Miracle-dz/UniFAR-FTUs huggingface dataset:
CD74: an emerging opportunity as a therapeutic target in cancer and autoimmune disease

Introduction: CD74, also known as the invariant chain, participates in several key processes of the immune system, including antigen presentation, B-cell differentiation and inflammatory signaling. Despite being described more than 3 decades ago, new functions and novel interactions for this evolutionarily conserved molecule are still being unraveled. As a participant in several immunological processes and an indicator of disease in some conditions, it has potential as a therapeutic target. Areas covered: The relationship between the structure of CD74 variants and their physiological functions is detailed in this review. The function of CD74 in several cell lineages is examined with a focus on the interactions with cathepsins and, in an inflammatory milieu, the pro-inflammatory cytokine macrophage migratory inhibitory factor. The role of CD74 signaling in inflammatory and carcinogenic processes is outlined as is the use of CD74 as a therapeutic target (in cancer) and tool (as a vaccine). Expert opinion: CD74 has several roles within the cell and throughout the immune system. Most prominent amongst these are the complex relationships with MIF and cathepsins. Modulation of CD74 function shows promise for the effective amelioration of disease.
Position-specific binding of FUS to nascent RNA regulates mRNA length

More than half of all human genes produce prematurely terminated polyadenylated short mRNAs. However, the underlying mechanisms remain largely elusive. CLIP-seq (cross-linking immunoprecipitation [CLIP] combined with deep sequencing) of FUS (fused in sarcoma) in neuronal cells showed that FUS is frequently clustered around an alternative polyadenylation (APA) site of nascent RNA. ChIP-seq (chromatin immunoprecipitation [ChIP] combined with deep sequencing) of RNA polymerase II (RNAP II) demonstrated that FUS stalls RNAP II and prematurely terminates transcription. When an APA site is located upstream of an FUS cluster, FUS enhances polyadenylation by recruiting CPSF160 and up-regulates the alternative short transcript. In contrast, when an APA site is located downstream from an FUS cluster, polyadenylation is not activated, and the RNAP II-suppressing effect of FUS leads to down-regulation of the alternative short transcript. CAGE-seq (cap analysis of gene expression [CAGE] combined with deep sequencing) and PolyA-seq (a strand-specific and quantitative method for high-throughput sequencing of 3' ends of polyadenylated transcripts) revealed that position-specific regulation of mRNA lengths by FUS is operational in two-thirds of transcripts in neuronal cells, with enrichment in genes involved in synaptic activities.
A New Single-Phase Controlled Rectifier Using Single-Phase Matrix Converter

This paper presents the applications of single-phase matrix converter (SPMC) as an AC-DC controlled rectifier. For basic operation the multiple-PWM technique was used to calculate the switch duty ratio to synthesize the output. Safe commutation strategy was developed to avoid voltage spikes due to inductive load. Active current wave-shaping technique are also proposed to ensure that the supply current waveform is continuous, sinusoidal and in phase with the supply voltage. This approach utilizes boost rectifier technique for compensation. Selected experimental results are presented to verify the concept.
Mean Platelet Volume Could Reflect Disease Activity of Adult Patients With Systemic Lupus Erythematosus.

BACKGROUND In recent years, research regarding mean platelet volume (MPV) has been expanded to numerous diseases. The aim of the present study was to assess whether MPV could reflect disease activity of adult patients with systemic lupus erythematosus (SLE). METHODS A total of 128 adult patients with SLE were enrolled in the present study and allocated into two subgroups (99 with active phase and 29 with inactive phase) according to SLE disease activity index (SLEDAI). Demographic data, MPV, complement 3 (C3), and complement 4 (C4) were recorded. Independent sample t-test was used for comparison of quantitative variables between the active and inactive groups. Pearson's correlation test was used to evaluate the correlation between the above laboratory indices and the SLEDAI score. RESULTS The mean MPV level in active patients was significantly higher than inactive subjects (8.3 ± 1.3 vs. 7.7 ± 0.7, p < 0.001). The correlation between MPV level and SLEDAI score was moderate (r = 0.520, p < 0.001). CONCLUSIONS MPV might be a promising marker to reflect disease activity of adult patients with SLE.
Transdermal buprenorphine in cancer pain and palliative care

