Miracle-dz/UniFAR-FTUs huggingface dataset:
Lack of Obesity and Normal Response to Fasting and Thyroid Hormone in Mice Lacking Uncoupling Protein-3*

Uncoupling protein-3 (UCP3) is a mitochondrial protein that can diminish the mitochondrial membrane potential. Levels of muscle Ucp3 mRNA are increased by thyroid hormone and fasting. Ucp3 has been proposed to influence metabolic efficiency and is a candidate obesity gene. We have produced aUcp3 knockout mouse to test these hypotheses. TheUcp3 (−/−) mice had no detectable immunoreactive UCP3 by Western blotting. In mitochondria from the knockout mice, proton leak was greatly reduced in muscle, minimally reduced in brown fat, and not reduced at all in liver. These data suggest that UCP3 accounts for much of the proton leak in skeletal muscle. Despite the lack of UCP3, no consistent phenotypic abnormality was observed. The knockout mice were not obese and had normal serum insulin, triglyceride, and leptin levels, with a tendency toward reduced free fatty acids and glucose. Knockout mice showed a normal circadian rhythm in body temperature and motor activity and had normal body temperature responses to fasting, stress, thyroid hormone, and cold exposure. The base-line metabolic rate and respiratory exchange ratio were the same in knockout and control mice, as were the effects of fasting, a β3-adrenergic agonist (CL316243), and thyroid hormone on these parameters. The phenotype ofUcp1/Ucp3 double knockout mice was indistinguishable fromUcp1 single knockout mice. These data suggest thatUcp3 is not a major determinant of metabolic rate but, rather, has other functions.
Modelo de interoperabilidad de la historia clínica electrónica utilizando HL7-CDA basado en computación en la nube

Resumen. La implementación exitosa de la Historia Clínica Electrónica (HCE) ayuda a mejorar la calidad de la atención de los pacientes, actualmente existe el problema de interoperabilidad entre las instituciones de salud, debido al uso variado de metodologías y tecnologías para su desarrollo. La Arquitectura de Documento Clínico (CDA) desarrollado por HL7 es un estándar de documentos para garantizar la interoperabilidad, la propagación de este formato de documento es fundamental para la interoperabilidad. El modelo presentado propone el desarrollo de sistemas orientados a la gestión de conocimiento clínico basándose en la generación de documentos CDA y su integración a través de la computación en la nube. Los desarrolladores que manejan diferentes plataformas podrán utilizar este modelo para mejorar la interoperabilidad. Los resultados obtenidos fueron la implementación de un modelo de uso general para desarrollo de HCE usando sintaxis basadas en XML para representar el conocimiento clínico mediante plantillas CDA.
Expression of metabotropic glutamate receptors in rat meningeal and brain microvasculature and choroid plexus

This study investigated the distribution of metabotropic glutamate receptors (mGluRs) in meningeal and parenchymal microvasculature and in choroid plexus by means of Western blot analysis and immunohistochemistry. Western blot analysis demonstrated mGluR expression in both rat and human leptomeningeal tissues. In the rat, mGluR expression was developmentally regulated, with only mGluR2/3 showing expression at the embryonic day 19 developmental stage. In contrast, mGluR1α, mGluR2/3, mGluR4a, and mGluR7 were expressed in leptomeninges from adult rats. Immunohistochemical analyses showed intense mGluR1α immunoreactivity in the pia mater and blood vessels in the subarachnoid space and in the arachnoid layer of the meninges. mGluR2/3, mGluR4a, mGluR5, and mGluR7 were also expressed in meningeal microvasculature. In addition, the parenchymal microvasculature and choroid plexus were strongly immunoreactive for mGluR1α, mGluR2/3, mGluR4a, mGluR5, and mGluR7. We used antibodies specific for phenotypic markers of microvascular and glial cells to characterize the cell type(s) immunopositive for mGluRs. Comparison of staining with anti–von Willebrand factor antibody and anti‐mGluR antibodies revealed that mGluR immunoreactivity was present in cells that surrounded the luminal surface labeled by the endothelial cell marker. In these cells, smooth muscle actin and mGluR immunoreactivity overlapped, suggesting that, in addition to endothelial cells, pericytes within the microvasculature also express mGluRs. Furthermore, expression of mGluR1α was also observed in pure pericyte cultures isolated from bovine retina. These data suggest that glutamate by means of activation of mGluRs may have a broad sphere of physiological influence in the brain which in addition to modulating synaptic transmission may also have a role in determining microvascular function and dysfunction. J. Comp. Neurol. 461:317–332, 2003. © 2003 Wiley‐Liss, Inc.
Prospective evaluation of adenosine-induced proarrhythmia in the emergency room

