Miracle-dz/UniFAR-FTUs huggingface dataset:
Intrarenal alterations of the angiotensin‐converting enzyme type 2/angiotensin 1–7 complex of the renin‐angiotensin system do not alter the course of malignant hypertension in Cyp1a1‐Ren‐2 transgenic rats

The role of the intrarenal renin‐angiotensin system (RAS) in the pathophysiology of malignant hypertension is not fully understood. Accumulating evidence indicates that the recently discovered vasodilator axis of the RAS, angiotensin‐converting enzyme (ACE) type 2 (ACE2)/angiotensin 1–7 (ANG 1–7), constitutes an endogenous system counterbalancing the hypertensiogenic axis, ACE/angiotensin II (ANG II)/AT1 receptor. This study aimed to evaluate the role of the intrarenal vasodilator RAS axis in the pathophysiology of ANG II‐dependent malignant hypertension in Cyp1a1‐Ren‐2 transgenic rats. ANG II‐dependent malignant hypertension was induced by 13 days′ dietary administration of indole‐3‐carbinol (I3C), a natural xenobiotic that activates the mouse renin gene in Cyp1a1‐Ren‐2 transgenic rats. It was hypothesized that pharmacologically‐induced inhibition of the ACE2/ANG 1–7 complex should aggravate, and activation of this axis should attenuate, the course of ANG II‐dependent malignant hypertension. Blood pressure (BP) was monitored by radiotelemetry. ACE2 inhibitor (DX 600, 0.2 μg/day) and ACE2 activator (DIZE, 1 mg/day) were administrated via osmotic minipumps. Even though ACE2 inhibitor significantly decreased and ACE2 activator increased intrarenal ANG 1–7 concentrations, the course of BP, as well as of albuminuria, cardiac hypertrophy and renal glomerular damage, were not altered. It was shown that intrarenal alterations in the ACE2/ANG 1–7 complex did not significantly modify the course of malignant hypertension in I3C‐induced Cyp1a1‐Ren‐2 transgenic rats. Thus, in our experimental setting alterations of this intrarenal vasodilator complex of the RAS do not significantly modify the form of malignant hypertension that clearly depends on the inappropriately increased activity of the ACE/ANG II/AT1 receptor axis.
α-Galactosidase Aggregation Is a Determinant of Pharmacological Chaperone Efficacy on Fabry Disease Mutants*

Background: Deficiency in α-galactosidase activity leads to Fabry disease, for which treatment employing pharmacological chaperones is being developed. Results: Aggregating α-galactosidase mutants are not responsive to the treatment with the pharmacological chaperone, 1-deoxygalactonojirimycin (DGJ). Conclusion: Aggregation of α-galactosidase is a decisive factor for DGJ efficiency. Significance: Combining pharmacological chaperones treatment with suppression of aggregation might be beneficial for future therapeutic strategy against Fabry disease. Fabry disease is a lysosomal storage disorder caused by loss of α-galactosidase function. More than 500 Fabry disease mutants have been identified, the majority of which are structurally destabilized. A therapeutic strategy under development for lysosomal storage diseases consists of using pharmacological chaperones to stabilize the structure of the mutant protein, thereby promoting lysosomal delivery over retrograde degradation. The substrate analog 1-deoxygalactonojirimycin (DGJ) has been shown to restore activity of mutant α-galactosidase and is currently in clinical trial for treatment of Fabry disease. However, only ∼65% of tested mutants respond to treatment in cultured patient fibroblasts, and the structural underpinnings of DGJ response remain poorly explained. Using computational modeling and cell culture experiments, we show that the DGJ response is negatively affected by protein aggregation of α-galactosidase mutants, revealing a qualitative difference between misfolding-associated and aggregation-associated loss of function. A scoring function combining predicted thermodynamic stability and intrinsic aggregation propensity of mutants captures well their aggregation behavior under overexpression in HeLa cells. Interestingly, the same classifier performs well on DGJ response data of patient-derived cultured lymphoblasts, showing that protein aggregation is an important determinant of chemical chaperone efficiency under endogenous expression levels as well. Our observations reinforce the idea that treatment of aggregation-associated loss of function observed for the more severe α-galactosidase mutants could be enhanced by combining pharmacological chaperone treatment with the suppression of mutant aggregation, e.g. via proteostatic regulator compounds that increase cellular chaperone expression.
Update Exchange With Mappings and Provenance

