Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular Characterization of the Key Switch F Provides a Basis for Understanding the Rapid Divergence of the Sex-Determining Pathway in the Housefly

The housefly, Musca domestica, is an excellent model system to study the diversification of the pathway that specifies the sexual fate. A number of different mechanisms have been described in the housefly, which reflects in part the broad diversity of sex-determining strategies used in insects. In this study we present the molecular identification and characterization of F, which acts as the master switch in the housefly pathway. We provide evidence that F corresponds to the transformer ortholog in Musca (Mdtra), which, as a result of alternative processing, expresses functional products only in individuals committed to the female fate. We demonstrate that, once activated, a self-sustaining feedback loop will maintain the female-promoting functions of Mdtra. Absence of Mdtra transcripts in eggs of Arrhenogenic (Ag) mutant females suggests that maternally deployed Mdtra activity initiates this self-sustaining loop in the zygote. When an M factor is paternally transmitted to the zygote, the establishment of the loop is prevented at an early stage before cellularization and splicing of Mdtra shifts irreversibly to the male nonproductive mode. On the basis of the analysis of two mutant alleles we can explain the different sex-determining systems in the housefly largely as deviations at the level of Mdtra regulation. This plasticity in the housefly pathway may provide a suitable framework to understand the evolution of sex-determining mechanisms in other insect species. For instance, while sex determination in a close relative, the tsetse fly Glossina morsitans, differs at the level of the instructive signal, we find that its tra ortholog, Gmtra, is regulated in a mode similar to that of Mdtra.
The role of PfEMP1 as targets of naturally acquired immunity to childhood malaria: prospects for a vaccine

SUMMARY The Plasmodium falciparum erythrocyte membrane protein 1 antigens that are inserted onto the surface of P. falciparum infected erythrocytes play a key role both in the pathology of severe malaria and as targets of naturally acquired immunity. They might be considered unlikely vaccine targets because they are extremely diverse. However, several lines of evidence suggest that underneath this molecular diversity there are a restricted set of epitopes which may act as effective targets for a vaccine against severe malaria. Here we review some of the recent developments in this area of research, focusing on work that has assessed the potential of these molecules as possible vaccine targets.
Profiling of Phenolic Compounds and Antioxidant Activity of Dry Extracts from the Selected Sorbus Species

The antioxidant efficiency of dry extracts from inflorescences and/or leaves of seven Sorbus species was studied using four in vitro tests of SET (single electron transfer) and HAT-type (hydrogen atom transfer) mechanisms. The 70% methanol extracts and its diethyl ether, ethyl acetate, n-butanol and water fractions were tested in parallel with the phenolic standards, e.g., caffeic acid, quercetin, BHA, BHT, and Trolox®. The SET-type activity of the extracts depended primarily on the extraction solvent. The most valuable extracts were n-butanol and ethyl acetate ones, which activity was high in the DPPH (EC50 = 3.2–5.2 μg/mL), TEAC (2.8–4.0 mmol Trolox®/g), and FRAP (9.8–13.7 mmol Fe2+/g) tests, and strongly correlated with the total phenolic levels (39.6–58.2% of gallic acid equivalents). The HPLC-PDA analysis of the extracts led to the identification of chlorogenic acid, isoquercitrin, hyperoside, rutin, quercetin 3-O-sophoroside, and sexangularetin 3-O-β-D-glucopyranoside as the main components. Apart from flavonoids and hydroxycinnamic acids, proanthocyanidins have also a significant impact on the SET-type activity. The HAT-reactivity of the extracts in the linoleic acid peroxidation test (IC50 = 36.9–228.3 μg/mL) depended more strongly on the plant tissue than on the extraction solvent, and its correlation with the phenolic content was weak. Both SET and HAT-type activity of the most potent Sorbus extracts was comparable with the activity of the standards, indicating their great potential as effective sources for health products.
Knowledge Management Systems: Issues, Challenges, and Benefits

