Miracle-dz/UniFAR-FTUs huggingface dataset:
Healing for destruction: tRNA intron degradation in yeast is a two-step cytoplasmic process catalyzed by tRNA ligase Rlg1 and 5′-to-3′ exonuclease Xrn1

In eukaryotes and archaea, tRNA splicing generates free intron molecules. Here, Wu and Hopper discover a mechanism for tRNA intron turnover in yeast. A genome-wide screen for genes involved in tRNA metabolism and subcellular trafficking indicated that tRNA introns accumulate in cells lacking the 5′-to-3′ exonuclease Xrn1. The data indicate that tRNA intron decay is a two-step process that requires healing of the 5′ termini of linear introns by the tRNA ligase Rlg1 and destruction by the cytoplasmic tRNA quality control nuclease Xrn1.
Current management and future directions in metastatic pancreatic adenocarcinoma

Of the anticipated 50,000 individuals expected to be diagnosed with pancreatic cancer in 2016, the majority will have metastatic disease. Given the noncurative nature of advanced pancreatic adenocarcinoma, treatment is aimed at inducing disease regression, controlling symptom, and extending life. The last 5 years have been marked by advances in the treatment of metastatic pancreatic cancer, specifically the approval by the US Food and Drug Administration of 2 combination chemotherapy regimens and the widespread use of a third, which have reproducibly been shown to improve survival. Ongoing studies are building on these regimens along with targeted and immunotherapeutic agents. This article will review the current treatment standards and emerging targets for metastatic pancreatic cancer. Cancer 2016;122:3765–3775. © 2016 American Cancer Society.
The Internal Clock: Evidence for a Temporal Oscillator Underlying Time Perception with Some Estimates of its Characteristic Frequency

Evidence for the proposition that human time perception is determined by an internal clock is largely indirect. It would strengthen the case for this hypothesis if a model for the internal clock were available from which predictions could be derived and tested, and if the basic parameter of such a model, the frequency at which the clock runs, could be estimated. A model for an internal temporal pacemaker is briefly described and its properties are explored by computer simulation. Results are obtained that provide a basis for predicting that, under appropriate conditions, interference between an imposed rhythm and the frequency of a temporal oscillator may cause perturbations in temporal judgment which are related to the characteristic frequency of that oscillator. Experimental data are reported which appear to demonstrate such an interference pattern. These results allow some estimates of the characteristic frequency of the temporal oscillator to be obtained.
A disruption‐replacement approach for the targeted integration of foreign genes in Hansenula polymorpha

A system has been developed which allows the selection of integrative transformants with replacement of the Hansenula polymorpha methanol oxidase gene (MOX) with expression cassettes carrying heterologous gene under the control of the MOX promoter. The system is convenient for comparison of the expression levels of different constructs integrated into the same locus of the H. polymorpha genome. This system was used to compare the secretion levels of human urinary plasminogen activator, the secretion of which was directed by different signal sequences.
Active Integrated Antenna Design Using a Contact-Less, Proximity Coupled, Differentially Fed Technique

A novel contact-less, differential feeding technique suitable for integrated active antenna design is demonstrated. This technique utilizes an odd mode signal to generate fringing fields on either side of a microstrip gap under the antenna. This allows electromagnetic energy to be efficiently coupled from the transmission lines to the radiating antenna. In a balanced integrated antenna amplifier configuration, the proposed non-contact feeding method removes the need for any balun or power combining network. Hence in theory, a compact RF front-end design with lower losses can be realized. This feeding method has been successfully applied to the design of simple passive microstrip patch antennas and active integrated antennas (AIA). Simulated and measured results are also included to validate the proposed feeding concept and antenna designs. The performance of the proposed differential feeding technique on a simple microstrip patch antenna has been systematically studied. The study suggests that the proposed proximity method is broadband in nature, allowing antennas operating at different resonant frequencies to be swapped without the need to change the feed dimensions and without degrading the matching performance
Prostate segmentation in MRI using fused T2-weighted and elastography images