The arrhythmogenic hazard of adenosine treatment in an emergency room (ER) has not been established. Thus, in this study, we set out to prospectively determine the prevalence and clinical consequences of the arrhythmogenic effects associated with urgent adenosine treatment in the ER. One hundred and sixty consecutive patients treated with adenosine for regular wide or narrow complex tachyarrhythmias at our ER were included in the study. An initial bolus of 3 mg of adenosine was used, up to a maximum dose of 18 mg (mode 6 mg). Proarrhythmia was defined as the new appearance of any brady- or tachyarrhythmia within 1 minute from the bolus administration of adenosine. Of the 160 study patients, 84% had narrow complex tachycardia and 16% had wide complex tachycardia. Adenosine was effective in the diagnosis and/or treatment of the underlying arrhythmia in 92%. The overall prevalence of adenosine-induced proarrhythmia was 13%, including prolonged AV block inducing asystole >4 seconds (7%), paroxysmal atrial fibrillation (1%) and non-sustained ventricular tachycardia (5%). All adenosine-induced arrhythmias were transient and subsided spontaneously. It is concluded, firstly, that adenosine-induced proarrhythmia proved to be frequent in a consecutive ER series, and included potentially dangerous arrhythmias. Secondly, nevertheless, all adenosine-induced arrhythmias subsided spontaneously and did not require treatment. Therefore, urgent adenosine treatment is safe and can be recommended in an emergency setting, provided a strict protocol of administration under close monitoring by highly trained personnel.
Comparing Taiwan's foreign aid to Japan, South Korea and DAC

ABSTRACT Taiwan has been all but left out of comparative studies of foreign aid donors. This article places Taiwan's aid program in context, through a comparison with its East Asian neighbors – Japan and Korea – and the OECD Development Assistance Committee (DAC) donors as group. It finds that while Taiwan differs from Japan and Korea in key respects, there are also notable similarities between the three in relation to other DAC donors.
Independent Analysts’ Estimates of Firm Value

We provide new evidence on the quality of independent analysts’ firm value estimates (i.e., price targets). Whereas prior literature generally finds that independent analysts’ research underperforms that of sell-side analysts using earlier sample periods, we show that, in a recent sample period, independent analysts’ research performs more favorably. That is, we find independent analysts’ price targets are less optimistic than investment-bank analysts’ forecasts with limited evidence of lower accuracy. Moreover, independent analysts’ price targets are less optimistic for firms with characteristics previously associated with overall analyst optimism, including higher stock price momentum and higher valuations. Our evaluation of the fundamental inputs from which independent analysts form their price targets suggests that less optimistic long-term growth forecasts could be responsible for the lower relative optimism in their price targets. Yet, even though independent analysts’ price targets provide less optimistic forecasts of firm value, the market reacts relatively less strongly to independent analysts’ price target revisions. These findings suggest that investors as well as those interested in extending empirical research into firm valuation can benefit from independent analysts’ price targets.
Vasomotor responses to decreased venous return: effects of cardiac deafferentation in humans

We compared haemodynamic and peripheral vasomotor responses to lower body negative pressure (LBNP) in cardiac transplant recipients who had undergone bicaval anastomoses, involving right atrial deafferentation (−RA), and the conventional procedure in which some atrial baroreceptor afferents remain intact (+RA). We measured mean forearm blood flow (FBF) responses using Doppler/ultrasound during three randomised trials involving 0 (baseline), −20 and −40 mmHg LBNP in 15 transplant recipients (9 −RA, 6 +RA) and in eight healthy matched controls. A significant effect of LBNP on FBF existed between control and transplant groups (P < 0.05; two‐way ANOVA). Mild LBNP (−20 mmHg), significantly decreased FBF by 29.7 ± 10.0% relative to baseline in +RA subjects (P < 0.05), whereas the 17.7 ± 10.3% decrease in −RA subjects was not significant. In response to −40 mmHg LBNP, FBF significantly decreased in control (42.4 ± 4.6%, P < 0.05) and +RA subjects (33.3 ± 11.4%, P < 0.05) with no significant change in the −RA group. The response of systolic blood pressure (SBP) to −40 mmHg significantly differed between groups (P < 0.05): −RA subjects decreased significantly (P < 0.05) whilst the decrease in SBP in +RA subjects did not achieve significance and control subjects exhibited an increase. The heart rate increase from baseline to −40 mmHg was significantly attenuated in −RA relative to controls and the +RA group (P < 0.05). The present study demonstrates that atrial deafferentation impairs reflex vasomotor control of the circulation in response to low‐ and high‐level LBNP, indicating that atrial deafferentation may contribute to abnormal arterial pressure regulation.
Extraction of mono-aural vocal and non-vocal components exploiting ‘ANOVA’ computational method in REPET

