Miracle-dz/UniFAR-FTUs huggingface dataset:
Folding and Dimerization of Tick-Borne Encephalitis Virus Envelope Proteins prM and E in the Endoplasmic Reticulum

ABSTRACT Flavivirus envelope proteins are synthesized as part of large polyproteins that are co- and posttranslationally cleaved into their individual chains. To investigate whether the interaction of neighboring proteins within the precursor protein is required to ensure proper maturation of the individual components, we have analyzed the folding of the flavivirus tick-borne encephalitis (TBE) virus envelope glycoproteins prM and E by using a recombinant plasmid expression system and virus-infected cells. When expressed in their polyprotein context, prM and E achieved their native folded structures with half-times of approximately 4 min for prM and about 15 min for E. They formed heterodimeric complexes within a few minutes after synthesis that were required for the final folding of E but not for that of prM. Heterodimers could also be formed in trans when these proteins were coexpressed from separate constructs. When expressed without prM, E could form disulfide bonds but did not express a specific conformational epitope and remained sensitive to reduction by dithiothreitol. This is consistent with a chaperone-like role for prM in the folding of E. PrM was able to achieve its native folded structure without coexpression of E, but signal sequence cleavage at the N terminus was delayed. Our results show that prM is an especially rapidly folding viral glycoprotein, that polyprotein cleavage and folding of the TBE virus envelope proteins occurs in a coordinated sequence of processing steps, and that proper and efficient maturation of prM and E can only be achieved by cosynthesis of these two proteins.
Mesangial Expansion as a Central Mechanism for Loss of Kidney Function in Diabetic Patients

Diabetic nephropathy leading to kidney failure is a major complication of both type I (insulin-dependent) and type II (non-insulin-dependent) diabetes mellitus, and glomerular structural lesions (especially expansion of the mesangium) may constitute the principal cause of decline in kidney function experienced by a significant fraction of diabetic patients. Although the biochemical bases of these mesangial abnormalities remain unknown, an understanding of the natural history of diabetic nephropathy from a combined structural and functional approach can lead to greater pathophysiological insight. Work in animals has supported the concept that the metabolic disturbances of diabetes mellitus cause diabetic nephropathy, with structural and functional lesions prevented or reversed with improved or normalized glycemie control. Additional research must address this fundamental issue in humans, especially the response of advancing mesangial lesions to improved glycemie control. Factors not directly related to the metabolic perturbations of diabetes may serve to accelerate or diminish the pathophysiological processes of diabetic nephropathy. The elucidation and management of these factors, when coupled with improved glycemie control, may moderate the development or progression of diabetic kidney lesions in humans.
Isolation of a novel retinoic acid-responsive gene by selection of genomic fragments derived from CpG-island-enriched DNA

One of the primary goals in transcription factor research is the elucidation of the genetic networks controlled by a factor or by members of a family of closely related factors. The pleiotropic effects of retinoic acid (PA) in the developing and adult animal are mediated by ligand-inducible transcription factors (RA receptors [RARs] and retinoid X receptors [RXRs]) that belong to the superfamily of nuclear receptors. Regulatory regions of PA effector genes contain RAR and RXR binding sites (RAR elements [RAREs] and RXR elements [RXREs]) that generally consist of direct or everted repeats of the core half-site motif, (A/G)G(G/T)TCA. In order to identify novel genes regulated by RA, we devised a selection strategy based on the premise that regulatory regions of a large number of housekeeping and tissue-specific genes are embodied within CpG island DNA. In this method, referred to as CpG-selected and amplified binding, fragments derived from the CpG island fraction of the murine genome are selected by a gel mobility shift assay using in vitro-transcribed and -translated RXR-RAR. Multiple rounds of selection coupled with amplification of the fragments by PCR enabled us to clone a population of CG-rich fragments of which approximately one-fifth contained consensus RAREs or RXREs. Twelve genomic fragments containing novel response elements are described, and the transcription unit associated with one of them, NN-84AG, was characterized in detail. The mouse NN-84AG transcript is upregulated by RA in F9 embryonal carcinoma cells and is homologous to an expressed sequence tag (EST41159) derived from a human infant brain cDNA library. Cloning of the murine NN8-4AG genomic sequence places the RXRE in the proximity of the transcription initiation sites of the gene. Although sequence analysis indicates that the EST41159 gene product is novel, a region of amino acid identity with sequences of a yeast polypeptide of, as yet, unknown function and the Drosophila trithorax protein suggests the presence of an evolutionarily and functionally conserved domain. Our study demonstrates that transcription factor binding sites and corresponding regulated genes can be identified by selecting fragments derived from the CpG island fraction of the genome.
Acute and chronic effects of nitrendipine in patients with precapillary pulmonary hypertension due to pulmonary fibrosis

