Miracle-dz/UniFAR-FTUs huggingface dataset:
Bleached pigment activates transduction in isolated rods of the salamander retina.

1. We have used suction electrode recording together with rapid steps into Li+ solution and 0.5 mM IBMX solution to estimate the rates of the guanylyl phosphodiesterase (PDE) and guanylyl cyclase in isolated rods of the salamander, Ambystoma tigrinum. 2. We show that both the PDE and cyclase velocities are accelerated by steady background light. The steady velocities of both enzymes appear to be saturating functions of background intensity. 3. Bleaching also accelerates both the PDE and cyclase. This effect is maintained long after the bleaching stimulus is removed (up to 2 h) and is reversed only if the photopigment is regenerated with exogenous chromophore. 4. The estimated steady‐state PDE and cyclase velocities appear to be linear functions of the amount of pigment bleached, as if each bleached pigment molecule activated the transduction cascade with the same probability and gain. 5. The effectiveness of bleached pigment in activating transduction is only 10(‐6) to 10(‐7) times that of activated rhodopsin (Rh*), but this is sufficient after large bleaches to produce an ‘equivalent background’ excitation of the rod, which is probably responsible, at least in part, for bleaching desensitization.
Hereditary nonpolyposis colorectal cancer: Frequent occurrence of large genomic deletions in MSH2 and MLH1 genes

Hereditary nonpolyposis colorectal cancer (HNPCC) is often caused by a deficiency in DNA mismatch repair. By using conventional methods of mutation analysis, point mutations in the DNA mismatch repair genes MSH2 and MLH1 have been detected in up to 64% of patients suspected of HNPCC. However, large genomic deletions cannot be detected by these methods. In our study, we applied a semiquantitative multiplex PCR to detect the proportion of large deletions in patients meeting the Bethesda criteria whose tumours exhibited microsatellite instability (MSI). Of 368 unrelated patients, 180 exhibited MSI. In these patients, 68 disease‐causing point mutations (38%) had previously been detected in the MSH2 and MLH1 genes by SSCP, heteroduplex analysis or DHPLC followed by direct sequencing. The remaining 112 patients (including 24 patients with rare missense or other unclarified variants) were examined for large deletions. We identified deletions in 19 patients (10.6%); 11/19 (58%) deletions were located in MSH2 and 8/19 (42%) in MLH1, respectively. The size of deletions ranged from 1 exon to a deletion of a whole gene. Five breakpoints of deletions were sequenced; Alu‐repetitive elements were involved in all of them. In patients meeting the Amsterdam criteria the proportion of large deletions was 12.6%. A similar proportion of deletions was found in the group of patients with a positive family history for colorectal cancer and MSI tumours, not meeting the Amsterdam criteria. The results of our study suggest that large genomic deletions in both MSH2 and MLH1 genes play a considerable role in the pathogenesis of HNPCC and should be part of the routine HNPCC mutation detection protocols. © 2002 Wiley‐Liss, Inc.
Clinical Manifestations of Parkinson's Disease and Parkinsonism

The most common disorder in a patient presenting to a movement disorder clinic will be parkinsonism. The challenge is to provide the patient with the most accurate diagnosis and prognosis possible. The assumption at the time of initial presentation of the clinical diagnosis of Parkinson's disease is often wrong (20-25%). Waiting to see the pattern of progression, and response to medication provides invaluable additional information. This manuscript summarizes the clinical manifestations of Parkinson's disease and the main akinetic-rigid syndromes (progressive supranuclear palsy, multiple system atrophy, cortical-basal ganglionic degeneration, and dementia with Lewy bodies) that make up the differential diagnosis.
The Functioning of a Cortex without Layers

