gebhart/patrepeval huggingface dataset:
The HLA Region and Autoimmune Disease: Associations and Mechanisms of Action (2007)

The HLA region encodes several molecules that play key roles in the immune system. Strong association between the HLA region and autoimmune disease (AID) has been established for over fifty years. Association of components of the HLA class II encoded HLA-DRB1-DQA1-DQB1 haplotype has been detected with several AIDs, including rheumatoid arthritis, type 1 diabetes and Graves' disease. Molecules encoded by this region play a key role in exogenous antigen presentation to CD4+ Th cells, indicating the importance of this pathway in AID initiation and progression. Although other components of the HLA class I and III regions have also been investigated for association with AID, apart from the association of HLA-B*27 with ankylosing spondylitis, it has been difficult to determine additional susceptibility loci independent of the strong linkage disequilibrium (LD) with the HLA class II genes. Recent advances in the statistical analysis of LD and the recruitment of large AID datasets have allowed investigation of the HLA class I and III regions to be re-visited. Association of the HLA class I region, independent of known HLA class II effects, has now been detected for several AIDs, including strong association of HLA-B with type 1 diabetes and HLA-C with multiple sclerosis and Graves' disease. These results provide further evidence of a possible role for bacterial or viral infection and CD8+ T cells in AID onset. The advances being made in determining the primary associations within the HLA region and AIDs will not only increase our understanding of the mechanisms behind disease pathogenesis but may also aid in the development of novel therapeutic targets in the future.
State of the art--treatment of peripheral occlusive arterial disease (POAD) with drugs vs. vascular reconstruction or amputation. (1997)

Peripheral occlusive arterial disease (POAD) is a disease with a progressive course in about half of the patients affected. The Fontaine stage II and III have been treated not always successfully in the last decades with physical exercise, vasoactive substances (pentoxifyllin, naftidrofuryl, buflomedil) and with alprostadil. Recently methods of vascular surgery such as PTA, stent implantation and bypass operations are introduced in the treatment of Fontaine POAD stages III and IV, but these procedures are not recommended in patients younger than 50 years in order to delay amputation of a limb. The vasoactive substances are seen in a new light, because they improve processes of the microcirculation such as decreasing plasma viscosity, the raised plasma fibrinogen level and increasing the deformability of red blood cells and inhibiting platelet aggregation. According to a number of studies pentoxifylline and naftidrofuryl may delay the progression of arteriosclerosis. Therefore, a new concept of the treatment of POAD must be evaluated (1) resulting in a combination of vascular surgery and intermittent drug therapy with vasoactive agents, (2) leading to a decrease in the risk of amputation frequency and (3) reducing the treatment costs in spite of a higher frequency of the disease and a longer average life expectancy.
Estrogen and Androgen Protection of Human Neurons against Intracellular Amyloid 1-42 Toxicity through Heat Shock Protein 70 (2004)

Intracellular amyloidbeta peptide (iAbeta1-42) accumulates in the Alzheimer's disease brain before plaque and tangle formation (Gouras et al., 2000) and is extremely toxic to human neurons (Zhang et al., 2002). Here, we investigated whether androgen and estrogen could prevent iAbeta1-4) toxicity, because both these hormones have a wide range of neuroprotective actions. At physiological concentrations, 17-beta-estradiol, testosterone, and methyl testosterone reduce iAbeta1-42-induced cell death by 50% in neurons treated after the injection and by 80-90% in neurons treated 1 hr before the injection. The neuroprotective action of the hormones is mediated by receptors, because the estrogen receptor (ER) antagonist tamoxifen and the androgen receptor (AR) antagonist flutamide completely block the estrogen- and androgen-mediated neuroprotection, respectively. Transcriptional activity is required for the neuroprotective action, because dominant negative forms of the receptors that block the transcriptional activity of the ER and AR prevent estrogen- and androgen-mediated neuroprotection. Proteomics followed by Western blot analyses identified increased levels of heat shock protein 70 (Hsp70) in testosterone- and estrogen-treated human neurons. Comicroinjection of Hsp70 with the iAbeta1-42 blocks the toxicity of iAbeta1-42. We conclude that estrogen and androgens protect human neurons against iAbeta1-42 toxicity by increasing the levels of Hsp70 in the neurons.
Targeting Gallium to Cancer Cells through the Folate Receptor (2008)

