Input: Claim: CRISPR technology allows scientists to make precise changes to DNA sequences. [SEP] Text: (2017) used “co-” methods to target exon 4 of ATP1A1 concurrently with a second locus of interest in established human cell lines. By selecting ATP1A1 mutations using ouabain, the percentage of cells harboring an INDEL at the second locus increased (Agudelo et al. , 2017). However, the co-strategy was not applied to human iPSCs and in the cell lines that were tested the HDR rate was not significantly improved. Here, we report the use of a -Cas9 editing system that targets intron 4 of ATP1A1 in human iPSCs. By introducing a repair template to substitute the two N-terminal amino acids Q118 and N129, we specifically created an HDR-directed mutation that confers resistance to cardiac glycosides. We then applied different types of repair templates to investigate the efficiency of HDR. Furthermore, by co-targeting with the second locus of interest, we examined the efficiency of HDR-directed mutation after selection with the cardiac glycoside digoxin. Materials & ofCas9 plasmids and donor templates guide RNAs were designed obeying the sequence rule. The construction of plasmids followed the protocol established by Ran et al. (2013). To generate construct targeting ATP1A1, a guide sequence (5′--3′) was cloned into PX459 pSpCas9(BB)-2A-Puro plasmid following the fast digest protocol (Ran et al. , 2013). The gRNAs targeting the other locus were cloned in to PX459 via the same procedure and the sequences of gRNAs were listed as below: (DGUOK exon1: 5′--3′; DGUOK exon4: 5′--3′; POLG exon10: 5′--3′; GATA6 exon4: 5′--3′; RYR2B exon50: 5′--3′). Single-stranded oligodeoxynucleotides (ssODNs) were obtained as Ultramer® DNA oligonucleotides (). Designed double-stranded DNAs were generated through GeneArt™ synthesis with the addition of restriction enzyme cutting sequences at both ends ().

Output: corroborate


Input: Claim: Cryptocurrencies are entirely anonymous, providing complete privacy for users. [SEP] Text: , an indication that reading the information is socially desirable), or the default selection of the choice (e. g. , button “more information” is pre-selected). However, it remains unclear whether nudging users to, e. g. , click on a button labeled “more information” actually leads to users engaging with the text behind the button or rather to frustration that the privacy decision is delayed. Thus, nudges in this regard should be designed carefully with a focus on the effort for the user and evaluated in future work. Reflecting on the decision: As outlined above, designing nudges that target reflection on the decision is a challenging task as the original definition of the nudge includes targeting automatic cognitive processes instead of reflective cognitive processes. In the context of information disclosure, some studies successfully tested nudges that made users aware of and potentially reflect on the consequences of their choices. For example, Wang et al. [52, 53] confronted users with visual reminders of the audience of their social media post to prevent them from disclosures they might regret later. Harbach et al. [24] made users aware of the potential consequences of the app permissions granted. For example, if an app had been granted access to the user’s photos, the user was shown a random photo stored on their phone along with the message that the specific app had access to this photo. A common password nudge is a so-called password meter [17, 51, 56]. It often takes the form of a bar that dynamically provides visual and textual feedback on the strength of the currently selected password. It is supposed to nudge users to increase password strength and close potential gaps between user’s security perception and technical security requirements. This type of nudge can be classified as a transparent Type 2 nudge as it is not only easily visible for the user but also triggers reflective processes. For example, users might ask themselves why their password score is low and try to enhance their score so that the bar fills and changes its color from red to green. Thereby, users might reflect on the changes they made to their password. Similar feedback meters have already been applied to other authentication mechanisms such as pattern unlock [46] and might also be helpful for supporting informed privacy decisions. For example, users might receive feedback on the “privacy score” of their selected option that might trigger them to rethink their choice and to try different options to see how the score changes.

Output: contrast


Input: Claim: Reinforcement learning algorithms mimic the way humans learn through rewards and punishments. [SEP] Text: Lettice YardThe good-night or a MaidUpon a Lady that dyed in child-bed, and left a daughter behind herA New-yeares gift sent to StewardMattens, or morning PrayerEvensongto JuliaMilitantA short Hymne to LarrAnother to NeptuneUpon Greedy. EpigHis embalming to JuliaGold, before GoodnesseThe Kisse. A DialogueThe admonitionTo his honoured kinsman Soame. EpigOn himselfeTo LarrThe departure of the good DæmonClemencyHis age, dedicated to his peculiar friend, M. John Wickes, under the name of PosthumusA short hymne to VenusTo a Gentlewoman on just dealingThe hand and tongueUpon a delaying LadyTo the Villars, Governesse to the Princesse HenrettaUpon his JuliaTo FlowersTo my ill ReaderThe power in the peopleA Hymne to Venus, and CupidOn Julia's her AlmesRewardsNothing newThe RainbowThe meddow verse or Aniversary to LowmanThe parting verse, the feast there endedUpon Judith. EpigLong and lazieUpon Ralph. EpigTo the right honourable, Philip, Earle of Pembroke, and MontgomerieAn hymne to JunoUpon Mease. EpigUpon Sapho, sweetly playing, and sweetly singinga DraperChop-CherryTo the most learned, wise, and Arch-Antiquary, M. John SeldenUpon himselfUpon wrinklesUpon PriggUpon MoonPray and prosperHis Lachrimæ or Mirth, turn'd to mourningUpon ShiftUpon CutsGain and GettingsTo the most fair and lovely Mistris, Anne Soame, now Lady AbdieUpon his kinswoman HerrickA Panegerick to PembertonTo his Valentine, on S. Valentines dayUpon Doll. EpigUpon Skrew. EpigUpon Linnit. EpigUpon M. Ben Johnson. EpigAnotherTo his Nephew, to be prosperous in his art of PaintingUpon Glasse. EpigA Vow to MarsTo his maid PrewA Canticle to ApolloA just manUpon a hoarse singeror Hearts-ease came firstTo his peculiar friend 's portion, and the Poets partUpon ManLibertyLots to be likedGriefesUpon Eeles.

Output: pass


Input: Claim: CRISPR technology allows scientists to make precise changes to DNA sequences. [SEP] Text: In order to generate the amino-acid substitution allele, we designed a 153 single-stranded oligodeoxynucleotides (ssODN) with the sequences that replace glutamine with arginine at position 118 and asparagine with aspartic acid at position 129 (Fig. 1A). After transfecting both sp-Cas9-gRNA (px459-ATP1A1-intron4) and donor template into the cells and treating these cells with a high dose of digoxin, we collected the surviving clones for genotyping (Fig. 1B). Using primers outside the targeted homology arms to perform PCR (out-out PCR) and restriction fragment length polymorphism (RFLP) analysis, we observed that all the cells that were resistant to digoxin or ouabain were successfully repaired through HDR, and both heterozygous and homozygous mutations were identified (Fig. 2A). The genotype was confirmed by genomic sequencing. In order to determine the optimum dosage of digoxin and ouabain, we performed a dose–response assay of both drugs on wild-type and ATP1A1 homozygous mutant iPSCs. We effectively eliminated all wild-type iPSCs at 1 µM after 72 h of exposure. In contrast to the parental iPSCs, homozygous ATP1A1 mutant iPSCs survived in the presence of either drug and were indistinguishable from untreated cells (Figs. 2B–2F). These results demonstrate that cardiac glycosides can be used to effectively identify HDR-driven mutations at the endogenous ATP1A1 locus. Figure 1: Design ofCas9 targeting ATP1A1. (A) The design of ATP1A1 guide RNA and single-stranded oligonucleotide (ssODN) donor. Guide RNA was designed to target intron 4 of the ATP1A1 gene. The expected cut site is 3–4′ nucleotides upstream of the Motif (PAM) sequence and 20 nucleotides downstream of the exon 4 region. The donor template was designed to introduce nucleotide substitutions that result in the replacement of Glutamine with Arginine (Q118R) and Asparagine with Aspartic acid (N129D). The EcoRI cut site was introduced to allow identification of positive clones.

Output: corroborate


Input: Claim: Cryptocurrencies are entirely anonymous, providing complete privacy for users. [SEP] Text: Increasing Users’ in the Internet of Things: Download book PDF Download book 4,5 & Florian Alt6 2255 Accesses AbstractAn increasing number of devices and sensors in the environments we access daily are capable of collecting personal data about us. Surveillance cameras in public spaces, smart speakers in friends’ living rooms, or smartphones carried by individuals are just a few examples. At the same time, many users are unaware of sensors being in place, in particular, those deployed in unfamiliar environments. Hence, it becomes increasingly challenging for users to keep control over their personal data being tracked and/or processed. Crucially, for users to be able to make informed decisions and privacy choices, they first of all need to be aware of potential privacy intrusions in their surroundings. In this 2. 1) and current mechanisms aiming at increasing users’ privacy awareness (Sect. 2. 2). 2. 1 Privacy ChallengesPrivacy, which is individual control over when, where, and how personal data are being collected and shared [13], becomes increasingly challenging as sensing and computing technologies are seamlessly integrated into our daily lives [57]. The number of devices capable of collecting personal data is steadily rising, and sensing technology is placed in both private and public places. The variety of devices is huge. For instance, smart vacuum cleaning robots scan floor maps of our homes to operate;Footnote 1 smart fridges reorder groceries; smart electricity meters monitor energy consumption and can thus infer users’ activities [48]; smart voice assistants listen to our conversations [35]; cameras record and analyze semi-public and public spaces for security purposes; smart door locks provide access to homes or offices via biometric features [42]. Also, devices come with various functionality and data collection capabilities, with different impacts on users’ privacy. For instance, conversations—as potentially captured by a smart speaker—might be, from a privacy perspective, of different values as compared to grocery orders by a smart fridge. As a consequence, it is hard for users to correctly assess the privacy implications of specific devices, even if they have a general understanding of the technology [39]. Moreover, IoT devices are usually shared among multiple users, and the ecosystem of stakeholders is complex [23, 27, 61]. It not only includes device owners as those who set up and primarily use devices, but also secondary users such as, e. g.

Output: contrast


Input: Claim: Reinforcement learning algorithms mimic the way humans learn through rewards and punishments. [SEP] Text: a Spectacle-maker with a flat noseClothes do but cheat and cousen usTo DianemeUpon ElectraTo his BookeOf LoveUpon himselfAnotherUpon Skinns. EpigUpon Pievish. Epigand Jilly, EpigThe mad Maids songand FountainsUpon Julia's unlacing her selfTo Bacchus, a a footman, EpigUpon Bridget. EpigTo SycamoresA Pastorall sung to the King; Montano, Silvio, and Mirtillo, Shepheardsloves a Mistresse, but not to marryUpon Flimsey. EpigUpon Shewbread. to CrewUpon Roots. quick of flightPutrefactionPassionJack and JillBeanesThe crowd and companyShort and long both likesPollicie in PrincesUpon Rook, EpigUpon the Nipples of Julia's BreastTo Daisies, not to shut so sooneTo the little SpinnersOberons PalaceTo his peculiar friend in the TempleTo OenoneHis weakness in woesFame makes us forwardTo Grovesupon a VirginTo the right gratious Prince, Lodwick, Duke of Richmond and LenoxTo JealousieTo live FreelyUpon Spunge. EpigHis AlmesUpon himselfTo enjoy the TimeUpon LoveTo the right Honourable Mildmay, Earle of WestmorlandThe PlunderLittlenesse no cause of LeannesseUpon one who said she was always youngUpon Huncks. EpigRing, or True-love-knotThe parting Verse, or charge to his supposed Wife when he travelledTo his Kinsman, Sir Tho. SoameTo BlossomsMans dying-place uncertainNothing Free-costFew fortunateTo PerennaTo the LadyesThe old Wives PrayerUpon a cheap Laundresse. EpigUpon his departure henceThe WassaileUpon a Lady faire, but fruitlessecame firstand BaiesUpon SkurffeUpon a Scarre in a Virgins FaceUpon his eye-sight failing himTo his worthy Friend, M. Tho.