Transdermal buprenorphine has been assessed as a therapy for chronic cancer and non-cancer pain in both clinical and postmarketing surveillance studies. Data from 239 patients who had participated in a follow-up study of up to six years have shown efficacy and safety, and good tolerability over prolonged treatment periods with a marked stability of doses. From the cancer pain population (134 patients), 20% stayed on transdermal buprenorphine until the end of their lives. Postmarketing surveillance study data from 13 179 patients, including 3690 cancer patients assessed during a 10-week observation period, showed that 81% of patients achieved good/very good pain relief with transdermal buprenorphine. Furthermore, 49.6% of patients did not require any analgesic comedication or rescue therapy, a point that is particularly important in the elderly population. Results from the Spanish Pain Society on transdermal buprenorphine in chronic non-cancer, neuropathic and cancer-related pain, and on switching from morphine, also confirmed its beneficial efficacy and safety, and showed that buprenorphine does not antagonize pain relief, or cause withdrawal when combined with full μ-agonists. The effectiveness of buprenorphine is further supported by evidence of its pronounced anti-hyperalgesic effect in a human pain model, which may be a factor in explaining the efficacy of buprenorphine in neuropathic pain. When switching of opioids is indicated to improve pain relief or reduce adverse events, equipotency dosage ratios are important. The equipotency ratio for morphine to buprenorphine, previously established as 75:1, is now being questioned as new data from a retrospective cohort study were published indicating a ratio of 100:1. Moreover, transdermal buprenorphine has superior safety in respect to respiratory depression, immunological and renal effects compared with standard World Health Organization step III opioids, which makes it highly suitable for treating moderate-to-severe pain also in cancer patients, a per se vulnerable patient population requiring a sensible selection of potent analgesics.
Controlling the Switch from Neurogenesis to Pluripotency during Marmoset Monkey Somatic Cell Reprogramming with Self-Replicating mRNAs and Small Molecules

Induced pluripotent stem cells (iPSCs) hold enormous potential for the development of cell-based therapies for many currently incurable diseases. However, the safety and efficacy of potential iPSC-based treatments need to be verified in relevant animal disease models before their application in the clinic. Moreover, in order to reduce possible risks for the patients, it is necessary to use reprogramming approaches that ensure to the greatest extent possible the genomic integrity of the cells. Here, we report the derivation of iPSCs from common marmoset monkeys (Callithrix jacchus) using self-replicating mRNA vectors based on the Venezuelan equine encephalitis virus (VEE-mRNAs). By transfection of marmoset fetal fibroblasts with Tomato-modified VEE-mRNAs carrying the human OCT4, KLF4, SOX2, and c-MYC (VEE-OKS-iM-iTomato) and culture in medium supplemented with two small molecule inhibitors, we first established intermediate primary colonies with neural progenitor-like properties. In the second reprogramming step, we converted these colonies into transgene-free pluripotent stem cells by further culturing them with customized marmoset iPSC medium in feeder-free conditions. The resulting cell lines possess pluripotency characteristics, such as expression of various pluripotency markers, long-term self-renewal, stable karyotype, and ability to differentiate into derivatives of the three primary germ layers in vitro and in vivo. Our experiments reveal a novel paradigm for flexible reprogramming of somatic cells, where primary colonies obtained by a single VEE-mRNA transfection can be directed either towards the neural lineage or further reprogrammed to pluripotency. These results (i) will further enhance the role of the common marmoset as animal disease model for preclinical testing of iPSC-based therapies and (ii) establish an in vitro system to experimentally address developmental signal transduction pathways in primates.
Power to Detect Linkage Based on Multiple Sets of Data in the Presence of Locus Heterogeneity: Comparative Evaluation of Model-Based Linkage Methods for Affected Sib Pair Data