The development of gallium(III) compounds as anti-cancer agents for both treatment and diagnosis is a rapidly developing field of research. Problems remain in exploring the full potential of gallium(III) as a safe and successful therapeutic agent or as an imaging agent. One of the major issues is that gallium(III) compounds have little tropism for cancer cells. We have combined the targeting properties of folic acid (FA) with long chain liquid polymer poly(ethylene glycol) (PEG) 'spacers’. This FA-PEG unit has been coupled to the gallium coordination complex of 1,4,7,10-tetraazacyclo-dodecane-N, N′, N′, N′′-tetraacetic acid (DOTA) through amide linkages for delivery into target cells overexpressing the folate receptor (FR). In vitro cytotoxicity assays were conducted against a multi-drug resistant ovarian cell line (A2780/AD) that overexpresses the FR and contrasted against a FR free Chinese hamster ovary (CHO) cell line. Results are rationalized taking into account stability studies conducted in RPMI 1640 media and HEPES buffer at pH 7.4.
Urinary Tract Infections in Females (1994)

Journal Article Urinary Tract Infections in Females Get access Calvin M. Kunin Calvin M. Kunin From the Department of Internal Medicine, The Ohio Stale University, Columbus, Ohio Reprints or correspondence: Dr. Calvin M. Kunin, Room M110 Starling Loving Hall, 320 West 10th Avenue, Columbus, Ohio 43210. Search for other works by this author on: Oxford Academic PubMed Google Scholar Clinical Infectious Diseases, Volume 18, Issue 1, January 1994, Pages 1–12, https://doi.org/10.1093/clinids/18.1.1 Published: 01 January 1994 Article history Received: 16 September 1993 Published: 01 January 1994
Interaction between glucocorticoid hormones, stress and psychostimulant drugs* (2002)

In this review we summarize data obtained from animal studies showing that glucocorticoid hormones have a facilitatory role on behavioural responses to psychostimulant drugs such as locomotor activity, self-administration and relapse. These behavioural effects of glucocorticoids involve an action on the meso-accumbens dopamine system, one of the major systems mediating the addictive properties of drugs of abuse. The effects of glucocorticoids in the nucleus accumbens are site-specific; these hormones modify dopamine transmission in only the shell of this nucleus without modifying it in the core. Studies with corticosteroid receptor antagonists suggest that the dopaminergic effects of these hormones depend mostly on glucocorticoid, not on mineralocorticoid receptors. These data suggest that an increase in glucocorticoid hormones, through an action on mesolimbic dopamine neurons, could increase vulnerability to drug abuse. We also discuss the implications of this finding with respect to the physiological role of glucocorticoids. It is proposed that an increase in glucocorticoids, by activating the reward pathway, could counteract the aversive effects of stress. During chronic stress, repeated increases in glucocorticoids and dopamine would result in sensitization of the reward system. This sensitized state, which can persist after the end of the stress, would render the subject more responsive to drugs of abuse and consequently more vulnerable to the development of addiction.
Channel allocation and downlink beamforming in an SDMA mobile radio system (2002)

On the downlink of an SDMA mobile radio system, co-channel interference has to be kept down by beamforming. In this paper two DOA-based beamforming approaches are presented minimizing array signal power while maintaining given signal-to-noise-and-interference ratios for all users. The linear approach is computationally cheap, so that it is suited for channel allocation as well, quickly evaluating the spatial separability of a specific mobile radio scenario. The nonlinear algorithm yields optimum results but only converges quickly, if provided with a good starting point. Therefore, its basic application is burst-to-burst updating of the beamformer.
Creation of “Humanized” Mice to Study Human Immunity (2008)

"Humanized" mice are a promising translational model for studying human hematopoiesis and immunity. Their utility has been enhanced by the development of new stocks of immunodeficient hosts, most notably mouse strains such as NOD-scid IL2rgamma(null) mice that lack the IL-2 receptor common gamma chain. These stocks of mice lack adaptive immune function, display multiple defects in innate immunity, and support heightened levels of human hematolymphoid engraftment. Humanized mice can support studies in many areas of immunology, including autoimmunity, transplantation, infectious diseases, and cancer. These models are particularly valuable in experimentation where there is no appropriate small animal model of the human disease, as in the case of certain viral infections. This unit details the creation of humanized mice by engraftment of immunodeficient mice with hematopoietic stem cells or peripheral blood mononuclear cells, provides methods for evaluating engraftment, and discusses considerations for choosing the appropriate model system to meet specific goals.
Calcium mass transfer in peritoneal dialysis patients using 2.5 mEq/l calcium dialysate. (1992)