Eleven patients with histologically confirmed fibrosis of the lung were investigated for the effects of the dihydropyridine calcium antagonist nitrendipine on pulmonary hemodynamics. After 5 mg of acute sublingual nitrendipine, mean pulmonary artery pressure was significantly lowered (p≤0.05) from 32 ± 3 to 29 ± 3 mmHg at rest, and significantly lowered (p≤0.05) during exercise from 55 ± 4 to 49 ± 4 mmHg. Short‐term oxygen application at rest significantly reduced this parameter to 28 ± 3 mmHg(p≤0.01). Nitrendipine lowered total pulmonary vascular resistance during both rest (from 412 ± 50 to 351 ± 49 dyn•S•cm‐5; p≤0.05) and exercise (from 433 ± 61 to 383 ± 54 dyn•s•cm‐5; p≤0.05), although it did not affect pulmonary arteriolar resistance. Also, oxygen treatment at rest influenced only total pulmonary vascular resistance (reduction from 412 ± 50 to 373 ± 48 dyn•s•cm‐5; p≤0.01), but not pulmonary arteriolar resistance. Pressure‐flow curves, which were derived from cardiac output at rest and during exercise and from the corresponding gradient between mean pulmonary artery pressure and pulmonary capillary wedge pressure, remained unchanged by acute medication. Since a change in arterial oxygen partial pressure was not noticed after nitrendipine, arteriovenous shunting or a worsening of ventilation perfusion relationships can be excluded. Long‐term (3 weeks) treatment (double‐blind parallel design) with 10 mg of nitrendipine (4 patients) once daily showed no advantage in comparison to placebo (6 patients). From these observations we conclude that the reduction of lower circulatory pressures after nitrendipine is not caused by pulmonary arteriolar vasodilation, but rather by indirect effects due to the reduction of total peripheral resistance and left ventricular filling pressure.
Determination of the Termination Efficiency of the Transcription Terminator Using Different Fluorescent Profiles in Green Fluorescent Protein Mutants

An approach in determining the intrinsic termination efficiency (% T ) of transcription termination using green fluorescent protein (GFP) mutants was developed. This approach utilizes a cassette vector in which the tested terminator is introduced between two GFP mutant genes: an ultraviolet-optimized mutant (GFPuv: F99S, M153T, V163A) and a blue-shifted mutant (BFP: F64L, S65T, T145F). The ratio of the fluorescence intensity of BFP to GFPuv after transcription and translation represents the termination efficiency of the terminator. E. coli ribosomal RNA operon Tl terminator, phage lambda terminator site R2, E. coli tryptophane attenuater were introduced into the vector, and their transcriptional efficiencies were estimated as 89, 79, and 24%, respectively, showing good agreement with published data.
Dietary conjugated linoleic acid and long-chain n-3 fatty acids in mammary and prostate cancer protection: a review

The role of dietary fatty acids on cancer is still controversial. To examine the current literature on the protective role of conjugated linoleic acid (CLA) and marine long-chain fatty acids [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] and the risk of breast and prostate cancer, data from 41 case-control and cohort studies and relevant in vitro and animal experiments were included in this 2000–2010 revision. Epidemiological studies on CLA intake or its tissue concentration related to breast and prostate tumorigenesis are not conclusive; EPA and DHA intake have shown important inverse associations just in some studies. Additional research on the analysed association is required.
Morphology and structure of starch granules in storage root of purple sweet potato