We consider systems for data sharing among heterogeneous peers related by a network of schema mappings. Each peer has a locally controlled and edited database instance, but wants to ask queries over related data from other peers as well. To achieve this, every peer’s updates propagate along the mappings to the other peers. However, this update exchange is filtered by trust conditions — expressing what data and sources a peer judges to be authoritative — which may cause a peer to reject another’s updates. In order to support such filtering, updates carry provenance information. These systems target scientific data sharing applications, and their general principles and architecture have been described in [21]. In this paper we present methods for realizing such systems. Specifically, we extend techniques from data integration, data exchange, and incremental view maintenance to propagate updates along mappings; we integrate a novel model for tracking data provenance, such that curators may filter updates based on trust conditions over this provenance; we discuss strategies for implementing our techniques in conjunction with an RDBMS; and we experimentally demonstrate the viability of our techniques in the Orchestra prototype system. This technical report supersedes the version which appeared in VLDB 2007 [17] and corrects certain technical claims regarding the semantics of our system (see errata in Sections [3.1] and [4.1.1]). Comments University of Pennsylvania Department of Computer and Information Science Technical Report No. MSCIS-07-26. This technical report is available at ScholarlyCommons: http://repository.upenn. edu/cis_reports/763 Update Exchange with Mappings and Provenance Technical Report MS-CIS-07-26 Department of Computer and Information Science University of Pennsylvania Todd J. Green Grigoris Karvounarakis Zachary G. Ives Val Tannen University of Pennsylvania {tjgreen,gkarvoun,zives,val}@cis.upenn. edu
Short-Term Treatment with Metformin Improves the Cardiovascular Risk Profile in First-Degree Relatives of Subjects with Type 2 Diabetes Mellitus who have a Metabolic Syndrome and Normal Glucose Tolerance without Changes in C-Reactive Protein or Fibrinogen

OBJECTIVE: To study if metformin, when administered to first-degree relatives of type 2 diabetes mellitus subjects who have metabolic syndrome and normal glucose tolerance, could improve the cardiovascular risk profile and reduce the levels of both C-reactive protein and fibrinogen. INTRODUCTION: Metabolic syndrome is associated with higher cardiovascular morbidity and mortality. Metformin has vasculo-protective effects even in normoglycemic subjects, and C-reactive protein and fibrinogen are considered markers of endothelial injury and inflammation. METHODS: Thirty-one non-diabetic first-degree relatives of type 2 diabetes mellitus subjects with metabolic syndrome were randomized (1:1) and double-blinded for placement in the placebo and metformin groups (850mg bid/±90days); 16 subjects were administered metformin (mean age 40.0 [33.5–50] years; 13 females) and 15 subjects were in the placebo group (mean age 37.0 [32–42] years; 9 females). Blood samples were collected at baseline and at the end of treatment for biochemical analyses, including an assessment of C-reactive protein and fibrinogen levels. RESULTS: Metformin improved the lipid profile and decreased fasting plasma glucose, systolic blood pressure, weight and body mass index without changing body composition. For those in the placebo we identified no changes in fibrinogen (282.2 [220.4–323.7] mg/L vs. 286.7 [249.6–295.1] mg/L; NS) or in C-reactive protein levels (0.68 [0.3–1.2] vs. 0.64 [0.3–1.0] mg/L; NS). The same was also observed for the levels of fibrinogen (303.9 [217.6–347.6] mg/L vs. 290.9 [251.5–301.9] mg/L; NS) and C-reactive proteins (0.78 [0.3–1.1] vs. 0.80 [0.4–0.9] mg/L; NS) in the metformin group. CONCLUSIONS: Metformin treatment in first-degree relatives of type 2 diabetes mellitus sufferers who have metabolic syndrome and normal glucose tolerance improved the cardiovascular risk profile without changing the levels of C-reactive protein and fibrinogen.
Lung Ultrasound Accuracy in Respiratory Distress Syndrome and Transient Tachypnea of the Newborn

