Miracle-dz/UniFAR-FTUs huggingface dataset:
What is the evidence of a role for host genetics in susceptibility to influenza A/H5N1?

SUMMARY The apparent family clustering of avian influenza A/H5N1 has led several groups to postulate the existence of a host genetic influence on susceptibility to A/H5N1, yet the role of host factors on the risk of A/H5N1 disease has received remarkably little attention compared to the efforts focused on viral factors. We examined the epidemiological patterns of human A/H5N1 cases, their possible explanations, and the plausibility of a host genetic effect on susceptibility to A/H5N1 infection. The preponderance of familial clustering of cases and the relative lack of non-familial clusters, the occurrence of related cases separated by time and place, and the paucity of cases in some highly exposed groups such as poultry cullers, are consistent with a host genetic effect. Animal models support the biological plausibility of genetic susceptibility to A/H5N1. Although the evidence is circumstantial, host genetic factors are a parsimonious explanation for the unusual epidemiology of human A/H5N1 cases and warrant further investigation.
CMT4A: Identification of a Hispanic GDAP1 founder mutation

Mutations of the ganglioside‐induced differentiation‐associated protein 1 gene (GDAP1) cause autosomal recessive Charcot–Marie–Tooth disease type 4A. We report four additional families with recessive mutations (487C→T, Q163X; 359G→A, R120Q) of GDAP1; Q163X occurred in three unrelated Hispanic families that had the same haplotype suggesting a Spanish founder mutation. Both the Q163X and the R120Q mutation cause demyelination and axonal loss. The patients had symptoms within the first two years of life and involvement of cranial, sensory, and enteric nerves. Neuropathology showed loss of large myelinated fibers, onion bulb formations and focal folding of the outer myelin lamina. Ann Neurol 2003;53:400–405
Eosinophil‐derived cytokines in health and disease: unraveling novel mechanisms of selective secretion

Over the past two decades, our understanding of eosinophils has evolved from that of categorically destructive effector cells to include active participation in immune modulation, tissue repair processes, and normal organ development, in both health and disease. At the core of their newly appreciated functions is the capacity of eosinophils to synthesize, store within intracellular granules, and very rapidly secrete a highly diverse repertoire of cytokines. Mechanisms governing the selective secretion of preformed cytokines from eosinophils are attractive therapeutic targets and may well be more broadly applicable to other immune cells. Here, we discuss recent advances in deciphering pathways of cytokine secretion, both from intact eosinophils and from tissue‐deposited cell‐free eosinophil granules, extruded from eosinophils undergoing a lytic cell death.
Conjugal transfer of the 5-nitroimidazole resistance plasmid pIP417 from Bacteroides vulgatus BV-17: characterization and nucleotide sequence analysis of the mobilization region

Three small 5-nitroimidazole (5-Ni) resistance plasmids (pIP417, pIP419, and pIP421) from Bacteroides clinical isolates are transferable by a conjugative process during homologous or heterologous matings. The mobilization properties of pIP417 originated from strain BV-17 of Bacteroides vulgatus were studied. The plasmid was successfully introduced by in vitro conjugation into different strains of Bacteroides and Prevotella species and could be transferred back from these various strains to a plasmid-free 5-Ni-sensitive Bacteroides fragilis strain, indicating that in vivo spread of the resistance gene may occur. The transfer of plasmid pIP417 harbored by the Tc(r) strain BF-2 of B. fragilis was stimulated by low concentrations of tetracycline or chlorotetracycline. This suggests a possible role for coresident conjugative transposons in the dissemination of 5-Ni resistance among gram-negative anaerobes. The nucleotide sequence of the 2.1-kb DNA mobilization region was determined. It contains a putative origin of transfer (oriT) in an A+T-rich-region, including three inverted repeats, and two integration host factor binding sites. The two identified mobilization genes (mobA and mobB) are organized in one operon and were both required for efficient transfer. Southern blotting indicated that the mobilization region of plasmid pIP417 is closely related to that of both the erythromycin resistance plasmid pBFTM1O and the 5-Ni resistance plasmid pIP419 but not to that of the 5-Ni resistance plasmid pIP421.
COLONIZATION HISTORY AND POPULATION GENETICS OF THE COLOR‐POLYMORPHIC HAWAIIAN HAPPY‐FACE SPIDER THERIDION GRALLATOR (ARANEAE, THERIDIIDAE)

