gebhart/patrepeval huggingface dataset:
Heat Shock Protein-chaperoned Peptides but Not Free Peptides Introduced into the Cytosol Are Presented Efficiently by Major Histocompatibility Complex I Molecules (2001)

The studies reported here bear on the events in the cytosol that lead to trafficking of peptides during antigen processing and presentation by major histocompatibility complex (MHC) I molecules. We have introduced free antigenic peptides or antigenic peptides bound to serum albumin or to cytosolic heat shock proteins hsp90 (and its endoplasmic reticular homologue gp96) or hsp70 into the cytosol of living cells and have monitored the presentation of the peptides by appropriate MHC I molecules. The experiments show that (i) free peptides or serum albumin-bound peptides, introduced into the cytosol, become ligands of MHC I molecules at a far lower efficiency than peptides chaperoned by any of the heat shock proteins tested and (ii) treatment of cells with deoxyspergualin, a drug that binds hsp70 and hsp90 with apparent specificity, abrogates the ability of cells to present antigenic peptides through MHC I molecules, and introduction of additional hsp70 into the cytosol overcomes this abrogation. These results suggest for the first time a functional role for cytosolic chaperones in antigen processing.
Interleukin-8 Production by Human Airway Epithelial Cells in Response to Pseudomonas aeruginosa Clinical Isolates Expressing Type a or Type b Flagellins (2010)

Pseudomonas aeruginosa lung infection is a major cause of morbidity and mortality worldwide. P. aeruginosa flagellin, the main structural protein of the flagellar filament, is a virulence factor with proinflammatory activity on respiratory epithelial cells. P. aeruginosa bacteria express one of two isoforms of flagellin (type a or b) that differ in their primary amino acid sequences as well as in posttranslational glycosylation. In this study, the distribution of type a and b flagellins among 3 P. aeruginosa laboratory strains and 14 clinical isolates (1 ulcerative keratitis, 3 cystic fibrosis, and 10 acute pneumonia isolates) was determined, and their abilities to stimulate interleukin-8 (IL-8) production by human airway epithelial cells was compared. By comparison with the PAK (type a) and PAO1 (type b) prototype laboratory strains, 10/14 (71.4%) of clinical isolates expressed type a and 4/14 (28.6%) expressed type b flagellins. Among four cell lines surveyed, BEAS-2B cells were found to give the greatest difference between constitutive and flagellin-stimulated IL-8 production. All 17 flagellins stimulated IL-8 production by BEAS-2B cells (range, 700 to 4,000 pg/ml). However, no discernible differences in IL-8 production were evident when comparing type a versus type b flagellins or flagellins from laboratory versus clinical strains or among the clinical strains.
Channel Plasmon-Polariton Guiding by Subwavelength Metal Grooves (2005)

We report on realization of channel plasmon-polariton (CPP) propagation along a subwavelength metal groove. Using imaging with a near-field microscope and end-fire coupling with a tapered fiber connected to a tunable laser at telecommunication wavelengths (1425-1620 nm), we demonstrate low-loss (propagation length approximately 100 microm) and well-confined (mode width approximately 1.1 microm) CPP guiding along a triangular 0.6 microm-wide and 1 microm-deep groove in gold. We develop a simple model based on the effective-index method that accounts for the main features of CPP guiding and provides a clear physical picture of this phenomenon.
Pharmacology of opioids. (1983)

The concept of multiple opioid receptors reconciles a large body of clinical and pharmacological data. Recent studies have shown that there are also multiple opioid binding sites. It would appear that there is considerable variability between species in both the specificity and selectivity of opioid receptors. This issue has not been explored systematically regarding opioid binding sites. Better characterization of the pharmacological profiles and receptor binding specificity for different species may help resolve some of the apparent disparities. The number of putative receptors now number nearly a dozen. Already subspecies of mu, kappa, and sigma receptors are being postulated. Both pharmacological and neurochemical methods may reveal even more. Some of the newer kappa agonists differ in their pharmacology from the prototypic kappa agonist ethylketazocine.
ACG Clinical Guidelines: Diagnosis and Management of Celiac Disease (2013)

