Miracle-dz/UniFAR-FTUs huggingface dataset:
Sordarin antifungal agents

Sordarins are natural products from a range of different producer fungi that show antifungal activity. Results from studies with a series of semi-synthetic sordarin derivatives from Glaxo Wellcome indicates the molecules show potential for broad spectrum activity, with a high antifungal specificity based on the nature of their interaction with protein elongation factor 2. Several of the compounds have demonstrated efficacy by sc. or oral administration in mouse models of Candida albicans, Histoplasma capsulatum, Coccidioides immitis and Pneumocystis carinii infection and early toxicological studies show no serious potential for adverse effects. However, the t½ of the compounds in several animal species is very short, suggesting that high and repeated dosing may prove to be necessary for management of some serious fungal diseases. Patents for sordarin antifungals and for their target have been published principally from Glaxo Wellcome and from Merck & Co. However, Glaxo Wellcome has now terminated their own development programme for the agents and no details are yet available to indicate a candidate for clinical development will soon appear from Merck. The sordarins offer interesting potential thanks to the novelty of their mode of action; they may require substantially more research to reveal an ideal candidate for clinical development.
Cytotoxicity Burst? Differentiating Specific from Nonspecific Effects in Tox21 in Vitro Reporter Gene Assays

Background: High-throughput screening of chemicals with in vitro reporter gene assays in Tox21 has produced a large database on cytotoxicity and specific modes of action. However, the validity of some of the reported activities is questionable due to the “cytotoxicity burst,” which refers to the supposition that many stress responses are activated in a nonspecific way at concentrations close to cell death. Objectives: We propose a pragmatic method to identify whether reporter gene activation is specific or cytotoxicity-triggered by comparing the measured effects with baseline toxicity. Methods: Baseline toxicity, also termed narcosis, is the minimal toxicity any chemical causes. Quantitative structure–activity relationships (QSARs) developed for baseline toxicity in mammalian reporter gene cell lines served as anchors to define the chemical-specific threshold for the cytotoxicity burst and to evaluate the degree of specificity of the reporter gene activation. Measured 10% effect concentrations were related to measured or QSAR-predicted 10% cytotoxicity concentrations yielding specificity ratios (SR). We applied this approach to our own experimental data and to ∼8,000 chemicals that were tested in six of the high-throughput Tox21 reporter gene assays. Results: Confirmed baseline toxicants activated reporter gene activity around cytotoxic concentrations triggered by the cytotoxicity burst. In six Tox21 assays, 37%–87% of the active hits were presumably caused by the cytotoxicity burst (SR<1) and only 2%–14% were specific with SR≥10 against experimental cytotoxicity but 75%–97% were specific against baseline toxicity. This difference was caused by a large fraction of chemicals showing excess cytotoxicity. Conclusions: The specificity analysis for measured in vitro effects identified whether a cytotoxicity burst had likely occurred. The SR-analysis not only prevented false positives, but it may also serve as measure for relative effect potency and can be used for quantitative in vitro–in vivo extrapolation and risk assessment of chemicals. https://doi.org/10.1289/EHP6664
Bounds of compression of unknown alphabets

It is known that the redundancy of universally compressing i.i. d. strings increases to infinity as the alphabet size grows. It is also apparent that any string can be described by separately conveying its symbols, and their pattern-the order in which they appear. Concentrating on the latter, we show that the patterns of iid strings drawn from any, possibly infinite or even unknown, alphabet, can be universally compressed with diminishing worst-case redundancy, both in block, and sequentially.
Driving Accidents, Driving Violations, Symptoms of Attention-Deficit-Hyperactivity (ADHD) and Attentional Network Tasks