Past geological and climatological processes shape extant biodiversity. In the Hawaiian Islands, these processes have provided the physical environment for a number of extensive adaptive radiations. Yet, single species that occur throughout the islands provide some of the best cases for understanding how species respond to the shifting dynamics of the islands in the context of colonization history and associated demographic and adaptive shifts. Here, we focus on the Hawaiian happy‐face spider, a single color‐polymorphic species, and use mitochondrial and nuclear allozyme markers to examine (1) how the mosaic formation of the landscape has dictated population structure, and (2) how cycles of expansion and contraction of the habitat matrix have been associated with demographic shifts, including a “quantum shift” in the genetic basis of the color polymorphism. The results show a marked structure among populations consistent with the age progression of the islands. The finding of low genetic diversity at the youngest site coupled with the very high diversity of haplotypes on the slightly older substrates that are highly dissected by recent volcanism suggests that the mosaic structure of the landscape may play an important role in allowing differentiation of the adaptive color polymorphism.
Networked target tracking With Doppler sensors

This paper deals with the problem of tracking a moving target by means of a network of geographically dispersed nodes with Doppler sensing, communication, and processing capabilities. The problem is addressed both in a hierarchical setting, i.e., in the presence of a fusion center that can fuse data from all the local nodes, and in a peer-to-peer setting wherein each node (peer) has to locally estimate the target kinematic state only on the grounds of local measurements and of data received from its neighbors. A suitable nonlinear observability decomposition is introduced in order to single out state coordinates that can be fully observed from a single Doppler sensor. Based on such a decomposition, a novel dual-stage filtering approach to distributed Doppler-only tracking is developed. In particular, it is shown how the proposed approach can be adopted both in the presence of a fusion center by means of covariance intersection and in the peer-to-peer case by exploiting consensus algorithms. The effectiveness of the proposed algorithms is evaluated via computer simulations.
Cloning of a carbofuran hydrolase gene from Achromobacter sp. strain WM111 and its expression in gram-negative bacteria

A 14-kilobase-pair (kbp) EcoRI DNA fragment that encodes an enzyme capable of rapid hydrolysis of N-methylcarbamate insecticides (carbofuran hydrolase) was cloned from carbofuran-degrading Achromobacter sp. strain WM111. When used to probe Southern blots containing plasmid and total DNAs from WM111, this 14-kbp fragment hybridized strongly to a 14-kbp EcoRI fragment from the greater than 100-kbp plasmid harbored by this strain but weakly to EcoRI-digested total DNA from Achromobacter sp. strain WM111, indicating that the gene for N-methylcarbamate degradation (mcd) is plasmid encoded. Further subcloning localized the mcd gene on a 3-kbp ScaI-ClaI fragment. There was little or no expression of this gene in the alternative gram-negative hosts Pseudomonas putida, Alcaligenes eutrophus, Acinetobacter calcoaceticus, and Achromobacter pestifer. Western blotting (immunoblotting) of the protein products produced by low-level expression in P. putida confirmed that this 3-kbp fragment encodes the two 70+-kilodalton protein products seen in sodium dodecyl sulfate-polyacrylamide gel electrophoresis of purified carbofuran hydrolase.
Effects of Aspirin and Mefenamic Acid on Soman Poisoning–Induced Neuropathology in Mice

The efficacy of aspirin and mefenamic acid to counteract soman-induced brain damage was investigated in mice. Neuronal damage was evaluated in the hippocampus and amygdala by performing ω3 receptor density measurements and hemalun–phloxin staining. The effect of both drugs on the proliferation of neural progenitors after soman exposure was also assessed. Mefenamic acid aggravated the soman-induced hippocampal neuropathology. On the other hand, aspirin recorded a weak neuroprotective effect in the amygdala. However, this drug also diminished the proliferation of neural precursor cells. The possible neurochemical mechanisms underlying such differences in the efficacy of the two drugs are also reviewed.
The Thermic Effect of Food is Reduced in Older Adults

