gebhart/patrepeval huggingface dataset:
Obesity impairs cardiolipin-dependent mitophagy and therapeutic intercellular mitochondrial transfer ability of mesenchymal stem cells (2023)

Mesenchymal stem cell (MSC) transplantation alleviates metabolic defects in diseased recipient cells by intercellular mitochondrial transport (IMT). However, the effect of host metabolic conditions on IMT and thereby on the therapeutic efficacy of MSCs has largely remained unexplored. Here we found impaired mitophagy, and reduced IMT in MSCs derived from high-fat diet (HFD)-induced obese mouse (MSC-Ob). MSC-Ob failed to sequester their damaged mitochondria into LC3-dependent autophagosomes due to decrease in mitochondrial cardiolipin content, which we propose as a putative mitophagy receptor for LC3 in MSCs. Functionally, MSC-Ob exhibited diminished potential to rescue mitochondrial dysfunction and cell death in stress-induced airway epithelial cells. Pharmacological modulation of MSCs enhanced cardiolipin-dependent mitophagy and restored their IMT ability to airway epithelial cells. Therapeutically, these modulated MSCs attenuated features of allergic airway inflammation (AAI) in two independent mouse models by restoring healthy IMT. However, unmodulated MSC-Ob failed to do so. Notably, in human (h)MSCs, induced metabolic stress associated impaired cardiolipin-dependent mitophagy was restored upon pharmacological modulation. In summary, we have provided the first comprehensive molecular understanding of impaired mitophagy in obese-derived MSCs and highlight the importance of pharmacological modulation of these cells for therapeutic intervention. A MSCs obtained from (HFD)-induced obese mice (MSC-Ob) show underlying mitochondrial dysfunction with a concomitant decrease in cardiolipin content. These changes prevent LC3-cardiolipin interaction, thereby reducing dysfunctional mitochondria sequestration into LC3-autophagosomes and thus impaired mitophagy. The impaired mitophagy is associated with reduced intercellular mitochondrial transport (IMT) via tunneling nanotubes (TNTs) between MSC-Ob and epithelial cells in co-culture or in vivo. B Pyrroloquinoline quinone (PQQ) modulation in MSC-Ob restores mitochondrial health, cardiolipin content, and thereby sequestration of depolarized mitochondria into the autophagosomes to alleviate impaired mitophagy. Concomitantly, MSC-Ob shows restoration of mitochondrial health upon PQQ treatment (MSC-ObPQQ). During co-culture with epithelial cells or transplantation in vivo into the mice lungs, MSC-ObPQQ restores IMT and prevents epithelial cell death. C Upon transplantation in two independent allergic airway inflammatory mouse models, MSC-Ob failed to rescue the airway inflammation, hyperactivity, metabolic changes in epithelial cells. D PQQ modulated MSCs restored these metabolic defects and restored lung physiology and airway remodeling parameters.
Reducing the computational complexity for whole word models (2017)

In a previous study, we demonstrated the feasibility to build a competitive, greatly simplified, large vocabulary continuous speech recognition system with whole words as acoustic units. In that system, we model about 100,000 words directly using deep bi-directional LSTM RNNs. To alleviate the data sparsity problem for word models, we train the model on 125,000 hours of semi-supervised acoustic training data. The resulting model works very well as an end-to-end all-neural speech recognition model without the use of any language model removing the need to decode. However, the very large output layer increases the computational cost substantially. In this work we address this issue by adding TDNN (Time Delay Neural Network) layers that reduce the frame rate to 120ms for the output layer. The TDNN layers are interspersed with the LSTM layers, gradually reducing the frame rate from 10ms to 120ms. The new model reduces the computational cost by 60% while improving the word error rate by 6% relative. Compared to a traditional LVCSR system, the whole word speech recognizer uses about the same CPU cycles and can easily be parallelized across CPU cores or run on GPUs.
Using utility functions to control a distributed storage system (2008)