This guideline presents recommendations for the diagnosis and management of patients with celiac disease. Celiac disease is an immune-based reaction to dietary gluten (storage protein for wheat, barley, and rye) that primarily affects the small intestine in those with a genetic predisposition and resolves with exclusion of gluten from the diet. There has been a substantial increase in the prevalence of celiac disease over the last 50 years and an increase in the rate of diagnosis in the last 10 years. Celiac disease can present with many symptoms, including typical gastrointestinal symptoms (e.g., diarrhea, steatorrhea, weight loss, bloating, flatulence, abdominal pain) and also non-gastrointestinal abnormalities (e.g., abnormal liver function tests, iron deficiency anemia, bone disease, skin disorders, and many other protean manifestations). Indeed, many individuals with celiac disease may have no symptoms at all. Celiac disease is usually detected by serologic testing of celiac-specific antibodies. The diagnosis is confirmed by duodenal mucosal biopsies. Both serology and biopsy should be performed on a gluten-containing diet. The treatment for celiac disease is primarily a gluten-free diet (GFD), which requires significant patient education, motivation, and follow-up. Non-responsive celiac disease occurs frequently, particularly in those diagnosed in adulthood. Persistent or recurring symptoms should lead to a review of the patient's original diagnosis to exclude alternative diagnoses, a review of the GFD to ensure there is no obvious gluten contamination, and serologic testing to confirm adherence with the GFD. In addition, evaluation for disorders associated with celiac disease that could cause persistent symptoms, such as microscopic colitis, pancreatic exocrine dysfunction, and complications of celiac disease, such as enteropathy-associated lymphoma or refractory celiac disease, should be entertained. Newer therapeutic modalities are being studied in clinical trials, but are not yet approved for use in practice. Given the incomplete response of many patients to a GFD-free diet as well as the difficulty of adherence to the GFD over the long term, development of new effective therapies for symptom control and reversal of inflammation and organ damage are needed. The prevalence of celiac disease is increasing worldwide and many patients with celiac disease remain undiagnosed, highlighting the need for improved strategies in the future for the optimal detection of patients.
Identification of 2‐Methyl‐3‐Furanthiol in the Steam Distillate from Canned Tuna Fish (1988)

ABSTRACT The volatile components of canned tuna fish were isolated by steam distillation followed by solvent extraction. Analysis of the extract using a sulfur‐specific detector and coupled gas chromatography ‐mass spectrometry permitted the identification of 2‐methyl‐3‐furanthiol, a compound with an intense beef extract aroma. Mass spectral data are presented.
THE ESCRT COMPLEXES: Structure and Mechanism of a Membrane-Trafficking Network (2006)

The ESCRT complexes and associated proteins comprise a major pathway for the lysosomal degradation of transmembrane proteins and are critical for receptor downregulation, budding of the HIV virus, and other normal and pathological cell processes. The ESCRT system is conserved from yeast to humans. The ESCRT complexes form a network that recruits monoubiquitinated proteins and drives their internalization into lumenal vesicles within a type of endosome known as a multivesicular body. The structures and interactions of many of the components have been determined over the past three years, revealing mechanisms for membrane and cargo recruitment and for complex assembly.
Isolation and functional expression of a mammalian prohormone processing enzyme, murine prohormone convertase 1. (1991)

We have combined gene cloning with an assay for prohormone biosynthesis and processing in Xenopus oocytes to identify the genes that encode mammalian prohormone processing enzymes. The coinjection of RNA encoding murine prohormone convertase 1 (mPC1), a mammalian endoprotease, along with proopiomelanocortin RNA into an oocyte results in the appropriate cleavage after paired basic residues in the proopiomelanocortin polyprotein necessary to generate corticotropin. The ability of mPC1 to generate corticotropin, along with the observation that mPC1 is specifically expressed in endocrine and neuronal cells, suggests that the mPC1 gene encodes the endopeptidase responsible for the pathway of proopiomelanocortin cleavage observed in the anterior pituitary.
The influence of elevated CO2 on non‐structural carbohydrate distribution and fructan accumulation in wheat canopies (1994)

