gebhart/patrepeval huggingface dataset:
Antigen-specific CD4+ T-cell help is required to activate a memory CD8+ T cell to a fully functional tumor killer cell. (2002)

Although the importance of CD4+ T-cell help for generation of an effective CD8+ effector cytotoxic T cell (CTL) response is well established, the role of T-cell help in the activation of memory T cells to become fully functional tumor killer cells is undefined. Using synthetic peptide immunizations corresponding to the major CTLs and T-helper epitopes of ovalbumin, adoptive transfers of ovalbumin-specific memory CTLs (mCTLs), and ovalbumin as the tumor-specific antigen in a mouse tumor model, we have determined that T help is essential for the activation of mCTLs to kill tumors. Our data show that T-helper cells specific for the tumor-associated antigen are required for the reactivation of mCTLs by antigen presented indirectly from tumor. In contrast, effector CTLs do not need T help to kill tumors. These results have implications for induction of tumor immunotherapy by immunization.
Capsule Design for Blue Light Therapy against Helicobacter pylori (2016)

A photo-medical capsule that emits blue light for Helicobacter pylori treatment was described in this paper. The system consists of modules for pH sensing and measuring, light-emitting diode driver circuit, radio communication and microcontroller, and power management. The system can differentiate locations by monitoring the pH values of the gastrointestinal tract, and turn on and off the blue light according to the preset range of pH values. Our experimental tests show that the capsule can operate in the effective light therapy mode for more than 32 minutes and the wireless communication module can reliably transmit the measured pH value to a receiver located outside the body.
INFLUENCE OF SODIUM NITRITE ON THE CARDIOVASCULAR SYSTEM AND ON RENAL ACTIVITY (1933)

The nitrites are chiefly used in the treatment of angina pectoris and related angiospastic disorders; nevertheless they have been and are being widely employed therapeutically for patients with arterial hypertension. In the present study it was desired to investigate the clinical effects of sodium nitrite on normal persons, on patients with primary arterial hypertension, with or without involvement of the kidneys, and on patients with certain other renal disorders. In addition to observations of the clinical state of the patient, cardiac rate and arterial blood pressure, determinations of the cardiac output were performed; and in particular, investigations were undertaken as to the nature of changes in the renal function as measured by the volume of urine, the urea clearance test of Van Slyke and the creatinine filtrate method of Rehberg. In view of the fact that the nitrites produce vasodilatation and often lower the arterial blood pressure, the effect on
DISPLAR: an accurate method for predicting DNA-binding sites on protein surfaces (2007)

Structural and physical properties of DNA provide important constraints on the binding sites formed on surfaces of DNA-targeting proteins. Characteristics of such binding sites may form the basis for predicting DNA-binding sites from the structures of proteins alone. Such an approach has been successfully developed for predicting protein-protein interface. Here this approach is adapted for predicting DNA-binding sites. We used a representative set of 264 protein-DNA complexes from the Protein Data Bank to analyze characteristics and to train and test a neural network predictor of DNA-binding sites. The input to the predictor consisted of PSI-blast sequence profiles and solvent accessibilities of each surface residue and 14 of its closest neighboring residues. Predicted DNA-contacting residues cover 60% of actual DNA-contacting residues and have an accuracy of 76%. This method significantly outperforms previous attempts of DNA-binding site predictions. Its application to the prion protein yielded a DNA-binding site that is consistent with recent NMR chemical shift perturbation data, suggesting that it can complement experimental techniques in characterizing protein-DNA interfaces.
A recurrent Vα17 / Vβ10 TCR-expressing T cell clone is involved in the pathogenicity of collagen-induced arthritis in DBA / 1 mice (1999)