The microstructure and formation process of starch granule in purple sweet potato tube were examined by light microscopy (LM), transmission electron microscopy (TEM), and scanning electron microscopy (SEM) in this study. The results showed that the proliferation of division activities of amyloplasts was followed by massive accumulation of amyloplasts in cells. The amyloplasts then produced several eccentric starch granules, and the structure of binary and tetrad starch granules was evident upon imaging by LM, TEM, and SEM. In the original formation of starch granule, there were no absolute crystals aggregated. Some blocklet crystals gradually appeared in the starch granules as numerous ‘microgranules’ were tightly connected into the chain, containing the double helix of amylopectin. Many ‘microgranules’ were observed on the exterior surface of the starch granule and formed multiple concentric shells which increased the diameter of starch.
Inferring linguistic structure in spoken language

We demonstrate the applications of Markov Chains and HMMs to modeling of the underlying structure in spontaneous spoken language. Experiments with supervised training cover the detection of the current dialog state and identi cation of the speech act as used by the speech translation component in our JANUS Speech-to-Speech Translation System. HMM training with hidden states is used to uncover other levels of structure in the task. The possible use of the model for perplexity reduction in a continuous speech recognition system is also demonstrated. To achieve improvement over a state independent bigram language model, great care must be taken to keep the number of model parameters small in the face of limited amounts of training data from transcribed spontaneous speech.
Classification structurée pour l'apprentissage par renforcement inverse

Résumé : Cette contribution traite du problème de l’apprentissage par imitation par le biais de l’apprentissage par renforcement inverse ( ARI ). Dans ce contexte, un expert accomplit une tâche qu’un agent artiﬁciel doit essayer de reproduire. L’ARI part du postulat que l’expert optimise avec succès une fonction de récompense; le problème consiste à deviner cette fonction à partir de traces du comportement de l’expert. Les algorithmes d’ARI existants nécessitent une ou plusieurs des conditions suivantes pour fonctionner : trajectoires complètes de la part de l’expert, un modèle génératif pour les estimations de type Monte-Carlo, la connaissance des probabilités de transition, la capacité de résoudre le problème direct (celui de l’apprentissage par renforcement) de manière répétée ou l’accès à la strategie complète de l’expert. Notre contribution consiste en un nouvel algorithme d’ARI levant l’ensemble de ces contraintes. En utilisant une méthode supervisée dans laquelle nous introduisons implicitement la structure du processus décisionnel de Markov ( PDM ) sous-jacent, nous créons un algorithme basé sur une descente de sous-gradient, possèdant une faible complexité tant en échantillons que calculatoire et surtout ne nécessitant pas la résolution du problème direct. Mots-clés : Apprentissage par renforcement inverse, classiﬁcation multi-classe,
Crayfish: A newly recognized vehicle for vibrio infections

We conducted a 1-year case-control study of sporadic vibrio infections to identify risk factors related to consumption of seafood products in two coastal areas of Louisiana and Texas. Twenty-six persons with sporadic vibrio infections and 77 matched controls were enrolled. Multivariate analysis revealed that crayfish (P<0·025) and raw oysters (P<0·009) were independently associated with illness. Species-specific analysis revealed an association between consumption of cooked crayfish and Vibrio parahemolyticus infection (or 9·24, P<0·05). No crayfish consumption was reported by persons with V. vulnificus infection. Although crayfish had been suspected as a vehicle for foodborne disease, this is the first time to our knowledge that consumption of cooked crayfish has been demonstrated to be associated with vibrio infection.
Absorbed fractions for electrons and beta particles in spheres of various sizes.