The development of rigorous methods for evaluating the overall strength of evidence for genetic linkage based on multiple sets of data is becoming increasingly important in connection with genomic screens for complex disorders. We consider here what happens when we attempt to increase power to detect linkage by pooling multiple independently collected sets of families under conditions of variable levels of locus heterogeneity across samples. We show that power can be substantially reduced in pooled samples when compared to the most informative constituent subsamples considered alone, in spite of the increased sample size afforded by pooling. We demonstrate that for affected sib pair data, a simple adaptation of the lod score (which we call the compound lod), which allows for intersample admixture differences can afford appreciably higher power than the ordinary heterogeneity lod; and also, that a statistic we have proposed elsewhere, the posterior probability of linkage, performs at least as well as the compound lod while having considerable computational advantages. The companion paper (this issue, pp 217–225) shows further that in application to multiple data sets, familiar model-free methods are in some sense equivalent to ordinary lod scores based on data pooling, and that they therefore will also suffer dramatic losses in power for pooled data in the presence of locus heterogeneity and other complicating factors.
The Gastro-oesophageal Region in Infants

The nature of the closing mechanism between the oesophagus and the stomach has attracted considerable anatomical study in the past 300 years. Main interest has centred on the adult; the anatomy of the infant, which does not necessarily correspond, has not received the same attention. The present investigation is therefore concerned with infants. It was undertaken with two objects: first, from the anatomical study, both macroscopic and micro-scopic, to assess the importance of the various components of the normal closing mechanism; consider in this mechanism is incompetent, in the light of clinical experience and radiological observation.
The relationship of governance mechanisms and customer loyalty in insurance industry: the difference of internet insurers and traditional insurers

Governance mechanisms could establish institutional interactions across customer relationship maintenance. This study aims to develop and empirically test a model exploring the long-term relationship of insurance company and customers. Data were collected online and via paper questionnaires from customers of the insurance industry in Taiwan. According to the results, four governance mechanisms (explicit contract, implicit contract, bonding, and trust) have significant positive impacts on customer loyalty. Gaining a steady and collaborative relationship with customers would need to apply governance mechanisms and personalised information technology. It would become a future standard of insurance services.
A digital BIST for operational amplifiers embedded in mixed-signal circuits

A new digital BIST structure is proposed in this paper. During test mode, the op amp under test is placed in a voltage follower configuration in order to detect its slew-rate deviation, or in a comparator configuration in order to detect its signal propagation delay deviation. The test stimuli and the BIST control signals are simply derived from the test control signal TST using delay elements and logical gates. The test response is analyzed by using pure digital circuitry. Simulation results show the effectiveness of the proposed technique with a low area overhead.
Effects of exposure to gradient magnetic fields emitted by nuclear magnetic resonance devices on clonogenic potential and proliferation of human hematopoietic stem cells

This study investigates effects of gradient magnetic fields (GMFs) emitted by magnetic resonance imaging (MRI) devices on hematopoietic stem cells. Field measurements were performed to assess exposure to GMFs of staff working at 1.5 T and 3 T MRI units. Then an exposure system reproducing measured signals was realized to expose in vitro CD34+ cells to GMFs (1.5 T‐protocol and 3 T‐protocol). CD34+ cells were obtained by Fluorescence Activated Cell Sorting from six blood donors and three MRI‐exposed workers. Blood donor CD34+ cells were exposed in vitro for 72 h to 1.5 T or 3 T‐protocol and to sham procedure. Cells were then cultured and evaluated in colony forming unit (CFU)‐assay up to 4 weeks after exposure. Results showed that in vitro GMF exposure did not affect cell proliferation but instead induced expansion of erythroid and monocytes progenitors soon after exposure and for the subsequent 3 weeks. No decrease of other clonogenic cell output (i.e., CFU‐granulocyte/erythroid/macrophage/megakaryocyte and CFU‐granulocyte/macrophage) was noticed, nor exposed CD34+ cells underwent the premature exhaustion of their clonogenic potential compared to sham‐exposed controls. On the other hand, pilot experiments showed that CD34+ cells exposed in vivo to GMFs (i.e., samples from MRI workers) behaved in culture similarly to sham‐exposed CD34+ cells, suggesting that other cells and/or microenvironment factors might prevent GMF effects on hematopoietic stem cells in vivo. Accordingly, GMFs did not affect the clonogenic potential of umbilical cord blood CD34+ cells exposed in vitro together with the whole mononuclear cell fraction. Bioelectromagnetics. 37:201–211, 2016. © 2016 Wiley Periodicals, Inc.
AIS Electronic Library (AISeL) Developing and Implementing eAssessment Strategies in Virtual Learning Environments

