Miracle-dz/UniFAR-FTUs huggingface dataset:
Expansion of the fusion stalk and its implication for biological membrane fusion

Significance We focus on computing lipidic fusion pathway energetics and interpret them in a biological context. We illustrate that the progression of fast synaptic fusion may not rely on the point-like forces that are being transmitted to the membrane via the transmembrane domains of SNARE molecules. Our work bridges the many present gaps between diverse but related experiments and their interpretation, thus providing a coherent and integrative picture. Over the past 20 years, it has been widely accepted that membrane fusion proceeds via a hemifusion step before opening of the productive fusion pore. An initial hourglass-shaped lipid structure, the fusion stalk, is formed between the adjacent membrane leaflets (cis leaflets). It remains controversial if and how fusion proteins drive the subsequent transition (expansion) of the stalk into a fusion pore. Here, we propose a comprehensive and consistent thermodynamic understanding in terms of the underlying free-energy landscape of stalk expansion. We illustrate how the underlying free energy landscape of stalk expansion and the concomitant pathway is altered by subtle differences in membrane environment, such as leaflet composition, asymmetry, and flexibility. Nonleaky stalk expansion (stalk widening) requires the formation of a critical trans-leaflet contact. The fusion machinery can mechanically enforce trans-leaflet contact formation either by directly enforcing the trans-leaflets in close proximity, or by (electrostatically) condensing the area of the cis leaflets. The rate of these fast fusion reactions may not be primarily limited by the energetics but by the forces that the fusion proteins are able to exert.
Using ClinicalTrials.gov to understand the state of clinical research in pulmonary, critical care, and sleep medicine.

RATIONALE ClinicalTrials.gov is the largest trial registry in the world. Strengthened registration requirements, including federal mandates in 2007, have increased study representation. A systematic evaluation of all registered studies has been limited by the absence of an aggregate data set and specialty-specific search terms. OBJECTIVES We leveraged a newly transformed database containing annotated data from ClinicalTrials.gov to define the portfolio of interventional clinical research in pulmonary, critical care, and sleep medicine. METHODS Analysis was restricted to studies registered after September 2007 through September 2010 and defined as "interventional" (n = 40,970). A specialty-specific study data set (n = 2,226) was created using disease condition terms provided by data submitters and medical subject heading terms generated by a National Library of Medicine algorithm. Trial characteristics were extracted and summarized using descriptive statistics. MEASUREMENTS AND MAIN RESULTS Pulmonary, critical care, and sleep medicine trials composed 5.4% of all interventional studies registered over the 3-year period. In contrast, oncology and cardiovascular disease composed 21.9 and 8.4% of trials, respectively. Within pulmonary trials, asthma and chronic obstructive pulmonary disease were the most studied conditions (27.4 and 21.8% of studies, respectively), and measures of lung function or safety were the most frequent primary outcomes. Nearly two-thirds of trials indicated enrollment of 100 patients or fewer, and a majority of studies were phase II or III trials. The single largest funding source (43.5%) was industry, and study characteristics varied by funding source. CONCLUSIONS We applied a novel approach to describe the portfolio of interventional clinical research in pulmonary medicine. Our results indicate a disparity between trial representation and the burden of respiratory disease. Resources should be targeted across the spectrum of pulmonary research to address this discrepancy.
Local Approximation of Centrality Measures

Centrality measures provide a means to differentiate the importance of vertices in a network. These measures are mathematically clear, but the algorithms to compute them often have quadratic time complexity or worse. This may lead to significant computational challenges when applied to large networks. In this paper, we propose a local strategy for three frequently used centrality measures: (i) closeness, (ii) betweenness and (iii) PageRank. This local approach uses only the vertices directly adjacent to a target vertex to derive an approximation of the true centrality measure. The approximations are accompanied with an analysis of the approximation error bounds. Our analysis and experiments show that local approximations are quite successful on undirected graphs, and on directed graphs depending on the reciprocity of edges.
Circadian Formation of Clock Protein Complexes by KaiA, KaiB, KaiC, and SasA in Cyanobacteria*