Background: Iran has serious problems with traffic-related injuries and death. A major reason for traffic accidents is cognitive failure due to deficits in attention. In this study, we investigated the associations between traffic violations, traffic accidents, symptoms of attention-deficit/hyperactivity disorder (ADHD), age, and on an attentional network task in a sample of Iranian adults. Methods: A total of 274 participants (mean age: 31.37 years; 80.7% males) completed questionnaires covering demographic information, driving violations, traffic accidents, and symptoms of ADHD. In addition, they underwent an objective attentional network task (ANT), based on Posner’s concept of attentional networks. Results: More frequent traffic violations, correlated with lower age and poorer performance on the attentional network tasks. Higher symptoms of ADHD were associated with more accidents and more traffic violations, but not with the performance of the attentional tasks. Higher ADHD scores, a poorer performance on attentional network tasks, and younger age predicted traffic violations. Only higher symptoms of ADHD predicted more traffic accidents. Conclusions: In a sample of Iranian drivers, self-rated symptoms of ADHD appeared to be associated with traffic violations and accidents, while symptoms of ADHD were unrelated to objectively assessed performance on an attentional network task. Poor attentional network performance was a significant predictor of traffic violations but not of accidents. To increase traffic safety, both symptoms of ADHD and attentional network performance appear to merit particular attention.
Researchers' ethical concerns regarding habituating wild‐nonhuman primates and perceived ethical duties to their subjects: Results of an online survey

While the process of habituation is essential for researchers to observe primates in their natural habitats, ethical dilemmas may arise from its consequences. We collected data from 286 participants via an online survey to investigate: (a) how primatologists perceive their ethical duties toward their subjects; (b) the extent to which primatologists are concerned about the potential ethical consequences of habituation; and (c) the methods primatologists use to reduce potential harms caused by habituation. Overall, primatologists felt an extremely strong duty to mitigate harms that they may cause (e.g., to not stress individuals during observation, treat injuries, and reunite separated individuals) and expressed very high concern for habituation's potential to increase the vulnerability of their subjects to poaching and disease transfer. Ratings for those items were so high that they could not be included in subsequent exploratory factor analyses that were designed to reveal constructs underlying respondents’ ratings of their ethical duties and concerns. Factor analysis of ratings of ethical duties revealed that primatologists reported a strong duty to mitigate harms caused by other humans and a lower perceived duty to mitigate naturally occurring harmful events. Factor analysis on ethical concern ratings revealed that respondents were concerned about harms during the habituation process, the presence of unhabituated behavior after habituation had been established, and indirect harms of habituation. Concerns for unhabituated behavior and indirect harms were rated slightly higher than concern for harms during the habituation process. To mitigate potential harms, primatologists primarily reported engaging in strategies to reduce stress in their subjects. Our findings reveal a disconnect between primatologists' ratings of their ethical concerns and their reported mitigation practices that may, in part, stem from gaps in knowledge about the true impacts of habituation. We suggest areas of discussion and research in the field necessary to address those gaps.
Molecular characterization of rotaviruses in mid-western Turkey, 2006–2007

Vaccines against rotaviruses are now available in numerous countries, including Turkey. As the vaccines may show various efficiencies against different type specificities and routine vaccination in infants might result in selection and immune escape of wild-type rotavirus strains, strain surveillance has been initiated before and during the vaccine introduction. We aimed to provide corresponding information on local strain prevalence in Anatolia, mid-western Turkey during the introduction of rotavirus vaccines. Stool samples positive for group A rotavirus by commercial enzyme immunoassay were subjected to reverse transcription-polymerase chain reaction based genotyping of the outer capsid antigens, VP7 and VP4, determining G and P type specificities respectively. Among 36 fully and 5 partially typeable strains we detected genotype G1, G2, and G9 VP7 specificities and genotype P[4], P[6] and P[8] VP4 specificities in 5 individual and 4 mixed combinations. The most common strain was G2P[4] (n=17), followed by G9P[8] (n=9). Other strains were G1P[8] (n=2), G2P[8] (n=2), G1+2P[8] (n=2), G9P[4] (n=1), G2+9P[8] (n=1), G4+9P[6] (n=1), and G2P[4+8] (n=1). Partially typed strains included 2 G1P[NT] and 3 G2P[NT] strains. Our data may help determine a baseline of the rotavirus genotype prevalence in Turkey and see if changes in the incidence of individual strains will be observed after routine use of vaccine.
Early Initiation and Exclusivity of Breastfeeding in Rural Zimbabwe: Impact of a Breastfeeding Intervention Delivered by Village Health Workers

