Miracle-dz/UniFAR-FTUs huggingface dataset:
Cardiac S100A1 Protein Levels Determine Contractile Performance and Propensity Toward Heart Failure After Myocardial Infarction

Background— Diminished cardiac S100A1 protein levels are characteristic of ischemic and dilated human cardiomyopathy. Because S100A1 has recently been identified as a Ca2+-dependent inotropic factor in the heart, this study sought to explore the pathophysiological relevance of S100A1 levels in development and progression of postischemic heart failure (HF). Methods and Results— S100A1-transgenic (STG) and S100A1-knockout (SKO) mice were subjected to myocardial infarction (MI) by surgical left anterior descending coronary artery ligation, and survival, cardiac function, and remodeling were compared with nontransgenic littermate control (NLC) and wild-type (WT) animals up to 4 weeks. Although MI size was similar in all groups, infarcted S100A1-deficient hearts (SKO-MI) responded with acute contractile decompensation and accelerated transition to HF, rapid onset of cardiac remodeling with augmented apoptosis, and excessive mortality. NLC/WT-MI mice, displaying a progressive decrease in cardiac S100A1 expression, showed a later onset of cardiac remodeling and progression to HF. Infarcted S100A1-overexpressing hearts (STG-MI), however, showed preserved global contractile performance, abrogated apoptosis, and prevention from cardiac hypertrophy and HF with superior survival compared with NLC/WT-MI and SKO-MI. Both Gq-protein–dependent signaling and protein kinase C activation resulted in decreased cardiac S100A1 mRNA and protein levels, whereas Gs-protein–related signaling exerted opposite effects on cardiac S100A1 abundance. Mechanistically, sarcoplasmic reticulum Ca2+ cycling and &bgr;-adrenergic signaling were severely impaired in SKO-MI myocardium but preserved in STG-MI. Conclusions— Our novel proof-of-concept study provides evidence that downregulation of S100A1 protein critically contributes to contractile dysfunction of the diseased heart, which is potentially responsible for driving the progressive downhill clinical course of patients with HF.
Muscle adenine nucleotide metabolism during and in recovery from maximal exercise in humans.

The relationship between changes in the muscle total adenine nucleotide pool (TAN = ATP + ADP + AMP) and IMP during and after 30 s of sprint cycling was examined. Skeletal muscle samples were obtained from the vastus lateralis muscle of seven untrained men (23. 9 +/- 2.3 yr, 74.4 +/- 3.6 kg, and 55.0 +/- 2.9 ml. kg(-1). min(-1) peak oxygen consumption) before and immediately after exercise and after 5 and 10 min of passive recovery. The exercise-induced increase in muscle IMP was linearly related to the decrease in muscle TAN (r = -0.97, P < 0.01), and the slope of this relationship (-0.83) was not different from 1.0 (P > 0.05), indicating a 1:1 stoichiometric relationship. This interpretation must be treated cautiously, because all subjects displayed a greater decrease in TAN compared with the increase in IMP content, and the TAN + IMP + inosine + hypoxanthine content was lower (P < 0.05) immediately after exercise compared with during rest. During the first 5 min of recovery, the increase in TAN was not correlated with the decrease in IMP (r = -0.18, P > 0.05). In all subjects, the magnitude of TAN increase was higher than the magnitude of IMP decrease over this recovery period. In contrast, the increase in TAN was correlated with the decrease in IMP throughout the second 5 min of recovery (r = -0.80, P < 0.05), and it was a 1:1 stoichiometric relationship (slope = -1.12). These data indicate that a small proportion of the TAN pool was temporarily lost from the muscle purine stores during sprinting but was rapidly recovered after exercise.
A fast algorithm and datalog inexpressibility for temporal reasoning

We introduce a new tractable temporal constraint language, which strictly contains the Ord-Horn language of Bürkert and Nebel and the class of AND/OR precedence constraints. The algorithm we present for this language decides whether a given set of constraints is consistent in time that is quadratic in the input size. We also prove that (unlike Ord-Horn) the constraint satisfaction problem of this language cannot be solved by Datalog or by establishing local consistency.
Detecting Digital Forgeries Using Bispectral Analysis