Physical interactions among clock-related proteins KaiA, KaiB, KaiC, and SasA are proposed to be important for circadian function in the cyanobacterium Synechococcus elongatus PCC 7942. Here we show that the Kai proteins and SasA form heteromultimeric protein complexes dynamically in a circadian fashion. KaiC forms protein complexes of ∼350 and 400–600 kDa during the subjective day and night, respectively, and serves as a core of the circadian protein complexes. This change in the size of the KaiC-containing complex is accompanied by nighttime-specific interaction of KaiA and KaiB with KaiC. In various arrhythmic mutants that lack each functional Kai protein or SasA, circadian rhythms in formation of the clock protein complex are abolished, and the size of the protein complexes is dramatically affected. Thus, circadian-regulated formation of the clock protein complexes is probably a critical process in the generation of circadian rhythm in cyanobacteria.
Apolipoprotein E and Alpha-1-Antichymotrypsin Polymorphisms in Sporadic Inclusion Body Myositis

Sporadic inclusion body myositis (s-IBM) is a progressive muscle disease of unknown aetiology. Characteristically, intracellular amyloid deposits are detectable, including β-amyloid precursor protein, phosphorylated tau, α1-antichymotrypsin (α1-ACT) and apolipoprotein E (ApoE). Polymorphisms and mutations of the encoding genes have been identified in a variety of neurodegenerative diseases including Alzheimer’s disease (AD). Beside other factors, polymorphisms may lead to protein accumulation in both diseases. In particular, polymorphisms within the ApoE and α1-ACT gene have been implicated in the aetiology of AD and s-IBM. We analysed ApoE and α1-ACT gene polymorphisms in 35 s-IBM patients. We could not identify any statistical significant correlation between distinct ApoE and α1-ACT genotypes and the risk of developing s-IBM. Additionally, ApoE and α1-ACT genotypes seem not to influence the onset age of s-IBM. A combination of different α1-ACT and ApoE genotypes appears not to enhance the risk of developing s-IBM. Therefore, allelic variations of α1-ACT and ApoE are unlikely to be genetic key factors in the aetiology of s-IBM.
The KDEL receptor mediates a retrieval mechanism that contributes to quality control at the endoplasmic reticulum

Newly synthesized proteins in the endoplasmic reticulum (ER) must fold and assemble correctly before being transported to their final cellular destination. While some misfolded or partially assembled proteins have been shown to exit the ER, they fail to escape the early secretory system entirely, because they are retrieved from post‐ER compartments to the ER. We elucidate a mechanistic basis for this retrieval and characterize its contribution to ER quality control by studying the fate of the unassembled T‐cell antigen receptor (TCR) α chain. While the steady‐state distribution of TCRα is in the ER, inhibition of retrograde transport by COPI induces the accumulation of TCRα in post‐ER compartments, suggesting that TCRα is cycling between the ER and post‐ER compartments. TCRα associates with BiP, a KDEL protein. Disruption of the ligand‐binding function of the KDEL receptor releases TCRα from the early secretory system to the cell surface, so that TCRα is no longer subject to ER degradation. Thus, our findings suggest that retrieval by the KDEL receptor contributes to mechanisms by which the ER monitors newly synthesized proteins for their proper disposal.
Intracellular amorphous carbonates uncover a new biomineralization process in eukaryotes

Until now, descriptions of intracellular biomineralization of amorphous inclusions involving alkaline‐earth metal (AEM) carbonates other than calcium have been confined exclusively to cyanobacteria (Couradeau et al., 2012). Here, we report the first evidence of the presence of intracellular amorphous granules of AEM carbonates (calcium, strontium, and barium) in unicellular eukaryotes. These inclusions, which we have named micropearls, show concentric and oscillatory zoning on a nanometric scale. They are widespread in certain eukaryote phytoplankters of Lake Geneva (Switzerland) and represent a previously unknown type of non‐skeletal biomineralization, revealing an unexpected pathway in the geochemical cycle of AEMs. We have identified Tetraselmis cf. cordiformis (Chlorophyta, Prasinophyceae) as being responsible for the formation of one micropearl type containing strontium ([Ca,Sr]CO3), which we also found in a cultured strain of Tetraselmis cordiformis. A different flagellated eukaryotic cell forms barium‐rich micropearls [(Ca,Ba)CO3]. The strontium and barium concentrations of both micropearl types are extremely high compared with the undersaturated water of Lake Geneva (the Ba/Ca ratio of the micropearls is up to 800,000 times higher than in the water). This can only be explained by a high biological pre‐concentration of these elements. The particular characteristics of the micropearls, along with the presence of organic sulfur‐containing compounds—associated with and surrounding the micropearls—strongly suggest the existence of a yet‐unreported intracellular biomineralization pathway in eukaryotic micro‐organisms.
“Colonization Pressure” and Risk of Acquisition of Methicillin-Resistant Staphylococcus aureus in a Medical Intensive Care Unit