Collagen-induced arthritis (CIA) is an experimental model that mimics clinical and histological features of rheumatoid arthritis. In this disease, a crucial role in initiating the pathological changes has been assigned to T lymphocytes expressing the Th1 phenotype. Aiming at identifying type II collagen (CII)-specific T cells involved in CIA, T cell clones were generated in vitro from the lymph nodes (LN) of CII-immunized DBA / 1 mice. In three independent experiments, we repeatedly isolated CD4(+) Th1 clones recognizing the immunodominant epitope in the CB11 fragment of bovine CII and expressing a unique alpha betaTCR produced by the rearrangement of Valpha17/Jalpha20 and Vbeta10/Dbeta1.1/Jbeta2.5 gene segments. By reverse transcriptase-PCR, we demonstrated the presence of mRNA transcripts specific for the beta complementary-determining region 3 of this clonotype in the LN of the majority (73%) of mice with CIA whereas it was never detected in control animals. When transferred to CII-immunized DBA/1 mice, this recurrent Th1 clone augmented the incidence, aggravated significantly the clinical signs of CIA and greatly enhanced the anti-CII antibody response. Altogether, these results provide evidence that a CD4(+) Th1 clone belonging to the public arm of the response toward the immunodominant epitope of CII is involved in the cascade of events leading to CIA.
PTEN--Coupling Tumor Suppression to Stem Cells? (2001)

Mutations in the tumor suppressor protein PTEN are found in many different tumors. As
 Penninger and Woodgett
 discuss in their Perspective, new findings implicate PTEN in the control of neuronal cell size and in the proliferation and self-renewal of neuronal stem cells (
 Groszer
 et al .). This surprising finding may yield both research and therapeutic benefits.
BC-box protein domain-related mechanism for VHL protein degradation (2013)

The tumor suppressor VHL (von Hippel-Lindau) protein is a substrate receptor for Ubiquitin Cullin Ring Ligase complexes (CRLs), containing a BC-box domain that associates to the adaptor Elongin B/C. VHL targets hypoxia-inducible factor 1α to proteasome-dependent degradation. Gam1 is an adenoviral protein, which also possesses a BC-box domain that interacts with the host Elongin B/C, thereby acting as a viral substrate receptor. Gam1 associates with both Cullin2 and Cullin5 to form CRL complexes targeting the host protein SUMO enzyme SAE1 for proteasomal degradation. We show that Gam1 protein expression induces VHL protein degradation leading to hypoxia-inducible factor 1α stabilization and induction of its downstream targets. We also characterize the CRL-dependent mechanism that drives VHL protein degradation via proteasome. Interestingly, expression of Suppressor of Cytokine Signaling (SOCS) domain-containing viral proteins and cellular BC-box proteins leads to VHL protein degradation, in a SOCS domain-containing manner. Our work underscores the exquisite ability of viral domains to uncover new regulatory mechanisms by hijacking key cellular proteins.
Charged Derivatives for Peptide Sequencing Using a Magnetic Sector Instrument (2003)

Peptides are sequenced using a magnetic sector tandem mass spectrometer by analyzing the product ions resulting from high-energy collisions between the peptide precursor ion and an inert gas (1). These collisions result in product ion spectra with features specific to high-energy collision-induced dissociation (CID). Ideally, the product ion pattern will be sufficient to sequence the peptide analyte. For some peptides, however, the fragmentation pattern will not be amenable to complete interpretation, and further measures must be taken to improve the results. One such measure that has been found to improve the interpretability of CID spectra is derivatization of the N-terminus of the peptide with a fixed-charge bearing group (2–4). Section 1.1. summarizes the salient features of the high-energy CID spectra of peptides and describes the rationale behind the best use of N-terminal charged derivatives. Several examples are shown in which charged derivatives improve the interpretability of CID spectra. Section 1.2. discusses synthetic schemes for attaching a charged group to a peptide N-terminus, and Sections 2. and 3. describe the synthesis of trimethylammoniumacetyl (TMAA)-peptide derivatives.
Mature T cells of autoimmune lpr/lpr mice have a defect in antigen-stimulated suicide. (1993)

