gebhart/patrepeval huggingface dataset:
Huntington's disease: from pathology and genetics to potential therapies (2008)

Huntington's disease (HD) is a devastating autosomal dominant neurodegenerative disease caused by a CAG trinucleotide repeat expansion encoding an abnormally long polyglutamine tract in the huntingtin protein. Much has been learnt since the mutation was identified in 1993. We review the functions of wild-type huntingtin. Mutant huntingtin may cause toxicity via a range of different mechanisms. The primary consequence of the mutation is to confer a toxic gain of function on the mutant protein and this may be modified by certain normal activities that are impaired by the mutation. It is likely that the toxicity of mutant huntingtin is revealed after a series of cleavage events leading to the production of N-terminal huntingtin fragment(s) containing the expanded polyglutamine tract. Although aggregation of the mutant protein is a hallmark of the disease, the role of aggregation is complex and the arguments for protective roles of inclusions are discussed. Mutant huntingtin may mediate some of its toxicity in the nucleus by perturbing specific transcriptional pathways. HD may also inhibit mitochondrial function and proteasome activity. Importantly, not all of the effects of mutant huntingtin may be cell-autonomous, and it is possible that abnormalities in neighbouring neurons and glia may also have an impact on connected cells. It is likely that there is still much to learn about mutant huntingtin toxicity, and important insights have already come and may still come from chemical and genetic screens. Importantly, basic biological studies in HD have led to numerous potential therapeutic strategies.
Gene Expression and Isoform Variation Analysis using Affymetrix Exon Arrays (2008)

The Exon Array is a valuable tool that can be used to profile gene expression while providing important additional information regarding the types of gene isoforms that are expressed and variable. However, analysis of alternative splicing requires much more hands on effort and visualization of results in order to correctly interpret the data, and generally results in considerably higher false positive rates than expression analysis. One of the main sources of error in the MAQC dataset is variation in amplification efficiency across transcripts, most likely caused by joint effects of elevated GC content in the 5' ends of genes and reduced likelihood of random-primed first strand synthesis in the 3' ends of genes. These effects are currently not adequately corrected using existing statistical methods. We outline approaches to reduce such errors by filtering out potentially problematic data.
Mitochondrial Abnormalities in Alzheimer's Disease (2001)

The finding that oxidative damage, including that to nucleic acids, in Alzheimer's disease is primarily limited to the cytoplasm of susceptible neuronal populations suggests that mitochondrial abnormalities might be part of the spectrum of chronic oxidative stress of Alzheimer's disease. In this study, we used in situ hybridization to mitochondrial DNA (mtDNA), immunocytochemistry of cytochrome oxidase, and morphometry of electron micrographs of biopsy specimens to determine whether there are mitochondrial abnormalities in Alzheimer's disease and their relationship to oxidative damage marked by 8-hydroxyguanosine and nitrotyrosine. We found that the same neurons showing increased oxidative damage in Alzheimer's disease have a striking and significant increase in mtDNA and cytochrome oxidase. Surprisingly, much of the mtDNA and cytochrome oxidase is found in the neuronal cytoplasm and in the case of mtDNA, the vacuoles associated with lipofuscin. Morphometric analysis showed that mitochondria are significantly reduced in Alzheimer's disease. The relationship shown here between the site and extent of mitochondrial abnormalities and oxidative damage suggests an intimate and early association between these features in Alzheimer's disease.
A Diversified Generative Latent Variable Model for WiFi-SLAM (2017)

WiFi-SLAM aims to map WiFi signals within an unknown environment while simultaneously determining the location of a mobile device. This localization method has been extensively used in indoor, space, undersea, and underground environments. For the sake of accuracy, most methods label the signal readings against ground truth locations. However, this is impractical in large environments, where it is hard to collect and maintain the data. Some methods use latent variable models to generate latent-space locations of signal strength data, an advantage being that no prior labeling of signal strength readings and their physical locations is required. However, the generated latent variables cannot cover all wireless signal locations and WiFi-SLAM performance is significantly degraded. Here we propose the diversified generative latent variable model (DGLVM) to overcome these limitations. By building a positive-definite kernel function, a diversity-encouraging prior is introduced to render the generated latent variables non-overlapping, thus capturing more wireless signal measurements characteristics. The defined objective function is then solved by variational inference. Our experiments illustrate that the method performs WiFi localization more accurately than other label-free methods.
Matrix Effect in Quantitative LC/MS/MS Analyses of Biological Fluids:  A Method for Determination of Finasteride in Human Plasma at Picogram Per Milliliter Concentrations (1998)

