Miracle-dz/UniFAR-FTUs huggingface dataset:
The nucleoplasmin nuclear location sequence is larger and more complex than that of SV-40 large T antigen

The carboxy-terminal tail of nucleoplasmin, which specifies entry into the cell nucleus, contains four short sequences that are similar to previously identified nuclear location sequences. We show that none of these is able to locate chicken muscle pyruvate kinase to the cell nucleus. Deletion analysis was used to determine the limits of a nuclear location sequence and indicated that a 14-amino acid segment (RPAATKKAGQAKKK) should function as a minimal nuclear location sequence. When tested directly, however, this sequence was unable to locate pyruvate kinase to the cell nucleus. Restoration of three amino acids of nucleoplasmin sequence at either end of this sequence generated sequences that were able to locate pyruvate kinase to the cell nucleus. The 14-amino acid proposed minimal nuclear location sequence is present in the functional sequences, AVKRPAATKKAGQAKKK, RPAATKKAGQAKKKKLD, and the sequence AVKRPAATKKAGQAKKKKLD, which has additional amino acids at both ends. The minimal sequence element is therefore necessary but not sufficient for transport into the cell nucleus. This unusual feature of the nucleoplasmin nuclear location sequence suggests ways in which it could interact with the nuclear transport mechanism.
Congruence for SOS with data

While studying the specification of the operational semantics of different programming languages and formalisms, one can observe the following three facts. Firstly, Plotkin's style of structured operational semantics (SOS) has become a standard in defining operational semantics. Secondly, congruence with respect to some notion of bisimilarity is an interesting property for such languages and it is essential in reasoning about them. Thirdly, there are numerous languages that contain an explicit data part in the state of the operational semantics. The first two facts have resulted in a line of research exploring syntactic formats of operational rules to derive the desired congruence property for free. However, the third point (in combination with the first two) is not sufficiently addressed and there is no standard congruence format for operational semantics with an explicit data state. In this paper, we address this problem by studying the implications of the presence of a data state on the notion of bisimilarity. Furthermore, we propose a number of formats for congruence.
Comparison of the Electrochemical Behaviors Among 5083/6082 Friction Stir Welding Dissimilar Weld and Parent Materials

At the ambient temperature, in the 0.2 M NaHSO3 and 0.6 M NaCl solution, by gravimetric test, potentiodynamic polarization curve test and electrochemical impedance spectra (EIS), the electrochemical behavior of 5083/6082 friction stir welding dissimilar weld and two parent materials were comparatively investigated. The results indicated: at the given processing parameters, the anti-corrosion ability of the dissimilar weld was superior to those of the 6082 and 5083 parent materials.
Neurobiology of Schizophrenia: Search for the Elusive Correlation with Symptoms

In the last half-century, human neuroscience methods provided a way to study schizophrenia in vivo, and established that it is associated with subtle abnormalities in brain structure and function. However, efforts to understand the neurobiological bases of the clinical symptoms that the diagnosis is based on have been largely unsuccessful. In this paper, we provide an overview of the conceptual and methodological obstacles that undermine efforts to link the severity of specific symptoms to specific neurobiological measures. These obstacles include small samples, questionable reliability and validity of measurements, medication confounds, failure to distinguish state and trait effects, correlation–causation ambiguity, and the absence of compelling animal models of specific symptoms to test mechanistic hypotheses derived from brain-symptom correlations. We conclude with recommendations to promote progress in establishing brain-symptom relationships.
Perceived Control and Learned Helplessness Among Mentally Retarded and Nonretarded Children : A Developmental Analysis

