Miracle-dz/UniFAR-FTUs huggingface dataset:
Mutational analysis of SEC4 suggests a cyclical mechanism for the regulation of vesicular traffic.

Mutant alleles of SEC4, an essential gene required for the final stage of secretion in yeast, have been generated by in vitro mutagenesis. Deletion of the two cysteine residues at the C terminus of the protein results in a soluble non‐functional protein, indicating that those two residues are required for normal localization of Sec4p to secretory vesicles and the plasma membrane. A mutant allele of SEC4 generated to mimic an activated, transforming allele of H‐ras, as predicted, does not bind GTP. The presence of this allele in cells containing wild‐type SEC4 causes a secretory defect and the accumulation of secretory vesicles. The results of genetic studies indicate that this allele behaves as a dominant loss of function mutant and as such prevents wild‐type protein from functioning properly. We propose a model in which Sec4p cycles between an active and an inactive state in order to mediate the fusion of vesicles to the plasma membrane.
Letrozole once a week normalizes serum testosterone in obesity-related male hypogonadism.

OBJECTIVE Isolated hypogonadotropic hypogonadism (IHH) is frequently observed in severely obese men, probably as a result of increased estradiol (E(2)) production and E(2)-mediated negative feedback on pituitary LH secretion. Aromatase inhibitors can reverse this process. This study evaluates whether letrozole once a week can normalize serum testosterone in severely obese men and maintain its long term effect. DESIGN Open, uncontrolled 6-month pilot study in 12 severely obese men (body mass index>35.0 kg/m(2)) with obesity-related IHH and free testosterone levels <225 pmol/l, treated with 2.5 mg letrozole once a week for 6 months. RESULTS Six weeks of treatment reduced total E(2) from 123+/-11 to 58+/-7 pmol/l (P<0.001, mean+/-s.e.m.), and increased serum LH from 4.4+/-0.6 to 11.1+/-1.5 U/l (P<0.001). Total testosterone rose from 5.9+/-0.5 to 19.6+/-1.4 nmol/l (P<0.001), and free testosterone from 163+/-13 to 604+/-50 pmol/l (P<0.001). Total testosterone rose to within the normal range in all subjects, whereas free testosterone rose to supraphysiological levels in 7 out of 12 men. The testosterone and E(2) levels were stable throughout the week and during the 6-month treatment period. CONCLUSION Letrozole 2.5 mg once a week produced a sustained normalization of serum total testosterone in obese men with IHH. However, free testosterone frequently rose to supraphysiological levels. Therefore, a starting dose <2.5 mg once a week is recommended.
Amnesia after a discrete basal forebrain lesion

Destructive lesions of the basal forebrain are often associated with memory impairment and this structure is thought to contribute to memory function by providing a cholinergic input to critical structures associated with memory such as the hippocampus and amygdala. In previously reported cases of amnesia associated with damage in the basal forebrain, multiple neuroanatomical regions were damaged, and the critical lesion responsible for amnesia has not been identified clearly. We report a patient who developed primarily anterograde amnesia after clipping of an unruptured anterior communicating artery aneurysm. Postoperative magnetic resonance imaging showed a discrete lesion, centring in the right diagonal band of Broca and including the anterior hypothalamus, septal nucleus, lamina terminalis, and paraterminal gyrus, and an indiscrete patchy lesion in the corresponding area on the opposite side. The nucleus basalis of Meynert was minimally affected and the diencephalon was not damaged. Single photon emission computed tomography showed marked hypoperfusion in the midline frontobasal region corresponding to the MRI lesion and hypoperfusion in the hippocampus bilaterally. It is concluded that disconnection of the pathway between the diagonal band of Broca and the hippocampus contributed to memory impairment.
ALMA SPECTROSCOPIC SURVEY IN THE HUBBLE ULTRA DEEP FIELD: SURVEY DESCRIPTION

