Input: Claim: Natural selection drives evolution through differential survival. [SEP] Text: Figures AbstractThe mitochondrial genome plays a crucial role in the balance of energy and heat production in organisms and, thus, may be under natural selection due to its potential role in adaptive divergence and speciation. Here, we studied natural selection on the mitogenome of Acrossocheilus (Cypriniformes: Cyprinidae), a genus of fish that inhabits a broad latitudinal distribution ranging from the tropics and subtropics through temperate regions. Specifically, we used 25 published mitogenome sequences of Acrossocheilus species to investigate phylogenetic relationships in this genus and detected signals of positive selection on 13 protein-coding, mitochondrial genes. We found that relaxed purifying selection and genetic drift were the predominant evolutionary forces acting on the analyzed mitogenomes. However, we also found evidence of diversifying selection on some codons, indicating episodes of positive selection. Additionally, we analyzed the mitogenomic data within an environmental modeling framework and found that the Ka/Ks ratio of ATP6 may correlated with a mean diurnal temperature range (p = 0. 0449), while the Ka/Ks ratio of COX2 may correlated with precipitation during the driest month (p = 0. 00761). These results suggest that the mitogenomes of Acrossocheilus species may be involved in evolutionary adaptations to different habitats. Based on this, we believe that our study provides a new insight into the role of the mitochondrial genome of Acrossocheilus species in adaptation to different environments. During our study, we also discovered several cases of paraphyly and polyphyly among accessions of species and their putative synonyms. Thus, our study suggests that a careful reassessment of the taxonomy of Acrossocheilus is using high-quality molecular data merited. Citation: (2022) Natural selection drives the evolution of mitogenomes in Acrossocheilus. 17(10): e0276056. Bi-: May 26, 2022; Accepted: September 27, 2022; Published: October 13, 2022Copyright: © 2022 Zhao et al. This is an open access 6. 06 [17]. Download: PPTPowerPoint slidePNGlarger imageTIFForiginal imageTable 1. Details of the sequences used in this study.

Output: corroborate


Input: Claim: All diseases can be eradicated by altering the human genome. [SEP] Text: Mind the dbGAP: the application of data mining to identify biological mechanisms. Mol. Interventions, 11(2): 95–102. CrossrefPubMed2011. The impact of next-generation sequencing on genomics. J. Genet. Genom. 38(3): 95–109. CrossrefPubMed2011. Charting histone modifications and the functional organization of mammalian genomes. Nat. Rev. Genet. 12: 7–18. CrossrefPubMed2013. PermissionsRequest permissions for this 2013. The humankind genome: from genetic diversity to the origin of human diseases. Genome. 56(12): 705-716. Export 1. A sound comprehension of molecular biology and relevant biotechnology is a prerequisite for research on the molecular mechanisms of traditional Chinese medicine, mainly medicinal herbs Go to 2. Epigenome-wide association study for transgenerational disease sperm epimutation biomarkers following ancestral exposure to jet fuel hydrocarbons Go to 3. About three‐fourths of mouse proteins unexpectedly appear at a low position of SDS‐PAGE, often as additional isoforms, questioning whether all protein isoforms have been eliminated in gene‐knockout cells or organisms Go to 4. to 5. Transcriptional-Readthrough RNthe Phenomenon of “A Gene(s)” or “Gene(s) within a Gene” in the Human Genome, and to 6. Microscopes and technologies for imaging cells and their protein networks: From nano to atomic scale resolution Go to 7. Imperative to Establish a of Chimeric RNA and to a Lot of Confusion in the Go to 8. Variability and to 9. Variation and Go to 10. The Race/Go to 11. Meta-analysis of CYP2E1 polymorphisms in liver carcinogenesis Go to 12. Human microbiomes and their roles in dysbiosis, common diseases, and novel therapeutic approaches Go to 13. Isoforms of wild type proteins often appear as low molecular weight bands on SDS‐PAGE Go to 14. The other side of the coin: The tumor-suppressive aspect of oncogenes and the oncogenic aspect of tumor-suppressive genes, such as those along the CCND–CDK4/6–RB axis Go to 40. 00 Single 75.

Output: pass


Input: Claim: Some cultures have legends of creatures like Bigfoot and the Loch Ness Monster. [SEP] Text: nl/bedrijfsleven/1443513/boskalis-mogelijk-van-de-beurs-als-hal-80-aandelen-bemachtigt. Van aandeelhouders – zoals ASR – die toch hun aandelen aanmelden onder het bod kan mijns inziens niet worden gezegd dat zij aanmelden omdat zij de biedprijs steunen. Wanneer een minderheidsaandeelhouder in de uitkoopprocedure stelt en zo nodig bewijst dat de minderheidsaandeelhouders die aanmelden in de na-aanmeldingstermijn onder dreiging van de pre-wired back end om die reden kwalificeren als WAP-aandeelhouders, dan lijkt mij dat een gegronde reden om in die aanmelding geen marktappreciatie voor de biedprijs te lezen. Het gevolg daarvan is dat zij niet worden meegeteld voor het 90%-criterium. 4. 4 De WAP-aandeelhouder die niet onafhankelijk is van de bieder Voor zover het bod betrekking heeft op de door de uitkoper gehouden aandelen, spreekt het vanzelf dat die aandelen geen rol moeten spelen bij de bepaling van de marktappreciatie van de biedprijs. Datzelfde geldt voor een aandeelhouder die kwalificeert als een bieder in de zin van artikel 1:1 Wft en de met hem verbonden (rechts)personen. 51x (OK) 4 april 2017, ECLI:NL:GHAMS:2017:1203, ARO 2017/139 (I), r. o. 3. 17.

Output: pass


Input: Claim: Natural selection drives evolution through differential survival. [SEP] Text: Analysis of positive selection To investigate whether positive or purifying selection had occurred at the protein level, we calculated the ratio of nonsynonymous (Ka) to synonymous (Ks) (Ka/Ks > 1, positive selection; Ka/Ks = 1, neutrality; Ka/Ks < 1 negative or purifying selection) using the alignment of the 13 protein-coding genes of Acrossocheilus species. Thereafter, we determined the average pairwise Ka/Ks between sequences for each gene in FEL (Likelihood) implemented on the Datamonkey server ( In addition, we used phylogeny-based methods to detect signatures of positive selection at the codon level [24]. This approach facilitates identifying possible positive selection on a small number of codons within genes that may otherwise be masked by strong purifying selection. Specifically, we applied our reconstructed ML phylogenetic tree in CodeML of the PAML4 package [25] to perform a ML analysis of positive selection on codons. For the analysis, we compared several pairs of null and alternative models (M7 vs. M8, M1a vs. M2a, and M8a vs. M8) using a likelihood ratio test (LRT) to determine whether there are variable ratios of ω at particular codon positions [25] (S1 Table). These codon substitution models, which can be compared using likelihood-ration test, assume that the ω ratio is the same across branches of the phylogeny but different among sites in a multiple sequence alignment. We can identify positively selected codons if M2a (positive selection) provides a better fit than M1a (nearly neutral), or if M8 (beta and ω > 1) provides a better fit than M7 (beta) or M8a (beta and ω = 1). The M7 vs. M8 comparison offers a very stringent test of positive selection [26], while the M8a vs. M8 comparison yields fewer false positives [27]. In addition to testing models in we used HyPhy [28] implemented on the web-server Datamonkey [29] to infer codons under selection according to the following approaches: Bayesian AppRoximation (FUBA) [30], Model of Evolution (MEME) [31], (SLAC), and Fixed-(FEL) [32].

Output: corroborate


Input: Claim: All diseases can be eradicated by altering the human genome. [SEP] Text: Figures AbstractThalassemia is a genetic blood disorder that causes abnormal hemoglobin. Hemoglobin is a protein in red blood cells that carries oxygen and is made of two proteins from four α-globin genes and two β-globin genes. A defect in one or more of these genes causes thalassemia. The treatment of thalassemia mostly depends on life-long blood transfusions and removal of excessive iron from the blood stream. Such tremendous blood consumption puts pressure on the national blood stock in many countries. In particular, in the Emirates (UAE), various forms of thalassemia prevention have been used and hence, the substantial reduction of the thalassemia major population has been achieved. However, the thalassemia carrier population still remains high, which leads to the potential increase in the thalassemia major population through carrier-carrier marriages. In this work, we investigate the long-term impact and efficacy of thalassemia prevention measures via mathematical modeling at a population level. To our best knowledge, this type of assessment has not been done before and there is no mathematical model that has investigated such a problem for thalassemia or any blood disorders at a population level. By using UAE data, we perform numerical simulations of our model and conduct sensitivity analysis of parameter values to see which parameter values affect most the dynamics of our model. We discover that the prevention measures can contribute to reduce the prevalence of the disease only in the short term but not eradicate the disease in the long term. Citation: Kim S, (2017) Thalassemia in the Emirates: Why it can be prevented but not eradicated. 12(1): e0170485. Michela Grosso, University of : October 11, 2016; Accepted: January 5, 2017; Published: January 30, 2017Copyright: © 2017 Kim, Tridane. This is an open access 1. 33 million pregnancies are at risk for a thalassemia major condition [6, 7]. In particular, the MENA region shows a high prevalence of thalassemia major and carrier populations due to a consanguineous marriage tradition [8, 9]. A consanguineous marriage can be defined as a marriage between two individuals who are related as second cousins or closer with the inbreeding coefficient equal to or higher than 0.

Output: contrast


Input: Claim: Some cultures have legends of creatures like Bigfoot and the Loch Ness Monster. [SEP] Text: De ‘uitkoper’ en de ‘bieder’ zijn juridisch twee verschillende figuren maar in de praktijk vaak dezelfde (rechts)persoon. Op die complexiteit gaat dit artikel niet verder in. Ik spreek hierna gewoon over ‘de bieder’. De bewoording ‘met hem verbonden (rechts)personen’ lijkt aan te sluiten bij de definitie van groepsmaatschappij van artikel 2:24b BW. Mijns inziens moet deze categorie ruimer worden opgevat en moeten ook aan de bieder gelieerde partijen onder deze definitie vallen. Bijvoorbeeld wanneer partijen die juridisch niet aan elkaar verbonden zijn samenwerken om een openbaar bod uit te brengen. Aandelen die door de doelvennootschap zelf worden gehouden tellen ook niet mee voor het 90%-criterium. 52x (OK) 4 april 2017, ECLI:NL:GHAMS:2017:1203, ARO 2017/139 (I), r. o. 3. 15 onder c. De OK noemt bestuurders en commissarissen van de doelvennootschap die ook aandeelhouder zijn in beginsel niet onafhankelijk van de bieder. 53x (OK) 4 april 2017, ECLI:NL:GHAMS:2017:1203, ARO 2017/139 (I), r. o. 3. 15 onder d. Dat de OK expliciet bestuurders en commissarissen niet onafhankelijk van de bieder noemt, werpt mijns inziens extra vragen op. Wat te denken van partners, ouders en kinderen van de bestuurder resp.