Antigen receptor-stimulated cell death of developing, immature T cells plays an important role in shaping the repertoire of antigens to which mature T cells will respond, but a role for receptor-stimulated death in controlling responses of mature T cells is controversial. Mutant lpr/lpr mice exhibit an autoimmune syndrome similar to systemic lupus erythematosus. Here we demonstrate that these mice have a defect in antigen-stimulated suicide of activated T cells in mature CD4+ and CD8+ T cell compartments. The defective suicide pathway is evident when the T cells are stimulated with antigen on antigen-presenting cells or with immobilized anti-CD3 in the absence of antigen-presenting cells. These studies, in concert with the work of others, suggest that antigen-stimulated death of mature cells may be important both in establishing peripheral tolerance and in limiting inflammation during normal immune responses.
Effective Octane And Efficiency Advantages Of Direct Injection Alcohol Engines (2008)

Ethanol is receiving great interest as an alternative fuel. Methanol is another alcohol fuel that could serve as a replacement for gasoline. Although it is currently receiving much less attention, it has the potential to play an important role. Like ethanol, methanol also has the advantage of being a liquid fuel and it can be produced from gasification of a variety of feedstocks using well established thermal chemical technology. These feedstocks include coal, natural gas, biomass and various types of waste. This paper discusses the high effective octane number and efficiency advantages of methanol and ethanol when used in direct injection engines. Octane number represents the resistance of a spark ignition engine to knock (unwanted detonation which can damage the engine). The high intrinsic octane numbers of ethanol and methanol are well known. However, a much greater effective octane number can be effectively realized through the knock resistance provided by the high level of vaporization cooling that occurs when methanol or ethanol is directly injected into the engine cylinders. A computational model is used in this paper to determine the knock resistance and effective octane number of these alcohol fuels when they are directly injected. The model indicates that the effective octane numbers are around 160 for ethanol and 180 for methanol. The high compression ratio, high degree of turbocharging and aggressive engine downsizing enabled by the high effective octane number of methanol could provide an efficiency gain of 30 –35 % (for combined city-highway driving) relative to conventional port fueled gasoline engines. An additional gain of around 10 % can be obtained by using reforming of methanol to enable ultra lean operation at low loads. The combination of these gains could thus potentially provide an efficiency gain of 40–45 % for direct injection methanol engines. This efficiency gain is significantly greater than the typical 25–30 % gain of turbocharged diesel engines. 3I.
Obesity-Dependent Metabolic Signatures Associated with Nonalcoholic Fatty Liver Disease Progression (2012)

Our understanding of the mechanisms by which nonalcoholic fatty liver disease (NAFLD) progresses from simple steatosis to steatohepatitis (NASH) is still very limited. Despite the growing number of studies linking the disease with altered serum metabolite levels, an obstacle to the development of metabolome-based NAFLD predictors has been the lack of large cohort data from biopsy-proven patients matched for key metabolic features such as obesity. We studied 467 biopsied individuals with normal liver histology (n=90) or diagnosed with NAFLD (steatosis, n=246; NASH, n=131), randomly divided into estimation (80% of all patients) and validation (20% of all patients) groups. Qualitative determinations of 540 serum metabolite variables were performed using ultraperformance liquid chromatography coupled to mass spectrometry (UPLC-MS). The metabolic profile was dependent on patient body-mass index (BMI), suggesting that the NAFLD pathogenesis mechanism may be quite different depending on an individual's level of obesity. A BMI-stratified multivariate model based on the NAFLD serum metabolic profile was used to separate patients with and without NASH. The area under the receiver operating characteristic curve was 0.87 in the estimation and 0.85 in the validation group. The cutoff (0.54) corresponding to maximum average diagnostic accuracy (0.82) predicted NASH with a sensitivity of 0.71 and a specificity of 0.92 (negative/positive predictive values=0.82/0.84). The present data, indicating that a BMI-dependent serum metabolic profile may be able to reliably distinguish NASH from steatosis patients, have significant implications for the development of NASH biomarkers and potential novel targets for therapeutic intervention.
Percutaneous Laser Disc Decompression (1992)

