gebhart/patrepeval huggingface dataset:
703. Liver-Directed Gene Therapy for Primary Hyperoxaluria Type 1 (2015)

Primary hyperoxaluria type 1 (PH1) is an inborn error of liver metabolism due to deficiency of peroxisomal enzyme alanine:glyoxylate-aminotransferase (AGT) which catalyzes the conversion of glyoxylate to glycine. In PH1 patients, glyoxylate cannot be converted into glycine and is oxidized to oxalate resulting in hyperoxaluria. The excess of oxalate causes deposition of insoluble calcium oxalate in the kidney and other tissues leading to nephrolithiasis, nephrocalcinosis, kidney failure, and systemic tissue damage. Combined liver/kidney transplantation is the only available therapeutic strategy for disease treatment. Gene therapy is an attractive option to provide a definitive cure for PH1. Towards this goal, we investigated helper-dependent adenoviral (HDAd) vectors for liver-directed gene therapy of PH1. We injected PH1 mice with an HDAd encoding AGT under the control of a liver-specific promoter and observed normalization of urinary oxalate at the doses of 5×10e12 and 1×10e13 vector particles (vp)/kg and partial correction with 1×10e12 vp/kg. Following challenge with Ethylene Glycol (EG), a precursor of glyoxylate, we observed reduced elevations of urinary oxalate in HDAd-injected mice compared to saline controls. Next, we hypothesized that overexpression of glyoxylate reductase/hydroxypyruvate reductase (GRHPR) or glutamate-pyruvate transaminase (GPT) results in reduction of hyperoxaluria in PH1 by steering glyoxylate towards glycolate synthesis or transamination, respectively. To test this hypothesis, we injected PH1 mice with HDAd vectors expressing GRHPR or GPT. Both vectors resulted in significant reduction of hyperoxaluria and co-injection of the two vectors resulted in long-term normalization of oxalate excretion. Therefore, metabolic diversion towards non-toxic metabolites has potential for treatment of hyperoxaluria and vector-mediated GRHPR and/or GPT overexpression may be an alternative or adjunctive strategy to enhance efficiency of gene replacement therapy for PH1. We have recently developed a minimally invasive method to improve the therapeutic index of HDAd based on balloon occlusion catheter to achieve preferential delivery of the vector to the liver (Brunetti-Pierri et al., 2009 and 2012). This method may permit in humans correction of PH1 using clinically relevant lower doses of HDAd. Based on risk:benefit assessment, PH1 is an attractive disease for clinical application of this method.
Positive and negative photopatterning of metal oxides on silicon via bipolar electrochemical deposition (2001)

Negative and positive microscale patterning of metal oxides is efficiently and rapidly carried out on flat Si(100) surfaces via a simple white light assisted bipolar electrochemical process.
Mode of action of psoralens, benzofurans, acridinons, and coumarins on the ionic currents in intact myelinated nerve fibres and its significance in demyelinating diseases. (1994)

The actions of psoralens, benzofurans, acridinons and coumarins on the ionic currents in intact myelinated nerve fibres were investigated. All 6 substances blocked the potassium currents in a time-dependent manner, producing so-called K+ transients. Only 5-methoxypsoralen is a largely selective blocker of predominantly the axolemmal potassium channels, which is the characteristic required by our previously proposed working hypothesis for the mechanism of potassium-channel blockers in demyelinating diseases, in particular multiple sclerosis. If the observed K+ transients were to arise by blocking of the potassium channels of the Schwann cell, that is, by the periaxonal accumulation of K+ and a resulting collapse of the electromotive driving force for potassium-ions, according to a modified version of our previous hypothesis the other substances tested could also have a beneficial effect on the impaired impulse conduction in demyelinated axons. In this case a large number of new potential drugs would be available for the symptomatic therapy of MS.
<title>Optical receiver module for very high bit rates</title> (1997)