eLearning collaborative pedagogy assumes that interaction is important for successful courses, yet questions exist regarding the nature and extent of the interaction and its effects on student performance. Although the majority of past studies focus on students’ perceptions of the quality and quantity of their interactions and the benefits they gained in e-learning, no research has examined the impact of online student participation on their performance. This study fills in this gap by proposing and testing a model for examining the relationship between online performance and students’ type/level of participation in online forums. Findings provide suggestions for developing effective elearning. to enhance classroom-based instruction. Findings provide useful suggestions for developing successful e-learning.
Perceived Burdensomeness And Suicidality: Two Studies On The Suicide Notes Of Those Attempting And Those Completing Suicide

Abstract From an evolutionary-psychological perspective, it has been argued that a sense of burdensomeness toward kin may erode self-preservational motives, which in turn, fosters suicidality. We reasoned that if this were so, perceived burdensomeness should specifically characterize those who complete suicide, even as compared to those who attempt suicide, whereas other dimensions (e.g., hopelessness, emotional pain) may not differentiate completers from attempters. Moreover, we predicted that perceived burdensomeness may be related to more lethal means of suicide among those who complete suicide. Two samples of suicide notes were rated on dimensions of burdensomeness, desire to control one's own feelings, desire to control others, emotional pain, and hopelessness. Perceived burdensomeness significantly correlated with completer status and with more lethal means of suicide, even controlling for other relevant dimensions. The other dimensions, in contrast, did not significantly correlate with suicide comp.
CD8+ T cells can mediate almost complete short-term and partial long-term immunity to rotavirus in mice

We have recently shown that CD8+ T cells mediate clearance of rotavirus infection in mice. B-cell-deficient J(H)D knockout (-/-) mice depleted of CD8+ T cells become chronically infected with murine rotavirus, and beta2 microglobulin -/- and other mice depleted of CD8+ T cells have a 1- to 4-day delay in clearance of primary rotavirus infection. A role for CD8+ T cells in protection from reinfection with rotavirus was suggested by these studies, because J(H)D -/- mice rechallenged 6 to 8 weeks after primary infection shed smaller quantities of viral antigen and for fewer days than naive mice. Here we show that 8, 11, 13, and 18 days after primary infection the J(H)D -/- mice are almost completely resistant to reinfection and that they are still partially protected from reinfection 6 weeks, 5 months, and 8 months after primary infection. Protection against reinfection was dependent on CD8+ T cells, since J(H)D -/- mice depleted of CD8+ T cells by administration of an anti-CD8 monoclonal antibody became chronically infected with rotavirus upon rechallenge 13 days, 18 days, 6 weeks, and 5 months after primary infection. Thus, CD8+ T cells can actively mediate almost complete short-term and partial long-term protection from reinfection.
An Ensemble Model with Ranking for Social Dialogue

Open-domain social dialogue is one of the long-standing goals of Artificial Intelligence. This year, the Amazon Alexa Prize challenge was announced for the first time, where real customers get to rate systems developed by leading universities worldwide. The aim of the challenge is to converse "coherently and engagingly with humans on popular topics for 20 minutes". We describe our Alexa Prize system (called 'Alana') consisting of an ensemble of bots, combining rule-based and machine learning systems, and using a contextual ranking mechanism to choose a system response. The ranker was trained on real user feedback received during the competition, where we address the problem of how to train on the noisy and sparse feedback obtained during the competition.
Sodium channel permeation in squid axons. II: Non‐independence and current‐voltage relations.