Background: Lung ultrasound (LUS) is a promising technique for the diagnosis of neonatal respiratory diseases. Preliminary data has shown a good sensitivity and specificity of LUS in the diagnosis of respiratory distress syndrome (RDS) and transient tachypnea of the newborn (TTN). Objective: The aim of this study was to calculate the sensitivity, specificity, and negative (NPV) and positive predictive value (PPV) of LUS for RDS and TTN, using an external reader blinded to the clinical condition. Design and Methods: Neonates with respiratory distress had a LUS within 1 h of admission. Images were uploaded and sent to the external reader, who made the ultrasound diagnosis according to the appearance of the images. The final clinical diagnosis was made according to all the available data, except LUS data. Sensitivity, specificity, PPV, and NPV were calculated considering the final clinical diagnosis as the gold standard. Results: Fifty-nine neonates were studied (mean gestational age: 33 ± 4 weeks, mean birth weight: 2,145 ± 757 g). Twenty-three infants had a final diagnosis of RDS and 30 of TTN. LUS showed a sensitivity of 95.6% and specificity of 94.4%, with a PPV of 91.6% and a NPV of 97.1% for RDS, and a sensitivity of 93.3% and specificity of 96.5% with a PPV of 96.5% and a NPV of 93.4% for TTN. Conclusions: LUS showed high sensitivity and specificity in diagnosing RDS and TTN.
Segmentation of Clustered Nuclei With Shape Markers and Marking Function

We present a method to separate clustered nuclei from fluorescence microscopy cellular images, using shape markers and marking function in a watershed-like algorithm. Shape markers are extracted using an adaptive H-minima transform. A marking function based on the outer distance transform is introduced to accurately separate clustered nuclei. With synthetic images, we quantitatively demonstrate the performance of our method and provide comparisons with existing approaches. On mouse neuronal and Drosophila cellular images, we achieved 6%-7% improvement of segmentation accuracies over earlier methods.
On reliability, performance and Internet power consumption

With the increasing concern for global warming, the impact of Internet power consumption is gaining interest. In this paper, we explore, for the first time, the relationship between network robustness, performance and Internet power consumption. We first discuss such a relationship based on data collected from Internet sources. Next, we propose a modeling framework to size that relationship. It is shown that when designing networks based on power consumption, careful attention should be paid to the trade-off between energy consumption and network performance since doing otherwise would lead to unreliable networks.
GPEC: A Real-Time–Capable Tokamak Equilibrium Code

Abstract A new parallel equilibrium reconstruction code for tokamak plasmas—the Garching Parallel Equilibrium Code (GPEC)—is presented. GPEC allows one to compute equilibrium flux distributions sufficiently accurate to derive parameters for plasma control within 1 ms of run time, which enables real-time applications at the ASDEX Upgrade (AUG) experiment and other machines with a control cycle of at least this size. The underlying algorithms are based on the well-established off-line–analysis code CLISTE, following the classical concept of iteratively solving the Grad-Shafranov equation and feeding in diagnostic signals from the experiment. The new code adopts a hybrid parallelization scheme for computing the equilibrium flux distribution and extends the fast, shared-memory-parallel Poisson solver that we have described previously by a distributed computation of the individual Poisson problems corresponding to different basis functions. The code is based entirely on open-source software components and runs on standard server hardware and software environments. The real-time capability of GPEC is demonstrated by performing an off-line computation of a sequence of 1000 flux distributions that are taken from 1 s of operation of a typical AUG discharge and deriving the relevant control parameters with a time resolution of 1 ms. On the current server hardware, the new code allows employing a grid size of 32 × 64 zones for the spatial discretization and up to 15 basis functions. It takes into account about 90 diagnostic signals while using up to four equilibrium iterations and computing more than 20 plasma-control parameters, including the computationally expensive safety factor q on at least four different levels of the normalized flux.
Fuzzy interpolative reasoning via scale and move transformations

