Miracle-dz/UniFAR-FTUs huggingface dataset:
Critical differences in HIV‐1 and HIV‐2 protease specificity for clinical inhibitors

Clinical inhibitor amprenavir (APV) is less effective on HIV‐2 protease (PR2) than on HIV‐1 protease (PR1). We solved the crystal structure of PR2 with APV at 1.5 Å resolution to identify structural changes associated with the lowered inhibition. Furthermore, we analyzed the PR1 mutant (PR1M) with substitutions V32I, I47V, and V82I that mimic the inhibitor binding site of PR2. PR1M more closely resembled PR2 than PR1 in catalytic efficiency on four substrate peptides and inhibition by APV, whereas few differences were seen for two other substrates and inhibition by saquinavir (SQV) and darunavir (DRV). High resolution crystal structures of PR1M with APV, DRV, and SQV were compared with available PR1 and PR2 complexes. Val/Ile32 and Ile/Val47 showed compensating interactions with SQV in PR1M and PR1, however, Ile82 interacted with a second SQV bound in an extension of the active site cavity of PR1M. Residues 32 and 82 maintained similar interactions with DRV and APV in all the enzymes, whereas Val47 and Ile47 had opposing effects in the two subunits. Significantly diminished interactions were seen for the aniline of APV bound in PR1M and PR2 relative to the strong hydrogen bonds observed in PR1, consistent with 15‐ and 19‐fold weaker inhibition, respectively. Overall, PR1M partially replicates the specificity of PR2 and gives insight into drug resistant mutations at residues 32, 47, and 82. Moreover, this analysis provides a structural explanation for the weaker antiviral effects of APV on HIV‐2.
Dendritic connectivity shapes spatial patterns of genetic diversity: a simulation‐based study

Landscape features notoriously affect spatial patterns of biodiversity. For instance, in dendritic ecological networks (such as river basins), dendritic connectivity has been proposed to create unique spatial patterns of biodiversity. Here, we compared genetic datasets simulated under a lattice‐like, a dendritic and a circular landscape to test the influence of dendritic connectivity on neutral genetic diversity. The circular landscape had a level of connectivity similar to that of the dendritic landscape, so as to isolate the influence of dendricity on genetic diversity. We found that genetic diversity and differentiation varied strikingly among the three landscapes. For instance, the dendritic landscape generated higher total number of alleles and higher global Fst than the lattice‐like landscape, and these indices also varied between the dendritic and the circular landscapes, suggesting an effect of dendricity. Furthermore, in the dendritic landscape, allelic richness was higher in highly connected demes (e.g. confluences in rivers) than in low‐connected demes (e.g. upstream and downstream populations), which was not the case in the circular landscape, hence confirming the major role of dendricity. This led to bell‐shaped distributions of allelic richness along an upstream–downstream gradient. Conversely, genetic differentiation (Fst) was lower in highly than in low‐connected demes (which was not observed in circular landscape), and significant patterns of isolation by distance (IBD) were also observed in the dendritic landscape. We conclude that in dendritic networks, the combined influence of dendricity and connectivity generates unique spatial patterns of neutral genetic diversity, which has implications for population geneticists and conservationists.
Concentrations of trace elements in eggs and blood of spectacled and common eiders on the Yukon‐Kuskokwim Delta, Alaska, USA

We examined the relations among nesting success, egg viability, and blood and egg concentrations of As, Cd, Pb, Hg, and Se in a threatened population of spectacled eiders (Somateria fischeri) and a sympatric population of common eiders (S. mollissima) on the Yukon‐Kuskokwim Delta, Alaska, USA, during 1995 and 1996. During the early breeding season, males and females had mean Se concentrations in their blood of 19.2 μg/g and 12.8 μg/g wet weight, respectively. Blood Se concentrations of females were correlated with egg concentrations. During brood rearing, blood Se levels were higher in adult females than in ducklings. Blood concentrations of Pb in spectacled eider females were higher than in common eider females captured at hatching, but blood concentrations of Se were similar. Trace element concentrations were not related to nest success or egg viability. We submit that nest success and egg viability of spectacled eiders are not related to concentrations of the trace elements we measured. Because blood Se concentrations declined rapidly through the breeding season and were not related to nest success or egg viability, we suggest that spectacled eiders are exposed to high concentrations of Se during winter that pose little threat to this population.
Skeletal Muscle Hypertrophy and Muscle Myostatin Reduction After Resistive Training in Stroke Survivors