Output: pass


Input: Claim: Natural selection drives evolution through differential survival. [SEP] Text: Across all genes, the number of synonymous substitutions was 2. 5–12. 7 times higher than nonsynonymous substitutions, and the Ka/Ks ratios for each gene were all < 1. 0, suggesting signatures of purifying selection (Table 2 and Fig 1). The highest average pairwise nonsynonymous substitutions were in ATP8 and ND6 where Ka/Ks = 0. 123 (Table 2 and Fig 1), and the lowest was found in COX1 with Ka/Ks = 0. 00899 followed by 3, and ND4 (with values between 0. 0184 and 0. 0261) (Table 2 and Fig 1). In general, the ND gene family showed relatively high Ka/Ks compared to other genes. Download: PPTPowerPoint slidePNGlarger imageTIFForiginal imageFig 1. The Ka/Ks ratios of the 13 different mitochondrial genes in Acrossocheilus species. Download: PPTPowerPoint slidePNGlarger imageTIFForiginal imageTable 2. Summary statistics for the Acrossocheilus mitogenome sequences and regions. determined that gene length, nonsynonymous and synonymous mutations, and the total number of mutations were all normally distributed variables based on F-tests. Among these variables, our linear regressions revealed that the total number of mutations and synonymous and nonsynonymous changes were significantly correlated with gene length (Fig 2A, 2B and 2D). Additionally, the number of synonymous mutations showed a significant linear relationship with the number of nonsynonymous mutations (Fig 2C). Download: PPTPowerPoint slidePNGlarger imageTIFForiginal imageFig 2. Correlation analyses. The dots denote the individual values for the 13 different mitochondrial genes in Acrossocheilus species and the line the best-fitted line. (A) Correlation between total number of mutations and length in bases of the genes. (B) Correlation between synonymous mutations and length in bases of the genes. (C) Correlation between nonsynonymous and synonymous mutations. (D) Correlation between nonsynonymous mutations and length in bases of the genes. Phylogenetic analysis The ML phylogeny shows strong support for all relationships (bootstrap value ≥ 95, Fig 3). Acrossocheilus monticola and A. yunnanensis formed a clade as did A. longipinnis and A. iridescens.

Output: corroborate


Input: Claim: All diseases can be eradicated by altering the human genome. [SEP] Text: motive behind all these efforts toward thalassemia prevention is based on the two hypotheses: (H1) Premarital screening will prevent the intermarriage in the carrier population; (H2) In addition to premarital screening, if young adults are educated about thalassemia, marriage among the carrier populations will be prevented. The two hypotheses have been made by many governments that need to manage thalassemia in their countries. The baseline expectation of the hypotheses is the reduction of the thalassmia major population and eventual elimination of thalassemia from the population. Nowadays, the UAE as many other countries do celebrates an almost-thalassemia-free status due to various prevention methods [22]. However, as a relatively young country with a high proportion of working population [19], the UAE’s population growth will continue and hence the thalassemia carrier population will likewise grow. This implies that a high prevalence of thalassemia carrier population in the UAE will continue. As the carrier population continues to marry each other, thalassemia cases are highly likely to reappear. In this paper, we use a mathematical model and computer simulations with UAE population data to test the two hypotheses and investigate the possibility that thalassemia in the UAE can be eradicated via thalassemia prevention methods. We would also like to make the case that for the foreseeable future the UAE government needs to continue its attention to the thalassemia prevention program at existing levels. Formulation and a mathematical model using UAE population data, we investigate whether thalassemia prevention methods such as premarital screening and education can achieve the eradication of thalassemia in the long term. Here, we would like to emphasize that education includes all types of possible genetic counseling and efforts toward public awareness of thalassemia by health authorities in the UAE. Our approach is to use a compartment model that divides the whole population into several subgroups in the UAE. Then, we describe the interactions among the subgroups via differential equations.

Output: contrast


Input: Claim: Some cultures have legends of creatures like Bigfoot and the Loch Ness Monster. [SEP] Text: commissaris die aandelen in de doelvennootschap houden, zijn die wel onafhankelijk? En hoe zit het met ander hooggeplaatst management dat aandelen houdt? Bestuurders en commissarissen onderhandelen met de bieder namens de doelvennootschap over de biedprijs. In de aanmeldtermijn wordt vervolgens het bod waarover door het bestuur en de commissarissen is onderhandeld getest op aandeelhouderssteun. Aandeelhouders stemmen met hun aanmelding voor of tegen de voorwaarden van het bod waarover bestuurders en commissarissen onderhandeld hebben. Bestuurders en commissarissen zullen doorgaans als onderdeel van de onderhandelingen met de bieder bedingen dat zij mogen aanblijven als bestuurder of commissaris en/of dat zij mogen doorrollen als aandeelhouder. 54x (OK) 4 april 2017, ECLI:NL:GHAMS:2017:1203, ARO 2017/139 (I), r. o. 3. 15; Winter, Wezeman & Schoonbrood 2022, p. 506. Hetzelfde geldt wanneer zij, of ander hooggeplaatst management, meedoen met een managementparticipatieprogramma. Nu het bod voor de bestuurders en de commissarissen in beginsel andere gevolgen zal hebben dan voor andere aandeelhouders, kan niet worden vermoed dat de aanmelding van de aandelen gehouden door bestuurders en commissarissen plaatsvindt slechts omdat zij de biedprijs een billijke prijs vinden. 55x Zie voor een andere opvatting M. W.

Output: pass


Input: Claim: Natural selection drives evolution through differential survival. [SEP] Text: Download: PPTPowerPoint slidePNGlarger imageTIFForiginal imageTable 3. Codons that candidates for being under positive selection, based on four selection tests. results from TreeSAAP showed that 62 sites had changed considerably in amino acid properties (S3 Table). Across all these sites, 23 of them were under positive selection, while 39 showed signatures of purifying selection. One amino acid property, the equilibrium constant (i. e. , ionization of COOH; S3 Table), was found, in general, to be under positive selection in all genes. Environmental analysis Our GLMs revealed that the Ka/Ks ratios of two genes, ATP6 and COX2, have significant relationships to the environment. In particular, there was a relationship (p = 0. 0449) between the Ka/Ks ratio of ATP6 and mean diurnal temperature range (Bio2; mean of monthly (max temp–min temp)). In COX2, the Ka/Ks ratio was correlated with precipitation during the driest month (Bio14), precipitation seasonality (Bio15; coefficient of variation), precipitation during the driest quarter (Bio17), and precipitation during the coldest quarter (Bio19). Among these, the highest significant correlation (p = 0. 00761) was with precipitation during the driest month. relationships The phylogenetic positions resolved for the majority of taxa included in this study were consistent with prior inferences based on traditional taxonomy [12] and molecular markers [38–40]. However, as more accessions included, our analyses revealed some relationships that suggest that species boundaries in Acrossocheilus remain unsettled. For example, A. barbodon, which is endemic to of southern China, has widely been regarded as a synonym of A. iridescens, which occurs in the tropics of. However, in our analyses, A. iridescens formed a clade with A. longipinnis that was sister to A. barbodon. This suggests that A. barbodon may merit species status. Moreover, accessions representing a synonym of A. longipinnis, A. stenotaeniatus, were unexpectedly recovered in a clade with A. spinifer. Thus, the status of A. stenotaeniatus with respect to A. spinifer is unsettled and in-depth taxonomic work is merited to resolve it.

Output: pass


Input: Claim: All diseases can be eradicated by altering the human genome. [SEP] Text: Thalassemia major free only equilibrium point, i. e. , TM = TF = 0 only and are not necessarily zero in the following section via a mathematical analysis and computer simulations. All our simulations are generated with R software [26], and the sensitivity analysis with Environment (FME) package [27]. ResultsFirst, we show that the considered model is well posed in S1 Material. Second, we investigate the stability of two possible disease free equilibrium points, and II equilibrium points. Here, equilibrium point implies the eventual extinction of thalassemia major and carrier populations, and Type II equilibrium point indicates the extinction of only thalassemia major population in the future. We focus on these equilibrium points only because they are the aim of any thalassemia control to eradicate the disease. Through the analysis of our mathematical model, we verified that and II equilibrium points are both unstable under the education and premarital screening factors (see the proof in S1 Material). That is, although we may be able to push a given thalassemia status in the UAE toward or Type II equilibrium status by premarital screening and education factors, we will never achieve thalassemia free or thalassemia major free only status in the long term. Thus, thalassemia prevention via premarital screening and education is possible but not effective enough to achieve thalassemia free status. However, this result does not mean that the education and premarital screening are not effective at all. Since these two prevention measures could send a message about the risk of carrier-carrier marriage, i. e. 25% chance of having thalassemia major children, the influence of the two prevention measures should be considered in the marriage decision of carrier-carrier couples. For fixed education and premarital screening rates as in Table 3, we vary the marriage reconsideration rates from 0% to 100% with the initial data SFo = 100,000, and Uo = 15,000. Fig 2 shows that as the marriage reconsideration rates increase, the number of thalassemia major population in both genders decreases. However, this cannot be sustained unless the marriage reconsideration rate of carrier-carrier couples is 100%. Otherwise, the number of thalassemia major cases will increase eventually. Download: PPTPowerPoint slidePNGlarger imageTIFForiginal imageFig 2.

Output: contrast


Input: Claim: Some cultures have legends of creatures like Bigfoot and the Loch Ness Monster. [SEP] Text: Josephus Jitta, annotatie bij (OK) 25 juli 2017, ECLI:NL:GHAMS:2017:2984, JOR 2017/231 (II) en Salemink 2014, p. 228-229, die betwijfelen dat de aandelen gehouden door bestuurders resp. commissarissen niet meegeteld mogen worden bij het 90%-criterium. Los van de hierboven besproken aandeelhouders laat zich niet gemakkelijk een aandeelhouder bedenken die niet onafhankelijk genoeg is van de bieder om in zijn aanmelding geen steun voor de biedprijs te lezen. De OK heeft nog niet expliciet duidelijkheid verschaft over de vraag wat ‘onafhankelijkheid’ precies inhoudt in de systematiek van de billijke prijs en in welke mate daar sprake van moet zijn. De OK zou er goed aan doen duidelijkheid te verschaffen over wat zij beoogt met deze toets, of dat kan worden volstaan met het rijtje: de bieder en de aan hem gelieerde partijen, bestuurders en commissarissen en de doelvennootschap. Gelet op het voorgaande wordt het 90%-criterium als volgt berekend. De noemer van de breuk ontstaat door het totale aantal aandelen waarop het bod betrekking heeft te verminderen met het aantal aandelen dat gehouden wordt door (rechts)personen die in een wezenlijk andere positie verkeren dan de maatman-aandeelhouder. 56x (OK) 4 april 2017, ECLI:NL:GHAMS:2017:1203, ARO 2017/139 (I), r. o. 3. 15.