Interpolative reasoning does not only help reduce the complexity of fuzzy models but also makes inference in sparse rule-based systems possible. This paper presents an interpolative reasoning method by means of scale and move transformations. It can be used to interpolate fuzzy rules involving complex polygon, Gaussian or other bell-shaped fuzzy membership functions. The method works by first constructing a new inference rule via manipulating two given adjacent rules, and then by using scale and move transformations to convert the intermediate inference results into the final derived conclusions. This method has three advantages thanks to the proposed transformations: 1) it can handle interpolation of multiple antecedent variables with simple computation; 2) it guarantees the uniqueness as well as normality and convexity of the resulting interpolated fuzzy sets; and 3) it suggests a variety of definitions for representative values, providing a degree of freedom to meet different requirements. Comparative experimental studies are provided to demonstrate the potential of this method
Memantine reduces stealing behavior and impulsivity in kleptomania: a pilot study

Kleptomania is characterized by repetitive stealing behavior and has been associated with deleterious unwanted outcomes including forensic contact and increased rates of suicidal behavior. Very few trials have been conducted to investigate pharmacological treatment options for this neglected condition. Memantine is an NMDA-receptor antagonist that has shown promising results in the treatment of other behavioral addictions and substance addictions. Twelve individuals with kleptomania received memantine (10 mg/day, titrated to 30 mg/day maximum depending on clinical response and tolerability) over the course of 8 weeks, in an open-label trial. The effects of treatment were quantified using well-validated measures and select neurocognitive tests (last observation carried forward analyses). Kleptomania disease severity scores decreased across all measures considered, and 11 (91.7%) of the participants met the responder criteria (35% improvement on the primary effectiveness measure plus CGI improved/very much improved; significant improvements were also observed in terms of mood, anxiety, and disability scores along with a significant improvement in stop-signal response inhibition. Memantine was generally well tolerated. This study shows the effectiveness of memantine in reducing urges to shoplift and shoplifting behavior along with improving impulsivity, mood, anxiety, and psychosocial functioning.
Impulsive responding and the sustained attention to response task

Two studies investigated whether the sustained attention to response task (SART) is a better measure of impulsive responding than of sustained attention. Participants performed target detection tasks with global–local letter stimuli using one of two response formats: standard, responding to targets; and SART, withholding to targets. In the first experiment, performance in the SART changed rapidly over time, whereas performance in the standard format was stable over time. In the second experiment, performance in the SART was susceptible to global–local condensation tasks, a result previously found with highly impulsive individuals. Overall the results indicate that the SART is sensitive to impulsive responding.
Involvement of glycosaminoglycans in vesicular stomatitis virus G glycoprotein pseudotyped lentiviral vector‐mediated gene transfer into airway epithelial cells

The involvement of surface molecules in HIV‐1‐derived lentivirus (LV)‐mediated transduction of airway epithelial cells has not been studied so far. The present study aimed to evaluate the role of glycosaminoglycans (GAGs) in gene transfer mediated by a third generation vesicular stomatitis virus G glycoprotein (VSV‐G) pseudotyped LV vector in an in vitro model of polarized airway epithelial cells.
Neural-network-based segmentation of multi-modal medical images: a comparative and prospective study

This work presents an investigation of the potential of artificial neural networks for classification of registered magnetic resonance and X-ray computer tomography images of the human brain. First, topological and learning parameters are established experimentally. Second, the learning and generalization properties of the neural networks are compared to those of a classical maximum likelihood classifier and the superiority of the neural network approach is demonstrated when small training sets are utilized. Third, the generalization properties of the neural networks are utilized to develop an adaptive learning scheme able to overcome interslice intensity variations typical of MR images. This approach permits the segmentation of image volumes based on training sets selected on a single slice. Finally, the segmentation results obtained both with the artificial neural network and the maximum likelihood classifiers are compared to contours drawn manually.
Properties of Rice Husk Ash Silica Filled Prevulcanized Deproteinized Natural Rubber Latex Film