ABSTRACT Background Suboptimal breastfeeding contributes to >800,000 global child deaths annually. Optimal breastfeeding includes early initiation (EI) and exclusive breastfeeding (EBF) for the first 6 mo. Objectives We tested the hypothesis that an intervention targeting context and infant age-specific barriers to EI and EBF will achieve a higher EI and EBF prevalence than those of women participating in the concurrently conducted 2015 Zimbabwe Demographic Health Survey (Z-DHS). Methods We designed an intervention to promote EI and EBF, and implemented it within the Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial in rural Zimbabwe. Intervention modules were delivered at 4 perinatal time points by government-employed village health workers. We compared EI and EBF prevalence among SHINE women who provided outcomes at 1 mo (n = 2442) and 3 mo (n = 2728), with women in the 2015 Z-DHS. Results In cross-sectional analyses EI prevalence was 86.6% and 64.3% in the SHINE and Z-DHS samples, respectively; absolute difference (95% CI) = 22.4% (17.5%, 27.3%). EBF prevalence was similarly high (>80%) in both surveys during the first month of life; during 1 to <2 mo, 2 to <3 mo, 3 to <4 mo, 4 to <5 mo, and 5 to <6 mo, EBF prevalence was, respectively, 85%, 90%, 90%, 84%, and 75% in SHINE, and 71%, 65%, 35%, 26%, and 25% in Z-DHS; absolute difference (95% CI) = 50.2% (34.7%, 65.7%) at 5 to <6 mo. Cesarean delivery, mother's belief that intimate partner violence was sometimes justifiable, and having a male infant negatively modified the effects of the intervention. Conclusions The SHINE intervention achieved a high prevalence of EI and EBF. Concurrently addressing gender norms will be critical to make further progress. Formative studies to identify context- and infant age-specific barriers to EI and EBF may inform improvement of breastfeeding practices elsewhere. Important work remains to scale up this intervention beyond a research setting. SHINE was registered at www.clinicaltrials. gov as NCT01824940.
Quantitative and Qualitative Aspects of Bacterial Communities Associated with Cultures of Chlorella minutissima

Microbiological conditions in 200 L cultures of microalgae Chlorella minutissima in polyethylene sleeves were examined. The influence of addition of antibiotic (nitrofurantoin) was studied. Samples were taken 2, 5, 9, and 14 d after inoculation and were spread on solid Zobell medium and on thiosulfate citrate bile salts sucrose agar for the enumeration of total numbers of bacteria and numbers of presumptive Vibrio bacteria, respectively. Microalgae grew well in the cultures and high numbers of culturable bacteria (about 107 bacteria/mL) were present in all microalgae cultures. Addition of antibiotic in 200-L cultures of C. minutissima did not result in a significant decrease of total counts of bacteria per unit volume (P > 0.05), while the numbers of presumptive Vibrio were higher in cultures added antibiotic compared with the control treatment (P < 0.05). The numbers of presumptive Vibrio per unit volume and the percentage of fast-growing bacteria were higher in microalgae supernatant than in noncentrifuged samples. Representative colonies were taken from all samples and in total 649 bacterial strains were isolated during this study. A range of phylotypes was identified by amplification and sequencing of the 16S rDNA gene and phylogenetic trees were constructed. Several members of the Roseobacter clade were dominant among the culturable isolates.
Spatial and Temporal Variation in Soil and Vegetation Impacts on Campsites