Standard peritoneal dialysate has a relatively high calcium concentration of 3.5 mEq/l. Peritoneal dialysis patients thus gain calcium from the dialysate which contributes to the risk of hypercalcemia. Dialysate with 2.5 mEq/l calcium is now available. Theoretically, using dialysate with this calcium content, calcium transfer should be negative (from the patient into the dialysate) when the patient is hypercalcemic, and positive when the patient is normocalcemic or hypercalcemic. Thus, 2.5 mEq/l calcium dialysate may allow larger doses of calcium carbonate to be prescribed. We compared calcium mass transfer (CMT) in 17 stable peritoneal dialysis patients using 3.5 and 2.5 mEq/l calcium dialysate. A solution of 2.05 l, 1.5 g/dl dextrose was dwelled for 4 hours. Calcium was measured in the drained dialysate and serum (total and ionized). Mean CMT was 0.7 +/- 0.5 mEq/exchange using 3.5 mEq/l calcium dialysate and -0.9 +/- 0.9 mEq/exchange using 2.5 mEq/l calcium dialysate (p less than 0.0001). At the time of the CMT studies, the mean serum ionized calcium levels were identical for the two groups (2.6 mEq/l). CMT correlated inversely with serum total calcium, serum ionized calcium, and drained dialysate volume. During hypercalcemia calcium transfer was from the dialysate to the patient when 3.5 mEq/l calcium dialysate was used, but from the patient to the dialysate when 2.5 mEq/l calcium dialysate was used. We conclude that 2.5 mEq/l calcium dialysate is effective in removing calcium and will be helpful in preventing hypercalcemia when large doses of oral calcium compounds are prescribed as a phosphate binder.
Numerical investigation of the possibility of macroscopic turbulence in porous media: a direct numerical simulation study (2015)

Abstract When a turbulent flow in a porous medium is determined numerically, the crucial question is whether turbulence models should account only for turbulent structures restricted in size to the pore scale or whether the size of turbulent structures could exceed the pore scale. The latter would mean the existence of macroscopic turbulence in porous media, when turbulent eddies exceed the pore size. In order to determine the real size of turbulent structures in a porous medium, we simulated the turbulent flow by direct numerical simulation (DNS) calculations, thus avoiding turbulence modelling of any kind. With this study, which for the first time uses DNS calculations, we provide benchmark data for turbulent flow in porous media. Since perfect DNS calculations require the resolution of scales down to the Kolmogorov scale, often only approximate DNS solutions can be obtained, especially for high Reynolds numbers. This is accounted for by using and comparing two different DNS approaches, a finite volume method (FVM) with grid refinement towards the wall and a lattice Boltzmann method (LBM) with equal grid distribution. The solid matrix was simulated by a large number of rectangular bars arranged periodically. The number of bars in the solution domain with periodic boundary conditions was reduced systematically until a minimum size was found that does not suppress any large-scale turbulent structures. Two-point correlations, integral length scales and energy spectra were determined in order to answer the question of whether or not macroscopic turbulence can be found in porous media.
Biosynthesis of bacterial glycogen. Primary structure of Escherichia coli 1,4-alpha-D-glucan:1,4-alpha-D-glucan 6-alpha-D-(1, 4-alpha-D-glucano)-transferase as deduced from the nucleotide sequence of the glg B gene. (1986)

The nucleotide sequence of the glg B gene, coding for branching enzyme (EC 2.4.1.18), was elucidated. It consists of 2181 base pairs specifying a protein of 727 amino acids. The deduced amino acid sequence was consistent with the amino acid analysis that was obtained with the pure protein as well as with the molecular weight determined from sodium dodecyl sulfate-gel electrophoresis. The deduced amino acid sequence was also consistent with the amino-terminal amino acid sequence and the amino acid sequence analysis of various peptides obtained from CNBr degradation of purified branching enzyme.
Chiron: translating nanopore raw signal directly into nucleotide sequence using deep learning (2018)