Output: pass


Input: Claim: CRISPR technology allows scientists to make precise changes to DNA sequences. [SEP] Text: 9060/fig-2 Comparing the HDR efficiency while using different repair templates Although single-stranded oligodeoxynucleotides (ssODNs) have commonly been used as repair donor templates, the efficiency is generally low when using iPSCs (Radecke et al. , 2010; Yoshimi et al. , 2016). Double-strand DNAs with long homologous arms have been shown to improve the efficiency of introducing changes through genome editing in HEK293T cells (Song & Stieger, 2017). We therefore proposed to compare the efficiency of HDR-mediated mutagenesis between ssODNs and dsDNA at the ATP1A1 locus using endogenous selection. We co-transfected human iPSCs with px459-ATP1a1-intron4 and donor template presented in the following formats: ssODNs, dsDNAs, or dsDNAs cloned into a plasmid. HDR-positive clones were then selected using a 72-hour exposure of 1 µM digoxin (Fig. 3A). As shown in Fig. 3B, up to two positive clones were observed when co-transfected with 150 base-pair (bp) template either as ssODN, dsDNA, or linearized plasmid (Fig. 3B). Strikingly, when cells were co-transfected with 400 bp template either as dsDNA or linearized plasmid, the surviving colonies increased 11-fold and 35-fold, respectively when compared to transfection using 150 bp donors. These results indicate that double-stranded repair templates with ≥400 bp length have a higher efficiency of generating HDR-positive cells. Moreover, assembling the dsDNA into a plasmid vector improved the effectiveness by a further ∼3-fold (Fig. 3B). Figure 3: Provision of long HA dsDNA donor template during gene editing increases HDR-mediated mutagenesis. (A) Diagram of approach used to edit ATP1A1 using different donor templates. 1 × 107 of human iPSCs were transfected with PX459 containing guide RNAs which target intron 4 via electroporation. Cells were also transfected with 0. 01 nmole of ssODN, dsDNA, and linearized donor plasmid, respectively.

Output: corroborate


Input: Claim: Cryptocurrencies are entirely anonymous, providing complete privacy for users. [SEP] Text: , co-inhabitants of a smart home [9, 23, 24, 34], guests in a rental apartment [9, 38, 40], or passers-by in semi-public and public spaces [9, 46]. Manufacturers of devices, as well as providers of single services, are also relevant parties. This makes it unclear as to who is responsible for even providing privacy-relevant information and to whom. Lastly, it is unclear what information is relevant to users in which context, for them to be able to make informed privacy decisions. 2. 2 MechanismsAn increasing number of devices in our environments are capable of collecting personal data about us with built-in sensors. This may happen inconspicuously and without direct interaction [9]. Even worse, users are oftentimes unaware of this, let alone the privacy implications of this data collection [3, 9, 34, 62]. Users, however, want to be informed about data being collected about them and shared with device providers [18, 28, 43, 52]. Moreover, awareness of privacy implications is a prerequisite for users to be able and preserve their privacy, and to decide with whom they are willing to share their personal data [9, 40, 41]. As such, there is a need to design suitable mechanisms that help increase privacy awareness [52, 58] among all affected individuals [9, 60]. Prior work suggested mechanisms that provide general privacy information (to, e. g. , support purchase decisions) and information on installed devices (i. e. , that are already in use and collecting data). 2. 2. 1 InformationPrior to data collection, providers of devices and services must provide privacy-relevant information. The default approach to this is privacy notices [11, 21], a textual description of which data are collected and how it is processed. These policies, however, tend to be long, are hard to understand for users, and thus are oftentimes not read thoroughly [56]. Research tried to address this challenge and make privacy-relevant information more accessible to users, to ultimately increase their awareness. Ebert et al. found that more concise and salient privacy notices can successfully increase users’ privacy awareness [15]. Others suggested ways to make privacy policies more appealing and understandable. Polisis is a framework for automated analysis of privacy policies, to, e. g. , assign icons [25].

Output: contrast


Input: Claim: Reinforcement learning algorithms mimic the way humans learn through rewards and punishments. [SEP] Text: FalconbirgeUpon Julia's haire fill'd with DewAnother on herLosse from the leastRewards and punishmentsShame, no himselfeand CreamAn Ecologue, or Pastorall between set and sungTo a Bed of TulipsA CautionTo the Water Nymphs, drinking at the FountainTo his a Flieand Jill. he would drinke his Winecame yellowThe broken ChristallPreceptsTo the right Earle of DorsetUpon himselfHope well and Have well: or, Faire after Foule weatherUpon LoveTo his Kinswoman, Mrs. Penelope WheelerAnother upon herKissing and BussingCrosse and PileTo the Lady Crew, upon the death of her ChildHis Winding-sheetMary WillandChange gives contenta frequenter of OrdinariesOn himselfeFortune favoursto love, and live with himTo his her cheeksUpon her EyesUpon her feetTo his honoured friend, MyntsUpon his gray hairesAccusationPride allowable in PoetsA Vow to MinervaOn JoneUpon Letcher. not disadvantageousthe Flaminica Dialis, or Queen-PriestAnacreontikeMeat without mirthdoe but bury usUpon Ursleyto CrewTo his worthy Kinsman, Mr. Stephen SoameTo his Tomb-makersuperviveNone free from faultUpon himselfe being buriedPitie to the prostrateWay in a crowdHis content in the CountryThe credit of the ConquerorOn himselfeUpon one-ey'd Broomsted. EpigThe FairiesTo his honoured friend, M. have their Linings, and Bookes their BuckramArt above Nature, to JuliaUpon SibillaUpon his kinswoman a comely, and curious MaideUpon the losse of his FingerUpon IreneUpon Electra's TearesUpon ToolyA Hymne to the GracesTo SilviaUpon Blanch. EpigUpon Umber. Epighath lost his pipeTrue Friendshipof his Mistresse calling him to EliziumLife is the Bodies LightUpon Urles. EpigUpon FranckLove lightly pleasedThe PrimroseThe Tythe.

Output: pass


Input: Claim: CRISPR technology allows scientists to make precise changes to DNA sequences. [SEP] Text: 7717/peerj. 9060/fig-4 HDR-driven event varies between genomic location To determine if the co-selection for the ATP1A1Q118R/N129D increases efficiency across different loci, we tested the same approach at other genes of interest, including RYR2, GATA6, and POLG, all of which are located on different chromosomes. We also targeted the DGUOK gene at a different independent locus. Each gene was targeted individually or along with ATP1A1. Transfected cells with or without digoxin selection were collected for out-out PCR, and INDEL-HDR rates were determined using TIDE/TIDER analysis. As shown in Table 1, the INDEL rates without digoxin selection ranged from 1. 3% to 45. 6%, which is likely due to different inherent guide targeting efficiencies. After digoxin selection, INDEL efficiency significantly increased among all targeted loci (Table 1). HDR rates remained low without digoxin selection, ranging from 0 to 4. 18%. After digoxin treatment, the cells showed an increase of HDR at both DGUOK regions; however, this increase was not observed at the other targeted loci (Table 1) presumably due to the excessively low efficiency of HDR at these specific sites. In summary, the results indicate that the ATP1A1 co-targeting approach successfully selected targeted cells, and although HDR efficiency increases, the rate remains variable between loci. Table 1: The population of HDR and INDEL-mediated mutagenesis after co-targeting ATP1A1 and a second locus of interest. Five different loci were targeted by -Cas9 in human iPSCs along with two linear repair templates (ATP1A1 and a second locus of interest). After transfection cells were cultured in the presence or absence of digoxin selection, cells were collected and sequenced for TIDE(R) analysis. The percent population of INDELs and HDR events are shown. (−) Digoxin (+) Digoxin (−) Digoxin (+) DGUOK_EX1 2 16. 53% 43. 10% 0% 10. 85% DGUOK_EX4 2 11. 76% 39. 03% 4. 18% 13. 23% RYR2_EX50 1 12. 40% 43. 53% 1. 35% 3.

Output: corroborate


Input: Claim: Cryptocurrencies are entirely anonymous, providing complete privacy for users. [SEP] Text: 1 Contextual FactorsIndividual privacy perceptions and (dis)comfort with personal data being recorded are highly impacted by contextual factors, as highlighted in our previous work [46]: and Trust:: Users consider trust and relationships when deciding with whom to share their personal data [19, 36, 59, 60]. For instance, users rely on friends’ opinions regarding data sharing [19] and consider who is collecting their data [36] as well as who is the owner of a particular device [40]. Environment:: Also, users’ current environment impacts their concerns. As such, data collection in private spaces (e. g. , the home) is less acceptable as compared to data collection in other spaces, such as restaurants (semi-public) or public spaces [18, 37]. It is also important to users whether they are familiar with the environment [46]. In unfamiliar settings, users are particularly concerned about (hidden) data collection, especially when they consider the space private at the same time, as is the case for, e. g. , rental apartments [38, 46, 51]. 3. 2 Privacy-Relevant InformationPrivacy-relevant information can comprise various content and be made available to users in various ways. 3. 2. 1 ContentDepending on users’ current context, various information could become relevant for users to decide whether or not they are willing to share their personal data: Type of Sensor(s):: The type of sensors—and, respectively, the type of data being collected—impacts users’ privacy perceptions. For instance, cameras and microphones (i. e. , video and audio recordings) are usually considered particularly sensitive [32]. Tracking Space:: The area of data collection can further help users assess privacy intrusions, particularly bystanders who are not familiar with the space devices are in [9]. Device Owner:: The relationship to the device owner crucially impacts users’ willingness to be recorded by devices [9, 19, 36, 41, 59, 60]. For instance, users are more comfortable with devices being placed in trusted environments (e. g. , in friends’ homes) [39, 40, 46] as compared to devices being installed by (unknown) hosts of rental apartments [9, 38]. Purpose:: Users are more likely to accept data collection if it suits their own needs and purpose. For instance, for health-related purposes, even long-term data tracking is acceptable [5].