With the rapid increase in low-cost and sophisticated digital technology the need for techniques to authenticate digital material will become more urgent. In this paper we address the problem of authenticating digital signals assuming no explicit prior knowledge of the original. The basic approach that we take is to assume that in the frequency domain a ``natural'''' signal has weak higher-order statistical correlations. We then show that ``un-natural'''' correlations are introduced if this signal is passed through a non-linearity (which would almost surely occur in the creation of a forgery). Techniques from polyspectral analysis are then used to detect the presence of these correlations. We review the basics of polyspectral analysis, show how and why these tools can be used in detecting forgeries and show their effectiveness in analyzing human speech.
A Longitudinal Investigation of the Friendship Model of Relational Interdependent Self-Construal

A four-wave longitudinal study examined how relational-interdependent self-construal (RISC) or the tendency to think of one’s self in terms of close relationships, was related to cognitions and behaviors within friendships. In same-sex friendships, in both concurrent and prospective analyses, own RISC was associated with perceived friend’s RISC, own relationship supportive behaviors, and own relationship quality. Perceived friend’s RISC predicted perceived friend’s relationship supportive behaviors. Own behaviors predicted fulfillment of own friendship functions, which predicted own relationship quality. In prospective analyses, behaviors mediated the RISC-friendship function relation, and behaviors and friendship functions both mediated the RISC-relationship quality relation. However, the influence of perceived friend’s RISC on subsequent variables was through its association with perceived friend’s behavior, which was associated with own friendship functions concurrently.
Assessment of Breast Specimens With or Without Calcifications in Diagnosing Malignant and Atypia for Mammographic Breast Microcalcifications Without Mass

Abstract Presence of microcalcifications within the specimens frequently signifies a successful attempt of stereotactic vacuum-assisted breast biopsy (VABB) in obtaining a pathologic diagnosis of the breast microcalcifications. In this study, the authors aimed to assess and compare the accuracy and consistency of calcified or noncalcified specimens obtained from same sites of sampling on isolated microcalcifications without mass in diagnosing high-risk and malignant lesions. To the best of our knowledge, an individual case-based prospective comparison has not been reported. With the approval from institutional review board of our hospital (Chang Gung Memorial Hospital), the authors retrospectively reviewed all clinical cases of stereotactic VABBs on isolated breast microcalcifications without mass from our database. The authors included those having either surgery performed or had clinical follow-up of at least 3 years for analysis. All the obtained specimens with or without calcification were identified using specimen radiographs and separately submitted for pathologic evaluation. The concordance of diagnosis was assessed for both atypia and malignant lesions. A total of 390 stereotactic VABB procedures (1206 calcified and 1456 noncalcified specimens) were collected and reviewed. The consistent rates between calcified and noncalcified specimens were low for atypia and malignant microcalcifications (44.44% in flat epithelial atypia, 46.51% in atypical ductal hyperplasia, 55.73% in ductal carcinoma in situ, and 71.42% in invasive ductal carcinoma). The discordance in VABB diagnoses indicated that 41.33% of malignant lesions would be misdiagnosed by noncalcified specimens. Furthermore, calcified specimens showed higher diagnostic accuracy of breast cancer as compared with the noncalcified specimens (91.54 % versus 69.49%, respectively). The evaluation of both noncalcified specimens and calcified specimens did not show improvement of diagnostic accuracy as compared with evaluating calcified specimens alone (91.54% versus 91.54%, respectively). The high prevalence of diagnostic discordance between the calcified and noncalcified specimens indicated the higher value of calcified specimens in diagnosing atypia and malignant microcalcifications. Noncalcified specimens did not provide additional diagnostic benefit from this study. The separation of calcified and noncalcified specimens may facilitate more focused interpretation from pathologists among the large number of specimens.
Golgi Cell-Mediated Activation of Postsynaptic GABAB Receptors Induces Disinhibition of the Golgi Cell-Granule Cell Synapse in Rat Cerebellum

