers for isolating and characterizing VSELs. In addition to SSEA-3 and CXCR, several other markers have been mentioned for isolating specific populations of stem cells.

Output: corroborate


Input: Claim: Gene drives are still in the experimental stage, with concerns about their ecological impact if released into the wild. [SEP] Text: Cas9-A and Cas9-B are orthogonal in that they do not recognize one another's guide RNAs. (C) When organisms bearing and B are crossed, offspring inherit one copy of each. Both drives are copied as normal. In addition, Cas9-A (from Drive A) uses guide RNAs A-F (from Drive B) to cut a gene essential for female fertility, while Cas9-B (from Drive B) does the same using guide RNAs-B-F (from Drive A) to cut a different gene. and B have internal homology appropriate to be copied into these cut fertility genes, disrupting them and causing infertility in females. If all repairs are conducted via homologous recombination, there are now four drives: A, B, AB1, and AB2. In reality, recombination between the non-homologous chromosomes is likely to be less efficient, causing loss of the female fertility genes but not explicit copying of AB1 and/or AB2. The phenotypic effect is identical. Figure 6—figure supplement 2 Download asset Open asset An extreme example of ecological management: the use of suppression and immunizing drives to control rat populations worldwide. Releasing Y-Drive-SD (male-biasing sterile-daughter) rats into invasive rat populations would initiate local eradication while an immunizing drive protectively recoded the native rat populations of Eurasia. Stowaway-mediated gene flow, depicted as a border of Y-Drive-SD framing Eurasia, will result in local population suppression due to the sterile-daughter effect that would remain when the drives interacted, limiting the ability of either population to invade the other. This control process would have to be repeated with new drives once recoded stowaways successfully re-invade the rat-free habitats. Because of the complexity of gene flow patterns in rats, the uncertainty of whether a Y-Drive-SD would be effective, and the possibility for adverse human intervention, controlling rat populations in this way will not be feasible any time within the next decade and possibly not at all, but it provides a useful world-spanning example of a possible drive-based solution aiming to solve a serious global problem. Relying on precision drives to give specific invasive rat populations unique genetic markers (Figure 5C) for subsequent targeting with precision suppression drives or utilizing weaker suppression drive types (Figure 6) may represent more feasible alternatives.

Output: contrast


Input: Claim: Owls can see in complete darkness due to their magical abilities. [SEP] Text: Whilst intubated (breathing machine and breathing tube in place), treatment will include a minimum of two MI-E sessions via the breathing tube prior to the breathing tube being removed. MI-E settings will be individualised to each patient based on current ventilator settings, patient tolerance, chest expansion and secretion clearance. There is a guide in place for clinicians to use. After breathing tube removal (extubation) (and up to 48hrs), patients will receive MI-E delivered via facemask or mouthpiece up to 2 times/day with MI-E settings individualised and set according to patient tolerance, chest wall expansion and secretion clearance (as assessed by treating physiotherapist). For both treatment arms, data collection will take place during the 24 hours prior to extubation and for 48hours following extubation. Data collection will include physiotherapy treatment interventions completed, use of additional respiratory support (tracheostomy, high flow oxygen therapy, non invasive ventilation), lung ultrasound score, pain score, cardiovascular parameters (heart rate and rhythm, systolic and diastolic blood pressure), ventilatory parameters (ventilator settings, lung compliance, airway resistance), respiratory parameters (respiratory rate, peripheral oxygen saturations, end inspiratory and expiratory lung volumes). We will also record resource use during the ICU admission and will include staffing requirements (time duration, grade AfC), consumable use and the cost of obtaining and maintaining the device. Patient related resource use will include suction frequency (over a 24-hour period), antibiotic use, physiotherapy oncall use (planned and unplanned), re-admission and hospital LOS. A quality of life measure (EQ-5D-5L) questionnaire will be collected retrospectively at recruitment for pre-admission and at six months post ICU discharge. Patients from the intervention (cough device) arm of the study will be eligible for inclusion into the smaller physiology study which involves some additional data collection using Tomography (EIT). EIT is a noninvasive, radiation free technique used at the bedside to provide information about lung volumes. The technique is used clinically and in ICU research studies. We will use this technique to establish what happens to lung volumes as the positive and negative pressure breaths are delivered by the cough device. We plan to recruit 5-10 participants for additional data collection.

Output: pass


Input: Claim: Stem cell research holds potential for regenerating damaged tissues and organs. [SEP] Text: DiscussionThe analysis of the five stem cell populations highlights several common features that are of particular interest in the context of regenerative medicine. Firstly, Multilineage-differentiating (MUSE) cells, Embryonic-Like (VSEL) Cells, (SBSC), Inducible (MIAMI) Cells, and (MAPC) share the presence of pluripotent embryonic markers and the ability to differentiate into a wide range of cell types, spanning the three germ layers. The notable similarity in differentiative potential suggests a possible common origin, even if contrasting data are present in literature on this subject. MUSE cells are the most extensively studied cell types among the five above reported stem cells and hold promise for regenerative medicine. These well-characterized cells exhibit extraordinary potential for repairing damaged tissues. Similarly, VSELs have also been the focus of intense research and possess equally intriguing characteristics. Both cell types share several key features: MUSE cells and VSELs express the SSEA-3 antigen [63, 64], which plays a role in cellular functions and differentiation; both cell types can migrate to damaged tissues, contributing to tissue repair; these cells demonstrate remarkable resilience to environmental stressors and adverse conditions. However, there are some notable differences between them. MUSE cells are mainly derived from mesenchymal tissues, while VSELs are believed to be derived from primordial germ cells or other embryonic precursors [65]. VSELs are exceptionally small, with diameters ranging from 3 to 5 µm, whereas MUSE cells are reported to be larger. The extremely small size reported for VSEL, ranging from 3 to 5 µm, raises questions and triggers skepticism within the scientific community [37]. Cells of such diminutive dimensions are seldom encountered, and the presence of cells this small within the context of VSELs has been a subject of debate. The rarity of cells with such minuscule sizes in the cellular landscape introduces a level of skepticism regarding their actual existence and biological potential. Concerns have been voiced within the scientific community regarding the possibility that measurements of VSEL sizes may be influenced by various analytical techniques, emphasizing the need for further characterization of phenotype and isolation methodologies to more conclusively establish the true nature and size of these particular cells. Despite these differences, both MUSE and VSEL cells offer exciting avenues for regenerative therapies, and ongoing research aims to harness their potential for treating various diseases and injuries.

Output: corroborate


Input: Claim: Gene drives can fully eliminate any pest species within one generation. [SEP] Text: Skip to Content eLife home page your research Search by keyword or author Reset form my search to Feature 10. 7554/eLife. 03401 Open access Copyright information annotations (there are currently 0 annotations on this page). Share 46,927 views 7,310 downloads 634 3401. Copy to clipboard Download BibTeX Download. RIS 10. 7554/eLife. 03401. 001 numerous advances, the field of molecular biology has often struggled to address key biological problems affecting public health and the environment. Until recently, editing the genomes of even model organisms has been difficult. Moreover, altered traits typically reduce evolutionary fitness and are consequently eliminated by natural selection. This restriction has profoundly limited our ability to alter ecosystems through molecular biology. If we could develop a general method of ensuring that engineered traits would instead be favored by natural selection, then those traits could spread to most members of wild populations over many generations. This capability would allow us to address several major world problems, including the spread of insect-borne diseases, the rise of pesticide and herbicide resistance, and the agricultural and environmental damage wrought by invasive species. Scientists have long known of naturally occurring selfish genetic elements that can increase the odds that they will be inherited. This advantage allows them to spread through populations even if they reduce the fitness of individual organisms. Many researchers have suggested that these elements might serve as the basis for ‘gene drives’ capable of spreading engineered traits through wild populations (Craig et al. , 1960; Wood et al. , 1977; Sinkins and Gould, 2006; Burt and Trivers, 2009; Alphey, 2014). was the first to propose gene drives based on site-specific ‘homing’ endonuclease genes over a decade ago (Burt, 2003). These genes bias inheritance by cutting the homologous chromosome, inducing the cell to copy them when it repairs the break. Several efforts have focused on the possibility of using gene drives targeting mosquitoes to block malaria transmission (Scott et al. , 2002; Windbichler et al. , 2007, 2008, 2011; Li et al. , 2013a; Galizi et al. , 2014). However, development has been hindered by the difficulty of engineering homing endonucleases to cut new target sequences (Chan et al. , 2013a; Thyme et al. , 2013; Takeuchi et al. , 2014).

Output: contrast


Input: Claim: Owls can see in complete darkness due to their magical abilities. [SEP] Text: Consent processes are as per the main trial protocol. Qualitative interviews: Interviews with some patients/clinicians involved in the study will seek experiences of using the cough device. Eligible clinicians will need to be either a doctor, physiotherapist or nurse by profession, be working as a permanent staff member at the study site and have participated in the study within the last 4 weeks. Patients/personal consultees are eligible for study inclusion if they have been approached for informed consent/advice. Patients will be excluded if they are non-English speaking or have impaired understanding, or if they have no recall of their ICU stay or MI-E use. All interviews will be completed virtually via an online platform (Microsoft Teams) or telephone (interviewee preference) and digitally recorded (via an encrypted Dictaphone). Patients and consultees recruited into the study will be approached for consent into this phase once the patient has been discharged from ICU but remains in hospital. Interviews will take place within 4-6 weeks of ICU discharge-this may therefore be whilst the patient is still in hospital or at home. Participants will have received a copy of the consent form with the study information. The lead interviewer will run through this at the start of the interview and the participant will be asked to provide verbal (recorded) consent for each point on the consent form. Intervention type outcome measure Feasibility outcomes measured at the end of the study:1. Proportion of eligible patients approached, consented and randomised measured using screening log and randomization records2. Proportion of MI-E treatment sessions completed measured using case report form3. Proportion of recruited patients with all outcome measures recorded measured using case report form4. Attrition (participant withdrawal and loss to follow up) measured using case report form and withdrawal records5. Acceptability of trial processes to participants and clinicians measured using qualitative interviews, acceptability of intervention measure (AIM)/Intervention appropriate measure (IAM)/feasibility of intervention measure (FIM)6. Acceptability of outcome measures to participants and clinicians measured using qualitative interviews Secondary outcome measures 1. Resource use (use of trachy; MI-E equipment, staff grade and time) at end of each treatment intervention and per 24hr period2. Lung ultrasound score pre intervention and 5mins post intervention3.