A microoptical receiver module for very high bitrates was designed and realized. We employed well established silicon technologies for integrating the optical components of the microoptical system. For reducing the optical spot size on the photo diode due to the beam divergence of the transmission fiber a monolithically integrated silicon microlens was used. The microlenses were fabricated by melting of photoresist and transferring the preforms into the silicon substrate. We characterized the lenses by lateral shearing interferometry in transmission. The beam diameter on the photodetector (l/e<SUP>2</SUP>) could be reduced by about one order of magnitude to less than 10 micrometers . The sensitivity of the modules was about 0.5 A/W at 1310 nm and 0.6 A/W at 1550 nm.
Phosphorus Removal by Expanded Clay—Six Years of Pilot‐Scale Constructed Wetlands Experience (2010)

Constructed wetlands, which facilitate phosphorus removal via precipitation, adsorption, and biological assimilation, offer a promising appropriate technology for advanced treatment in wastewater treatment plants. Because adsorption and precipitation are pointed out as the major phosphorus-removal mechanisms, the selection of a medium with high phosphorus-sorption capacity is important to obtain a sustained phosphorus removal. The objective of this study was to evaluate two kinds of lightweight expanded clay aggregates (LWAs)--Filtralite NR and Filtralite MR (Maxit Group, Avelar, Portugal)--as substrates in constructed wetlands to improve phosphorus-removal performance. Laboratory experiments were performed to test the potential of the LWAs to remove phosphorus from a phosphate solution. The experimental data were well-fitted by both the Langmuir and Freundlich isotherm models. Pilot-scale investigations were carried out to evaluate the phosphorus removal under field conditions. Four subsurface constructed wetlands were operated since June 2002; two of them were planted with Phragmites australis, and the other two were unplanted. The beds were filled with the two kinds of LWAs. Total phosphorous and pH were monitored since 2003, at a mean hydraulic load of 50 +/- 4 L/(m2 x d), during 6 years. The inflow phosphorus concentration was in the range 4 to 13 mg/L. Under the conditions used, beds with Filtralite MR had better efficiency, and the bed with Filtralite MR planted with Phragmites australis provided a phosphorus effluent mean concentration of 0.7 +/- 0.2 mg/L, during the trial period. This study presents the first long-term pilot-scale data for constructed wetlands using LWAs.
hStorage-DB: Heterogeneity-aware Data Management to Exploit the Full Capability of Hybrid Storage Systems (2012)

As storage systems become increasingly heterogeneous and complex, it adds burdens on DBAs, causing suboptimal performance even after a lot of human efforts have been made. In addition, existing monitoring-based storage management by access pattern detections has difficulties to handle workloads that are highly dynamic and concurrent. To achieve high performance by best utilizing heterogeneous storage devices, we have designed and implemented a heterogeneity-aware software framework for DBMS storage management called hStorage-DB, where semantic information that is critical for storage I/O is identified and passed to the storage manager. According to the collected semantic information, requests are classified into different types. Each type is assigned a proper QoS policy supported by the underlying storage system, so that every request will be served with a suitable storage device. With hStorage-DB, we can well utilize semantic information that cannot be detected through data access monitoring but is particularly important for a hybrid storage system. To show the effectiveness of hStorage-DB, we have implemented a system prototype that consists of an I/O request classification enabled DBMS, and a hybrid storage system that is organized into a two-level caching hierarchy. Our performance evaluation shows that hStorage-DB can automatically make proper decisions for data allocation in different storage devices and make substantial performance improvements in a cost-efficient way.
Content-Based Analysis of Digital Video (2004)

Content-Based Analysis Of Digital Video focuses on fundamental issues underlying the development of content access mechanisms for digital video. It treats topics that are critical to successfully automating the video content extraction and retrieval processes, and includes coverage of: - Video parsing, - Video content indexing and representation, - Affective video content analysis. In this well illustrated book the author integrates related information currently scattered throughout the literature and combines it with new ideas into a unified theoretical approach to video content analysis. The material also suggests ideas for future research. Systems developers, researchers and students working in the area of content-based analysis and retrieval of video and multimedia in general will find this book invaluable
Evaluation of the antimicrobial activity of cationic polyethylenimines on dry surfaces (2008)