The knowledge-based theory of the firm suggests that knowledge is the organizational asset that enables sustainable competitive advantage in hypercompetitive environments. The emphasis on knowledge in today’s organizations is based on the assumption that barriers to the transfer and replication of knowledge endow it with strategic importance. Many organizations are developing information systems designed specifically to facilitate the sharing and integration of knowledge. Such systems are referred to as Knowledge Management System (KMS). Because KMS are just beginning to appear in organizations, little research and field data exists to guide the development and implementation of such systems or to guide expectations of the potential benefits of such systems. This study provides an analysis of current practices and outcomes of KMS and the nature of KMS as they are evolving in fifty organizations. The findings suggest that interest in KMS across a variety of industries is very high, the technological foundations are varied, and the major
Molecular dynamics guided study of salt bridge length dependence in both fluorinated and non‐fluorinated parallel dimeric coiled‐coils

The α‐helical coiled‐coil is one of the most common oligomerization motifs found in both native and engineered proteins. To better understand the stability and dynamics of the coiled‐coil motifs, including those modified by fluorination, several fluorinated and nonfluorinated parallel dimeric coiled‐coil protein structures were designed and modeled. We also attempt to investigate how changing the length and geometry of the important stabilizing salt bridges influences the coiled‐coil protein structure. Molecular dynamics (MD) and free energy simulations with AMBER used a particle mesh Ewald treatment of the electrostatics in explicit TIP3P solvent with balanced force field treatments. Preliminary studies with legacy force fields (ff94, ff96, and ff99) show a profound instability of the coiled‐coil structures in short MD simulation. Significantly, better behavior is evident with the more balanced ff99SB and ff03 protein force fields. Overall, the results suggest that the coiled‐coil structures can readily accommodate the larger acidic arginine or S‐2,7‐diaminoheptanedoic acid mutants in the salt bridge, whereas substitution of the smaller L‐ornithine residue leads to rapid disruption of the coiled‐coil structure on the MD simulation time scale. This structural distortion of the secondary structure allows both the formation of large hydration pockets proximal to the charged groups and within the hydrophobic core. Moreover, the increased structural fluctuations and movement lead to a decrease in the water occupancy lifetimes in the hydration pockets. In contrast, analysis of the hydration in the stable dimeric coiled‐coils shows high occupancy water sites along the backbone residues with no water occupancy in the hydrophobic core, although transitory water interactions with the salt bridge residues are evident. The simulations of the fluorinated coiled‐coils suggest that in some cases fluorination electrostatically stabilizes the intermolecular coiled‐coil salt bridges. Structural analyses also reveal different side chain rotamer preferences for leucine when compared with 5,5,5,5′,5′,5′‐hexafluoroleucine mutants. These observed differences in the side chain rotamer populations suggest differential changes in the side chain conformational entropy upon coiled‐coil formation when the protein is fluorinated. The free energy of hydration of the isolated 5,5,5,5′,5′,5′‐hexafluoroleucine amino acid is calculated to be 1.1 kcal/mol less stable than leucine; this hydrophobic penalty in the monomer may provide a driving force for coiled‐coil dimer formation. Estimation of the ellipticity at 222 nm from a series of snapshots from the MD simulations with DicroCalc shows distinct increases in the ellipticity when the coiled‐coil is fluorinated, which suggests that the helicity in the folded coiled‐coils is greater when fluorinated. Proteins 2009. © 2008 Wiley‐Liss, Inc.
Finding effective support-tree preconditioners