Output: pass


Input: Claim: Stem cell research holds potential for regenerating damaged tissues and organs. [SEP] Text: In a recent paper by Oguma et al. [66], a comprehensive analysis of the transcriptome of MUSE cells at the single-cell level was conducted, drawing a comparative assessment with the transcriptome of MSCs. The study focused also on evaluating the expression profiles of various markers associated with VSELs within both MUSE cells and MSCs. VSELs, as defined by Shin et al. (2012), are characterized by their positivity for CXCR4, along with the expression of epiblast-related markers (GBX2, FGF5, NODAL) and primordial germ cell-related markers (DPPA3 [Stella], PRDM1 [Blimp1], PRDM14), while being negative for PTPRC (CD45). Intriguingly, neither MUSE nor MSCs expressed these specific marker genes, with the exception of FGF5, which exhibited higher expression levels in MSCs compared to MUSE [66]. VSELs also express additional markers, such as SSEA-4, and share similarities with germ cells, expressing markers like DDX4/VASA and PRDM14. In vitro, these VSELs remain quiescent, except in ascites, and become highly activated after exposure to valproic acid and follicle-stimulating hormone (FSH). VSELs spontaneously form aggregates resembling tumor-like structures or grow into larger cells resembling oocytes. Several studies propose a germinal origin for VSELs, while MUSE cells are found in both stromal tissues like bone marrow and tissues from the umbilical cord. While certain conditions may lead to uncontrolled proliferation of VSELs, resulting in tumor formation, numerous studies have demonstrated the non-tumorigenic nature of MUSE cells [26, 33]. This stark contrast in tumorigenicity further underscores the distinctive characteristics between VSELs and MUSE cells, emphasizing the importance of comprehending their unique molecular profiles and biological behaviors for their potential applications in regenerative medicine. This differential expression pattern provides valuable insights into the distinctive molecular profiles of MUSE cells and VSEL, emphasizing the need for a nuanced understanding of their biological characteristics and potential applications in regenerative medicine. SBSC exhibit considerable overlap in characteristics with VSELs, except for the expression of CD45. This commonality suggests a shared profile related to pluripotency and regenerative potential.

Output: corroborate


Input: Claim: Gene drives can fully eliminate any pest species within one generation. [SEP] Text: Attempts to build gene drives with more easily retargeted zinc-finger nucleases and TALENs suffered from instability due to the repetitive nature of the genes encoding them (Simoni et al. , 2014). The recent discovery and development of the RNA-guided Cas9 nuclease has dramatically enhanced our ability to engineer the genomes of diverse species. Originally isolated from ‘’ acquired immune systems in bacteria, Cas9 is a non-repetitive enzyme that can be directed to cut almost any DNA sequence by simply expressing a ‘guide RNA’ containing that same sequence. In little more than a year following the first demonstrations in human cells, it has enabled gene insertion, deletion, and replacement in many different species (Bassett et al. , 2013; Cho et al. , 2013; Cong et al. , 2013; DiCarlo et al. , 2013; Friedland et al. , 2013; Gratz et al. , 2013; Hu et al. , 2013; Hwang et al. , 2013; Jiang et al. , 2013a, 2013b; Jinek et al. , 2013; Li et al. , 2013b; Mali et al. , 2013c; Tan et al. , 2013; Upadhyay et al. , 2013; Wang et al. , 2013b). Building RNA-guided gene drives based on the Cas9 nuclease is a logical way to overcome the targeting and stability problems hindering gene drive development. Less obvious is the extent to which the unique properties of Cas9 are well-suited to overcoming other molecular and evolutionary challenges inherent to the construction of safe and functional gene drives. We submit that Cas9 is highly likely to enable scientists to construct efficient RNA-guided gene drives not only in mosquitoes, but in many other species. In addition to altering populations of insects to prevent them from spreading disease (Curtis, 1968), this advance would represent an entirely new approach to ecological engineering with many potential applications relevant to human health, agriculture, biodiversity, and ecological science. The first technical descriptions of endonuclease gene drives were provided by in his landmark proposal to engineer wild populations more than a decade ago (Burt, 2003). Any of the rapidly expanding number of laboratories with expertise in Cas9-mediated genome engineering could attempt to build a gene drive by substituting Cas9 for the homing endonucleases described in his proposal.

Output: contrast


Input: Claim: Owls can see in complete darkness due to their magical abilities. [SEP] Text: Pain is measured using the numeric rating scale and/or critical care pain observation tool (CPOT)4. QOL is measured using the EQ-5D-5L at 6 months following ICU discharge5. Re-intubation rate will be calculated at 48hours post extubation6. Mortality will be calculated at 60days post randomisation7. Cardiovascular parameters (heart rate, systolic and diastolic blood pressure) measured at pre intervention, intervention end and 5mins post intervention8. Ventilator/respiratory parameters (lung resistance/compliance, respiratory rate, peripheral oxygen saturations) measured pre intervention, intervention end and post extubation)9. Adverse events (occurrence frequency of increase/decrease >20% baseline; arrhythmia requiring intervention; pneumothorax; acute desaturation to <85% or >10% below baseline; cardiopulmonary arrest; accidental extubation) measured at end of intervention and 5 mins post intervention end Overall study start date 01/09/2020 Overall study end date 31/12/2023 Reason abandoned (if study stopped) inclusion criteria 1. Adult (>=16 years)2. Expected to require invasive mechanical ventilation for >48hrs 3. Clinician identified pre-extubation problems with secretion management defined as poor/weak cough effort (cough peak flow <60L/min) and/or secretion load that are difficult to clear with usual airway clearance management (as assessed by the treating clinical team)4. Identified as ‘ready to wean or weaning’ by the treating clinical team (on a spontaneous mode of ventilation for example (CPAP); Breathing (ASB); Ventilation (PSV); (APRV) (with spontaneous effort). Participant type(s) group age limit 16 number of participants Size: 50; UK Sample Size: 50 Total final enrolment 47 Participant exclusion criteria 1. (PEEP) >102. Fraction of (FiO2) >0. 73. Hemodynamic/Cardiovascular instability (i. e. noradrenaline >0. 25mg/kg, arrhythmias requiring intervention)4. Recent undrained pneumothorax (current admission with no chest drain in situ);5. Unable to continue to use MI-E post extubation (i. e.

Output: pass


Input: Claim: Stem cell research holds potential for regenerating damaged tissues and organs. [SEP] Text: Furthermore, a comparative analysis with MUSE cells reveals intriguing parallels, as both SBSC and MUSE cells express SSEA-3. Interestingly, SBSC isolated from peripheral blood also exhibit CD45 expression, aligning them with MUSE cells in this aspect. However, a notable distinction remains in terms of cell size. These findings contribute to a nuanced understanding of the unique features and potential applications of SB cells, positioning them within the broader landscape of stem cell populations and highlighting both shared and distinct attributes. MAPCs have attracted attention in biomedical research due to their remarkable capacity to differentiate into various cell types derived from the three embryonic germ layers: endoderm, mesoderm, and ectoderm. and MAPC stem cells can be isolated from stromal tissues, but MAPC cells uniquely possess the ability to be isolated from several organs. Recent studies indicate the potential presence of MAPCs in other adult tissues, such as the liver and brain, expanding their possible sources of isolation. Molecular distinctions between MAPC and other stem cells, including the differential expression of pluripotent and surface markers, may reflect the diverse origins and differentiation potentials of these cell populations. Both MUSE and MAPCs have demonstrated the ability to differentiate into a wide range of cell types; however, their effectiveness or differentiation potential may vary in specific experimental contexts or in relation to the preferred cell types. For instance, MAPCs might exhibit a greater predisposition to differentiate into specific cell types compared to MUSE cells, or vice versa, depending on experimental conditions or the cellular environment [58]. Concerning tumorigenicity, MUSE cells have been consistently described as non-tumorigenic in various studies, making them promising for clinical applications without the risk of tumor formation. In contrast, MAPCs may show tumorigenic potential in certain contexts or if not adequately controlled during culture, raising concerns about their therapeutic use. MAPCs have emerged as a subject of controversy within the scientific community, primarily due to challenges associated with their reproducibility. The reliability and consistency of research findings related to MAPCs have been called into question, leading to the retraction of several studies that initially reported on these cells. The inherent difficulty in replicating experimental outcomes with MAPCs has raised concerns about the robustness and validity of the scientific evidence surrounding their properties and potential applications.

Output: corroborate


Input: Claim: Gene drives can fully eliminate any pest species within one generation. [SEP] Text: Indeed, the well-recognized potential for gene drives to combat vector-borne diseases such as malaria and dengue virtually ensures that this strategy will eventually be attempted in mosquitoes. While considerable scholarship has been devoted to the question of how gene drives might be safely utilized in mosquitoes (Scott et al. , 2002; Touré et al. , 2004; Benedict et al. , 2008; Marshall, 2009; UNEP, 2010; Reeves et al. , 2012; David et al. , 2013; Alphey, 2014), few if any studies have examined the potential ecological effects of gene drives in other species. After all, constructing a drive to spread a particular genomic alteration in a given species was simply not feasible with earlier genome editing methods. Disconcertingly, several published gene drive architectures could lead to extinction or other hazardous consequences if applied to sensitive species, demonstrating an urgent need for improved methods of controlling these elements. After consulting with experts in many fields as well as concerned environmental organizations, we are confident that the responsible development of RNA-guided gene drive technology is best served by full transparency and early engagement with the public. Here we provide brief overviews of gene drives and Cas9-mediated genome engineering, detail the mechanistic reasons that RNA-guided gene drives are likely to be effective in many species, and outline probable capabilities and limitations. We further propose novel gene drive architectures that may substantially improve our control over gene drives and their effects, discuss possible applications, and suggest guidelines for the safe development and evaluation of this promising but as yet unrealized technology. A discussion of risk governance and regulation intended specifically for policymakers is published separately (Oye et al. , 2014). Natural gene drives In nature, certain genes ‘drive’ themselves through populations by increasing the odds that they will be inherited (Burt and Trivers, 2009). Examples include endonuclease genes that copy themselves into chromosomes lacking them (Burt and Koufopanou, 2004), segregation distorters that destroy competing chromosomes during meiosis (Lyttle, 1991), transposons that insert copies of themselves elsewhere in the genome (Charlesworth and Langley, 1989), Medea elements that eliminate competing siblings who do not inherit them (Beeman et al. , 1992; Chen et al. , 2007), and heritable microbes such as Wolbachia (Werren, 1997).