We grew 2.4 m2 wheat canopies in a large growth chamber under high photosynthetic photon flux (1000 micromoles m-2 s-1) and using two CO2 concentrations, 360 and 1200 micromoles mol-1. Photosynthetically active radiation (400-700 nm) was attenuated slightly faster through canopies grown in 360 micromoles mol-1 than through canopies grown in 1200 micromoles mol-1, even though high-CO2 canopies attained larger leaf area indices. Tissue fractions were sampled from each 5-cm layer of the canopies. Leaf tissue sampled from the tops of canopies grown in 1200 micromoles mol-1 accumulated significantly more total non-structural carbohydrate, starch, fructan, sucrose, and glucose (p < 0.05) than for canopies grown in 360 micromoles mol-1. Non-structural carbohydrate did not significantly increase in the lower canopy layers of the elevated CO2 treatment. Elevated CO2 induced fructan synthesis in all leaf tissue fractions, but fructan formation was greatest in the uppermost leaf area. A moderate temperature reduction of 10 degrees C over 5 d increased starch, fructan and glucose levels in canopies grown in 1200 micromoles mol-1, but concentrations of sucrose and fructose decreased slightly or remained unchanged. Those results may correspond with the use of fructosyl-residues and release of glucose when sucrose is consumed in fructan synthesis.
Selection and fading of resistance mutations in women and infants receiving nevirapine to prevent HIV-1 vertical transmission (HIVNET 012) (2001)

NVP(R) was detected more frequently in infants than women following NVP prophylaxis, and different patterns of NVP(R) mutations were detected in women versus infants. NVP(R) was detected infrequently in infants with late HIV-1 infection. NVP-resistant HIV-1 faded from detection in women and infants over time.
A distributed reputation approach to cooperative Internet routing protection (2005)

The security of the Internet's interdomain routing system hinges on whether autonomous systems (ASes) can trust the information they receive from each other via the border gateway protocol (BGP). Frequently, this trust has been misguided, resulting in wide-spread outages and significant concerns about future attacks. Despite the seriousness of these problems, proposals for a more secure version of BGP have been stymied by serious impediments to practical deployment. Instead, we argue that the existing trust relationships between network operators (and the institutions they represent) are a powerful force for improving the security of BGP, without changing the underlying routing protocol. Our approach leverages ideas from online reputation systems to allow ASes to form a peer-to-peer overlay that integrates results from local network-management tools for detecting attacks and configuration errors. The proposed architecture is incrementally deployable, protects against shilling attacks, and deters malicious operator behavior.
DNA assembly for synthetic biology: from parts to pathways and beyond (2011)

The assembly of DNA from small fragments into large constructs has seen significant recent development, becoming a pivotal technology in the ability to implement the vision of synthetic biology. As the cost of whole gene synthesis is decreasing, whole genome synthesis at the other end of the spectrum has expanded our horizons to the prospect of fully engineered synthetic cells. However, the recently proven ability to synthesise genome-scale DNA is at odds with our ability to rationally engineer biological devices, which lags significantly behind. Most work in synthetic biology takes place on an intermediate scale with the combinatorial construction of networks and metabolic pathways from registries of modular biopart components. Implementation for rapid prototyping of engineered biological circuits requires quick and reliable DNA assembly according to specific architectures. It is apparent that DNA assembly is now a limiting technology in advancing synthetic biology. Current techniques employ standardised restriction enzyme assembly protocols such as BioBricks™, BglBricks and Golden Gate methods. Alternatively, sequence-independent overlap techniques, such as In-Fusion™, SLIC and Gibson isothermal assembly are becoming popular for larger assemblies, and in vivo DNA assembly in yeast and bacillus appears adept for chromosome fabrication. It is important to consider how the use of different technologies may impact the outcome of a construction, since the assembly technique can direct the architecture and diversity of systems that can be made. This review provides a critical examination of recent DNA assembly strategies and considers how this important facilitating aspect of synthetic biology may proceed in the future.
Guard cells in albino leaf patches do not respond to photosynthetically active radiation, but are sensitive to blue light, CO2 and abscisic acid (2006)

