Miracle-dz/UniFAR-FTUs huggingface dataset:
Activity of 3,19-isopropylidinyl andrographolide against herpes simplex virus type 1 in an animal model

Background In our previous study, the semi-synthetic analog of andrographolide, 3,19-isopropylideneandrographolide (IPAD), acts more effectively against herpes simplex virus (HSV) infection in cell culture than does acyclovir. IPAD inhibits cytopathic effect and production of HSV wild types and drug-resistant strains. Its effect is associated with the reduction of immediate-early regulatory protein (ICP27) and early proteins (ICP8 and UL42), indicating a mode of action different from that of acyclovir. Therefore, studies of the anti-HSV activity of IPAD in animal models are required before further application. Material & Method Prednisolone-treated BALB/c mice were cutaneously infected with HSV-1 wild-type KOS strain. Experimental groups included control groups (untreated or treated only with the cream base) and treatment groups (with acyclovir or IPAD creams). Creams were applied four times daily for 10 days after infection to the relevant groups. The skin lesion score was assessed twice a day for 10 days. In addition, the effect of IPAD on HSV copy number and HSV late gene (gD) expression was investigated in skin lesion cells by quantitative real-time polymerase chain reaction. Result IPAD cream was significantly effective in delaying the development of skin lesions and regression of the skin lesion score by day 5 (P < 0.01) compared with untreated controls. In addition, this IPAD cream significantly reduced HSV DNA copy number and gD gene expression (P < 0.01). No signs of irritation were observed at the application site. Conclusion Topical administration of IPAD cream reduced skin lesions in mice cutaneously infected with HSV-1 KOS.
Small mammal personalities generate context dependence in the seed dispersal mutualism

Significance Mutualisms are foundational components of ecosystems and give rise to essential services such as seed dispersal and pollination. Ecologists believe that nearly every species is involved in one or more mutualisms, but it is unknown how consistent behavioral differences among individuals, or personalities, may influence an individual’s role. We scored individuals on a continuum from antagonistic to mutualistic given their contributions to the seed dispersal mutualism and found that personalities affect the extent to which individuals are mutualistic. These findings suggest a novel mechanism generating context dependence in mutualisms and underscore the need to incorporate behavioral diversity into conservation and restoration efforts.
Helical self-assembly of a mucin segment suggests an evolutionary origin for von Willebrand factor tubules

Significance Extracellular proteins with mechanical functions often require specialized assembly processes to form covalent oligomers. Progress in tissue bioengineering and repair will benefit from an understanding of how to harness and manipulate these processes. Here, we show that a particular supramolecular assembly mode was pre-encoded in the ancient domain organization common to gel-forming mucins and von Willebrand factor, glycoproteins that are deceptively different due to their divergence for distinct mechanical tasks. This finding highlights symmetry principles and building blocks retooled in nature to construct polymers with wide-ranging properties. These building blocks and knowledge of their self-assembly can be used to design new polymeric structures.
Sequence and tissue targeting specificity of ZFP36L2 reveals Elavl2 as a novel target with co-regulation potential

Abstract Zinc finger protein 36 like 2 (ZFP36L2) is an RNA-binding protein that destabilizes transcripts containing adenine-uridine rich elements (AREs). The overlap between ZFP36L2 targets in different tissues is minimal, suggesting that ZFP36L2-targeting is highly tissue specific. We developed a novel Zfp36l2-lacking mouse model (L2-fKO) to identify factors governing this tissue specificity. We found 549 upregulated genes in the L2-fKO spleen by RNA-seq. These upregulated genes were enriched in ARE motifs in the 3′UTRs, which suggests that they are ZFP36L2 targets, however the precise sequence requirement for targeting was not evident from motif analysis alone. We therefore used gel-shift mobility assays on 12 novel putative targets and established that ZFP36L2 requires a 7-mer (UAUUUAU) motif to bind. We observed a statistically significant enrichment of 7-mer ARE motifs in upregulated genes and determined that ZFP36L2 targets are enriched for multiple 7-mer motifs. Elavl2 mRNA, which has three 7-mer (UAUUUAU) motifs, was also upregulated in L2-fKO spleens. Overexpression of ZFP36L2, but not a ZFP36L2(C176S) mutant, reduced Elavl2 mRNA expression, suggesting a direct negative effect. Additionally, a reporter assay demonstrated that the ZFP36L2 effect on Elavl2 decay is dependent on the Elavl2-3′UTR and requires the 7-mer AREs. Our data indicate that Elavl2 mRNA is a novel target of ZFP36L2, specific to the spleen. Likely, ZFP36L2 combined with other RNA binding proteins, such as ELAVL2, governs tissue specificity.
Exposure‐Response Characterization of Tofacitinib Efficacy in Moderate to Severe Ulcerative Colitis: Results From Phase II and Phase III Induction and Maintenance Studies