The distinction of the lead varying vocals from the background music in an audio recording is an extremely demanding and exigent task. The speech-separation research usually inculcates Time-frequency masking technique that ultimately appraises the hearing-aid design. The core principle in music which is capitalized to discriminate underlying non-vocals from vocals (speech) is Repetition. The `Repetition' feature is especially enacted for pop songs where the singer often overlays frequently changing vocals on a periodically repeating background in a mixture. The basic approach of this research paper is the recognisation of periodically repeating segments in audio excerpts, analogize them with a repeating model and finally discrimate the repeating musical patterns via Time-Frequency masking. A TF mask is grounded on the basis of TF representation of any signal. In the proposed algorithm, the quality of foreground vocals and accompanying background can be adjudicated in terms of SIR (Signal to Interference Ratio) value utilizing `ANOVA' (Analysis Of Variation) computational method on six different genres of musical audios.
Autoimmune dermatologic toxicities from immune checkpoint blockade with anti‐PD‐1 antibody therapy: a report on bullous skin eruptions

Monoclonal antibodies against the immune checkpoint programmed cell death receptor 1 (PD‐1) improve the hosts' antitumor immune response and have showed tremendous promise in the treatment of advanced solid tumors and hematologic malignancies. Reports of serious autoimmune dermatologic toxicities from immune checkpoint blockade therapy, however, are emerging. We report our experience with five patients who presented with pruritic vesicles and blisters on the skin while treated with anti‐PD‐1 antibody immunotherapy with either nivolumab or pembrolizumab. Four of the patients' skin biopsies revealed subepidermal bullae with immunohistochemical study for type IV collagen labeling the floor of the blister cavity and direct immunofluorescence studies (in three of the four patients tested) decorated linear IgG and C3 immune deposits on the blister roof, diagnostic of bullous pemphigoid. One patient developed bullous erythema multiforme. All patients had partial or complete resolution of skin lesions following treatment with systemic corticosteroid and cessation of checkpoint blockade. Recognition and treatment of rare immune‐related bullous dermatologic toxicities will become increasingly important as more patients are treated with effective and newer immune checkpoint blockade therapy.
Involvement of Protein Kinase C Activation and Cell Survival/ Cell Cycle Genes in Green Tea Polyphenol (−)-Epigallocatechin 3-Gallate Neuroprotective Action*

Studies from our laboratory have demonstrated that the major green tea polyphenol, (−)-epigallocatechin 3-gallate (EGCG), exerts potent neuroprotective actions in the mice model of Parkinson's disease. These studies were extended to neuronal cell culture employing the parkinsonism-inducing neurotoxin, 6-hydroxydopamine (6-OHDA). Pretreatment with EGCG (0.1–10 μm) attenuated human neuroblastoma (NB) SH-SY5Y cell death, induced by a 24-h exposure to 6-OHDA (50 μm). Potential cell signaling candidates involved in this neuroprotective effect were further examined. EGCG restored the reduced protein kinase C (PKC) and extracellular signal-regulated kinases (ERK1/2) activities caused by 6-OHDA toxicity. However, the neuroprotective effect of EGCG on cell survival was abolished by pretreatment with PKC inhibitor GF 109203X (1 μm). Because EGCG increased phosphorylated PKC, we suggest that PKC isoenzymes are involved in the neuroprotective action of EGCG against 6-OHDA. In addition, gene expression analysis revealed that EGCG prevented both the 6-OHDA-induced expression of several mRNAs, such as Bax, Bad, and Mdm2, and the decrease in Bcl-2, Bcl-w, and Bcl-xL. These results suggest that the neuroprotective mechanism of EGCG against oxidative stress-induced cell death includes stimulation of PKC and modulation of cell survival/cell cycle genes.
Regulation of the Protocadherin Celsr3 Gene and Its Role in Globus Pallidus Development and Connectivity