Output: contrast


Input: Claim: Reinforcement learning algorithms mimic the way humans learn through rewards and punishments. [SEP] Text: To the BrideA FrolickChange common to allTo JuliaNo luck in LoveIn the darke none daintyA charme, or an allay for LoveUpon a free Maid, with a foule breathUpon Coone. EpigTo his Brother in -akeOn himselfeUpon a MaideUpon Spalta Comb-makerUpon the troublesome timesCruelty base in CommandersUpon a sowre-breath Lady. EpigUpon LuciaLittle and loudShip-wrackPaines without profitTo his Booketo Ben. JohnsonPoverty and RichesAgainstill his MuseThe bad season makes the Poet sadTo VulcanLike Pattern, like PeoplePurposesTo the Maids to walke abroadHis own EpitaphA to Lee, now Lady TracieThe Night-piece, to not lastingA KisseGloriePoetsNo despight to the deadTo his VersesHis charge to Julia at his death. EpigUpon Snare, an UsurerUpon GrudgingsConnubii Flores, or the well-wishes at WeddingsTo his lovely MistressesUpon LoveUpon Gander. EpigUpon Lungs. Epigto Mab, the Fairie QueenAn end decreedUpon a childPainting sometimes permittedFarewell Frost, or welcome the SpringThe HagUpon an old man a æ to ParentsUpon Cob. EpigUpon Lucie. EpigUpon Skoles. EpigTo SilviaTo his Closet-GodsA Bacchanalian VerseLong lookt for comes at lastTo YouthNever too late to dyeA Hymne to the MusesOn himselfeand life, to the honoured M. End. Porter, Groome of the Bed-Chamber to His Maj. To ElectraTo his worthy friend, M. Arthur BartlyWhat kind of Mistresse he would haveUpon Zelotbranchæticall, or Advisive Verse, to his friend, M. John WicksOnce seen, and no moreLoveTo M. Denham, on his Prospective PoemA Hymne, to the LaresDeniall in women no disheartning to menhis VersesDistance betters DignitiesHealthTo Dianeme.

Output: pass


Input: Claim: CRISPR technology allows scientists to make precise changes to DNA sequences. [SEP] Text: 13% GATA6_EX4 18 45. 60% 81. 80% 0. 40% 0% PolG_EX10 15 1. 38% 25. 33% 0% 0% DOI: 10. 7717/peerj. 9060/table-1 the present study, we used -Cas9 to edit the ATP1A1 locus in human iPSCs. The introduced mutations inhibited the binding of cardiac glycosides, thus conferring resistance to high dosage of this class of drug. More importantly, we were able to obtain genomic-modified clones that were specifically repaired by HDR after ouabain and digoxin selection. We showed that using 400 bp dsDNA as the repair template increased HDR efficiency compared to 150 bp ssODNs, while delivering the template in a linearized plasmid further improved HDR rates. Moreover, by co-targeting ATP1A1 with a second locus of interest, we were able to increase both INDEL and HDR selection efficiency in two different iPSC lines. Although HDR-driven events varied between genomic loci, the overall efficiency of selecting genetically-modified clones increased. The optimization of the genome-editing strategy in human iPSCs provided by this study will pave the way for future disease modeling and gene therapy research. Optimizing repair templates to obtain increased HDR-driven mutations after double-strand breaks has been well studied (Baker et al. , 2017; Song & Stieger, 2017; Zhang et al. , 2017). Due to difficulties in generating ssODNs longer than 200 bp, researchers have used single strand DNA with 30–70 base homology arms (HA) as donor template for small edits (Ran et al. , 2013; Richardson et al. , 2016; Yang et al. , 2013). The dsDNAs are generally used as the repair templates for fragment insertions (Byrne et al. , 2015; Urnov et al. , 2005). In human iPSCs, the optimal HA length is reported to be ∼2 kb (Byrne et al. , 2015). Our study tested the efficiency of ssODN, dsDNA and linearized plasmid for -based genomic editing through HDR. We found that homology arms that are less than 200 bp showed no significant difference between all three forms of donor DNA.

Output: corroborate


Input: Claim: Cryptocurrencies are entirely anonymous, providing complete privacy for users. [SEP] Text: This particularly holds true for personal physiological data [45]. In contrast, video and audio recordings are less acceptable, regardless of the purpose [37]. 3. 2. 2 Availability and OutputThe privacy-relevant information could be made available to users in various ways. For instance, information could be provided in relation to the environment, e. g. , on a personal device such as a smartphone or tablet [50], or using contextual images [51]. Another opportunity is to provide information only on specific devices similar to, e. g. , the privacy labels [17, 30]. Accordingly, privacy-relevant information is available at different times. For instance, information that is bound to the device’s packaging [17, 30] is available to support purchase decisions. Hence, users would need to actively search for and inform themselves about devices to receive this information. Information that is provided independently on a personal device, however, would be always available to users as they are moving around. Lastly, privacy mechanisms can act in various degrees of proactivity (e. g. , low, medium, high in the context of smart homes [29]). Privacy-relevant information could thus be provided actively, e. g. , through push notifications on personal devices, e. g. , when entering an unfamiliar area with data collection being in place. 4 Sample ScenariosTo further emphasize the relevance of increasing privacy awareness in the IoT, we illustrate three concrete scenarios in the following, along with sample applications. In particular, privacy awareness can and should be increased, in various ways, in the following cases: (1) supporting decisions for purchasing IoT devices with privacy-relevant information (PriCheck [55]); (2) allowing users to consult privacy-relevant information on demand (e. g. , using their mobile phones, PriView (mobile) [46]); (3) providing privacy-relevant information and guidance within the environment (e. g. , by means of augmented reality, PriView (HMD) [46]). For an overview of relevant design space dimensions per scenario, refer to Table 1. Table 1 Scenarios vs. Design Space: We see several scenarios in which privacy-relevant information is needed (left, Sect. 4), and how the design space dimensions would come into play in each scenario (right, Sect. 3)Full size table4.

Output: contrast


Input: Claim: Reinforcement learning algorithms mimic the way humans learn through rewards and punishments. [SEP] Text: A Ceremonie in GlocesterTo the KingRites of the RoseThe Rainbow: or curious CovenantThe last stroke strike sureFortuneStool-ballof BeggarsThe May-poleMen mind no state in sicknesseAdversityWantGriefeLove palpableNo action hard to affectionMeane things overcome mightyof Pearle: to Silviacame redKingsFirst work, and then wagesTeares, and LaughterGloryPossessionsLaxare fibulamHis returne to LondonNot every day fit for VersePoverty the greatest packA Beucolick, or discourse of NeatherdsTrue safetyA PrognostickUpon Julia's sweatProof to no purposeFameBy use comes easinesseTo the Genius of his houseHis Grange, or private wealthGood precepts, or counsellMoney makes the mirthUp tailes allUpon Franckdabbled in the deawCharon and Phylomel, a Dialogue sungUpon Paul. EpigrUpon Sibb. EpigrA Ternarie of littles, upon a pipkin of Jellie sent to a LadyUpon the Roses in Julias bosomeMaids nay's are nothingThe smell of the SacrificeLovers how they come and partTo women, to hide their teeth, if they be rotten or rustyIn praise of womenof Flowersof Julias teethUpon her weepingAnother upon her weepingof ExeterTo Electra. Love looks for LoveRegression spoiles ResolutionContentionConsultationLove dislikes nothingOur own sinnes unseenNo Paines, no GainesUpon SlouchVertue best unitedThe eyeCharles upon his coming to ExeterA SongPrinces and FavouritesExamples, or like Prince, like -pennyAlablasterUpon his Kinswoman Mrs. M. S. Felicitie knowes no FenceDeath ends all woeA Conjuration, to ElectraCourage cool'dThe SpellHis wish to privacieA good HusbandA Hymne to Bacchusand her Prentice.

Output: pass


Input: Claim: CRISPR technology allows scientists to make precise changes to DNA sequences. [SEP] Text: Easy quantification of template-directedCas9 editing. Research 46:e58. 2015. Crispr-mediated gene targeting of human induced pluripotent stem cells. in Biology 35:5A. 8. 1-5A. 8. 22. 2015. Multi-kilobase homozygous targeted gene replacement in human induced pluripotent stem cells. Research 43:e21 Chen YH, Pruett-Miller SM. 2018. Improving single-cell cloning workflow for gene editing in human pluripotent stem cells. Research 31:186-192 Chen F, Pruett-. 2011. High-frequency genome editing using ssDNA oligonucleotides with zinc-finger nucleases. 8:753-755. 2015. Increasing the efficiency of homology-directed repair for -Cas9-induced precise gene editing in mammalian cells. 33:543-548. 2019. iPSC-derived hepatocytes as a platform for disease modeling and drug discovery. Frontiers in Medicine 6:265. 2017. Refining strategies to translate genome editing to the clinic. 23:415-423. 2018. Gene therapy for neurological disorders: progress and prospects. 17(9):641-659 El-. 2019. Cardiac glycosides in human physiology and disease: update for entomologists. Insects 10(4):102. 2013. High-frequency off-target mutagenesis induced by -Cas nucleases in human cells. 31:822-826 3rd CF. 2013. andCas-based methods for genome engineering. Trends in Biotechnology 31:397-405. 2014. An iplatform for rapid. multiplexable, and inducible genome editing in human pluripotent stem cells. Cell 15:215-226 Guo Q, Mintier G, Ma-. 2018. ‘Cold shock’ increases the frequency of homology directed repair gene editing in induced pluripotent stem cells. 8:2080. 2013. DNA targeting specificity of RNA-guided Cas9 nucleases. 31:827-832 -. 2018. p53 inhibits -Cas9 engineering in human pluripotent stem cells. 24:939-946. 2018. A screen using iPSC-derived hepatocytes reveals NAD(+) as a potential treatment for mtDNA depletion syndrome. 25:1469-1484 e1465 Johnson RD, Jasin M. 2001.

Output: corroborate


Input: Claim: Cryptocurrencies are entirely anonymous, providing complete privacy for users. [SEP] Text: Figure from [46]Full size image Privacy-on Demand with PriView (mobile) To summarize, PriView (mobile) [46] supports users as follows: Context active device search, scanning the (unfamiliar/untrusted) environment Device(s) potentially multiple devices that are already installed and in use User(s) primary users as well as bystanders, potentially unknown device owners Content device position (all visualizations); built-in sensors, textual information (including device owner), tracking space, recording state Availability on-demand, push notifications possible 4. 3 Providing Privacy- SituTo provide users with privacy-relevant information in arbitrary environments, augmented reality (AR) can serve as a means for in situ information and guidance. For instance, PriView employed in a head-mounted display (HMD) provides users with visualizations of potential privacy intrusions within the environment [46]. Similar to the mobile application, it shows: device position (red frame), textual information, tracking space in 3D, a general warning icon, and tracking space on the floor (Fig. 2 right). This can particularly help users in arbitrary environments to increase privacy awareness, particularly when they are new to a place. Participants of our study (N = 21) liked the visualizations being available in situ using the HMD. They wished for more details in spaces they considered private (e. g. , a rental apartment), while simpler indications were sufficient in places where data collection is obvious (e. g. , security cameras at a train station) [46]. Privacy-with PriView (HMD) To summarize, PriView (HMD) [46] supports users as follows: Context information within the (unfamiliar/untrusted) environment Device(s) potentially multiple devices that are already installed and in use User(s) primary users as well as bystanders, potentially unknown device owners Content device position (all visualizations); built-in sensors, textual information (including device owner), tracking space, recording state Availability always-on, push notifications possible 5 Directions for Future ResearchIn the following, we illustrate and discuss interesting directions for future research that arise from privacy awareness challenges and mechanisms within the IoT. 5. 1 Amount of InformationAn interesting question for future research is how much information on IoT devices users will need to make informed privacy decisions. Is a simple device indicator enough to increase awareness, or would users prefer a deeper understanding of data collection and policies?