In 1995, Gremban, Miller, and Zagha introduced support-tree preconditioners and a parallel algorithm called support-tree conjugate gradient (STCG) for solving linear systems of the form <b><i>Ax = b</i></b>, where <i>A</i> is an <i>n</i> x <i>n</i> Laplacian matrix. A Laplacian is a symmetric matrix in which the off-diagonal entries are non-positive, and the row and column sums are zero. A Laplacian <i>A</i> with 2<i>m</i> off-diagonal non-zeros can be interpreted as an undirected positively-weighted graph <i>G</i> with <i>n</i> vertices and <i>m</i> edges, where there is an edge between two vertices <i>i</i> and <i>j</i> with weight <i>c</i>((<i>i,j</i>)) = --<i>A<inf>i,j</inf></i> = --<i>A<inf>j,i</inf></i> if <i>A<inf>i,j</inf></i> = <i>A<inf>j,i</inf></i> ‹ 0. Gremban <i>et al</i> showed experimentally that STCG performs well on several classes of graphs commonly used in scientific computations. In his thesis, Gremban also proved upper bounds on the number of iterations required for STCG to converge for certain classes of graphs. In this paper, we present an algorithm for finding a preconditioner for an arbitrary graph <i>G</i> = (<i>V,E</i>) with <i>n</i> vertices, <i>m</i> edges, and a weight function <i>c</i> › 0 on the edges, where w.l. o.g. , min<inf>e∈e</inf> <i>c</i>(<i>e</i>) = 1. Equipped with this preconditioner, STCG requires <i>O</i>(log<sup>4</sup> <i>n</i> · √Δ/α) iterations, where α = min<inf>U⊂V,|U|≤|V|/2</inf> <i>c</i>(<i>U,V\U</i>)/|U| is the minimum edge expansion of the graph, and Δ = max<inf>υ∈V</inf> <i>c</i>(υ) is the maximum incident weight on any vertex. Each iteration requires <i>O</i>(<i>m</i>) work and can be implemented in <i>O</i>(log <i>n</i>) steps in parallel, using only <i>O</i>(<i>m</i>) space. Our results generalize to matrices that are symmetric and diagonally-dominant (SDD).
BARC NEWSLETTER Founder ’ s Day STRUCTURE BASED VARIATION IN THE ANTIMUTAGENIC / ANTIOXIDANT PROPERTIES OF DIFFERENT NAPHTHOQUINONES

The structure-function relationships of the naphthoquinone phytochemicals, plumbagin (5-hydroxyl-2-methyl-1,4naphthoquinone), juglone (5-hydroxyl-1,4-naphthoquinone), and menadione (2-methyl-1,4-naphthoquinone), have been studied. Plumbagin showed strong antimutagenic and antioxidant activities, whereas juglone displayed only strong antimutagenic, and menadione only strong antioxidant activities. Thus, functional groups (5-OH/2CH3) seem to play important roles in the differential bioactivity of naphthoquinones. Escherichia coli microarray analysis as well as studies with its single-gene knockouts showed that ybaK (tRNA editing) and speE (spermidine synthesis), reported to prevent mistranslation, are likely to be involved in the antimutagenicity displayed by juglone, and sodC (superoxide dismutase) to be involved in the antioxidant activity of menadione. This paper received the Best poster award at the XXXVIII Annual Conference of Environmental Mutagen Society of India (EMSI) on “Current Perspectives on Environmental Mutagenesis and Human Health”, Mumbai, Jan. 28-30, 2013
Evolutionary Cognitive Neuroscience

Since Darwin we have known that evolution has shaped all organisms and that biological organs -- including the brain and the highly crafted animal nervous system -- are subject to the pressures of natural and sexual selection. It is only relatively recently, however, that the cognitive neurosciences have begun to apply evolutionary theory and methods to the study of brain and behavior. This landmark reference documents and defines the emerging field of evolutionary cognitive neuroscience. Chapters by leading researchers demonstrate the power of the evolutionary perspective to yield new data, theory, and insights on the evolution and functional modularity of the brain. Evolutionary cognitive neuroscience covers all areas of cognitive neuroscience, from nonhuman brain-behavior relationships to human cognition and consciousness, and each section of Evolutionary Cognitive Neuroscience addresses a different adaptive problem. After an introductory section that outlines the basic tenets of both theory and methodology of an evolutionarily informed cognitive neuroscience, the book treats neuroanatomy from ontogenetic and phylogenetic perspectives and explores reproduction and kin recognition, spatial cognition and language, and self-awareness and social cognition. Notable findings include a theory to explain the extended ontogenetic and brain development periods of big-brained organisms, fMRI research on the neural correlates of romantic attraction, an evolutionary view of sex differences in spatial cognition, a theory of language evolution that draws on recent research on mirror neurons, and evidence for a rudimentary theory of mind in nonhuman primates. A final section discusses the ethical implications of evolutionary cognitive neuroscience and the future of the field. Contributors: C. Davison Ankney, Simon Baron-Cohen, S. Marc Breedlove, William Christiana, Michael Corballis, Robin I. M. Dunbar, Russell Fernald, Helen Fisher, Jonathan Flombaum, Farah Focquaert, Steven J.C. Gaulin, Aaron Goetz, Kevin Guise, Ruben C. Gur, William D. Hopkins, Farzin Irani, Julian Paul Keenan, Michael Kimberly, Stephen Kosslyn, Sarah L. Levin, Lori Marino, David Newlin, Ivan S. Panyavin, Shilpa Patel, Webb Phillips, Steven M. Platek, David Andrew Puts, Katie Rodak, J. Philippe Rushton, Laurie Santos, Todd K. Shackelford, Kyra Singh, Sean T. Stevens, Valerie Stone, Jaime W. Thomson, Gina Volshteyn, Paul Root Wolpe
A RHO GTPase-mediated pathway is required during P cell migration in Caenorhabditis elegans