A major hallmark of cortical organization is the existence of a variable number of layers, i.e., sheets of neurons stacked on top of each other, in which neurons have certain commonalities. However, even for the neocortex, variable numbers of layers have been described and it is just a convention to distinguish six layers from each other. Whether cortical layers are a structural epiphenomenon caused by developmental dynamics or represent a functionally important modularization of cortical computation is still unknown. Here we present our insights from the reeler mutant mouse, a model for a developmental, “molecular lesion”-induced loss of cortical layering that could serve as ground truth of what an intact layering adds to the cortex in terms of functionality. We could demonstrate that the reeler neocortex shows no inversion of cortical layers but rather a severe disorganization that in the primary somatosensory cortex leads to the complete loss of layers. Nevertheless, the somatosensory system is well organized. When exploring an enriched environment with specific sets of whiskers, activity-dependent gene expression takes place in the corresponding modules. Precise whisker stimuli lead to the functional activation of somatotopically organized barrel columns as visualized by intrinsic signal optical imaging. Similar results were obtained in the reeler visual system. When analyzing pathways that could be responsible for preservation of tactile perception, lemniscal thalamic projections were found to be largely intact, despite the smearing of target neurons across the cortical mantle. However, with optogenetic experiments we found evidence for a mild dispersion of thalamic synapse targeting on layer IV-spiny stellate cells, together with a general weakening in thalamocortical input strength. This weakening of thalamic inputs was compensated by intracortical mechanisms involving increased recurrent excitation and/or reduced feedforward inhibition. In conclusion, a layer loss so far only led to the detection of subtle defects in sensory processing by reeler mice. This argues in favor of a view in which cortical layers are not an essential component for basic perception and cognition. A view also supported by recent studies in birds, which can have remarkable cognitive capacities despite the lack of a neocortex with multiple cortical layers. In conclusion, we suggest that future studies directed toward understanding cortical functions should rather focus on circuits specified by functional cell type composition than mere laminar location.
Glucagon Represses Signaling through the Mammalian Target of Rapamycin in Rat Liver by Activating AMP-activated Protein Kinase*

The opposing actions of glucagon and insulin on glucose metabolism within the liver are essential mechanisms for maintaining plasma glucose concentrations within narrow limits. Less well studied are the counterregulatory actions of glucagon on protein metabolism. In the present study, the effect of glucagon on amino acid-induced signaling through the mammalian target of rapamycin (mTOR), an important controller of the mRNA binding step in translation initiation, was examined using the perfused rat liver as an experimental model. The results show that amino acids enhance signaling through mTOR resulting in phosphorylation of eukaryotic initiation factor 4E-binding protein (4E-BP)1, the 70-kDa ribosomal protein (rp)S6 kinase, S6K1, and rpS6. In contrast, glucagon repressed both basal and amino acid-induced signaling through mTOR, as assessed by changes in the phosphorylation of 4E-BP1 and S6K1. The repression was associated with the activation of protein kinase A and enhanced phosphorylation of LKB1 and the AMP-activated protein kinase (AMPK). Surprisingly, the phosphorylation of two S6K1 substrates, rpS6 and eukaryotic initiation factor 4B, was not repressed but instead was increased by glucagon treatment, regardless of the amino acid concentration. The latter finding could be explained by the glucagon-induced phosphorylation of the ERK1 and the 90-kDa rpS6 kinase p90rsk. Thus, glucagon represses phosphorylation of 4E-BP1 and S6K1 through the activation of a protein kinase A-LKB-AMPK-mTOR signaling pathway, while simultaneously enhancing phosphorylation of other downstream effectors of mTOR through the activation of the extracellular signal-regulated protein kinase 1-p90rsk signaling pathway. Amino acids also enhance AMPK phosphorylation, although to a lesser extent than glucagon and amino acids combined.
Adenovirus-mediated transfer of tissue-type plasminogen activator gene to human endothelial cells.