Silica extracted from rice husk ash (RHA-Si) was incorporated in deproteinized natural rubber (DPNR) latex compounds up to 20 phr. The cast films were prepared after the prevulcanization at 70°C for 2 hours. The effect of RHA-Si loading on swelling and tensile properties was investigated. Scanning electron microscope (SEM) was used to examine morphology of the prevulcanized films. Dynamic mechanical behaviors of filled prevulcanizates were studied using the dynamic mechanical analyzer (DMA). Two types of tests, namely, temperature sweep and strain sweep test were performed. Swelling test revealed the decrease in crosslink density with increasing RHA-Si loading more than 10 phr. Tensile strength and elongation at break decreased with increasing RHA-Si loading. Conversely, the presence of RHA-Si increased the modulus at 100% strain of the prevulcanized DPNR latex films. The poor filler-rubber distribution was evidenced by SEM image. The DMA results exhibited that storage modulus (G′) and damping factor (tanδ) increased with increasing RHA-Si loading. The narrow linear viscoelastic (LVE) region was noticed for prevulcnizates filled with high RHA-Si content. Glass transition temperature (Tg) of highly filled DPNR shift to low temperature.
An Information Theoretic Approach for Active and Effective Object Recognitions

This paper describes the strategy of optimal action selection for recognition of the observed object among those registered in the image data base from an information theoretic point of view. The goal is to reduce the number and effort of the recognition steps to reach the final decision of the recognition. We have chosen an information theoretic framework, motivated by the fact that sensored image data is not noiseless or ideal, nor can the effect of a certain action be completely determined in advance. We present the strategy of the recognition process, and then, the results of the feasibility study by experiments
A Forward Genetic Screen in Mice Identifies Sema3AK108N, which Binds to Neuropilin-1 but Cannot Signal

We have performed a three-generation, forward genetic screen to identify recessive mutations that affect the patterning of the peripheral nervous system. Using this assay, we identified Sema3AK108N, a novel loss-of-function allele of Sema3A. Class 3 semaphorins, which include Sema3A, are structurally conserved secreted proteins that play critical roles in the development and function of the nervous system. Sema3AK108N mutant mice phenocopy Sema3A-null mice, and Sema3AK108N protein fails to repel or collapse DRG axons in vitro. K108 is conserved among semaphorins, yet the loss-of-function effects associated with K108N are not the result of impaired expression, secretion, or binding of Sema3A to its high-affinity receptor Neuropilin-1 (Npn-1). Using in silico modeling and mutagenesis of other semaphorin family members, we predict that Sema3AK108N interacts poorly with the Npn-1/PlexA holoreceptor and, thus, interferes with its ability to signal at the growth cone. Therefore, through the use of a forward-genetic screen we have identified a novel allele of Sema3A that provides structural insight into the mechanism of Sema3A/Npn-1/PlexinA signaling.
The SCL/TAL1 Transcription Factor Represses the Stress Protein DDiT4/REDD1 in Human Hematopoietic Stem/Progenitor Cells

Hematopoietic stem/progenitor cells (HSPCs) are regulated through numerous molecular mechanisms that have not been interconnected. The transcription factor stem cell leukemia/T‐cell acute leukemia 1 (TAL1) controls human HSPC but its mechanism of action is not clarified. In this study, we show that knockdown (KD) or short‐term conditional over‐expression (OE) of TAL1 in human HSPC ex vivo, respectively, blocks and maintains hematopoietic potentials, affecting proliferation of human HSPC. Comparative gene expression analyses of TAL1/KD and TAL1/OE human HSPC revealed modifications of cell cycle regulators as well as previously described TAL1 target genes. Interestingly an inverse correlation between TAL1 and DNA damage‐induced transcript 4 (DDiT4/REDD1), an inhibitor of the mammalian target of rapamycin (mTOR) pathway, is uncovered. Low phosphorylation levels of mTOR target proteins in TAL1/KD HSPC confirmed an interplay between mTOR pathway and TAL1 in correlation with TAL1‐mediated effects of HSPC proliferation. Finally chromatin immunoprecipitation experiments performed in human HSPC showed that DDiT4 is a direct TAL1 target gene. Functional analyses showed that TAL1 represses DDiT4 expression in HSPCs. These results pinpoint DDiT4/REDD1 as a novel target gene regulated by TAL1 in human HSPC and establish for the first time a link between TAL1 and the mTOR pathway in human early hematopoietic cells. Stem Cells 2015;33:2268–2279