Abstract Objective: To determine the roles of “colonization pressure,” work load or patient severity in patient acquisition of methicillin-resistant Staphylococcus aureus (MRSA) in intensive care units (ICUs). Design: Prospectively collected data from October 1996 through December 1998. Setting: A 12-bed medical ICU in a university-affiliated general hospital. Patients: Patients with risk factors for MRSA admitted to the ICU were screened within 72 hours of admission and weekly thereafter. MRSA was considered imported if detected during the first 72 hours of admission and nosocomial if detected only thereafter. Three screening strategies were used on admission during three consecutive periods. Interventions: The unit of time chosen for measurements was the week. Weekly colonization pressure (WCP) was defined as the number of MRSA-carrier patient-days/total number of patient-days. Patient severity (number of deaths, Simplified Acute Physiologic Score [SAPS] II), work load (number of admissions. Omega score), and colonization pressure (number of MRSA carriers at the time of admission, WCP) were compared with the number of MRSA-nosocomial cases during the following week. Results: Of the 1,016 patients admitted over 116 weeks, 691 (68%) were screened. MRSA was imported in 91 (8.9%) admitted patients (13.1% of screened patients) and nosocomial in 46 (4.5%). The number of MRSA-nosocomial cases was correlated to the SAPS II (P=.007), the Omega 3 score (P=.007), the number of MRSA-imported cases (P=.01), WCP (P<.0001), and the screening period (P<.0001). In multivariate analysis, WCP was the only independent predictive factor for MRSA acquisition (P=.0002). Above 30% of WCP, the risk of acquisition of MRSA was approximately fivefold times higher (relative risk, 4.9;95% confidence interval, 1.2-19.9; P<.0001). Conclusion: Acquisition of MRSA in ICU patients is strongly and independently influenced by colonization pressure.
Antibacterial activity of GO 10213, a nitroimidazole derivative

Compound GO 10213, a 5-nitroimidazole substituted at the 2 position, is more active against aerobic, microaerophilic, and anaerobic bacteria than metronidazole. The MICs for Salmonella typhimurium (2 to 128 micrograms/ml), Campylobacter spp. (0.06 to 16 micrograms/ml) and Bacteroides spp. (0.03 to 0.25 micrograms/ml) are definitely lower than those of metronidazole. Niridazole, a 5-nitrothiazole, is still more active.
Simulation of intensity based triangular fringe projection technique for surface shape measurements

3D shape measurements are used in many applications such as object recognitions, gaming industry, medical diagnosis, and many other industrial applications. One of the popular 3D shape measurement techniques is the use of fringe projection methods. In this paper we present a simulation study for a triangular intensity variation structured light fringe pattern usage in 3D shape measurements. This technique is supposed to solve issues that appeared in a previous technique that is using saw-tooth intensity variations, particularly, the large distortion in pixels' intensities at fringe boundaries. The technique relies on fringe projection of a single triangular fringe pattern on the surface of the object under study. The reflected image is enhanced and noise is reduced using a tailored weighted average noise removal filter. The enhanced image is then analyzed to extract the height distribution of the targeted object. Two different objects with smoothly varying surfaces are simulated with and without noise. The algorithm is capable of reconstructing original objects to an acceptable degree with a relatively low root mean square error. The new algorithm is faster than the saw-tooth algorithm by a factor of 2 approximately. MAT LAB software was used for all programming purposes in this study.
LIDERAZGO DE LA MUJER GERENTE EN UNIVERSIDADES Y SUS IMPLICACIONES PARA EL APRENDIZAJE ORGANIZACIONAL

