gebhart/patrepeval huggingface dataset:
H-2Kd-restricted antigenic peptides share a simple binding motif. (1991)

We have defined structural features that are apparently important for the binding of four different, unrelated antigenic epitopes to the same major histocompatibility complex (MHC) class I molecule, H-2Kd. The four epitopes are recognized in the form of synthetic peptides by cytotoxic T lymphocytes of the appropriate specificity. By analysis of the relative potency of truncated peptides, we demonstrated that for each of the four epitopes, optimal antigenic activity was present in a peptide of 9 or 10 amino acid residues. A comparison of the relative competitor activity of the different-length peptides in a functional competition assay, as well as in a direct binding assay based on photoaffinity labeling of the Kd molecule, indicated that the enhanced potency of the peptides upon reduction in length was most likely due to a higher affinity of the shorter peptides for the Kd molecule. A remarkably simple motif that appears to be important for the specific binding of Kd-restricted peptides was identified by the analysis of peptides containing amino acid substitutions or deletions. The motif consists of two elements, a Tyr in the second position relative to the NH2 terminus and a hydrophobic residue with a large aliphatic side chain (Leu, Ile, or Val) at the COOH-terminal end of the optimal 9- or 10-mer peptides. We demonstrated that a simple peptide analogue (AYP6L) that incorporates the motif can effectively and specifically interact with the Kd molecule. Moreover, all of the additional Kd-restricted epitopes defined thus far in the literature contain the motif, and it may thus be useful for the prediction of new epitopes recognized by T cells in the context of this MHC class I molecule.
Intestinal Bacteria and the Regulation of Immune Cell Homeostasis (2010)

The human intestine is colonized by an estimated 100 trillion bacteria. Some of these bacteria are essential for normal physiology, whereas others have been implicated in the pathogenesis of multiple inflammatory diseases including IBD and asthma. This review examines the influence of signals from intestinal bacteria on the homeostasis of the mammalian immune system in the context of health and disease. We review the bacterial composition of the mammalian intestine, known bacterial-derived immunoregulatory molecules, and the mammalian innate immune receptors that recognize them. We discuss the influence of bacterial-derived signals on immune cell function and the mechanisms by which these signals modulate the development and progression of inflammatory disease. We conclude with an examination of successes and future challenges in using bacterial communities or their products in the prevention or treatment of human disease.
How to explore the patient with a rising PSA after radical prostatectomy: defining local versus systemic failure. (1999)

We report on the various methods used to determine local or distant recurrences in patients with detectable serum prostate-specific antigen (PSA) after radical prostatectomy (RP). Studies show that variables that help predict distant metastases are PSA recurrence less than 2 years following surgery, tumors with Gleason score (GS) greater than 7, and positive seminal vesicles or positive lymph nodes at the time of surgery. In addition, studies in PSA kinetics show that short PSA doubling times, especially less than 6 months, are associated with distant recurrence and better correlated with the pattern and incidence of clinical recurrence than preoperative PSA, specimen GS, or stage alone. Studies show that although positive surgical margins are a significant risk factor for recurrence, only 40% to 50% of patients with positive margins developed an elevated PSA level within 5 years. When suspecting a local recurrence, transrectal ultrasound (TRUS) and TRUS-guided biopsies enhance the relatively inaccurate detection of local recurrence by digital rectal examination and initial prostate fossa biopsies. For distant recurrence, bone scintigrams of patients with a PSA recurrence following RP are only rarely positive and are found to have limited usefulness until the PSA increases to above 30 ng/mL. The role of immunoscintography to differentiate between local and distant recurrence is still evolving and requires further investigation. Further studies are clearly needed to enhance our ability to distinguish local from distant recurrence and to ultimately help guide therapy.
Effects of Vesnarinone on Morbidity and Mortality in Patients with Heart Failure (1993)

Six months of therapy with 60 mg of vesnarinone per day resulted in lower morbidity and mortality and improved the quality of life of patients with congestive heart failure. However, a higher dose of vesnarinone (120 mg per day) increased mortality, suggesting that this drug has a narrow therapeutic range; the long-term effects of vesnarinone are unknown.
Abdominal MRI using a negative contrast agent (1993)

