Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of the Protein Kinase Activity of TRPM7/ChaK1, a Protein Kinase Fused to the Transient Receptor Potential Ion Channel*

Channel-kinase TRPM7/ChaK1 is a member of a recently discovered family of protein kinases called α-kinases that display no sequence homology to conventional protein kinases. It is an unusual bifunctional protein that contains an α-kinase domain fused to an ion channel. The TRPM7/ChaK1 channel has been characterized using electrophysiological techniques, and recent evidence suggests that it may play a key role in the regulation of magnesium homeostasis. However, little is known about its protein kinase activity. To characterize the kinase activity of TRPM7/ChaK1, we expressed the kinase catalytic domain in bacteria. ChaK1-cat is able to undergo autophosphorylation and to phosphorylate myelin basic protein and histone H3 on serine and threonine residues. The kinase is specific for ATP and cannot use GTP as a substrate. ChaK1-cat is insensitive to staurosporine (up to 0.1 mm) but can be inhibited by rottlerin. Because the kinase domain is physically linked to an ion channel, we investigated the effect of ions on ChaK1-cat activity. The kinase requires Mg2+ (optimum at 4-10 mm) or Mn2+ (optimum at 3-5 mm), with activity in the presence of Mn2+ being 2 orders of magnitude higher than in the presence of Mg2+. Zn2+ and Co2+ inhibited ChaK1-cat kinase activity. Ca2+ at concentrations up to 1 mm did not affect kinase activity. Considering intracellular ion concentrations, our results suggest that, among divalent metal ions, only Mg2+ can directly modulate TRPM7/ChaK1 kinase activity in vivo.
Influence of diapirs on the development of non-cylindrical arcuate fold-and-thrust belts: Results from analogue models of progressive arcs

espanolEn este articulo, se presentan modelos analogicos ideados para testar el papel de diapiros sobre el patron estructural de cinturones de pliegues y cabalgamientos en arcos progresivos. Para modelizar el arco progresivo, se usa un backstop cuyo grado de protrusion aumenta progresivamente. El paralelepipedo inicial esta formado por silicona y arena, con cilindros de silicona anadidos para simular los diapiros. Se hicieron varios modelos con distintos tamanos y distribucion de diapiros, para indagar en el modo de particion de la deformacion alrededor de estas heterogeneidades. El estilo de deformacion de los modelos esta caracterizado por cinturones de pliegues y cabalgamientos no cilindricos, divididos en bloques por fallas normales y de salto en direccion, que rotan independientemente. Al principio del experimento, se nuclean las estructuras sobre los diapiros. Cuando aumenta el acortamiento, su influencia disminuye con respecto a la protrusion del arco. EnglishIn this paper, we present analogue models built to test the diapir role on the along-strike segmentation of fold-and-thrust belts in progressive arcs. To model the progressive arc, we used a protruding backstop that deformed in map view while the experiments run. This backstop indented a parallelepiped formed by silicone at the bottom and sand, in which silicone cylinders were added to simulate diapirs. Various types of models with different size and distribution of the diapirs were made in order to investigate the strain partitioning modes around these heterogeneities. The deformation style of the models is characterized by a highly non-cylindrical arcuate fold-and-thrust belt with blocks bounded by normal or strike-slip faults that strongly rotated clockwise or anti-clockwise. The diapirs are key heterogeneities for the nucleation and linking of structures at the beginning of the experiment. When shortening proceed, their influence on the fold-and-thrust belt geometry diminished with respect to that of the backstop protrusion.
Performance Modeling and Optimization for Single- and Multi-Wall Carbon Nanotube Interconnects

Based on physical circuit models the performances of signal and power interconnects at the local, semi-global and global levels are modeled at 100degC. For local signal interconnects, replacing copper wires with a typical aspect ratio of 2 by thin SWNT interconnects can lower power dissipation by 50%. This would also improve their speed by up to 50% by the end of the ITRS. Copper wires and large diameter MWNTs offer the lowest resistance for power distribution in the first and second interconnect levels, respectively. SWNT-bundles and MWNTs can be used to lower the delay of signal interconnects in semi-global levels. MWNTs with diameters of 50 nm and 100 nm can potentially increase the bandwidth density of global interconnects by up to 50% and 100%, respectively.
Brain- and intestine-specific variants of reovirus serotype 3 strain dearing are selected during chronic infection of severe combined immunodeficient mice