Segmentation of the prostate in medical imaging is a challenging and important task for surgical planning and delivery of prostate cancer treatment. Automatic prostate segmentation can improve speed, reproducibility and consistency of the process. In this work, we propose a method for automatic segmentation of the prostate in magnetic resonance elastography (MRE) images. The method utilizes the complementary property of the elastogram and the corresponding T2-weighted image, which are obtained from the phase and magnitude components of the imaging signal, respectively. It follows a variational approach to propagate an active contour model based on the combination of region statistics in the elastogram and the edge map of the T2-weighted image. The method is fast and does not require prior shape information. The proposed algorithm is tested on 35 clinical image pairs from five MRE data sets, and is evaluated in comparison with manual contouring. The mean absolute distance between the automatic and manual contours is 1.8mm, with a maximum distance of 5.6mm. The relative area error is 7.6%, and the duration of the segmentation process is 2s per slice.
Multi-stage heterogeneous ensemble meta-learning with hands-off user-interface and stand-alone prediction using principal components regression : The R package EnsemblePCReg

Despite the fact that ensemble meta-learning of a heterogeneous collection of base learners is an effective means to reduce the generalization error in predictive models, several factors have impeded a broad adoption of such techniques among practitioners. These factors include an intractable number of choices of base learners and their tuning parameters, complex methodology required for integration of base learners, the ensuing complexity of software needed to support stand-alone prediction, and significant CPU and memory consumption of heterogeneous ensemble meta-learning techniques. The R package EnsemblePCReg overcomes the above barriers by combining several features. Sensible base-learner parameter grids provide a hands-off API for non-experts while allowing expert users to exert control by overriding default settings. Sophisticated ensemble generation and integration methods, combining stacked generalization and principal components regression, offer favorable generalization performance. Finally, computational optimizations such as advanded thread scheduling for improved parallelization scaling and file methods for relieving memory consumption during training and prediction, significantly increase the range of data sizes that can be handled on personal computers. In combining these features, EnsemblePCReg significantly lowers the barrier for practitioners to apply heterogeneous ensemble meta-learning techniques to their everyday regression problems.
Usefulness of the Hospital Anxiety and Depression Scale for screening for psychiatric morbidity in Chinese patients with Graves' ophthalmopathy.

OBJECTIVE To examine the usefulness of the Hospital Anxiety and Depression Scale (HADS) for screening psychiatric morbidity in Chinese patients with Graves' ophthalmopathy. METHODS A cross-sectional study was conducted from 1 January 2010 to 31 December 2010 at the specialist eye outpatient clinic at Pamela Youde Nethersole Eastern Hospital. All euthyroid patients diagnosed with Graves' ophthalmopathy were recruited. They were interviewed with the Chinese version of the HADS and the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis I. Demographic data and clinical background information were collected from the patients and their hospital records were reviewed. RESULTS In all, 124 patients were recruited into the study. Current prevalence of psychiatric disorders was 32%, of which 19% were current depressive disorders and 19% were current anxiety disorders. The HADS provided the best discriminating power for screening for psychiatric morbidity at a cut-off threshold of 10/11. For screening of depressive and anxiety disorders, the cut-off thresholds were 4/5 and 6/7 respectively. CONCLUSION Depression and anxiety disorders were common in the local population of patients with Graves' ophthalmopathy. Recognising the predictors for psychiatric morbidity could assist clinicians to identify those patients with a predisposition to developing psychiatric complications, and refer them for appropriate treatment. The HADS can be considered as a screening tool for psychiatric morbidity in patients with Graves' ophthalmopathy.
Impact of Extracellular Matrix on Cellular Behavior: A Source of Molecular Targets in Disease