Background and Purpose— Stroke survivors experience disproportionate muscle atrophy and other detrimental tissue composition changes on the paretic side. The purpose was to determine whether myostatin levels are higher in paretic vs nonparetic muscle and the effects of resistive training (RT) on paretic and nonparetic mid-thigh muscle composition and myostatin mRNA expression in stroke survivors. Methods— Fifteen stroke survivors (50–76 years) underwent bilateral multi-slice thigh CT scanning from the knee to the hip, bilateral vastus lateralis skeletal muscle tissue biopsies, a total body scan by dual-energy X-ray absorptiometry, and 1-repetition maximum strength test before and after a 12-week, (3 times/week) RT intervention. Results— Total body fat mass and fat-free mass did not change. Bilateral leg press and leg extension 1-repetition maximum strength increased 31% to 56% with RT (P<0.001). Paretic and nonparetic muscle area of the mid-thigh increased 13% (P<0.01) and 9% (P<0.05), respectively, after RT. Muscle attenuation of the mid-thigh increased 15% and 8% (both P<0.01) in the paretic and nonparetic thigh, respectively, representing reduced intramuscular fat. Muscle volume increased 14% (P<0.001) in the paretic thigh and 16% (P<0.05) in the nonparetic thigh after RT. Myostatin mRNA expression levels were 40% higher in the paretic than nonparetic muscle (P=0.001) at baseline and decreased 49% in the paretic muscle (P<0.005) and 27% in the nonparetic muscle (P=0.06) after RT. Conclusions— Progressive RT stimulates significant muscle hypertrophy and intramuscular fat reductions in disabled stroke survivors. The increased myostatin mRNA in the paretic thigh and reduction with RT imply an important regulatory role for myostatin after stroke.
A transparent non-invasive file data model for algorithmic skeletons

A file data model for algorithmic skeletons is proposed, focusing on transparency and efficiency. Algorithmic skeletons correspond to a high-level programming model that takes advantage of nestable programming patterns to hide the complexity of parallel/distributed applications. Transparency is achieved using a workspace factory abstraction and the proxy pattern to intercept calls on File type objects. Thus allowing programmers to continue using their accustomed programming libraries, without having the burden of explicitly introducing non-functional code to deal with the distribution aspects of their data. A hybrid file fetching strategy is proposed (instead of lazy or eager), that takes advantage of annotated functions and pipelined multithreaded interpreters to transfer files in-advance or on-demand. Experimentally, using a BLAST skeleton application, it is shown that the hybrid strategy provides a good tradeoff between bandwidth usage and CPU idle time.
Atmospheric Volatilization and Distribution of (Z)- and (E)-1,3-Dichloropropene in Field Beds with and without Plastic Covers

Abstract The fumigant 1,3-dichloropropene (1,3-D) is considered to be a potential replacement for methyl bromide when methyl bromide is phased out in 2005. This study on surface emissions and subsurface diffusion of 1,3-D in a Florida sandy soil was conducted in field beds with or without plastic covers. After injection of the commercial fumigant Telone II by conventional chisels to field beds at 30 cm depth which were covered with polyethylene film (PE), virtually impermeable film, or no cover (bare), (Z)- and (E)-1,3-D rapidly diffused upward. Twenty hours after injection, majority of (Z)- and (E)-1,3-D had moved upward from 30 cm depth to the layer of 5–20 cm depth. Downward movement of the two isomers in the beds with or without a plastic cover was not significant. (Z)-1,3-D diffused more rapidly than (E)-1,3-D. Virtually impermeable films (VIF) had a good capacity to retain (Z)- and (E)-1,3-D in soil pore air space. Vapor concentrations of the two isomers in the shallow subsurface of the field bed covered with VIF were greater than that in the two beds covered with polyethylene film (PE) or no cover (bare). In addition, VIF cover provided more uniform distribution of (Z)- and (E)-1,3-D in shallow subsurface than PE cover or no cover. Virtually impermeable film also had a better capability to retard surface emissions of the two isomers from soil in field beds than PE cover or no cover.
Sex Differences and Menstrual Cycle Dependent Changes in Cognitive Strategies during Spatial Navigation and Verbal Fluency

Men typically outperform women in spatial navigation tasks, while the advantage of women in verbal fluency is more controversial. Sex differences in cognitive abilities have been related to sex-specific cognitive strategies on the one hand and sex hormone influences on the other hand. However, sex hormone and menstrual cycle influences on cognitive strategies have not been previously investigated. In the present study we assessed cognitive strategy use during spatial navigation and verbal fluency in 51 men and 49 women. In order to evaluate sex hormone influences, all participants completed two test sessions, which were time-locked to the early follicular (low estradiol and progesterone) and mid-luteal cycle phase (high estradiol and progesterone) in women. As hypothesized, men outperformed women in navigation, whereas women outperformed men in phonemic verbal fluency. Furthermore, women switched more often between categories in the phonemic fluency condition, compared to men, indicating sex-specific strategy use. Sex differences in strategy use during navigation did, however, not follow the expected pattern. Menstrual cycle phase, however, did modulate strategy use during navigation as expected, with improved performance with the landmark strategy in the luteal, compared to the follicular phase. No menstrual cycle effects were observed on clustering or switching during verbal fluency. This suggests a modulation of cognitive strategy use during spatial navigation, but not during verbal fluency, by relative hormone increases during the luteal phase of the menstrual cycle.
Data‐driven confounder selection via Markov and Bayesian networks