Output: contrast


Input: Claim: Reinforcement learning algorithms mimic the way humans learn through rewards and punishments. [SEP] Text: EpigBlame the reward of PrincesClemency in KingsAngerA Psalme or Hymne to the Gracesto the MusesUpon Julia's his MaidThe InvitationCeremonies for ChristmasseChristmass-Eve, another CeremonieAnother to the MaidsAnotherPower and PeaceTo his deare of choice, long a comingPoetry perpetuates the a good speaker but an ill singer, EpigAny way for wealthUpon an old WomanUpon Pearch. EpigTo SaphoTo his faithfull friend, Crofts, Cup-bearer to the KingThe Bride-CakeTo be merry-blushThe MeaneHaste hurtfullmy dearest Sister M. Mercie HerrickThe TransfigurationSuffer that thou canst not shiftTo the PassengerUpon NodesTo the his taking of LeicesterTo Julia, in her Dawn, or Day-breakeCounsellpill their PeopleMost Words, less and DrinkeUpon Puchin. EpigTo OenoneUpon Blinks. EpigPeapes. a a Schoolmaster. EpigUpon Peason. EpigTo his BookeReadinesseWritingSocietyUpon a MaidSatisfaction for sufferingsThe delaying BrideTo M. Henry Lawes, the excellent Composer of his LyricksAge unfit for LoveThe Bed-man, or Grave-makerlipsTwilightTo his Friend, Master J. JincksOn himselfeKings and TyrantsCrossesUpon LoveNo difference i' th' darkThe BodyTo SaphoOut of Time, out of TuneTo his BookeTo his Honour'd friend, HealeThe Sacrifice, by way of Discourse betwixt himselfe and to CupidTo ElectraHow his soule came ensnared's haire, bundled up in a golden netUpon TrugginThe showre of BlossomesUpon SpenkeA defence for to bring in the Witchfor StablesCeremonies for Candlemasse Evefor Candlesmasse daydaySurfeitsUpon NisTo Biancha, to bless himJulia's Churching, or PurificationTo his BookTearesTo his friend to avoid contention of wordsTruthUpon Prickles. Epigbefore the EaresWantTo a FriendUpon M. William Lawes, the rare MusitianA song upon SilviaThe Hony-combeUpon Ben.

Output: pass


Input: Claim: CRISPR technology allows scientists to make precise changes to DNA sequences. [SEP] Text: Editing ofDownload book PDF Download book 7 & Goetz Hensel7 4293 Accesses AbstractTargeted mutagenesis usingCas technology has become routine in elucidating biological processes or their application in breeding and agriculture. This means that the change to be achieved can be accurately predicted. However, knockout of a gene function is not always desirable, as reducing activity or affecting a protein domain can influence its properties and, thus, the phenotype. This 1. Applications of precise genome editing in plants have been summarised several times (for review, see [10,11,12]). These reach into all areas of modern plant research. Starting with pure basic research, i. e. , the identification and characterization of genes and their phenotypic expressions, the methods are also used to master the current challenges of agriculture. Here, agronomic parameters play a similarly important role in improving product characteristics. Plants with enhanced resistance to fungal or viral pathogens are being developed and tested. Plants should be better adapted to changing climatic conditions and thus have better water and nutrient utilization. Plants should become heat or drought-tolerant but also be able to grow with an increased salt concentration in the soil. There are examples of all these experiments in barley and/or wheat (Fig. 9. 1). The only publication on applyingCas technology in triticale, a cross between wheat and rye, shows its functionality exclusively in protoplasts [13]. Fig. 9.

Output: corroborate


Input: Claim: Cryptocurrencies are entirely anonymous, providing complete privacy for users. [SEP] Text: Moreover, the preferred amount of information varies depending on the environment [46]. For instance, in environments with multiple devices, including such that are firmly installed as well as such carried by passers-by, there is a high potential for an awareness mechanism to cause visual overload. As such, the amount of information should most likely be reduced, with the opportunity to still receive details on demand. 5. 2 Contextualize and AdaptAs a next step, privacy awareness mechanisms could automatically adapt to the context and/or their users. For instance, different scenarios (cf. Sect. 4) might require different support for users’ privacy awareness. For purchasing a new device to install it within their own environment, users might need awareness as to how it can be configured in a privacy-preserving way. Being in unfamiliar environments with installed devices, however, rather calls for information on spaces being covered by data collection, for users to be able to avoid these as they wish. Also, for scenarios that users encounter more often (e. g. , visiting a certain place), awareness cannot be assumed at first but might increase over time as a mechanism is being used in this scenario. Moreover, an awareness mechanism could also adapt to users’ prior knowledge (e. g. , reduce information that users already received earlier) or technical expertise (e. g. , use simpler versions for lay users, while providing more details for advanced users). 5. 3 Enabling ControlWhile awareness is a prerequisite for users to be able to make informed privacy decisions [9, 40, 41], it is only a first step. In particular, users need to be given means to execute (or: enforce) these decisions on nearby devices. For instance, PARA is an augmented reality interface that provides privacy controls and allows users to filter data being collected about them [6]. Mobile applications, such as, e. g. , the IoT assistant,6 likewise allow users to control nearby devices but require to do so for each and every device or sensor separately, increasing complexity as the number of devices rises. The PriKey tries to tackle this challenge by summarizing privacy decisions per sensor in a tangible device [47]. Personalized privacy assistants [10, 14] can recommend privacy settings or even act autonomously based on users’ privacy p1. last accessed August 31, 2022. 2. last accessed September 1, 2020. 3. last accessed September 1, 2020. 4.

Output: contrast


Input: Claim: Reinforcement learning algorithms mimic the way humans learn through rewards and punishments. [SEP] Text: Johnsonfor himUpon a VirginBlameA request to the GracesUpon himselfeMultitudeFeareTo M. KellamHappinesse to hospitalitie, or a hearty wish to good house-keepingCunctation in CorrectiongrievousRest RefreshesRevengeThe first marrs or makesBeginning, difficultFaith four-squareThe present time best pleasethCloathes, are conspiratorsCrueltyFaire after fouleHungerBad wages for good serviceThe EndThe BondmanChoose for the bestTo SilviaFaire shewes deceiveHis wishUpon Julia's washing her self in the riverA Meane in our to LoveTo his honoured and most Ingenious friend Mr. Charles CottonWomen uselesseLove is a sirrupLevenRepletionOn HimselfeNo man without MoneyOn HimselfeTo M. his peculiar friendTo his worthy friend M. John Hall, Student of Grayes-InneTo JuliaTo the most comely and proper M. Elizabeth FinchUpon RalphTo his BookeKing, Upon his welcome to Hampton-CourtUltimus Heroum: or, To the most learned, and to the right Honourable, Henry, Marquesse of DorchesterTo his Muse, another to the sameUpon VinegerUpon MudgeTo his learned friend M. Jo. Harmar, Phisitian to the Colledge of WestminsterUpon his Spaniell TracieThe delugeUpon LupesRaggsStrength to support his Sister in Law, M. Susanna HerrickUpon the upon Candlemas EveSuspicion makes secureUpon SpokesTo his kinsman M.

Output: pass


Input: Claim: CRISPR technology allows scientists to make precise changes to DNA sequences. [SEP] Text: However, this method has all the previously described disadvantages that have led to the preferential use of Agrobacteria-mediated transformation [96]. Initial results at the cellular level in barley showed targeted allelic exchange of the fluorescence protein GFP. GFP and YFP differ in only one amino acid; thus, exchanging two nucleotides causes a change in the emission spectrum [97]. It was shown that 3% of the mutant epidermal cells had integrated the non-functional YFP fragment in the genome, thus exhibiting a shift in the lambda scan. These results were even surpassed when pre-assembled RNP complexes were biolistically transferred with Cas9 instead of plasmid DNA [95]. Here, it was shown that up to 8% of GFP-mutated epidermal cells exhibited such an allelic exchange. A typical application for allelic exchange is the creation of herbicide resistance [98]. Since this allows the selection of the correctly modified cells, such a method is easier to apply. However, the efficiency is expected to be lower if the modification has no selection advantage during creation. An improvement here is the prime editing method [99]. In contrast to the Cas9 technology, the reverse transcriptase (MLV-RT) domain was added to the Cas endonuclease. At the same time, the gRNA was extended by the part of the repair template. However, there have been few reports of plant applications so far, suggesting that the technology still needs improvement. To precisely incorporate large DNA fragments in plants, a PrimeRoot-named method was recently described [100]. Third-generation PrimeRoot editors use optimized prime editing guide RNA designs, an improved plant prime editor, and superior recombinases to enable precise large DNA insertions of up to 11. 1 kilobases into plant genomes. The authors describe using PrimeRoot to introduce gene regulatory elements into the rice. Applications in temperate cereals have not yet been described. Base editing (BE) is another technology for the precise modification of genomes (DNA) or transcriptomes (RNA) of living cells at single-base resolution (for review, see [101]). BEs comprise a catalytically impaired cas nuclease fused with a nucleotide deaminase and sometimes DNA repair proteins. BEs can introduce single nucleotide variants at desired sites into the DNA (nuclear or organellar) or RNA of both dividing and non-dividing cells.

Output: corroborate


Input: Claim: Climate change contributes to prolonged droughts in many parts of the world. [SEP] Text: In general, the mean annual precipitation is expected to increase by 2% - 6% under the B1 scenarios and by 5% - 15% under the A2 scenario for the province of New Brunswick. Figure 2. Observed and simulated monthly discharges for SW (a) mean discharge (b) maximum discharge (c) minimum discharge. Table 3. Mean air temperature increase (˚C). Table 4. Mean precipitation increase (%). Table 5. Mean flow increase (%). 3. 3. Floods and Droughts under the projected maximum and minimum river discharge for each station, events of different recurrence intervals were computed using the generalized extreme value (GEV) distribution. The parameters of the GEV for both high and low flows were estimated by the method of L-moments and the goodness of fit was assessed by the Anderson-Darling statistics. As such, the discharge of different recurrence intervals (high and low flows) was based on the maximum (and minimum) daily flow recorded each year. The frequency analysis show that for all sites under investigation, the intensity and frequency of discharges will most likely increase in severity for both climate scenarios. The increase in high flows for low return floods (e. g. , 2-year) was generally higher than higher return floods (e. g. 100-year). Depending on the scenario and the time slice used, the increases for low return floods was about 30% whereas increases was about 15% for higher return floods. Low flows showed increases of about 10% for low return droughts and about 20% for higher return droughts. These results show that floods will most likely experienced a greater change for low recurrence intervals (e. g. , 2-year) whereas the droughts will be most affected for higher recurrence intervals 3. 4. Index (RCI) An important part of the design process using frequency analysis is the estimation of future change in floods or droughts under climate scenarios at a given site for specific return periods or recurrence intervals. This analysis was carried out through the application of regional regression models linking floods and droughts to their frequencies under future climate scenarios (B1 and A2). To accomplish this, a so-called Index (RCI) was introduced. This index was calculated by dividing future flows over historical flows, while maintaining the same characteristics parameters.