Learned helplessness is produced by successive failures and by feedback attributing failure to uncontrollable causes. Retarded children appear to encounter both causal factors frequently and may thus be susceptible to helplessness. To test this possibility, children of low, average, and high IQ at three mental age levels were administered a response-initiation measure, a puzzle-repetition measure of perseverance after failure, and a questionnaire designed to gauge attributions for failure. Teachers also rated the children on a helplessness scale. Helplessness, as measured by the two questionnaires, declined with MA. On the three helplessness measures derived from the children themselves, there was an IQ x MA interaction: The low-IQ group showed more helplessness relative to nonretarded children at the upper MA level than to nonretarded children at the two lower levels. The results, although qualified in some respects, are consistent with the view that helplessness can be learned over time by children who repeatedly fail to effect the outcomes that they desire and who learn to attribute failure to factors beyond their control.
Allowing sensing as a supplement: An approach to the weakly-localized whitespace device problem

In this paper, we consider the problem of granting whitespace access to devices which have neither certified sensing capabilities nor a means of direct geolocation. These devices, called “slaves,” use a nearby “master” device to assist in determining which channels are available for secondary use. Such devices must be supported since even a “master” device which uses GPS for geolocation will need to become a “slave” when operating indoors where GPS operation is notoriously poor. The two regulatory bodies that are most active in this space, the Federal Communications Commission (FCC) in the United States and Ofcom in the United Kingdom, have similar yet slightly different approaches to the problem. While in the US the slave is directed to use the channels which are available at the master's location, slaves in the UK are given operating parameters which should be reasonably safe anywhere within the master's coverage area. We demonstrate in this paper that the first approach is too permissive while the latter is too conservative. Ultimately, we believe that the problems with these approaches are due to the misconception that whitespace devices need to determine their locations. In truth, the actual goal is to determine a set of channels on which it is safe for the device to transmit. For example, it is clear how a whitespace database (WSDB) should respond to a weakly-localized device which can reliably say “I am located either in New York City or San Francisco, but I don't know which. ” In this case, the WSDB should compute the set of channels which are simultaneously available for use in both NYC and SF, then direct the device to choose from that set. To demonstrate the power of this shift in perspective, we propose an enhancement to Ofcom's necessarily-conservative approach which safely increases the number of whitespace channels available to slave devices via simply sensing for strong signals. However, our actual goal is much larger than a particular method. We believe that regulators should certify “localization” in a broader sense of the term, and this work simply serves as a proof-of-concept/need for that argument.
Effectiveness of Laser Therapy in the Management of Recurrent Aphthous Stomatitis: A Systematic Review

Objectives. Laser therapy is a promising new treatment for patients with recurrent aphthous stomatitis (RAS). However, the clinical effect and security issue of laser therapy remain controversial. This systematic review was conducted to evaluate the clinical effectiveness and security of laser treatment in RAS patients. Methods. Five electronic databases were searched (MEDLINE (PubMed), EMBASE, ScienceDirect, the Cochrane Library, and Web of Science) to identify all studies that were about randomized controlled clinical trials, involving the effect of laser therapy in RAS patients. Conclusion. Twenty-three studies were retained for full-text analysis after screening the titles and abstracts of potential articles, but only 10 studies satisfied the inclusion criteria after the full texts were reviewed. The included studies reported a comparison of the effectiveness between the laser treatment and placebo laser therapy (or conventional drug therapy) when managing the RAS patients. It can be concluded that laser therapy has the superiority in relieving ulcer pain and shortening healing time when compared with placebo group or medical treatment group. Although laser therapy is a promising effective treatment for RAS, high-quality clinical studies with large sample size must be further performed to confirm the effectiveness of this therapy.
Alternative Antigen Processing for MHC Class I: Multiple Roads Lead to Rome