Tofacitinib is an oral small molecule JAK inhibitor for the treatment of ulcerative colitis. Relationships between plasma tofacitinib concentration and efficacy were characterized using exposure‐response (E‐R) models, with demographic and disease covariates evaluated as potential predictors of efficacy. Data were from phase II and III (OCTAVE Induction 1 and 2) induction studies, and a phase III maintenance study (OCTAVE Sustain). Induction studies included 1,355 patients (tofacitinib 0.5, 3, 10, or 15 mg b.i.d. or placebo). The maintenance study included 592 patients (tofacitinib 5 or 10 mg b.i.d. or placebo). E‐R models, including induction patients predicted placebo‐adjusted remission rates of 6.4% and 12.7% at week 8 for tofacitinib 5 and 10 mg b.i. d. , respectively; corresponding rates in patients without prior tumor necrosis factor inhibitor (TNFi) failure were 12.8% and 20.4%. Estimates to achieve/maintain remission at week 52 of maintenance were 29% and 18% (tofacitinib 5 mg b.i.d.), and 41% and 26% (tofacitinib 10 mg b.i.d.), for patients in remission or not following induction, respectively. During maintenance, patients with prior TNFi failure had lower probability of remission on 5 mg b.i. d. (24.9%) than 10 mg b.i. d. (35.0%). Results indicated tofacitinib 10 mg b.i. d. was an appropriate induction dose but suggested efficacy with 5 mg b.i. d. in patients without prior TNFi failure. Tofacitinib 5 mg b.i. d. was efficacious for maintenance, although patients with prior TNFi failure might see additional benefit on 10 mg b.i. d. Per product labeling, recommended tofacitinib induction dose is 10 mg b.i. d. , then maintenance at 5 mg b.i. d. For patients who lose response during maintenance, 10 mg b.i. d. may be considered, limited to the shortest duration.
Foot and ankle Osteoarthritis and Cognitive impairment in retired UK Soccer players (FOCUS): protocol for a cross-sectional comparative study with general population controls

Introduction Professional footballers commonly experience sports-related injury and repetitive microtrauma to the foot and ankle, placing them at risk of subsequent chronic pain and osteoarthritis (OA) of the foot and ankle. Similarly, repeated heading of the ball, head/neck injuries and concussion have been implicated in later development of neurodegenerative diseases such as dementia. A recent retrospective study found that death from neurodegenerative diseases was higher among former professional soccer players compared with age matched controls. However, well-designed lifetime studies are still needed to provide evidence regarding the prevalence of these conditions and their associated risk factors in retired professional football players compared with the general male population. Objectives To determine whether former professional male footballers have a higher prevalence than the general male population of: (1) foot/ankle pain and radiographic OA; and (2) cognitive and motor impairments associated with dementia and Parkinson’s disease. Secondary objectives are to identify specific football-related risk factors such as head impact/concussion for neurodegenerative conditions and foot/ankle injuries for chronic foot/ankle pain and OA. Methods and analysis This is a cross-sectional, comparative study involving a questionnaire survey with subsamples of responders being assessed for cognitive function by telephone assessment, and foot/ankle OA by radiographic examination. A sample of 900 adult, male, ex professional footballers will be recruited and compared with a control group of 1100 age-matched general population men between 40 and 100 years old. Prevalence will be estimated per group. Poisson regression will be performed to determine prevalence ratio between the populations and logistic regression will be used to examine risk factors associated with each condition in footballers. Ethics and dissemination This study was approved by the East Midlands-Leicester Central Research Ethics Committee on 23 January 2020 (REC ref: 19/EM/0354). The study results will be disseminated at national and international meetings and submitted for peer-review publication.
Strength of TCR Signaling Cell Cycle Progression Independent of the Cutting Edge: B7/CD28 Interactions Regulate