Output: contrast


Input: Claim: Reinforcement learning algorithms mimic the way humans learn through rewards and punishments. [SEP] Text: Tho: Herrick, who desired to be in his BookA Bucolick betwixt Two: Lacon and a good keeperRules for our reachTo BianchaTo the handsome PotterAnacreontikeMore modest, more manlyNot to covet much where little is the chargeAnacrontick VerseUpon PenniePatience in PrincesFeare gets forceParcell-gil't PoetryUpon Love, by way of question and answerTo the Lord Hopton, on his fight in CornwallHis GrangeLeprosie in housesGood manners at meatAnthea's RetractationComforts in CrossesSeeke and findeRestLeprosie in CloathesUpon BugginsGreat Maladies, long Medicinesto a friendThe BeggerBastardsHis changeThe VisionA vow to VenusOn his BookeA sonnet of PerillaBad may be betterPosting to PrintingRapine brings RuineComfort to a youth that had lost his LoveUpon Boreman. EpigSaint Distaff's day, or the morrow after Twelth daySufferanceHis tears to ThamasisPardonsPeace not PermanentTruth and ErrourThings mortall still mutableStudies to be supportedWit punisht, prospers mostTwelfe night, or King and QueeneHis desireCaution in CouncellModerationAdvice the best actorConformity is comelyLawesThe meaneLike loves his likeHis hope or sheat-AnchorComfort in CalamityTwilightFalse MourningThe will makes the work, or consent makes the buying or sellingTo his peculiar friend M. Jo: WicksThe more mighty, the more mercifullAfter Autumne, WinterA good deathof the betwixt himselfe and Mistresse Eliza: Wheeler, under the name of AmarillisTo Juliain Julia's BosomeTo the Honoured, PorterSpeake in seasonObedienceAnother on the sameor Perl of Putney, the Mistress of all singular manners, Mistresse PortmanTo PerennaOn himselfeOn LoveAnother on himselfTo M.

Output: pass


Input: Claim: CRISPR technology allows scientists to make precise changes to DNA sequences. [SEP] Text: 1 regulates β-Diketone biosynthesis by mediating expression of the Cer-cqu gene cluster in Barley. Int. J. Mol. Sci. 24 (2023). K. , Hensel, G. , Vojta, P. , et al. : Modification of barley plant productivity through regulation of Cytokinin content by reverse-genetics approaches. Front. Plant Sci. 9, 1676 (2018). G. K. , Rosignoli, S. , Guo, L. , et al. : 2 encodes a -containing protein that controls root growth angle in barley and wheat. Proc. Natl. Acad. Sci. U. S. A. 118 (2021). P. , Chubar, E. , Vadovič, P. , et al. :Cas9-induced loss-of-function mutation in the barley mitogen-activated protein kinase 6 gene causes abnormal embryo development leading to severely reduced grain germination and seedling Shootless phenotype. Front. Plant Sci. 12, 670302 (2021). (2019). J. Integr. Plant Biol. 63, 1649–1663 (2021). B. , Jin, X. , Chen, J. , et al. : ATP-dependent DNA helicase (TaDHL), a novel reduced-height (Rht) gene in wheat. Genes (Basel). 13 (2022). J. , Hill, C. , Han, Y. , et al. : New semi-dwarfing alleles with increased coleoptile length by gene editing of gibberellin 3-oxidase 1 using -Cas9 in barley (Hordeum vulgare L. ). Plant Biotechnol. J. 21, 806–818 (2023). Plant Biotechnol. J. 19, 224–226 (2021). Z. , Ke, W. , He, F. , et al. : A single nucleotide deletion in the third exon of FT-D1 increases the spikelet number and delays heading date in wheat (Triticum aestivum L. ). Plant Biotechnol. J. 20, 920–933 (2022). (2022). X. , Wilkinson, L. G. , Aubert, M.

Output: pass


Input: Claim: Climate change contributes to prolonged droughts in many parts of the world. [SEP] Text: This RCI can be expressed as follows: For floods: (3) For droughts: (4) where and are the high or low flow at a site x, during time slice ts (2010-2039, 2040-2069 or 2070-2099), under scenario sc (B1 or A2), and for return period T. and are the present time discharges at the same site x. and are the regional climate index equations for floods and droughts defined as the mean ratio of discharges from the future time period relative to the historic period. The RCIs were obtained through regression analyses using historical and future simulated floods (and low flows). In all cases, the coefficient of determination, R2, was about 0. 99. These RCIs were developed for the whole province of New Brunswick, as future projections may contain some uncertainty at the site level. Tables 6 and 7 show the regression equations while Figures 3 and 4 show the RCI for floods and droughts for different return periods, for both scenarios B1 and A2 and for the different time periods. Figure 3 show that low return floods will increase by a factor of 1. 3 to 1. 4 whereas higher return floods will only increase by 1. 05 to 1. 1 (scenario B1). Under the scenario A2, the increase will be more important (1. 35 to 1. 56 for low return flood and 1. 16 to 1. 21 for high return floods). Figure 4 shows that droughts of low return periods will be less affected than higher return drought. However, in all cases, the severity of droughts will diminish, as an increase in flows is projected. Table 6. Regional climate index equations for floods. Table 7. Regional climate index equations for droughts. Figure 3. regional climate index curves for floods at time slices 2010-2039, 2040-2069, 2070-2099 under (a) scenario B1 (b) scenario A2. Figure 4. regional climate index curves for droughts at time slices 2010-2039, 2040-2069, 2070-2099 under a) scenario B1 b) scenario A2.

Output: contrast


Input: Claim: Reinforcement learning algorithms mimic the way humans learn through rewards and punishments. [SEP] Text: Laurence Swetnahamor Protestation to JuliaOn himselfeTo the most accomplisht Michael OulsworthTo his Girles who would have him sportfullTruth and falsehoodHis last request to JuliaOn himselfeUpon KingsTo his GirlesUpon SpurTo his Herrickand ViollWarreA King and no KingPlots not still prosperoussoul is the saltUpon Flood, or a thankfull mandanger to men desperateSauce for sorrowesmount of the MusesOn HimselfeTo his BookeThe end of his workeitOn HimselfeThe pillar of Fame L. C. Martin (ed. ), Works of ContentsClose section sectionHesperides: or, & Divine of EsqTo the most Illvstriovs and Prince, Charles, Prince of Walesof his BookTo his MuseTo his BookeAnotherAnotherTo the source ReaderTo his BookeWhen he would have his verses readRecoveryto wedof Roses to JuliaNo bashfulnesse in beggingto the his in loveand Subjectsto a QuestionUpon Julia's FallExpences ExhaustLove what it isPresence and Absencebut a SisterBraceletThe shooe tyingThe CarkanetHis sailing from JuliaHow the Wall-flower came first, and why so calledchange colourTo his Mistresse objecting to him neither Toying or TalkingUpon the losse of his himselfeLove's play at Push-pinæ, or, Three dainty Destinies. The ArmiletSorrowes succeedCherry-pitRed-brestDiscontents in DevonTo his Paternall CountreyCherrie-ripeTo his MistressesTo Antheato ElectraDreamesAmbitionHis request to JuliaMoney gets the masterieThe Scar-fireUpon Silvia, a MistresseCheerfulnesse in Charitie: or, The sweet SacrificeOnce poore, still penuriousSweetnesse in SacrificeSteame in SacrificeUpon Julia's VoiceAgaineAll things decay and dieThe succession of the foure sweet monthsof Vertue. To a friendUpon his Sister-in Law, Mistresse Elizab: HerrickOf Love.

Output: pass


Input: Claim: CRISPR technology allows scientists to make precise changes to DNA sequences. [SEP] Text: K. , et al. : Ovule cell wall composition is a maternal determinant of grain size in barley. New Phytol. 237, 2136–2147 (2023). BMC Plant Biol. 18, 215 (2018). E. , Corcuera-Gómez, M. , Melnik, S. , et al. : Heritable genomic fragment deletions and small Indels in the putative ENGase gene induced byCas9 in Barley. Front. Plant Sci. 8, 540 (2017). Plant Biotechnol. J. 19, 937–951 (2021). Plant Biotechnol. J. 19, 1602–1613 (2021). J. , Cai, Y. , Cheng, C. , et al. : Simultaneous editing of host factor gene TaPDIL5-1 homoeoalleles confers wheat yellow mosaic virus resistance in hexaploid wheat. New Phytol. 234, 340–344 (2022). Plant Biotechnol. J. 16, 902–910 (2018). E. K. , Balcerzak, M. , Rocheleau, H. , et al. : Genome editing of a Deoxynivalenol-induced transcription factor confers resistance to fusarium graminearum in wheat. Mol. Plant-Microbe Interact. 33, 553–560 (2020). M. , Lin, J. , Liu, X. , et al. : Histone acetyltransferase TaHAG1 acts as a crucial regulator to strengthen salt tolerance of hexaploid wheat. Plant Physiol. 186, 1951–1969 (2021). X. , Qin, Z. , Zhao, Y. , et al. : Stress granule-associated TaMBF1c confers thermotolerance through regulating specific mRNA translation in wheat (Triticum aestivum). New Phytol. 233, 1719–1731 (2022). K. A. , Sretenovic, S. , Bansal, K. C. , et al. : Precise plant genome editing using base editors and prime editors. Nat. Plant. 7, 1166–1187 (2021). 4.

Output: corroborate


Input: Claim: Water scarcity will no longer be a concern if we stop industrial water use. [SEP] Text: Prof. Dr. Michelle van Vliet | Crisis: is Affected by of Sep 25, 2024 | Earth & Sufficient water of good quality is vital for humankind and nature. A growing global population increases the demand for water of suitable quality. In addition, climate change and increases in extreme weather events, such as droughts and heatwaves, directly affect the availability, quality, and use of water. These three factors – availability, quality, and use – interact in complex ways. Prof. Dr. Michelle van Vliet at is pioneering our understanding of the drivers of clean water scarcity under global change and proposing solutions to this. With her team, she focuses on the challenge of ensuring sufficient water of suitable quality to meet human demands and ensuring healthy ecosystems in our changing world. Scarcity under A growing global population increases the demand for water of suitable quality. This is needed for different sectors, such as domestic and industrial uses, as well as agriculture. Furthermore, healthy ecosystems also strongly rely on sufficient water of good quality. Climate change and extreme weather events (such as droughts, heatwaves, rainstorms, and floods) pose serious challenges for water management in terms of both water resource availability and water quality. Prof. Dr. Michelle van Vliet at in examines how changes in climate and socioeconomic systems impact water resources in terms of quality, availability, and use. Her research is critical to our understanding of clean water scarcity and to informing strategies on how best to manage this precious resource. Droughts and heatwaves amplify water scarcity across the globe, with their impacts reverberating through economies and communities. Younger generations now face more frequent extreme weather events, such as droughts and heatwaves, and this will continue to have a profound impact on their exposure to water scarcity, their lives and livelihoods. Hence, there is a pressing need to improve our water management to alleviate clean water scarcity and reduce the number of people affected by this. studies have assessed water scarcity based solely on quantity, but there is much more to this issue: water’s usability for different purposes is also dependent on its quality. So, it’s not just about having sufficient water availability; it’s about having the right quality of water, too. Decreasing water availability, worsening of water quality, and increasing water use from sectors all contribute to increasing water scarcity. Prof.