The Rho family of guanine triphosphate hydrolases controls various cellular processes, including cell migration. We describe here the demonstration of a role for a RhoA GTPase homologue during cell migration in Caenorhabditis elegans. We show that eliminating or reducing rho-1 gene function by using a dominant-negative transgene or dsRNA interference results in a severe defect in migration of hypodermal P cells to a ventral position. Biochemical and genetic data also suggest that unc-73, which encodes a Trio-like guanine nucleotide exchange factor, may act as an activator of rho-1 in the migration process. Mutations in let-502 ROCK, a homologue of a RhoA effector in mammals, also cause defects in P cell migration, suggesting that it may be one of several effectors acting downstream of rho-1 during P cell migration. Finally, we provide evidence to support the idea that other small Rac subfamily small GTPases act redundantly and in parallel to RHO-1 in this specific cell migration event.
Deep convolutional neural networks for classification of mild cognitive impaired and Alzheimer's disease patients from scalp EEG recordings

In spite of the worldwide financial and research efforts made, the pathophysiological mechanism at the basis of Alzheimer's disease (AD) is still poorly understood. Previous studies using electroencephalography (EEG) have focused on the slowing of oscillatory brain rhythms, coupled with complexity reduction of the corresponding time-series and their enhanced compressibility. These analyses have been typically carried out on single channels. However, limited investigations have focused on the possibility yielded by computational intelligence methodologies and novel machine learning approaches applied to multichannel schemes. The study at screening level on EEG recordings of subjects at risk could be useful to highlight the emergence of underlying AD progression (or at least support any further clinical investigation). In this work, the representational power of Deep Learning on Convolutional Neural Networks (CNN) is exploited to generate suitable sets of features that are then able to classify EEG patterns of AD from a prodromal version of dementia (Mild Cognitive Impairment, MCI) and from age-matched Healthy Controls (HC). The processing system here used enforces a series of convolutional-subsampling layers in order to derive a multivariate assembly of latent, novel patterns, finally used to categorize sets of EEG from different classes of subjects. The final processor here proposed is able to reach an averaged 80% of correct classification with good performance on both sensitivity and specificity by using a Multilayered Feedforward Perceptron (MLP) of the standard type as a final block of the procedure.
A chlorophyll fluorescence‐based method for the integrated characterization of the photophysiological response to light stress

&NA; This work introduces a new experimental method for the comprehensive description of the physiological responses to light of photosynthetic organisms. It allows the integration in a single experiment of the main established manipulative chlorophyll fluorescence‐based protocols. It enables the integrated characterization of the photophysiology of samples regarding photoacclimation state (generating non‐sequential light‐response curves of effective PSII quantum yield, electron transport rate or non‐photochemical quenching), photoprotection capacity (running light stress‐recovery experiments, quantifying non‐photochemical quenching components) and the operation of photoinactivation and photorepair processes (measuring rate constants of photoinactivation and repair for different light levels and the relative quantum yield of photoinactivation). The new method is based on a previously introduced technique, combining the illumination of a set of replicated samples with spatially separated actinic light beams of different intensity, and the simultaneous measurement of the fluorescence emitted by all samples using an imaging fluorometer. The main novelty described here is the independent manipulation of light intensity and duration of exposure for each sample, and the control of the cumulative light dose applied. The results demonstrate the proof of concept for the method, by comparing the responses of cultures of Chlorella vulgaris acclimated to low and high light regimes, highlighting the mapping of light stress responses over a wide range of light intensity and exposure conditions, and the rapid generation of paired light‐response curves of photoinactivation and repair rate constants. This approach represents a chlorophyll fluorescence ‘protocol of everything’, contributing towards the high throughput characterization of the photophysiology of photosynthetic organisms.
The effects of intermittent negative pressure on the lower extremities' peripheral circulation and wound healing in four patients with lower limb ischemia and hard‐to‐heal leg ulcers: a case report