BACKGROUND Seeding of vascular grafts with genetically engineered human endothelial cells (hECs) secreting antithrombogenic or fibrinolytic agents has considerable clinical potential. METHODS An adenoviral vector was used to transfer the human tissue-type plasminogen activator (htPA) gene to hECs, and the ability of the transduced hECs to secrete htPA was examined. Cultured hECs on plates were incubated with various concentrations of recombinant adenoviruses containing the htPA or LacZ gene for various times to determine the optimal transfer conditions. Transduced hECs were seeded onto fibronectin-coated expanded polytetrafluoroethylene grafts (4 mm in diameter), some of which were exposed to pulsatile flow in vitro. RESULTS Effective transduction of the htPA gene into hECs (htPAhECs) was achieved with viral soup at a multiplicity of infection of 30 after incubation for 1 day, which yielded 4.8 +/- 0.20 x 10(3) ng/10(6) cells/6 hr htPA antigen on plates (n = 3), 2.2 +/- 2.0 x 10(3) ng/10(6) cells/6 hr on grafts (n = 6), and 6.8 +/- 1.7 x 10(2) ng/10(6) cells/6 hr on perfused grafts (n = 6). The retention of htPAhECs by perfused grafts was 84.0% +/- 3.0%, comparable with the noninfected (82.1% +/- 8.0%) and mock-infected (94.2% +/- 0.4%) hEC values. CONCLUSIONS By adenoviral vector-mediated gene transfer, 10(2-3)-fold enhancement of htPA secretion was demonstrated, which did not affect cell retention by grafts.
When physicians counsel about stress: results of a national study.

The prevalence of stress in primary care is high; 60–80% of visits may have a stress-related component.1 44% of Americans report an increase in psychological stress over the past five years.2 Stress is associated with more office visits and disease, but little is known about stress management counseling in primary care.3,4 Our study objective was to examine the rates of stress management counseling by U.S. primary care physicians and to identify associated factors.
Sélection de caractéristiques pour l'étude de la maturation cérébrale

La caracterisation des images IRM cerebrales fœtales par la mise en place de biomarqueurs est un outil essentiel pour l'aide au diagnostic precoce. Dans ce contexte, il est interessant d'extraire des marqueurs fiables de maturation cerebrale in-utero par le biais de methodes de selection de caracteristiques permettant de conserver l'interpretation physique des parametres. Dans ce travail, nous etudions la morphometrie de la surface corticale du lobe frontal chez le fœtus.
Chronic Hepatitis B: Current and Future Treatment Options

Hepatitis B, a major viral infection that can lead to cirrhosis and hepatocellular carcinoma, is the ninth most common cause of death worldwide. Prevention of hepatitis B virus transmission is key to reducing the spread of this serious condition. Management of chronic hepatitis B requires significant knowledge of approved pharmacotherapeutic agents and their limitations. Today, agents approved by the Food and Drug Administration for this infection are interferon‐α‐2b and lamivudine. Newer agents are being developed and hold promise: adefovir, famciclovir, ganciclovir, lobucavir, entecavir, emtricitabine, L‐deoxythymidine, clevudine, a therapeutic vaccine, and thymosin α‐1. Therapeutic options for managing hepatitis infection after liver transplantation are also evolving. These include hepatitis B immunoglobulin and nucleoside analogues.
Genetic analysis of mutations that compensate for loss of Escherichia coli DNA topoisomerase I

A transposon Tn10 insertion in topA, the structural gene of Escherichia coli DNA topoisomerase I, behaves as an excluded marker in genetic crosses with many strains of E. coli. However, derivative strains that accept this mutant topA allele are readily selected. We show that many of these topA mutant strains contain additional mutations that compensate for the loss of DNA topoisomerase I. Genetic methods for mapping and manipulating such compensatory mutations are described. These methods include a plate-mating test for the ability of strains to accept a topA::Tn10 allele and a powerful indirect selection for transferring compensatory mutations from male strains into non-compensatory female strains. One collection of spontaneous compensatory mutants is analyzed in detail and is shown to include compensatory mutations at three distinct loci: gyrA and gyrB, the genes that encode the subunits of DNA gyrase, and a previously unidentified locus near tolC. Mutations at this third locus, referred to as toc (topoisomerase one compensatory) mutations, do not behave as point mutations in transductional crosses and do not result in lowered DNA gyrase activity. These results show that wild-type strains of E. coli require DNA topoisomerase I, and at least one class of compensatory mutations can relieve this requirement by a mechanism other than reduction of DNA gyrase activity.
Finding of residues crucial for supersecondary structure formation