To unbiasedly estimate a causal effect on an outcome unconfoundedness is often assumed. If there is sufficient knowledge on the underlying causal structure then existing confounder selection criteria can be used to select subsets of the observed pretreatment covariates, X, sufficient for unconfoundedness, if such subsets exist. Here, estimation of these target subsets is considered when the underlying causal structure is unknown. The proposed method is to model the causal structure by a probabilistic graphical model, for example, a Markov or Bayesian network, estimate this graph from observed data and select the target subsets given the estimated graph. The approach is evaluated by simulation both in a high‐dimensional setting where unconfoundedness holds given X and in a setting where unconfoundedness only holds given subsets of X. Several common target subsets are investigated and the selected subsets are compared with respect to accuracy in estimating the average causal effect. The proposed method is implemented with existing software that can easily handle high‐dimensional data, in terms of large samples and large number of covariates. The results from the simulation study show that, if unconfoundedness holds given X, this approach is very successful in selecting the target subsets, outperforming alternative approaches based on random forests and LASSO, and that the subset estimating the target subset containing all causes of outcome yields smallest MSE in the average causal effect estimation.
Character Decomposition and Transposition Processes in Chinese Compound Words Modulates Attentional Blink

The attentional blink (AB) is the phenomenon in which the identification of the second of two targets (T2) is attenuated if it is presented less than 500 ms after the first target (T1). Although the AB is eliminated in canonical word conditions, it remains unclear whether the character order in compound words affects the magnitude of the AB. Morpheme decomposition and transposition of Chinese two-character compound words can provide an effective means to examine AB priming and to assess combinations of the component representations inherent to visual word identification. In the present study, we examined the processing of consecutive targets in a rapid serial visual presentation (RSVP) paradigm using Chinese two-character compound words in which the two characters were transposed to form meaningful words or meaningless combinations (reversible, transposed, or canonical words). We found that when two Chinese characters that form a compound word, regardless of their order, are presented in an RSVP sequence, the likelihood of an AB for the second character is greatly reduced or eliminated compared to when the two characters constitute separate words rather than a compound word. Moreover, the order of the report for the two characters is more likely to be reversed when the normal order of the two characters in a compound word is reversed, especially when the interval between the presentation of the two characters is extremely short. These findings are more consistent with the cognitive strategy hypothesis than the resource-limited hypothesis during character decomposition and transposition of Chinese two-character compound words. These results suggest that compound characters are perceived as a unit, rather than two separate words. The data further suggest that readers could easily understand the text with character transpositions in compound words during Chinese reading.
Transgenic Overexpression of Tissue‐Nonspecific Alkaline Phosphatase (TNAP) in Vascular Endothelium Results in Generalized Arterial Calcification

Background Ectopic vascular calcification is a common condition associated with aging, atherosclerosis, diabetes, and/or chronic kidney disease. Smooth muscle cells are the best characterized source of osteogenic progenitors in the vasculature; however, recent studies suggest that cells of endothelial origin can also promote calcification. To test this, we sought to increase the osteogenic potential of endothelial cells by overexpressing tissue‐nonspecific alkaline phosphatase (TNAP), a key enzyme that regulates biomineralization, and to determine the pathophysiological effect of endothelial TNAP on vascular calcification and cardiovascular function. Methods and Results We demonstrated previously that mice transgenic for ALPL (gene encoding human TNAP) develop severe arterial medial calcification and reduced viability when TNAP is overexpressed in smooth muscle cells. In this study, we expressed the ALPL transgene in endothelial cells following endothelial‐specific Tie2‐Cre recombination. Mice with endothelial TNAP overexpression survived well into adulthood and displayed generalized arterial calcification. Genes associated with osteochondrogenesis (Runx2, Bglap, Spp1, Opg, and Col2a1) were upregulated in the aortas of endothelial TNAP animals compared with controls. Lesions in coronary arteries of endothelial TNAP mice showed immunoreactivity to Runx2, osteocalcin, osteopontin, and collagen II as well as increased deposition of sialoproteins revealed by lectin staining. By 23 weeks of age, endothelial TNAP mice developed elevated blood pressure and compensatory left ventricular hypertrophy with preserved ejection fraction. Conclusions This study presented a novel genetic model demonstrating the osteogenic potential of TNAP‐positive endothelial cells in promoting pathophysiological vascular calcification.
Deep HST Vand I-Band Observations of the Halo of M 31 : Evidence for Multiple Stellar Populations 1