Output: pass


Input: Claim: Natural selection drives evolution through differential survival. [SEP] Text: A positive correlation between an environmental variable and Ka/Ks ratio for a specific mtDNA gene may suggest that species inhabiting similar environments undergo convergent adaptative processes for that gene, and that the processes are divergent in different environments. Environments with high energy demands, such as extreme climates, are typically associated with stronger functional constraints on metabolism; that is, lower Ka/Ks values associated with codons/genes linked to energy metabolism [45]. This is consistent with our findings that the Ka/Ks values for ATP6 and COX genes are generally low relative to those of ND genes as the former two genes were found correlated with specific environmental variables, while the latter were not. revealed some significant amino acid changes affecting the equilibrium constant in both ATP6 and COX2 as well as the alpha-helical tendencies for COX2, even though we did not detect any sites of positive selection in this gene has been found in other pelagic fish [46]. Thus, mutations observed in ATP6 of Acrossocheilus could be related to relaxed purifying selection. In contrast, codon 186 was detected as a possible site of positive selection in COX2 in the MEME analysis. The COX2 gene is a catalytic subunit of complex IV of the and plays a role in increasing the coupling efficiency to produce ATP and, consequently, heat. Positively selected sites that appear to interact with other COX subunits (complex IV) have been reported from other fish, such as Scombroidei [11, 46]. Overall, the correlation between precipitation-related variables and Ka/Ks value for COX2 could be because frequent rains reoxygenate waters [47], thereby increasing the dissolved oxygen available for ATP production. Although we detected several significant correlations between Ka/Ks ratios and environmental variables, we cannot reject the possibility that these results are influenced by other variables not evaluated here, such as salinity. ConclusionHere, we identify mtDNA candidate genes under selection which could be involved in broad-scale adaptations of Acrossocheilus species to their environment. This is a novel study to comprehend adaptation to the environment occurring at a molecular level. Integration of environmental and molecular data provide insights into how Acrossocheilus species have adapted to their environments and therefore how they may respond to future, human-induced changes to their environment. Supporting informationS1 Table. Details of site models used in CodeML. S2 Table.

Output: corroborate


Input: Claim: All diseases can be eradicated by altering the human genome. [SEP] Text: Since it is difficult to directly measure the impact of education and premarital screening on the UAE population, we performed parameter sensitivity analysis of the model with respect to the thalassemia major populations and uneducated and educated carrier populations as shown in Figs 3–5. We found that as birth rates increased, the thalassemia major population increased; and that as marriage reconsideration rates increased, the thalassemia major population decreased. The birth rate effect is due to the rapid population growth of the UAE whereby the thalassemia carrier populations who still marry and could produce thalassemia major children increase. Interestingly, the sensitivity regarding education and premarital screening rates showed two opposite directions. That is, as the rate of education about thalassemia increased, the number of thalassemia cases decreased. On the other hand, as the rate of premarital screening increased, the thalassemia major population tended to increase. As mentioned before, the UAE population growth results in the growth of carrier population. Thus, as the carrier population grows, the premarital screening will identify the increasing number of carrier population, which implies the future growth of thalassemia major children in the UAE. Therefore, the sensitivity result regarding premarital screening measures the depth of the potential problem of carrier-carrier marriages. Our mathematical analysis and simulations in Fig 2 showed that although these control measures such as education about thalassemia and premarital screening seem to help in reducing the number of thalassemia cases in the the UAE, this decrease in cases is not an indicator of a possible thalassemia-free status in the future. In fact, the number of thalassemia cases will increase eventually. Thus, we summarize what we found from our mathematical modeling as follows: Premarital screening and education about thalassemia do not effectively reduce marriages between carrier populations; Unless all carrier-carrier marriages are stopped, the eradication of thalassemia can not be guaranteed; As long as a carrier population is present in the whole population, a thalassemia major population will always exist; Unless the birth rate is strictly smaller than the death rate of the whole population, thalassemia-free status will never be achieved no matter what control measures are used.

Output: contrast


Input: Claim: Some cultures have legends of creatures like Bigfoot and the Loch Ness Monster. [SEP] Text: Een correctie voor een kleine WAP-aandeelhouder uit de teller en de noemer leidt slechts tot een beperkte verschuiving in de berekening van het 90%-criterium (zie in gelijke zin M. W. Josephus Jitta, annotatie bij (OK) 4 april 2017, ECLI:NL:GHAMS:2017:1203, JOR 2017/162, punt 9). Naarmate een grote WAP-aandeelhouder alleen of meer WAP-aandeelhouders samen over een groter belang beschikken, zal de eliminatie uit het 90%-criterium sneller leiden tot het buiten werking stellen van het billijke prijsvermoeden. Dit brengt namelijk een grotere verschuiving in het 90%-criterium met zich. Doordat WAP-aandeelhouders vaak grootaandeelhouders zullen zijn, die andere voorwaarden kunnen bedingen dan kleinere aandeelhouders, is deze constatering relevant voor de praktijk. 5 Een weerlegbaar prijsvermoeden? 5. 1 Onder welke omstandigheden kan het prijsvermoeden worden weerlegd? Het billijke prijsvermoeden is volgens de wetsgeschiedenis57x Kamerstukken II 2005/06, 30419, nr. 3, p. 49; zie het woord ‘geacht’ in art. 15 lid 5 (voorlaatste alinea) van Richtlijn 2004/25/EG; Group of Experts 2002, p. 69. en jurisprudentie58x (OK) 5 september 2010, ECLI:NL:GHAMS:2010:BO5174, ARO 2010/155 (Schuitema), r. o. 3. 9. een weerlegbaar wettelijk bewijsvermoeden.

Output: pass


Input: Claim: Natural selection drives evolution through differential survival. [SEP] Text: Natural selection drives rapid evolution of mouse embryonic heart enhancers 2 Proceedings of the 23rd on (GIW 2012) access Published: 12 December 2012 Natural selection drives rapid evolution of mouse embryonic heart enhancers Ben-Yang Liao1 & Meng-Pin Weng1 BMC 11. 5 embryonic heart enhancers were found to exhibit exceptionally weak sequence conservation during vertebrate evolution compared to enhancers of other developing organs. However, it is unknown whether this phenomenon is due to elevated mutation rates, or is a consequence of natural selection. ResultsIn this study, based on the aligned orthologous genomic sequences of mouse and other closely related mammals, the substitution rates of fourfold degenerate sites or intron sequences in neighboring genes were used as neutral 11. 5 stage were examined in p300 ChIP-seq experiments [9], the "specific enhancers" defined in the present study may function in other tissues or developmental stages during mouse embryogenesis. Furthermore, the term "pleiotropic" was used to describe enhancers that are likely to significantly affect the developmental processes of at least two of the examined embryonic organs in [9] when they are absent from the genome. The recombination rate of the mouse genome segment in which an enhancer was located was obtained from the Supplementary table of [29]. Properties of the mouse genesThe coordinates of the mouse genes analyzed were retrieved from the BioMart ( For mouse genes with a null phenotype, the essentiality of each gene was defined based on phenotypic annotations of Informatics 4. 21 ( according to [30]. When premature death or infertility were the knockout phenotype, these genes were considered essential. All other genes with at least one documented null phenotype were considered non-essential. The gene expression profiles for the mouse genes analyzed were obtained from microarray data collected using 61 mouse tissues, including 53 adult tissues, 3 cell lines, and 5 early embryos from E6. 5 to E10. 5 [31]. Expression levels were calculated by averaging microarray-based expression signals from all tissues according to the previous studies [22, 26].

Output: corroborate


Input: Claim: All diseases can be eradicated by altering the human genome. [SEP] Text: The result of our study regarding premarital screening and carrier-carrier marriages are consistent with the situation in other MENA countries, such as Jordan and the Kingdom of Saudi Arabia, that have a high rate of consanguineous marriage as shown in Table 1. These countries implemented mandatory premarital screening but do not allow termination of pregnancy for thalassemia prevention like the UAE. It has been reported that premarital screening contributed toward detecting carrier population and that carriers who knew their genetic status prior to marriage were more likely to cancel marriage with another carrier in these countries [28]. However, premarital screening did not effectively reduce the carrier-carrier marriages in these countries [28, 29]. The limitation of this work is lack of data on the impact of education about thalassemia and marriage reconsideration of carrier-carrier couples in the UAE. In fact, collecting this type of data, in particular, the impact of education about thalassemia will require the collaboration between local schools and government bodies, valid questionnaires to assess the impacts, and work force to process the collected data. Thus, it may take several years to complete the assessment. The significance of our work is providing a scientific assessment about the impact of education and marriage reconsideration of carrier-carrier couples via mathematical modeling and sensitivity analysis without such data. Furthermore, the result of our study can raise public awareness about the implication of carrier-carrier marriages that have a 1-in-4 chance of having thalassemia major child and the fact that only 100% marriage reconsideration of carrier-carrier couples can lead to the thalassemia eradication in the UAE. In conclusion, the UAE’s current almost-thalassemia-free status does not imply that the population is approaching true thalassemia free status because there is still a large carrier population in the UAE. The UAE might experience a decrease in thalassemia major population due to government efforts to reduce carrier-carrier marriages, but as soon as the government stops its emphasis on thalassemia control at present level, the thalassemia major population will experience a resurgence. Therefore, we suggest that the UAE government continue its current level of thalassemia management and develop various additional ways to reduce carrier-carrier marriages. Supporting InformationS1 Material. Supplementary material for mathematical model. Conceptualization: SK. Formal analysis: SK.

Output: contrast


Input: Claim: Some cultures have legends of creatures like Bigfoot and the Loch Ness Monster. [SEP] Text: Volgens de huidige jurisprudentie van de OK betekent dit dat het billijke prijsvermoeden nog weerlegd kan worden nadat de OK heeft vastgesteld dat is voldaan aan het 90%-criterium. Weerleggen kan volgens de OK in twee gevallen: (1) wanneer er aanwijzingen bestaan dat de biedprijs niet ten minste overeenstemt met de waarde van de aandelen op het moment van het bod (par. 5. 2), of (2) wanneer een groot deel van het geplaatste kapitaal in handen is van enkele aandeelhouders waardoor slechts een geringe free float bestaat (par. 5. 3). 59x (OK) 4 april 2017, ECLI:NL:GHAMS:2017:1203, ARO 2017/139 (I), r. o. 3. 21. Ik meen dat een alternatieve benadering beter is. Deze omstandigheden moeten een rol spelen bij de vraag of aan het 90%-criterium is voldaan. Het ligt niet in de lijn van de ratio achter het prijsvermoeden om na het vervullen van het 90%-criterium een weerleggingsmogelijkheid open te houden. Hieronder ga ik in op de redenen daarvoor. 5. 2 De werkelijke waarde van de aandelen ligt hoger dan de biedprijs Volgens de OK kunnen zich ondanks het hoge aanmeldpercentage aanwijzingen voordoen dat de biedprijs niet overeenstemt met de werkelijke waarde van de aandelen op het moment van het bod. 60x (OK) 4 april 2017, ECLI:NL:GHAMS:2017:1203, ARO 2017/139 (I), r. o.