We present the rationale for and the observational description of ASPECS: the ALMA SPECtroscopic Survey in the Hubble Ultra-Deep Field (UDF), the cosmological deep field that has the deepest multi-wavelength data available. Our overarching goal is to obtain an unbiased census of molecular gas and dust continuum emission in high-redshift (z > 0.5) galaxies. The ∼1′ region covered within the UDF was chosen to overlap with the deepest available imaging from the Hubble Space Telescope. Our ALMA observations consist of full frequency scans in band 3 (84–115 GHz) and band 6 (212–272 GHz) at approximately uniform line sensitivity ( 2 × 109 K km s−1 pc2), and continuum noise levels of 3.8 μJy beam−1 and 12.7 μJy beam−1, respectively. The molecular surveys cover the different rotational transitions of the CO molecule, leading to essentially full redshift coverage. The [C ii] emission line is also covered at redshifts . We present a customized algorithm to identify line candidates in the molecular line scans and quantify our ability to recover artificial sources from our data. Based on whether multiple CO lines are detected, and whether optical spectroscopic redshifts as well as optical counterparts exist, we constrain the most likely line identification. We report 10 (11) CO line candidates in the 3 mm (1 mm) band, and our statistical analysis shows that <4 of these (in each band) are likely spurious. Less than one-third of the total CO flux in the low-J CO line candidates are from sources that are not associated with an optical/NIR counterpart. We also present continuum maps of both the band 3 and band 6 observations. The data presented here form the basis of a number of dedicated studies that are presented in subsequent papers.
School desegregation and white flight: an investigation of competing models and their discrepant findings.

The authors test three alternative models that have been developed to explore the relationship between the desegregation of inner city schools and white flight to the suburbs. The results of these models are discussed using recent, more extensive data. Comparisons of white student loss are made between central city districts that did and did not desegregate. The most appropriate models for analysis of white flight are identified, and their ability to forecast future trends is considered
Experimental warming altered rates of carbon processes, allocation, and carbon storage in a tallgrass prairie

Climate warming affects ecosystem functioning by altering the rates of carbon (C) fixation and release. Modeling warming effect on terrestrial C cycling is critical given the feedbacks between climate and C cycling. However, the effect of warming on key model parameters and the resulting long-term C dynamics has not been carefully examined. In this study, measurements from a nine-year warming experimental site in a tallgrass prairie were assimilated into a terrestrial ecosystem C cycle model to assess warming effect on key model parameters and to quantify uncertainties of long-term C projection. Warming decreased allocation of gross primary production (GPP) to shoot, and turnover rate of the live C pools (i.e., shoot and root C), but increased the turnover rates of litter and fast soil C pools. Consequently, warming increased live C pools, but decreased litter and soil C pools, and overall decreased total ecosystem C in a 90-year model projection. Information content gained from assimilated datasets was m.
Hepatic endoplasmic reticulum stress in obesity: Deeper insights into processes, but are they relevant to nonalcoholic steatohepatitis?

The endoplasmic reticulum (ER) is the main site of protein and lipid synthesis, membrane biogenesis, xenobiotic detoxification and cellular calcium storage, and perturbation of ER homeostasis leads to stress and the activation of the unfolded protein response. Chronic activation of ER stress has been shown to have an important role in the development of insulin resistance and diabetes in obesity. However, the mechanisms that lead to chronic ER stress in a metabolic context in general, and in obesity in particular, are not understood. Here we comparatively examined the proteomic and lipidomic landscape of hepatic ER purified from lean and obese mice to explore the mechanisms of chronic ER stress in obesity. We found suppression of protein but stimulation of lipid synthesis in the obese ER without significant alterations in chaperone content. Alterations in ER fatty acid and lipid composition result in the inhibition of sarco/endoplasmic reticulum calcium ATPase (SERCA) activity and ER stress. Correcting the obesity‐induced alteration of ER phospholipid composition or hepatic Serca over‐expression in vivo both reduced chronic ER stress and improved glucose homeostasis. Hence, we established that abnormal lipid and calcium metabolism are important contributors to hepatic ER stress in obesity. (HEPATOLOGY 2011
The Role of Explicit and Tacit Knowledge in Process Improvement

In this paper we empirically examine the role of knowledge creation mechanisms in process improvement projects. Using scales adapted from the knowledge management literature, we collect data on 98 Six Sigma process improvement projects and analyze these data using regression. Results support our hypotheses linking knowledge creation mechanisms to project performance. Specifically, we find that the inclusion of softer, socially oriented mechanisms for capturing tacit knowledge explains a significant amount of variance in project performance, over and above that explained by the more technically focused mechanisms that capture explicit knowledge.
Size isn't everything