The authors present a new advance in the treatment of herniated disc disease using percutaneous Nd:YAG laser to vaporize a small portion of nucleus pulposus, thereby decompressing the disc. In vitro and in vivo animal data are presented. Three hundred seventy-seven magnetic resonance imaging or computed tomography scan-documented, herniated, nonsequestered lumbar intervertebral discs with corresponding clinical findings in 333 patients were so treated in an outpatient setting. The longest follow-up was 62 months, with a mean of 26 months. According to the Macnab criteria, there was a good to fair response in 261 patients (78.4%), and a poor response in 72 (21.6%); 166 patients experienced relief of pain during the procedure. One-third of repeat magnetic resonance imaging scans at 4-6 months postlaser treatment showed modest to moderate decrease of disc herniation.
Natural Killer T Cells: An Ecological Evolutionary Developmental Biology Perspective (2017)

Type I natural killer T (NKT) cells are innate-like T lymphocytes that recognize glycolipid antigens presented by the MHC class I-like protein CD1d. Agonistic activation of NKT cells leads to rapid pro-inflammatory and immune modulatory cytokine and chemokine responses. This property of NKT cells, in conjunction with their interactions with antigen-presenting cells, controls downstream innate and adaptive immune responses against cancers and infectious diseases, as well as in several inflammatory disorders. NKT cell properties are acquired during development in the thymus and by interactions with the host microbial consortium in the gut, the nature of which can be influenced by NKT cells. This latter property, together with the role of the host microbiota in cancer therapy, necessitates a new perspective. Hence, this review provides an initial approach to understanding NKT cells from an ecological evolutionary developmental biology (eco-evo-devo) perspective.
Nucleosides and nucleotides: natural bioactive substances in milk and colostrum (2000)

Nucleotides, nucleosides and nucleobases belong to the non-protein-nitrogen (NPN) fraction of milk. The largest amounts of ribonucleosides and ribonucleotides--ribose forms only were considered in this review--were measured directly after parturition in bovine milk and other ruminants as well as in the milk of humans. Generally, concentrations of most of the nucleos(t)ides tend to decrease gradually with advancing lactation period or nursing time. The species-specific pattern of these minor constituents in milk from different mammals is a remarkable property and confirms, at least, the specific physiological impact of these minor compounds in early life. The physiological capacity of these compounds in milk is given by the total potentially available nucleosides. The main dietary sources of nucleos(t)ides are nucleoproteins and nucleic acids which are converted in the course of intestinal digestion into nucleosides and nucleobases the preferred forms for absorption in the intestine. Thus, nucleosides and nucleobases are suggested to be the acting components of dietary and/or supplemented nucleic acid-related compounds in the gut. They are used by the body as exogenous trophochemical sources and can be important for optimal metabolic functions. Up to 15 % of the total daily need for a breast-fed infant was calculated to come from this dietary source. Concerning their biological role they not only act as metabolites but are also involved as bioactive substances in the regulation of body functions. Dietary nucleotides affect immune modulation, e.g. they enhance antibody responses of infants as shown by a study with more than 300 full-term healthy infants. Dietary nucleos(t)ides are found to contribute to iron absorption in the gut and to influence desaturation and elongation rates in fatty acid synthesis, in particular long-chain polyunsaturated fatty acids in early stages of life. The in vitro modulation of cell proliferation and apoptosis has been described by ribonucleosides, in particular by modified components using human cell culture models. Due to the bio- and trophochemical properties of dietary nucleos(t)ides, the European Commission has allowed the use of supplementation with specific ribonucleotides in the manufacture of infant and follow-on formula. From the technochemical point of view, the ribonucleoside pattern is influenced by thermal treatment of milk. In addition ribonucleosides are useful indicators for quantifying adulterations of milk and milk products.
Peroxisome proliferator-activated receptor gamma: A key regulator of adipogenesis and systemic insulin sensitivity. (1997)