Output: pass


Input: Claim: Natural selection drives evolution through differential survival. [SEP] Text: Tests of natural selection on enhancer sequencesTo study the patterns and determinants of enhancer evolution rates, aligned mouse-rat (Rattus norvegicus), mouse-human (Homo sapiens), and mouse-rat-human orthologous genomic regions were retrieved from Ensembl ( [32], or the ( [33] (genome versions: mouse: mm9; rat: rn4; human: hg18). Sequence divergence was subsequently calculated, and the numbers of substitutions were computed. Based on the genomic alignments retrieved from the ( [33], the sequence divergence of enhancer regions (D) from mouse versus other mammal sequences was calculated according to baseml of PAML [34] using a GTR model with gamma distribution for site heterogeneity (model = 7; ncatG = 5). Fourfold degenerate sites and intron sequences of the nearest gene with an ortholog in the rat or human genome were used as neutral 0. 01<P≦0. 05 and ***P≦0. 001 by Mann-test). FB, forebrain; MB, midbrain; LB, limb; HT, heart. Full size imageFurthermore, based on alignments of mouse-rat-human orthologous DNAs, the number of nucleotides that were ancestrally A or T before mouse-rat divergence (human and rat are both either A or T of the aligned site) and had a substitution event in the mouse lineage was calculated and defined as "NsubstitutedA/T" for each enhancer. The number of mouse lineage-specific substitutions from A/T to G/C (NA/T→G/C) was also calculated for each enhancer. If heart enhancers underwent more GC-biased gene conversion events, they would be predicted to have a higher NA/T→G/C to NsubstitutedA/T ratio. However, heart enhancers were associated with a significantly lower ratio of NA/T→G/C to NsubstitutedAT (Figure 2B) compared to the enhancers of other tissues. In combination, the results shown in Figure 2 indicate that heart enhancers did not experience more GC-biased gene conversion events over their evolution. Therefore, mechanisms associated with GC-biased gene conversion did not explain the rapid evolution of heart enhancers and the selective pressure acting on them.

Output: corroborate


Input: Claim: All diseases can be eradicated by altering the human genome. [SEP] Text: MainGiven the disappointing results obtained by the Human Genetics community through systematic linkage screenings of the genome, Risch and Merinkangas1argued that ‘the future of the genetics of complex diseases is likely to require large scale testing by association studies’. If linkage studies have low power to detect common variants with small odds ratios (OR), they are also doing a poor job at detecting very frequent variants with high genotypic or allelic ORs, a situation where association tests might perform better. A good illustration of this point is provided by the VNTR flanking the insulin gene. The association between the locus and type I diabetes is easily detected, and the risk allele is frequent (about 70% in the general population) with an allelic OR around 3. 9. 2 The distribution of alleles shared identical by descent (IBD) in sib-pairs, however, is very close to its null expectation and linkage is very difficult to detect. Even on large sib-pair samples, discordant results have been described. 3, 4 An additional interesting feature of association studies is to allow a much more precise location of risk factors. Whereas the precision of location provided by linkage studies is sized in cM, it is sized in kb or even bp for association studies. Technological developments have rapidly made large-scale association studies a reality. The HapMap project (www. hapmap. org) launched by an international consortium by the end of 2002 publicly released the first data in 2005. The first genome-wide association studies have been published recently. 5, 6, 7 Large-scale association studies using maps of anonymous and frequent SNPs are presented as the new tool that will accelerate the discovery of genes related to common diseases' (HapMap Press Release, 7 February 2005). In the present paper, we would like to debate around two questions that are central to the discussion on the power of genome-wide association studies: will most genetic variants involved in complex diseases be detectable by systematic association testing and, in the best-case scenario where a signal is observed, what will be its contribution to the understanding of the pathological process? Will most genetic variants involved in complex diseases be detectable by systematic association testing? The standard strategy for systematic association testing is to perform allelic tests using SNPs tagging common variants and/or haplotypes to limit both the multiple testing correction and the genotyping cost.

Output: contrast


Input: Claim: Some cultures have legends of creatures like Bigfoot and the Loch Ness Monster. [SEP] Text: 3. 21. Ik meen dat alleen aanwijzingen die zich voordoen vóór de peildatum en die niet bekend zijn in de markt een indicatie kunnen opleveren dat de waarde van de aandelen niet overeenkomt met de biedprijs. De systematiek van de peildatum dwingt tot uitsluiting van aanwijzingen die zich voordoen ná de peildatum. De reden daarvoor is dat de peildatum het moment is waarop het aan de aandelen verbonden risico in verband met waardeverschuivingen overgaat op de bieder. Of zich daarna nog omstandigheden voordoen die de waarde van de onderneming beïnvloeden, komt voor rekening van de bieder en is daarom niet van belang bij de vraag wat een billijke prijs voor de aandelen is. Daarnaast geldt in de bedrijfseconomie dat de waarde van een vermogensbestanddeel gelijk is aan de netto contante waarde van de op de peildatum verwachte toekomstige kasstromen die uit dat aandeel voortvloeien. Centraal staan daarom de verwachtingen over toekomstige nettokasstromen en de opportuniteitskosten van het aandeel op de peildatum en niet verwachtingen die daarna ontstaan. 61x K. W. M. Scheepers, Waarderen bij uitkoopprocedures na Unit4 en DIM Vastgoed, in: J. Huizink (red. ), Waardering van aandelen na Unit4, Deventer: 2016, p. 33-35.

Output: pass


Input: Claim: Natural selection drives evolution through differential survival. [SEP] Text: To control for the expression level of adjacent genes, enhancers were divided into three groups depending on the expression level of the adjacent gene, < 200, 200-400, and ≥ 400. D and D/d4 were then compared for the enhancers of the four tissues within a given group. After such controls, embryonic heart enhancers still had the highest D (Figure 5A) and D/d4 (Figure 5B) values. These results suggest that the relatively low pleiotropy of embryonic heart enhancers, and their physical proximity to highly expressed genes, only partially accounts for their high rate of evolution and biases in selection. Figure 5Pleiotropy and expression levels of adjacent genes do not explain enhancer evolutionary rate variations. Comparisons of D (A) and D/d4 (B) for mouse forebrain (FB), midbrain (MB), limb (LM), and heart (HT) enhancers after controlling for the enhancer pleiotropy and the expression level of adjacent genes. Only specific enhancers are included in the analysis. The values of upper quartile, median, and lower quartile are indicated in each box, whereas the bars outside the box indicate semi-quartile ranges. Pairwise comparisons showing significant difference in D or D/d4 are connected with gray lines (***P≦0. 001 by Mann-test). Full size imageConclusionsThe rapid evolution rates of mouse embryonic heart enhancers can potentially be explained by elevated rates of mutation and/or changes in the direction or intensity of natural selection. In the present study, neutral sites of the neighboring gene were used as 11. 5 heart enhancers cannot be explained by potential confounding factors examined in the present study, and therefore, may be directly associated with embryonic tissue factors. The identification and understanding of regulatory DNAs in the mammalian genome is a major goal in the post-genomic era. This study employed a simple, yet effective, method to explore the role of natural selection on the evolution of non-coding sequences. Although the present study indicates that the rapid evolution of heart enhancers is likely to have been the result of a selective force associated with the type of embryonic tissue involved, the underlying causes for the relaxed selective constraint, or the higher frequency/intensity of positive selection, remain to be discovered.

Output: corroborate


Input: Claim: All diseases can be eradicated by altering the human genome. [SEP] Text: By construction, this approach has been recognized to have low power to detect the effects of rare variants, which are poorly tagged by common SNPs. Relatively rare variants are known to contribute to a variety of common, complex diseases. In Crohn's disease, the three risk alleles in the NOD2 gene have frequencies smaller than 5% in populations of European descent. 8, 9 Population genetics modelling of the expected genetic variation at disease susceptibility loci has also suggested that rare variants may play an important role in complex disease susceptibility. 10, 11 When selection is weak, as seems likely for many complex disease mutations, genetic drift becomes important, and the total frequency of susceptibility mutations is expected to vary widely among loci. In contrast, almost all common SNP-based variation as well as other SNP-correlated common variants (including common deletions12, 13) can be interrogated either directly or by surrogate SNPs or haplotypes. The issue is whether we will be able to design studies powerful enough to detect them. A number of variants with both high frequency and sizeable effects have been identified, including ApoE4 in Alzheimer's disease and cardio-vascular diseases or HLA factors in autoimmune diseases. Variants with similar sizeable effects may still have to be discovered. Some may have escaped identification by linkage studies because of a very high susceptibility allele frequency. Others may be located in regions already broadly detected by linkage as in the recent whole genome association successes. 6, 7Aside from these large effect variants, common susceptibility alleles or haplotypes with quite modest ORs – in the range of 1. 15–1. 5, with the majority in the range of 1. 15–1. 2514 have been shown to have reproducible effects (via meta-analysis) on various phenotypes. These variants with low marginal risks may, in fact, have strong effects on disease, but restricted to particular genetic background or environment. Indeed, complex models of interaction between genes, sex and environment have been extensively described in animal models for various complex traits. 15 Identifications of these variants – that may be far from exceptions in humans – may thus constitute important steps in the understanding of the physiopathology of the diseases, but very challenging ones. Finally, to control for the multiple testing in genome-wide context, effects of SNPs may only be tested at the allelic6, 7 or simple haplotypic level (haplotypes made of 2 or 3 markers).