In the cerebellar glomerulus, GABAergic synapses formed by Golgi cells regulate excitatory transmission from mossy fibers to granule cells through feed-forward and feedback mechanisms. In acute cerebellar slices, we found that stimulating Golgi cell axons with a train of 10 impulses at 100 Hz transiently inhibited both the phasic and the tonic components of inhibitory responses recorded in granule cells. This effect was blocked by the GABAB receptor blocker CGP35348, and could be mimicked by bath-application of baclofen (30 µM). This depression of IPSCs was prevented when granule cells were dialyzed with GDPβS. Furthermore, when synaptic transmission was blocked, GABAA currents induced in granule cells by localized muscimol application were inhibited by the GABAB receptor agonist baclofen. These findings indicate that postsynaptic GABAB receptors are primarily responsible for the depression of IPSCs. This inhibition of inhibitory events results in an unexpected excitatory action by Golgi cells on granule cell targets. The reduction of Golgi cell-mediated inhibition in the cerebellar glomerulus may represent a regulatory mechanism to shift the balance between excitation and inhibition in the glomerulus during cerebellar information processing.
Product Standards, Trade Disputes, and Protectionism

Trade disputes over national product standards are a growing source of tension in the international trading system. The usual pattern is that a country introduces a new product standard for all sales of a good in its local market, which is justified as necessary for consumer or environmental protection. Importers into the local market, however, challenge the standard as a 'disguised barrier to trade' or 'green protectionism'. The paper develops a two country political economy model to explain such disputes. It is shown how the political process can lead to a 'political failure' which takes the form of either too many or too few product standards and disagreement between politicians in different countries over the optimal policy. In a second step the model is used to evaluate whether two common proposals to settle or avoid such disputes, mutual recognition of standards and harmonization, can improve the political process.
Identification of a Hematopoietic Cell Dedifferentiation‐Inducing Factor

It has long been realized that hematopoietic cells may have the capacity to trans‐differentiate into non‐lymphohematopoietic cells under specific conditions. However, the mechanisms and the factors for hematopoietic cell trans‐differentiation remain unknown. In an in vitro culture system, we found that using a conditioned medium from proliferating fibroblasts can induce a subset of hematopoietic cells to become adherent fibroblast‐like cells (FLCs). FLCs are not fibroblasts nor other mesenchymal stromal cells, based on their expression of type‐1 collagen, and other stromal cell marker genes. To identify the active factors in the conditioned medium, we cultured fibroblasts in a serum‐free medium and collected it for further purification. Using the fractions from filter devices of different molecular weight cut‐offs, and ammonium sulfate precipitation collected from the medium, we found the active fraction is a protein. We then purified this fraction by using fast protein liquid chromatography (FPLC) and identified it by mass spectrometer as macrophage colony‐stimulating factor (M‐CSF). The mechanisms of M‐CSF‐inducing trans‐differentiation of hematopoietic cells seem to involve a tyrosine kinase signalling pathway and its known receptor. The FLCs express a number of stem cell markers including SSEA‐1 and ‐3, OCT3/4, NANOG, and SOX2. Spontaneous and induced differentiation experiments confirmed that FLCs can be further differentiated into cell types of three germ layers. These data indicate that hematopoietic cells can be induced by M‐CSF to dedifferentiate to multipotent stem cells. This study also provides a simple method to generate multipotent stem cells for clinical applications. J. Cell. Physiol. 231: 1350–1363, 2016. © 2015 Wiley Periodicals, Inc.
Statistical modeling and analysis of P2P replication to support VoD service

Traditional Video-on-Demand (VoD) systems reply purely on servers to stream video content to clients, which does not scale. In recent years, Peer-to-peer assisted VoD (P2P VoD) has proven to be practical and effective [1]. In P2P VoD, each peer contributes some storage to store videos (or segments of videos) to help the video server. Assuming peers have sufficient bandwidth for the given video playback rate, a fundamental question is what is the relationship between the storage capacity (at each peer), the number of videos, the number of peers and the resultant off-loading of video server bandwidth. In this paper, we use a simple statistical model to derive this relationship. We propose and analyze a generic replication algorithm RLB which balances the service to all movies, for both deterministic and random demand models, and both homogeneous and heterogeneous peers (in upload bandwidth). We use simulation to validate our results, for sensitivity analysis and for comparisons with other popular replication algorithms. This study leads to several fundamental insights for design P2P VoD systems in practice.
Human memory T cells from the bone marrow are resting and maintain long-lasting systemic memory