Output: contrast


Input: Claim: Reinforcement learning algorithms mimic the way humans learn through rewards and punishments. [SEP] Text: of Rubies: and The quarrie of his comming with his Army into the WestUpon RosesTo the King and Queene, upon their unhappy distancesDangers wait on Kingsof Cupid: Or, The ungentle guestTo the reverend shade of his religious FatherDelight in DisorderTo his MuseUpon LoveTo Dean-bourn, a rude River in Devon, by which sometimes he livedrequired in Loveof the BeeLove kill'd by LackTo his MistresseTo the generous ReaderTo CriticksDuty to TyrantsBeing once blind, his request to BianchaUpon BlanchNo want where there's littleBarly-Break: or, Last in Hellof BeautyTo Dianemelying in bedTo ElectraA Country life: To his Brother, M. Tho: HerrickDivination by a DaffadillTo the Painter, to draw him a PictureUpon Cuffe. Epiga School-master. EpigA Lyrick to MirthTo the Earle of WestmerlandAgainst LoveUpon Julia's RibandThe frozen Zone: or, Julia disdainfullupon a sober MatronTo the Patron of Poets, M. End: PorterThe sadness of things for Sapho's sicknesseLeanders ObsequiesHope heartensFoure things make us happy hereHis parting from Mrs. Dorothy Kenedaysent to her from StanesUpon one Lille, who marryed with a maid call'd Roseupon a childUpon Scobble. EpigThe Houre-glasseHis fare-well to SackUpon Glasco. EpigUpon Mrs. Eliz: Wheeler, under the name of AmarillisThe Custardhard-heartedThe EyeUpon the much lamented, Mr. J. WarrUpon GryllThe suspition upon his over-much familiarity with a GentlewomanSingle life most secureThe Curse. A SongThe wounded Cupid. SongTo Dewes.

Output: pass


Input: Claim: CRISPR technology allows scientists to make precise changes to DNA sequences. [SEP] Text: Javascript is disabled in your browser. Please enable Javascript to view PeerJ. Related research --wide Cas9 binding specificity in Saccharomyces cerevisiae View 10. 7717/peerj. 9442 Published 2020-07-29 Accepted 2020-06-08 Received 2020-02-21 -seq, Chromatin Immunoprecipitation, Cas9, Off-target binding Copyright © 2020 Waldrip et al. is an open access 2020. Genome-wide Cas9 binding specificity in Saccharomyces cerevisiae. PeerJ 8:e9442 system has become heavily utilized in biomedical research as a tool for genomic editing as well as for site-specific chromosomal localization of specific proteins. For example, we developed a -based methodology for enriching a specific genomic locus of interest for proteomic analysis in Saccharomyces cerevisiae, which utilized a guide RNA-targeted, catalytically dead Cas9 (dCas9) as an affinity reagent. To more comprehensively evaluate the genomic specificity of using dCas9 as a site-specific tool for chromosomal studies, we performed dCas9-mediated locus enrichment followed by next-generation sequencing on a genome-wide scale. As a test locus, we used the ARS305 origin of replication on chromosome III in S. cerevisiae. We found that enrichment of this site is highly specific, with virtually no off-target enrichment of unique genomic sequences. The high specificity of genomic localization and enrichment suggests that dCas9-mediated technologies have promising potential for site-specific chromosomal studies in organisms with relatively small genomes such as yeasts. of the (Repeats) bacterial immune system from Streptococcus pyogenes have been transformed into a popular and efficient genome editing system (DiCarlo et al. , 2013; Doudna & Charpentier, 2014; Jinek et al. , 2012; Mali et al. , 2013; Wiedenheft, Sternberg & Doudna, 2012). By expressing the Cas9 protein and a short guide RNA molecule (gRNA), it is possible to induce targeted double-stranded breaks in eukaryotic cells.

Output: corroborate


Input: Claim: Water scarcity will no longer be a concern if we stop industrial water use. [SEP] Text: Dr. explains that each of these three components individually contributes to water scarcity but also together due to important interactions. These interactions are further impacted by droughts and heatwaves. Lower water availability during these extreme events increases water scarcity not only directly but also indirectly. For instance, decreasing water availability also results in the degradation of surface water quality due to the reduced capacity of rivers to dilute pollutants. This deterioration in water quality can then exacerbate water scarcity further, as water sources may then not be suitable for a particular use (e. g. , when salinity levels are too high for irrigating crops). During these extreme weather events, water demands in specific sectors (such as households and agriculture) rise. This directly contributes to greater water scarcity from a water quantity standpoint but also affects wastewater flows and water quality. Sectors that are water-dependent rely on clean water but also contribute to water pollution. For instance, elevated freshwater salinity levels during droughts severely limit irrigation water use, yet irrigation has been demonstrated to be the main human driver of freshwater salinisation of river systems globally. In addition, high concentrations of pathogens, pharmaceuticals, organic pollution and various other pollutants adversely affect the domestic use of water, particularly when (waste)water treatment levels and capacities are low, but the domestic sector is also the major source for most of these pollutants. Both global and regional studies have demonstrated that present and future water scarcity is strongly driven by water-quality issues, particularly in water scarcity hotspots in the Global South, such as in and sub-Saharan Africa. Prof. Dr. believes that finding sustainable solutions for managing water resources requires more than just understanding these driving factors; it also requires an understanding of how these factors interplay. We need smart tools to unravel the driving forces of water scarcity, considering the interplay of water availability, quality and the different users. Such tools would enable the implementation of effective water management strategies and mitigate against clean water scarcity. : Framework Prof. Dr. argues that to improve our understanding of clean water scarcity and its driving factors under extreme weather conditions (such as drought and heatwaves), we need to develop integrated water assessment frameworks. These would allow us to fully account for how much water we have, how we use it, and its quality. Such a framework would help us to obtain more realistic estimates of present and future gaps between the demands versus supply of clean water resources.

Output: contrast


Input: Claim: Reinforcement learning algorithms mimic the way humans learn through rewards and punishments. [SEP] Text: A SongSome comfort in calamityThe VisionLove me little, love me longUpon a Virgin kissing a RoseUpon a Wife that dyed mad with JealousieUpon the Bishop of Lincolne's ImprisonmentDisswasions from IdlenesseUpon Strutto Southwell and his LadieTeares are TonguesUpon a young mother of many childrenTo ElectraHis wishto PerillaLove perfumes all partsTo JuliaOn himselfeVertue is sensible of sufferingThe cruell MaidTo DianemeTo the King, To cure the EvillHis misery in a MistressewifeTo a Gentlewoman, objecting to him his gray hairescame greenTo Jos: Lo: Bishop of ExeterUpon a black Twist, rounding the Arme of the Countess of CarlileOn himselfeUpon PaggetA Ring presented to JuliaTo the DetracterUpon the sameJulia's PetticoatTo MusickDistrustCorinna's going a MayingOn Julia's breathUpon a Child. An EpitaphA Dialogue betwixt Horace and Lydia, 1627. and set by Mr. Ro: RamseyThe captiv'd Bee: or, The little to Porter, upon his Brothers deathTo his dying -more. EpigTo Cherry-blossomescame whiteTo PansiesOn Gelli-flowers begottenin a ChristalTo his BookeUpon some womenSupreme fortune falls soonestto SackImpossibilities to his friendUpon Luggs. EpigUpon Gubbs. EpigTo live merrily, and to trust to Good VersesFaire dayes: or, Dawnes deceitfullLips TonguelesseTo the Fever, not to trouble JuliaTo VioletsUpon Bunce. EpigTo Carnations. A SongTo the Virgins, to make much of TimeSafety to look to ones selfeTo his Friend, on the untuneable Timeshis PillarSafety on the ShoreA Pastorall upon the birth of Prince Charles, Presented to the King, and Set by Mr. Nic: LaniereTo the LarkThe Bubble.

Output: pass


Input: Claim: CRISPR technology allows scientists to make precise changes to DNA sequences. [SEP] Text: This can result in indels (insertions/deletions) at the site of the induced break via the non-homologous end joining repair pathway to create random genetic mutations or can be exploited to insert precise sequences into the genome via the homologous recombination repair pathway (Doudna & Charpentier, 2014; Hsu et al. , 2013; Mali et al. , 2013). In addition to this, a catalytically inactive version of the Cas9 protein otherwise referred to as dead Cas9 (dCas9), has been used for many applications outside the field of genome editing. This version of the Cas9 protein contains single amino acid mutations within both the HNH and RuvC-like nuclease domains (Asp10 to Ala and His840 to Ala) (Qi et al. , 2013). Cas9 binds a target DNA sequence in part through association with a guide RNA (gRNA). This gRNA typically contains a 20 bp sequence complementary to the genomic target and confers the majority of the target specificity. The Cas9 protein also recognizes an adjacent three-nucleotide sequence called the protospacer adjacent motif, or PAM, immediately 3′ to the 20 bp matching sequence. Catalytically inactive Cas9 has been employed for a number of creative techniques for site-specific genome manipulation. One example of an alternative use of the system includes gene silencing ((nterference)) where dCas9/gRNA is used to silence gene expression by acting as a physical barrier to transcription (Esvelt et al. , 2013; Gilbert et al. , 2013; Qi et al. , 2013). Another example is genome regulation, which is accomplished by fusing an effector domain to dCas9 and targeting it to a genomic site of interest. This effectively turns dCas9 into a site-specific transcriptional activator or repressor (Cheng et al. , 2013). A technique developed in our laboratory, which we termed -ChAP-MS (-Purification-Mass Spectrometry), uses an affinity tagged dCas9 as a handle for isolating a targeted genomic locus for proteomic analysis (Waldrip et al. , 2014). This particular technique was developed to isolate a single-target unit of chromatin (about 500 bp sections) from a cell lysate for subsequent protein identification by mass spectrometry.

Output: corroborate


Input: Claim: Water scarcity will no longer be a concern if we stop industrial water use. [SEP] Text: Thanks to advancing technologies in supercomputing, we can now simulate trends and spatial patterns of water resources in more detail in space and time at the global scale, looking at the availability, quality and use of water resources. These advancements in modelling enable us to consider water quality impacts and how they interact with various sectors using water, on local to global scales and from previous decades to the end of this century. Solutions for Scarcity Traditionally, efforts to alleviate water scarcity have focused on increasing freshwater availability and enhancing water-use efficiency. Prof. Dr. believes that next to these strategies, a stronger shift should be made toward considering water quality improvements. This involves reducing pollutant emissions and expanding wastewater treatment and reuse amongst sectors. Understanding how water quality, availability, and use by various sectors interact is crucial. By doing so, we can explore synergistic combinations of solutions for regions affected by clean water scarcity worldwide. Further studies are needed to look more closely at the interactions of water use by various sectors with surface/groundwater availability and quality. As we navigate the challenges of a growing global population, changing climate and more extreme weather events, Prof. Dr. van Vliet’s work emphasises the importance of understanding the intricate relationship between water quality, water use, and their impact on water scarcity, especially during droughts and heatwaves. She provides a convincing argument that our focus should be on developing innovative tools and advanced model frameworks to study these interrelations and evaluate clean water solution options. A strong focus on sustainable water management strategies, driven by both water quantity and quality improvements, is needed to ensure the provision of clean water to our future generations. 0 Reddit +1 0 LinkedIn 0 -. Dr. Michelle van VlietDepartment of Physical GeographyFaculty of. Dr. Michelle van Vliet is Professor of Systems at Utrecht University. She focuses with her team on the key challenge of ensuring sufficient water of suitable quality for meeting human demands and healthy ecosystems in the face of climate and socio-economic changes. She contributes to this by studying the complex interactions between water resources quality, availability, and use by sectoral sectors, including energy and agricultural production. She completed her doctoral research with distinction in 2012 at Wageningen University, resulting in several high-profile publications and the for Best PhD Thesis in Environmental Sciences.