Abstract The thermic effect of food accounts for ̴ 10% of daily energy expenditure. A reduction in the thermic effect of food, which has been variably observed in the older adults, could predispose to fat gain. We tested whether the thermic effect of food is reduced in older adults compared with young adults by analyzing our database of standardized studies conducted at the Mayo Clinic between 1999 and 2009. Data were available from 136 older adult volunteers aged 60–88 (56 females) and 141 young adults aged 18–35 years (67 females). Basal energy expenditure was measured by indirect calorimetry to assess basal metabolic rate. Body fat, fat free mass, and visceral fat were measured using a combination of dual energy X-ray absorptiometry and an abdominal CT scan. The thermic effect of food and postprandial insulinemia were measured in 123 older adults (52 females) and 86 young adults (38 females) of these volunteers. Basal metabolic rate adjusted for fat-free mass was less in older adults (p=0.01) and the thermic effect of food was ̴ 1% (p=0.02) less in the older adults. After controlling for meal size and fat-free mass, body fat and fat distribution did not predict the thermic effect of food. Both basal metabolic rate and the thermic effect of food are less in older adults than young adults, even when they have similar amounts of lean tissue and consume a similar size meal. These factors contribute to lower daily energy expenditure in the older adults.
H-Ras forms dimers on membrane surfaces via a protein–protein interface

Significance Ras is a key signaling molecule in living cells, and mutations in Ras are involved in 30% of human cancers. It is becoming progressively more clear that the spatial arrangement of proteins within a cell, not just their chemical structure, is an important aspect of their function. In this work, we use a series of quantitative physical techniques to map out the tendency of two Ras molecules to bind together to form a dimer on membrane surfaces. Insights from this work, as well as the technical assays developed, may help to discover new therapeutic drugs capable of modulating the errant behavior of Ras in cancer. The lipid-anchored small GTPase Ras is an important signaling node in mammalian cells. A number of observations suggest that Ras is laterally organized within the cell membrane, and this may play a regulatory role in its activation. Lipid anchors composed of palmitoyl and farnesyl moieties in H-, N-, and K-Ras are widely suspected to be responsible for guiding protein organization in membranes. Here, we report that H-Ras forms a dimer on membrane surfaces through a protein–protein binding interface. A Y64A point mutation in the switch II region, known to prevent Son of sevenless and PI3K effector interactions, abolishes dimer formation. This suggests that the switch II region, near the nucleotide binding cleft, is either part of, or allosterically coupled to, the dimer interface. By tethering H-Ras to bilayers via a membrane-miscible lipid tail, we show that dimer formation is mediated by protein interactions and does not require lipid anchor clustering. We quantitatively characterize H-Ras dimerization in supported membranes using a combination of fluorescence correlation spectroscopy, photon counting histogram analysis, time-resolved fluorescence anisotropy, single-molecule tracking, and step photobleaching analysis. The 2D dimerization Kd is measured to be ∼1 × 103 molecules/µm2, and no higher-order oligomers were observed. Dimerization only occurs on the membrane surface; H-Ras is strictly monomeric at comparable densities in solution. Analysis of a number of H-Ras constructs, including key changes to the lipidation pattern of the hypervariable region, suggest that dimerization is a general property of native H-Ras on membrane surfaces.
The Oracle of Dodona

The true site of the oracle of Dodona was discovered only in comparatively recent years. Christopher Wordsworth was the first to identify it, and the Greek archaeologist Carapanos the first to explore it. It lies to the south-west of Ioannina, at a spot most easily accessible from the coast of Thesprotiaby way of the valley of the Thyamis (Fig. 1). It is reached today by a branch road some ten miles to the south of loannina. The long, narrow valley in which it stands is completely dominated on its western side, and for much of the day overshadowed, by the almost precipitous mountain Tomaros (Olitzika), which rises to a height of 6,500 feet. This mountain bears a chain of craggy peaks, and its flank is scarred with gorges and torrents, fed by the snow which lasts some four months of the year on the upper slopes. The climate of the district is severe and well substantiates Homer's description of Δωδώνη δυσχωί-μερος. The valley is remarkable for its violent thunderstorms, which bring torrential rain to fill the mountain cataracts in the summer, and its soil is thus unusually swampy. The foothills of Tomaros are covered with pine trees, while in the plain below a few rather ragged oaks are still to be seen. The rivers of the district are the Acheron and the Kokytos, both associated with the underworld; and not far away is the Acheloos which makes its way down into Akarnania. (See Pl. VI.)
Long time scale kinetic Monte Carlo simulations without lattice approximation and predefined event table

