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71.
For over a century, the paradigm has been that sex invariably increases genetic variation, despite many renowned biologists asserting that sex decreases most genetic variation. Sex is usually perceived as the source of additive genetic variance that drives eukaryotic evolution vis-à-vis adaptation and Fisher's fundamental theorem. However, evidence for sex decreasing genetic variation appears in ecology, paleontology, population genetics, and cancer biology. The common thread among many of these disciplines is that sex acts like a coarse filter, weeding out major changes, such as chromosomal rearrangements (that are almost always deleterious), but letting minor variation, such as changes at the nucleotide or gene level (that are often neutral), flow through the sexual sieve. Sex acts as a constraint on genomic and epigenetic variation, thereby limiting adaptive evolution. The diverse reasons for sex reducing genetic variation (especially at the genome level) and slowing down evolution may provide a sufficient benefit to offset the famed costs of sex. 相似文献
72.
James B. Gerken Colin W. Anson Yuliya Preger Peter G. Symons J. David Genders Yang Qiu Wenzhen Li Thatcher W. Root Shannon S. Stahl 《Liver Transplantation》2020,10(20)
Quinones are appealing targets as organic charge carriers for aqueous redox flow batteries (RFBs), but their utility continues to be constrained by limited stability under operating conditions. The present study evaluates the stability of a series of water‐soluble quinones, with redox potentials ranging from 605–885 mV versus NHE, under acidic aqueous conditions (1 m H2SO4). Four of the quinones are examined as cathodic electrolytes in an aqueous RFB, paired with anthraquinone‐2,7‐disulfonate as the anodic electrolyte. The RFB data complement other solution stability tests and show that the most stable electrolyte is a tetrasubstituted quinone containing four sulfonated thioether substituents. The results highlight the importance of substituting all C–H positions of the quinone in order to maximize the quinone stability and set the stage for design of improved organic electrolytes for aqueous RFBs. 相似文献
73.
Tal Burt Savita Dhillon Pooja Sharma Danish Khan Deepa MV Sazid Alam Sarika Jain Bhavana Alapati Sanjay Mittal Padam Singh 《PloS one》2013,8(7)
Background
A public that is an informed partner in clinical research is important for ethical, methodological, and operational reasons. There are indications that the public is unaware or misinformed, and not sufficiently engaged in clinical research but studies on the topic are lacking. PARTAKE – Public Awareness of Research for Therapeutic Advancements through Knowledge and Empowerment is a program aimed at increasing public awareness and partnership in clinical research. The PARTAKE Survey is a component of the program.Objective
To study public knowledge and perceptions of clinical research.Methods
A 40-item questionnaire combining multiple-choice and open-ended questions was administered to 175 English- or Hindi-speaking individuals in 8 public locations representing various socioeconomic strata in New Delhi, India.Results
Interviewees were 18–84 old (mean: 39.6, SD±16.6), 23.6% female, 68.6% employed, 7.3% illiterate, 26.3% had heard of research, 2.9% had participated and 58.9% expressed willingness to participate in clinical research. The following perceptions were reported (% true/% false/% not aware): ‘research benefits society’ (94.1%/3.5%/2.3%), ‘the government protects against unethical clinical research’ (56.7%/26.3%/16.9%), ‘research hospitals provide better care’ (67.2%/8.7%/23.9%), ‘confidentiality is adequately protected’ (54.1%/12.3%/33.5%), ‘participation in research is voluntary’ (85.3%/5.8%/8.7%); ‘participants treated like ‘guinea pigs’’ (20.7%/53.2%/26.0%), and ‘compensation for participation is adequate’ (24.7%/12.9%/62.3%).Conclusions
Results suggest the Indian public is aware of some key features of clinical research (e.g., purpose, value, voluntary nature of participation), and supports clinical research in general but is unaware of other key features (e.g., compensation, confidentiality, protection of human participants) and exhibits some distrust in the conduct and reporting of clinical trials. Larger, cross-cultural surveys are required to inform educational programs addressing these issues. 相似文献74.
Andrews MD Fish PV Blagg J Brabham TK Brennan PE Bridgeland A Brown AD Bungay PJ Conlon KM Edmunds NJ af Forselles K Gibbons CP Green MP Hanton G Holbrook M Jessiman AS McIntosh K McMurray G Nichols CL Root JA Storer RI Sutton MR Ward RV Westbrook D Whitlock GA 《Bioorganic & medicinal chemistry letters》2011,21(9):2715-2720
New pyrimido[4,5-d]azepines 7 are disclosed as potent 5-HT2C receptor agonists. A preferred example, 7b had minimal activation at either the 5-HT2A or 5-HT2B receptors combined with robust efficacy in a preclinical canine model of stress urinary incontinence (SUI) and attractive pharmacokinetic and safety properties. Based on this profile, 7b (PF-3246799) was identified as a candidate for clinical development for the treatment of SUI. In addition, it proved to be critical to build an understanding of the translation between recombinant cell-based systems, native tissue preparations and in vivo preclinical models. This was a significant undertaking and proved to be crucial in compound selection. 相似文献
75.
76.