Mutants of mammalian reoviruses, enteric double-stranded-RNA-containing viruses that spread systemically after primary replication in intestinal tissue, have been extensively studied as models of viral pathogenesis. While reovirus serotype 3 strain Dearing (T3D) causes acute encephalitis in newborn mice, adult severe combined immunodeficient (SCID) mice develop chronic infection with T3D, with some mice living more than 100 days after infection (B. L. Haller, M. L. Barkon, G. P. Vogler, and H. W. Virgin IV, J. Virol. 69:357-364, 1995). To determine whether organ-specific reovirus variants are selected during chronic infection, we characterized the pathogenetic properties of two variants of T3D isolated 87 days after intraperitoneal infection of adult SCID mice. A brain-specific variant (T3DvBr) (i) grew to a higher titer than T3D in SCID mouse brain (but not intestine) after intraperitoneal inoculation, (ii) killed adult SCID mice faster than T3D, and (iii) grew well in neonatal NIH Swiss [NIH(s)] mouse brain tissue after intramuscular but not peroral inoculation. An intestine-specific variant (T3DvInt) (i) grew to a higher titer than T3D in SCID mouse intestine (but not brain) after intraperitoneal inoculation, (ii) killed SCID mice with kinetics equivalent to those of T3D, (iii) was much less virulent than T3D in neonatal NIH(s) mice, (iv) grew better than T3D in intestines after intramuscular or peroral inoculation into neonatal NIH(s) mice, and (v) grew poorly in brain tissue of neonatal NIH(s) mice after intramuscular inoculation. During prolonged infection of SCID mice, organ-specific variants of T3D, which are more efficient than wild-type T3D at one specific stage in reovirus pathogenesis, are selected.
Document Retrieval with Unlimited Vocabulary

In this paper, we describe a classifier based retrieval scheme for efficiently and accurately retrieving relevant documents. We use SVM classifiers for word retrieval, and argue that the classifier based solutions can be superior to the OCR based solutions in many practical situations. We overcome the practical limitations of the classifier based solution in terms of limited vocabulary support, and availability of training data. In order to overcome these limitations, we design a one-shot learning scheme for dynamically synthesizing classifiers. Given a set of SVM classifiers, we appropriately join them to create novel classifiers. This extends the classifier based retrieval paradigm to an unlimited number of classes (words) present in a language. We validate our method on multiple datasets, and compare it with popular alternatives like OCR and word spotting. Even on a language like English, where OCRs have been fairly advanced, our method yields comparable or even superior results. Our results are significant since we do not use any language specific post-processing for obtaining this performance. For better accuracy of the retrieved list, we use query expansion. This also allows us to seamlessly adapt our solution to new fonts, styles and collections.
Dysregulated miR-361-5p/VEGF Axis in the Plasma and Endothelial Progenitor Cells of Patients with Coronary Artery Disease

Dysfunction and reduction of circulating endothelial progenitor cell (EPC) is correlated with the onset of cardiovascular disorders including coronary artery disease (CAD). VEGF is a known mitogen for EPC to migrate out of bone marrow to possess angiogenic activities, and the plasma levels of VEGF are inversely correlated to the progression of CAD. Circulating microRNAs (miRNAs) in patient body fluids have recently been considered to hold the potential of being novel disease biomarkers and drug targets. However, how miRNAs and VEGF cooperate to regulate CAD progression is still unclear. Through the small RNA sequencing (smRNA-seq), we deciphered the miRNome patterns of EPCs with different angiogenic activities, hypothesizing that miRNAs targeting VEGF must be more abundant in EPCs with lower angiogenic activities. Candidates of anti-VEGF miRNAs, including miR-361-5p and miR-484, were enriched in not only diseased EPCs but also the plasma of CAD patients. However, we found out only miR-361-5p, but not miR-484, was able to suppress VEGF expression and EPC activities. Reporter assays confirmed the direct binding and repression of miR-361-5p to the 3′-UTR of VEGF mRNA. Knock down of miR-361-5p not only restored VEGF levels and angiogenic activities of diseased EPCs in vitro, but further promoted blood flow recovery in ischemic limbs of mice. Collectively, we discovered a miR-361-5p/VEGF-dependent regulation that could help to develop new therapeutic modalities not only for ischemia-related diseases but also for tumor angiogenesis.
Plant Diversity Changes during the Postglacial in East Asia: Insights from Forest Refugia on Halla Volcano, Jeju Island