Provisioning, and later optimizing, a storage system involves an extensive set of trade-offs between system metrics, including purchase cost, performance, reliability, availability and power. Previous work has tried to simplify provisioning and tuning tasks by allowing a system administrator to specify goals for various storage metrics. While this helps by raising the level of specification from low-level mechanisms to high-level storage system metrics it does not permit trade-offs between those metrics. 
This dissertation goes beyond goal-based requirements by allowing the system administrator to use a utility function to specify his objectives. Using utility, both the costs and benefits of configuration and tuning decisions can be examined within a single framework. This permits a provisioning system to make automated trade-offs across system metrics, such as performance, data protection and power consumption. It also allows an automated optimisation system to properly balance the cost of data migration with its expected benefits. 
This work develops a prototype storage provisioning tool that fuses an administrator-specified utility function to generate cost-effective storage configurations. The tool is then used to provide examples of how utility can be used to balance competing objectives (e.g., performance and data protection) and to provide guidance in the presence of external constraints. A framework for using utility to evaluate data migration is also developed. This framework balances data migration costs (decreases to current system metrics) against the potential benefits by discounting future expected utility. Experiments show that, by looking at utility over time, it is possible to choose the migration speed as well as weigh alternate optimization choices to provide the proper balance of current and future levels of service.
Fine-Mapping, Gene Expression and Splicing Analysis of the Disease Associated LRRK2 Locus (2013)

Association studies have identified several signals at the LRRK2 locus for Parkinson's disease (PD), Crohn's disease (CD) and leprosy. However, little is known about the molecular mechanisms mediating these effects. To further characterize this locus, we fine-mapped the risk association in 5,802 PD and 5,556 controls using a dense genotyping array (ImmunoChip). Using samples from 134 post-mortem control adult human brains (UK Human Brain Expression Consortium), where up to ten brain regions were available per individual, we studied the regional variation, splicing and regulation of LRRK2. We found convincing evidence for a common variant PD association located outside of the LRRK2 protein coding region (rs117762348, A>G, P = 2.56×10(-8), case/control MAF 0.083/0.074, odds ratio 0.86 for the minor allele with 95% confidence interval [0.80-0.91]). We show that mRNA expression levels are highest in cortical regions and lowest in cerebellum. We find an exon quantitative trait locus (QTL) in brain samples that localizes to exons 32-33 and investigate the molecular basis of this eQTL using RNA-Seq data in n = 8 brain samples. The genotype underlying this eQTL is in strong linkage disequilibrium with the CD associated non-synonymous SNP rs3761863 (M2397T). We found two additional QTLs in liver and monocyte samples but none of these explained the common variant PD association at rs117762348. Our results characterize the LRRK2 locus, and highlight the importance and difficulties of fine-mapping and integration of multiple datasets to delineate pathogenic variants and thus develop an understanding of disease mechanisms.
Light-Weight Overlay Path Selection in a Peer-to-Peer Environment (2006)

Large-scale peer-to-peer systems span a wide range of Internet locations. Such diversity can be leveraged to build overlay "detours" to circumvent periods of poor performance on the default path. However, identifying which peers are "good" relay choices in support of such detours is challenging, if one is to avoid incurring an overhead that grows with the size of the peer- to-peer system. This paper proposes and investigates the Earliest Branching Rule (EBR) to perform such a selection. EBR builds on the Earliest Diverging Rule (EDR) that selects relay nodes whose AS path diverges from the default path at the earliest possible point, but calls for monitoring a much smaller number of paths. As a result, it has a much lower overhead. The paper explores the performance and overhead of EBR, and compares them to that of EDR. The results demonstrate that EBR succeeds in selecting good relay nodes with minimum control overhead. Hence, providing a practical solution for dynamically building good overlays in large peer-to-peer systems.
Gevoeligheid van Belgische Mycoplasma hyopneumoniae-isolaten voor antimicrobiële middelen (2007)