Contrary to common perceptions, the reliability of quantitative assays for the determination of drugs in biological fluids using high-performance liquid chromatography with tandem mass spectrometric (LC/MS/MS) detection methods and the integrity of resulting pharmacokinetic data may not be absolute. Results may be adversely affected by lack of specificity and selectivity due to ion suppression caused by the sample matrix, interferences from metabolites, and "cross-talk" effects. In this paper, an example of the effect of the sample matrix on the determination of finasteride (I) in human plasma is presented. The ion suppression effect was studied by analyzing standards of I injected directly in mobile phase and comparing the response (peak areas) of I and an internal standard (II) with the peak areas of the same analytes spiked before extraction into five different plasma pools and standards spiked into the plasma extracts after extraction. The LC/MS/MS analyses were performed using a turbo ion spray interface (TISP) under chromatographic conditions, characterized by minimal (total run time of 2 min, capacity factors, k' of 1.50 and 1.75 for I and II, respectively) and high retention of the analytes (total run time 6 min, k' of 3.25 and 13.25 for I and II, respectively). The absolute peak areas for I and II in different plasmas were calculated, and the slopes and peak area ratios at all concentrations within the standard curve ranges were compared. When analyses were performed under conditions of minimal HPLC retention, the slope of the standard line for one set of plasma samples was substantially different (about 50% higher) from that from other plasma sources. The precision of the assay, expressed as coefficient of variation (CV, %) was also inadequate and varied from 15 to 30% at all concentrations within the standard curve range. When the same experiments were repeated using high HPLC retention, the slopes from different plasma sources were practically the same, and the CV was improved to 6-14%. By increasing k' and providing more chromatographic retention of analytes, the "unseen" interferences from plasma matrix were mostly separated from analytes, practically eliminating the ion suppression. In addition, by eliminating from plasma extracts a number of endogenous components through more selective extraction, the ion suppression was also minimized. The detailed data and the design of these experiments are presented. In addition, development of a highly sensitive assay for I in human plasma at low picogram per milliliter concentrations using LC/MS/MS with a heated nebulizer (HN) interface, instead of a TISP interface, is described. In this case, the effects of sample matrixes were not observed.
Effects of anti‐CD4 antibody treatment on lymphocyte subsets and stimulated tumor necrosis factor alpha production (1997)

T lymphocytes may play a central role in MS. The search for more targeted immunosuppression than is currently available has led to recent clinical trials of novel therapeutics. We studied 29 patients in a double-blind placebo-controlled trial of the chimeric monoclonal anti-CD4 antibody, cM-T412 (Centocor, Leiden, Holland) over a period of 18 months. Total and differential WBC counts; T, B, and natural killer lymphocytes; CD4+ and CD8+ T cells; CD4+ and CD4- naive cells; CD4+ and CD4- memory cells; interleukin-2 receptor- and major histocompatibility class II-positive T cells; serum tumor necrosis factor alpha (TNF-alpha); and PHA (phytohemagglutinin)/LPS (lipopolysaccharide)-stimulated whole blood TNF-alpha production were all examined serially in peripheral blood for the duration of the trial. In addition, for the first two treatment cycles, the above variables were tested 1 and 7 days after treatment. The results demonstrated significant long-term reductions, lasting up to 12 months after the last treatment cycle in all CD4+ subsets studied, but with a relative preservation of CD4+ memory cells as opposed to CD4+ naive cells. CD4- subsets also showed significant reductions after treatment but returned to baseline levels within 7 days. Monocyte counts were unaffected by cM-T412. Serum TNF-alpha and 2- and 18-hour PHA/LPS-stimulated TNF-alpha levels were also unchanged in the long term, although significant increases were observed in the 2- and 18-hour PHA/LPS-stimulated TNF-alpha levels the day immediately after treatment. There was no significant correlation between any of the immunologic markers studied and MRI measures of disease activity.
Click-Reagent Version of Sonogashira Coupling Protocol to Conjugated Fluorescent Alkynes with No or Reduced Homocoupling (2011)