Jody L. Bonnevier and Daniel L. Muellerhttp://www.jimmunol.org/content/169/12/6659J Immunol€2002; 169:6659-6663; ;Referenceshttp://www.jimmunol.org/content/169/12/6659.full#ref-list-1This article cites 11 articles, 7 of which you can access for free at: Subscriptionshttp://jimmunol.org/subscriptionsInformation about subscribing to The Journal of Immunology is online at: Permissionshttp://www.aai. org/ji/copyright.htmlSubmit copyright permission requests at: Email Alertshttp://jimmunol.org/cgi/alerts/etocReceive free email-alerts when new articles cite this article. Sign up at:
Serial ATA Storage Architecture and Applications: Designing High-Performance, Cost-Effective I/O Solutions

From the Publisher: Written for systems engineers, architects, and product managers involved in the planning process for a transition to Serial ATA, this book will contribute to a better understanding of this new interconnect technology. Answered are questions such as why make the change, what problems does serial ATA solve, what potential problems could Serial ATA create and how can they be avoided, and how to transition systems from Parallel ATA or SCSI to Serial ATA. Topics include PHY signaling and interface states, protocol encoding, programming model, flow control, performance, legacy compatibility, enclosure management, signal routing, hot=plug, presence detect, and cable/connector standards. Insights are also provided on the goals driving the Serial ATA standard development, the advantages Serial ATA provides for OEMs, IHVs, and -users, and how to design and build real-world systems that use Serial ATA. Author Biography: Knut Grimsrud is the Intel principal engineer for definition of Serial ATA 1.0 and Serial ATA II. He was the technical working group chairman during the Serial ATA 1.0 definition effort and continues to be Intel's technical lead for ongoing Serial ATA definition work. Knut holds a PhD in electrical and computer engineering. During his nine years with Intel, Knut has led design work on storage architecture and performance in both the server and the desktop market segments. Hubbert Smith is a Program Manager with Intel's Platform Networking Group, where he specializes in producing Serial ATA-related building blocks. He currently serves as the chairman of the Serial ATA II cable/connector focus group and has contributed many of the Serial ATA II Use Cases. Hubbert has more than 15 years professional experience with technology related to servers and storage.
Exponential flux-controlled memristor model and its floating emulator

As commercial memristors are still unavailable in the market, mathematic models and emulators which can imitate the features of the memristor are meaningful for further research. In this paper, based on the analyses of characteristics of the q–φ curve, an exponential flux-controlled model, which has the quality that its memductance (memristance) will keep monotonically increasing or decreasing unless the voltage’s polarity reverses (if not approach the boundaries), is constructed. A new approach to designing the floating emulator of the memristor is also proposed. This floating structure can flexibly meet various demands for the current through the memristor (especially the demand for a larger current). The simulations and experiments are presented to confirm the effectiveness of this model and its floating emulator.
Can female guppies learn to like male colours? A test of the role of associative learning in originating sexual preferences

How do female sexual preferences for male ornamental traits arise? The developmental origins of female preferences are still an understudied area, with most explanations pointing to genetic mechanisms. One intriguing, little-explored, alternative focuses on the role of associative learning in driving this process. According to this hypothesis, a preference learned in an ecological context can be transferred into a sexual context, resulting in changes in mating preferences as a by-product. I tested this hypothesis by first training female guppies to associate either orange or black colour with food delivery; I then presented videos of males with computer-manipulated coloured spots and measured female preference towards them. I also allowed females from both treatments to mate with males differing in their ratio of orange-to-black spots and measured the males' reproductive success. After training, female sexual preferences significantly diverged among treatments in the expected direction. In addition, orange males sired a greater proportion of offspring with females food-conditioned on orange compared to those conditioned on black. These results show that mating preferences can arise as a by-product of associative learning, which, via translation into variation in male fitness, can become associated with indirect genetic benefits, potentially leading to further evolution.
The principles of pedestrian route choice