Stomatal openings can be stimulated by light through two signalling pathways. The first pathway is blue light specific and involves phototropins, while the second pathway mediates a response to photosynthetically active radiation (PAR). This second pathway was studied with the use of albino Vicia faba plants and variegated leaves of Chlorophytum comosum. Treatment of V. faba with norflurazon (Nf) inhibits the synthesis of carotenoids and leads to albino leaves with guard cells that lack functional green chloroplasts. Guard cells in albino leaf patches of C. comosum, however, do contain photosynthetically active chloroplasts. Stomata in albino leaf patches of both plants did not respond to red light, although blue light could still induce stomatal opening. This shows that the response to PAR is not functioning in albino leaf patches, even though guard cells of C. comosum harbour chloroplasts. Stomata of Nf-treated plants still responded to CO2 and abscisic acid (ABA). The size of Nf-treated guard cells was increased, but impalement studies with double-barrelled microelectrodes revealed no changes in ion-transport properties at the plasma membrane of guard cells. Blue light could hyperpolarize albino guard cells by triggering outward currents with peak values of 37 pA in albino plants and 51 pA in green control cells. Because of the inhibition of carotenoid biosynthesis, Nf-treated V. faba plants contained only 4% of the ABA content found in green control plants. The ABA dose dependence of anion channel activation in guard cells was shifted in these plants, causing a reduced response to 10 microM ABA. These data show that despite the dramatic changes in physiology caused by Nf, the gross responsiveness of guard cells to blue light, CO2 and ABA remains unaltered. Stomata in albino leaf patches, however, do not respond to PAR, but require photosynthetically active mesophyll cells for this response.
Formation of Soy Protein Isolate Cold‐set Gels: Protein and Salt Effects (2005)

ABSTRACT: The influence of protein and calcium concentration on soy protein cold‐set gel formation and rheology has been investigated. Cold‐set gels can be formed at soy protein concentrations from 6% to 9% and calcium concentrations from 10 to 20 mM. Gel properties can be modulated by changing the protein and/or CaCl 2 concentrations. An increase in CaCl 2 concentration from 10 to 20 mM increased gel opacity while an increase in protein concentration from 6% to 9% decreased opacity. Water‐holding capacity improved with increasing protein concentration and decreasing CaCl 2 concentration. The elastic modulus (G') increased with protein and calcium chloride concentrations. Microscopy revealed an increase in the diameters of aggregates and pores as CaCl 2 concentration increased and as protein concentration decreased. Cold‐set gels with a broad range of characteristics can be obtained from soy protein.
A study of skin diseases in dogs and cats. VI. Microflora of the major canine pyodermas. (1981)

From 40 dogs with pyoderma swabs from areas with representative lesions were examined bacteriologically. Staph. aureus was found in 98% of the areas, beta-hemolytic streptococci in 30%, and Gram-negative organisms, mainly Proteus spp., in 30% (Table I). Pure infection with Staph. aureus was found in 55% of the areas. Staph. aureus and beta-hemolytic streptococci were found in 15%, Staph. aureus and Gram-negative organisms in 15%, Staph. aureaus and beta-hemolytic streptococci as well as Gram-negative organisms in 13%, and beta-hemolytic streptococci and Gram-negative organisms in 3% (Table II). Compared to normal and eczematous skin areas, Staph. aureus was found more often, and in greater numbers, in areas with pyoderma, whereas micrococci, alpha-hemolytic streptococci, and Acinetobacter spp. were rarer. Gram-negative organisms such as Proteus spp., E. coli, and Pseudomonas spp. were found with equal frequency in eczema and pyoderma, while beta-hemolytic streptococci were almost exclusively associated with suppurative lesions (Tables IV and V).
The Binding of Thrombin to the Surface of Human Platelets (1974)