A click-reagent version of the Sonogashira-coupling protocol has been developed. Diarylalkynes with donor and/or acceptor substituents have been synthesized via this protocol at moderate to excellent yields and with no or drastically reduced quantities of undesired homocoupled side products. This protocol is green-solvent compatible, air-insensitive, and effective under microwave conditions.
Intravenous ibuprofen: the first injectable product for the treatment of pain and fever (2010)

This paper reviews the current data on the use of the first approved intravenous ibuprofen product for the management of post-operative pain and fever in the United States. The management of acute and post-operative pain and fever with nonsteroidal anti-inflammatory agents (NSAIDs) is well documented. A search in Medline and International Pharmaceutical Abstracts of articles until the end of November 2009 and references of all citations were conducted. Available manufacturer data on file were also analyzed for this report. Several randomized controlled studies have demonstrated the opioid-sparing and analgesic effects of 400 and 800 mg doses of intravenous ibuprofen in a series of post-operative patient populations. Two recent studies have also noted the improvement in fever curves in critically ill and burn patients. These data, along with pharmacokinetic and pharmacologic properties, are explored in this review, which addresses the clinical utility of a parenteral NSAID in a hospitalized patient for post-operative pain management and fever reduction. Further data on intravenous ibuprofen are needed to define long-term utilization, management of acute pain, and use in special populations.
BCCIP Functions through p53 to Regulate the Expression of p21Waf1/Cip1 (2004)

The BCCIP protein is a BRCA2 and CDKN1A (p21(Waf1/Cip1)) Interacting Protein, which binds to a highly conserved domain of BRCA2, and a C-terminal domain of the CDK-inhibitor p21. We have previously reported that overexpression of BCCIP increases p21 mRNA and protein levels, and inhibits G(1) to S progression. In this report, we show that a partial shutdown of BCCIP expression by RNA interference reduces p21 levels and impairs G(1)/S checkpoint activation in response to ionizing radiation in HT1080 cells. We further show that the regulation of p21 expression by BCCIP is dependent on p53, and BCCIP regulates p53 transcription activity. These data provide a new mechanism by which BCCIP regulates p21 functions.
Cold injury to nerves is not due to ischaemia alone (1998)

The effect of cold on nerve fibre populations may be quite selective. Thus it was possible in the present study, with precise timing of a non-freezing cold nerve injury, to destroy myelinated fibres, but leave unmyelinated fibres intact. The aetiology of this cold-induced selective peripheral nerve pathology remains controversial, but recent evidence suggests that ischaemia plays an important role. To investigate this matter further, we have sought to determine whether ischaemia alone might account for such discrete nerve pathology, in a series of non-freezing cold injury paradigms. Compared with previous 'pure' ischaemic peripheral nerve models, notable differences were found in the present paradigms (early post-ischaemic luxury perfusion and severe nerve pathology), suggesting a multifactorial aetiology. Nonetheless a tight correlation was evident, with increasing duration of cold injury resulting in a progressively more severe reduction in post-cold nerve blood flow. Given these findings, we would propose that the pathological basis of non-freezing cold nerve injury is one of ischaemia, accelerated and enhanced by direct cold injury.
Realizations of focus invariance in optical–digital systems with wave-front coding (1997)

We report experimental verification of an extended depth of focus (EDF) system with near-diffraction-limited performance capabilities. Dowski and Cathey [Appl. Opt. 34, 1859-1866 (1995)] described the theory of this system in detail. We can create an EDF system by modifying a standard incoherent optical system with a special cubic phase plate placed at the aperture stop. We briefly review the theory and present the first optical experimental verification of this EDF system. The phase plate codes the wave front, producing a modified optical transfer function. Once the image is transformed into digital form, a signal-processing step decodes the image and produces the final in-focus image. We have produced a number of images from various optical systems using the phase plate, thus demonstrating the success of this EDF system.
Assessment of the carcinogenic N-nitrosodiethanolamine in tobacco products and tobacco smoke (1981)