Clinical trials now often involve thousands of patients, and statisticians emphasize the importance of trial size in ensuring that ‘correct’ answers are obtained. However, when a good treatment appears for a disease that was hitherto untreatable – for example, oranges for scurvy or streptomycin for tuberculosis – only a small trial is needed. Large trials are only needed to demonstrate small effects. The meta‐analysis of small trials is often misleading, and may hide undesirable effects of individual drugs. The concept of equivalence between treatments is important, and while a statistically adequate equivalence trial may have to be very large, many clinicians will question the need for extreme statistical propriety. Clinical trials often do not reflect ‘real world’ practice, and the clinical relevance of a trial is more important than its size. Copyright © 2002 John Wiley & Sons, Ltd.
Impactos associados ao uso de tecnologias da comunicação em contextos de aprendizagem: a perceção e a influência do género nos estudantes do ensino superior português

Neste artigo apresentam-se e discutem-se alguns dos resultados obtidos no âmbito de uma investigacao que teve como objetivo principal identificar e caracterizar o uso que os estudantes do Ensino Superior Publico Portugues (ESPP) fazem das Tecnologias da Comunicacao (TC) para suporte a aprendizagem, com especial enfoque na dimensao do genero. Para a prossecucao dos objetivos propostos, desenvolveu-se um estudo de âmbito nacional, de cariz descritivo e exploratorio e optou-se pela disponibilizacao de um questionario online para a recolha de dados. No âmbito do presente artigo, contextualiza-se o estudo, apresentam-se os objetivos e as opcoes metodologicas, bem como alguns dos resultados obtidos, especificamente os que dizem respeito aos impactos associados ao uso de TC em contexto de aprendizagem e a influencia do genero na percecao desses impactos. Os resultados obtidos sugerem que um dos impactos mais referidos pelos participantes e o facto de o uso de TC em contextos de aprendizagem lhes ter permitido o desenvolvimento de novas competencias tecnologicas, bem como lhes ter facilitado a construcao das suas aprendizagens e o acesso a conteudos que de outra forma nao conseguiriam aceder. A variavel genero parece ter influencia na percecao de alguns dos impactos associados ao uso de TC no suporte a aprendizagem, sendo que o sexo feminino perceciona, na generalidade, mais impactos do que o sexo masculino.
Ionotropically-gelled mucoadhesive beads for oral metformin HCl delivery: Formulation, optimization and antidiabetic evaluation

2factorial design. The optimized mucoadhesive beads exhibited 94.86 ± 3.92 % drug encapsulation efficiency and good mucoadhesivity with the biological membrane in wash-off test, and sustained drug release profile over 10 h. The in vitro drug release from these beads was followed controlled-release (zero-order) pattern (R 2 = 0.9873 to 0.9980) with super case-II transport mechanism. The optimized TSPalginate mucoadhesive beads containing metformin HCl showed significant antidiabetic effect in alloxan-induced diabetic rats over prolonged period after oral administration. These results clearly demonstrated that the developed mucoadhesive beads was found suitable for prolonged systemic absorption of metformin HCl through sustained drug release and mucoadhesive properties after oral administration in the management of non-insulin dependent diabetes mellitus with maintenance of blood glucose level.
ICU and 6-month outcome of oncology patients in the intensive care unit.

BACKGROUND Advances in oncological care have led to improved short- and long-term prognosis of cancer patients but admission to the intensive care unit (ICU) remains controversial. AIM The objective was to assess the outcome of patients with haematological malignancies and solid tumours admitted to the ICU as emergencies, and to identify risk factors for mortality. DESIGN AND METHODS Retrospective and prospective analysis of 185 cancer patients admitted to the ICU at Guy's Hospital (259 admissions), a large tertiary referral oncology centre between February 2004 and July 2008. RESULTS One hundred and fifteen patients had haematological malignancies of whom 30.4% died in ICU. Seventy patients had solid tumours. ICU mortality was 27.1%. Fifty-four patients had >1 admission to ICU. ICU survivors had significantly lower acute physiology and chronic health evaluation II scores and less failed organ systems on admission to ICU and less organ failure during stay in the ICU. Neutropenia, sepsis and re-admission were not associated with an increased mortality. Six-month mortality rates for patients with haematological malignancies and solid tumours were 73 and 78.6%, respectively. CONCLUSION Short-term outcome of critically ill cancer patients in ICU is better than previously reported. The decision to admit cancer patients to ICU should depend on the severity of the acute illness rather than factors related to the malignancy. In appropriate patients, invasive organ support and re-admission should not be withheld.
Did Lanthanum Carbonate Improve Prognosis in Patients Requiring Chronic Hemodialysis in the Kawashima Study?