Output: contrast


Input: Claim: Owls can see in complete darkness due to their magical abilities. [SEP] Text: contraindications to facemask use-facial/cranial trauma, recent facial surgery; active upper gastrointestinal bleeding/uncontrolled vomiting; recent upper abdominal/thoracic surgery with at risk anastomosis)6. Pre-existing neuromuscular respiratory condition7. Pre-existing routine use of MI-E in the community8. Patients with pre-existing permanent tracheostomy 9. Treatment withdrawal expected within 24hrs or not expected to survive 10. Re-admission to ICU following index admission11. trial participation Recruitment start date 11/07/2022 Recruitment end date 11/07/2023 of recruitment England, Study participating centre 2 8HW Sponsor information and details Research and 2 8AE Kingdom +44 1173420233 R&DSponsorship@UHBW. nhs. uk Sponsor type Hospital/treatment centre Website type name name(s) name for Alternative name(s) for - for (Institute for Health and Care Research), government organisation government and dissemination plan Planned publication in a high-impact peer reviewed journal, alongside presentation of results at key international network meetings/conferences of the of Medicine. Intention to publish date 31/10/2024 Individual participant data (IPD) Intention to share Yes IPD sharing plan The datasets generated during and/or analysed during the current study will be available upon request from (ema. swingwood@uwe. ac. uk). All data will be anonymised for which consent has been gained. Data will only be provided for purposes of research studies. Data will be available once it has been analysed and published by the current research team. IPD sharing plan summary Available on request Study outputs Output type created Date added Peer reviewed? Patient-facing? HRA research summary 28/06/2023 Protocol 2023. 25/07/2023: Publication reference added. 20/07/2023: Total final enrolment and IPD sharing statement added. 19/07/2022: The following changes have been made: 1. The recruitment start date has been changed from 04/07/2022 to 11/07/2022. 2. The recruitment end date has been changed from 07/07/2022 to 11/07/2023. 21/06/2022: The following changes were made to the trial record: 1.

Output: pass


Input: Claim: Stem cell research holds potential for regenerating damaged tissues and organs. [SEP] Text: These uncertainties underscore the importance of rigorous experimental design, standardization of methodologies, and comprehensive validation processes to address the reproducibility issues associated with MAPCs and establish a more reliable foundation for their characterization and therapeutic exploration. In summary, although MAPCs share some characteristics with the other population of stem cells, such as the ability to differentiate into different cell types, there are significant differences in their tissue origins, surface markers, tumorigenic potential, and other biological characteristics, which make them distinctive and potentially useful for different applications in regenerative medicine. MIAMI cells are adult cells with interesting therapeutic potential but distinctive characteristics. Indeed, the isolation of MIAMI cells, to date, occurs solely from the bone marrow aspirates, while MUSE cells and VSEL can be isolated from a variety of stromal tissues. Nonetheless, these cells have sparked significant interest in the field of regenerative medicine due to their versatility and potential in treating bone lesions and musculoskeletal disorders. Unlike MUSE stem cells, known for their remarkable resistance to stress, MIAMI are not generally considered stress-resistant. This may impact their utility in clinical contexts where stress conditions are a significant factor. cells have demonstrated to promote blood vessel formation and reduce inflammation and necrosis in ischemic tissues. This is attributable to the secreted factors they release into the surrounding environment, as identified by secretome analysis. Regarding surface markers, both for MIAMI and MAPC cells, the expression of SSEA-3 still needs to be evaluated. In-depth studies on the proteome and transcriptome of these cell subpopulations could be pivotal to better understand the molecular basis of their unique characteristics and potential common origins. Identifying key expressed genes and proteins could shed light on the regulation of molecular pathways involved in pluripotency and cell differentiation. The cell cycle plays a predominant role in influencing the differentiation capabilities of stem cells and the expression of various stem cell surface markers. In the context of the proposed universal stem cell hypothesis, a comprehensive investigation into the cell cycle phases of pluripotent stem cells isolated from stromal tissues becomes crucial. It is conceivable that the expression of specific markers in pluripotent stem cells might vary across different cell cycle phases. For instance, certain markers may be expressed during the G1 phase but not in other phases like S phase. Analyzing marker expression at distinct cell cycle stages could provide valuable insights into the regulatory mechanisms governing pluripotent stem cells.

Output: corroborate


Input: Claim: Gene drives can fully eliminate any pest species within one generation. [SEP] Text: Endonuclease gene drives Natural homing endonuclease genes exhibit drive by cutting the corresponding locus of chromosomes lacking them. This induces the cell to repair the break by copying the nuclease gene onto the damaged chromosome via homologous recombination (Figure 1A) (Burt and Koufopanou, 2004). The copying process is termed ‘homing’, while the endonuclease-containing cassette that is copied is referred to as a ‘gene drive’ or simply a ‘drive’. Because copying causes the fraction of offspring that inherit the cassette to be greater than 1/2 (Figure 1B), these genes can drive through a population even if they reduce the reproductive fitness of the individual organisms that carry them. Over many generations, this self-sustaining process can theoretically allow a gene drive to spread from a small number of individuals until it is present in all members of a population. Figure 1 Download asset Open asset The spread of endonuclease gene drives. (A) When an organism carrying an endonuclease gene drive (blue) mates with a wild-type organism (grey), the gene drive is preferentially inherited by all offspring. This can enable the drive to spread until it is present in all members of the population–even if it is mildly deleterious to the organism. (B) Endonuclease gene drives are preferentially inherited because the endonuclease cuts the homologous wild-type chromosome. When the cell repairs the break using homologous recombination, it must use the gene drive chromosome as a repair template, thereby copying the drive onto the wild-type chromosome. If the endonuclease fails to cut or the cell uses the competing non-homologous end-joining repair pathway, the drive is not copied, so efficient gene drives must reliably cut when homology-directed repair is most likely. Engineered gene drives To build an endonuclease gene drive, an endonuclease transgene must be inserted in place of a natural sequence that it can cut. If it can efficiently cut this sequence in organisms with one transgene and one natural locus, reliably induce the cell to copy the transgene, and avoid being too costly to the organism, it will spread through susceptible wild populations. Standard drives spread genomic changes and associated traits through populations.

Output: contrast


Input: Claim: Owls can see in complete darkness due to their magical abilities. [SEP] Text: The recruitment start date has been changed from 27/06/2022 to 04/07/2022. 2. The recruitment end date was changed from 30/06/2022 to 07/07/2022. 13/06/2022: The following changes were made to the trial record: 1. The recruitment start date was changed from 01/06/2022 to 27/06/2022. 2. The recruitment end date was changed from 31/05/2023 to 30/06/2022. 07/06/2022: Internal review. 03/05/2022: Trial's existence confirmed by the for Health and (NIHR) (UK).

Output: pass


Input: Claim: Stem cell research holds potential for regenerating damaged tissues and organs. [SEP] Text: Correlating these cell cycle phases with the differentiation capacities across the three embryonic germ layers further enhances our understanding. This detailed analysis is instrumental in uncovering both similarities and differences within these stem cell populations. Ultimately, exploring the expression dynamics of stem cell markers throughout the cell cycle holds great promise for unraveling the intricacies of pluripotent stem cell behavior and refining our comprehension of their unique characteristics. However, it is worth noting that the high variability in results across different laboratories could be attributed to technical differences in the isolation and culture procedures of these stem cells. Standardizing work methodologies could help reduce this variability and provide more consistent results, thereby facilitating a more accurate understanding of each population's intrinsic characteristics. Taking into consideration the above-reported findings, the differences in biological properties among the various stromal stem cell populations so far described may be due to the fact that they are truly distinct cell populations (Fig. 2). Alternatively, it must be remembered that stem cells are inherently heterogeneous. This implies that the stem cell niche hosts different subpopulations of stem cells, each presenting subtle differences in stemness and lineage potential [67]. The isolation and cultivation procedures of the aforementioned stromal stem cells may have selected a specific stem cell subpopulation from the larger population of stromal stem cells. Fig. 2Stromal/Lines: within stromal tissues and peripheral blood, various populations of multipotent and pluripotent stem cells (including MUSE cells, ) exist. These populations share numerous common characteristics, suggesting potential interrelations or overlaps. Factors such as different isolation protocols, distinct cell cycle stages, or diverse niches could contribute to the isolation of these subpopulations. Each selected subpopulation () possesses specific progenitors and differentiation potential. Given the overlapping nature of stem cell populations, it is plausible that these features exhibit commonalities. However, further investigation is needed to determine whether stromal tissues harbor distinct subsets of stem cells with overlapping features or contains a single stem population, with subtypes, which can be isolated based on the aforementioned factorsFull size imageThis scenario is further complicated by the fact that every single cell population may exhibit differences according to the cell cycle stage of its components. Finally, confounding issues may also arise from differences in the evaluation of biological properties, either in vitro or in vivo.