ABSTRACT The globus pallidus (GP) is a central component of basal ganglia whose malfunctions cause a variety of neuropsychiatric disorders as well as cognitive impairments in neurodegenerative diseases such as Parkinson's disease. Here we report that the protocadherin gene Celsr3 is regulated by the insulator CCCTC-binding factor (CTCF) and the repressor neuron-restrictive silencer factor (NRSF, also known as REST) and is required for the development and connectivity of GP. Specifically, CTCF/cohesin and NRSF inhibit the expression of Celsr3 through specific binding to its promoter. In addition, we found that the Celsr3 promoter interacts with CTCF/cohesin-occupied neighboring promoters. In Celsr3 knockout mice, we found that the ventral GP is occupied by aberrant calbindin-positive cholinergic neurons ectopic from the nucleus basalis of Meynert. Furthermore, the guidepost cells for thalamocortical axonal development are missing in the caudal GP. Finally, axonal connections of GP with striatum, subthalamic nucleus, substantia nigra, and raphe are compromised. These data reveal the essential role of Celsr3 in GP development in the basal forebrain and shed light on the mechanisms of the axonal defects caused by the Celsr3 deletion.
Endocranial Morphology of the Primitive Nodosaurid Dinosaur Pawpawsaurus campbelli from the Early Cretaceous of North America

Background Ankylosaurs are one of the least explored clades of dinosaurs regarding endocranial anatomy, with few available descriptions of braincase anatomy and even less information on brain and inner ear morphologies. The main goal of this study is to provide a detailed description of the braincase and internal structures of the Early Cretaceous nodosaurid Pawpawsaurus campbelli, based on recently made CT scans. Methodology/Principal Findings The skull of Pawpawsaurus was CT scanned at University of Texas at Austin (UTCT). Three-dimensional models were constructed using Mimics 18.0 (Materialise). The digital data and further processed 3D models revealed inaccessible anatomic structures, allowing a detailed description of the lateral wall of the braincase (obscured by other bones in the articulated skull), and endocranial structures such as the cranial endocast, the most complete inner ear morphology for a nodosaurid, and the interpretation of the airflow system within the nasal cavities. Conslusions/Significance The new information on the endocranial morphology of Pawpawsaurus adds anatomical data to the poorly understand ankylosaur paleoneurology. The new set of data has potential use not only in taxonomy and phylogeny, but also in paleobiological interpretations based on the relative development of sense organs, such as olfaction, hearing and balance.
Nitric oxide modulates specific steps of auxin-induced adventitious rooting in sunflower

Present work on indole-3-acetic acid (IAA)-induced adventitious rooting in sunflower hypocotyl highlights a clear demarcation of nitric oxide (NO)-dependent and NO-independent roles of auxin in this developmental process. Of the three phases of adventitious rooting, induction is strictly auxin-dependent though initiation and extension are regulated by an interaction of IAA with NO. A vital role of auxin-efflux transporters (PIN) is also evident from 1-napthylphthalamic acid (NPA)-triggered suppression of adventitious roots (AR). Use of actin depolymerizing agent, Latrunculin B (Lat B), has demonstrated the necessity of functional actin filaments in auxin-induced AR response, possibly through its effect on actin-mediated recycling of auxin transporter proteins. Thus, evidence for a linkage between IAA, NO and actin during AR formation has been established.
EFFECT OF BARNIDIPINE ON BLOOD FLOW TO MAJOR ORGANS AND RENAL FUNCTION IN ANAESTHETIZED DOGS AND SPONTANEOUSLY HYPERTENSIVE RATS

1. The effects of barnidipine on blood flow to major organs and on renal function were investigated in anaesthetized dogs and conscious spontaneously hypertensive rats (SHR), and the results were compared with those for nicardipine, nitrendipine, nisoldipine, manidipine and amlodipine.
Monoclonal IgM from patients with peripheral demyelinating neuropathies cross‐react with bacterial polypeptides