Van 21 Mycoplasma hyopneumoniae-isolaten die in Belgi verzameld werden tussen 2000 en 2002, werd de gevoeligheid bepaald voor 12 antimicrobile middelen die frequent worden gebruikt in de varkenshouderij. Hierbij werd gebruik gemaakt van een microdilutietechniek. Verworven resistentie tegen spectinomycine, oxytetracycline, doxycycline, gentamicine, florfenicol en tiamuline werd niet waargenomen. En isolaat was zowel resistent tegen lincomycine als tegen tilmicosine en tylosine, maar gevoelig voor alle andere geteste antimicrobile middelen. De minimale inhibitorische concentratie (MIC)-waarden van flumequine waren > 16 g/ml voor 5 isolaten, terwijl de MIC 50 2 g/ml bedroeg. De MIC-waarden voor enrofloxacine waren 0,5 g/ml voor deze 5 isolaten, terwijl de MIC 50 0,06 g/ml bedroeg.
First pass of an MR susceptibility contrast agent through normal and ischemic heart: Gradient‐recalled echo‐planar imaging (1993)

Gradient-recalled echo-planar magnetic resonance (MR) imaging was used to monitor the first pass of a magnetic susceptibility contrast agent through the heart of normal rats and rats subjected to 60-minute occlusion of the anterior branch of the left main coronary artery. Each animal (six normal and six ischemic) received four doses (0.05, 0.1, 0.15, and 0.2 mmol/kg) of Dy-DTPA-BMA [diethylenetriaminepentaacetic acid-bis(methylamide)] administered as a bolus volume of 1.0 mL/kg. In both normal and ischemic rats, signal intensity in nonischemic myocardium was reduced by the contrast agent in a dose-dependent manner. Signal intensity in the ischemic zone was reduced much less, so that at a contrast agent dose of 0.1 mmol/kg or greater the ischemic zone was clearly defined as a high-intensity zone on echo-planar images. Plots of the change in the apparent T2* relaxation rate (delta R2*) during the peak bolus effect versus injected dose were well fit by straight lines for normal, nonischemic, and ischemic myocardium but not for blood in the left ventricle. No difference was seen between myocardial response in normal animals and in nonischemic regions in animals with coronary artery occlusion. These findings suggest that the contrast agent-induced changes in tissue T2* are monoexponential and support the idea that data derived from contrast transit studies may be useful for calculation of myocardial blood flow.
CDK9-mediated transcription elongation is required for MYC addiction in hepatocellular carcinoma (2014)

One-year survival rates for newly diagnosed hepatocellular carcinoma (HCC) are <50%, and unresectable HCC carries a dismal prognosis owing to its aggressiveness and the undruggable nature of its main genetic drivers. By screening a custom library of shRNAs directed toward known drug targets in a genetically defined Myc-driven HCC model, we identified cyclin-dependent kinase 9 (Cdk9) as required for disease maintenance. Pharmacological or shRNA-mediated CDK9 inhibition led to robust anti-tumor effects that correlated with MYC expression levels and depended on the role that both CDK9 and MYC exert in transcription elongation. Our results establish CDK9 inhibition as a therapeutic strategy for MYC-overexpressing liver tumors and highlight the relevance of transcription elongation in the addiction of cancer cells to MYC.
Whole genome comparison ofAspergillus flavusandA. oryzae (2006)

Aspergillus flavus is a plant and animal pathogen that also produces the potent carcinogen aflatoxin. Aspergillus oryzae is a closely related species that has been used for centuries in the food fermentation industry and is Generally Regarded As Safe (GRAS). Whole genome sequences for these two fungi are now complete, providing us with the opportunity to examine any genomic differences that may explain the different ecological niches of these two fungi, and perhaps to identify pathogenicity factors in A. flavus. These two fungi are very similar in genome size and number of predicted genes. The estimated genome size (36·8 Mb) and predicted number of genes (12 197) for A. flavus is similar to that of A. oryzae (36·7 Mb and 12 079, respectively). These two fungi have significantly larger genomes than Aspergillus nidulans (30·1) and Aspergillus fumigatus (29·4). The A. flavus and A. oryzae genomes are enriched in genes for secondary metabolism, but do not differ greatly from one another in the predicted number of polyketide synthases, nonribosomal peptide synthases or the number of genes coding for cytochrome P450 enzymes. A micro-scale analysis of the two fungi did show differences in DNA correspondence between the two species and in the number of transposable elements. Each species has approximately 350 unique genes. The high degree of sequence similarity between the two fungi suggests that they may be ecotypes of the same species and that A. oryzae has resulted from the domestication of A. flavus.
javar: A prototype Java restructuring compiler (1997)