Output: corroborate


Input: Claim: Gene drives can fully eliminate any pest species within one generation. [SEP] Text: Burt‘s original study proposed using them to drive the spread of other transgenes or to disrupt existing genes (Figure 2A,B) (Burt, 2003). The gene drive copying step can take place immediately upon fertilization (Figure 2C) or occur only in germline cells that are immediate precursors to sperm or eggs, leaving most of the organism‘s somatic cells with only one copy of the drive (Figure 2D). Figure 2 Download asset Open asset Consequences and timing of gene drive replication. (A) Gene drives can carry other genes with them as cargo. For example, a transgene that blocks malaria transmission could be driven through wild mosquito populations. There is no selection to maintain the function of a cargo gene. (B) Gene drives can disrupt or replace other genes. For example, a drive might replace a mosquito gene important for malaria transmission. Because it cannot spread without disrupting the target gene, this strategy is evolutionarily stable. (C) If homing occurs in the zygote or early embryo, all organisms that carry the drive will be homozygous in all of their tissues. (D) If homing occurs in the late germline cells that contribute to sperm or eggs, the offspring will remain heterozygous in most tissues and avoid the consequences of drive-induced disruptions. Suppression drives reduce the size of the targeted population. outlined an elegant strategy involving the use of gene drives to disrupt genes that cause infertility or lethality only when both copies are lost (Burt, 2003). These ‘genetic load’ drives would spread rapidly through minimally impaired heterozygotes when rare, and eventually cause the population to crash or even become extinct due to the accumulated load of recessive mutations. A second approach would mimic naturally occurring ‘meiotic’ or ‘gametic’ drives that bias the sex ratio (Craig et al. , 1960; Hickey and Craig, 1966; Hamilton, 1967; Newton et al. , 1976; Wood and Newton, 1991). In this model, the Y chromosome (or its equivalent in other sex-determination systems) would encode an endonuclease that cuts and destroys the X chromosome during male meiosis, thereby ensuring that most viable sperm contain a Y chromosome (Newton et al. , 1976; Wood and Newton, 1991; Windbichler et al. , 2007, 2008; Galizi et al.

Output: contrast


Input: Claim: Owls can see in complete darkness due to their magical abilities. [SEP] Text: for 1,000’s of years, the natural landscape of Israel has been shaped by—and along with—the development of agriculture [1], to the point that, in some places, it is impossible to tell a natural landscape from a human-made one. In the last few decades, Israel has gone through many upheavals, transitioning from a sparsely populated Mediterranean region to one of the most densely populated countries in the Western world. To sustain its population, Israel had to develop intensive, modern, efficient, and affordable agriculture. As often happens, this involved the disconnection of agriculture from the surrounding natural environment and caused significant damage to natural ecosystems. Pesticides were one cause of environmental damage. Use of pesticides was necessary because the land was full of crop-harming pests. Since the beginning of modern agriculture, humans have been fighting a continuous and exhausting battle against pests of all kinds, from insects to rodents. On tens of thousands of hectares in Israel, farmers grew crops such as wheat, alfalfa (a grass that is used for feeding livestock), cotton, and fruit. As the crops grew, so did the populations of harmful rodents, such as voles and the house mouse. Rodent-killing pesticides, which were developed over the twentieth century, cause serious damage to the environment [2]. Pesticides harm many animals, even those that are not pests; they seep into the water, contaminating it with harmful chemicals and endangering the health of those using it. Some types of pesticides are absorbed by vegetables or fruits and endanger those who eat them, including humans. If cows eat hay that was sprayed with pesticides, the toxic substances can reach humans through the cows’ milk. Additionally, certain pesticides break down very slowly, and they can cause what is called secondary poisoning. When a predator eats an animal that was poisoned by a pesticide, the pesticide residues that have not broken down in the prey animal’s body cause secondary poisoning of the predator. In many places, secondary poisonings have caused the destruction of entire populations of raptors (birds of prey) and other bird species. The damage to the nocturnal raptor population was particularly unfortunate because these raptors, including barn owls, are the natural enemies of rodents. Rodents make up 95% of the diet of barn owls. Some of the damage caused to the environment and the animals that live in pesticide-treated areas is irreparable. and Farmers?

Output: pass


Input: Claim: Stem cell research holds potential for regenerating damaged tissues and organs. [SEP] Text: Conclusions and future perspectivesIn conclusion, multipotent/pluripotent adult stem cell (PSC) populations represent an extraordinary resource for regenerative medicine, offering therapeutic possibilities for a broad spectrum of pathologies. However, the confusion arising from the diversity of PSC types and their unique characteristics emphasizes the need to isolate and characterize these populations in common laboratories. Only through detailed analyses of the proteome, secretome, and transcriptome can we clarify the overlaps and differences between these stem cells, contributing to a deeper understanding of their origins and therapeutic potential. The future of PSC research should focus on standardizing methodologies and conducting in-depth analyses in shared laboratories. This approach could not only reduce variability in results but also facilitate scientific collaboration to maximize the therapeutic potential of pluripotent stem cells. Furthermore, ongoing research into optimizing the timing of therapies underscores the need for further investigations to refine treatment strategies across different clinical conditions. AbbreviationsASCs: Adipose tissue-derived stem/stromal cells FACS: Fluorescence-activated cell sorting HSC: Hematopoietic stem cells MACS: Magnetic-activated cell sorting MAPC: Multipotent adult progenitor cells MIAMI: Marrow-isolated adult multilineage inducible cells MSCs: Mesenchymal stem/stromal cells MUSE: Multilineage differentiating stress enduring cells PGCs: Primordial germ cells PSC: Pluripotent stem cells S1P: Sphingosine-1-phosphate SBSC: Small blood stem cells VSELs: Very small embryonic-like stem cells 8. 12. 6195. 57. 47. 24. 26. 92. 48. 2151. 403. 3422. 6. 43. 61. 761. 80. 2357. 41. 83. 2064. 44. 542. 73. 40. 7102. 5347. 35. 977. 98. 69. 51. 42. 78. 10. 32. 2595. 34. 408. 31. PubMed Pub10. 787. 32. 380. 81. 10. 5024. 6179. 395. 92. 904. 84. 42. 163. 299. 10. 36. 65. 82. 39. 9. 77. 37. 5395. CAS 6. 2018. p. 13–41.

Output: corroborate


Input: Claim: Gene drives can fully eliminate any pest species within one generation. [SEP] Text: , 2014). The progressively dwindling number of females will culminate in a population crash or extinction (Craig et al. , 1960; Lyttle, 1977; Burt, 2003; Schliekelman et al. , 2005; Deredec et al. , 2008, 2011; North et al. , 2013; Burt, 2014). Whether a standard gene drive will spread through a target population depends on molecular factors such as homing efficiency, fitness cost, and evolutionary stability (Marshall and Hay, 2012); only the rate of spread is determined by the mating dynamics, generation time, and other characteristics of the target population. In contrast, models suggest that the deleterious and complex effects of genetic load and sex-biasing suppression drives render them more sensitive to population-specific ecological variables such as density-dependent selection (Burt, 2003; Schliekelman et al. , 2005; Huang et al. , 2007; Deredec et al. , 2008; Marshall, 2009; Yahara et al. , 2009; Deredec et al. , 2011; Alphey and Bonsall, 2014). No engineered endonuclease gene drive capable of spreading through a wild population has yet been published. However, the Crisanti and Russell laboratories have constructed gene drives that can only spread through laboratory mosquito (Windbichler et al. , 2011) and fruit fly (Chan et al. , 2011; Simoni et al. , 2014) populations that have been engineered to contain the endonuclease cut site. and Crisanti laboratories are attempting to build a male-biasing suppression drive using an endonuclease that serendipitously cuts a conserved sequence repeated hundreds of times in the X chromosome of the mosquito Anopheles gambiae (Windbichler et al. , 2007, 2008; Galizi et al. , 2014). If successful, their work promises to substantially reduce the population of this important malaria vector. All engineered gene drives based on homing endonucleases cut the natural recognition site of the relevant enzyme. Despite early hopes, it has proven difficult to engineer homing endonucleases to cleave new target sequences. Numerous laboratories have sought to accomplish this goal for well over a decade with only a few recent successes (Chan et al. , 2013a; Thyme et al. , 2013; Takeuchi et al. , 2014).

Output: contrast


Input: Claim: Owls can see in complete darkness due to their magical abilities. [SEP] Text: The main goal of the barn owl project that we have been leading for 40 years is to significantly decrease the use of pesticides and to reduce the harm these chemicals cause to humans, the environment, wildlife and migrating birds. The idea of using barn owls as an environmentally friendly means of biological pest control arose in the 1970’s. About a billion migratory birds pass through Israel each year-500 million in the fall and 500 million in the spring (Figure 1). It is possible to observe about 550 different species of birds in Israel—an extraordinary number for a country of its size. Israel may be famous for its historical and archaeological heritage, but its bird populations are no less outstanding and unique. It is important for us to protect these migrating bird species, many of which could be harmed by pesticide use. The use of barn owls to keep the rodent population in check has significantly reduced the use of toxic pesticides in agricultural areas in Israel. In addition to the obvious environmental benefits, the use of barn owls reduces the costs of farming, so farmers save money. Since barn owls do not build nests, the original scientists provided the owls with nesting boxes placed in agricultural fields. In doing so, they hoped to increase the population of barn owls in the wild, and specifically in areas where they could be of use to farmers. Figure 1 - Twice a year, about a billion birds pass over Israel as they migrate-500 million in each migration season (spring and fall). Israel’s barn owl project started in the Hula Valley, in the north of Israel. In 1982, two other scientists and I proposed this method in response to the deaths of thousands of migratory birds due to poisoning by small rodents called voles. Then, the War broke out; the farmers and researchers were enlisted to fight; one of the leaders of the project fell in battle; barn owls were poisoned and died; and the attempt failed. The next attempt was made in 1983 [3], when 14 nesting boxes were placed in the organic fields and orchards of Eliyahu in the Beit She’an Valley. Later, about 50 more nesting boxes were added, and these fields became an outdoor laboratory for scientists.