We studied the impacts of camping on soil and vegetation at Delaware Water Gap National Recreation Area. We assessed the magnitude of impact on campsites that varied in amount of use and in topographic position. We also evaluated change over a 5- yr period on long-established, recently opened, and recently closed campsites, as well as on plots subjected to experimental trampling. Campsite impacts were intense and spatially variable. Amount of use and topographic position explained some of this variation. Soil and vegetation conditions changed rapidly when campsites were initially opened to use and when they were closed to use. Changes were less pronounced on the long-established campsites that remained open to use. In the trampling experiments, impact varied greatly with trampling intensity and between vegetation types. An open-canopy grassland vege- tation type was much more resistant to trampling than a forb-dominated forest vegetation type. Campsite impacts increased rapidly with initial disturbance, stabilized with ongoing disturbance, and-in contrast to what has been found in most other studies increased rapidly once disturbance was terminated. Implications of these results for campsite man- agement strategies, such as use concentration or dispersal, and rotation or closure of camp- sites, are discussed.
Low bone mineral density and its risk factors in an urban adult population of South India

BACKGROUND AND OBJECTIVES: Low bone mineral density (BMD) is widely prevalent in Indian populations. Very few studies that reported risk factors for low BMD and osteoporosis did not explore its relationship with age and sex. Objectives were to determine the prevalence of low BMD and osteoporosis in urban adults, and study the age- and sex-wise trends of changing BMD. METHODOLOGY: BMD of 521 healthy adults aged 20 years or more was tested using quantitative ultrasound of right tibia, and T-scores thus obtained indicated normal or low BMD. Multivariate analysis was done to calculate odds ratios for risk factors for low BMD and osteoporosis. RESULTS: Eighty-four percent participants had low BMD. Low BMD increased significantly with increasing age in both genders. An increase in age per standard deviation (SD) was associated with four-fold increase in risk of low BMD for both women (odds ratio [OR]: 4.83, 95% confidence interval [CI]: 2.61–8.92) and men (OR: 4.14, 95% CI: 2.44–7.05). Age per SD (OR: 2.28, 95% CI: 1.37–3.81) and age–gender interaction (OR: 1.09, 95% CI: 1.02-1.17) was positively associated with osteoporosis. Increasing age by one SD was associated with seven-fold increase (OR: 7.35, 95% CI: 3.51–15.40) in risk of osteoporosis among women. CONCLUSIONS: Low BMD is highly prevalent in South Indian urban population. Low BMD and osteoporosis were positively associated with increasing age. Loss of BMD appeared to begin at young ages thereby indicating the need for early institution of prevention measures.
Sex‐ratio bias in an aphid parasitoid‐hyperparasitoid association: a test of two hypotheses

Abstract. 1 We tested the hypothesis that biased sex ratios in the aphidiid parasitoid, Aphidius ervi, are the result of sex‐specific mortality of immatures due to hyperparasitism. The solitary hyperparasitoid, Dendrocerus carpenteri, deposits its eggs on the prepupa or pupa of the primary parasitoid after its pea‐aphid host is mummified. 2 In dichotomous choice tests, females of D.carpenteri accepted immatures of both sexes of A.ervi with equal frequency. Independent of the sex of the primary parasitoid, the probability of a mummified pea aphid being hyperparasitized did not differ between large (adult at the time of death) and small (fourth nymphal instar) mummies. 3 As predicted by‘host quality’models of offspring sex allocation, D.carpenteri produced a higher proportion of female than male offspring in large mummies. These laboratory results were supported by field data. 4 Because hyperparasitism by D.carpenteri is random with regard to host sex, it should have no influence on optimal sex allocation by the primary parasitoid.
Epigenetic Suppression of Transgenic T-cell Receptor Expression via Gamma-Retroviral Vector Methylation in Adoptive Cell Transfer Therapy.