UNLABELLED The use of electron-emitting radionuclides in tumor imaging and therapy has presented some new challenges to conventional radiation dosimetry. The fraction of electron energy absorbed in most source regions has usually been assumed to be unity. In small structures such as localized tumors or isolated regions containing moderate to high energy electron emitters, however, this may not always be the case. METHODS Using an extension of Berger's scaled absorbed dose distributions for point sources to represent a spherical geometry, absorbed fractions of electron energy for sources uniformly distributed in spheres of various sizes have been calculated. RESULTS Beta particle and monoenergetic electron energies studied range from 0.025 to 4.0 MeV and sphere masses range from 0.01 to 1000 g. S values have also been calculated for 90Y, 123I and 131I based on the results of the absorbed fraction calculations. CONCLUSION These calculated absorbed fractions are valuable in estimating electron energy loss from small spherical structures and may be useful in estimating the radiation dose to these small volumes.
Modular DC/DC converter: Comparison of modulation methods

This paper presents a bidirectional modular DC/DC converter. It consists of two Modular Multilevel Converters (MMC) linked by a transformer to achieve galvanic isolation. This topology serves as “DC transformer” interfacing low and medium voltage DC grids. By the means of the “front-to-front” connection, the converter is able to handle short circuits without additional protection. A higher operating frequency makes it possible to decrease the size of the transformer, the capacitors and the branch inductances. Two fundamental frequency modulation methods are presented with the aim to reduce the switching frequencies without penalizing the performance of the transformer. The multilevel modulation yields a conventional staircase voltage waveform, whereas the two-level modulation, which is inspired by the conventional double active bridge converter, results in a two-level voltage waveform. A case study of a wind power converter will serve as point of comparison between the two methods. The semiconductor losses are evaluated and the efficiencies for different transformer designs are discussed.
Mediators of injury in lupus nephritis

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by the production of autoantibodies and the development of immune complex glomerulonephritis. Lupus nephritis (LN) remains a leading cause of morbidity and mortality in SLE. As a result, defining pathogenetic mediators in LN remains a major research effort. Progression to LN in SLE is dependent on the host breaking immune tolerance and forming autoantibodies that deposit in the kidney. A variety of predisposing factors in the host must then be present for this event to result in renal pathology. In this article, the authors review recent reports that advance our understanding of LN disease mediators, from autoantibody production and immune complex deposition to end stage fibrosis.
Vascular Cell Kinetics in Response to Intimal Injury ex vivo

Background: Recent studies indicate that the smooth muscle-like cells contributing to neointimal hyperplasia after vascular injury derive from circulating precursor cells. Here, we define the time course of precursor cell influx, the roles of separate vascular layers, and the relative role of migration versus proliferation to intimal hyperplasia. Methods and Results: After rat aortic denudation injury the neointimal cell number increased several 100-fold between days 4 and 28, preceded by a 5-fold increase in the number of adventitial cells and a 4-fold increase in the number of adventitial microvessels. The influx, migration, and maturation of neointimal cells were quantitated by culturing whole vessel explants at different time points after injury. Explant outgrowth increased 14-fold, and cell migration 3.5-fold on days 2–14 after injury. Cell proliferation increased less than 2-fold. The frequency of precursors to outgrowing cells, determined using limiting dilution analysis, increased 8-fold between days 2 and 4 after injury. Many outgrowing cells displayed characteristics of undifferentiated cells. Conclusions: Adventitial activation precedes development of the neointima, and precursor cell influx occurs on days 2–14 after injury. Cell migration, more than proliferation, contributes to fibrointimal dysplasia. These findings underline the importance of early therapeutic intervention with antimigratory compounds to prevent neointimal hyperplasia.
Neurologic Complications of Anesthesia

Neurologic complications after anesthesia are relatively uncommon but occasionally severe. Intraoperative intracranial hypertension in patients with brain masses, delayed arousal, and postoperative delirium and cognitive dysfunction are among the main complications of general anesthesia. Neuropathy and transient gluteal and leg pain are the most frequent complications of regional blockade. Seizures are infrequent with both anesthesia modalities. Patients with primary neurologic disorders, such as neurodegenerative or neuromuscular conditions, can be at risk for specific complications, and the anesthesia plan must be cautiously adjusted in these patients. In the neurointensive care unit, the complications from large doses of anesthetic agents used for suppression of seizures or control of intracranial pressure are different from those seen perioperatively. Propofol infusion syndrome can be life-threatening when administered for those indications.
Talent identification and deliberate programming in skeleton: Ice novice to Winter Olympian in 14 months