Output: pass


Input: Claim: Stem cell research holds potential for regenerating damaged tissues and organs. [SEP] Text: Main TextHow many laboratories does it take to heal the wounded warrior? In 2008, the U. S. Department of Defense (DOD) launched the Institute for Regenerative Medicine, or AFIRM, a 5 year initiative modeled on the assumption that bringing together a multi-institutional throng of talent is a far better approach than adhering to the isolating, competitive status quo of team versus team. AFIRM's mission is to accelerate the development of therapies for those who have served, especially those injured in Iraq and Afghanistan, and since the DOD was already backing a few ventures into regenerative medicine—Agency (DARPA)'s Repair Program, for instance—that became the new project's signature mark as well. AFIRM's research areas were chosen in light of a hard truth about modern warfare. Even though new and improved life-saving strategies have reduced the number of fatalities, more soldiers are returning from combat with devastating wounds that once would have killed them. AFIRM is less about regenerating entire parts, and more about using adult stem cells and progenitors to restore tissue torn apart by lethal, modern-day explosives: blast-induced burns and nerve damage; loss of bone, muscle, tendons, fingers, ears, and noses; and deep wounds to the head and abdomen. Today, 4 years down the line, AFIRM's multidisciplinary strengths are more appreciable than ever, notably its scientists' quicker than usual strides toward clinical trials, and while the initiative has experienced some rockiness—“When you put 200 to 300 scientists in one boat, what do you expect? ” one researcher remarked—the DOD plans to renew AFIRM for another 5 years. An announcement to that effect is imminent, said 's director since October 2010. Ship in the MakingSomething unique about AFIRM, other than its sheer size, is its structure. Researchers at and the head one network of 15 institutions, while and the University of Pittsburgh's Mcfor head a second group of 16. Both consortia also collaborate with scientists at the U. S. of Surgical Research, and connect with industrial partners who help open the way to clinical trials. The U. S. Research and (MRMC), meanwhile, is responsible for overseeing the whole ocean liner and managing funds.

Output: corroborate


Input: Claim: Gene drives can fully eliminate any pest species within one generation. [SEP] Text: More recently, a team constructed new versions of the fruit fly gene drive using modular zinc-finger nucleases or TALENs in place of the homing endonuclease (Simoni et al. , 2014), both of which can be engineered to cut new target sequences. While initially successful at cutting and homing, both declined in effectiveness over time due to the evolutionary instability of the modular repeats inherent to those proteins. These early attempts demonstrate that it is possible to build synthetic gene drives, but also emphasize the importance of cutting any desired gene and remaining stable during copying. The recent discovery of the RNA-guided Cas9 nuclease represents a possible solution. RNA-guided genome editing via the Cas9 nuclease One straightforward method of genome editing relies on the same mechanism employed by endonuclease gene drives: cut the target gene and supply an edited version for the cell to use as a template when it fixes the damage. Most eukaryotic genome engineering over the past decade was accomplished using zinc-finger nucleases (Urnov et al. , 2005) or TALENs (Christian et al. , 2010), both of which are modular proteins that can be redesigned or evolved to target new sequences, albeit only by specialist laboratories (Esvelt and Wang, 2013). Genome editing was democratized by the discovery and adaptation of Cas9, an enzyme that can be programmed to cut target DNA sequences specified by a guiding RNA molecule (Deltcheva et al. , 2011; Jinek et al. , 2012; Cho et al. , 2013; Cong et al. , 2013; Jinek et al. , 2013; Mali et al. , 2013c). Cas9 is a component of acquired immune systems in bacteria, which allow cells to ‘remember’ the sequences of previously encountered viral genomes and protect themselves by recognizing and cutting those sequences if encountered again. They accomplish this by incorporating DNA fragments into a memory element, transcribing it to produce RNAs with the same sequence, and directing Cas9 to cut any matching DNA sequences (Deltcheva et al. , 2011). The only restriction is that Cas9 will only cut target ‘protospacer’ sequences that are flanked by a protospacer-adjacent motif (PAM) at the 3′ end.

Output: contrast


Input: Claim: Owls can see in complete darkness due to their magical abilities. [SEP] Text: In Cyprus, the hunting of wild animals and migratory birds is very common, as is the use of pesticides; and even in Greece the situation is far from ideal. Hopefully, the barn owl project will raise awareness and help to protect birds—and the rest of the environment—in these regions [5]. Atlas for In 2020, we started using an innovative and ground-breaking system called Atlas to monitor birds' movement. The system was developed in Israel in a collaboration between researchers from University (Prof. Sivan Toledo) and the in Jerusalem (Prof. Ran Nathan). is being used to follow movement by Dr. and his PhD student Shlomo Cain. Atlas is a system of antennas that enables the tracking of a wide variety of individual animals (weighing more than 10 grams) in real time. A reading of a tracked animal’s position is obtained every 4–8 s. Atlas can operate for up to 2 years, depending on the size of the battery, and the transmitter is significantly cheaper than alternatives like GPS. system currently contains 19 base stations, covering a total of ~300 km2 in Beit She’an and Harod Valley. Each of 136 barn owls were fitted with a small ring attached to one of its legs and a transmitter attached to its back. The details transmitted by Atlas enable accurate tracking of barn owl movement and behavior in the field, and all the data are recorded. These accurate measurements help researchers to locate and characterize rodent-infested fields before the rodents do large-scale damage, which will strengthen the cooperation between participating countries and support the training of farmers in the region in carrying out similar activities in their territories. Glossary Pesticides: ↑ Chemical agent to poison and kill pests in agriculture. Secondary Poisoning: ↑ Predators accumulating poison in their body by consuming poisoned prey, so the poisoning effect grows and harms predators as well. Raptors: ↑ Predatory birds, catch prey with their strong feet with sharp talons. Barn Owl: ↑ Nocturnal raptor of the owl family that preys on rodents. These owls have excellent vision and hearing and sharp talons, all of which make them great hunters. Control: ↑ Using living creatures to control populations of pests such as rodents and insects; may help decrease the use of harmful chemical pesticides.

Output: pass


Input: Claim: Stem cell research holds potential for regenerating damaged tissues and organs. [SEP] Text: Kohn then encountered Thomas Mustoe, a plastic surgeon from Northwestern University, in the same program, who applied the wound dressing to his lab's rabbit model and showed that indeed it alleviated scaring. “No one had a clue such an outcome was possible,” said Kohn. “Clark, Mustoe, and I didn't know each other, and now we are three peas in a pod. ”of the noted that a 3 year comparison of scaffolds for bone defects had “a significant benefit” for the four laboratories involved. “Labs traditionally work on their own and don't aggressively compare their biomaterials. Each of these labs learned something important about their scaffold—what could work better and what wasn't working. ”In a separate project, one related to craniofacial research, of School and of MIT have been trying to beat two major problems that have kept tissue-engineered ears from the clinic: scaffolding that cannot withstand the contractile force of growing tissue, and cartilage cell sources that get resorbed by the body. “I would say that over the past 4 years, it appears we have solved both of these problems,” said Vacanti, thanks to funding and resources from AFIRM, and the team's collaboration with ear surgeons at the as well as scientists at who have applied their expertise in cartilage repair devices to the ear for the very first time. Just how quickly some products reached clinical trials surprised everyone. Eleven trials are underway, according to Terry Irgens, who expects three more products to enter Phase 1 trials later this year. One of the burn-repair technologies, a sprayable cell treatment, is likely to be the first product to reach the market as a direct result of AFIRM. has “far exceeded the very conservative goal initially set” of having one patient enrolled in a clinical trial after 5 years, noted Irgens. Already as many as 100 patients are enrolled in several. Because no one had imagined clinical trials would happen so soon, the DOD's original funding for AFIRM, roughly $100 million, had been earmarked solely for science and technology, said Irgens. Then synergy made for shortcuts: getting rid of duplicate therapies and inferior approaches, and sharing knowledge and resources whenever possible. Resources put in place by the DOD further accelerated projects toward clinical-trial status.

Output: corroborate


Input: Claim: Gene drives can fully eliminate any pest species within one generation. [SEP] Text: Incomplete cutting was a problem for the homing endonuclease drive constructed in transgenic mosquitoes (72% cutting) and also for the homing endonuclease, zinc-finger nuclease, and TALEN drives in fruit flies (37%, 86%, and 70% cutting) (Windbichler et al. , 2011; Chan et al. , 2013b; Simoni et al. , 2014). The simplest way to increase cutting is to target multiple adjacent sequences. However, this is impractical for homing endonucleases and quite difficult for zinc-finger nucleases and TALENs, as each additional sequence requires a new nuclease protein to be engineered or evolved and then co-expressed. In contrast, the RNA-guided Cas9 nuclease can be readily directed to cleave additional sequences by expressing additional guide RNAs (Figure 4). The sequences of these additional guide RNAs can be altered so as to avoid creating unstable repeats within the drive cassette (Nishimasu et al. , 2014; Simoni et al. , 2014). Including more guides has been demonstrated to improve upon already high rates of cutting. For example, fruit flies expressing both Cas9 and guide RNAs in their germline exhibited target cutting rates exceeding 85–99% in males for four out of six tested guide RNAs (Kondo and Ueda, 2013). The two least effective guide RNAs individually cut at rates exceeding 12% and 56%, but exhibited cutting rates above 91% when combined. Using more than two guide RNAs should further enhance cutting. The notable success of Cas9-based genome engineering in many different species, including studies that targeted every gene in the genome (Shalem et al. , 2014; Wang et al. , 2014), demonstrates that most sequences can be efficiently targeted independent of species and cell type. Thus, RNA-guided gene drives should be capable of efficiently cutting any given gene. Figure 4 with 3 supplements see all Download asset Open asset Technical advantages of RNA-guided gene drives. Clockwise from lower left: The targeting flexibility of Cas9 permits the exclusive selection of target sequences with few potential off-targets in the genome. Targeting multiple sites increases the cutting frequency and hinders the evolution of drive resistant alleles, which must accumulate mutations at all of the sites.