We present a method for carrying out long time scale dynamics simulations within the harmonic transition state theory approximation. For each state of the system, characterized by a local minimum on the potential energy surface, multiple searches for saddle points are carried out using random initial directions. The dimer method is used for the saddle point searches and the rate for each transition mechanism is estimated using harmonic transition state theory. Transitions are selected and the clock advanced according to the kinetic Monte Carlo algorithm. Unlike traditional applications of kinetic Monte Carlo, the atoms are not assumed to sit on lattice sites and a list of all possible transitions need not be specified beforehand. Rather, the relevant transitions are found on the fly during the simulation. A multiple time scale simulation of Al(100) crystal growth is presented where the deposition event, occurring on the time scale of picoseconds, is simulated by ordinary classical dynamics, but the time i.
Measuring driving styles: a validation of the multidimensional driving style inventory

The aim of this study was to validate the stability of the different factors of the Multidimensional Driving Style Inventory (MDSI) [16], which was originally developed and validated with participants in different geographical areas of Israel. In this study, the questionnaire was distributed in the Netherlands and Belgium. A factor analysis of the data of 364 participants revealed five of the eight factors that resulted from the original factor analysis: Angry driving, Anxious driving, Dissociative driving, Distress-reduction driving, and Careful driving style. In addition, 24 items divided over the five factors seem to be stable compared to the 44 items divided over the eight factors of the original analysis. The factors revealed through the analysis of these data were used to determine driver profiles, consisting of one or two driving styles. The next step is to compare self-report data on driving style to actual driving behaviour.
An improved Maximum Uniform SIR power control in ad hoc networks

Power control is quite important for battery powered ad hoc networks, and affects the network capacity, interference and network lifetime, etc. So, the reasonable power control scheme is necessary. In this paper, a modified MUSIR (Maximum Uniform Signal to Interference Noise Ratio) based on the SIR matrix but with better power updating algorithm is proposed to achieve power control in ad hoc networks. It utilizes the advantage of the MUSIR power control algorithm with less information to be transmitted and distributed power control mode. The simulation results show that the proposed power control algorithm is better than the MUSIR power control algorithm in terms of dynamic and stable performance. It not only can adapt the environment fastly but also can save more energy and prolong the network lifetime.
Seaweed extract improve drought tolerance of soybean by regulating stress-response genes

Ascophyllum nodosum extract (ANE) improved growth of soybean plants under drought stress. ANE treatment resulted in an increase in stomatal conductance and anti-oxidant activity in the leaf tissue. The application of ANE also modulated the expression of stress-responsive genes that ultimately resulted in improved growth under drought stress conditions. The results suggest ANE amplifies the plants' natural response to drought stress through change in the pattern of expression of stress response genes. This might be one plausible mode of action of ANE.
A comparison of structure and strategy in electronic commerce

The study of interorganizational systems (IOSs) has been an important area of interest in information systems research. Proponents of “transaction cost” economic theory predict that IOSs will tend towards a market‐driven orientation over time. Other researchers, however, suggest that there is a reverse trend occurring towards more hierarchical systems (fewer and closer relationships between buyers and sellers). This study examines the theoretical and strategic perspectives that tend to promote one form of network relationship over the other. An exploratory qualitative study of both a market (Amazon.com’s Internet book sales system) and a hierarchical (the Wallace Information Network system) network structure supports the development of a framework to guide future research and strategy.
Behavioral performance of multi-robots driven by human drawing

This work addresses the problem of behavioral performance of multi-robots corresponding to human drawing inputs in the sense of friendly human-robot interaction. We propose a drawing interface algorithm with multi-robots based on the centroidal Voronoi tessellation and the continuous-time Lloyd algorithms which have popularly been used for sensing and coverage control of multi-robots. Multi-robots can perform some meaningful behaviors through the realtime density functional update which reflects human drawings. Three drawing modes (distribution, following, and dancing modes) are implemented. Simulation tests verify the feasibility of the proposed algorithm.
αvβ5 Integrin/FAK/PGC-1α Pathway Confers Protective Effects on Retinal Pigment Epithelium

