gebhart/patrepeval huggingface dataset:
Differential role of conserved and polymorphic residues of the binding groove of MHC class I molecules in the selection of peptides. (1993)

A set of 17-point mutants of H-2Kd was produced as secreted single-chain MHC molecules in the yeast Kluyveromyces lactis. Using a library of 648 synthetic peptides displaying the Kd-specific motif, the repertoire of peptides selected by each mutant was compared by a two-dimensional analysis technique. When conserved residues of Kd were substituted by an alanine, no binding was observed. When polymorphic residues were changed, two outcomes were observed. For residues 95, 99, and 116, no binding was observed, implying that the side chains of these residues contribute directly to the interaction with the peptide. When positions 9, 45, 97, and 114 were changed to alanine, the repertoire of selected peptides was enlarged. Position 97 was also changed to all four possible residues found in natural variants of mouse MHC class I molecules. The repertoires of selected peptides were analyzed and appeared to be included one in another. Their dimension was inversely correlated with the size of the side-chain of residue 97. We conclude that during the course of evolution some polymorphic residues may have been selected for their capacity to reduce the size of the peptide repertoire by preventing certain peptides from binding.
Chitinase effects on immune cell response in neuromyelitis optica and multiple sclerosis (2010)

Chitinases increased in the CSF from patients with NMO in response to IL-13. These enhanced levels could contribute to central nervous system inflammation by increasing immune cell migration across the BBB.
Inhibition of Heparin-induced Tau Filament Formation by Phenothiazines, Polyphenols, and Porphyrins (2004)

Tau protein is the major component of the intraneuronal filamentous inclusions that constitute defining neuropathological characteristics of Alzheimer's disease and other tauopathies. The discovery of tau gene mutations in familial forms of frontotemporal dementia has established that dysfunction of the tau protein is sufficient to cause neurodegeneration and dementia. Here we have tested 42 compounds belonging to nine different chemical classes for their ability to inhibit heparin-induced assembly of tau into filaments in vitro. Several phenothiazines (methylene blue, azure A, azure B, and quinacrine mustard), polyphenols (myricetin, epicatechin 5-gallate, gossypetin, and 2,3,4,2',4'-pentahydroxybenzophenone), and the porphyrin ferric dehydroporphyrin IX inhibited tau filament formation with IC(50) values in the low micromolar range as assessed by thioflavin S fluorescence, electron microscopy, and Sarkosyl insolubility. Disassembly of tau filaments was observed in the presence of the porphyrin phthalocyanine. Compounds that inhibited tau filament assembly were also found to inhibit the formation of Abeta fibrils. Biochemical analysis revealed the formation of soluble oligomeric tau in the presence of the inhibitory compounds, suggesting that this may be the mechanism by which tau filament formation is inhibited. The compounds investigated did not affect the ability of tau to interact with microtubules. Identification of small molecule inhibitors of heparin-induced assembly of tau will form a starting point for the development of mechanism-based therapies for the tauopathies.
Accelerated Neuronal Cell Recovery from Botulinum Neurotoxin Intoxication by Targeted Ubiquitination (2011)

Botulinum neurotoxin (BoNT), a Category A biodefense agent, delivers a protease to motor neuron cytosol that cleaves one or more soluble NSF attachment protein receptors (SNARE) proteins involved in neurotransmission to cause a flaccid paralysis. No antidotes exist to reverse symptoms of BoNT intoxication so severely affected patients require artificial respiration with prolonged intensive care. Time to recovery depends on toxin serotype because the intraneuronal persistence of the seven known BoNT serotypes varies widely from days to many months. Our therapeutic antidote strategy is to develop 'targeted F-box' (TFB) agents that target the different intraneuronal BoNT proteases for accelerated degradation by the ubiquitin proteasome system (UPS), thus promoting rapid recovery from all serotypes. These agents consist of a camelid heavy chain-only V(H) (VHH) domain specific for a BoNT protease fused to an F-box domain recognized by an intraneuronal E3-ligase. A fusion protein containing the 14 kDa anti-BoNT/A protease VHH, ALcB8, joined to a 15 kDa F-box domain region of TrCP (D5) was sufficient to cause increased ubiquitination and accelerate turnover of the targeted BoNT/A protease within neurons. Neuronal cells expressing this TFB, called D5-B8, were also substantially resistant to BoNT/A intoxication and recovered from intoxication at least 2.5 fold quicker than control neurons. Fusion of D5 to a VHH specific for BoNT/B protease (BLcB10) led to accelerated turnover of the targeted protease within neurons, thus demonstrating the modular nature of these therapeutic agents and suggesting that development of similar therapeutic agents specific to all botulinum serotypes should be readily achievable.
Regulatory T cell depletion enhances tumor specific CD8 T-cell responses, elicited by tumor antigen NY-ESO-1b in hepatocellular carcinoma patients, in vitro (2010)