Output: contrast


Input: Claim: Some cultures have legends of creatures like Bigfoot and the Loch Ness Monster. [SEP] Text: Het gebruiken van een historische peildatum en de manier waarop vermogensbestanddelen gewaardeerd worden, maken dat alleen aanwijzingen die zich voordeden vóór de datum van de betaalbaarstelling onder het bod invloed kunnen hebben op de billijke prijs. 62x (OK) 7 juli 2015, ECLI:NL:GHAMS:2015:2775, ARO 2015/178 (Unit4), r. o. 3. 17. De OK kiest in beginsel voor een historische peildatum. Dit standpunt is later bevestigd in onder meer (OK) 14 juli 2015, ECLI:NL:GHAMS:2015:2897, ARO 2015/200 (Nutreco) (voor art. 2:92a BW) en (OK) 14 juli 2015, ECLI:NL:GHAMS:2015:2914, ARO 2015/204 (Exact Holding) (voor art. 2:359c BW); en Bulten bepleitten deze systematiek al in 2014: M. W. & C. D. J. Bulten, Kroniek uitkoop en geschillenregeling 2014, in: M. Holtzer, A. F. J. A. Leijten & D. J. Oranje, Geschriften vanwege de Litigation 2014-2015 (VDHI nr. 128), Deventer: 2015, p. 148-153. In de inleiding noemde ik dat er één arrest is waarin – ambtshalve63x kan de OK ambtshalve afwijken van het prijsvermoeden en zelfstandig een uitkoopprijs vaststellen wanneer de omstandigheden daartoe nopen, zie Salemink 2014, p. 232. – is afgeweken van het billijke prijsvermoeden. In de Mediq-casus werd een openbaar bod gedaan door AI Garden B. V.

Output: pass


Input: Claim: Natural selection drives evolution through differential survival. [SEP] Text: Javascript is disabled in your browser. Please enable Javascript to view PeerJ. Natural selection drives chemical resistance of Datura stramonium All reviews of published 2023. Peer reviewers are encouraged (but not required) to provide their names to the authors when submitting their peer review. If they agree to provide their name, then their personal profile page will reflect a public acknowledgment that they performed a review (even if the 2016. The first revision was submitted on March 10th, 2016 and was reviewed by 2 reviewers and the Academic Editor. A further revision was submitted on March 14th, 2016 and was reviewed by the Academic Editor. The 2016. Version 0. 3 (accepted) Marion Röder · Mar 15, 2016 · to a very good manuscript. 0. 3 (PDF) Download author's response letter - submitted Mar 14, 2016 Version 0. 2 Marion Röder · Mar 13, 2016 · Both reviewers agree that the manuscript was significantly improved. There are remaining minor concerns about typos in the manuscript. Please, review your manuscript carefully for typing errors, before it can finally be accepted. Reviewer 1 · Mar 11, 2016 Basic reporting Very good. The initial version was good and this version is even better. Experimental design Good. I can see the argument for changing the statistical analyses and think that the authors did a good job on those reanalyses. Validity of the findings The results seem to be carefully interpreted. Additional comments The manuscript could use one more reading for typos, for example: line 234: length, not lenght line 578: This points that. . . " A word seems to be missing line: 705: predator, add s Cite this review as (2016) #1 of "Natural selection drives chemical resistance of Datura stramonium (v0. 2)". PeerJ · Mar 10, 2016 Basic reporting Experimental design Validity of the findings Additional comments The manuscript is greatly improved. In my opinion this 0. 2)". PeerJ 0. 2 (PDF) Download author's response letter - submitted Mar 10, 2016 Version 0. 1 (original submission) Marion Röder · Jan 22, 2016 · Both reviewers agree that the study is valuable and performed well. Both have some minor comments regarding mainly formal things, which should be easy to comply. Please, also take in consideration the attached annotated manuscript.

Output: corroborate


Input: Claim: All diseases can be eradicated by altering the human genome. [SEP] Text: But interaction between alleles or between distant SNPs within a susceptibility gene may be poorly detected at the allele level even in the presence of non-negligible effects at the genotype/haplotype level. Whether we will be able to power studies to detect common risk alleles with OR<1. 25 for all diseases is a critical issue. Apart from the challenge to collect huge samples without compromising on the quality of phenotypes, the crucial issue is whether human samples of sufficient sizes with homogeneous allele frequencies and pattern of linkage disequilibrium (LD) do exist. For some diseases, the inter-population variability may be too large to allow the recruitment of samples not subject to population stratification and large enough to detect variants with small effects. Similarly, once the variant is detected in a first study, it might be difficult to obtain samples to perform replication studies. First, these samples will need to be as large or even larger16 and, second, the difference in both variant frequencies and LD pattern among populations may make the signal undetectable in other populations. The difficulty of replication is well illustrated in the recent work of Reich et al. 17 on multiple sclerosis, (MS) where an association on chromosome 1 in African-Americans is not replicated in another sample of Afro-Caribbeans. Consequently, it is not possible to decide whether the association described is driven by a causal variant or whether it is just another false positive result. Altogether, we believe that these different elements invite cautiousness regarding the ability of genome-wide association studies to detect most genetic variants involved in complex diseases. In the best-case scenario where a signal is observed, what will be its contribution to the understanding of the pathological process? The main motivation behind looking for genetic risk factors for complex diseases is to get a better insight into the pathological process of the diseases. However, to go from an association signal to a deeper knowledge on the causal variants and their effect measurements is not that simple. The study of the HLA component in auto-immune diseases well illustrates the caveats encountered. If the association between type I diabetes (IDDM) and the HLA class II regions has been known for more than 20 years, the causal variants of the region have still to be identified.

Output: contrast


Input: Claim: Some cultures have legends of creatures like Bigfoot and the Loch Ness Monster. [SEP] Text: op de aandelen Mediq N. V. De biedprijs bedroeg EUR 14 en er was voldaan aan het 90%-criterium. 64x (OK) 11 maart 2014, ECLI:NL:GHAMS:2014:785 (Mediq II). Ter ondersteuning van de gevorderde uitkoopprijs, die gelijk was aan de biedprijs, heeft de bieder een assurancerapport overlegd. Uit het eindarrest blijkt dat de OK op basis van een nieuwe deskundigenverklaring afwijkt van het billijke prijsvermoeden omdat de waarde van de onderneming is gestegen in het jaar nadat de uitkoopprocedure aanhangig is gemaakt. 65x (OK) 13 mei 2014, ECLI:NL:GHAMS:2014:1976 (Mediq III), r. o. 2. 4. Veranderde marktomstandigheden na afloop van het bod rechtvaardigen een hogere prijs. De waarde van de aandelen steeg in de uitkoopprocedure van EUR 14 naar EUR 17. 66x (OK) 13 mei 2014, ECLI:NL:GHAMS:2014:1976 (Mediq III), r. o. 2. 3. De oplettende lezer ziet dat de veranderende marktomstandigheden waardoor de waarde van de aandelen steeg, zich in deze casus voordeden na de datum van de betaalbaarstelling onder het bod. Doordat de OK is omgegaan in het Unit4-arrest kunnen omstandigheden die zich voordoen na de datum van betaalbaarstelling onder het bod – zoals de veranderende marktomstandigheden uit de Mediq-casus – niet meer noodzaken tot een aanpassing van de billijke prijs.

Output: pass


Input: Claim: Natural selection drives evolution through differential survival. [SEP] Text: In addition to this reviewer 2 has suggestions about alternative or additional forms of statistical analysis. I let it for the decision of the authors if they want to pick up these suggestions. If they do not want to change their analysis, please give some comments about this decision. Download annotated manuscript Reviewer 1 · Jan 16, 2016 Basic reporting This is an excellent study. The questions are clear and the analyses are appropriate. and Figures need some clarifications to help readers. Table 1: add sample sizes Table 2: In the table caption, identify T as the test statistical and expand the acronym AIC and and briefly explain how it is used here. Most readers will know, but everything in a table should be briefly identified in table captions. Figure 2: Briefly explain in the table caption the meaning of infestation intensity so that readers can understand the scale on the Y-axis without going back to the Methods. Figures 3 and 4: Give correlation values and p-values on the figures so that readers can assess the lines that are shown Figure 4: Indicate whether the error bars are standard errors, confidence limits, or something else. The manuscript should be proof-read for a few remaining typographical errors (e. g. , unknow rather than unknown in one place; a missing "to" on line 289). I do not know if "All appropriate raw data have been made available. . . " Experimental design The methods are clearly described and the statistical analyses are appropriate. There are multiple ways of analyzing results such as these, but the authors have taken a reasonable approach. Validity of the findings The results are convincing and suggest strong, geographically variable, and potentially reciprocal, selection on these interacting species. This study appears to have been carefully done, carefully interpreted, and not over-interpreted. The conclusions do not go beyond the results. This is a very good paper, requiring considerable field and laboratory work. It is among the few studies have have assessed selection differentials among potentially coevolving species in many populations. The results suggest ongoing selection on the species and potentially ongoing reciprocal selection in some localities. Additional comments This is a nicely designed and analyzed study, suggesting the potential of a geographic mosaic of coevolution between these species. Cite this review as (2016) #1 of "Natural selection drives chemical resistance of Datura stramonium (v0. 1)".

Output: corroborate


Input: Claim: All diseases can be eradicated by altering the human genome. [SEP] Text: A particular amino acid (non-‘Asp57’) of the DQβ chain was suspected for a while18 as it is strongly associated with the disease: patients with an aspartic acid at position 57 in the DQβ chain are very rare. However, this hypothesis was rejected,19 because it could neither explain the overall HLA genotype distribution nor the HLA haplotype sharing of affected sibs. 19 This example illustrates the importance of not only considering allelic association but also genotypic distributions and the importance of identifying models that can explain both the association and linkage information and not only one of them. In celiac disease, genetic susceptibility in the HLA region is mainly explained by one DQ heterodimer whose two components (DQA1 and DQB1 alleles) can either be on the same HLA haplotype (cis-position) or one on each complementary haplotype (trans-position). 20 This functionally relevant model was found using both biological elements on the structure and function of HLA molecules21 and the observed genotype distribution in patients. However, because it cannot clearly explain the HLA sharing among affected sibs and because there are geographical differences in the risks conferred by the DQ heterodimers,22 this model cannot account for the whole HLA component of the disease, which suggests that other HLA factors must be involved. In these two examples, the HLA component acts differently, through complex interactions of numerous variants. Deeper understanding could be obtained only through more detailed knowledge of gene diversity, patient genotype distributions, IBD sharing in affected siblings conditional on patient genotype, and biological understanding of the function of genes in the HLA region. Detection of an association was only the very first step. In a recent study, Lincoln et al. 23 used a large-scale SNP association strategy for studying the involvement of the MHC in MS. The strongest association is observed with haplotype blocks in the HLA class II region and, conditional on this association, there is no evidence for other HLA-region risk factors for MS. These results are an additional illustration of the limits of strategies relying on only association information. Despite the use of large numbers of simplex and multiplex families with dense SNP typing, the study just ends at a result which has been known for many years.