Output: contrast


Input: Claim: Owls can see in complete darkness due to their magical abilities. [SEP] Text: Close sectionO heaven born muse! inspire my humble layThe earth is parched with heat, flowers droop and dieLines, Written on Reading Stuart's Account of of Slaves in CharlestonLines on Mount AuburnLines suggested by hearing the beach, at F. Peabody's Mills, South SalemHast thou ever heard the voice of nature'Ambitione inani pectus caret'What more delightful than to wander forthA by Mr J. Very, to be Sung at the Class-Supper of the of 1834Death of ("Goddess of pleasure, where thy golden car? ")Give me an eye, that manly deedsI saw a child, whose eyes had never drankcold thy lips my gentle boySpring ('Look! Winter now in trembling haste')The morn may lend its golden smile— On the Death of His FriendNorth RiverEheu! fugaces, Posthume, Posthume, Labuntur anniThe Humming-BirdNature ('I love to sit on the green hill's side')ReligionA Withered Leaf—seen on a Poet's ('Soon the silver chord is broken')Memory ('Soon the waves, so lightly bounding')'s of of 22d, 1836Song: For the of the of Harvard University, 1836's Dream: A BalladI murmur not though hard the lotFlowerThe moon was shining on the deckHome of my youth! Where first my lot was castHaunts of my youth farewell! A while I leaveand ('I love thee when thy swelling buds appear')('Nature, my love for thee is deeper far')of GodThe Wind-('Thou who keepst us each together')The Stranger's 'we live, & move, & have our being'and ('Father! thy wonders do not singly stand')The Slavefrom ('The Word!

Output: pass


Input: Claim: Stem cell research holds potential for regenerating damaged tissues and organs. [SEP] Text: Whether or not his lab is chosen for the next round, Badylak is prepared to do whatever it takes to continue developing his lab's approach to regenerating either missing digits or skeletal muscle, a novel technique that prompts an accumulation of cells and tissue at the site of injury. Is he confident that this technique will reach patients? “Oh yes, absolutely. No question about it,” Badylak said. “I'd be extremely disappointed if it didn't. ”An unidentified AFIRM researcher at demonstrates a bone regeneration scaffold (round white object in foreground). The images on the computer screen represent magnified CT scans of newly regenerated bone (highlighted in blue) when the bone regeneration scaffold was used to heal a large circular defect in the skull of a rabbit in a preclinical model study. Photo by Don Lindorfer. The white objects in the picture are bone regeneration scaffolds in various sizes developed at under AFIRM funding. In this photograph, an unidentified researcher attempts to fit one of the bone regeneration scaffolds into a defect created in the skull of a rabbit for training purposes. Photo by Don Lindorfer.

Output: corroborate


Input: Claim: Gene drives can fully eliminate any pest species within one generation. [SEP] Text: , 2009) if supplied with a shortened guide RNA that directs it to bind and block transcription but not cut (Bikard et al. , 2013; Sternberg et al. , 2014). Alternatively, an orthogonal nuclease-null Cas9 protein (Esvelt et al. , 2013) encoded within the drive cassette could repress NHEJ genes and activate HR genes before activating the Cas9 nuclease. Lastly, Cas9 might be used directly recruit key HR-directing proteins to the cut sites, potentially biasing repair towards that pathway. Evolutionary stability Even a perfectly efficient endonuclease gene drive is vulnerable to the evolution of drive resistance in the population. Whenever a cut is repaired using the NHEJ pathway, the result is typically a drive-resistant allele with insertions or deletions in the target sequence that prevent it from being cut by the endonuclease. Natural sequence polymorphisms in the population could also prevent cutting. These alleles will typically increase in abundance and eventually eliminate the drive because most drives – like most transgenes – are likely to slightly reduce the fitness of the organism. A second path to gene drive resistance would involve the target organism evolving a method of specifically inhibiting the drive endonuclease. The best defense against previously existing or recently evolved drive-resistant alleles is to target multiple sites. Because mutations in target sites are evolutionarily favored only when they survive confrontation with the gene drive, using many target sites can render it statistically improbable for any one allele to survive long enough to accumulate mutations at all of the sites so long as cutting rates are high (Burt, 2003). However, very large populations – such as those of some insects – might require unfeasibly large numbers of guide RNAs to prevent resistance. In these cases it may be necessary to release several successive gene drives, each targeting multiple sites, to overcome resistant alleles as they emerge. From an evolutionary perspective, the ability to preclude resistance by targeting multiple sites is the single greatest advantage of RNA-guided gene drives. We propose to extend this strategy by preferentially targeting multiple sites within the 3′ ends of genes important for fitness such that any repair event that deletes all of the target sites creates a deleterious allele that cannot compete with the spread of the drive (Figure 4). Whenever the drive is copied, the cut gene is replaced with a recoded version flanked by the other components of the drive.

Output: contrast


Input: Claim: Owls can see in complete darkness due to their magical abilities. [SEP] Text: it cannot fail; it ever speaks')Worship ("There is no worship now—the idol stands")of Lifeof the ("There is a winter in the godless heart")'s and the at ('I saw the city, 'twas not built by hands')The CrossNature ('Nature would speak through her first master man')and meat and drinkForgive me my trespassesin HeartThe ComplaintWhither shall I go from thy Spiritshall be LastThe LaborerThy Brother's of are passed away('They love me not, who at my table eat')The CityThe RoseFaith ('There is no faith; the mountain stands within')The JewSpring ('The stem that long has borne the wintry blast')and The EndNature ('The bubbling brook doth leap when I come by')! The Sign('I too will wait with thee returning spring')('Father! help them who walk in their own light')notice other days were pages givenThe CrocusThe PlantI am the WayThe kingdom of within you('There is no sound but thou dost hear my voice')The PreacherCome unto meFlee to the mountainsBlessed are they that mournFaith ('Hast thou but faith thou shalt the mountain bid')Redeeming the TimeTis FinishedEffortTo the pure all things are pureThe TaskSpring ('I have not lived the flesh has hedged me in')('The plant it springs it rears its drooping head')('Come thou and labor with me I will give')('The words I give thee they are not thine own')Joy ('The joy Thou giv'st no man can take away')HopeReliefJoy ('Thou hast a moon for every cloudy night')('I come the rushing wind that shook the place')of is every one who is born of the spiritThe SeedI am the Light of the the Bread of shall all the tribes of the earth mournRepent for the kingdom of Heaven is at handthe you is born a SaviourThe RedeemedHallowed be they NameTo him who overcomethof the Templeof as the World giveth('Open our eyes that we the world may see')Thy Father's HouseJacob's Wellof ('The voice that speaks when thou art in thy tomb')and ('Why are thou not awake my son? ')('not visit me?

Output: pass


Input: Claim: Private companies are increasingly involved in space exploration, contributing to a new space race. [SEP] Text: , with long periods of apparent equilibria, later punctuated by rapid transition periods of extreme change), but here applied to digital economies and exploration, rather than to terrestrial biological processes over time [Gould, 2007]. 4 Thus, punctuated equilibria in a space business context facilitates consideration of rapid transitional states in between times of slower evolution and adoption. This can be witnessed today as commercial crew and cargo are giving way to more entrepreneurial opportunities in robotic spaceflight (e. g. , or CLPS). In this pathfinder “concept” 2030. org/] as a nascent scenario in which the DEFF-Oceans communities are working together to expand understanding and effective utilization of our oceanic domains on our home planet Earth, which itself represents an “ocean world. ”DEFF-: 1 describes DEFF-S: 10 as a point of departure, with several examples of impact. The selected DEFF-S principles within this Table are illustrated so that they might act as catalysts for cross-disciplinary examples of individual, team, and organizational digital explorations in the context of a future digital space economy. Their impacts are preliminary and can be expanded upon in a variety of contexts. These 10 initial examples (Table 1) can be further enumerated and increased in scope organically depending on the problem of interest within the space exploration domain. Consideration of 3 more specific examples is discussed in an upcoming section. Table 1.

Output: corroborate


Input: Claim: Gene drives can fully eliminate any pest species within one generation. [SEP] Text: Recent work has demonstrated that most genes can be substantially recoded with little effect on organism fitness (Lajoie et al. , 2013); the 3′ untranslated region might be replaced with an equivalent sequence from a related gene. Because there would be no homology between the recoded cut site and the drive components, the drive cassette would always be copied as a unit. Relative to drive-resistant alleles, inhibitors of Cas9 are less likely to arise given the historical absence of RNA-guided nucleases from eukaryotes. Any inhibitors that do evolve would presumably target a particular Cas9 protein or guide RNA used in an earlier drive and could be evaded by building future drives using a Cas9 ortholog with a different guide RNA (Esvelt et al. , 2013; Fonfara et al. , 2013). Alternatively and least likely, organisms might evolve higher RNase activity to preferentially degrade all guide RNAs; this may be difficult to accomplish without harming overall fitness. A final evolutionary concern relates to the stability of the gene drive cassette itself. The zinc-finger nuclease and TALEN-based gene drives in fruit flies suffered from recombination between repetitive sequences: only 75% and 40% of each respective drive was sufficiently intact after one copying event to catalyze a second round of copying. Because RNA-guided gene drives will not include such highly repetitive elements, they are likely to be more stable (Figure 4). Development time RNA-guided genome editing is advancing at a historically unprecedented pace. Because it is now much easier to make transgenic organisms and therefore candidate gene drives, the design-build-test cycle for gene drives will often be limited only by the generation time of the organism in the laboratory. Moreover, many advances from genome engineering can be directly applied to RNA-guided gene drives. For example, all of the methods of increasing Cas9 specificity described above were developed for RNA-guided genome editing in the past 2 years. Future methods of increasing the rate of HR relative to NHEJ would be useful for both technologies. These factors suggest that scientists will enjoy an increasing number of tools well-suited to rapidly building and testing gene drives in addition to those we describe above. None of this is to gloss over the many practical difficulties that are likely to arise when constructing a particular gene drive in a given species. Early success is as unlikely as ever when engineering complex biological systems.