Immunotherapy in hepatocellular carcinoma based on one or a few tumor specific antigens have shown limited antitumor efficacy. As a major suppressive factor in tumor immune response, better understanding of the role of regulatory T cells (Tregs) in hepatocellular carcinoma might be important for design of future immunotherapy-based clinical protocols. Tregs from 49 HCC patients and 40 controls were identified by flow cytometric analysis for the phenotype. Functional studies were performed by analyzing their inhibition to immune responses. Finally investigating whether elimination of Tregs was capable of enhancing the immunostimulatory efficacy of NY-ESO-1b peptides. In HCC peripheral blood and tumor-infiltrating lymphocytes, we found increased numbers of Tregs, which expressed high levels of HLA-DR, GITR and CD103. The prevalence of Tregs increased with during progressive stages in HCC patients. Moreover, the elimination of Treg cells followed by stimulating with NY-ESO-1b peptide significantly improved the anti-tumor cytotoxic T lymphocytes responses in HCC patients compared with stimulating with NY-ESO-1b peptide alone. The immune response efficiency increased from 37.5 to 62.5%. In conclusion, the increase in frequency of Treg cells might play a role in suppression of the immune response against HCC and for the design of immunotherapy the incorporation of the Treg cell depletion strategy will achieve potent anti-tumor immunity with therapeutic impact.
Unique Evidence for a RhIII to RhI Reduction by Deoxygenation of a Carbonate Moiety to CO2 by an Out-of-Sphere Phosphane (2001)

RhIII carbonate generated from either a peroxocarbonate complex [RhCl(CO4)(PR3)3] or [RhCl3(PR3)3] and Na2CO3, is reduced to RhI by deoxygenation of the carbonate moiety to CO2 by an out-of-sphere phosphane. The reaction takes place in mild conditions and is implied in the catalytic activity shown by RhI in the oxidation of styrene with O2/CO2 mixtures.
Adalimumab real-world dosage pattern and predictors of weekly dosing: Patients with Crohn's disease in the United States (2011)

The adalimumab weekly dosing rate in a real-world, managed-care setting is less than that in clinical trials and academic centres. Geographic region and not starting on 160-/80-mg induction therapy were significantly associated with weekly adalimumab use for patients with CD.
Pomegranate juice: a heart-healthy fruit juice (2008)

Pomegranate juice is a polyphenol-rich fruit juice with high antioxidant capacity. In limited studies in human and murine models, pomegranate juice has been shown to exert significant antiatherogenic, antioxidant, antihypertensive, and anti-inflammatory effects. Pomegranate juice significantly reduced atherosclerotic lesion areas in immune-deficient mice and intima media thickness in cardiac patients on medications. It also decreased lipid peroxidation in patients with type 2 diabetes, and systolic blood pressure and serum angiotensin converting enzyme activity in hypertensive patients. Thus, the potential cardioprotective benefits of pomegranate juice deserve further clinical investigation, and evidence to date suggests it may be prudent to include this fruit juice in a heart-healthy diet.
Encoding of high dynamic range video with a model of human cones (2006)

A recently developed quantitative model describing the dynamical response characteristics of primate cones is used for rendering high dynamic range (HDR) video. The model provides range compression, as well as luminance-dependent noise suppression. The steady-state (static) version of the model provides a global tone mapping algorithm for rendering HDR images. Both the static and dynamic cone models can be inverted, enabling expansion of the HDR images and video that were compressed with the cone model.
The molecular biology of chronic myeloid leukemia (2000)