The antimicrobial activity of cationic N-dodecyl-N-methylpolyethylenimine (PEI+) against S. aureus, A. baumannii, and E. coli was evaluated when the polymer was applied as a coating to various surfaces using a paint-like procedure. Antimicrobial activity of PEI+ as a function of time was determined using an assay for long-term survival involving placement of single drops of various bacterial concentrations on dry surfaces. These data were compared with an assay method where bacteria were applied by spraying and surfaces were incubated overnight under agar. PEI+-coated surfaces were found to be highly bactericidal after 30 min when bacteria were sprayed onto surfaces. However, when bacteria were applied as single drops, PEI+-coated surfaces were less biocidal at short contact times particularly for A. baumannii and E. coli. The observations are explained in the context of the difference in drying time between drops deposited on uncoated surfaces and PEI+-coated surfaces and the sensitivity of bacterial survival to dehydration. These results demonstrate that PEI+-coated surfaces are not effectively biocidal for some types of bacteria under certain conditions and that the method of assaying bactericidal efficiency can greatly affect the results obtained.
Whisky in the Car? (2010)

Some might quip that Scotland already runs on the stuff. Now a scientist at Edinburgh Napier University has patented a process to turn the byproducts of Scotch whisky production—Scotland's biggest industry—into butanol to fuel cars.
The genetic analysis of cancer (1998)

During the past two decades an overwhelming amount of knowledge has been acquired on the molecular genetics of human cancer. It is now evident that cancer is essentially a genetic disease, arising from inherited and/or somatically acquired mutations at different genetic loci, and that tumourigenesis is a multistep process. Gene mapping studies of inherited cancer syndromes have resulted in the identification of many genes implicated in the initiation of tumours. Importantly, alterations of the same genes were also found to play a role in the development of common, non-familial tumours. The genes involved belong to distinct functional classes, and include proto-oncogenes and tumour suppressor genes, which are regulators of cellular growth and proliferation, cell adhesion and programmed cell death. Another class of cancer susceptibility genes consists of DNA repair genes, which are involved in maintaining genomic stability. In unravelling the genetic basis of cancer, the localization and identification of genes involved in tumourigenesis can be considered as the 'easy' part; determination of the normal physiological function of these genes and their precise role in tumourigenesis has proved to be much more difficult. In this review, we highlight some of the major breakthroughs in the field of cancer genetics, and discuss recent insights in the putative role of proto-oncogenes, tumour suppressor genes and DNA repair genes in the initiation and progression of cancer. Also, we point to some of the challenges to be faced in the coming years.
Au Nanoparticles Prepared in Ionic Liquid by Sputter-Deposition Technique : What Determines the Particle Size? (2013)

Sputter deposition of metals into a capture medium with extremely low vapor pressure is a simple and convenient method to generate the metal nanoparticles (NPs) without chemical reactions. By careful selection of the capture medium and its temperature, the size of synthesized NPs can be controlled. Sputtering conditions also play an important role in determining the size of NPs. We synthesized Au NPs in a standard ionic liquid, 1-butyl-3-methylimidazolium tetrafluoroborate by systematically varying the sputtering conditions. It is proved that the temperature of the target and applied voltages have a strong influence on the size of Au NPs, while the working distance between the target and the surface of the capture media, sputtering time, and discharge current have little or no influence. Lower temperatures of the ionic liquid and of the target and higher applied voltage are desired for generating size-controlled smaller NPs.
Structure-Based Design of Potent Retinoid X Receptor α Agonists (2004)

A series of tetrahydrobenzofuranyl and tetrahydrobenzothienyl propenoic acids that showed potent agonist activity against RXRalpha were synthesized via a structure-based design approach. Among the compounds studied, 46a,b showed not only very good potency against RXRalpha (K(i) = 6 nM) but was also found to be greater than 167-fold selective vs RARalpha (K(i) > 1000 nM). This compound profiled out as a full agonist in a cell-based transient transfection assay (EC(50) = 3 nM). The two antipodes were separated via chiral chromatography, and 46b was found to be 40-fold more potent than 46a. Interestingly, cocrystallization of 46a,b with the RXRalpha protein generated a liganded structure whereby the (S)-antipode was found in the binding pocket. Given orally in db/db mice or ZDF rats, 46a,b showed a significant glucose-lowering effect and an increase in liver mass. Triglycerides decreased significantly in db/db mice but increased in the ZDF rats. A dose-dependent decrease of nonesterified free fatty acids was seen in ZDF rats but not in db/db mice. These differences indicate a species specific effect of RXR agonists on lipid metabolism.
Transient Pressure Behavior off Commingled Reservoirs (1991)