Significance Memory T cells are essential components of immunological memory. In the apparent absence of antigen, numbers of recirculating antigen-specific memory T cells dwindle, provoking the question of whether there is immunological memory without memory T cells. Here we show that human memory T cells can reside in the bone marrow as resting cells in terms of proliferation, transcription, and mobility. The repertoire of bone marrow memory T cells is enriched for systemic pathogens representing persistent, recent, and childhood challenges. In terms of absolute numbers, memory T cells specific for systemic antigens are maintained predominantly in the bone marrow, in particular those representing historic encounters. In the bone marrow, a population of memory T cells has been described that promotes efficient secondary immune responses and has been considered to be preactivated, owing to its expression of CD69 and CD25. Here we show that human bone marrow professional memory T cells are not activated but are resting in terms of proliferation, transcription, and mobility. They are in the G0 phase of the cell cycle, and their transcriptome is that of resting T cells. The repertoire of CD4+ bone marrow memory T cells compared with CD4+ memory T cells from the blood is significantly enriched for T cells specific for cytomegalovirus-pp65 (immunodominant protein), tetanus toxoid, measles, mumps, and rubella. It is not enriched for vaccinia virus and Candida albicans-MP65 (immunodominant protein), typical pathogens of skin and/or mucosa. CD4+ memory T cells specific for measles are maintained nearly exclusively in the bone marrow. Thus, CD4+ memory T cells from the bone marrow provide long-term memory for systemic pathogens.
PERENCANAAN PENGELOLAAN WILAYAH PESISIR PULAU JAWA DITINJAU DARI ASPEK KERENTANAN KAWASAN DAN IMPLIKASINYA TERHADAP KEMUNGKINAN BENCANA KENAIKAN MUKA LAUT

Dampak pemanasan global, yaitu berupa kenaikan muka laut dengan kecepatan 2-8 mm/tahun yang tampaknya lambat dan tidak berarti, akan tetapi dalam 100 tahun mendatang kenaikan muka laut tersebut mampu untuk menggenangi kawasan pesisir P. Jawa yang memiliki morfologi pantai yang landai dan bersudut lereng kecil. Kenaikan muka laut merupakan bencana alam yang lambat dan bisa diprediksi, namun dengan sifat yang demikian justru manusia cenderung lupa segera menanganinya. Oleh karena itu, untuk mengantisipasi kemungkinan terjadinya bencana, serta mengurangi bahkan memperkecil dampak negatif risiko bencana tersebut, perlu memasukan komponen manajemen risiko bencana alam (risk management of natural disaster) di dalam penyusunan tata ruang wilayah (RTRW). Kata kunci: kenaikan muka laut, manajemen risiko bencana alam, Pulau Jawa, pesisir The impact of global warming, in the form of sea level rise by the rate 2-8 mm/year which seems slow and insignificant, but in the next 100 years sea level rise are can inundate coastal areas of Java which has a low slope beach morphology and small slope angles. Sea-level rise is a natural disaster that slow and predictable, but the nature of such people tend to forget it immediately. Therefore, to anticipate disasters and reduce or even minimize the negative impact of disaster risks, it is need to include components of risk management of natural disaster in the preparation of the spatial planning. Keywords: sealevel rise, risk management of natural disaster, Java, coastal
BDNF stabilizes synapses and maintains the structural complexity of optic axons in vivo

Brain-derived neurotrophic factor (BDNF) modulates synaptic connectivity by increasing synapse number and by promoting activity-dependent axon arbor growth. Patterned neuronal activity is also thought to influence the morphological maturation of axonal arbors by directly influencing the stability of developing synapses. Here, we used in vivo time-lapse imaging to examine the relationship between synapse stabilization and axon branch stabilization, and to better understand the participation of BDNF in synaptogenesis. Green fluorescent protein (GFP)-tagged synaptobrevin II was used to visualize presynaptic specializations in individual DsRed2-labeled Xenopus retinal axons arborizing in the optic tectum. Neutralizing endogenous tectal BDNF with function-blocking antibodies significantly enhanced GFP-synaptobrevin cluster elimination, a response that was paralleled by enhanced branch elimination. Thus, synapse dismantling was associated with axon branch pruning when endogenous BDNF levels were reduced. To obtain a second measure of the role of BDNF during synapse stabilization, we injected recombinant BDNF in tadpoles with altered glutamate receptor transmission in the optic tectum. Tectal injection of the NMDA receptor antagonists APV or MK801 transiently induced GFP-synaptobrevin cluster dismantling, but did not significantly influence axon branch addition or elimination. BDNF treatment rescued synapses affected by NMDA receptor blockade: BDNF maintained GFP-synaptobrevin cluster density by maintaining their addition rate and rapidly inducing their stabilization. Consequently, BDNF influences synaptic connectivity in multiple ways, promoting not only the morphological maturation of axonal arbors, but also their stabilization, by a mechanism that influences both synapses and axon branches.
Role of Ionotropic Glutamate Receptors in Long-Term Potentiation in Rat Hippocampal CA1 Oriens-Lacunosum Moleculare Interneurons