Output: contrast


Input: Claim: Some cultures have legends of creatures like Bigfoot and the Loch Ness Monster. [SEP] Text: Dit heeft tot gevolg dat deze casus zich niet meer voor kan doen na het Unit4-arrest. Deze foto van het monster van blijkt toch een drijvende boomstam te zijn. Er kunnen zich bijzondere omstandigheden voordoen die noodzaken tot afwijking van de peildatum, waardoor omstandigheden na de datum van betaalbaarstelling wel van invloed kunnen zijn op de hoogte van de billijke prijs. Afwijking is, voor zover dat in de jurisprudentie aan de orde is geweest, alleen mogelijk bij een lang tijdsverloop tussen de betaalbaarstelling onder het bod en het uitbrengen van de dagvaarding. Die situatie doet zich bij het billijke prijsvermoeden niet voor, omdat het billijke prijsvermoeden alleen gebruikt kan worden wanneer de minderheidsaandeelhouders binnen drie maanden gedagvaard worden. 67x (OK) 7 juli 2015, ECLI:NL:GHAMS:2015:2775, ARO 2015/178 (Unit4), r. o. 3. 18. Er is dan per definitie geen sprake van een lang tijdsverloop tussen de betaalbaarstelling onder het bod en de dagvaarding. Lang tijdsverloop in de procedure zelf lijkt geen reden te zijn voor een andere peildatum. 68x In Unit4 werd ondanks een vertraging in de procedure van negen maanden de datum van de betaalbaarstelling onder het bod nog steeds als peildatum toegepast. De ratio achter het prijsvermoeden verplicht tot een tweede beperking op welke aanwijzingen in acht kunnen worden genomen.

Output: pass


Input: Claim: Natural selection drives evolution through differential survival. [SEP] Text: PeerJ · Jan 21, 2016 Basic reporting Experimental design This is a great dataset with a correct “experimental” design. With those data it is possible to study how T. soror affects defensive alkaloids in seeds and leaves of the plants and whether these selective pressures affect the geographic variation on plant traits –such as the variation on levels of defensive compounds. However the current treatment of data is not completely satisfactory. Important but easy-to-fix changes in the analytical approach should we made in order to make this research correct. The general approach is great but there are some mistakes regarding the types of model used, or even the response variable in the latest two models (which are the more important in this ms). Note that I took the opportunity to analyze the data myself (from the dataset in the submission) and actually found that the effect of natural selection drives among populations variation on the concentration of alkaloids, thus the main message in the manuscript is not going to change once it is properly analyzed. I think that the phenotypic trait which should be studied in the latest two models is the content on defensive compounds. It should be analyzed how quantity of atropine and scopolamine in seeds and leaves (or altogether) affect the number of seeds surviving from predation. It would be also possible to make combinations of these four traits (for example, total alkaloids in seeds or in leafs, or total atropine or scopolamine in plants). The first step (which in my opinion is optional) could be to analyze how number of seeds saved from predation depends on the population, the number of fruits per plant, the atropine in seeds, atropine in leafs, scopolamine in leafs, scopolamine in seeds (correlations between phenotypic traits should be taken into controlling for colinearity issues). In this model interaction between population and each of the phenotypic traits should be included. This would shed some light in the issue of whether defensive compounds affect the reproductive output of plants (after predation, i. e. the number of seeds saved from predation) and whether that relationship is constant or varies among populations. Second step would be what you already have correctly performed. You properly run phenotypic selection analyses at the level of population.

Output: corroborate


Input: Claim: All diseases can be eradicated by altering the human genome. [SEP] Text: HLA is certainly a unique region of the genome for its genetic complexity (level of polymorphism, pattern of LD and clustering of many functionally related genes). Therefore, the challenges encountered in this region are not fully representatives of the ones that we face elsewhere on the genome. Still, the HLA region is one of the most extensively studied and one exhibiting the strongest genetic factors for many complex diseases described so far. This, together with the accumulation of experiences in other regions of the genome, makes us believe that, though different, these non-HLA challenges may not be less complex. The availability of tools (e. g. high-throughput genotyping platforms) and information (e. g. a haplotype map of the human genome) are a valued and welcome addition to the armamentarium geneticists can use to identify and characterize the genetic component to common diseases with complex transmission. But we should resist the temptation to assume that the models most favourable for the utility of these new tools must be the right models for all the variants involved in complex diseases just because our studies will work better if these most favourable models are correct. We can ill afford to go from a generation of underpowered and ultimately disappointing linkage and family studies directly to a generation of underpowered and disappointing association studies. At the same time, the impressive diversity of causal variant models already identified favours continued diversification of strategies. Identification of biologically relevant novel pathways of disease susceptibility followed by candidate gene strategies allowing for the simultaneous consideration of these connected genes may be quite effective at identifying new variants affecting susceptibility. Linkage data contain considerable additional information capable of aiding the discrimination of causal variation from the nearby variation that is merely in LD. Consequently, linkage studies may still pay dividends even if the newer tools are as successful as we all hope, and we believe efforts to recruit family data should not be given up too quickly in favour of only large samples of cases and controls. Linkage and association studies should be considered as complementary strategies and not as concurrent.

Output: contrast


Input: Claim: Some cultures have legends of creatures like Bigfoot and the Loch Ness Monster. [SEP] Text: Aanwijzingen dat de biedprijs niet overeenstemt met de daadwerkelijke waarde van de aandelen moeten aanwijzingen zijn waarvan de maatman-aandeelhouder niet op de hoogte kan zijn. Het moet gaan om informatie die niet bekend is in de markt. 69x Scheepers 2016, p. 33-35. De geïnformeerde maatman-aandeelhouder heeft alle beschikbare informatie namelijk tot zich genomen en daarop de beslissing gebaseerd dat de biedprijs een billijke prijs is en om zijn aandelen aan te melden. Alleen niet-beschikbare informatie had hem tot een ander oordeel kunnen brengen. Dat bepaalde informatie niet beschikbaar is, zal zich in de praktijk niet vaak voordoen. Een openbaar bod is in de regel goed gedocumenteerd, met onder meer een biedingsbericht, fairness opinion(s) en analistenrapporten. De informatie over de waarde van de aandelen op de peildatum zal daarom zo accuraat mogelijk beschikbaar zijn. Het argument dat beursvennootschappen die lijken op de doelvennootschap een hogere beurskoers hebben en daarom de biedprijs hoger had moeten zijn,70x Dit argument werd door minderheidsaandeelhouders aangedragen in de NIBC-uitkoopprocedure. (OK) 12 april 2022, ECLI:NL:GHAMS:2022:1217, ARO 2022/107 (NIBC), r. o. 3. 27. kan dus niet opgaan.

Output: pass


Input: Claim: Natural selection drives evolution through differential survival. [SEP] Text: By regressing each phenotypic trait (for example atropine in seeds) on the plant relative fitness (number of seed saved from predation relative to the average of the population) selective differentials are assessed (S). Also you understood, and I agree, that the important question in here is not the significance of those selective differentials within populations. The relevant question here is addressed on the next step –which is studying how the selective pressures explain variation on phenotypic traits among populations. On the third step selective pressures should be covariates explaining phenotypic traits at the population level (one model for each trait as response variable, one for average population atropine in seeds, another for average population scopolamine in seeds etc. ). This is where you performed an important conceptual mistake by running the models for the response variable “infestation” instead of the selected phenotypic traits which would be “alkaloids”. I agree with you with the importance of adding environmental covariates to control for other sources of variation in these models. If selective differentials are found to be significant in explaining the among population variation on defensive traits (and my analyses using your dataset shows they are indeed), then it would be actually possible to state that “natural selection by T. soror drives, at least in part, the variation on defensive compounds across D. stramonium populations”. Some minor considerations (Please also see notes on attached pdf) • Please use GLM instead of LMM because your response variables are not normal. It is better to analyze actual distribution of variables by means of Models which allow fitting response variables to different error distributions and link functions depending on the nature of the response variables. • Please send table 1 to supplementary materials. • Analyses in figure 3 should be done at the plant level including populations as random factor (not using population averages) and only necessary for the sound seeds, the rest (in my opinion) is redundant. You are trying to show that infestation changes fitness. If you use sound seeds as response, and infestation levels as predictors, at the same time population as random factor that would be a better approach. If you add the interaction of population with infestation level, and it proves significant, that would show how selective pressures by weevils on defenses vary among population. Another possibility is to escape this step altogether and show the analyses done only from the calculations of selection coefficients on.

Output: corroborate


Input: Claim: All diseases can be eradicated by altering the human genome. [SEP] Text: As described above, mutations were reported, therefore, only if the disease associated protein has a close homolog that has been proven experimentally to interact with a protein that contains the same binding partner domain as seen in the PDB structure the interaction was modeled from (the 'structural template'). For example, [OMIM:+264900. 0011] is a Ser576Arg mutation of the human coagulation factor IX (PTA). The residue is part of a trypsin domain and seen to interact with Ecotin. However, the interaction between PTA and Ecotin is not yet recorded in any interaction database; therefore, the mutation cannot be included in our predictions. Using these criteria, 1,428 mutations from 264 proteins were predicted to be interaction-related (Figure 3). The full list is available in Additional data file 1. In total, we collected 25,322 mutations from OMIM and UniProt. This means that approximately 4% of all mutations could be linked to a protein interaction. Figure 3Data integration steps for interacting residue prediction. Schematic outline of data integration for the prediction of interacting residues. Mutations from OMIM and UniProt for which a residue in a homologous structure is involved in an interaction are selected. This set is restricted further by searching for homologous proteins with known interactions, taken from a range of protein interaction databases. We require that the the homologous interacting proteins contain the same pair of Pfam domains that was observed in the structural template. This results in a set of 1,428 interaction related mutations. Full size image Amongst these mutations, 454 mapped to a structure that exhibits an interaction between different proteins (hetero-interaction), while 1,094 mutations mapped to a structure with an interaction between two identical proteins (homo-interaction). This means that 120 mutations are found in structures of both homo- and hetero-interactions. The large proportion of homo-interactions can be explained by the overrepresentation of homo-interactions in the structural templates set: 70% of all distinct protein pairs in iPfam are homo-interactions, which is in accordance with recent findings that homo-interactions are more common than hetero-interactions [30].

Output: contrast


Input: Claim: Some cultures have legends of creatures like Bigfoot and the Loch Ness Monster. [SEP] Text: We moeten ervan uitgaan dat de maatman-aandeelhouder die informatie in zijn keuze om de biedprijs te steunen heeft verwerkt. De maatman-aandeelhouder vindt de biedprijs voor deze vennootschap namelijk nog steeds een billijke prijs, ondanks een afwijkende beurskoers van soortgelijke beursvennootschappen. Uit het voorgaande volgt dat alleen aanwijzingen die zich voordeden vóór de peildatum en die niet bekend waren in de markt een indicatie kunnen zijn dat de waarde van de aandelen niet overeenkomt met de biedprijs. Die aanwijzingen zullen zich slechts in zeer uitzonderlijke situaties voordoen. 71x Duynstee & 2017, p. 177. De Xeikon-casus is hier een voorbeeld van. Voor de overname van Xeikon door XBC – dus voor de peildatum – zijn er enkele onzakelijke transacties verricht waarvan de exacte impact op Xeikon niet bekend was. Hangende de uitkoopprocedure werd de impact op Xeikon via een enquêteprocedure duidelijk. Door de onzakelijke transacties verdampte op papier minstens EUR 30 miljoen van de ondernemingswaarde. Die waarde zat echter nog steeds in de vennootschap, bestaande uit vorderingen die Xeikon had op de oud-bestuurders die aan de onzakelijke transacties hadden meegewerkt.