Understanding how past climate changes affected biodiversity is a key issue in contemporary ecology and conservation biology. These diversity changes are, however, difficult to reconstruct from paleoecological sources alone, because macrofossil and pollen records do not provide complete information about species assemblages. Ecologists therefore use information from modern analogues of past communities in order to get a better understanding of past diversity changes. Here we compare plant diversity, species traits and environment between late-glacial Abies, early-Holocene Quercus, and mid-Holocene warm-temperate Carpinus forest refugia on Jeju Island, Korea in order to provide insights into postglacial changes associated with their replacement. Based on detailed study of relict communities, we propose that the late-glacial open-canopy conifer forests in southern part of Korean Peninsula were rich in vascular plants, in particular of heliophilous herbs, whose dramatic decline was caused by the early Holocene invasion of dwarf bamboo into the understory of Quercus forests, followed by mid-Holocene expansion of strongly shading trees such as maple and hornbeam. This diversity loss was partly compensated in the Carpinus forests by an increase in shade-tolerant evergreen trees, shrubs and lianas. However, the pool of these species is much smaller than that of light-demanding herbs, and hence the total species richness is lower, both locally and in the whole area of the Carpinus and Quercus forests. The strongly shading tree species dominating in the hornbeam forests have higher leaf tissue N and P concentrations and smaller leaf dry matter content, which enhances litter decomposition and nutrient cycling and in turn favored the selection of highly competitive species in the shrub layer. This further reduced available light and caused almost complete disappearance of understory herbs, including dwarf bamboo.
Secrecy rate maximization of a miso channelwith multiple multi-antenna eavesdroppers via semidefinite programming

The advances of multi-antenna techniques has recently led to renewed interest in physical-layer secrecy, a meaningful topic that enables us to prevent eavesdroppers from retrieving information intended for a legitimate user through physical layer designs. This paper address a secrecy-rate maximization problem for the scenario of a multi-input single-output channel listened by multiple multi-antenna eavesdroppers; e.g., in downlink. This problem is nonconvex and has no analytical solution. Through a careful analysis and reformulation, we show that the secrecy-rate maximization problem has a convex equivalent in form of a semidefinite program (SDP). We also prove that the respective optimal transmit covariance generally can yield a rank-one structure, implying that transmit beamforming is secrecy-rate optimal in the considered scenario. Simulation results are also provided to illustrate that the optimal transmit design solved by our SDP approach can yield significantly improved secrecy rates than an existing closed-form design.
The NICT/ATR speech translation system for IWSLT 2008.

This paper describes the National Institute of Information and Communications Technology/Advanced Telecommunications Research Institute International (NICT/ATR) statistical machine translation (SMT) system used for the IWSLT 2008 evaluation campaign. We participated in the Chinese‐ English (Challenge Task), English‐Chinese (Challenge Task), Chinese‐English (BTEC Task), Chinese‐Spanish (BTEC Task), and Chinese‐English‐Spanish (PIVOT Task) translation tasks. In the English‐Chinese translation Challenge Task, we focused on exploring various factors for the English‐Chinese translation because the research on the translation of English‐Chinese is scarce compared to the opposite direction. In the Chinese‐English translation Challenge Task, we employed a novel clustering method, where training sentences similar to the development data in terms of the word error rate formed a cluster. In the pivot translation task, we integrated two strategies for pivot translation by linear interpolation.
Climate change: implications for montane mammals of the Great Basin