In the last few decades, outstanding strides have been made on understanding the impact of extracellular matrices (ECMs) on cellular behavior in health and disease. It is now clear that ECMs are not inactive space-filling materials but, in contrast, apart from their structural roles they interact with cells and generate signals to control a multitude of vital cellular functions. Currently, there are strong indications that ECMs could potentially play a groundbreaking role in drug discovery since they comprise an invaluable source of multiple molecular targets. The established key roles of specific ECM effectors, such as proteoglycans, hyaluronan (HA), biosynthetic enzymes, cytokines, and growth factors, in the development and progression of several diseases suggest that ECMs hold a great potential in driving the design and development of novel disease targeting tools.
An extension of the Maximum Lod Score method to X‐linked loci

The Maximum Lod Score method for affected relative‐pair analysis, introduced by Risch, is a powerful method for detecting linkage between an autosomal marker locus and disease. In order to use the method to detect linkage to markers on the X‐chromosome, some modification is necessary. Here we extend the method to be applicable to X‐chromosomal data, and derive genetic restrictions on the haplotype‐sharing probabilities analogous to the ‘possible triangle’ restrictions described by Holmans for the autosomal case. Size criteria are derived using asymptotic theory and simulation, and the power is calculated for a number of possible underlying models. The method is applied to data from 284 type 1 diabetic families and evidence is found for the presence of one or more diabetogenic loci on the X‐chromosome.
Perceived support needs of family caregivers and implications for a telephone support service.

The purposes of this study were: to identify the perceived support needs of family caregivers of persons living with chronic illness (physical or cognitive) and receiving home-care services, and to describe the types of telephone services that would meet the expressed needs of caregivers. The qualitative design used semi-structured interviews. A total of 34 caregivers (mean age 62 years) participated in the study. The care recipients (mean age 78 years) were primarily the husband/wife or parent of the caregiver. The most commonly expressed caregiver needs were: a social life, instrumental support (e.g., respite, assistance with physical care, financial compensation), informational support, and emotional support. Most caregivers said they would use a telephone support service provided by a professional (71%) or a fellow caregiver (59%) if available. The results of this study support a pilot study and evaluation of a telephone support service for family caregivers.
CD73 Engagement Promotes Lymphocyte Binding to Endothelial Cells Via a Lymphocyte Function-Associated Antigen-1-Dependent Mechanism1

CD73 is a GPI-anchored lymphocyte adhesion molecule possessing an ecto-5′-nucleotidase enzyme activity. In this work, we show that engagement of lymphocyte CD73 increases lymphocyte binding to cultured endothelial cells (EC) in an LFA-1-dependent fashion. Engagement of CD73 by an anti-CD73 mAb 4G4 increases the adhesion of lymphocytes to cultured EC by about 80% compared with that of lymphocytes treated with a negative control Ab, and the increased adhesion can be blocked by an anti-CD18 mAb. The CD73-regulated increase in lymphocyte adhesion is not due to a conformational change leading to high-affinity LFA-1 receptors as assayed using mAb 24 against an activation-induced epitope of the molecule. Instead, CD73 engagement induces clustering of LFA-1 that is inhibitable by calpeptin, indicating involvement of Ca2+-dependent activation of a calpain-like enzyme in this process. In conclusion, the results shown here demonstrate that CD73 regulates the avidity of LFA-1 by clustering. This indicates a previously undescribed role for CD73 in controlling the poorly characterized activation step in the multistep cascade of lymphocyte extravasation. Moreover, these results suggest that in physiological conditions the activation step may result in clustering of LFA-1 rather than in an affinity change of the molecule.
Protein and energy relations in the broiler chicken