Some interneurons of the hippocampus exhibit NMDA receptor-independent long-term potentiation (LTP) that is induced by presynaptic glutamate release when the postsynaptic membrane potential is hyperpolarized. This “anti-Hebbian” form of LTP is prevented by postsynaptic depolarization or by blocking AMPA and kainate receptors. Although both AMPA and kainate receptors are expressed in hippocampal interneurons, their relative roles in anti-Hebbian LTP are not known. Because interneuron diversity potentially conceals simple rules underlying different forms of plasticity, we focus on glutamatergic synapses onto a subset of interneurons with dendrites in stratum oriens and a main ascending axon that projects to stratum lacunosum moleculare, the oriens-lacunosum moleculare (O-LM) cells. We show that anti-Hebbian LTP in O-LM interneurons has consistent induction and expression properties, and is prevented by selective inhibition of AMPA receptors. The majority of the ionotropic glutamatergic synaptic current in these cells is mediated by inwardly rectifying Ca2+-permeable AMPA receptors. Although GluR5-containing kainate receptors contribute to synaptic currents at high stimulus frequency, they are not required for LTP induction. Glutamatergic synapses on O-LM cells thus behave in a homogeneous manner and exhibit LTP dependent on Ca2+-permeable AMPA receptors.
Girdin-mediated interactions between cadherin and the actin cytoskeleton are required for epithelial morphogenesis in Drosophila

E-cadherin-mediated cell-cell adhesion is fundamental for epithelial tissue morphogenesis, physiology and repair. E-cadherin is a core transmembrane constituent of the zonula adherens (ZA), a belt-like adherens junction located at the apicolateral border in epithelial cells. The anchorage of ZA components to cortical actin filaments strengthens cell-cell cohesion and allows for junction contractility, which shapes epithelial tissues during development. Here, we report that the cytoskeletal adaptor protein Girdin physically and functionally interacts with components of the cadherin-catenin complex during Drosophila embryogenesis. Fly Girdin is broadly expressed throughout embryonic development and enriched at the ZA in epithelial tissues. Girdin associates with the cytoskeleton and co-precipitates with the cadherin-catenin complex protein α-Catenin (α-Cat). Girdin mutations strongly enhance adhesion defects associated with reduced DE-cadherin (DE-Cad) expression. Moreover, the fraction of DE-Cad molecules associated with the cytoskeleton decreases in the absence of Girdin, thereby identifying Girdin as a positive regulator of adherens junction function. Girdin mutant embryos display isolated epithelial cell cysts and rupture of the ventral midline, consistent with defects in cell-cell cohesion. In addition, loss of Girdin impairs the collective migration of epithelial cells, resulting in dorsal closure defects. We propose that Girdin stabilizes epithelial cell adhesion and promotes morphogenesis by regulating the linkage of the cadherin-catenin complex to the cytoskeleton. SUMMARY: The cytoskeletal adaptor protein Girdin physically and functionally interacts with cadherin-catenin complex components to regulate adherens junctions and hence cell adhesion during Drosophila embryogenesis.
Location privacy protection in asynchronous localization networks by resource allocation approaches

High precision location information formulates the basis of many modern wireless location based services (LBS). However, location privacy becomes an important issue along with the advantages that LBS offers. In this paper, we first show that, a novel eavesdropper is able to perform position estimation of the agent by purely overhearing the measurement signals between agents and anchors, using a time difference of arrival (TDOA) way. Optimal resource allocation based approaches are presented to protect the location privacy against the eavesdropper. High accuracy approximation algorithms are presented to solve the essential non-convex power optimization problems. According to the numeric results, we can see that, the presented power allocation strategies are able to prevent the eavesdropper performing accurate position estimation of the agent. We can also see that there exists an optimal tradeoff between the system localization performance and privacy protection, which can be achieved by the presented frameworks.