quality of life (HRQOL) is a key factor in the treatment strategy: it depends on not only the major complications but also the minor ones. These minor ones are not to be downplayed when it comes to bettering general health management of dialysis patients. Undoubtedly, improving the quality of treatment in patients could easily reduce dialysis complications. This scales up HRQOL in such patients and consequently, upgrades dialysis outcomes (4). Inattention tominor complicationsmay result in decreasingHRQOL and, certainly, deteriorating results.
Risk of end‐stage liver disease, hepatocellular carcinoma, and liver‐related death by fibrosis stage in the hepatitis C Alaska Cohort

Long‐term prospective studies of the outcomes associated with hepatitis C virus (HCV) infection are rare and critical for assessing the potential impact of HCV treatment. Using liver biopsy as a starting point, we analyzed the development of end‐stage liver disease (ESLD), hepatocellular carcinoma (HCC), and liver‐related death (LRD) according to fibrosis stage among a cohort of American Indian/Alaska Native persons in Alaska. Persons were classified as having no/mild (Ishak = 0,1), moderate (Ishak = 2), or severe (Ishak = 3,4) fibrosis or cirrhosis (Ishak = 5,6). We examined time until development of ESLD, HCC, and LRD and report survival probabilities at 3, 5, 7, and 10 years. Of 407 persons, 39% (n = 150) had no/mild fibrosis, 32% (n = 131) had moderate fibrosis, 22% (n = 88) had severe fibrosis, and 9% (n = 38) had cirrhosis. The average time of follow‐up was 7.3 years. Within 5 years of biopsy, 1.7% (95% confidence interval [CI]: 0.4‐6.8) of persons with no/mild fibrosis developed ESLD compared with 7.9% (95% CI, 4.0‐15.2), 16.4% (95% CI, 9.6‐27.2), and 49.0% (95% CI, 33.0‐67.7) with moderate, severe fibrosis, and cirrhosis, respectively (P < 0.01). The 5‐year outcome of HCC was 1.0% (95% CI, 0.1‐7.0), 1.0% (95% CI, 0.1‐6.6), 1.1% (95% CI, 0.2‐7.7), and 13.4% (95% CI, 4.4‐36.7) among persons with no/mild fibrosis, moderate fibrosis, severe fibrosis, and cirrhosis, respectively (P < 0.01). Five years after biopsy, 0.0% (95% CI, 0.0‐14.8) of persons with no/mild fibrosis had suffered an LRD compared with 1.0% (95% CI, 0.2‐7.5) of persons with moderate fibrosis, 4.7% (95% CI, 1.5‐14.1) with severe fibrosis, and 16.3% (95% CI, 7.0‐35.1) with cirrhosis (P < 0.01). Conclusion: For prevention of HCC, LRD, and ESLD in the short term, HCV therapy should target individuals who have more than mild fibrosis. (Hepatology 2017;66:37–45).
Long Loop Reflex 2 in Patients with Cortical Dementias: A Pilot Study

Introduction: Dementia is a major public health problem and it appears to be a global epidemic. The prevalence is doubling every 5 years and it is expected that 70% of persons above 60 years will live in developing countries by 2020 and 15% of them are likely to suffer from dementia. Disease modifying treatments work only if initiated very early; however, diagnostic tools are not always able to clearly differentiate the different types in very early stage. Therefore, inexpensive and easily available biomarkers are needed to know if collectively they will improve the sensitivity of specific diagnosis. Therefore, in this pilot study, we have tried to analyze if long loop reflex (LLR2) is differentially affected in these two conditions early in the course of Alzheimer's dementia (AD) and frontotemporal dementia (FTD) based on hypothesis taking into account the anatomical substrates involved. Patients and Methods: Mild cases of clinically probable AD and FTD after appropriate inclusion criteria were subjected for LLR testing in the upper limb at median nerve. The presence or absence of LLR was assessed and also the latency, amplitude, and duration assessed. Results and Conclusion: LLR 2 is differentially affected in both these conditions. Absence of LLR2 was consistently seen in FTD which can be explained by early break down of frontal subcortical circuits in this condition as against AD. This is likely to serve as a very cheap and very early biomarker to differentiate the two common types of cortical dementias.
The Common Descent Group in China and Its Functions