Summary This paper presents a new general analytic formulation for pressure-transient behavior of commingled systems (layered reservoirs without crossflow). The formulation includes the effects of surface and downhole flow-rate variations and of wellbore storage resulting from the wellbore volume's location below the flow-rate measuring point (at any location in the wellbore, including the surface and sandface). The method can be applied to a variety of layered reservoirs. Each individual subzone (reservoir) in the system can be different, with different initial and outer-boundary conditions, and each zone can start to produce at a different time. The well completion for each layer can also be different. New Laplace-domain solutions are presented for partially penetrating slanted wells and partially penetrated wells with and without a gas cap. The solution for slanted wells is based on that of Cinco-Ley et al. but includes the correct effective wellbore radius for the case of an anisotropic formation. Solutions to a few selected commingled systems are also presented to explore the application of the formulation.
A Privacy-preserving Covid-19 Updatable Test Result and Vaccination Provenance based on Blockchain and Smart contract (2019)

It is undisputable fact that Coronavirus pandemic will go into the annals of history as one of the devastating plagues. From the healthcare perspective, a lot of efforts are underway geared towards testing, management and vaccination whereas industry and research communities explore innovative solutions. Quite a number of solutions have emerged zooming in on contact tracing, combating misinformation, data aggregation and analysis as well as test result certification with blockchain technology been the core. Aside the reliance on centralized architectures and use of permissioned/consortium blockchain, conspicuously missing in existing solutions based on blockchain is the work around the immutability feature of the technology given the fact that a person's test result is not static but dynamic. In this paper, we propose a solution using blockchain and smart contract that allows for state changes to be made by authorized entities. We leverage distributed storage technology using InterPlanetary File System (IPFS) for storage of user encrypted records and subsequent retrieval for verification purposes. We extend our solution by incorporating vaccination status to provide comprehensive source of information and show proof of concept. The full code of our proposed solution is made publicly available on GitHub.
Automatic detection of causal relations for Question Answering (2003)

Causation relations are a pervasive feature of human language. Despite this, the automatic acquisition of causal information in text has proved to be a difficult task in NLP. This paper provides a method for the automatic detection and extraction of causal relations. We also present an inductive learning approach to the automatic discovery of lexical and semantic constraints necessary in the disambiguation of causal relations that are then used in question answering. We devised a classification of causal questions and tested the procedure on a QA system.
Efficient Differentiation of Mouse Embryonic Stem Cells into Motor Neurons (2012)

Direct differentiation of embryonic stem (ES) cells into functional motor neurons represents a promising resource to study disease mechanisms, to screen new drug compounds, and to develop new therapies for motor neuron diseases such as spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS). Many current protocols use a combination of retinoic acid (RA) and sonic hedgehog (Shh) to differentiate mouse embryonic stem (mES) cells into motor neurons. However, the differentiation efficiency of mES cells into motor neurons has only met with moderate success. We have developed a two-step differentiation protocol that significantly improves the differentiation efficiency compared with currently established protocols. The first step is to enhance the neuralization process by adding Noggin and fibroblast growth factors (FGFs). Noggin is a bone morphogenetic protein (BMP) antagonist and is implicated in neural induction according to the default model of neurogenesis and results in the formation of anterior neural patterning. FGF signaling acts synergistically with Noggin in inducing neural tissue formation by promoting a posterior neural identity. In this step, mES cells were primed with Noggin, bFGF, and FGF-8 for two days to promote differentiation towards neural lineages. The second step is to induce motor neuron specification. Noggin/FGFs exposed mES cells were incubated with RA and a Shh agonist, Smoothened agonist (SAG), for another 5 days to facilitate motor neuron generation. To monitor the differentiation of mESs into motor neurons, we used an ES cell line derived from a transgenic mouse expressing eGFP under the control of the motor neuron specific promoter Hb9. Using this robust protocol, we achieved 51 ± 0.8% of differentiation efficiency (n = 3; p < 0.01, Student's t-test). Results from immunofluorescent staining showed that GFP+ cells express the motor neuron specific markers, Islet-1 and choline acetyltransferase (ChAT). Our two-step differentiation protocol provides an efficient way to differentiate mES cells into spinal motor neurons.
Digital sound synthesis by physical modelling (2002)