Pedestrian route choice, the process by which individuals decide on their walking path between two locations, is a fundamental problem across disciplines. Because this behaviour is investigated from different conceptual and methodological angles, and because it strongly depends on the environmental context, it is challenging to establish a systematic framework for research. Here, by reviewing previous work, we identify four principles for pedestrian route choice that are relevant across disciplines. First, ‘information perception’ deals with how pedestrians can perceive information selectively and purposely, given the limited available information. Second, ‘information integration’ considers how pedestrians subjectively integrate environmental spatial information into mental representations. Third, ‘responding to information’ is concerned with how pedestrians tend to be attracted and repelled by specific attributes individually and how this can lead to positive or negative feedback loops across many individuals. Fourth ‘decision-making mechanisms' describe how pedestrians trade off the evidence provided by different attributes. How pedestrians perceive, integrate, respond to, and act upon information is not fixed but varies with the context. We give examples for each principle and explain how these principles shape pedestrian choice behaviours. We hope this contribution provides a systematic overview of the field and helps to spark inspiration among specialists.
Artificial SA-I, RA-I and RA-II/vibrotactile afferents for tactile sensing of texture

Robot touch can benefit from how humans perceive tactile textural information, from the stimulation mode to which tactile channels respond, then the tactile cues and encoding. Using a soft biomimetic tactile sensor (the TacTip) based on the physiology of the dermal–epidermal boundary, we construct two biomimetic tactile channels based on slowly adapting SA-I and rapidly adapting RA-I afferents, and introduce an additional sub-modality for vibrotactile information with an embedded microphone interpreted as an artificial RA-II channel. These artificial tactile channels are stimulated dynamically with a set of 13 artificial rigid textures comprising raised-bump patterns on a rotating drum that vary systematically in roughness. Methods employing spatial, spatio-temporal and temporal codes are assessed for texture classification insensitive to stimulation speed. We find: (i) spatially encoded frictional cues provide a salient representation of texture; (ii) a simple transformation of spatial tactile features to model natural afferent responses improves the temporal coding; and (iii) the harmonic structure of induced vibrations provides a pertinent code for speed-invariant texture classification. Just as human touch relies on an interplay between slowly adapting (SA-I), rapidly adapting (RA-I) and vibrotactile (RA-II) channels, this tripartite structure may be needed for future robot applications with human-like dexterity, from prosthetics to materials testing, handling and manipulation.
The right tool for the right question: contrasting biogeographic patterns in the notothenioid fish Harpagifer spp. along the Magellan Province

Molecular-based analysis has become a fundamental tool to understand the role of Quaternary glacial episodes. In the Magellan Province in southern South America, ice covering during the last glacial maximum (20 ka) radically altered the landscape/seascape, speciation rates and distribution of species. For the notothenioid fishes of the genus Harpagifer, in the area are described two nominal species. Nevertheless, this genus recently colonized South America from Antarctica, providing a short time for speciation processes. Combining DNA sequences and genotyping-by-sequencing SNPs, we evaluated the role of Quaternary glaciations over the patterns of genetic structure in Harpagifer across its distribution in the Magellan Province. DNA sequences showed low phylogeographic structure, with shared and dominant haplotypes between nominal species, suggesting a single evolutionary unit. SNPs identified contrastingly two groups in Patagonia and a third well-differentiated group in the Falkland/Malvinas Islands with limited and asymmetric gene flow. Linking the information of different markers allowed us to infer the relevance of postglacial colonization mediated by the general oceanographic circulation patterns. Contrasting rough- and fine-scale genetic patterns highlights the relevance of combined methodologies for species delimitation, which, depending on the question to be addressed, allows discrimination among phylogeographic structure, discarding incipient speciation, and contemporary spatial differentiation processes.
Education Racial and Gender Disparities in COVID-19 Worry, Stress, and Food Insecurities across Undergraduate Biology Students at a Southeastern University