The well described conventional antigen-processing pathway is accountable for most peptides that end up in MHC class I molecules at the cell surface. These peptides experienced liberation by the proteasome and transport by the peptide transporter TAP. However, there are multiple roads that lead to Rome, illustrated by the increasing number of alternative processing pathways that have been reported during last years. Interestingly, TAP-deficient individuals do not succumb to viral infections, suggesting that CD8 T cell immunity is sufficiently supported by alternative TAP-independent processing pathways. To date, a diversity of viral and endogenous TAP-independent peptides have been identified in the grooves of different MHC class I alleles. Some of these peptides are not displayed by normal TAP-positive cells and we therefore called them TEIPP, for “T-cell epitopes associated with impaired peptide processing. ” TEIPPs are hidden self-antigens, are derived from normal housekeeping proteins, and are processed via unconventional processing pathways. Per definition, TEIPPs are presented via TAP-independent pathways, but recent data suggest that part of this repertoire still depend on proteasome and metalloprotease activity. An exception is the C-terminal peptide of the endoplasmic reticulum (ER)-membrane-spanning ceramide synthase Trh4 that is surprisingly liberated by the signal peptide peptidase (SPP), the proteolytic enzyme involved in cleaving leader sequences. The intramembrane cleaving SPP is thereby an important contributor of TAP-independent peptides. Its family members, like the Alzheimer’s related presenilins, might contribute as well, according to our preliminary data. Finally, alternative peptide routing is an emerging field and includes processes like the unfolded protein response, the ER-associated degradation, and autophagy-associated vesicular pathways. These data convince us that there is a world to be discovered in the field of unconventional antigen processing.
Lessons Learned from Implementing Web-Based Simulations to Teach Operations Management Concepts

The usage of Web-based computer simulations to facilitate experiential learning of operations management concepts continues to increase; however, successfully administering and incorporating them into a curriculum can be challenging. Littlefield Technologies is a popular simulation used in operations management education; however, there is limited literature providing guidance on how to successfully implement the simulation into a postsecondary course. Based on years of experience employing Littlefield and other computer-based simulations to over 2,500 students, we provide five keys specifically for implementing Littlefield and guidance on administering computer-based simulations in general. Student survey results reveal that over 86% recommend the continued usage of Littlefield, and that over two-thirds of students report increased interest in operations management because of the simulation. A comparison of results by course type indicates that MBA students outperformed undergraduate students, and that performance appears to improve when results-based marks are incorporated into their final grade rather than bonus marks. Finally, we discuss some forthcoming improvements to the Littlefield simulation and provide some additional improvement recommendations.
EFFECT OF THIOACETAMIDE ON ADENYLIC ACID DEAMINASE ACTIVITY AND NUCLEAR RIBONUCLEIC ACID METABOLISM IN RAT LIVER.

Thioacetamide was administered to rats to determine whether increases in hepatic adenylic acid (AMP) deaminase activity could be achieved in shorter time intervals than had been previously observed with azo dyes (23). Thioacetamide was added to a semisynthetic diet at 0.033% or 0.066% and was fed to rats for 12 weeks. Within 2 weeks hepatic AMP deaminase activity was significantly elevated and remained elevated throughout 12 weeks. When thioacetamide was injected intraabdominally once daily for 9 days at 50 mg/kg body weight, hepatic AMP deaminase activity was significantly elevated after 3 injections. This regimen also caused increases in the amount of nuclear ribonucleic acid (RNA), and in the diameters of nuclei and nucleoli. Nuclear RNA was subfractionated into “non-nucleolar” nuclear (NNN) and “nucleolar” fractions and it was observed that nearly all the increase in nuclear RNA occurred in the “nucleolar” fraction. The rates at which orotic acid-6-14C was incorporated into these 2 fractions indicated that 3 injections of thioacetamide increased “nucleolar” RNA synthesis; whereas 3, 6, or 9 injections increased NNN RNA synthesis.
Piezoelectric effect on transition behavior in large deflection of layered-bossed plate under pretension