This work evaluates the hypothesis that proteins with an identical supersecondary structure (SSS) share a unique set of residues—SSS-determining residues—even though they may belong to different protein families and have very low sequence similarities. This hypothesis was tested on two groups of sandwich-like proteins (SPs). Proteins in each group have an identical SSS, but their sequence similarity is below the “twilight zone. ” To find the SSS-determining residues specific to each group, a unique structure-based algorithm of multiple sequences alignment was developed. The units of alignment are individual strands and loops rather than whole sequences. The algorithm is based on the alignment of residues that form hydrogen bonds between corresponding strands. Structure-based alignment revealed that 30–35% of the positions in the sequences in each group of proteins are “conserved positions” occupied either by hydrophobic-only or hydrophilic-only residues. Moreover, each group of SPs is characterized by a unique set of SSS-determining residues found at the conserved positions. The set of SSS-determining residues has very high sensitivity and specificity for identifying proteins with a corresponding SSS: It is an “amino acid tag” that brands a sequence as having a particular SSS. Thus, the sets of SSS-determining residues can be used to classify proteins and to predict the SSS of a query amino acid sequence.
Frequência de sinéquia nasal após cirurgia de septoplastia com turbinectomia com e sem uso de splint nasal

Este estudo retrospectivo foi feito para avaliar o curso e a eficacia pos-operatoria do splint nasal para impedir a formacao de sinequias. O objetivo foi comparar a frequencia de sinequias nasais em paciente submetidos ao uso de splint nasal, bem como em relacao ao nivel de dor. This retrospective study was designed to evaluate the immediate postoperative course and efficacy of nasal splint to prevent the formation of synechias. The objective to was to compare the frequency of nasal sinechias in patient submitted with the nasal use of splint, as well as in relation to the pain level.
Extra-ovarian effect of prolactin on vaginal mucification in the rat.

The hormonal regulation of vaginal mucification in rats has been investigated employing chemical measurement of vaginal sialic acid as a means of quantifying mucification response to various hormonal treatments. Ovariectomized rats, pretreated for 3 days with 0.25 μg estradiol-17β (E2)/day, were treated for 7 days, twice daily, with or without 0.125 μg E2 and 2 mg progesterone in a 2 × 2 factorial design experiment. Compared with vehicle treated controls, E2 alone decreased vaginal sialic acid concentration by approximately 50%, progesterone alone was without an effect, and combined E2 plus progesterone increased the concentration by approximately 290%. A histological indicator of vaginal mucification was well correlated with the vaginal sialic acid concentrations. In hypophysectomized-ovariectomized rats pretreated for 3 days with 0.25 μ E2 followed by a 7 day treatment twice daily with or without 0.125 μg E2, 2 mg progesterone and 100 μg prolactin in a 2 × 2 × 2 factorial design experiment, combined tre.
Uma Nova Versão do Método LTAN

Recentemente, foi proposta uma solucao da equacao de transporte de neutrons em uma placa atraves de uma versao do metodo LTAN baseada na diagonaliza cao de uma matriz (2Nx2N). Neste trabalho, visando melhorar o tempo computacional do metodo LTAN, apresentamos uma nova versao deste metodo baseada na diagonalizacao de uma matriz NxN. Simulacoes numericas sao apresentadas para um problema de transporte com alto grau de anisotropia.
Some Emendations of Gödel's Ontological Proof

A new version of the ontological argument for the existence of God was outlined by Kurt Godel and elaborated by Dana Scott. J. Howard Sobel has given a careful explication of the details and has provided a powerful critique l , I believe that Sobel's main objection is conclusive against the argument as sketched by Godel. But it is possible to correct the argument, making changes which can be independently motivated, and in such a way that the revised argument is immune to the objection. And a definition of one of Godel's primitive concepts enables the proof of some of his axioms. For the sake of those who do not enjoy symbolism, I give a statement of Godel's argument and the suggested revisions in the vernacular. Some corollaries and a lemma have been separated off in order to clarify the proof and to isolate the difficulty. A brief statement of the formalities is given in the appendix. To see a full formalization of Godel's original version, consult Sobel.
BMI but not stage or etiology of nonalcoholic liver disease affects the diagnostic utility of carbohydrate-deficient transferrin.