Chickens were fed on diets containing either 12.8 MJ, 150 g crude protein (nitrogen x 6.25)/kg or 12.8 MJ, 200 g crude protein/kg to determine differences in metabolism. The diet containing 12.8 MJ, 150 g crude protein/kg contained either 8 or 12 g lysine/kg. Treatment variables examined in vitro were lipogenesis, glucose production and hepatic enzyme activities to compare metabolism in chicks fed on a low-protein, lysine-supplemented diet and a diet formulated to contain the required amount of lysine from intact protein. Growth was similar in chicks fed on diets containing either 12.8 MJ, 154 g crude protein with 12 g lysine/kg or 12.8 MJ, 200 g crude protein/kg. Net glucose production was greater (p < 0.05) in liver explants from chickens fed on diets containing either 12.8 MJ, 154 g crude protein with 12 g lysine/kg or 12.8 MJ, 200 g crude protein/kg than in explants from chickens fed on 12.8 MJ, 150 g crude protein with 8 g lysine/kg. Pyruvate use for glucose production was greater (p < 0.05) in chickens fed on a diet containing 12.8 MJ, 150 g crude protein with 8 g lysine/kg. The findings from the present study suggest that crystalline and ‘natural’ lysine additions to chick diets may influence metabolism differently.
Discontinued drugs in 2012: oncology drugs

This year's analysis of discontinued drugs in oncology reports on 29 drugs dropped from the global pipeline in 2012. Similar to the trends that were observed in 2011, there were a large number (13) of Phase I terminations reported, largely due to strategic or unspecified reasons. Only one of these Phase I discontinued drugs appeared to incorporate a patient stratification biomarker in the study design and only four studies incorporated pharmacodynamic biomarker analysis. Out of seven drugs failing in Phase III, six were reported to display a lack of efficacy. None of the Phase III studies investigating these agents incorporated stratification biomarkers in the trial design. The aim of this article is to highlight the cohort of drugs discontinued in 2012 and discuss their profile in the context of the evolving paradigm for anticancer drug development. It is noteworthy that while there is clearly still room for improvement in the efficiency of drug development, increased collaboration among academics, industry, regulators, government and not-for-profit organisations appears to be contributing to increased numbers of new drug approvals.
Force Field Analysis: A Person‐Centered Approach to Behavioral Change

&NA; Rehabilitation of patients with long‐term illnesses of ten includes recommendations for modification or change of behavior. Force field analysis is a method of promoting behavioral change that is systematic, patient‐centered, and comprehensive. The process of change includes unfreezing behavioral movement and refreezing behavior at the new level. A patient situation is described in which the behavior to be changed was smoking. Force field analysis is particularly helpful as a way of giving hope and assisting patients whose past efforts to change were unsuccessful. It may be useful for collecting data on decision‐making and behavioral change strategies among specific patient populations.
ADHD-problematikkens sociale aspekter

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Interactive Events Subserving the Pupillary Light Reflex in Pigmented and Albino Rats

The consensual pupilloconstrictor response requires the intensity information that is delivered to each eye to be integrated to produce an averaged response such that the pupillary diameter in each eye is equal. Here we have examined how luminance information from each eye is integrated in the rat and where the integration occurs, using a pupillometry system to record pupillary diameter after illumination of one or both eyes. In albino rats the size of the uncrossed optic pathway to the pupilloconstrictor centre, the olivary pretectal nucleus, is reduced three‐fold and there is a concomitant but less dramatic reduction in the size of the consensual response. Unilateral lesions of the olivary pretectal nucleus in pigmented rats restrict all optic input to the opposite pretectum. Stimulation of one or both eyes in these animals suggests that integration occurs not only at the level of the olivary pretectal nucleus, but also downstream in the Edinger‐Westphal nucleus. Parallels with human studies and the opportunity to perform secondary lesions suggests the rat may provide a good model in which to study the substrates of the pupilloconstrictor response and mechanisms of integration of convergent parallel inputs in general.
Serum FGF21 and RBP4 levels in patients with chronic hepatitis C