We present deep (V ' 27) V and I-band stellar photometry obtained using the Hubble Space Telescope’s WFPC2 in two fields in the M31 halo. These fields are located 32′ and 50′ from the center of M31 approximately along the SE minor axis at the locations of the M31 globular star clusters G302 and G312 respectively. The M31 halo luminosity functions are not consistent with a single high-metallicity population but are consistent with a mix of 50% to 75% metal-rich stars and 25% to 50% metal-poor stars. This is consistent with the observed red giant branch morphology, the luminosity of the horizontal branch, and the presence of RR Lyrae stars in the halo of M31. The morphology of the red giant branch indicates a spread in metallicity of −2 ∼< [m/H] ∼< −0.2 with the majority of stars having [m/H] ' −0.6, making the halo of M31 significantly more metal-rich than either the Galactic halo or the M31 globular cluster system. The horizontal branch is dominated by a red clump similar to the horizontal branch of the metal-rich Galactic globular cluster 47 Tuc but a small number of blue horizontal branch stars are visible, supporting the conclusion that there is a metal-poor component to the stellar population of the halo of M31. The number of blue horizontal stars is smaller than would be expected from the observed metallicity distribution but it is not clear if this is due to the photometric limits of our data or a second parameter effect in the halo of M31. We find a lower limit to the helium abundance of Y ' 0.20 to 0.27, comparable with the Galactic value. Luminosity functions show weak evidence that the RM31 = 50 ′ field contains a higher fraction of metal-poor stars than the RM31 = 32 ′ field but the metallicity distributions of the RGB stars in each field strongly suggest that both fields have the same mix of stellar populations. Based in observations with the NASA/ESA Hubble Space Telescope, obtained at the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS5-26555.
CONCURRENCY AND COMPUTATION : PRACTICE AND EXPERIENCE Concurrency Computat

A serious difficulty in concurrent programming of a distributed system is how to deal with scheduling and load balancing of such a system which may consist of heterogeneous computers. In this paper, we formulate the static load-balancing problem in single class job distributed systems as a cooperative game among computers. The computers comprising the distributed system are modeled as M/M/1 queueing systems. It is shown that the Nash bargaining solution (NBS) provides an optimal solution (operation point) for the distributed system and it is also a fair solution. We propose a cooperative load-balancing game and present the structure of NBS. For this game an algorithm for computing NBS is derived. We show that the fairness index is always equal to 1 using NBS, which means that the solution is fair to all jobs. Finally, the performance of our cooperative load-balancing scheme is compared with that of other existing schemes. Copyright © 2008 John Wiley & Sons, Ltd.
Stress-Induced Endocrine and Immune Dysfunctions in Caregivers of People with Eating Disorders

Caregivers have to cope repeatedly with acute stressors in their daily lives, and this is associated with disturbances in the hypothalamic–pituitary–adrenal (HPA) axis and the immune system. Such disturbances could contribute to the development of health problems in informal caregivers of people with chronic illnesses, such as eating disorders (EDs). The main objective of this study was to examine endocrine (salivary cortisol levels (Csal)), immune (immunoglobulin-A (IgA)), and psychological (anxiety, mood, and anger feelings) responses to an acute psychological stressor in a sample of informal caregivers of individuals with EDs compared to a sample of non-caregivers. In addition, it also aimed to analyze the potential relationship of the aforementioned endocrine and immune response parameters with psychological variables in the caregivers. Caregivers had lower Csal and IgA levels at all assessment points except baseline. Moreover, they also exhibited lower Csal and IgA responses and greater worsening of mood in response to acute psychosocial stress than the non-caregivers, which suggests that caregivers had dampened endocrine and immune reactivity to acute stress. On the other hand, endocrine and immune parameters were unrelated to psychological variables. These findings advance our understanding of how a chronically stressed population reacts to acute stress, and should be considered for the development of effective interventions focused on stress management that could help caregivers to reduce their stress levels, which, in turn, would improve their health.
Localized anodization of the aluminum alloy EN AW-7075 T6 by closed electrolytic free jet

Anodizing with closed electrolytic free jet enables the resource-efficient, local conversion and surface structuring of the high-strength alloy EN AW-7075 T6 aiming at the local improvement of the tribological behavior of functional surface areas. The objective of the present work was to confine the current distribution on the specimen’s surface and to achieve a stronger localization of the coating oxide layer. For this purpose, the processing parameters working distance, voltage and process duration were varied systematically. Based on the refractive index of the porous oxide and laser scanning microscope imaging of the interference lines, the maximum thicknesses of the anodized spots were calculated. Moreover, the coating microstructure was investigated by scanning electron microscopy and the surface topography was measured with a stylus profiler. The results show that the reduction of the working distance to 100 μm enables a significantly improved localization of the coating growth at substantially lowered process voltages. Thus, the energy-efficient production of localized, wear-resistant oxide spots for tribological applications with local functionalization of surfaces through anodization by closed electrolytic free jet is proven.