Purpose To elucidate the mechanism of the induction of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) by photoreceptor outer segments (POS) and its effects on retinal pigment epithelium (RPE). Methods PGC-1α upregulation by POS was confirmed in ARPE-19 cells and in RPE ex vivo. To elucidate the mechanism, siRNAs against β5 integrin, CD36, Mer tyrosine kinase (MerTK), and Atg5, blocking antibodies against CD36 and MerTK, and a specific inhibitor for focal adhesion kinase (FAK) were used. We examined the effect of POS-induced PGC-1α upregulation on the levels of reactive oxygen species (ROS), mitochondrial biogenesis, senescence-associated β-galactosidase (SA-β-gal) after H2O2 treatment, and lysosomal activity. Lysosomal activity was evaluated through transcriptional factor EB and its target genes, and the activity of cathepsin D. Lipid metabolism after POS treatment was assessed using Oil Red O and BODIPY C11. RPE phenotypes of PGC-1α-deficient mice were examined. Results POS-induced PGC-1α upregulation was suppressed by siRNA against β5 integrin and a FAK inhibitor. siRNAs and blocking antibodies against CD36 and MerTK enhanced the effect of POS on PGC-1α. The upregulation of PGC-1α increased the levels of mRNA for antioxidant enzymes and stimulated mitochondrial biogenesis, decreased ROS levels, and reduced SA-β-gal staining in H2O2-treated ARPE-19 cells. PGC-1α was critical for lysosomal activity and lipid metabolism after POS treatment. PGC-1α-deficient mice demonstrated an accumulation of type 2 lysosomes in RPE, thickening of Bruch’s membrane, and poor choriocapillaris vasculature. Conclusions The binding, but not the internalization of POS confers protective effects on RPE cells through the αvβ5 integrin/FAK/PGC-1α pathway.
Genotype and clinical course in 2 Chinese Han siblings with Wilson disease presenting with isolated disabling premature osteoarthritis

Rationale: Premature osteoarthritis (POA) is a rare condition in Wilson disease (WD). Particularly, when POA is the only complaint of a WD patient for a long time, there would be misdiagnosis or missed diagnosis and then treatment delay. Patient concerns and diagnosis: Two Chinese Han siblings were diagnosed as WD by corneal K-F rings, laboratory test, and mutation analysis. They presented with isolated POA during the first 2 decades or more of their disease course, and were of missed diagnosis during that long time. The older affected sib became disabled due to his severe osteoarthritis when he was as young as 38 years old. Two compound heterozygous pathogenic variants c. 2790_2792del and c.2621C>T were revealed in the ATP7B gene through targeted next-generation sequencing (NGS). Lessons: Adolescent-onset POA could be the only complaint of WD individual for at least 2 decades. Long delay in the treatment of WD's POA could lead to disability in early adulthood. Detailed physical examination, special biochemical test, and genotyping through targeted NGS should greatly reduce diagnosis delay in atypical WD patients with isolated POA phenotype.
Problem-based learning: how do the outcomes compare with traditional teaching?

Problem-based learning (PBL) was first introduced into the medical curriculum in the UK in 1995.1 With the support of the General Medical Council, who state that ‘modern educational theory and research must influence teaching and learning’,2 it has now been adopted in the majority of UK medical schools and is a core component of teaching in the four new English medical schools.3 It is thought that PBL will better equip doctors for lifelong learning, but is there a good evidence base for such a paradigm shift beyond the application of modern educational theory? PBL essentially involves small groups of students discussing some trigger material (the problem), determining what they need to study, then meeting again to share the results of their learning. However some see PBL as a more general educational strategy embracing philosophy, curriculum, learning environment and outcomes.4 There is no agreed definition of PBL making comparison of studies difficult.5 PBL is one of the most researched educational interventions,6 but little published has been of high quality.5 Authors frequently cite five reviews6–10 covering 91 papers, only four of which were randomised controlled trials. There was little overlap in the papers included between …