Abstract Introduction. Fibroblast growth factor-21 (FGF21) regulates glucose, lipid, and energy homeostasis. Retinol-binding protein-4 (RBP4) controls metabolic and proliferative cell functions. Aims and methods. Aims of the study were to assess (1) serum FGF21 and RBP4 levels in 75 non-obese chronic hepatitis C (CHC) patients and 41 healthy controls similar in age and BMI; (2) the relationship between their serum concentration and insulin resistance, liver histology, and biochemical parameters; (3) their effectiveness as diagnostic markers. Results. FGF21 levels increased significantly in CHC patients compared with controls (p = 0.04). CHC patients with steatosis had significantly higher FGF21 levels compared with those without steatosis (p = 0.01). FGF21 concentration was positively related to steatosis grade (r = 0.39, p = 0.007). RBP4 levels did not differ between CHC patients and controls, but were negatively associated with necro-inflammatory activity grade (r = (-0.34), p = 0.04), with significantly higher levels in patients with minimal inflammatory activity (G1 vs. G2/3, p < 0.001; G1 vs. G2, p = 0 < 001; G1 vs. G3, p = 0.01). After stepwise linear regression analysis adjusting for potential confounders, RBP4 levels retained their independent significance as a predictor of necro-inflammatory activity (β = -0.31; t = -2.15, p = 0.035) and FGF21 levels as a predictor of steatosis (β = 0.34; t = 2.31, p = 0.024). Serum FGF21 correlated with serum RBP4 levels (r = 0.32, p = 0.02). Conclusions. Serum FGF21 levels increased in CHC patients, especially in those with steatosis and were associated with steatosis grade. FGF21 seems to be a useful diagnostic marker in determining hepatic steatosis in CHC. A negative association between serum RBP4 and necro-inflammatory activity indicates that disease severity may determine RBP4 levels.
Attractin/mahogany protein expression in the rodent central nervous system

Attractin/Mahogany protein (Atrn) is known to be involved in a number of physiological and neuropathological events. Although the ubiquitous distribution of atrn mRNA has been described in neurons, lack of detailed information concerning the cellular and subcellular localization of protein product is impeding understanding of the role of Atrn. The present study immunohistochemically examined distributions of Atrn in rat and mouse central nervous systems (CNSs) by using a novel antibody for Atrn. Atrn was intensely expressed in most neurons and dendrites of large neurons, such as cortical pyramidal neurons and cerebellar Purkinje neurons. Intense Atrn expression was also observed in the neuropil of gray matter in many regions of the CNS, such as the main and accessory olfactory bulb, cerebral cortex, caudate putamen, dorsal lateral geniculate nucleus, medial eminence, superior colliculus, hippocampus, dentate gyrus, and layers 1 and 2 of the spinal cord. Furthermore, we found that astrocytes, microglia, and ependymal cells also express Atrn protein. Immunoelectron microscopy showed the subcellular distribution of Atrn in the plasma membrane of cell soma, dendrites, and spines in neurons and in the cytoplasmic membrane of Golgi apparatus, endoplasmic reticulum, and mitochondria in neurons and glial cells. These findings indicate that Atrn is more widely expressed throughout the CNS than previously reported, and expression of Atrn by various cell types suggests that Atrn may serve multiple functions in the CNS. J. Comp. Neurol. 508:94–111, 2008. © 2008 Wiley‐Liss, Inc.
Mechanisms of actin stress fibre assembly

Stress fibres are contractile acto‐myosin structures found from many types of non‐muscle cells, where they are involved in adhesion, motility and morphogenesis. Stress fibres typically display a periodic α‐actinin–myosin II pattern and are thus suggested to resemble the sarcomeric actin filament structures of muscle cells. Mammalian cells contain three categories of stress fibres: ventral stress fibres that are attached to focal adhesions at both ends, dorsal stress fibres that are attached to focal adhesions typically at one end and transverse arcs that are curved acto‐myosin bundles, which do not directly attach to focal adhesions. In this review, we discuss the definition of stress fibres, organization of actin filaments and other components within these contractile structures, and the mechanisms of stress fibre assembly.