La reciente incorporacion de la mujer al trabajo remunerado, ocurre principalmenteen cargos de menor o mediana jerarquia y remuneracion y disminuyede manera importante en centros de mayor poder y decision. A pesarde esto, muchas decidieron aceptar el desafio y participar con exito en elcampo laboral inclusive en aquellas areas que hasta hace poco eran predominiodel hombre, tales como la gerencia publica y privada. Por ello hoydia cobra cada vez mayor importancia el estudio del liderazgo femenino.En Venezuela las mujeres participan activamente en organizaciones civilesy en el ambito laboral, destacandose en el sistema educativo (Universidades),donde ejercen cargos de mediana y alta gerencia. Este estudio tiene comoobjetivo derivar del Modelo Interpretativo las implicaciones que el tipo deliderazgo predominante en la mujer gerente tiene para el Aprendizaje Organizacionalde las instituciones donde ellas actuan. Se fundamenta en los enfoquesteoricos sobre Liderazgo y Aprendizaje Organizacional de Argyris ySchon (1978), Senge (1992) y Covey (1995). Esta investigacion es de tipodescriptivo-analitico con un diseno metodologico cualitativo. Son sujetos lasgerentes femeninas que desempenan cargos directivos de primer nivel gerencialen universidades oficiales (Rectoras). Se utilizo el Metodo ComparativoConstante de Glasser y Strauss (1967) y la Escalera de la inferencia.Como tecnicas de recoleccion de datos, la Entrevista en Profundidad y elAnalisis del Discurso.
Travelocity Becomes a Travel Retailer

In 2002, Travelocity lost revenue and market share to competition as the business environment changed. Travelocity and Sabre collaborated to develop the enterprise network model (ENM). The ENM combines discrete choice customer modeling with simulation and large-scale optimization to improve Travelocity's management supplier agreements, customer marketing, and product pricing. The ENM has helped Travelocity become a more effective retailer and has contributed over $54 million to Travelocity earnings, at a current rate of $43 million per year.
Molecular cloning and expression of two alpha-amylase genes from Streptococcus bovis 148 in Escherichia coli

The alpha-amylase genes of Streptococcus bovis 148 were cloned in Escherichia coli MC1061, using pBR322. The recombinant plasmids were classified into two groups on the basis of their restriction maps. Southern blot analysis did not show homology between the two types of alpha-amylase genes, and the two alpha-amylase genes existed on the chromosomal DNA of S. bovis 148. The enzymatic properties and N-terminal amino acid sequences of the two purified enzymes produced by the cloned E. coli strains were quite different from each other. Particularly, one alpha-amylase (Amy I) was adsorbed on raw corn starch and hydrolyzed raw corn starch, and another (Amy II) was not adsorbed on raw corn starch and did not hydrolyze raw corn starch. Amy I was considered to be the same as the extracellular alpha-amylase of S. bovis 148 in raw starch absorbability, ability to hydrolyze raw corn starch, enzymatic characteristics, N-terminal amino acid sequence, and mode of action on soluble starch. Amy II showed a unique pattern of oligosaccharide production from soluble starch compared with the extracellular alpha-amylase of S. bovis 148. Amy II was suggested to be an intracellular alpha-amylase of S. bovis 148.
Fungal Membrane Responses Induced by Plant Defensins and Thionins*

Treatment of hyphae of Neurospora crassa with antifungal plant defensins, i.e. Rs-AFP2 and Dm-AMP1 isolated from radish and dahlia seed, respectively, induced a rapid K+ efflux, Ca2+ uptake, and alkalinization of the incubation medium. The Rs-AFP2-induced alkalinization of the incubation medium could be inhibited with G-protein inhibitors. α-Hordothionin, an antifungal thionin from barley seed, caused a sustained increased Ca2+ uptake at subinhibitory concentrations but only a transient increased uptake at inhibitory concentrations. α-Hordothionin also caused increased K+ efflux and alkalinization of the medium, but these fluxes occurred more rapidly compared to those caused by plant defensins. Furthermore, α-hordothionin caused permeabilization of fungal hyphae to the non-metabolite α-aminoisobutyric acid and, in addition, altered the electrical properties of artificial lipid bilayers, consistently leading to rupture of the lipid bilayers. The plant defensins did not form ion-permeable pores in artificial membranes and did not exhibit substantial hyphal membrane permeabilization activity. Our results are consistent with the notion that thionins inhibit fungal growth as a result of direct protein-membrane interactions, whereas plant defensins might act via a different, possibly receptor-mediated, mechanism.
Mesodiencephalic projections to the vestibular complex in the cat