Climate change threatens biodiversity; in particular, species with narrow distributions and specific habitat requirements. The Great Basin provides an excellent model system to evaluate the effects of climate change on species with isolated distributions and specific habitat requirements. I have evaluated the McDonald and Brown (1992) model that examined the effects of climate change on montane mammals of the Great Basin based on its underlying assumptions and model predictions. I have modeled the distributions of twelve montane mammal species found in the Great Basin and identified potential local extinctions by using maximum entropy modeling (Maxent) for two emission scenarios of changing climate for the year 2050: a minimum (b2a) and a maximum (a2a). Overall, a majority of Great Basin mammal species examined are predicted to experience reductions in distribution ranging from approximately 2-64% for a minimum emission scenario (b2a) and 39-79% for a maximum emission scenario (a2a). In particular, there was agreement between my model predictions and the MacDonald and Brown (1992) model predictions for four local extinctions for a minimum emission scenario (b2a), and five local extinctions for a maximum emission scenario (a2a). Instances in which model predictions relative to species distributions and abundances are consistent might provide a basis on which conservationists can develop generalities about biotic responses to changing environmental conditions. By understanding what environmental factors influence species occurrence, we can infer how climate change is likely to affect biodiversity and their spatial distributions, possibly allowing us to better manage and conserve populations.
Apoptotic Damage of Pancreatic Ductal Epithelia by Alcohol and Its Rescue by an Antioxidant

Alcohol abuse is a major cause of pancreatitis. However alcohol toxicity has not been fully elucidated in the pancreas and little is known about the effect of alcohol on pancreatic ducts. We report the molecular mechanisms of ethanol-induced damage of pancreatic duct epithelial cells (PDEC). Ethanol treatment for 1, 4, and 24 h resulted in cell death in a dose-dependent manner. The ethanol-induced cell damage was mainly apoptosis due to generation of reactive oxygen species (ROS), depolarization of mitochondrial membrane potential (MMP), and activation of caspase-3 enzyme. The antioxidant N-acetylcysteine (NAC) attenuated these cellular responses and reduced cell death significantly, suggesting a critical role for ROS. Acetaldehyde, a metabolic product of alcohol dehydrogenase, induced significant cell death, depolarization of MMP, and caspase-3 activation as ethanol and this damage was also averted by NAC. Reverse transcription-polymerase chain reaction revealed the expression of several subtypes of alcohol dehydrogenase and acetaldehyde dehydrogenase. Nuclear magnetic resonance spectroscopy data confirmed the accumulation of acetaldehyde in ethanol-treated cells, suggesting that acetaldehyde formation can contribute to alcohol toxicity in PDEC. Finally, ethanol increased the leakage of PDEC monolayer which was again attenuated by NAC. In conclusion, ethanol induces apoptosis of PDEC and thereby may contribute to the development of alcohol-induced pancreatitis.
NR2F6 Expression Correlates with Pelvic Lymph Node Metastasis and Poor Prognosis in Early-Stage Cervical Cancer

Background: There is an abnormal expression of nuclear receptor subfamily 2 group F member 6 (NR2F6) in human cancers such as breast cancer, colon cancer, and acute myelogenous leukemia. However, its clinical significance in cervical cancer has not been established. We explored NR2F6 expression and its clinicopathological significance in early-stage cervical cancer. Methods: NR2F6 expression in cervical cancer cell lines and cervical cancer tissues was determined by Western blotting, real-time PCR, and immunochemistry (IHC). NR2F6 expression in 189 human early-stage cervical cancer tissue samples was evaluated using IHC. The relevance between NR2F6 expression and early-stage cervical cancer prognosis and clinicopathological features was determined. Results: There was marked NR2F6 mRNA and protein overexpression in the cervical cancer cells and clinical tissues compared with an immortalized squamous cell line and adjacent noncancerous cervical tissues, respectively. In the 189 cervical cancer samples, NR2F6 expression was positively related to International Federation of Gynecology and Obstetrics (FIGO) stage (p = 0.006), squamous cell carcinoma antigen (p = 0.006), vital status (p < 0.001), tumor recurrence (p = 0.001), chemotherapy (p = 0.039), and lymph node metastasis (p < 0.001). Overall and disease-free survival was shorter in patients with early-stage cervical cancer and higher NR2F6 levels than in patients with lower levels of NR2F6. Univariate and multivariate analysis determined that NR2F6 was an independent prognostic factor of survival in early-stage cervical cancer. Conclusions: Taken together, our findings suggest that high NR2F6 expression predicts pelvic lymph node metastasis, tumor recurrence and poor prognosis in early-stage cervical cancer. NR2F6 might be a novel prognostic biomarker and potential therapeutic target of cervical cancer.
A Lightning Mapping Array in Southern Ontario, Canada, and Uses for Severe Weather Nowcasting