Background
The Evidence-Based Practice (EBP) Project has been investigating the implementation of evidence-based mental health practices (Assertive Community Treatment, Family Psychoeducation, Integrated Dual Diagnosis Treatment, Illness Management and Recovery, and Supported Employment) in state public mental health systems in the United States since 2001. To date, Project findings have yielded valuable insights into implementation strategy characteristics and effectiveness. This paper reports results of an effort to identify and classify state-level implementation activities and strategies employed across the eight states participating in the Project.Methods
Content analysis and Greenhalgh et al's (2004) definition of innovation were used to identify and classify state-level activities employed during three phases of EBP implementation: Pre-Implementation, Initial Implementation and Sustainability Planning. Activities were coded from site visit reports created from documents and notes from key informant interviews conducted during two periods, Fall 2002 – Spring 2003, and Spring 2004. Frequency counts and rank-order analyses were used to examine patterns of implementation activities and strategies employed across the three phases of implementation.Results
One hundred and six discreet implementation activities and strategies were identified as innovative and were classified into five categories: 1) state infrastructure building and commitment, 2) stakeholder relationship building and communications, 3) financing, 4) continuous quality management, and 5) service delivery practices and training. Implementation activities from different categories were employed at different phases of implementation.Conclusion
Insights into effective strategies for implementing EBPs in mental health and other health sectors require qualitative and quantitative research that seeks to: a) empirically test the effects of tools and methods used to implement EBPs, and b) establish a stronger evidence-base from which to plan, implement and sustain such efforts. This paper offers a classification scheme and list of innovative implementation activities and strategies. The classification scheme offers potential value for future studies that seek to assess the effects of various implementation processes, and helps establish widely accepted standards and criteria that can be used to assess the value of innovative activities and strategies. 相似文献77.
78.
Arangassery Rosemary Bastian Aakansha Nangarlia Lauren D. Bailey Andrew Holmes R. Venkat Kalyana Sundaram Charles Ang Diogo R. M. Moreira Kevin Freedman Caitlin Duffy Mark Contarino Cameron Abrams Michael Root Irwin Chaiken 《The Journal of biological chemistry》2015,290(1):529-543
Entry of HIV-1 into host cells remains a compelling yet elusive target for developing agents to prevent infection. A peptide triazole (PT) class of entry inhibitor has previously been shown to bind to HIV-1 gp120, suppress interactions of the Env protein at host cell receptor binding sites, inhibit cell infection, and cause envelope spike protein breakdown, including gp120 shedding and, for some variants, virus membrane lysis. We found that gold nanoparticle-conjugated forms of peptide triazoles (AuNP-PT) exhibit substantially more potent antiviral effects against HIV-1 than corresponding peptide triazoles alone. Here, we sought to reveal the mechanism of potency enhancement underlying nanoparticle conjugate function. We found that altering the physical properties of the nanoparticle conjugate, by increasing the AuNP diameter and/or the density of PT conjugated on the AuNP surface, enhanced potency of infection inhibition to impressive picomolar levels. Further, compared with unconjugated PT, AuNP-PT was less susceptible to reduction of antiviral potency when the density of PT-competent Env spikes on the virus was reduced by incorporating a peptide-resistant mutant gp120. We conclude that potency enhancement of virolytic activity and corresponding irreversible HIV-1 inactivation of PTs upon AuNP conjugation derives from multivalent contact between the nanoconjugates and metastable Env spikes on the HIV-1 virus. The findings reveal that multispike engagement can exploit the metastability built into virus the envelope to irreversibly inactivate HIV-1 and provide a conceptual platform to design nanoparticle-based antiviral agents for HIV-1 specifically and putatively for metastable enveloped viruses generally. 相似文献
79.
Macroevolution and climate change influence phylogenetic community assembly of North American hoofed mammals 下载免费PDF全文
Danielle Fraser Root Gorelick Natalia Rybczynski 《Biological journal of the Linnean Society. Linnean Society of London》2015,114(3):485-494
Animal richness, community composition, and phylogenetic community structure (PCS) vary across the modern landscape. Animal communities vary from phylogenetically clustered (i.e. higher relatedness amongst co‐occurring species than is expected by chance) to phylogenetically even (i.e. co‐occurring taxa are more distantly related than expected by chance), which is explained by abiotic or climatic filtering and competitive exclusion, respectively. Under this model, the contribution of historical origination and extinction events to modern animal PCS remains relatively unknown. Because origination and extinction determine the make‐up of the terrestrial community, the study of historical changes in animal PCS is tantamount to understanding formation of modern communities. In the present study, we test the effects of macroevolution and climate changes on ‘hoofed mammals’ (i.e. perissodactyl and artiodactyl) PCS from the late Cenozoic of North America because they experience large, phylogenetically dispersed extinctions of browsing species and phylogenetically dispersed originations of grazing species associated with the evolution of grassland ecosystems during the late Miocene. We show that the loss of numerically dominant nonhypsodont (putatively browsing and mixed feeding) clades and phylogenetically dispersed origination of less speciose clades following the mid Miocene climatic optimum led to an increase in phylogenetic evenness at the regional scale that is well explained by global climate changes. Phylogenetic evenness and a reduced richness during the late Cenozoic may have facilitated reduced niche overlap among co‐occurring hoofed mammal species as global climates cooled. © 2015 The Linnean Society of London, Biological Journal of the Linnean Society, 2015, 114 , 485–494. 相似文献
80.
J. Jeffrey Root Kevin T. Bentler Susan A. Shriner Nicole L. Mooers Kaci K. VanDalen Heather J. Sullivan Alan B. Franklin 《PloS one》2014,9(8)