After recent advances in coding of natural speech and audio signals, the synthetic creation of musical sounds is also gaining importance. Various methods for waveform synthesis are currently used in digital instruments and software synthesizers. A family of new synthesis methods is based on physical models of vibrating structures (string, drum etc.) rather than on descriptions of the resulting waveforms. This article describes various approaches to digital sound synthesis in general and discusses physical modelling methods in particular. Physical models in the form of partial differential equations are presented. Then it is shown, how to derive discrete-time models which are suitable for real-time DSP implementation. Applications to computer music are given as examples.
On the onset of motion of sliding drops (2014)

In this article we numerically investigate the onset of motion of liquid drops in contact with a plane and homogeneous substrate with contact angle hysteresis. The drops are driven by a body force F = ρgV, where ρ is the density of the liquid, g is the acceleration of gravity, and V is the volume of the drop. We compare two protocols to vary the bond number Bo = λ(v)/λ(c) by changes of either the drop size λ(v) = V(1/3) or the capillary length λ(c) = (γ/ρg)(1/2) where γ is the interfacial tension, revealing that the transition between pinned and steady moving states can be either continuous or discontinuous. In a certain range both pinned and moving states can be found for a given bond number Bo, depending on the history of the control parameters g and V. Our calculations are extended to arbitrary combinations of static advancing and receding contact angles and provide a comprehensive picture of the depinning transition induced by a quasi-static variation of the control parameters. Finally, we demonstrate that the particular form of the contact line mobility in our model has an impact on the interfacial shape of steady moving drops.
A Simulation Times Model of Multi-core Simulation (2009)

Chip multi-processor (CMP) increases processor throughput by duplicating resources for many threads. Due to the main frequency of a single processor approaching to limit, CMP is becoming more and more popular. However, it is not well studied how to evaluate a new CMP design by simulation. This paper analyzes the possible organizations of cores on a CMP and then presents a mathematical model for the simulation times. It also provides a sampling policy used to reduce the simulation times. The sampling experiments show that the simulation time is 7.5 days under condition that the required confidence level is 95% and confidence interval is 4 when the benchmarks in SPEC CPU2000 are used. As for the simulation of CMPs, the simulation time is very short.
Effect of doping treatment on gas transport properties and on separation factors of polyaniline memebranes (1995)

Abstract Gas permeation experiments of H 2 , O 2 , CO 2 , N 2 , and CH 2 were carried out with freestanding films of the conjugated polymer polyaniline (PANi). At first annealed to remove residual solvent, PANi membranes were doped (i.e., protonated) in a strongly acidic medium (HCl 4M ), undoped in a basic medium (NH 4 OH 1 M ), and redoped in a slightly acidic medium (HCl 10 −2 M ). Protonation and deprotonation kinetics were studied by elementary analysis Gas permeation experiments were performed with the annealed, doped, undoped, and redoped PANi films. The gas transport mechanism was clearly influenced by the diffusivity factor and it obeyed a Fickian diffusion model. From the variations in permeability coefficients with the doping treatment, gases could be divided in two subgroups comprising H 2 , O 2 , and CO 2 on one hand and N 2 and CH 4 on the other. After the doping–undoping–redoping process, gas fluxes were increased by 15% for the smaller gases and were decreased by 45% for the larger gases. As a consequence gas separation factors were approximately doubled for a gas pair involving the two subgroups and these were unchanged for a gas pair involving only one subgroup. The highest O 2 /N 2 and CO 2 /CH 4 selectivity coefficients were, respectively, equal to 14 and 78. © 1995 John Wiley & Sons, Inc.