1. The concentration and voltage dependence of current through the Na channels of squid giant axons was studied. The permeant cations Na, K and ammonium were used. 2. The Na channel current at a fixed voltage saturates as the internal permeant ion concentration is increased. The half‐saturation activities at 50 mV were found to be 623, 268, 161 mM for Na, NH4, and K, respectively. These Km values for Na and K appear to be voltage‐dependent. 3. Instantaneous current‐voltage relations were determined with two different internal Na concentrations and with Na outside and K inside. 4. A three‐barrier, two‐site ion permeation model previously used in describing Na channel reversal potentials is shown here to account for the Na channel currents as well.
Body Awareness in Anorexia Nervosa: Disturbances in “Body Image” and “Satiety”

&NA; Patients with anorexia nervosa have been shown previously to display distortions in body image perception. Bruch has postulated that these disturbances as well as disturbances in interoception are meaningfully related to the development of the syndrome. We hypothesized that disturbances in body image, as measured by a distorting photograph technique, and interoception, as measured by a satiety‐aversion to sucrose test, should be demonstrable in anorexic patients vs. normal controls. Furthermore, these disturbances should be modifiable by external cues (looking at one's image in a mirror and ingesting isocaloric “high” and “low” calorie connotation meals). We also hypothesized that body image and interoceptive disturbances would be interrelated in the same individuals. Results indicated that patients with anorexia nervosa (N = 26) differed from normal controls (N = 16) in overestimating their body sizes (p = 0.06) and in failing to develop an aversion to the sucrose tastes (p < 0.001). However, neither viewing one's image in a mirror nor ingesting both “high and “low” calorie connotation meals altered body size perception. Intrasubject body size estimates were very stable from week to week for the anorexic subjects (r = +0.75, p < 0.001) but less for the controls (r = +0.45, p < 0.05). The data revealed that overestimation of body size was closely related to the failure to develop an aversion to sucrose tastes in anorexic patients.
DFT Estimation of Exchange Coupling Constant of Cr8Molecular Ring using the Hybrid Functional B3LYP

A study of electronic and magnetic properties of an octametallic chromium-based homonuclear molecule Cr8F8(CO2 −C(CH3)3)16 is presented, using density functional theory (DFT) approach and linearized augmented plane wave (LAPW) method with Perdew, Burke and Ernzerhof (PBE) and Becke 3-term correlation (B3LYP) functionals. The exchange coupling parameters between transition metals ions are extracted, taking into account two di erent (ferroand antiferromagnetic) spin con gurations. The value J = 3.1 meV found for the hybrid B3LYP functional improves signi cantly the one obtained for the PBE functional and gives an evidence for the superiority of the former in simulation of molecular nanomgnets. Moreover, the hybrid functional yields excellent spin density localisation, an enhancement of the HOMO-LUMO gaps and the value 2. 81μB of magnetic moment at the chromium centre in good agreement with experiment.
Comment on "A Hydrogen-Rich Early Earth Atmosphere"

Tian et al. (Reports, 13 May 2005, p. 1014) proposed a hydrogen-rich early atmosphere with slow hydrogen escape from a cold thermosphere. However, their model neglects the ultraviolet absorption of all gases other than H2. The model also neglects Earth's magnetic field, which affects the temperature and density of ions and promotes nonthermal escape of neutral hydrogen.
Ambiguous pots: Everyday practice, migration and materiality. The case of medieval Baltic ware on the island of Bornholm (Denmark)

Archaeologists routinely deal with the remains of everyday life. Yet the significance and dimensions of daily practices are rarely reflected upon. Merging Bourdieu’s theory of practice, recent theories of everyday life and the materiality approach in archaeology, this study addresses the potential importance of daily practices and mundane objects in dealing with a rupture caused by migration. As a case study I use an example of medieval (eleventh century) Western Slavic migration to the island of Bornholm (Denmark) and production and daily handling of ceramic pots, the so-called Baltic ware. I explore the possible background to the introduction of the new pottery style, its significance for the local population of the island and above all the meanings these types of ceramics could have had for the immigrant Slavs.