A dose of 0.5 g of a negative oral contrast agent for labelling the bowel, was given to 40 patients in a clinical trial. Oral magnetic particles (OMP) consist of crystals of iron oxide with superparamagnetic properties, and are administered in 800 ml of a viscous suspension in order to obtain a uniform distribution. The aim of the study was to identify any adverse effects up to 1 week following ingestion, as well as the contrast distribution and effect, together with the induction of artifacts. A comparison of diagnostic value of the pre and postcontrast ingestion series was also performed. Vomiting followed ingestion in a single patient already nauseated and was the only adverse effect. Good contrast distribution and effect with no artifacts were present. The diagnostic information was greatly improved after OMP ingestion, and the diagnosis would not have been possible without the use of the contrast agent in 41% of the examinations.
A Five-Year Study of the Incidence of Dyskinesia in Patients with Early Parkinson's Disease Who Were Treated with Ropinirole or Levodopa (2000)

Early Parkinson's disease can be managed successfully for up to five years with a reduced risk of dyskinesia by initiating treatment with ropinirole alone and supplementing it with levodopa if necessary.
Chronic Rejection in the Heart (2006)

The dramatic improvements in 1-yr survival following cardiac transplantation have not been matched by similar improvements in long-term graft survival. Long-term survival of allografted hearts is limited by a progressive fibroproliferative disease, resulting in intimal thickening and occlusion of the grafted coronary vessels. This disease, variously known as accelerated transplant coronary artery disease or cardiac graft vasculopathy, is also known as chronic rejection. The histology and clinical sequelae are briefly described. The disease can be thought of as a model for non-transplant atherosclerosis, postangioplasty restenosis, and vein graft atherosclerosis. There is compelling evidence that it is driven by alloantigen-dependent mechanisms. The evolution of the disease consists of three phases, an antibody-mediated phase, a cell-mediated phase, and a phase of tissue remodeling that is dependent on cytokines and growth factors. Experimental studies show that adoptive transfer of immunoglobulin can transfer features of intimal hyperplasia to transplanted arteries in immunodeficient recipients. Damage to donor endothelium is likely to be an important initiating factor in this disease because it exposes a thrombogenic subendothelial matrix. Whether T cells of antibody are most important in damaging the endothelium is currently the subject of much research. Although T cells are sometimes present in atherosclerotic lesions, an association with acute rejection has never been consistently shown.
Influence of Metalorganic Sources on the Composition Uniformity of Selectively Grown GaXIn1-XP (1994)

In this work, selective epitaxial growth (SEG) of GaInP on a GaAs substrate patterned with silicon nitride is performed by low-pressure metalorganic chemical vapor deposition (LP-MOCVD). The group III sources employed are the combinations of triethylgallium and ethyldimethylindium (TEG+EDMI), triethylgallium and trimethylindium (TEG+TMI), and trimethylgallium and trimethylindium (TMG+TMI). Completely selective epitaxy can be achieved at a growth temperature of 675° C and a growth pressure of 40 Torr when TEG+EDMI is used; while completely selective epitaxy can be achieved under the conditions of 650° C and 40 Torr when the other two sources are used. For the three sources, GaP and InP incorporation increase near the edges of the patterns due to the extra flux of Ga-containing and In-containing species from the region of masking film. Different combinations of group III sources lead to different extents of these incorporations due to the decomposition and diffusion characteristics of the precursors.
Purification and Partial Characterization of a Highly Immunogenic Human Leukocyte Protein, the L1 Antigen (1983)