A simple, reproducible gas chromatography-thermal energy analyzer (g.c.-TEA) method has been developed for the analysis of N-nitrosodiethanolainlne (NDELA) in tobacco and tobacco smoke. The extract of tobacco or the trapped particulates of tobacco smoke are chromatographed on silica gel. The NDELA containing fractions are concentrated, silylated and analyzed with a modified g.c.-TEA system. [ 14 C]NDELA serves as internal standard for the quantitative analysis. Experimental cigarettes made from tobaccos which were treated with the sucker growth inhibitor maleic hydrazide-diethanolamlne (MH-DELA) contained 115–420 p.p.b. of NDELA and their smoke contained 20–290 ng/cigarette, whereas hand-suckered tobacco and its smoke were free of NDELA. The tobacco of US smoking products contained 115–420 p.p.b. of NDELA and the mainstream smoke from such products yielded 10–68 ng/cigar or cigarette. NDELA levels in chewing tobacco ranged from 220–280 p.p.b. and in two commercial snuff products were 3,200 and 6,800 p.p.b. Although the five analyzed MH-DELA preparations contained between 0.6–1.9 p.p.m. NDELA it is evident that the major portion of NDELA in tobacco is formed from the DELA residue during the tobacco processing. Based on bioassay data from various laboratories which have shown that NDELA is a relatively strong car cinogen and based on the results of this study the use of MH-DELA for the cultivation of tobacco is questioned.
Effect of Injection Rate on Emulsion Flooding for a Canadian and a Venezuelan Crude Oil (1991)

Abstract Non-thermal heavy oil recovery methods are important, because many heavy oilreservoirs are unsuited for thermal methods. Emulsion flooding is one of themore promising non-thermal methods. In this experimental research, the effectof injection rate was examined for a Lloydminster crude and for a Morichalcrude oil. Two different emulsions were used, one being oil-in-water and theother one water-inoil-type. Displacement tests were carried out at the reservoir temperature in eachcase. In all tests, the core initially contained irreducible water. Emulsionslugs, 3 and 12% pore volume, were driven by brine. It was found that oil recovery was sensitive to injection rate, insofar asthe recovery varied from 67% to 57% in the case of the Morichal crude, and 59%to 51% in the case of the Lloydmlnster crude, depending on the rate. The floodrate would determine the extent of mobility ratio variation, which in turn, depends on the drop size, the type and rheology of the emulsion. Themechanistic features of the process are discussed. Introduction Considering the large resources of moderately heavy oils that cannot beexploited by thermal methods, it is important that viable non-thermal recoverymethods be developed. At present, at least 10 billion m3 of oils inthe 100–2000 mPa.s viscosity range occur in reservoirs in Canada, which are toothin, too deep, or marginal for other reasons, and thus unsuitable for theapplication of thermal methods, particularly steam injection. The non-thermalmethods tested In the laboratory and in the field include chemical floods, ofwhich alkaline flooding has received considerable attention. Based uponprevious work, emulsion floods may be more effective than alkaline floods. Theemulsions formed in situ in the latter case must contend with the rock.alkalireactions and the concomitant loss.
Role of spacer‐1 in the maturation and function of GlcNAc‐1‐phosphotransferase (2016)

The UDP-GlcNAc:lysosomal enzyme, N-acetylglucosamine-1-phosphotransferase (GlcNAc-1-PT), is an α<sub>2</sub> β<sub>2</sub> γ<sub>2</sub> hexamer that mediates the initial step in the formation of the mannose 6-phosphate targeting signal on newly synthesized lysosomal acid hydrolases. The GNPTAB gene encodes the 1256 amino acid long α/β precursor which is normally cleaved at K928 in the early Golgi by Site-1 protease (S1P). Here, we show that removal of the so-called 'spacer-1' domain (residues 86-322) results in cleavage almost exclusively at a second S1P consensus sequence located upstream of K928. In addition, GlcNAc-1-PT lacking spacer-1 exhibits enhanced phosphorylation of several non-lysosomal glycoproteins, while the phosphorylation of lysosomal acid hydrolases is not altered. In view of these effects on the maturation and function of GlcNAc-1-PT, we suggest renaming `spacer-1' the `regulatory-1' domain.
The Emmetropic and the Iseikonic Implant Lens: Computer Calculation of the Refractive Power and its Accuracy (1975)