Output: pass


Input: Claim: Natural selection drives evolution through differential survival. [SEP] Text: • In the dataset and in the manuscript it is not clear when showing results on alkaloids if results are on alkaloids of seeds or leaves or a combination of both. In the next version of the paper this information should be clarified. Validity of the findings No comments Additional comments The manuscript “Natural selection drives chemical resistance of Datura stramonium to its specialized seed predator” constitutes a very interesting piece of information. The study of effects of natural selection on geographic variation of plant traits is not commonly addressed. This is a very meritorious approach which is very scarce in literature. The research aimed to find out if seed predation by T. soror on Datura stramonium caused selective pressures and if this natural selection drives differences in plant resistance among populations. It was already known that atropine in this species is a defensive compound to leaf herbivory but it was not known whether this defensive compound was also related to predation upon seeds. Besides this interesting approach I find another major strength on this manuscript. I commend the authors on the nice dataset they have collected. Ecological studies comprising a large number of populations across broad geographical scales are uncommon –despite many evolutionary questions in ecology should be addressed from this perspective. This study comprises 31 populations of D. stramonium across central Mexico in which between 21 and 30 individuals per population have been studied, although actually between 7 and 10 plants per populations were used in the main analyses. The level of infestation by T. soror and the levels of defensive alkaloids (atropine and scopolamine) both in leaves and seeds for 7-10 plants per population (278 plants) have been measured. Additionally, some environmental covariates at the level of populations (mean annual temperature and precipitation) have been collected –which is a very good idea so that some environmental variation can be controlled in analyses showing how T. soror affects defensive compounds in D. stramonium. Download annotated manuscript Cite this review as (2016) #2 of "Natural selection drives chemical resistance of Datura stramonium (v0. 1)". PeerJ Submission (PDF) - submitted Jan 7, 2016 All text and materials provided via this peer-review history page are made available under a Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Output: corroborate


Input: Claim: All diseases can be eradicated by altering the human genome. [SEP] Text: Properties of mutations in interaction interfacesCurated set of interaction-related mutationsIn addition to the automatically derived data, we collected 119 mutations in 65 distinct diseases from the scientific literature for which there is evidence that they change the interactions of the protein they occur in (see Materials and methods). We call this the 'curated set' of interaction-related mutations (Additional data file 2). To our knowledge, it represents the biggest collection of high confidence interaction-related mutations to date. Below, we explore differences between interaction-related mutations and non-interaction-related mutations. We focus on the mechanism of the mutation, the mode of inheritance and residue composition. For most of the 1,428 mutations from the automatically generated set, no information about their mode of inheritance or functional mechanism was instantly available. To allow a comparison with the manually curated set, we sampled 100 mutations randomly and conducted a manual search of the literature in order to annotate their properties. Classification according to functionWe suggest a classification that groups mutations according to their effects into loss of function (LOF) and gain of function (GOF). Below this broad distinction, the GOF mutations can be further divided into two groups: pathological aggregation and aberrant recognition. Similarly, LOF mutations can be split into one class that disrupts obligate interactions between protein subunits and another class that interferes with transient interactions. From the curated set of interaction-related mutations, 95 mutations result in LOF, 17 in GOF, 4 mutations were reported to change the interaction preference of the protein and 3 could not be determined. The class of GOF mutations that result in protein aggregation contains 12 cases, comprising amyloid diseases like Alzheimer's or Creutzfeldt-Jacob, but also, for example, sickle cell anemia [OMIM:+141900. 0243]. Five cases result in aberrant recognition; for example, a Gly233Val mutation in glycoprotein Ib that leads to von Willebrand disease [OMIM:*606672. 0003] by increasing the affinity for von Willebrand factor. Amongst the LOF mutations, 61 affect transient interactions and 34 affect obligate interactions. The latter usually render proteins dysfunctional, for example, in the case of lipoamide dehydrogenase deficiency caused by impaired dimerization [31].

Output: contrast


Input: Claim: Some cultures have legends of creatures like Bigfoot and the Loch Ness Monster. [SEP] Text: Vanwege de onbekendheid met het bestaan van de vorderingen is de waarde van de vorderingen niet verdisconteerd in de biedprijs en heeft de maatman-aandeelhouder die informatie niet mee kunnen nemen in zijn beslissing om de biedprijs te steunen. 72x (OK) 18 december 2018, ECLI:NL:GHAMS:2018:4684, ARO 2019/60 (Xeikon/Recalcico), r. o. 2. 27-2. 28. Omdat de billijke prijs de prijs is die de hypothetische meest biedende koper betaalt, kan worden gezegd dat de bieder een hogere biedprijs had betaald als hij van de schadevorderingen op de bestuurders had geweten. Daarmee is de billijke prijs in de systematiek van artikel 2:359c BW in deze casuspositie een hogere prijs dan de biedprijs. De maatman-aandeelhouder is een geïnformeerde aandeelhouder die deze biedprijs niet had geaccepteerd als hij bekend was geweest met deze prijsverhogende omstandigheid. In zijn aanvaarding van het bod kan geen steun voor de biedprijs worden gelezen. Dit heeft tot gevolg dat niet aan het 90%-criterium wordt voldaan. Het prijsvermoeden verliest al zijn waarde, nu de maatman-aandeelhouder geen betrouwbare beslissing heeft kunnen nemen over de billijkheid van de biedprijs. De OK kan in dat geval niet anders dan deskundigen benoemen die in hun advies over de uitkoopprijs rekening houden met de vorderingen die de doelvennootschap heeft op haar oud-bestuurders.

Output: pass


Input: Claim: Horizontal gene transfer allows bacteria to acquire new traits. [SEP] Text: of genes through horizontal gene transfer (HGT) allows microbes to rapidly gain new capabilities and adapt to new or changing environments. Identifying widespread HGT regions within multispecies microbiomes can pinpoint the molecular mechanisms that play key roles in microbiome assembly. We sought to identify horizontally transferred genes within a model microbiome, the cheese rind. Comparing 31 newly sequenced and 134 previously sequenced bacterial isolates from cheese rinds, we identified over 200 putative horizontally transferred genomic regions containing 4733 protein coding genes. The largest of these regions are enriched for genes involved in siderophore acquisition, and are widely distributed in cheese rinds in both Europe and the US. These results suggest that HGT is prevalent in cheese rind microbiomes, and that identification of genes that are frequently transferred in a particular environment may provide insight into the selective forces shaping microbial communities. eLife digest From the depths of the ocean to the lining of the human gut, almost every environment on Earth is home to a unique community of microorganisms referred to as a microbiome. Within these communities, unrelated microorganisms can exchange genetic information through a process known as horizontal gene transfer. For example, genes linked to antibiotic resistance are often transferred between different microorganisms, which can create increasingly drug resistant microbes and has important implications for human health. Horizontal gene transfer has been studied for almost 100 years, but examining it directly is challenging because, almost by definition, it requires studying a community of microbes rather than one microbe in isolation. As such, researchers are looking for simple models of microbial communities that can be easily manipulated in experiments. Bonham et al. have now turned to the outer surface of cheese, also known as cheese rind, to better understand horizontal gene transfer. As a model system, the cheese rind microbiome is relatively simple to work with because cheese rind is easy to replicate in the laboratory, and the microbes growing on cheese can be grown on their own or in combinations with other microbes. By comparing the genetic material of 165 cheese-associated bacteria to one another, Bonham et al. identified over 4,000 genes that were shared between the bacteria, including several large clusters of genes that were shared by many species. Many of the identified genes (about 23% to be precise) appear to help the microorganisms acquire nutrients that are known to be in short supply on the surface of cheese surface, including iron.

Output: corroborate


Input: Claim: All diseases can be eradicated by altering the human genome. [SEP] Text: LOF mutations in transient interactions cause changes in localization or transmission of information, exemplified by a mutation in the BRCA2 gene that predisposes women to early onset breast cancer: a Tyr42Cys mutation in BRCA2 inhibits the interaction of BRCA2 with replication protein A, a protein essential for DNA repair, replication and recombination [32]. Lack of this interaction inhibits the recruitment of double stranded break repair proteins and eventually leads to an accumulation of carcinogenic DNA changes. Mode of inheritanceWe investigated the mode of inheritance for all mutations in the curated set, if information was available in the literature. All GOF mutations showed dominant inheritance (the two hemoglobin mutations exhibit incomplete dominance). Out of 61 LOF mutations for which inheritance information was available, 24 were autosomal dominant and 37 were recessive. Jimenez-Sanchez et al. [33] studied the mode of inheritance of human disease genes. According to them, mutations in enzymes are predominantly recessive, while mutations in receptors, transcription factors and structural proteins are often dominant. Overall, they find a ratio of 188:335 of dominant to recessive diseases. In our data set, the ratio of dominant to recessive mutations is 41:37 (31:29 in terms of diseases). This enrichment for dominant mutations is statistically significant, as determined by a two-sided test for equality of proportions (P-value < 0. 014). The increase was seen across functional categories, in enzymes as well as regulators and signaling proteins (data not shown). In the 100 randomly chosen mutations from the predicted set, we found a ratio of dominant to recessive mutations of 38:41, which is very similar to the ratio observed in the curated set (two-sided test for equality of proportions; P-value > 0. 68; hypothesis of difference in proportions rejected). In GOF mutations, dominant inheritance is not surprising, but the high proportion (39%) of dominant LOF mutations is noteworthy. Dominant inheritance in LOF mutations can be explained by either haploinsufficency or dominant negative effects [34]. In yeast, dosage sensitivity of members of protein complexes has been shown [35]. According to what Papp et al. call the 'balance hypothesis', stoichiometric imbalances have negative effects on the function of protein complexes. Dominance would thus be a result simply of a lack of functional protein subunits.