Abstract We previously postulated that thrombin might initiate platelet aggregation and the release reaction by acting at the platelet surface. We have now demonstrated surface binding of thrombin using highly purified bovine thrombin labeled with 125I. At least two classes of binding sites have been demonstrated. When studies are done at relatively high thrombin concentrations, platelets bind 50,000 thrombin molecules per platelet at saturation with an apparent dissociation constant of 2.9 units per ml (30 nm thrombin). Binding studies carried out at lower thrombin concentrations disclose that approximately 500 thrombin molecules bind per platelet with an apparent dissociation constant of 0.02 unit per ml (0.21 nm thrombin). The other properties of these two types of thrombin-binding sites were identical. Diisopropyl fluorophosphate-treated thrombin (DIP-thrombin) binds to platelets with equal affinity and competes for the same sites as native thrombin, even though DIP-thrombin does not cause platelet aggregation or the release reaction. Experiments using high resolution electron microscopic autoradiography established that 125I-thrombin binds to the cell surface. The mean position of 400 grains was 490 ± 90 A (S.E.M.) external to the platelet plasma membrane, suggesting that bound thrombin is located in the glycoprotein coat of the platelet surface. Similar localization was found for 125I-lentil phytohemagglutinin, which is known to bind to a platelet surface oligosaccharide. Addition of excess unlabeled thrombin rapidly displaced g95% of 125I-thrombin previously bound to platelets, further suggesting that thrombin does not enter the cell. Although DIP-thrombin competitively inhibits binding of native thrombin, DIP-thrombin increases the extent of [14C]serotonin release when platelets are exposed to suboptimal concentrations of native thrombin. These findings suggest that thrombin induces the release reaction by a complicated mechanism involving both binding and proteolytic activities.
Enhancement of skeletal muscle fatigue by the calcium channel antagonist diltiazem. (1990)

This study sought to determine the effects of diltiazem on normal muscle twitches and on twitches evoked during repetitive stimulation. Initial experiments showed that diltiazem (5 and 30 microM) had slight, but insignificant, effects on peak twitch tension and the time course of the twitch. When muscles were stimulated at 1 or 5 Hz, 30 microM diltiazem significantly depressed the height and time course of the staircase period and increased the rate and magnitude of fatigue. Contrary to control, diltiazem caused a complete loss of developed tension during both stimulation protocols. Results suggest that although diltiazem has little effect on single twitches, it has marked inhibitory effects on twitches evoked during repetitive activity; the result being enhancement of the fatigue process.
CTCF mediates long-range chromatin looping and local histone modification in the β-globin locus (2006)

CTCF (CCCTC-binding factor) binds sites around the mouse beta-globin locus that spatially cluster in the erythroid cell nucleus. We show that both conditional deletion of CTCF and targeted disruption of a DNA-binding site destabilize these long-range interactions and cause local loss of histone acetylation and gain of histone methylation, apparently without affecting transcription at the locus. Our data demonstrate that CTCF is directly involved in chromatin architecture and regulates local balance between active and repressive chromatin marks. We postulate that throughout the genome, relative position and stability of CTCF-mediated loops determine their effect on enhancer-promoter interactions, with gene insulation as one possible outcome.
Case-Control Studies: Design, Conduct, Analysis. (1983)

Case-control studies, often called 'retrospective' studies, provide a research method for investigating factors that may prevent or cause disease. Basically the method involves comparison of patients (cases) with a group of controls that consists of persons who are free of the disease under study.
Histone deacetylase inhibitors reduce VEGF production and induce growth suppression and apoptosis in human mantle cell lymphoma (2005)

Based on these findings, we provide evidence that HDAC inhibitors have antiproliferative effects in MCL and may represent a promising therapeutic approach.
In vitro regulation of immunoglobulin synthesis after human marrow transplantation. II. Deficient T and non-T lymphocyte function within 3- 4 months of allogeneic, syngeneic, or autologous marrow grafting for hematologic malignancy (1982)

Immunoglobulin secretion was studied in 37 patients between 19 and 106 days after allogeneic HLA-identical (30 patients), allogeneic one HLA-haplotype-identical (three patients), syngeneic (three patients), or autologous (one patient) marrow grafting. E rosette-positive (T) and E rosette-negative (non-T) peripheral blood mononuclear cells were cocultured with pokeweed mitogen for 6 days. Polyvalent immunoglobulin secretion was determined by counting plaque forming cells in a reverse hemolytic plaque assay. The number of antibody secreting cells in cocultures of autologous T and non-T lymphocytes was low in 40 of 44 tests conducted on samples from the 37 patients. Mononuclear or non-T cells from 38 of 40 tests failed to produce antibody when cultured with normal helper T cells. T cells from 23 of 37 tests failed to help normal non-T cells secrete antibody. T lymphocytes from 23 of 41 tests suppressed antibody production greater than 80% by normal T and non-T cells. The suppressor cells were radiosensitive in 17 of the 25 tests. The abnormal function of lymphocyte subpopulations in patients during the first 3 mo after syngeneic, allogeneic or autologous marrow grafting was similar regardless of the type of graft or the presence of acute graft versus host disease.