The preoperative calculation of the power of a lens prosthesis and the resulting aniseikonia is given, as well as diagrams for reading the emmetropizing and the iseikonizing power of the lens. The consequences of an inaccuracy in the measurement of the dimensional and refractive properties of the eyes are calculated. It can be concluded that the main determinant for an accurate prediction of the power of the intraocular lens prosthesis is the axial length measurement. Since this measurement is carried out by means of ultrasound biometry, it is necessary to emphasize the adequate application of this technique. The problem as to whether an emmetropizing, or an iseikonizing lens should be implanted may be solved with the data supplied by the computer program. A flow chart for this program is given in an appendix.
A Bacterial Biofilm in a Hemodialysis System Assessment of Disinfection and Crossing of Endotoxin (1989)

Bacterial contamination may cause several adverse reactions, including pyrogenic consequences during hemodialysis. Some disorders, such as skin flush, pruritus, and other anaphylactoid reactions, are still unexplained. Bacterial bioproducts, i.e., endotoxins, are not removed by the highly porous membranes. Most studies have been done on the liquid phase of the dialysate. In this study, a biofilm has been made in a hemodialysis system, using an additional pump that continuously supplies several bioproducts: gram (+) or gram (-) bacteria, or extracted endotoxin. The attachment of bacteria and the role of the biofilm in different circumstances were determined: 1) A contaminated dialysate with 1,000 bacteria/ml i s necessary to set up a biofilm in the device. AAMI, Canadian, and French standards (200 bacteria/ml) are validated. 2) In the presence of non-endotoxic bacteria (Staphylococcus conhii, 6 hemolytic), and when solutions contaminated by endotoxin are used, the biofilm produces micellar forms of endotoxin that are not removed by the filter. 3) The efficiency of disinfectants differs. For example, the activities of sodium hypochlorite, formaldehyde, and hydrogen peroxide are lower in the biofilm than in static studies.
Multicast routing for multimedia communication (1993)

The authors present heuristics for multicast tree construction for communication that depends on: bounded end-to-end delay along the paths from source to each destination and minimum cost of the multicast tree, where edge cost and edge delay can be independent metrics. The problem of computing such a constrained multicast tree is NP-complete. It is shown that the heuristics demonstrate good average case behavior in terms of cost, as determined by simulations on a large number of graphs.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The genome of Geobacter bemidjiensis, exemplar for the subsurface clade of Geobacter species that predominate in Fe(III)-reducing subsurface environments. (2010)

Overall, the genome sequence of G. bemidjiensis offers surprising insights into the metabolism and physiology of Geobacteraceae in subsurface environments, compared to non-subsurface Geobacter species, such as the ability to disproportionate fumarate, more efficient oxidation of propionate, enhanced responses to oxygen stress, and dependence on the environment for a vitamin requirement. Therefore, an understanding of the activity of Geobacter species in the subsurface is more likely to benefit from studies of subsurface isolates such as G. bemidjiensis than from the non-subsurface model species studied so far.
Photonic crystals with controlled disorder (2011)

Photonic crystals are extremely sensitive to structural disorder even to the point of completely losing their functionalities. While, on one side, this can be detrimental for applications in traditional optical devices, on the other side, it gives also rise to very interesting new physics and maybe even new applications. We propose a route to introduce disorder in photonic crystals in a controlled way by creating a certain percentage of vacancies in the lattice. We show how the method works and what type of materials can be obtained this way. Also, we use this system to probe the role of disorder on the resulting transport properties from various points of view, including measurements of the transport and scattering mean free path and the diffusion constant.