BACKGROUND A reliable biomarker is required in hepatology clinics for detection and follow-up of heavy alcohol consumption. Carbohydrate-deficient transferrin (CDT) increases with sustained heavy alcohol consumption and is the most specific biomarker of ethanol (EtOH) consumption. Recent introduction of a standardized method for measuring CDT has improved its clinical application. This study was designed to determine whether alcohol-independent factors influence CDT levels in patients with chronic liver disease (CLD). METHODS The relationship between serum %CDT and self-reported history of alcohol consumption was examined in 254 patients referred for evaluation of liver disease. CDT analysis was performed on serum collected at time of liver biopsy. RESULTS CDT levels were not affected by severity or etiology of nonalcoholic liver disease. Thirteen of 254 subjects had a %CDT >1.7, predictive of heavy alcohol intake, 6 of whom did not acknowledge heavy drinking. Twelve of these 13 subjects were suspected heavy drinkers on review of their medical records and clinical results. Conversely, not all acknowledged heavy drinkers had %CDT >1.7. Heavy drinkers with a body mass index (BMI) in the overweight or obese range had significantly lower %CDT than lean heavy drinkers. This persisted even when lean body weight was used as an approximation of the EtOH volume of distribution. CONCLUSIONS An elevated BMI reduces the diagnostic utility of CDT at higher alcohol intake in subjects with CLD using the standardized method. In a hepatology outpatient setting, this assay is likely to be useful to confirm suspicion of heavy drinking in subjects who are not overweight, but cannot reliably identify moderate drinkers or heavy drinkers who are overweight.
Life events and post-traumatic stress: the development of a new measure for children and adolescents

Background. A new interview measure of life events and post-traumatic stress disorder (PTSD) has been developed for children and adolescents aged 9 through 17, for use in both epidemiological and clinical studies. It includes ‘high magnitude’ events associated with PTSD as well as other ‘low magnitude’ events. Method. The interview is designed as a module of the Child and Adolescent Psychiatric Assessment, an interviewer-based interview conducted with parent and child separately by trained lay interviewers. The module includes: (1) questions about a wide range of events; (2) a screen for key PTSD symptoms (painful recall, avoidance, hypervigilance); and (3) a detailed interview on all PTSD symptoms, including onset, duration, severity and co-morbidity. A test–retest reliability study was conducted with 58 parents and children, who were interviewed twice by different interviewers. Results. Intraclass correlations were 0·72 (child) and 0·83 (parent) for high magnitude events, and 0·62 (child) and 0·58 (parent) for low magnitude events. Kappa coefficients ranged from high for violence and sexual abuse to low for child reports of serious accidents and natural disasters. The reliability of the PTSD screen symptoms was fair to excellent (κ=0·40–0·79), and reliability of PTSD symptoms in those who passed the screen was excellent (ICC=0·94–0·99). Compared with a general population sample (N=1015), the clinic-referred subjects and their parents were twice as likely to report a traumatic event and, depending on the event, up to 25 times as likely to report symptoms of PTSD. Conclusions. The results support the reliability and discriminant validity of the measure.
Word Context and Token Representations from Paradigmatic Relations and Their Application to Part-of-Speech Induction

Representation of words as dense real vectors in the Euclidean space provides an intuitive definition of relatedness in terms of the distance or the angle between one another. Regions occupied by these word representations reveal syntactic and semantic traits of the words. On top of that, word representations can be incorporated in other natural language processing algorithms as features. In this thesis, we generate word representations in an unsupervised manner by utilizing paradigmatic relations which are concerned with substitutability of words. We employ an Euclidean embedding algorithm (SCODE) to generate word context and word token representations from the substitute word distributions, in addition to word type representations. Word context and word token representations are capable of handling syntactic category ambiguities of word types because they are not restricted to a single representation for each word type. We apply the word type, word context and word token representations to the part-of-speech induction problem by clustering the representations with k-means algorithm and obtain type and token based part-of-speech induction for Wall Street Journal section of Penn Treebank with 45 gold-standard tags. To the best of our knowledge, these part-of-speech induction results are the state-of-the-art for both type based and token based part-of-speech induction with Many-To-One mapping accuracies of 0.8025 and 0.8039, respectively. We also introduce a measure of ambiguity, Gold-standard-tag Perplexity, which we use to show that our token based part-of-speech induction is indeed successful at inducing part-of-speech categories of ambiguous word types.