L1 is a major and highly immunogenic protein component of human granulocytes. It was purified from random samples of blood-donor leukocytes. An antiserum to L1 was initially raised in rabbits by immunization with protein fractions from preparative agarose gel electrophoresis. The main problem in purifying L1 was its poor stability when carried through multiple steps. Preparative isoelectric focussing was therefore adopted as an efficient one-step method. The isoelectric focussing pattern of L1 was greatly influence by the presence of EDTA or calcium ions in the sample buffer. With low EDTA concentrations or calcium excess, L1 focussed as seven protein bands in two regions, pH 6.1-6.5 and pH 7.6-8.4. Conversely, L1 was found only in the pH-6.1-6.5 region when excess EDTA was added to the sample. Irrespective of conditions, the bulk of L1 focussed at pH 6.3 and pH 6.5. Also the electrophoretic mobility of L1 was strongly influenced by calcium ions, suggesting uptake of calcium by the protein. In the presence of calcium, L1 adhered to glass surfaces and filters used for concentration of protein solutions. The latter problem could be prevented by addition of EDTA. The molecular mass of L1 was determined to be about 36.5 kDa. The molecule was shown to consist of three non-covalently linked 12.5-kDa subunits.
Cyclotides: Natural, Circular Plant Peptides that Possess Significant Activity against Gastrointestinal Nematode Parasites of Sheep (2008)

The cyclotides are a novel family of backbone-cyclized cystine-knot containing peptides from plants that have been shown to possess insecticidal activity against Helicoverpa larvae, an important pest of corn and cotton. In the current study, we investigated the in vitro effects of the cyclotides on the viability of egg, larval, and adult life stages of two species of economically important gastrointestinal nematode parasites of livestock, Hemonchus contortus and Trichostrongylus colubriformis. The cyclotides showed significant activity in inhibiting development of nematode larvae and motility of adult worms. Activities were comparable to some currently used anthelmintic compounds in these in vitro assay systems. A series of alanine mutants of the prototypic cyclotide kalata B1 were assayed against larvae to determine regions of the peptide responsible for activity. It was observed that anthelmintic activity was dramatically reduced as a consequence of the mutation of a large number of residues that are found clustered on one surface. Activities toward larvae were equivalent in the naturally occurring L-isomer of kalata B1 and a synthetic all-D-isomer, indicating that there is no chiral requirement for anthelmintic activity. The clustering of important residues and the lack of chiral selectivity further support the proposed mode of action of the cyclotides, which involves a membrane-based interaction rather than an interaction at a specific receptor. The cyclotide-induced leakage of a fluorescent dye from vesicles used as a model membrane mimetic further confirms the membrane lytic ability of cyclotides. The relative potency of kalata B1 and kalata B2 in causing membrane leakage is consistent with the order of their anthelmintic activity. These results demonstrate that the cyclotides show potential for use in the control of gastrointestinal nematode parasites.
Sequence Analysis of the groESL-cotA Region of the Bacillus subtilis Genome, Containing the Restriction/Modification System Genes (1997)

We have determined a 35-kb sequence of the groESL-gutR-cotA (45 degrees-52 degrees) region of the Bacillus subtilis genome. In addition to the groESL, gutRB and cotA genes reported previously, we have newly identified 24 ORFs including gutA and fruC genes, encoding glucitol permease and fructokinase, respectively. The inherent restriction/modification system genes, hsdMR and hsdMM, were mapped between groESL and gutRB, and we have identified two open reading frames (ORFs) encoding 5-methylcytosine forming DNA methyl transferase and an operon probably encoding a restriction enzyme complex. The unusual genome structure of few ORFs and lower GC content around the restriction/modification genes strongly suggests that the region originated from a bacteriophage integrated during evolution.
The mTOR-Regulated Phosphoproteome Reveals a Mechanism of mTORC1-Mediated Inhibition of Growth Factor Signaling (2011)

The mammalian target of rapamycin (mTOR) protein kinase is a master growth promoter that nucleates two complexes, mTORC1 and mTORC2. Despite the diverse processes controlled by mTOR, few substrates are known. We defined the mTOR-regulated phosphoproteome by quantitative mass spectrometry and characterized the primary sequence motif specificity of mTOR using positional scanning peptide libraries. We found that the phosphorylation response to insulin is largely mTOR dependent and that mTOR exhibits a unique preference for proline, hydrophobic, and aromatic residues at the +1 position. The adaptor protein Grb10 was identified as an mTORC1 substrate that mediates the inhibition of phosphoinositide 3-kinase typical of cells lacking tuberous sclerosis complex 2 (TSC2), a tumor suppressor and negative regulator of mTORC1. Our work clarifies how mTORC1 inhibits growth factor signaling and opens new areas of investigation in mTOR biology.
A Novel Strategy To Obtain a Hyaluronan Monolayer on Solid Substrates (2007)