This paper describes the prototype restructuring compiler javar, which can be used to make implicit parallelism in a Java program explicit by means of multi-threading. Although the prototype does not provide a complete Java front-end (unicode escapes are not supported and only limited semantic analysis has been implemented) and relies completely on the identification of ‘implicit’ parallelism by means of annotations, we hope that the research tool still provides sufficient functionality to make the parallelization of Java programs less complex and less error-prone. © 1997 John Wiley & Sons, Ltd.
Hydrothermal catalytic conversion of oleic acid to heptadecane over Ni/ZrO2 (2023)

There is growing interest in the substitution of expensive noble metal catalysts with low-cost earth-abundant metals in applications targeting biofuels production from waste organic feedstocks. Here, nickel (Ni) catalysts supported on zirconium dioxide (ZrO2), both with and without copper (Cu) as a co-metal, were tested in hydrothermal reactions of unsaturated and saturated C18 fatty acids as models for waste oil feedstocks. In contrast to recent reports, this study showed no enhancement of nickel's activity for fatty acid conversion to alkane products when Cu was present. Ni/ZrO2 prepared by metal coprecipitation methods converted 100% of oleic acid with 25% selectivity to heptadecane after 5 h of reaction at 350 °C using methanol as a hydrogen donor source, increasing to 41% heptadecane after 20 h. Lower yields were observed with catalysts prepared by wet impregnation and using alternative hydrogen donor sources (glycerol, formic acid). Greater selectivity to heptadecane was also observed at higher temperatures (370 °C) and when the initial fatty acid had greater saturation. Longer term exposure to hydrothermal media led to metal sintering and catalyst deactivation. Findings support a path forward to the development of earth-abundant metal catalysts for the upgrading of waste organic feedstocks.
In vivo imaging through the entire thickness of human cornea by full-field optical coherence tomography (2018)

Despite obvious improvements in visualization of the in vivo cornea through the faster imaging speeds and higher axial resolutions, cellular imaging stays unresolvable task for OCT, as en face viewing with a high lateral resolution is required. The latter is possible with FFOCT, a method that relies on a camera, moderate numerical aperture (NA) objectives and an incoherent light source to provide en face images with a micrometer-level resolution. Recently, we for the first time demonstrated the ability of FFOCT to capture images from the in vivo human cornea1. In the current paper we present an extensive study of appearance of healthy in vivo human corneas under FFOCT examination. En face corneal images with a micrometer-level resolution were obtained from the three healthy subjects. For each subject it was possible to acquire images through the entire corneal depth and visualize the epithelium structures, Bowman’s layer, sub-basal nerve plexus (SNP) fibers, anterior, middle and posterior stroma, endothelial cells with nuclei. Dimensions and densities of the structures visible with FFOCT, are in agreement with those seen by other cornea imaging methods. Cellular-level details in the images obtained together with the relatively large field-of-view (FOV) and contactless way of imaging make this device a promising candidate for becoming a new tool in ophthalmological diagnostics.
Geometric Tiling for Reducing Power Consumption in Structured Matrix Operations (2006)

This work focuses on reducing power consumption while maintaining the efficiency and accuracy of matrix computations using both algorithmic and architectural means. We transform the algorithms, in adaptation to application specifics, to translate the matrix structures into power saving potential via geometric tiling. Instead of using blind tiling, we index and partition matrix elements according to the underlying geometry to claim a better estimate and control of numerical range within and across geometric tiles, which can then be exploited for power saving.
Scratch Testing of a Dental Restorative Material Based on Calcium Aluminate (2008)

To study the basic abrasive wear mechanisms of a new bioceramic dental restorative material scratch testing has been conducted. The material is a chemically bonded bioceramic with calcium aluminate as binder. It is intended to be used in small and medium sized posterior class I, II and V fillings. A spherical diamond tip scratched the surface under increasing load from O to 50 N. The scratch hardness was measured and the wear mechanisms were classified according to the scale suggested by Powers. For comparison a glass-ionomer cement and a polymer composite were also tested. The scratched surfaces were studied with light optical microscopy and scanning electron microscopy. The bioceramic material had a lower scratch hardness than that of the composite but higher than that of the glass-ionomer. Regarding the wear mechanisms, the bioceramic material showed a plastic deformation up to about 15 N and above cracking and flaking began. The composite material did not enter into a more severe wear until 35 N. The glass-ionomer cement was more unreliable and some samples broke completely already at low loads or showed extensive cracking.
Dynamic Resource Allocation Algorithm for mobile IPTV services in MBS (Multicast Broadcast Service) Zone (2007)