Chronic myeloid leukemia (CML) is probably the most extensively studied human malignancy. The discovery of the Philadelphia (Ph) chromosome in 19601 as the first consistent chromosomal abnormality associated with a specific type of leukemia was a breakthrough in cancer biology. It took 13 years
Piperazinyl Oxazolidinone Antibacterial Agents Containing a Pyridine, Diazene, or Triazene Heteroaromatic Ring (1998)

Oxazolidinones are a novel class of synthetic antibacterial agents active against gram-positive organisms including methicillin-resistant Staphylococcus aureus as well as selected anaerobic organisms. Important representatives of this class include the morpholine derivative linezolid 2, which is currently in phase III clinical trials, and the piperazine derivative eperezolid 3. As part of an investigation of the structure-activity relationships of structurally related oxazolidinones, we have prepared and evaluated the antibacterial properties of a series of piperazinyl oxazolidinones in which the distal nitrogen of the piperazinyl ring is substituted with a six-membered heteroaromatic ring. Compounds having MIC values </= 2 microg/mL vs selected gram-positive pathogens were discovered among each of the pyridine, pyridazine, and pyrimidine structural classes. Among these the cyanopyridine 17, the pyridazines 25 and 26, and the pyrimidine 31 exhibited in vivo potency vs S. aureus comparable to that of linezolid.
Noninvasive Ptco2initial slope index and invasive Ptco2arterial index as diagnostic criterion of the state of peripheral circulation (1988)

Transcutaneous PO2 (PtcO2), PaO2, PtcO2 arterial index (ARI; PtcO2/PaO2), and the initial slope index (ISI; [delta PO2/min]/starting PtcO2) were measured in 42 healthy volunteers, 12 patients with stable circulation and respiratory insufficiency, and ten patients with insufficient peripheral circulation in cardiogenic shock in order to investigate whether ARI and ISI can be used to detect insufficient circulation. The ISI was measured by placing a PtcO2 electrode on the forearm and interrupting blood flow by inflating a cuff until the PtcO2 dropped to zero. After releasing the cuff pressure, the initial slope of the PtcO2 trace was determined in order to calculate the ISI. In the PtcO2 range between 40 and 100 torr, the ARI and ISI did not depend on the PtcO2 magnitude. In all groups, the ISI behaved similarly to the ARI. We conclude that the noninvasive ISI and invasive ARI are able to differentiate between stable and insufficient peripheral circulation (ISI less than 0.75, ARI less than 0.8; p less than .001).
In vivo comparison of 2′‐O‐methyl phosphorothioate and morpholino antisense oligonucleotides for Duchenne muscular dystrophy exon skipping (2009)

Abstract Background Antisense‐mediated exon skipping is a putative treatment for Duchenne muscular dystrophy (DMD). Using antisense oligonucleotides (AONs), the disrupted DMD reading frame is restored, allowing generation of partially functional dystrophin and conversion of a severe Duchenne into a milder Becker muscular dystrophy phenotype. In vivo studies are mainly performed using 2′‐ O ‐methyl phosphorothioate (2OMePS) or morpholino (PMO) AONs. These compounds were never directly compared. Methods mdx and humanized (h)DMD mice were injected intramuscularly and intravenously with short versus long 2OMePS and PMO for mouse exon 23 and human exons 44, 45, 46 and 51. Results Intramuscular injection showed that increasing the length of 2OMePS AONs enhanced skipping efficiencies of human exon 45, but decreased efficiency for mouse exon 23. Although PMO induced more mouse exon 23 skipping, PMO and 2OMePS were more comparable for human exons. After intravenous administration, exon skipping and novel protein was shown in the heart with both chemistries. Furthermore, PMO showed lower intramuscular concentrations with higher exon 23 skipping levels compared to 2OMePS, which may be due to sequestration in the extracellular matrix. Finally, two mismatches rendered 2OMePS but not PMO AONs nearly ineffective. Conclusions The results obtained in the present study indicate that increasing AON length improves skipping efficiency in some but not all cases. It is feasible to induce exon skipping and dystrophin restoration in the heart after injection of 2OMePS and unconjugated PMO. Furthermore, differences in efficiency between PMO and 2OMePS appear to be sequence and not chemistry dependent. Finally, the results indicate that PMOs may be less sequence specific than 2OMePS. Copyright © 2009 John Wiley &amp; Sons, Ltd.
An Optical Fiber Dropping Method for Residential Premises Employing Pipe Cable and Fiber Blowing (1997)