The aim of this study was to find a novel simple method to obtain polysaccharide ultrathin layers on solid substrates to investigate the interaction between the surface and the biological environment. A Hyaluronan (Hyal) monolayer with a well-defined chemistry was obtained by exploiting the capability of organosilanes to spontaneously adhere onto glass surfaces. A silane alkylic chain was conjugated with Hyal, and the derivatized polysaccharide was allowed to spontaneously adhere onto a glass surface. The elemental analysis of the modified polysaccharide demonstrated that one out of five disaccharide units was conjugated with the alkyl silane chain, corresponding to a substitution degree of the carboxylate groups of approximately 20%. The film of the modified polysaccharide was characterized by means of X-ray photoelectron spectroscopy (XPS), water contact angle, and atomic force microscopy (AFM) measurements. XPS analysis demonstrated that we obtained a Hyal layer with a thickness of about 2.0 nm corresponding to a Hyal monolayer. The Hyal-coated surfaces appeared to be rather smooth and highly hydrophilic and showed significant resistance to nonspecific cell adhesion.
Identification of proteins from two-dimensional gel electrophoresis of human erythroleukemia cells using capillary high performance liquid chromatography/electrospray-ion trap-reflectron time-of-flight mass spectrometry with two-dimensional topographic map analysis of in-gel tryptic digest products (1999)

Protein spots from two-dimensional (2-D) gel electrophoresis of a human erythroleukemia cell line have been identified by analysis of the in-gel tryptic digests using capillary high performance liquid chromatography (HPLC) separation with on-line detection using electrospray ionization mass spectrometry (ESI-MS). This is performed using an electrospray/ion trap storage/reflectron time-of-flight mass spectrometer system (ESI-IT-reTOFMS). A 2-D topographic mapping display developed to process the on-line data acquired with this TOF system has been used to obtain mass identification of each peptide, even though the capillary HPLC only provides limited separation capability of the tryptic peptide mixtures studied herein. Using this method, a substantial fraction of the protein sequence can be covered and identified using the tryptic map. It is demonstrated that by entering the cell species, the approximate MW and pI range as determined by 2-D gel electrophoresis, and the tryptic peptide map into the database a unique match for identification of the protein generally results. It is also demonstrated that a much improved coverage of the protein sequence is obtained by this method relative to matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS).
Diet, Microbiota and Gut-Lung Connection (2018)

The gut microbial community (Gut microbiota) is known to impact metabolic functions as well as immune responses in our body. Diet plays an important role in determining the composition of the gut microbiota. Gut microbes help in assimilating dietary nutrients which are indigestible by humans. The metabolites produced by them not only modulate gastro-intestinal immunity, but also impact distal organs like lung and brain. Micro-aspiration of gut bacteria or movement of sensitized immune cells through lymph or bloodstream can also influence immune response of other organs. Dysbiosis in gut microbiota has been implicated in several lung diseases, including allergy, asthma and cystic fibrosis. The bi-directional cross-talk between gut and lung (termed as Gut-Lung axis) is best exemplified by intestinal disturbances observed in lung diseases. Some of the existing probiotics show beneficial effects on lung health. A deeper understanding of the gut microbiome which comprises of all the genetic material within the gut microbiota and its role in respiratory disorders is likely to help in designing appropriate probiotic cocktails for therapeutic applications.
Discovering Small‐Molecule Estrogen Receptor α/Coactivator Binding Inhibitors: High‐Throughput Screening, Ligand Development, and Models for Enhanced Potency (2011)