Lightning Mapping Array (LMA) technology was developed at the New Mexico Institute of Mining and Technology to locate sources of impulsive very high frequency (VHF, typically ~63 MHz) radiation produced by lightning flashes in three spatial dimensions and time (Rison et al. 1999). Radiation arrival times are measured at a network of ground stations using an accurate time base provided by Global Positioning System receivers. Both cloud-to-ground and in-cloud lightning flashes are detected (i.e., ‘total lightning’).
Decision Making During Nuclear Power Plant Incidents—A New Approach to the Evaluation of Precursor Events

Renewed interest in precursor analysis has shown that the evaluation of near misses is an interdisciplinary effort, fundamental within the life of an organization for reducing operational risks and enabling accident prevention. The practice of precursor analysis has been a part of nuclear power plant regulation in the United States for over 25 years. During this time, the models used in the analysis have evolved from simple risk equations to quite complex probabilistic risk assessments. But, one item that has remained constant over this time is that the focus of the analysis has been on modeling the scenario using the risk model (regardless of the model sophistication) and then using the results of the model to determine the severity of the precursor incident. We believe that evaluating precursors in this fashion could be a shortcoming since decision making during the incident is not formally investigated. Consequently, we present the idea for an evaluation procedure that enables one to integrate current practice with the evaluation of decisions made during the precursor event. The methodology borrows from technologies both in the risk analysis and the decision analysis realms. We demonstrate this new methodology via an evaluation of a U.S. precursor incident. Specifically, the course of the incident is represented by the integration of a probabilistic risk assessment model (i.e., the risk analysis tool) with an influence diagram and the corresponding decision tree (i.e., the decision analysis tools). The results and insights from the application of this new methodology are discussed.
Fluoxetine after weight restoration in anorexia nervosa: a randomized controlled trial.

CONTEXT Antidepressant medication is frequently prescribed for patients with anorexia nervosa. OBJECTIVE To determine whether fluoxetine can promote recovery and prolong time-to-relapse among patients with anorexia nervosa following weight restoration. DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind, placebo-controlled trial. From January 2000 until May 2005, 93 patients with anorexia nervosa received intensive inpatient or day-program treatment at the New York State Psychiatric Institute or Toronto General Hospital. Participants regained weight to a minimum body mass index (calculated as weight in kilograms divided by the square of height in meters) of 19.0 and were then eligible to participate in the randomized phase of the trial. INTERVENTIONS Participants were randomly assigned to receive fluoxetine or placebo and were treated for up to 1 year as outpatients in double-blind fashion. All patients also received individual cognitive behavioral therapy. MAIN OUTCOME MEASURES The primary outcome measures were time-to-relapse and the proportion of patients successfully completing 1 year of treatment. RESULTS Forty-nine patients were assigned to fluoxetine and 44 to placebo. Similar percentages of patients assigned to fluoxetine and to placebo maintained a body mass index of at least 18.5 and remained in the study for 52 weeks (fluoxetine, 26.5%; placebo, 31.5%; P = .57). In a Cox proportional hazards analysis, with prerandomization body mass index, site, and diagnostic subtype as covariates, there was no significant difference between fluoxetine and placebo in time-to-relapse (hazard ratio, 1.12; 95% CI, 0.65-2.01; P = .64). CONCLUSIONS This study failed to demonstrate any benefit from fluoxetine in the treatment of patients with anorexia nervosa following weight restoration. Future efforts should focus on developing new models to understand the persistence of this illness and on exploring new psychological and pharmacological treatment approaches. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00288574.