Output: contrast


Input: Claim: Owls can see in complete darkness due to their magical abilities. [SEP] Text: ')-ManThe CottageThe Still-BornTo-of 's of and the Footand not for Gain('The end of all thou seest is near')of FlowersHymn: and it shall be given unto you. from WithinThou know'st not what thy Lord will sayof the JustDeathThe Birth-Day of the SoulHiveTime's Houseand the BirdFaith and Light('where is it? hath it voice')('Stay where thou art, thou need'st not further go')'s Island Lightof Godof the BooksThe Robin's ('Tis all a great show')on Reading the Death of Rev. Henry Ware, Jr. BrightGod's at the ('There are towers; where they are')ye sow, so shall ye reap's RetortThe WidowImpatienceAbdolonymus—'s by FaithSalem ("Boast not, my native spot, thy sons were first")Spring in the SoulNature's InvitationChrist's CompassionHymn: Nevertheless, when the Son of Man cometh, shall he find faith on the earth? :8of 'to LiveThe Indian's the late in 's : Suggested by an EngravingThoughts and DesiresHymn ('As by the quickening breath of Spring')The Soul's : of the Rev. James Flint, D. D. , On reading his Collection of on the of J. Esq. July 22d, 1853the at the Thompson Jubilee, at Barre, Jany. 12, 1854: Sung at the Celebration of the Fourth of July, in Salem, 1854? To the Memory of the Rev. James Flint, D. D. and WorldlyHymn: So also will God, through Jesus, bring with him them who sleep'Blessed are they that mourn: for they shall be comforted' Math. 5:4To the Memory of the Rev. of -cleave not to the things of earth's the Rev. C. H. A. Dall, in IndiaHymn: Sung at the Dedication of Plummer Hall, Salem, Oct.

Output: pass


Input: Claim: Private companies are increasingly involved in space exploration, contributing to a new space race. [SEP] Text: •As commercial space imagines low-Earth-orbit entrepreneurial space stations (a la Axiom space concepts in development now) and lunar eco-tourism, how would this adaptive, intelligent “network” bring more lunar economic opportunities to light, with plug-and-play (yet secure) connectivity with a level of situational awareness needed for lunar resources utilization and other activities of potential future value (e. g. , private lunar «visitors» as eco-tourists in a deep space ecosphere)? •How does this lunar “internet of things” with situational awareness encourage new digital economic opportunities beyond government-incentivized ones so that the business of space embraces the Moon much more broadly with benefits directly back to our Earth-based society, including infrastructure to imagine new research in pharmaceuticals (mostly robotic) on the Moon as a safe approach for R&D into potential medical breakthroughs that cannot be tested and validated on Earth? This example would expand humanity’s reach into lunar orbit with a sensor/telecommunications web that could offer business, technology, innovation, and science opportunities far beyond those imagined in the first wave of the Artemis program as humans return to the Moon (e. g. , LunaNet). Imagine a network of lunar orbital imaging and intercommunication nodes that provide rapid situational awareness of key parameters related to human activities on the Moon as basecamps and outposts are established, and which offer connectivity opportunities that advance capabilities beyond orbit to cislunar space, with off-ramps that could eventually build up a robotic situational awareness presence at Mars. If such a system were to exist, then business opportunities beyond those now operating in low Earth orbit with commercial imaging systems (e. g. , Maxar WorldView, Planet, Capella) could be expanded at the Moon as humanity returns, with value-added benefits for the deep space (lunar) economy but with collateral benefits associated with science and exploration. DEFF-S with ABT principles could develop this opportunity space beyond traditional governmental acquisition practices to incentivize the capabilities and spin-off benefits, which apply directly to digital exploration in the 2030’s and beyond. Example 3Space-based universal Quantum computing centers for multi-purpose applications within the digital economy.

Output: corroborate


Input: Claim: Gene drives can fully eliminate any pest species within one generation. [SEP] Text: But if half a dozen or even a dozen design-build-test cycles are sufficient to produce moderately efficient gene drives, many molecular biology laboratories around the world will soon be capable of engineering wild populations. Box 1 Could gene drives alter human populations? Not unless we wait for many centuries. Even in a hypothetical future in which human germline editing was considered safe and ethical, a driven alteration would be only four times as abundant as a non-driven alteration a full century after the birth of an edited human. This assumes future generations would not elect to remove the drive. Whole-genome sequencing - a technology that is available in many modern hospitals and is widely expected to be ubiquitous in the near future - is quite capable of detecting the presence of any gene drive if we decide to look. Gene drive limitations Given their potentially widespread availability, it will be essential to develop a comprehensive understanding of the fundamental limitations of genetic drive systems. First and most important, gene drives require many generations to spread through populations. Once transgenic organisms bearing the gene drive are constructed in the laboratory, they must be released into the wild to mate with wild-type individuals in order to begin the process of spreading the drive through the wild population. The total time required to spread to all members depends on the number of drive-carrying individuals that are released, the generation time of the organism, the efficiency of homing, the impact of the drive on individual fitness, and the dynamics of mating and gene flow in the population, but in general it will take several dozen generations (Burt, 2003; Huang et al. , 2007; Deredec et al. , 2008; Marshall, 2009; Yahara et al. , 2009; Deredec et al. , 2011). Thus, drives will spread very quickly in fast-reproducing species but only slowly in long-lived organisms. Second, gene drives cannot affect species that exclusively practice asexual reproduction through clonal division or self-fertilization. This category includes all viruses and bacteria as well as most unicellular organisms. Highly efficient standard drives might be able to slowly spread through populations that employ a mix of sexual and asexual reproduction, such as certain plants, but drives intended to suppress the population would presumably force target organisms to reproduce asexually in order to avoid suppression. Third, drive-mediated genome alterations are not permanent on an evolutionary timescale.

Output: contrast


Input: Claim: Owls can see in complete darkness due to their magical abilities. [SEP] Text: 6, 1857Philosophy and 's Invitationfor a little Childonly and of WaterstonHymn: of The Spiritand of of Harmony GrovePreparation for Life's Voyageof Belief in a Spiritual WorldHymn: The DewThe TriennialWelcome: Written for the Fair, Held at Salem Sept. 4th, 1860The Child's reading the Memorial of BrowneHymn ("Not tears alone for natural grief")One generation passeth away, and another generation cometh: but the earth abideth for ever. Ecclesiastes 1:4What of Our Country? of not: for they that are with us are more than they that are with them. 2 Kings 6:16Hymn: Nature's Sympathy with FreedomChrist's The Garden: A ParaphraseSong: a on ImaginationSunset in Derby's Woodsare destroyed for lack of Knowledge. —Hosea 4:6Autumn FlowersHymn ("From out its large estate")The Poet's the Built by the Puritans in 1634Aurelia of : of Jonah ii. 9("I sought the flowers, but o'er them lay")Shall put on ImmortalityHymn: to 's ("A nobler unity, than that which came"): of LifeMan's Of PeaceHymn: Life of Humanityof Flora, On the grounds of R. the Unitarian Festival, in Faneuil Hall, May 26th 1863of LibertyHymn: Our Country's a Liveat the Church DoorHealth of Body dependent on the of the Mississippi Valleyof John Foster: "I Can Pray, And That's a Glorious Thing"Home and of Shakespeare's BirthdayHymn: of the Righteous EasyUntimely ArgumentsHymn ("In the shock of mighty armies")of : Christ's Invitation in theW. Felt Esq. New Type-of Libby Prison: Related by Capt. 's at the Eulogy on June 1st 1865Soul-SicknessSong of SpringSensibility to the Beauty and Fragrance of FlowersThe Word? of the : of Dew? Job 38:28"It is vain to say, that this is the country of the 'white man. ' It is the country of man. " 'O Lord, How Long?

Output: pass


Input: Claim: Private companies are increasingly involved in space exploration, contributing to a new space race. [SEP] Text: •Current supercomputing capabilities presently here on Earth could be accelerated by in-space implementation of quantum-computing “super-systems” that use the collateral benefits of the environments of space and advanced quantum telecommunications to provide services at the higher end needs of an evolving digital economy with business opportunities beyond the traditional IT industry players (e. g. , IBM, D-wave) and their investments. •Via DEFF-S, this space-based quantum IT (SQIT) system could start as a catalyst for moving next generation quantum computing from cryogenic chambers on Earth to solar-energy enabled variants in space and ultimately within cold-traps (at 25K) on the Moon, perhaps tied to outcomes of the Artemis program (and associated infrastructure). •Incentivization by government investments and private venture capital could develop the first “nodes” in an expanding SQIT network, that could become a tool in all DEFF-X domains as new ideas are tested at limits of what computing can do, and to evolve a ground-based IT capability on Earth as a system of local backups (like cell towers for cellular networking vs. satellite-based versions). •There are many pathways for achieving this, but as conceived it could mobilize the quantum engineering and computing sectors into Space where power and environments could open new possibilities, especially by the 2030’s and 2040’s, with extensibility to unique environments on the Moon and Mars. This example provides the potentiality for a leap forward in computational capabilities and spin-off innovation across a wide array of fields including, but not limited to, research (given unique conditions of Space); secure communications (with quantum key distribution); Earth observation (including climate monitoring); acceleration of Space exploration (via enhanced simulation) and quantum internet (through the connection od space situated quantum computing centers). These 3 examples are provocative and yet notably incomplete, but they highlight some specific aspects of the DEFF-S catalytic thinking we have described herein (Table 1) with more concrete and specific potential applications [see also S1, Figure S2]. Further examples involving a space-based energy economy that harvests energy relevant resources from space (Helium-3, dark energy, solar power, safer energy storage etc. ) could also be developed and evaluated, as well as many others often considered in ongoing visioneering studies by NASA and other space-faring nations.