This study investigates the piezoelectric effect on the transition behavior of a layered plate bossed with piezoelectric patches in large deflection due to lateral load. The approach follows von Karman's large deflection theory but extends to a layered case including piezoelectric patches. The governing equations thus derived are simplified to a modified Bessel or Bessel equation for the lateral slope, depending on the relative magnitude of the piezoelectric load. The associated analytical solutions were developed by imposing the clamped-end boundary condition and the interface continuity between the piezoelectric patched boss and the annular plate. The solution involves with modified Bessel functions of both the first kind and the second kind, rather than only the first kind for a flat plate in literature. A further integration is conducted to derive the expression for the center deflection for various applied voltages across the piezoelectric patches to explore how the bossed plate transits from a plate mode to a membrane mode as the pretension proceeds, namely, the transition behavior. Typical silicon-based materials commonly used for a sensing or actuating device were considered for the patched plate. A parametric study was also conducted to study the effects of varying the geometry of the patched region and also the effect of piezoelectricity. Essentially, it is observed that piezoelectric effect appears to be present only in a low pretension condition. Yet, the higher the applied voltage, the more earlier in pre-stretching for the plate to transmit to the membrane mode is revealed.
Heterogeneous Expression of Gap Junction Channels in the Heart Leads to Conduction Defects and Ventricular Dysfunction

Background—Heterogeneous remodeling of gap junctions is observed in many forms of heart disease. The consequent loss of synchronous ventricular activation has been hypothesized to result in diminished cardiac performance. To directly test this hypothesis, we designed a murine model of heterogeneous gap junction channel expression. Methods and Results—We generated chimeric mice formed from connexin43 (Cx43)-deficient embryonic stem cells and wild-type or genetically marked ROSA26 recipient blastocysts. Chimeric mice developed normally, without histological evidence of myocardial fibrosis or hypertrophy. Heterogeneous Cx43 expression resulted in conduction defects, however, as well as markedly depressed contractile function. Optical mapping of chimeric hearts by use of voltage-sensitive dyes revealed highly irregular epicardial conduction patterns, quantified as significantly greater negative curvature of the activation wave front (−1.86±0.40 mm in chimeric mice versus −0.86±0.098 mm in controls;P <0.01; n=6 for each group). Echocardiographic studies demonstrated significantly reduced fractional shortening in chimeric mice (26.6±2.3% versus 36.5±1.6% in age-matched 129/Sv×C57BL/6F1 wild-type controls;P <0.05). Conclusions—These data suggest that heterogeneous Cx43 expression, by perturbing the normal pattern of coordinated myocardial excitation, may directly depress cardiac performance.
Are simple noninvasive scoring systems for fibrosis reliable in patients with NAFLD and normal ALT levels?

Background Nonalcoholic fatty liver disease (NAFLD) is common and many affected individuals have normal-range alanine aminotransferase (ALT) levels. There is a need for a robust screening tool to triage individuals with advanced fibrosis for specialist care. Aim The aim of this study was to assess the performance of noninvasive fibrosis tests in patients with biopsy-proven NAFLD and normal levels of ALT. Methods Patients presenting at a fatty liver clinic between 1999 and 2009 were included in the study. Liver biopsies were assessed using the Kleiner score. The aspartate aminotransferase (AST)/ALT ratio, BARD, FIB-4 and NAFLD fibrosis scores were calculated. Results A total of 305 patients were included [70 with normal ALT levels (women: ALT⩽30 IU/l, men: ALT⩽45 IU/l) and 235 with elevated levels]. In total, 24% of patients with normal ALT levels and 17% of those with elevated ALT levels had advanced fibrosis (Kleiner stage 3–4). The FIB-4 performed best in identifying advanced fibrosis in patients with normal ALT (area under receiver operating characteristic curve=0.86, 82% sensitivity, 77% specificity and 92% negative predictive value). The sensitivity of the AST/ALT ratio and BARD and NAFLD fibrosis scores for advanced fibrosis was good in patients with normal ALT levels (94, 94 and 82%, respectively), but the specificity was low (44, 26 and 51%, respectively). The FIB-4 yielded best results in patients with elevated ALT levels. Using the FIB-4, 61% of patients with normal ALT levels and 63% of those with elevated ALT levels could avoid liver biopsy to exclude advanced fibrosis. In contrast, AST/ALT ratio and BARD and NAFLD scores would have led to a high proportion of patients with mild disease having to undergo a biopsy. Conclusion The FIB-4 yielded good results in patients with normal or elevated ALT levels, reliably excluding advanced fibrosis and reducing the need for liver biopsy.
The Epidermal Growth Factor Receptor: A Link Between Inflammation and Liver Cancer