The adipose cell is now known to play a complex role in energy homeostasis, storing energy and signaling to other tissues concerning the state of energy balance. The past several years have seen an explosive increase in our knowledge of the transcriptional basis of adipocyte differentiation. This review describes the role of peroxisome proliferator-activated receptor gamma in this process, and describes how other transcription factors may affect adipogenesis by modulating PPARgamma amount or activity. Furthermore, PPARgamma and other adipogenic transcription factors provide a focus for beginning to understand how various hormones and metabolites influence the development of this tissue in vivo.
Phylogenetic analysis of gag genes from 70 international HIV-1 isolates provides evidence for multiple genotypes (1993)

The genetic variation among HIV-1 isolates is more extensive than previously appreciated. At least seven distinct HIV-1 genotypes can be identified. Diversification, migration and establishment of local, temporal 'blooms' of particular variants may all occur concomitantly.
Wear of the polyethylene acetabular cup: The effect of head material, head diameter, and cup thickness studied with a hip simulator (1995)

Ultra-high molecular weight polyethylene acetabular cups backed by Ti-6Al-4V acetabular shells were articulated against Co-Cr-Mo alloy, ion-implanted Co-Cr-Mo alloy, and zirconia ceramic femoral heads in a hip joint simulator. Three tests of three million walking cycles each were run with five different head-cup combinations. The wear of the cups was measured gravimetrically at half a million cycle intervals. When the thickness of the cup was 10.9 mm, the mean wear rate was 0.14 mm/year against 28 mm dia. Co-Cr-Mo heads and 0.09 mm/year against ion-implanted 28 mm Co-Cr-Mo heads. When the thickness of the cup was 7.0 mm, the mean wear rate was 0.04 mm/year against 28 mm zirconia heads, but when the thickness was 10.9 mm, no wear occurred against 28 and 32 mm zirconia heads. The results indicate that a significant reduction in the wear of the polyethylene cup can be expected if zirconia is used as the head material, instead of Co-Cr-Mo alloy or ion-implanted Co-Cr-Mo alloy. The diameter of the zirconia head, 28 vs. 32 mm, seems unimportant, but a cup thickness much below 10 mm may be disadvantageous.
Reconstructing the human hematopoietic niche in immunodeficient mice: opportunities for studying primary multiple myeloma (2012)

Interactions within the hematopoietic niche in the BM microenvironment are essential for maintenance of the stem cell pool. In addition, this niche is thought to serve as a sanctuary site for malignant progenitors during chemotherapy. Therapy resistance induced by interactions with the BM microenvironment is a major drawback in the treatment of hematologic malignancies and bone-metastasizing solid tumors. To date, studying these interactions was hampered by the lack of adequate in vivo models that simulate the human situation. In the present study, we describe a unique human-mouse hybrid model that allows engraftment and outgrowth of normal and malignant hematopoietic progenitors by implementing a technology for generating a human bone environment. Using luciferase gene marking of patient-derived multiple myeloma cells and bioluminescent imaging, we were able to follow pMM cells outgrowth and to visualize the effect of treatment. Therapeutic interventions in this model resulted in equivalent drug responses as observed in the corresponding patients. This novel human-mouse hybrid model creates unprecedented opportunities to investigate species-specific microenvironmental influences on normal and malignant hematopoietic development, and to develop and personalize cancer treatment strategies.
Detection and Quantification of Methylation in DNA using Solid-State Nanopores (2013)

Epigenetic modifications in eukaryotic genomes occur primarily in the form of 5-methylcytosine (5 mC). These modifications are heavily involved in transcriptional repression, gene regulation, development and the progression of diseases including cancer. We report a new single-molecule assay for the detection of DNA methylation using solid-state nanopores. Methylation is detected by selectively labeling methylation sites with MBD1 (MBD-1x) proteins, the complex inducing a 3 fold increase in ionic blockage current relative to unmethylated DNA. Furthermore, the discrimination of methylated and unmethylated DNA is demonstrated in the presence of only a single bound protein, thereby giving a resolution of a single methylated CpG dinucleotide. The extent of methylation of a target molecule could also be coarsely quantified using this novel approach. This nanopore-based methylation sensitive assay circumvents the need for bisulfite conversion, fluorescent labeling, and PCR and could therefore prove very useful in studying the role of epigenetics in human disease.