Article An Optical Fiber Dropping Method for Residential Premises Employing Pipe Cable and Fiber Blowing was published on October 1, 1997 in the journal Journal of Optical Communications (volume 18, issue 5).
Identification of Small Signalling Molecules Promoting Cardiac-Specific Differentiation of Mouse Embryonic Stem Cells (2006)

Identification of signalling cascades involved in cardiomyogenesis is crucial for optimising the generation of cardiomyocytes from embryonic stem cells (ES cells) (in vitro). We used a transgenic ES cell lineage expressing enhanced green fluorescent protein (EGFP) under the control of the alpha-myosin heavy chain (alpha-MHC) promoter (palphaMHC-EGFP) to investigate the effects of 33 small molecules interfering with several signalling cascades on cardiomyogenesis. Interestingly, the L-Type Ca2+ channel blocker Verapamil as well as Cyclosporin, an inhibitor of the protein phosphatase 2B, exerted the most striking pro-cardiomyogenic effect. Forskolin (adenylate cyclase stimulator) exerted the most striking anti-cardiomyogenic effect. The cardiomyogenic effect of Cyclosporin and Verapamil correlated with an expression of early cardiac markers Nkx2.5 and GATA4. Compared to the effects on late developmental stage embryoid bodies (EBs) stimulation of early developmental stage EBs (1-day old) with Verapamil or Cyclosporin for 48 h resulted in a potent cardiomyogenic effect. Accordingly, enhanced expression of alpha-MHC mRNA and EGFP mRNA was observed after stimulation of the early developmental stage EBs for 48 h. No expression of alpha-smooth muscle actin or platelet endothelial cell adhesion molecule-1 (PECM-1) as well as of neuronal genes (Nestin, Neurofilament H) has been observed demonstrating a preferentially pro-cardiomyogenic effect by both molecules.
High‐frequency conductance measurement of the skin surface hydration state of dry skin using a new probe studded with needle‐form electrodes (MT‐8C) (1996)

The MT-8C probe yielded conductance values slightly higher than those recorded with the flat surfaced probe attached to Skicon in measuring the hydration state of moderately dry skin surface such as atopic xerosis and senile xerosis. It seems to be comparable or more sensitive than the capacitance recording with the Corneometer. The recorded values obtained with the MT-8C probe showed more variations than the latter because of its higher sensitivity and much smaller contact area, that makes it difficult to touch to the same spots repeatedly. No such a difference was observed on severely dry skin and thickly scaly psoriatic lesions.
Bortezomib: Proteasome Inhibition as an Effective Anticancer Therapy (2005)

Inhibition of the proteasome results in disruption of protein homeostasis within the cell that can lead to apoptosis, a phenomenon preferentially observed in malignant cells. Bortezomib (VELCADE) is a first-in-class proteasome inhibitor developed specifically for use as an antineoplastic agent. Its first indication, for the treatment of relapsed myeloma in patients who have received at least two prior treatments and progressed on their previous treatment, was based in part on the magnitude of activity demonstrated in Phase II trials. An interim analysis of a Phase III trial demonstrated a significant efficacy advantage of bortezomib over high-dose dexamethasone in patients with relapsed myeloma. Clinical development is ongoing to investigate its activity as monotherapy and in combination regimens for the treatment of non-Hodgkin's lymphoma, solid tumors, and early presentations of myeloma.
The UCSC Known Genes (2006)