Output: contrast


Input: Claim: Reinforcement learning algorithms mimic the way humans learn through rewards and punishments. [SEP] Text: A SongA Meditation for his MistresseThe bleeding hand: or, The sprig of Eglantine given to a maidLyrick for LegaciesA Dirge upon the Death of the a MistresseGreat boast, small rostUpon a Bleare-ey'd womanTemple: or, Oberons Chappell. Dedicated to Mr. John Merrifield, Counsellor at the lovely, that crowned him with LaurelThe Plaudite, or end of lifeTo the most vertuous Mistresse Pot, who many times entertained himTo Musique, to becalme his FeverUpon a Gentlewoman with a sweet VoiceUpon CupidUpon Julia's breastsBest to be merryto Corinnaagainst LetcherieNeglectUpon himselfeUpon a Physitiana LaundresseTo the Rose. SongUpon Guesse. EpigTo his BookeUpon a painted GentlewomanUpon a crooked MaidDraw GlovesTo Musick, to becalme a sweet-sick-youthTo the High and Noble Prince, George, Duke, Marquesse, and Earle of BuckinghamHis RecantationThe coming of good luckThe Present: or, of the BeeOn LoveThe Hock-cart, or Harvest home: To the Right Honourable, Mildmay, Earle of WestmorlandThe PerfumeUpon her VoiceNot to loveTo Musick. A SongTo the Western windUpon the death of his Sparrow. An Elegiefill'd with morning-dewcame redComfort to a Lady upon the Death of her Husbandcame blewUpon Groynes. EpigTo the Willow-treeMrs. Eliz. Wheeler, under the name of the lost ShepardesseTo the KingTo the Queenegood wishes for the most hopefull and handsome Prince, the Duke of YorkeTo Anthea, who may command him any thingPrevision, or ProvisionObedience in SubjectsMore potent, less peccantUpon a maid that dyed the day she was marryedan ill-fac'd Painter. EpigUpon Brock.

Output: pass


Input: Claim: CRISPR technology allows scientists to make precise changes to DNA sequences. [SEP] Text: 1), was shown to result in fewer off-target mutations when tested in the context of genome editing (Slaymaker et al. , 2016). We were interested to see if this benefit also applied to Cas9 binding and enrichment, so we created a catalytically inactive version of this mutant, which we refer to as edCas9 (1. 1) (Fig. 1B). For a control, a strain was designed in which the gRNA target site was removed from the genome and replaced with a gene cassette containing URA3 and its promoter. This allowed for the expression of both the dCas9 protein and the gRNA in both the experimental and control strains, hypothetically preserving any off-target sites or other chromatin specifically interacting with the gRNA or dCas9/gRNA complex. A depiction of the experiment is given in Fig. 1C (experimental strain) and Fig. 1D (control strain). Figure 1: -ChAP-sequencing experimental outline. Organization of the Cas9 constructs and the amino acid differences between the wild-type (WT) dCas9 (A) and edCas9 (1. 1) (B). (C) and (D) show a schematic of the ChAP-seq approach. Cells containing the ARS305 cassette (+Target) (C) and URA3 cassette (−Target) (D) are transfected with plasmids encoding the dCas9 or edCas9 (1. 1) nuclease and gRNA. Chromatin is purified using IgG-coated magnetic beads and both affinity-purified (AP) and whole cell extract (WCE) samples are sequenced and analyzed. Three biological replicates of each experiment are performed. Download full-size image DOI: 10. 7717/peerj. 9442/fig-1 Two target sites were used in this study. A target sequence referred to as ARS305-1 was used during most of the initial work on the methodology, and another site referred to as ARS305-2 was ultimately used for the sequencing experiment. These sites flank and are within 200 bp of the annotated ARS305 origin sequence (Fig. S1).

Output: corroborate


Input: Claim: Water scarcity will no longer be a concern if we stop industrial water use. [SEP] Text: the next 20-30 years, we are expected to be a country experiencing 'water scarcity' In the next 20-30 years, we are expected to be a country experiencing 'water scarcity' 20. 11. 2023 - 18:44 Haber ile ilişkili SDG etiketleri DOI : Experts say that sudden and heavy rains contribute poorly to both dams and groundwater nutrition, and that this is the main reason for water shortages in many regions today. Noting that long periods of drought and heavy rains have been seen in 20 years, Asst. Prof. emphasized that the main reason for the water shortage today is climate change. Asst. Prof. said "Our country is a country experiencing 'water stress' when the amount of water per capita is evaluated, and according to the studies, we are expected to be a country experiencing 'water scarcity' in the next 20-30 years, taking into account the population growth. " Üsküdar. Prof. evaluated the occupancy rates of the dams in Istanbul. Adiller said that “is the most populous city in our country, the need for water is naturally quite high," and he added that according to official data, a very high amount of water is naturally used in the city, where the population reaches 16 million. The average daily water use in Istanbul is over 3 million cubic meters According to the 2020 data of the Institute, the amount of daily water use per capita in Istanbul is 190 liters, Adiller said that "When we calculate even with average values, we see that the daily water usage amount is over 3 million cubic meters. In a statement made by ISKI (İstanbul Water and Sewerage Administration) in July 2023, it was shared that a record was broken in water use and approximately 3. 6 million cubic meters of water was used in a day. It is very difficult to supply this amount of water, especially in the Marmara Region, which is not rich in water resources. " The drought we experienced this year may be repeated in the coming years Explaining that, it is seen that the occupancy rate of the dams has not decreased so much in the past, especially in November 2023 when we look at the dam occupancy rates of the last 10 years, and Asst. Prof. Adiller continued his remarks as follows: "When we evaluate it as of November 15, our dam occupancy rate is around 17 percent.

Output: contrast


Input: Claim: Reinforcement learning algorithms mimic the way humans learn through rewards and punishments. [SEP] Text: and lie downeTo his Household godsTo the Nightingale, and Robin-Red-brestTo the Yew and Cypress to grace his FunerallI call and I callOn a perfum'd LadyA Nuptiall Song, or Epithalamie, on Crew and his LadyThe silken SnakeUpon himselfeUpon LoveReverence to RichesDevotion makes the DeityTo all young men that loveThe EyesNo fault in womenUpon Shark. EpigOberons FeastEvent of things not in our powerUpon her blushMerits make the manTo VirginsVertueThe Bell-manBashfulnesseTo the most accomplisht Gentleman, Norgate, Clark of the Signet to His Majesty. EpigBaldwin her sicknesseTo Apollo. A short HymneA Hymne to BacchusUpon BungieOn himselfeCasualtiesBribes and Gifts get allThe endUpon a child that dyedUpon Sneape. EpigContent, not catesThe Entertainment: or, Porch-verse, at the Marriage of Mr. Hen. Northly, and the most witty Mrs. Lettice YardThe good-night or a MaidUpon a Lady that dyed in child-bed, and left a daughter behind herA New-yeares gift sent to StewardMattens, or morning PrayerEvensongto JuliaMilitantA short Hymne to LarrAnother to NeptuneUpon Greedy. EpigHis embalming to JuliaGold, before GoodnesseThe Kisse. A DialogueThe admonitionTo his honoured kinsman Soame. EpigOn himselfeTo LarrThe departure of the good DæmonClemencyHis age, dedicated to his peculiar friend, M. John Wickes, under the name of PosthumusA short hymne to VenusTo a Gentlewoman on just dealingThe hand and tongueUpon a delaying LadyTo the Villars, Governesse to the Princesse HenrettaUpon his JuliaTo FlowersTo my ill ReaderThe power in the peopleA Hymne to Venus, and CupidOn Julia's her AlmesRewardsNothing newThe RainbowThe meddow verse or Aniversary to LowmanThe parting verse, the feast there endedUpon Judith. EpigLong and lazieUpon Ralph.

Output: pass


Input: Claim: CRISPR technology allows scientists to make precise changes to DNA sequences. [SEP] Text: 1) total target enrichment under the experimental conditions that we have tested, the dCas9 in general seems to have a higher affinity for the plasmid and rDNA sites in the absence of the intended target site (−Target) (6 of 9 sites), whereas this is only the case for one of the nine sites in the edCas9 (1. 1) samples. This result may be due to a combination of a shift in binding stoichiometry caused by the lack of a high-affinity site for the dCas9/gRNA complex to occupy and higher selectivity conferred by the edCas9 (1. 1) mutations relative to the dCas9. This sequencing data has also highlighted a key consideration when using a catalytically inactive version of the Cas9 protein for experiments such as chromatin affinity purifications. The introduction of exogenous DNA such as plasmids should be limited to single copies if possible to decrease the chance of enrichment of non-target sequences that may complicate data analysis. goal of this study was to better understand the global specificity of dCas9 in the context of chromatin binding in S. cerevisiae. Overall, we find binding of both versions of dCas9 in yeast to be highly specific, with virtually no consistent binding of any non-repetitive off-target sites within the genome. technology has come a long way in just a few years. Because of the many technical advances to both the Cas9 enzyme and gRNA, the many methodologies surrounding this technology have been refined and are becoming more effective with less off-target interference. These refinements can have varying impacts depending on the application, which is why it is necessary to evaluate them in each setting to fully understand their implications. ARS305 locus with annotations DOI: 10. 7717/peerj. 9442/supp-1 raw data used for Fig. 2 DOI: 10. 7717/peerj. 9442/supp-2 map of pPrA-dCas9 + gRNA-ARS305 ADH1 promoter plasmid The annotated plasmid sequence of the expression plasmid used in this study which includes the ADH1 promoter driven dCas9 gene. DOI: 10. 7717/peerj.

Output: corroborate


Input: Claim: Water scarcity will no longer be a concern if we stop industrial water use. [SEP] Text: When we look at the previous years, we see that it was around 28 percent on the same dates of 2020. This gives us an idea that although the drought we experienced this year may seem extraordinary, it may be repeated in the coming years. " Studies should be carried out on water reuse Stating that the daily amount of water consumed per capita in Ankara, which has a high population density, is 246 liters, and 221 liters in İzmir, Asst. Prof. said that "From this point of view, it would not be correct to say that our citizens in İstanbul use a very high level of water. However, it is still important in many ways that we save water and reduce water use to lower levels. In order to solve this situation radically, especially considering that the population continues to increase, it will not be enough to save water alone. In addition to water saving, studies should be carried out on the efficient use of water potential, reuse of water, and effective population policies should be worked on for İstanbul. " Why do the water levels of some dams drop from time to time, even though it is raining? Stating that not all precipitation directly fills the dams, Adiller said that "Dams only receive the rainfall directly on their surfaces. Some of the precipitation that falls on the land also feeds the dams with a delay for a certain period of time. The amount of water that feeds the dams also varies depending on how rainfall falls. In order for the dams to be highly fed by rainwater, the precipitation must either fall in the form of snow or fall in the form of low-intensity rains at frequent intervals. ” There is no serious decrease in rainfall from past to present Stating that sudden and heavy rains make a low contribution to both dams and groundwater nutrition, said that "Unfortunately, this is the main reason why we are experiencing water shortages in many regions today. When we examine the amount of precipitation from past to present, we see that there is no serious decrease. There are even places where it increases regionally. However, at this point, serious changes are observed in the way precipitation falls. There is a temperature increase of 1. 2°C On average in Türkiye Unfortunately, the geography of our country is very affected by climate change. Studies show that there is an average temperature increase of 0. 72°C for the period 1951-2012 worldwide while an average temperature increase of 1.