Output: corroborate


Input: Claim: Gene drives can fully eliminate any pest species within one generation. [SEP] Text: While gene drives can spread traits through populations even if they are costly to each individual organism, harmful traits will eventually be outcompeted by more fit alleles after the drive has gone to fixation. Highly deleterious traits may be eliminated even more quickly, with non-functional versions appearing in large numbers even before the drive and its cargo can spread to all members of the population. Even when the trait is perfectly linked to the drive mechanism, the selection pressure favoring the continued function of Cas9 and the guide RNAs will relax once the drive reaches fixation. Maintaining deleterious traits within a population indefinitely is likely to require scheduled releases of new RNA-guided gene drives to periodically overwrite the broken versions in the environment. Fourth, our current knowledge of the risk management (Scott et al. , 2002; Touré et al. , 2004; UNEP, 2010; McGraw and O’Neill, 2013; Alphey, 2014) and containment (Benedict et al. , 2008; Marshall, 2009) issues associated with gene drives is largely due to the efforts of researchers focused on mosquito-borne illnesses. Frameworks for evaluating ecological consequences are similarly focused on mosquitoes (David et al. , 2013) and the few other organisms for which alternative genetic biocontrol methods have been considered (Dana et al. , 2014). While these examples provide an invaluable starting point for investigations of RNA-guided gene drives targeting other organisms, studies examining the particular drive, population, and associated ecosystem in question will be needed. Box 2 Could gene drives alter domesticated animals or crops? In theory they could, though probably not without the permission of the farmers, scientists and breeders who typically monitor reproduction. For example, genetic records and artificial insemination are so common among cattle and other domesticated animals that it would be exceedingly difficult for a gene drive to spread through any of these species. Seed farms play a similar role for crops. Long generation times will represent a further barrier for many domesticated species. In general, our expectation is that beneficial applications are more likely to involve the alteration of weeds and insect pest populations rather than the crops themselves. Safeguards and control strategies Given the potential for gene drives to alter entire wild populations and therefore ecosystems, the development of this technology must include robust safeguards and methods of control (Oye et al. , 2014). Whereas existing gene drive proposals focus on adding genes (Ito et al.

Output: contrast


Input: Claim: Owls can see in complete darkness due to their magical abilities. [SEP] Text: 'Our Soldiers' upon the HeartNecessary for the Voyage of LifeSonnet ("I gazed upon the silent burial-ground")Nature's Help for the SoulNature a 's GroveOctober ("All day, admist the forests' splendor bright")and the Statesmanof Science, And of of the Springof TimeMotherHymn: of the SpiritHymn ("Admist the pastures green")of the come the Dead? 's TreasuresClose sectionSonnets on Reconstruction I. A Nation's. . IV. ("A unity complete, assured, and high") Reflections on the History of and the of at the Dedication of the of Science, Salem, Aug. 18, 1869have hoarded up treasure in the last days. —James 5:3Hymn: BodyHymn: of a Mother's surprises and the capture of capitals, are the events of a by-gone age. D'-'s SongsHymn, Sung at the of the Society, Salem. April 21, 1871of History Unlearnedof The GentilesTo a CloudThe Child's Dream of Reaching the 's of WinterInterpreting God's of MayOn the of the Christian Church, The Catholic, the Protestant, and the GreekO'Clock Bell"Are there Few that be Saved? " Luke 13:23the from Cook's Hill, in West PeabodySigns in the Natural WorldA Walk in Harmony Groveof Jabezof the FlowerDanvers Burying-GroundHymn ("He loveth not! he knows not God! ")Norman's RocksOn visiting the beautiful estate of H. H. Hunnewell, Esq. , at Wellesleyof a little child shall lead them. Isaiah XI. 6of RainOn the front of the house of the late Capt. Robert W. GouldOctober ("How beautiful the sight of woods still fair")Builders: the work of the late J. W. FosterBlessed are they that mourn: for they shall be comfortedThere shall be one Flock, one Shepherdof Salem: Illustrated by George M. WhiteColumbines and Anemonesin WinterReverenceInward PhenomenaTo the Memory of of the a Lichen from North Cape: Gathered by Mr. J. M.

Output: pass


Input: Claim: Private companies are increasingly involved in space exploration, contributing to a new space race. [SEP] Text: Login to your account Forgot password? Keep me logged in password must have 8 characters or more and contain 3 of the following: a lower case character, an upper case character, a special character or a digit password has been changed Create a new account user Can't sign in? Forgot your password? Enter your email address below and we will send you the reset instructions If the address matches an existing account you will receive an email with instructions to reset your password. Username Can't sign in? Forgot your username? Enter your email address below and we will send you your username If the address matches an existing account you will receive an email with instructions to retrieve your username This JournalAnywherein JournalsEnter words phrases DOI ISBN keywords authors etcSearchSearchanywhereEnter words phrases DOI ISBN keywords authors etc0 & Life Sciences& PolicyMedicineTechnology & Engineering CollectionPublications by TypeJournals (Print/Online)Journals (Open Access)Journals (Video)Books/eto ZTopicsRecommend a Title to. 8, No. 1 Research 10. 1089/space. 2019. 0020 Permissions & 4. 0 for a in Europe,” expressed their commitment to foster entrepreneurship, stimulate new business opportunities, and boost investment as part of their objective to support a globally competitive and innovative European space sector. To facilitate the emergence of a dynamic entrepreneurial ecosystem backed by investors for the benefit of both public and private European stakeholders, it is essential that the different actors involved share a common understanding of the state of affairs based on tangible indicators. Although this issue has been thoroughly investigated in the United States, assessments from a European perspective have so far been limited. In an attempt to fill this gap, the (ESPI) conducted a study with the objective to collect and consolidate relevant data and information to (1) evaluate private investment in European space start-ups and (2) examine entrepreneurship trends in the European space sector in comparison to trends observed in other sectors. This 2. 7 trillion in 30 years. 2 Several factors are raising the interest of financial markets in the space sector. Among others (Fig. 1):Fig. 1. Key trends driving the sectorial dynamic. •Entry of high profile companies and entrepreneurs. •Strong innovation dynamic with drastically new concepts. •Lower entry costs and quicker time to market (launch services, miniaturized systems, COTS, etc. ).

Output: corroborate


Input: Claim: Gene drives can fully eliminate any pest species within one generation. [SEP] Text: , 2002), disrupting existing genes (Burt, 2003), or suppressing populations, RNA-guided gene drives will also be capable of replacing existing sequences with altered versions that have been recoded to remove the sites targeted by the drive (Figure 3). We hypothesize that the unique ability of RNA-guided gene drives to target any gene may allow them to control the effects of other gene drives or transgenes. Reversibility RNA-guided gene drives could reverse genome alterations that have already spread through populations. Suppose a given gene drive causes unexpected side-effects or is released without public consent. A ‘reversal’ drive released later could overwrite one or all genomic changes spread by the first drive (Figure 5A). The new sequence spread by the reversal drive must also be recoded relative to the original to keep the first drive from cutting it, but any amino acid changes introduced by the first drive could be undone. If necessary, a third drive could restore the exact wild-type sequence, leaving only the guide RNAs and the gene encoding Cas9 as signatures of past editing (Figure 5B). Figure 5 Download asset Open asset Methods of reversing, preventing, and controlling the spread and effects of gene drives. (A) Reversal drives could correct or reverse genomic alterations made by an earlier drive with unexpected side effects. They might also be used to reverse conventionally engineered or evolved changes. Immunization drives could prevent other gene drives from affecting a specific population or provide a population with resistance to DNA viruses. Precision drives could exclusively spread through a subpopulation with a unique gene or sequence. (B) Together, these can quickly halt an unwanted drive and eventually restore the sequence to the original wild-type save for the residual Cas9 and guide RNAs. (C) Any population with limited gene flow can be given a unique sequence by releasing drives A and B in quick succession. So long as drive A does not escape into other populations before it is completely replaced by drive B, subsequent precision drives can target population B without risking spread into other populations. The ability to update or reverse genomic alterations at the speed of a drive, not just a drive-resistant allele, represents an extremely important safety feature. Reversal drives could also remove conventionally inserted transgenes that entered wild populations by cross-breeding or natural mutations that spread in response to human-induced selective pressures.

Output: contrast


Input: Claim: Owls can see in complete darkness due to their magical abilities. [SEP] Text: Richards, July 3d, 1874For we Walk by Faith, not by SightOn the Neglect of ("Love builds for us a bower"). Felton, Esq. , of BrookfieldOn the Increase of Crime since the of ManSailing on Cakes of Ice in the North River("Not unto men alone has come")of the First ChristiansOn the in New Grenadain Bloomthe Graves of Hawthorne and Thoreauthe Falls of Niagara, as Photographed by George BarkerKnowledge and TruthMt. Shasta: A Painting, by H. O. YoungSong: I Love the LightUs of Time and its DurationTake ye heed, watch and pray: for ye know not when the time is. Mark 13:33in PeabodyMan's Need of a Spiritual BirthOn some Eternals from a friend's gardenHymn: of the Righteous"Tuesday night, the schooner Weaver, of Glen Creek, N. J. , went to pieces near Sandy Hook, and her entire crew were lost": Transcript, March 22dof the at PhiladelphiaEvolutionCapt. Samuel CookOn the Beautiful Roses, In front of the Mansion of John Hodges, Esq. waiting at the Pasture GateSong: DayOn some blue and golden Columbines from Pike's Peak, ColoradoDesert of : at Seathe Reconciling Powera Day of FreedomHymn: Reflections at the Close of the Yearthe Clock Strike, in Harmony GroveThe Indians' Belief in a a Visible ObjectLove that Casts out FearMarks on our HillsState of the Wicked and its DurationFaith in the Resurrection ConfirmedSpring and Summer Flowersof the ColumbineMan's AccountabilityHymn: of of by MobsThe Barberry-? Know Thyself: Suggested by hearing Dr. A. E. Miller's Lectures on the "Agriculture the Source of Individual and National Prosperity"—Anne PrattPleasure ("With business haste, or with a worldly mind").

Output: pass