Output: contrast


Input: Claim: Some cultures have legends of creatures like Bigfoot and the Loch Ness Monster. [SEP] Text: 5. 3 Wat zegt een geringe free float over de billijkheid van de biedprijs? De tweede situatie waarin naar huidig recht het prijsvermoeden weerlegd kan worden, is de situatie dat er sprake is van een ‘geringe free float’. De OK heeft tot op heden niet duidelijk gemaakt wanneer daar sprake van is. Ik geef eerst een definitie. De ‘free float’ is het aantal aandelen dat vrij verhandelbaar is op de beurs: de uitstaande aandelen. 73x M. J. G. C. Raaijmakers, Ondernemingsrecht (Pitlo, deel 2), Deventer: 2017, p. 369. Een geringe free float is daarom een situatie waarbij er weinig aandelen uitstaan en er daarom weinig liquiditeit is. Dat wil zeggen dat een belegger zijn positie niet snel kan op- of afbouwen. Er is economisch onderzoek dat bevestigt dat een geringe free float leidt tot een grotere kans op informatieasymmetrie en een belemmering van efficiënte prijsvorming op de aandelenmarkt, ook wel prijsvolatiliteit genoemd. 74x X. S. Ding, Y. Ni & L. Zhong, Free float and market liquidity around the world, Journal of (38) 2016, p. 236-257; H. Le & A. Gregoriou, Liquidity and asset pricing: Evidence form a new free-float-adjusted price impact ratio, Journal of (49) 2002, afl. 4, p. 751-771. Dit wordt erkend in de wetsgeschiedenis, zie Kamerstukken II 2005/06, 30419, nr. 3, p. 49.

Output: pass


Input: Claim: Horizontal gene transfer allows bacteria to acquire new traits. [SEP] Text: Bacteria typically use specialized molecules called siderophores to scavenge for iron and uptake systems to carry the iron-bound siderophore back into the cell. Notably, only the genes associated with the uptake systems were found in some of the shared gene clusters. This finding suggests that horizontal gene transfer has allowed some microbes to “cheat” and take up iron-bound siderophores without expending energy to produce the siderophores themselves. Using the cheese rind microbiome as a model system, it becomes possible to explore how horizontal gene transfer works in more detail than before. A better understanding of this process can then be applied to other important microbiomes, including those where genes conferring antibiotic resistance are commonly exchanged. strides have been made in characterizing the composition of microbiomes, and in understanding their importance in the ecology of natural systems, in agriculture and in human health. However, despite these advances, the forces that shape the diversity, structure, and function of microbiomes remain poorly understood (Widder et al. , 2016). Investigating these underlying mechanisms in situ is difficult, as observational and sequenced-based analysis rarely enables causal conclusions (Nemergut et al. , 2013). Replicating microbial communities in vitro is also an enormous challenge, because of high levels of diversity and the difficulties in establishing pure cultures of most bacterial species. These obstacles significantly hamper our ability to move from observations of microbial diversity to the molecular mechanisms shaping key processes such as species interactions and microbial evolution. Horizontal gene transfer (HGT) is a major force in microbial evolution and can lead to the wholesale acquisition of novel functions. In some cases, these novel functions can have significant adaptive consequences, such as in the transfer of antibiotic resistance genes (Ochman et al. , 2000). HGT also allows rapid adaptation to new niches (Wiedenbeck and Cohan, 2011), as ecologically relevant genes may be acquired by species not previously adapted to a particular niche (Tasse et al. , 2010; Hehemann et al. , 2010). The movement of microbes to new environments has been shown to increase both the rate and impact of HGT, and HGT is most frequent for genes under positive selection (Niehus et al. , 2015).

Output: corroborate


Input: Claim: All diseases can be eradicated by altering the human genome. [SEP] Text: Genome-wide association studies are coming for human infectious diseases : 10 February 2009 Genome-wide association studies are coming for human infectious diseases Sonia Davila1 & Hibberd1 0. 1% [1]. Is this infectious disease distribution predominantly due to widespread general resistance over multiple genes or is susceptibility due to rare mutations in a few specific genes? This question on the nature of the genetic change, rare or common, has remained, despite numerous population studies of infectious disease. Candidate gene studiesAlthough family-specific mutations have been shown to have indisputable consequences in infectious disease [2–5], their effects in the general population are thought to be small [6]. There are also some very well established population-based mutations with clear effects on disease, from sickle cell trait protection against malaria [7] to CCR5, a known receptor of HIV, defective alleles in which have been associated with resistance to HIV infection [8]. Indeed, rare mutations leading to increased susceptibility to infectious disease can be identified in the general population, when looked for carefully [9]. Interestingly, the evidence from this field of work is currently pointing towards the concept of 'one gene, one infection' [10]. The strong evidence that a mutation in a single gene frequently leads to increased susceptibility to only one infection is also supported by animal studies, which have used forward genetics to show that, although many genes may be involved in recognizing a single pathogen, mutations in only one or a few lead to increased susceptibility to disease [11]. Despite the clear evidence identifying these so called 'major genes', it is unlikely that mutations in single genes are the only causes of genetic susceptibility in a population. So far, the work done to extend this approach to a population basis has used candidate gene studies and, in general, when they harmonize with the major genes findings, significant insights can be gained from them. For example, in meningococcal disease the 'major genes' lie in the complement pathway, with mutations in many of these genes (each restricted to just a few individuals) leading to greatly increased risk of disease [12]. Using one of these genes (that encoding mannose binding lectin) as a candidate gene in a population-based study has supported and extended these findings to the general population, revealing a polymorphism that can alter the initiation of this pathway, and thus the susceptibility to disease, in a large number of individuals [13].

Output: contrast


Input: Claim: Some cultures have legends of creatures like Bigfoot and the Loch Ness Monster. [SEP] Text: Als het bod ziet op een relatief klein aantal aandelen, is de biedprijs geen betrouwbaar referentiepunt voor de waarde van die aandelen, zo lijkt de gedachte achter deze weerleggingsgrond. 75x (OK) 4 april 2017, ECLI:NL:GHAMS:2017:1203, JOR 2017/162 m. nt. M. W. (I), r. o. 3. 21 en noot punt 9; (OK) 18 september 2012, ECLI:NL:GHAMS:2012:BX9490, ARO 2012/139 (IFCO Systems), r. o. 3. 10; in de IFCO Systems-uitkoopprocedure sluit de OK voor de waardering niet aan bij de biedprijs, onder meer omdat het bod slechts betrekking heeft op 3,33% van het geplaatste kapitaal. Er is geen overeenstemming over de vraag vanaf welk percentage vrij verhandelbare aandelen er sprake is van een ‘geringe’ free float. Ik vraag mij af of het altijd uitmaakt hoe gering de free float is. De vraag die ertoe doet is: maakt het aanwezig zijn van een geringe free float dat er geen marktappreciatie kan worden gelezen in de aanmelding van aandelen door aandeelhouders? Stel dat er een bod wordt uitgebracht op alle aandelen in een beursvennootschap met een 1%-free float. De grootaandeelhouder meldt zijn hele pakket aandelen aan en verkeert niet in een wezenlijk andere positie dan de maatman-aandeelhouder.

Output: pass


Input: Claim: Horizontal gene transfer allows bacteria to acquire new traits. [SEP] Text: In moving to a new environment, microbes can face novel abiotic conditions (temperature, moisture, salinity, pH, and nutrients) and novel biotic challenges and opportunities resulting from the presence of microbial neighbors. Evaluating HGT within the context of microbial communities could provide new insights concerning the extent, mechanisms, and ecological impact of this important process. Advances in genome sequencing have begun to provide a glimpse into HGT within environmentally, medically and economically important microbiomes (McDaniel et al. , 2010; Andam et al. , 2015). For example, extensive gene sharing has been observed throughout the commensal human microbiome, including sharing of genes that enable nutrient acquisition from novel food sources (Hehemann et al. , 2010; Smillie et al. , 2011), and pathogenicity islands and antibiotic resistance genes in pathogenic microbes (McCarthy et al. , 2014; Hiramatsu et al. , 2001; Forsberg et al. , 2012). There is evidence of extensive HGT in other natural habitats, such as soil (Coombs and Barkay, 2004; Heuer and Smalla, 2012) and aquatic environments (McDaniel et al. , 2010; Frischer et al. , 1994). Although these studies offer valuable insights into the frequency and potential impact of genes that can be transferred in microbial communities, the complexity of these systems makes difficult any further examination of the effects of these HGT events on their evolution and ecology. The microbial communities of fermented foods experience strong selection as a result of growing in novel, human-made environments. Previous work has demonstrated that HGT can be a major driver of adaptation in food systems and other human-managed environments (Andam et al. , 2015; Rossi et al. , 2014). Prior analysis of microbial species from cheese has revealed several instances of HGT in this environment. Lactic acid bacteria (LAB) such as Lactobacillus and Lactococcus, which are used in the initial fermentation of milk, are known to harbor antibiotic resistance genes and may be reservoirs for transfer to pathogenic enterococci (Wang et al. , 2006; Mathur and Singh, 2005) and other pathogenic microbes. Other food-associated bacteria may also contribute to antibiotic resistance gene transfer (Cocconcelli et al. , 2003; Delorme, 2008; Flórez et al. , 2005).

Output: corroborate


Input: Claim: All diseases can be eradicated by altering the human genome. [SEP] Text: However, candidate gene approaches are ultimately restricted to those few genes that can be strongly implicated by current knowledge, and there is little understanding of their overall contribution to disease in relation to other genes. Moving towards genome-wide studiesTwo of the first efforts to apply a genome-wide approach to multi-factorial infectious diseases were done in schistosomiasis and tuberculosis, carried out in Brazilian and African families, respectively [14, 15]. The tools available at the time only allowed linkage studies using a few hundred genetic markers spread across the whole genome. Nowadays, data generated after the sequencing of the human genome and the HapMap project have identified millions of single nucleotide polymorphisms facilitating the implementation of genome-wide association studies (GWASs). The GWAS approach, although new, is already well described and has significant methodological improvements compared with previous approaches; GWAS analysis has already enabled the successful identification and replication of novel genes for several complex disorders such as Crohn's disease, rheumatoid arthritis, type 1 and type 2 diabetes, macular degeneration and prostate cancer [16–18]. The first GWAS in infectious disease was done in 2007, when Fellay et al. [19] determined genetic components influencing the viral load of HIV-positive patients during the asymptomatic phase of the disease. However, this study did not investigate host genetic susceptibility. The first GWAS of infectious disease susceptibility was carried out in a group of patients affected with Kawasaki disease [20], a self-limiting acute vasculitis mostly affecting children below 5 years of age [21]. This study started by genotyping a small group of European origin patients and controls with an Affymetrix 250K Nsp chip; a follow-up group comprising affected children and parents was then used to confirm the initial findings; and finally a third stage, including fine-mapping of eight associated genes, further validated the genetic associations. Interestingly, five of the eight fine-mapped genes formed a connected network that also showed significant differences in transcript levels between acute and convalescent stages of the disease, suggesting that multiple genes in a pathway may be involved in susceptibility to disease, something that may turn out to be important for other infectious diseases.

Output: contrast