Small molecules, namely coactivator binding inhibitors (CBIs), that block estrogen signaling by directly inhibiting the interaction of the estrogen receptor (ER) with coactivator proteins act in a fundamentally different way to traditional antagonists, which displace the endogenous ligand estradiol. To complement our prior efforts at CBI discovery by de novo design, we used high-throughput screening (HTS) to identify CBIs of novel structure and subsequently investigated two HTS hits by analogue synthesis, finding many compounds with low micromolar potencies in cell-based reporter gene assays. We examined structure-activity trends in both series, using induced-fit computational docking to propose binding poses for these molecules in the coactivator binding groove. Analysis of the structure of the ER-steroid receptor coactivator (SRC) complex suggests that all four hydrophobic residues within the SRC nuclear receptor box sequence are important binding elements. Thus, insufficient water displacement upon binding of the smaller CBIs in the expansive complexation site may be limiting the potency of the compounds in these series, which suggests that higher potency CBIs might be found by screening compound libraries enriched with larger molecules.
Aminozuckersynthesen, XII 2.6‐Diamino‐2.6‐didesoxy‐D‐allose (1965)

Abstract Die Darstellung von 2.6‐Diamino‐2.6‐didesoxy‐ D ‐allose·2 HCl, ausgehend vom Benzyl‐ N ‐benzoyl‐β‐ D ‐allosaminid, wird beschrieben.
Improved Prediction of Foam Diversion in Matrix Acidization (1995)

Abstract Recent studies of foam-diversion processes for matrix acidization identify gas trapping during post-foam liquid injection as the key to foam effectiveness. Laboratory studies identify two degradation processes during this period: a rapid increase in mobility throughout the core, followed by a slower further rise in mobility starting at the core inlet. New coreflood results indicate that pressure gradient ∇P during the first process is insensitive to a shut-in period after foam injection but depends weakly on liquid flow rate. A small fall in gas saturation accounts for the first rise in mobility, which appears to depend on mobilization of foam bubbles (i.e., on ∇P) rather than foam collapse (i.e., on capillary pressure). The second rise in mobility appears to be due to gas dissolution in injected liquid. Therefore this transition, which is harmful to field performance, can be avoided by including a small amount of gas with the injected acid. Process modeling illustrates that some designs that appear successful in laboratory linear corefloods can perform poorly in the field due to the geometry of radial flow. The fractional-flow approach, together with coreflood pressure data for multiple sections along the core, provides a uniquely simple and insightful framework for interpretation of laboratory results and extrapolation to the field. The simple diversion model of Hill and Rossen1 can successfully model foam processes in which the secondary degradation of foam during liquid injection is avoided by including gas with the acid.
Polar Localization of PhoN2, a Periplasmic Virulence-Associated Factor of Shigella flexneri, Is Required for Proper IcsA Exposition at the Old Bacterial Pole (2014)

Proper protein localization is critical for bacterial virulence. PhoN2 is a virulence-associated ATP-diphosphohydrolase (apyrase) involved in IcsA-mediated actin-based motility of S. flexneri. Herein, by analyzing a ΔphoN2 mutant of the S. flexneri strain M90T and by generating phoN2::HA fusions, we show that PhoN2, is a periplasmic protein that strictly localizes at the bacterial poles, with a strong preference for the old pole, the pole where IcsA is exposed, and that it is required for proper IcsA exposition. PhoN2-HA was found to be polarly localized both when phoN2::HA was ectopically expressed in a Escherichia coli K-12 strain and in a S. flexneri virulence plasmid-cured mutant, indicating a conserved mechanism of PhoN2 polar delivery across species and that neither IcsA nor the expression of other virulence-plasmid encoded genes are involved in this process. To assess whether PhoN2 and IcsA may interact, two-hybrid and cross-linking experiments were performed. While no evidence was found of a PhoN2-IcsA interaction, unexpectedly the outer membrane protein A (OmpA) was shown to bind PhoN2-HA through its periplasmic-exposed C-terminal domain. Therefore, to identify PhoN2 domains involved in its periplasmic polar delivery as well as in the interaction with OmpA, a deletion and a set of specific amino acid substitutions were generated. Analysis of these mutants indicated that neither the (183)PAPAP(187) motif of OmpA, nor the N-terminal polyproline (43)PPPP(46) motif and the Y155 residue of PhoN2 are involved in this interaction while P45, P46 and Y155 residues were found to be critical for the correct folding and stability of the protein. The relative rapid degradation of these amino acid-substituted recombinant proteins was found to be due to unknown S. flexneri-specific protease(s). A model depicting how the PhoN2-OmpA interaction may contribute to proper polar IcsA exposition in S. flexneri is presented.