political groups, as well as constant co-operation with them during the period of tutelage. But is there not implicit in the idea of one-party rule the danger of removal or exclusion of political views and groups considered inimical to its interests? Those who wield power tend to attempt its maintenance and extension, although no group can expect to remain in power for long if it reflects the views and demands of only a small, elite group to the neglect of the vast majority of the population. Dr. Ch'ien has not given up the idea of party tutelage as the technique by which democracy might be achieved in China. The other alternative of democracy through a multiparty government has not been given a genuine opportunity but, in Dr. Ch'ien's view, does not find fertile ground in the structure of Chinese society. Until the question as to who shall wield political power in China has been settled, the question of how the government shall be organized will have little real meaning. While Dr. Ch'ien finds limitations and loopholes in Sun Yat-sen's five-power theory of government, he is just as critical of the Kuomintang's incorporation of it in the Nationalist Government of 1928. He considers its adoption "premature" and "not conducive to the realization of Sun Yat-sen's ideal, and to that extent. a misfortune for the Kuomintang" (p. 153). It resulted in the undue predominance of the executive yiian while Chiang was its president and the atrophy of the other yiian in power and functions. Dr. Ch'ien concludes that, without an alert, politically sophisticated people and a popular elective body representing them, the yiian could hardly have been expected to function as healthy, powerful organs of state. The Kuomintang's experience, while not conclusive, raises doubts concerning the effective operation of the five-yuan system of government. In analyzing some of these dilemmas of ends and means against the background of Kuomintang government, Dr. Ch'ien has not only contributed to further knowledge about that government but has also presented problems of vital concern to Americans having to make future decisions on foreign policy. He may also well be proud of having produced a book with a valuable appendix and a bibliography of both Western and Chinese sources.
Pseudomonas aeruginosa small protease (PASP), a keratitis virulence factor.

PURPOSE The virulence contribution of Pseudomonas aeruginosa small protease (PASP) during experimental keratitis was studied by comparing a PASP-deficient mutant with its parent and rescue strains. METHODS The pasP gene of P. aeruginosa was replaced with the tetracycline resistance gene via allelic exchange. A plasmid carrying the pasP gene was introduced into the PASP-deficient mutant to construct a rescue strain. The PASP protein in the culture supernatants was determined by Western blot analysis. Corneal virulence was evaluated in rabbit and mouse keratitis models by slit lamp examination (SLE), bacterial enumeration, and/or histopathological analysis. Various host proteins and the rabbit tear film were analyzed for their susceptibility to PASP degradation. RESULTS The PASP-deficient mutant produced a significantly lower mean SLE score when compared with the parent or rescue strain (P ≤ 0.03) at 29 hours postinfection (PI). All of the strains grew equally in the rabbit cornea (P = 0.971). Corneas infected with the PASP-deficient mutant showed moderate histopathology compared with those infected with the parent or rescue strain, which produced severe pathology inclusive of epithelial erosions, corneal edema, and neutrophil infiltration. In the mouse model, eyes inoculated with the PASP-deficient mutant had a significantly lower mean SLE score at 24 hours PI than the eyes inoculated with the parent or rescue strain (P ≤ 0.007). PASP was found to degrade complement C3, fibrinogen, antimicrobial peptide LL-37, and constituents of the tear film. CONCLUSIONS PASP is a commonly secreted protease of P. aeruginosa that contributes significantly to the pathogenesis of keratitis.
Movement Onset Detection and Target Estimation for Robot-Aided Arm Training

Abstract This paper presents a motion intention estimation algorithm that is based on the recordings of joint torques, joint positions, electromyography, eye tracking and contextual information. It is intended to be used to support a virtual-reality-based robotic arm rehabilitation training. The algorithm first detects the onset of a reaching motion using joint torques and electromyography. It then predicts the motion target using a combination of eye tracking and context, and activates robotic assistance toward the target. The algorithm was first validated offline with 12 healthy subjects, then in a real-time robot control setting with 3 healthy subjects. In offline crossvalidation, onset was detected using torques and electromyography 116 ms prior to detectable changes in joint positions. Furthermore, it was possible to successfully predict a majority of motion targets, with the accuracy increasing over the course of the motion. Results were slightly worse in online validation, but nonetheless show great potential for real-time use with stroke patients.