The distribution of cells in the rostral medial mesencephalon and caudal diencephalon which project to the vestibular complex was mapped in the cat by using retrograde axonal transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA‐HRP). Subsequent experiments using anterograde transport of WGA‐HRP clarified the position of the terminations of the mesodiencephalic‐derived afferents in the vestibular complex.
The development of practical guidelines for the care of deceased children is perhaps a utopia?

F or parents, when a child dies, the concluding and irreversible separation is a devastating experience. Studies demonstrate how the care of the deceased child immediately after death is extremely important and how it can impact the families’ capacity to cope with bereavement. Commonly experienced wishes and needs for parents after their child’s death are to be with their child; clean, arrange, and dress the body; accompany the child to the mortuary and then continue to see the child; and have privacy, adequate time, and space. Currently, no official guidelines on the procedures to follow during this delicate phase are available.
Exploring the No-Function-In-Structure principle

Abstract Although much of past work in AI has focused on compiled knowledge systems, recent research shows renewed interest and advanced efforts both in model-based reasoning and in the integration of this deep knowledge with compiled problem solving structures. Device-based reasoning can only be as good as the model used; if the needed knowledge, correct detail, or proper theoretical background is not accessible, performance deteriorates. Much of the work on model-based reasoning references the ‘no-function-in-structure’ principle, which was introduced by de Kleer and Brown. Although they were well motivated in establishing the guideline, this paper explores the applicability and workability of the concept as a universal principle for model representation. This paper first describes the principle, its intent and the concerns it addresses. It then questions the feasibility and the practicality of the principle as a universal guideline for model representation.
Site‐specific recombination in the immune system 1

Site‐specific DNA recombination has been identified in a wide variety of biological systems. In vertebrates, however, the only identified use of this genetic device is in the immune system. Here it plays a critical role in generating a diverse repertoire of surface receptors to intercept invading microbes and parasites. The mechanism and orchestration of this reaction are intriguing and are relevant to a broad array of related biological and biomedical issues. — Lieber, M. R. Site‐specific recombination in the immune system. FASEB J. 5: 2934‐2944; 1991.
Respiratory strategy is a major determinant of [3H]water and [14C]chlorpyrifos uptake in aquatic insects

Despite the extensive use of aquatic insects to evaluate freshwater ecosystem health, little is known about the underlying factors that result in sensitivity differences between taxa. Organismal characteristics (respiratory strategy and body size) were used to explore the rates of ( 3 H)H2O and ( 14 C)chlorpyrifos accumulation in aquatic insects. Ten aquatic insect taxa, including ephemeropteran, trichopteran, dipteran, hemipteran, and coleopteran species, were ex - posed to ( 14 C)chlorpyrifos (240 ng·L -1 ) and ( 3 H)H2O for up to 12 h. Because exchange epithelial surfaces on the integument are permeable to water, ( 3 H)H2O was used as a quantitative surrogate for exposed cellular surface area. ( 14 C)Chlorpyrifos uptake rates were highly correlated with water permeability in all 10 taxa tested and largely covaried with body size and respiratory strategy. Rates were highest among smaller organisms on a per-weight basis and in taxa with relatively large external cellular surfaces such as gills. Air-breathing taxa were significantly less permeable to both ( 3 H)H20 and ( 14 C)chlorpyrifos. A method for labeling exposed epithelial surfaces with a fluorescent dye was developed. This technique allowed discrimination between exchange epithelium and barrier tissue on the integument. Fluorescent dye distributions on the body surface provided a rapid method for estimating exposed epithelium consistent with ( 3 H)H20 and ( 14 C)chlorpyrifos accumulation.