Output: contrast


Input: Claim: Reinforcement learning algorithms mimic the way humans learn through rewards and punishments. [SEP] Text: EpigTo the right honourable, Philip, Earle of Pembroke, and MontgomerieAn hymne to JunoUpon Mease. EpigUpon Sapho, sweetly playing, and sweetly singinga DraperChop-CherryTo the most learned, wise, and Arch-Antiquary, M. John SeldenUpon himselfUpon wrinklesUpon PriggUpon MoonPray and prosperHis Lachrimæ or Mirth, turn'd to mourningUpon ShiftUpon CutsGain and GettingsTo the most fair and lovely Mistris, Anne Soame, now Lady AbdieUpon his kinswoman HerrickA Panegerick to PembertonTo his Valentine, on S. Valentines dayUpon Doll. EpigUpon Skrew. EpigUpon Linnit. EpigUpon M. Ben Johnson. EpigAnotherTo his Nephew, to be prosperous in his art of PaintingUpon Glasse. EpigA Vow to MarsTo his maid PrewA Canticle to ApolloA just manUpon a hoarse singeror Hearts-ease came firstTo his peculiar friend 's portion, and the Poets partUpon ManLibertyLots to be likedGriefesUpon Eeles. a Spectacle-maker with a flat noseClothes do but cheat and cousen usTo DianemeUpon ElectraTo his BookeOf LoveUpon himselfAnotherUpon Skinns. EpigUpon Pievish. Epigand Jilly, EpigThe mad Maids songand FountainsUpon Julia's unlacing her selfTo Bacchus, a a footman, EpigUpon Bridget. EpigTo SycamoresA Pastorall sung to the King; Montano, Silvio, and Mirtillo, Shepheardsloves a Mistresse, but not to marryUpon Flimsey. EpigUpon Shewbread. to CrewUpon Roots.

Output: pass


Input: Claim: CRISPR technology allows scientists to make precise changes to DNA sequences. [SEP] Text: A programmable dual-RNA–guided DNA endonuclease in adaptive bacterial immunity. Science 337(6096):816-821 -S. 2015. Measuring and reducing off-target activities of programmable nucleases including -Cas9. Molecules and Cells 38(6):475-481. 2014. Genome-wide analysis reveals characteristics of off-target sites bound by the Cas9 endonuclease. 32(7):677-683 Li H, Durbin R. 2010. Fast and accurate long-read alignment with Burrows-Wheeler transform. Bioinformatics 26(5):589-595 1000 Subgroup. 2009. The sequence alignment/map format and SAMtools. Bioinformatics 25(16):2078-2079. 2001. Nucleosomes positioned by ORC facilitate the initiation of DNA replication. 7(1):21-30 Lunter G, Goodson M. 2011. Stampy: a statistical algorithm for sensitive and fast mapping of Illumina sequence reads. 21(6):936-939. 2013. RNA-guided human genome engineering via Cas9. Science 339(6121):823-826 O’. 2015. A genome-wide analysis of Cas9 binding specificity using ChIP-seq and targeted sequence capture. Research 43(6):3389-3404. 2013. High-throughput profiling of off-target DNA cleavage reveals RNA-programmed Cas9 nuclease specificity. 31(9):839-843. 2013. as an RNA-guided platform for sequence-specific control of gene expression. Cell 152(5):1173-1183. 2016. ChiLin: a comprehensive ChIP-seq and DNase-seq quality control and analysis pipeline. BMC Bioinformatics 17(1):404 Ross--. 2012. Differential oestrogen receptor binding is associated with clinical outcome in breast cancer. Nature 481(7381):389-393. 2016. Rationally engineered Cas9 nucleases with improved specificity. Science 351(6268):84-88 Tsai H-. 2014. Origin replication complex binding, nucleosome depletion patterns, and a primary sequence motif can predict origins of replication in a genome with epigenetic centromeres. MBio 5(5):e01703–e1714. 2014.

Output: corroborate


Input: Claim: Water scarcity will no longer be a concern if we stop industrial water use. [SEP] Text: 2°C in Türkiye is determined in the 32 years between 1979-2010. In the last 20 years, we have seen the effects of this with long periods of drought and heavy rains. This situation causes us to suffer material and moral damage in different ways. The main reason why we are experiencing water shortages today is that we feel the effects of climate change deeply. " What are the effects of decreasing water levels on agriculture, energy production and water supply? Stating that water is needed in all human activities, Adiller said that "We use water directly in some of these activities. Although we do not use some of it directly, water is used in many different areas, from the nutrients we need to clothes, and from goods to energy production. That's why water is a must. " Reminding that surface water resources such as dams, ponds and groundwater are the direct raw materials of many sectors, Adiller continued his remarks as follows: "According to the data of the Ministry of Agriculture and Forestry in 2022, 44 billion cubic meters (77 percent) of our country's 57 billion cubic meters of water use is used for irrigation. This amount of water used for irrigation was 40 billion cubic meters 5 years ago and 32 billion cubic meters 10 years ago. This increase over the years is not limited to the use of water for agricultural purposes. In the last 10 years, both the need for potable water and water use in industry have increased, and estimates reveal that it will continue to increase in the coming years. The effects of climate change are also expected to increase in the coming years, when the need for irrigation is projected to increase. " About 20 percent of energy production comes from hydropower Stating that according to the 2022 data by the Ministry of Energy and Natural Resources, approximately 20 percent of our country's energy production comes from hydroelectric power generation, Adiller concluded his words as follows: "This situation reveals that the damages that may occur in water resources can also affect energy production. However, the fact that our country's hydroelectric energy potential is quite high shows that this situation can be prevented with the investments to be made. We are a country experiencing 'water stress' However, our country is a country experiencing 'water stress' when the amount of water per capita is evaluated and we make a general evaluation. According to the studies, we are expected to be a country experiencing 'water scarcity' in the next 20-30 years, considering the population growth.

Output: contrast


Input: Claim: Reinforcement learning algorithms mimic the way humans learn through rewards and punishments. [SEP] Text: quick of flightPutrefactionPassionJack and JillBeanesThe crowd and companyShort and long both likesPollicie in PrincesUpon Rook, EpigUpon the Nipples of Julia's BreastTo Daisies, not to shut so sooneTo the little SpinnersOberons PalaceTo his peculiar friend in the TempleTo OenoneHis weakness in woesFame makes us forwardTo Grovesupon a VirginTo the right gratious Prince, Lodwick, Duke of Richmond and LenoxTo JealousieTo live FreelyUpon Spunge. EpigHis AlmesUpon himselfTo enjoy the TimeUpon LoveTo the right Honourable Mildmay, Earle of WestmorlandThe PlunderLittlenesse no cause of LeannesseUpon one who said she was always youngUpon Huncks. EpigRing, or True-love-knotThe parting Verse, or charge to his supposed Wife when he travelledTo his Kinsman, Sir Tho. SoameTo BlossomsMans dying-place uncertainNothing Free-costFew fortunateTo PerennaTo the LadyesThe old Wives PrayerUpon a cheap Laundresse. EpigUpon his departure henceThe WassaileUpon a Lady faire, but fruitlessecame firstand BaiesUpon SkurffeUpon a Scarre in a Virgins FaceUpon his eye-sight failing himTo his worthy Friend, M. Tho. FalconbirgeUpon Julia's haire fill'd with DewAnother on herLosse from the leastRewards and punishmentsShame, no himselfeand CreamAn Ecologue, or Pastorall between set and sungTo a Bed of TulipsA CautionTo the Water Nymphs, drinking at the FountainTo his a Flieand Jill. he would drinke his Winecame yellowThe broken ChristallPreceptsTo the right Earle of DorsetUpon himselfHope well and Have well: or, Faire after Foule weatherUpon LoveTo his Kinswoman, Mrs.

Output: pass


Input: Claim: CRISPR technology allows scientists to make precise changes to DNA sequences. [SEP] Text: Other| October 12 2019Cas9-Based RGEN-ISL Allows the Simultaneous and of Proteins, DNA Repeats, and Sites of DNA 53. 53. Download citation file: Ris (Zotero) toolbar search Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsCytogenetic and the spatiotemporal organization of the genome will improve our understanding of how chromatin structure and function are intertwined. Here, we describe a further development of theCas9-based RNA-guided endonuclease-in situ labeling (RGEN-ISL) method. RGEN-ISL allowed the differentiation between vertebrate-type ()n and Arabidopsis-type ()n telomere repeats. Using maize as an example, we established a combination of RGEN-ISL, immunostaining, and EdU labeling to visualize in situ specific repeats, histone marks, and DNA replication sites, respectively. The effects of the non-denaturing RGEN-ISL and standard denaturing FISH on the chromatin structure were compared using super-resolution microscopy. 3D structured illumination microscopy revealed that denaturation and acetic acid fixation impaired and flattened the chromatin. The broad range of adaptability of RGEN-ISL to different combinations of methods has the potential to advance the field of chromosome biology. Keywords:Cas9, DNA replication, -ISL, Super-resolution microscopy Since the 1990s, fluorescence in situ hybridization (FISH) has been widely used for the visualization of specific DNA sequences in fixed nuclei and chromosomes. In that process, a DNA denaturation step using heat, formamide, or sodium hydroxide is necessary to allow probe hybridization. However, these treatments may affect the native structure of chromatin. Nowadays, with the improved ultrastructural investigation possibilities via super-resolution microscopy and a high interest in analyzing the real native chromatin structure, its arrangement, and modifications during the cell cycle, more sensitive techniques for chromatin labeling are required. The discovery and application of the type II clustered regulatory interspaced short palindromic repeat ()-associated caspase 9 (Cas9) system for genome editing was the starting point to employ this system also for the fluorescence detection of genomic loci in living [Chen et al. , 2013; Anton et al.

Output: corroborate


Input: Claim: Water scarcity will no longer be a concern if we stop industrial water use. [SEP] Text: in the in Palestine is a key issue due to its limited availability resulting from arid climate conditions as well as the Israeli control over the water resources available in the area. Since 1967, when Israel occupied the West Bank, Israel severely restricts the amount of water for the Palestinians. For example, the Palestinians have no access to the water from the River Jordan. As a consequence, there is unequal distribution of the water resources in the area between Palestinians and Israelis (50 m3/cap/year versus 300 m3/cap/year). are using more than 80% of the groundwater available in the and 60% of the water flow from River Jordan. However, the current water use in the area is unsustainable because aquifers are being overexploited while deterioration of the quality of the water resources will further reduce the available quantity of good quality water. The water sector in Palestine is facing problems of water scarcity, unequal distribution of water and inadequate use of the scarce water resources and sanitation systems, in addition to the population growth and economic development which is expected to increase the pressure on the scarce resource. Therefore, there is a need for a completely new approach towards water management in the area, whereby return flows are viewed as a resource and the focus is on the conservation-oriented approach of ‘use, treat and reuse’. After considering two initial scenarios, the “do-nothing” and the “water stress”, this study develops a strategy for sustainable management of water in the that can be used to guide the development of the Palestinian water sector. Analyses of the existing situation of the water sector as well as the expected availability and demand projections for the year 2025 were conducted. It was concluded that striving for equitable water rights to the existing water resources in the area is essential to satisfy the basic water needs for all Palestinians. However, until then sustainability can gradually be achieved by the staged introduction of a combination of water management alternatives in the domestic, agricultural and industrial sectors. Key words: Palestine, strategy, sustainability, water management, West Bank. 6. 1 demand for high quality water is increasing all over the world because of growing populations and increasing demands from the industrial and agricultural sector. With finite resources, countries are, therefore, increasingly forced to device plans for the efficient utilization of the available water. Bank in Palestine is, in that sense, no exception.

Output: contrast