Human monoclonal IgM associated with a demyelinating peripheral neuropathy often feature a distinct antibody activity directed against a glucuronyl sulphate epitope shared by myelin‐associated glycoprotein (MAG), nerve glycolipids and low molecular weight peripheral nerve polypeptides‐ Earlier studies showed that these IgM use a diverse repertoire of VH, and VL genes which exhibit somatic mutations, possibly indicative of an antigen‐driven process. Here, we investigated whether such monoclonal IgM may react with environmental bacterial antigens. We found that six patients' sera and purified monoclonal IgM, as well as IgM from supernatants of three clonal anti‐MAG‐secreting cell lines reacted with unique 90 ‐100kD polypeptides from extracts of two out of 10 bacterial species. Purified MAG was able to inhibit this reactivity. These results indicate molecular mimicry as a possible mechanism of this immunomediated neuropathy and associated clonal lymphoid disease.
Low-dose tacrolimus combined with donor-derived mesenchymal stem cells after renal transplantation: a prospective, non-randomized study

Calcineurin inhibitors, including tacrolimus, are largely responsible for advances in allotransplantation. However, the nephrotoxicity associated with these immunosuppressants impairs patients' long-term survival after renal allograft. Therefore, novel regimens that minimize or even eliminate calcineurin inhibitors could improve transplantation outcomes. In this pilot study, we investigated the use of low-dose tacrolimus in combination with mesenchymal stem cells (MSCs), which are immunosuppressive and prolong allograft survival in experimental organ transplant models. Donor-derived, bone marrow MSCs combined with a sparing dose of tacrolimus (0.04-0.05 mg/kg/day) were administered to 16 de novo living-related kidney transplant recipients; 16 other patients received a standard dose of tacrolimus (0.07-0.08 mg/kg/day). The safety of MSC infusion, acute rejection, graft function, graft survival, and patient survival were evaluated over ≥24 months following kidney transplantation. All patients survived and had stable renal function at the 24 month follow-up. The combination of low-dose tacrolimus and MSCs was as effective as standard dose tacrolimus in maintaining graft survival at least 2 years after transplantation. In addition, both groups had similar urea, urine protein, urinary RBC, urinary WBC, 24-h urine protein, and creatinine clearance rates from 7 days to 24 months after transplantation. Furthermore, no differences in the proportion of lymphocytes, CD19, CD3, CD34, CD38, and natural killer cells were detected between the control and experimental groups. None of the MSC recipients experienced immediate or long-term toxicity from the treatment. This preliminary data suggests that the addition of MSCs permits the use of lower dosages of nephrotoxic calcineurin inhibitors following renal transplantation.
Polarization-Maintaining Large Mode Area Fiber Design for 2- $\mu \text{m}$ Operation

Large mode area polarizing maintaining (PM) photonic crystal fiber (PCF) designs, for 2-μm operation, are studied. A commercial PM-PCF optimized for 1-μm operation has been scaled to obtain an 80-μm-diameter core, and then numerically analyzed with the help of a finite-element method-based software to investigate its behavior at different values of bending radius. From the problems emerged by this design, a new optimized design has been proposed and numerically simulated. The new fiber consists in a thulium-doped 19-cell core with a diameter of 80 μm. The holes lattice, which follows the stack-and-draw scheme, has been modified to include two boron-doped stress applying parts, in order to induce a consistent birefringence. The results show that it is possible to achieve a single mode, single polarization operation, efficiently suppressing one of the fundamental mode (FM) polarization and the most significant higher order modes, in a range of bending radius from 33 to 40 cm. A remarkable value of 2600 μm2 has been registered for the effective area of the survived FM polarization.
Software engineering and the SP theory of intelligence

This paper describes a novel approach to software engineering derived from the "SP Theory of Intelligence" and its realisation in the "SP Computer Model". Despite superficial appearances, it is shown that many of the key ideas in software engineering have counterparts in the structure and workings of the SP system. Potential benefits of this new approach to software engineering include: the automation or semi-automation of software development, with support for programming of the SP system where necessary; allowing programmers to concentrate on 'world-oriented' parallelism, without worries about parallelism to speed up processing; support for the long-term goal of programming the SP system via written or spoken natural language; reducing or eliminating the distinction between 'design' and 'implementation'; reducing or eliminating operations like compiling or interpretation; reducing or eliminating the need for verification of software; reducing the need for validation of software; no formal distinction between program and database; the potential for substantial reductions in the number of types of data file and the number of computer languages; benefits for version control; and reducing technical debt.