Abstract The aims of this study were to talent transfer, rapidly develop, and qualify an Australian female athlete in the skeleton event at the 2006 Torino Winter Olympic Games and quantify the volume of skeleton-specific training and competition that would enable this to be achieved. Initially, 26 athletes were recruited through a talent identification programme based on their 30-m sprint time. After attending a selection camp, 10 athletes were invited to undertake an intensified skeleton training programme. Four of these athletes were then selected to compete for Australia on the World Cup circuit. All completed runs and simulated push starts were documented over a 14-month period. The athlete who eventually represented Australia at the Torino Winter Olympic Games did so following approximately 300 start simulations and about 220 training/competition runs over a period of 14 months. Using a deliberate programming model, these findings provide a guide to the minimum exposure required for a novice skeleton athlete to reach Olympic representative standard following intensified sport-specific training. The findings of this study are discussed in the context of the deliberate practice theory and offer the term “deliberate programming” as an alternative way of incorporating all aspects of expert development.
Phosphorylation of ezrin on threonine 567 produces a change in secretory phenotype and repolarizes the gastric parietal cell

Phosphorylation of the membrane-cytoskeleton linker protein ezrin has been functionally linked to acid secretion and vesicle recruitment to the apical secretory membrane in gastric parietal cells. Phosphorylation of the conserved T567 residue of ezrin has been shown to alter the N/C oligomerization of ezrin and promote the formation of actin-rich surface projections in other cells. To test the importance of T567 as a regulatory site for ezrin in parietal cell activation, we incorporated wild-type (WT) and mutant forms of ezrin, including the nonphosphorylatable T567A mutation and a mutant mimicking permanent phosphorylation, T567D. All ezrin constructs included C-terminal cyan-fluorescent protein (CFP) and were incorporated into adenoviral constructs for efficient introduction into cultured parietal cells from rabbit stomach. Fluorescence microscopy was used to localize CFP-ezrin and monitor morphological responses. Accumulation of a weak base (aminopyrine) was used to monitor receptor-mediated acid secretory response of the cultured cells. Similar to endogenous ezrin, WT and T567A CFP-ezrin localized heavily to apical membrane vacuoles with considerably lower levels associated with the surrounding basolateral membrane. Interestingly, H,K-ATPase within cytoplasmic tubulovesicles was incorporated into the apical vacuoles along with WT and T567A mutant ezrin. In these parietal cells secretagogue stimulation produced a striking vacuolar expansion associated with HCl secretion and the secretory phenotype. Expression of T567D CFP-ezrin was quite different, being rarely associated with apical vacuoles. T567D was more typically localized to the basolateral membrane, often associated with long spikes and fingerlike projections. Moreover, the cells did not display secretagogue-dependent morphological changes and, to our surprise, H,K-ATPase was recruited to the T567D CFP-ezrin-enriched basolateral projections. We conclude that T567 phosphorylation, which is probably regulated through Rho signaling pathway, may direct ezrin to membrane-cytoskeletal activity at the basolateral membrane and away from apical secretory activity. The large basolateral expansion is predicted to recruit membranes from sources not normally targeted to that surface.
An Analysis of Morning Report at a Pediatric Hospital

The purpose of this study was to determine the types of cases residents select for morning report discussion and the educational value of postdischarge follow-up of unknown cases. Between April and December of 1994, at Cardinal Glennon Children's Hospital in St. Louis, Missouri, random, resident, and group-selected patients listed at morning report were followed up throughout hospitalization. Patients were categorized based upon whether or not their morning report and discharge diagnoses were the same or different. Patients discharged without a diagnosis were followed up by chart review at 6 months to determine whether a diagnosis had been made. Data were analyzed by Chi-square analysis with Bonfferoni adjustment factor for multiple comparisons. Residents were more than two times more likely to select cases for discussion in which the diagnosis changed during hospitalization (P<O.O1). The 6-month follow-up yielded new diagnoses in only 21% of previously unknown cases. We concluded that residents do an exceptional job of selecting difficult diagnostic cases for discussion at morning report. Postdischarge follow up of unknown cases adds little new information for discussion at morning report.