Sequencing by translocating DNA fragments through an array of nanopores is a rapidly maturing technology that offers faster and cheaper sequencing than other approaches. However, accurately deciphering the DNA sequence from the noisy and complex electrical signal is challenging. Here, we report Chiron, the first deep learning model to achieve end-to-end basecalling and directly translate the raw signal to DNA sequence without the error-prone segmentation step. Trained with only a small set of 4,000 reads, we show that our model provides state-of-the-art basecalling accuracy, even on previously unseen species. Chiron achieves basecalling speeds of more than 2,000 bases per second using desktop computer graphics processing units.
Transmissible plasmids from Campylobacter jejuni (1981)

Tetracycline resistance in clinical isolates of Campylobacter jejuni was shown to be plasmid mediated. Intra- and interspecies transfers to C. fetus subsp. fetus were demonstrated. The frequency of transfer was increased by approximately 100-fold on a solid surface by using a plate- or filter-mating procedure, as compared with a liquid-mating method. Results of experiments in which cell-free filtrates were used to replace the donor strain in mating experiments tend to rule out bacteriophage-mediated transduction in the transfer of tetracycline resistance. The plasmid-transfer frequency was not affected when deoxyribonuclease was added to the agar used in the mating experiments, indicating that transformation was not involved. Four transmissible plasmids from different tetracycline-resistant strains of C. jejuni each had a molecular weight of 38 x 10(6). Transfer of these plasmids to Escherichia coli was not demonstrated.
Point-of-Care Testing for Infectious Diseases: Past, Present, and Future (2017)

Point-of-care (POC) diagnostics provide rapid actionable information for patient care at the time and site of an encounter with the health care system. The usual platform has been the lateral flow immunoassay. Recently, emerging molecular diagnostics have met requirements for speed, low cost, and ease of use for POC applications. A major driver for POC development is the ability to diagnose infectious diseases at sites with a limited infrastructure. The potential use in both wealthy and resource-limited settings has fueled an intense effort to build on existing technologies and to generate new technologies for the diagnosis of a broad spectrum of infectious diseases.
Sestrin2 is a leucine sensor for the mTORC1 pathway (2015)

Leucine is a proteogenic amino acid that also regulates many aspects of mammalian physiology, in large part by activating the mTOR complex 1 (mTORC1) protein kinase, a master growth controller. Amino acids signal to mTORC1 through the Rag guanosine triphosphatases (GTPases). Several factors regulate the Rags, including GATOR1, aGTPase-activating protein; GATOR2, a positive regulator of unknown function; and Sestrin2, a GATOR2-interacting protein that inhibits mTORC1 signaling. We find that leucine, but not arginine, disrupts the Sestrin2-GATOR2 interaction by binding to Sestrin2 with a dissociation constant of 20 micromolar, which is the leucine concentration that half-maximally activates mTORC1. The leucine-binding capacity of Sestrin2 is required for leucine to activate mTORC1 in cells. These results indicate that Sestrin2 is a leucine sensor for the mTORC1 pathway.
Phosphatidylcholine in the treatment of localized fat. (2003)

Phosphatidylcholine was initially used in emergencies and in the treatment of atheroma plaques in cardiac diseases. Recently, it has also been used in the treatment of localized fat deposits. We report on the authors' clinical experience of the use of 250 mg/ml phosphatidylcholine injections in the treatment of subcutaneous fat deposits, showing the clinical response and side-effects. Volunteers received phosphatidylcholine injections in several areas of localized fat deposits, with a minimum interval of one week and mean interval of 15 days between applications. Laboratory tests were performed during the period of the drug use. Clinical results reflect that phosphatidylcholine was efficacious in reducing the fatty pads in the treated areas, with few side effects. From the authors' point of view, the off-label use of phosphatidylcholine in the treatment of fatty pads and small areas of localized fat is safe, low cost, and effective.
Two-photon holography in 3-D photopolymer host-guest matrix: errata (2000)

: Correction to References. Commercial codes of the chemicals are added.
68Ga-DOTATOC Versus 68Ga-DOTATATE PET/CT in Functional Imaging of Neuroendocrine Tumors (2011)