Transgenic T-cell receptor (TCR) adoptive cell therapies recognizing tumor antigens are associated with robust initial response rates, but frequent disease relapse. This usually occurs in the setting of poor long-term persistence of cells expressing the transgenic TCR, generated using murine stem cell virus (MSCV) y-retroviral vectors. Analysis of clinical transgenic adoptive cell therapy products in vivo revealed that despite strong persistence of the transgenic TCR DNA sequence over time, its expression was profoundly decreased over time at the RNA and protein levels. Patients with the greatest degrees of expression suppression displayed significant increases in DNA methylation over time within the MSCV promoter region, as well as progressive increases in DNA methylation within the entire MSCV vector over time. These increases in vector methylation occurred independently of its integration site within the host genomes. These results have significant implications for the design of future viral-vector gene engineered adoptive cell transfer therapies.
A Review of the Ephedra genus: Distribution, Ecology, Ethnobotany, Phytochemistry and Pharmacological Properties

Ephedra is one of the largest genera of the Ephedraceae family, which is distributed in arid and semiarid regions of the world. In the traditional medicine from several countries some species from the genus are commonly used to treat asthma, cold, flu, chills, fever, headache, nasal congestion, and cough. The chemical constituents of Ephedra species have been of research interest for decades due to their contents of ephedrine-type alkaloids and its pharmacological properties. Other chemical constituents such as phenolic and amino acid derivatives also have resulted attractive and have provided evidence-based supporting of the ethnomedical uses of the Ephedra species. In recent years, research has been expanded to explore the endophytic fungal diversity associated to Ephedra species, as well as, the chemical constituents derived from these fungi and their pharmacological bioprospecting. Two additional aspects that illustrate the chemical diversity of Ephedra genus are the chemotaxonomy approaches and the use of ephedrine-type alkaloids as building blocks in organic synthesis. American Ephedra species, especially those that exist in Mexico, are considered to lack ephedrine type alkaloids. In this sense, the phytochemical study of Mexican Ephedra species is a promising area of research to corroborate their ephedrine-type alkaloids content and, in turn, discover new chemical compounds with potential biological activity. Therefore, the present review represents a key compilation of all the relevant information for the Ephedra genus, in particular the American species, the species distribution, their ecological interactions, its ethnobotany, its phytochemistry and their pharmacological activities and toxicities, in order to promote clear directions for future research.
Impact of population bottlenecks on genetic variation and the importance of life-history; a case study of the northern elephant seal

This paper reviews some of the important factors related to the impact of population bottlenecks, using the northern elephant seal (Mirounga angustirostrus) as a case study for illustration. The northern elephant seal was hunted extensively in the 19th century and forced through a bottleneck of approximately 10–20 seals. All measures of molecular genetic variation show current levels for the northern elephant seal to be low. Levels of genetic variation were compared with expectations based on a simulation model that recapitulates demographic growth, based on age-specific data on reproduction and mortality. Predictions from the simulation model are then presented to illustrate the importance of differences in life-history strategy and skewed reproductive success. Either high reproductive skew (e.g. polygyny) or a low growth rate in a population can increase the impact of a bottleneck on molecular variation. Severe population bottlenecks can also disrupt aspects of developmental stability and thereby increase the fluctuating asymmetry and variability of quantitative traits. A comparison of skulls collected before and after the bottleneck showed this to have occurred for some elephant seal quantitative characters.
The Effect of Structure on the Memory for Procedural Text

The present study examined how the structure of procedural texts affected recall of those texts. Past research has found that procedural text is comprehended best when readers expend a moderate amount of effort in processing it; the amount of effort may depend on the structure of the procedural text. Sixty-three participants read six procedural texts describing how to construct simple machines. One group of participants read texts that contained a diagram of the object, whereas the other group read texts with no diagram. Two types of texts were presented: Narrative and list-like procedural texts. Results showed that rereading increased recall of the list-like text, but had little effect for the narrative text. The elaboration hypothesis explains the recall differences after a single reading, but it is still unclear why the list-like texts were recalled better than the narrative texts after a second reading.