In this paper, we propose dynamic resource allocation algorithm for mobile IPTV services in MBS (Multicast Broadcast Service) zone. This algorithm utilizes dynamic resource allocation to decrease the blocking probability of multicast connections within the limited capacity of system. Based on this algorithm, we derive the multicast blocking probability as unicast traffic load and multicast traffic load increase. In order to evaluate the performance, we compare proposed algorithm against best effort and fixed bound resource allocation schemes. Numerical results show that the proposed scheme improves multicast blocking probability.
Nucleotide sequence and transcriptional analysis of the redD locus of Streptomyces coelicolor A3(2) (1990)

Previous genetic evidence suggested that the redD gene product might be involved in the regulation of undecylprodigiosin (Red) biosynthesis in Streptomyces coelicolor. The redD+ gene was subcloned on a 2.2-kilobase-pair restriction fragment from the S. coelicolor redCD region by complementation of S. coelicolor JF1 (redD42). The DNA sequence of the 2.2-kilobase-pair redD-complementing region was determined, and the redD coding sequence was identified by computer analysis and deletion subcloning. Transcription at the redD locus was analyzed by using in vivo promoter probing, high resolution S1 mapping, and in vitro runoff transcription. A face-to-face arrangement of promoters was deduced, in which the proposed redD promoter was opposed by a cluster of four other promoters for another unidentified open reading frame. In time course experiments, redD transcription preceded that at two biosynthetic loci, redE and redBF; transcription at the latter two loci was reduced in redD42 mutants. The putative redD polypeptide lacked any strong sequence similarities to other known proteins.
Neural Mechanisms That Make Perceptual Decisions Flexible (2022)

Neural mechanisms of perceptual decision making have been extensively studied in experimental settings that mimic stable environments with repeating stimuli, fixed rules, and payoffs. In contrast, we live in an ever-changing environment and have varying goals and behavioral demands. To accommodate variability, our brain flexibly adjusts decision-making processes depending on context. Here, we review a growing body of research that explores the neural mechanisms underlying this flexibility. We highlight diverse forms of context dependency in decision making implemented through a variety of neural computations. Context-dependent neural activity is observed in a distributed network of brain structures, including posterior parietal, sensory, motor, and subcortical regions, as well as the prefrontal areas classically implicated in cognitive control. We propose that investigating the distributed network underlying flexible decisions is key to advancing our understanding and discuss a path forward for experimental and theoretical investigations.
Anhydrous Magnesium Sulfate Mediated Solvent-Free Synthesis of Dihydropyrimidin-2(1H)-ones at Ambient Temperature (2007)

An anhydrous magnesium sulfate mediated solvent-free protocol is described for the synthesis of dihydropyrimidinones (Biginelli compounds) at ambient temperature.
Reflection of focused sound beams from curved surfaces. (1992)

The reflection of focused sound beams from surfaces with spherical curvature is investigated theoretically and experimentally. Theoretical predictions for the incident and reflected beams are based on the parabolic wave equation. A circular source with a uniform amplitude and quadratic phase distribution is assumed. Solutions for the reflected beam are derived for both pulsed and continuous sources. The experiments were performed in water with a 3.5-MHz source that has a nominal radius of 2.5 cm and focal length of 15 cm. Accurate measurements of the incident beam, particularly very near the source, were used to characterize the effective radius and focal length. Reflection from both convex and concave surfaces was investigated. The targets were made of nickel with radii of curvature that vary from 5 cm up to infinity (planar targets). Measurements of the reflected beam were obtained with a needle hydrophone that passed through a small hole in the center of the source. Agreement between theory and experiment is excellent, and the results suggest novel ways to measure surface curvature. [Work supported by the David and Lucile Packard Foundation, ONR, and NSF.]