(68)Ga-DOTATOC and (68)Ga-DOTATATE possess a comparable diagnostic accuracy for the detection of NET lesions, with (68)Ga-DOTATOC having a potential advantage. The approximately 10-fold higher affinity for the sst2 of (68)Ga-DOTATATE does not prove to be clinically relevant. Quite unexpectedly, SUVmax of (68)Ga-DOTATOC scans tended to be higher than their (68)Ga-DOTATATE counterparts.
Improving performance of spectral subtraction in speech recognition using a model for additive noise (1998)

Addresses the problem of speech recognition with signals corrupted by additive noise at moderate signal-to-noise ratio (SNR). A model for additive noise is presented and used to compute the uncertainty about the hidden clean signal so as to weight the estimation provided by spectral subtraction. Weighted dynamic time warping (DTW) and Viterbi (HMM) algorithms are tested, and the results show that weighting the information along the signal can substantially increase the performance of spectral subtraction, an easily implemented technique, even with a poor estimation for noise and without using any information about the speaker. It is also shown that the weighting procedure can reduce the error rate when cepstral mean normalization is also used to cancel the convolutional noise.
Difluoromethylornithine Plus Sulindac for the Prevention of Sporadic Colorectal Adenomas: A Randomized Placebo-Controlled, Double-Blind Trial (2008)

Preclinical studies of chemoprevention drugs given in combination at low doses show remarkable efficacy in preventing adenomas with little additional toxicities, suggesting a strategy to improve risk to benefit ratios for preventing recurrent adenomas. Three hundred seventy-five patients with history of resected (> or =3 mm) adenomas were randomly assigned to receive oral difluoromethylornithine (DFMO) 500 mg and sulindac 150 mg once daily or matched placebos for 36 months, stratified by use of low-dose aspirin (81 mg) at baseline and clinical site. Follow-up colonoscopy was done 3 years after randomization or off-study. Colorectal adenoma recurrence was compared among the groups with log-binomial regression. Comparing the outcome in patients receiving placebos to those receiving active intervention, (a) the recurrence of one or more adenomas was 41.1% and 12.3% (risk ratio, 0.30; 95% confidence interval, 0.18-0.49; P < 0.001); (b) 8.5% had one or more advanced adenomas, compared with 0.7% of patients (risk ratio, 0.085; 95% confidence interval, 0.011-0.65; P < 0.001); and (c) 17 (13.2%) patients had multiple adenomas (>1) at the final colonoscopy, compared with 1 (0.7%; risk ratio, 0.055; 0.0074-0.41; P < 0.001). Serious adverse events (grade > or =3) occurred in 8.2% of patients in the placebo group, compared with 11% in the active intervention group (P = 0.35). There was no significant difference in the proportion of patients reporting hearing changes from baseline. Recurrent adenomatous polyps can be markedly reduced by a combination of low oral doses of DFMO and sulindac and with few side effects.
Anaerobicity Prepares Saccharomyces cerevisiae Cells for Faster Adaptation to Osmotic Shock (2004)

Yeast cells adapt to hyperosmotic shock by accumulating glycerol and altering expression of hundreds of genes. This transcriptional response of Saccharomyces cerevisiae to osmotic shock encompasses genes whose products are implicated in protection from oxidative damage. We addressed the question of whether osmotic shock caused oxidative stress. Osmotic shock did not result in the generation of detectable levels of reactive oxygen species (ROS). To preclude any generation of ROS, osmotic shock treatments were performed in anaerobic cultures. Global gene expression response profiles were compared by employing a novel two-dimensional cluster analysis. The transcriptional profiles following osmotic shock under anaerobic and aerobic conditions were qualitatively very similar. In particular, it appeared that expression of the oxidative stress genes was stimulated upon osmotic shock even if there was no apparent need for their function. Interestingly, cells adapted to osmotic shock much more rapidly under anaerobiosis, and the signaling as well as the transcriptional response was clearly attenuated under these conditions. This more rapid adaptation is due to an enhanced glycerol production capacity in anaerobic cells, which is caused by the need for glycerol production in redox balancing. Artificially enhanced glycerol production led to an attenuated response even under aerobic conditions. These observations demonstrate the crucial role of glycerol accumulation and turgor recovery in determining the period of osmotic shock-induced signaling and the profile of cellular adaptation to osmotic shock.