Peripheral circulation is severely compromised in the advanced stages of peripheral arterial disease. Recently, it was shown that the application of −40 mmHg intermittent negative pressure (INP) to the lower leg and foot enhances macro‐ and microcirculation in healthy volunteers. In this case report, we describe the effects of INP treatment on four patients with lower limb ischemia and hard‐to‐heal leg and foot ulcers. We hypothesized that INP therapy may have beneficial hemodynamic and clinical effects in the patients. Four patients (age range: 61–79 years) with hard‐to‐heal leg and foot ulcers (6–24 months) and ankle‐brachial pressure indices of ≤0.60 on the affected side were included. They were treated with an 8‐week intervention period of −40 mmHg INP (10 sec negative pressure and 7 sec atmospheric pressure) on the lower limbs. A custom‐made vacuum chamber was used to apply INP to the affected lower leg and foot for 2 h per day. After 8 weeks of INP therapy, one ulcer healed completely, while the other three ulcers were almost completely healed. These cases suggest that INP may facilitate wound healing. The theoretical foundation is that INP assists wound healing by improving blood flow to the small blood vessels in the affected limb, increasing the flow of oxygen and nutrients to the cells.
Mitochondrial Approaches to Protect Against Cardiac Ischemia and Reperfusion Injury

The mitochondrion is a vital component in cellular energy metabolism and intracellular signaling processes. Mitochondria are involved in a myriad of complex signaling cascades regulating cell death vs. survival. Importantly, mitochondrial dysfunction and the resulting oxidative and nitrosative stress are central in the pathogenesis of numerous human maladies including cardiovascular diseases, neurodegenerative diseases, diabetes, and retinal diseases, many of which are related. This review will examine the emerging understanding of the role of mitochondria in the etiology and progression of cardiovascular diseases and will explore potential therapeutic benefits of targeting the organelle in attenuating the disease process. Indeed, recent advances in mitochondrial biology have led to selective targeting of drugs designed to modulate or manipulate mitochondrial function, to the use of light therapy directed to the mitochondrial function, and to modification of the mitochondrial genome for potential therapeutic benefit. The approach to rationally treat mitochondrial dysfunction could lead to more effective interventions in cardiovascular diseases that to date have remained elusive. The central premise of this review is that if mitochondrial abnormalities contribute to the etiology of cardiovascular diseases (e.g., ischemic heart disease), alleviating the mitochondrial dysfunction will contribute to mitigating the severity or progression of the disease. To this end, this review will provide an overview of our current understanding of mitochondria function in cardiovascular diseases as well as the potential role for targeting mitochondria with potential drugs or other interventions that lead to protection against cell injury.
Two cases of heterotopic cornual pregnancy with initially missed diagnosis

With the recent increased use of assisted reproductive technology and the rise in the prevalence of tubal and pelvic diseases, the incidence of heterotopic pregnancy is increasing. We report two cases of heterotopic cornual pregnancy, for which the diagnoses were initially missed. Because of the delayed diagnosis, a laparatomy approach was adopted and a novel combination suturing method was used to repair the relatively large cornuostomy wound to provide effective haemostasis. Both patients eventually had a term live birth of the intrauterine pregnancy.
A Plug-in Architecture for Self-Adaptive Web Service Compositions

Several approaches have been proposed to introduce self-management capabilities for web service compositions.However, most of these works are limited as they are not extensible, i.e., new self-adaptation features cannot be supported, and even if that is possible then still this cannot be done dynamically while the composite services are running.In addition, many of these works are not based on the service composition standard WS-BPEL. In this paper, we propose a plug-in architecture for self-adaptive web service composition, in which self-adaptation features are well-modularized in aspect based plug-ins. Our approach supports application-specific adaptation scenarios, is easily extensible, and allows self-adaptation logic to be hot-deployed on running process instances. We have implemented this architecture and several plug-ins using the dynamic aspect-oriented workflow language AO4BPEL.