The global spread of the novel coronavirus first reported in December 2019 led to drastic changes in the social and economic dynamics of everyday life. Nationwide, racial, gender, and geographic disparities in symptom severity, mortality, and access to health care evolved, which impacted stress and anxiety surrounding COVID-19. ABSTRACT The global spread of the novel coronavirus first reported in December 2019 led to drastic changes in the social and economic dynamics of everyday life. Nationwide, racial, gender, and geographic disparities in symptom severity, mortality, and access to health care evolved, which impacted stress and anxiety surrounding COVID-19. On university campuses, drastic shifts in learning environments occurred as universities shifted to remote instruction, which further impacted student mental health and anxiety. Our study aimed to understand how students from diverse backgrounds differ in their worry and stress surrounding COVID-19 upon return to hybrid or in-person classes during the Fall of 2020. Specifically, we addressed the differences in COVID-19 worry, stress response, and COVID-19-related food insecurity related to race/ethnicity (Indigenous American, Asian/Asian American, black/African American, Latinx/Hispanic, white, or multiple races), gender (male, female, and gender expressive), and geographic origin (ranging from rural to large metropolitan areas) of undergraduate students attending a regional-serving R2 university, in the southeastern U.S. Overall, we found significance in worry, food insecurity, and stress responses with females and gender expressive individuals, along with Hispanic/Latinx, Asian/Asian American, and black/African American students. Additionally, students from large urban areas were more worried about contracting the virus compared to students from rural locations. However, we found fewer differences in self-reported COVID-related stress responses within these students. Our findings can highlight the disparities among students’ worry based on gender, racial differences, and geographic origins, with potential implications for mental health of university students from diverse backgrounds. Our results support the inclusion of diverse voices in university decisioning making around the transition through the COVID-19 pandemic.
Analysis of optical pulse’s position effect on temporal response characteristics of GaAs metal-semiconductor-metal photodetector

Photocurrents in a GaAs metal-semiconductor-metal (MSM) photodetector have been numerically modelled as a function of optical pulse’s position in a one-dimensional structure using Ambipolar transport theory and discrete Fourier transform method. The modelled results represent the carriers’ concentrations as well as the maximum value of the photocurrents that pass through the device when the optical pulse position changes on the device active region (i.e., the region between two top contacts). The simulation has been performed at low level injection of the excess carriers (i.e., photo-carriers) and with no bias voltage applied to the photodetector in equilibrium condition. The numerical simulation results show that for optical pulse position in the cathode region, the magnitude of the photocurrent is exactly the same but opposite direction of the anode region. The response of the photodetector is ‘zero’ when a pulse is positioned at the center of the active region. This important feature of the device could make it attractive for micro-scale positioning of high sensitive devices. The modelled results are qualitatively agreed with the experimentally observed behavior of the device.
Genetic diversity and population structure of Cinnamomum balansae Lecomte inferred by microsatellites

Abstract Cinnamomum balansae Lecomte (Lauraceae), an economically important forest tree, is distributed in the tropical forests of central and northern Vietnam, which has been threatened in recent decades due to the destruction of its habitat and over-exploitation. The genetic diversity and population structure of the species have not been fully evaluated. We used a set of 15 microsatellites to analyze 161 adult trees from 9 different populations, representing the geographical distribution of C. balansae. Ninety-two different alleles were identified. Here our results showed a low genetic diversity level with an average H o = 0.246 and H e = 0.262, and a high level of genetic differentiation (F ST = 0.601). The bottleneck tests indicated evidence of a reduction in the population size of the two populations (TC and CP). Additionally, all three clustering methods (Bayesian analysis, principal coordinate analysis, and Neighbor-joining tree) were identified in the two genetic groups. The Mantel test showed a significant positive correlation between genetic distance and geographic distance (R 2 = 0.7331). This study will provide a platform for the conservation of C. balansae both in ex-situ and in-situ plans.