Epidemiological studies have established that many tumours occur in association with persistent inflammation. One clear example of inflammation-related cancer is hepatocellular carcinoma (HCC). HCC slowly unfolds on a background of chronic inflammation triggered by exposure to infectious agents (hepatotropic viruses), toxic compounds (ethanol), or metabolic impairment. The molecular links that connect inflammation and cancer are not completely known, but evidence gathered over the past few years is beginning to define the precise mechanisms. A central role for cytokines such as interleukin-6 (IL-6) and IL-1 (α and β) in liver cancer has been established in experimental models. Besides these inflammatory mediators, mounting evidence points to the dysregulation of specific growth and survival-related pathways in HCC development. Among them is the pathway governed by the epidermal growth factor receptor (EGFR), which can be bound and activated by a broad family of ligands. Of special relevance is the fact that the EGFR engages in extensive crosstalk with other signaling pathways, serving as a “signaling hub” for an increasing list of growth factors, cytokines, and inflammatory mediators. In this review, we summarize the most recent evidences supporting a role for the EGFR system in inflammation-related cell signaling, with special emphasis in liver inflammation and HCC. The molecular dissection of the pathways connecting the inflammatory reaction and neoplasia will facilitate the development of novel and more effective antitumor strategies.
Nucleic Acids Research

The geometry of the phosphodiester backbone was analyzed for 7739 dinucleotides from 447 selected crystal structures of naked and complexed DNA. Ten torsion angles of a near-dinucleotide unit have been studied by combining Fourier averaging and clustering. Besides the known variants of the A-, Band Z-DNA forms, we have also identified combined A+B backbone-deformed conformers, e.g. with a/c switches, and a few conformers with a syn orientation of bases occurring e.g. in G-quadruplex structures. A plethora of Aand B-like conformers show a close relationship between the Aand B-form double helices. A comparison of the populations of the conformers occurring in naked and complexed DNA has revealed a significant broadening of the DNA conformational space in the complexes, but the conformers still remain within the limits defined by the Aand Bforms. Possible sequence preferences, important for sequence-dependent recognition, have been assessed for the main A and B conformers by means of statistical goodness-of-fit tests. The structural properties of the backbone in quadruplexes, junctions and histone-core particles are discussed in further detail.
Ontogeny of Epidermal Growth Factor Receptor/Kinase and of Lipocortin-1 in the Ovine Lung

ABSTRACT: We have examined the ontogeny and distribution of the epidermal growth factor receptor/kinase (EGF receptor) and of lipocortin-1, a major cellular substrate of the EGF receptor, in a developmental series of 13 normal ovine fetal lungs (44-145 d of gestation) using the peroxidase anti-peroxidase technique with two extensively characterized polyclonal antibodies recognizing the EFG receptor and one polyclonal antibody recognizing lipocortin-1. Immunoreactive EGF receptor/kinase and lipocortin-1 were detected in conducting airway epithelium by the end of the first trimester of pregnancy before bronchial glands could be identified. This was followed at two-thirds of gestation by immunoreactivity in bronchial glands and large bronchioles adjacent to postive bronchi. By seveneighths of gestation conducting airway epithelium no longer contained consistently detectable immunostaining for EGF receptor, although lipocortin-1 was identified until term in all levels of conducting airways. In contrast, neither EGF receptor nor lipocortin-1 immunoreactivity was detected in alveolar type I or type II epithelial cells, fibrocytes, chondrocytes, smooth muscle, or endothelial cells at any gestational age. These findings suggest that EGF receptor and lipocortin-1 may participate in early airway development.