The University of California Santa Cruz (UCSC) Known Genes dataset is constructed by a fully automated process, based on protein data from Swiss-Prot/TrEMBL (UniProt) and the associated mRNA data from Genbank. The detailed steps of this process are described. Extensive cross-references from this dataset to other genomic and proteomic data were constructed. For each known gene, a details page is provided containing rich information about the gene, together with extensive links to other relevant genomic, proteomic and pathway data. As of July 2005, the UCSC Known Genes are available for human, mouse and rat genomes. The Known Genes serves as a foundation to support several key programs: the Genome Browser, Proteome Browser, Gene Sorter and Table Browser offered at the UCSC website. All the associated data files and program source code are also available. They can be accessed at http://genome.ucsc.edu. The genomic coverage of UCSC Known Genes, RefSeq, Ensembl Genes, H-Invitational and CCDS is analyzed. Although UCSC Known Genes offers the highest genomic and CDS coverage among major human and mouse gene sets, more detailed analysis suggests all of them could be further improved.
Infertility: Ultrastructure of human ovarian primordial follicles after combination chemotherapy for Hodgkin's disease (1993)

Ovarian damage, with consequent permanent infertility, is one of the more common side-effects which occurs during chemotherapeutic treatment of patients affected by Hodgkin's disease. This damage is morphologically represented by a marked loss of primordial and primary follicles. The administration of contraceptive drugs before starting chemotherapy enhances survival of a greater number of ovarian follicles, as revealed by morphometric analyses, nevertheless, total ovarian protection is not assured. This study evaluated the number and the morphology of ovarian follicles, by means of transmission electron microscopy, in patients with Hodgkin's disease treated with multi-drug chemotherapeutic protocols following the administration of medroxyprogesterone acetate. Ovarian biopsies were performed prior to any pharmacological treatment, after medroxyprogesterone therapy, and after this therapy plus chemotherapy. Particular attention was given to the ultrastructure of primordial follicles. After morphometric evaluation, primordial follicles were numerous in controls and medroxyprogesterone therapy (28.55 +/- 6.59/mm3 of ovarian cortex). After chemotherapy and medroxyprogesterone acetate, the number of follicles was slightly reduced (19.37 +/- 3.41/mm3 of ovarian cortex) in contrast to the dramatic loss usually observed when protection is not given, although more follicles were atretic. Medroxyprogesterone may protect follicles only from acute, toxic effects of chemotherapy, which dramatically reduce their number and lead to sterility. Nevertheless, the quality of follicles is still impaired, and many undergo atresia, resulting in a shortened fertility period.
Comparative Correlation Structure of Colon Cancer Locus Specific Methylation: Characterisation of Patient Profiles and Potential Markers across 3 Array-Based Datasets (2015)

Abnormal DNA-methylation is well known to play an important role in cancer onset and development, and colon cancer is no exception to this rule. Recent years have seen the increased use of large-scale technologies, (such as methylation microarray assays or specific sequencing of methylated DNA), to determine whole genome profiles of CpG island methylation in tissue samples. Comprehensive study of methylation array data from transcriptome high-throughput platforms permits determination of gene methylation markers, important for cancer profiling. Here, three large-scale methylation datasets for colon cancer have been compared to determine locus-specific methylation agreement. These data are from the GEO database, where colon cancer and apparently healthy adjacent tissues are represented by sample sizes 125 and 29 respectively in the first dataset, 24 of each in the second and 118 of each in the third. Several data analysis techniques have been employed, including Clustering, Discriminant Principal Component Analysis, Discriminant Analysis and ROC curves, in order (i) to obtain a better insight on the locus-specific concomitant methylation structures for these diverse data and (ii) to determine a robust potential marker set for indicative screening, drawn from all data taken together. The extent of the agreement between the analysed datasets is reported. Further, potential screening methylation markers, for which methylation profiles are consistent across tissue samples and several datasets, are highlighted and discussed.
Effect of Baseline Anxious Depression on Initial and Sustained Antidepressant Response to Ketamine (2014)

ClinicalTrials.gov identifier: NCT00088699.
Protection of Sensory Function and Antihyperalgesic Properties of a Prosaposin-derived Peptide in Diabetic Rats (2000)

TX14(A) exhibits both neuroprotective and acute antihyperalgesic properties in diabetic rats without altering normal nociceptive function.
New Paths in Human Cancer Serology (1998)

Two questions have dominated the field of human cancer immunology throughout its history. Do cancer-specific antigens exist and, if so, are they recognized by the autologous host? Until recently, attempts to provide definitive answers to these questions have not been rewarded with much success.