gebhart/patrepeval huggingface dataset:
Facets of heat shock protein 70 show immunotherapeutic potential (2003)

Amongst the families of intracellular molecules that chaperone and assist with the trafficking of other proteins, notably during conditions of cellular stress, heat shock protein (hsp) 70 is one of the most studied. Although its name suggests that expression is exclusively induced during cellular hyperthermia, members of the hsp70 family of proteins can be constitutively expressed and/or induced by a range of other cellular insults. The ubiquitous presence of hsp70 in eukaryotic and prokaryotic cells, combined with its high degree of sequence homology and intrinsic immunogenicity, have prompted the suggestion that inappropriate immune reactivity to hsp70 might lead to pro-inflammatory responses and the development of autoimmune disease. Indeed, hsp70 has been shown to be a potent activator of innate immunity and aberrant expression of hsp70 in certain organs promotes immunopathology. However, studies also suggest that hsp70 might have immunotherapeutic potential, as hsp70 purified from malignant and virally infected cells can transfer and deliver antigenic peptides to antigen-presenting cells to elicit peptide-specific immunity and, in contrast to its reported pro-inflammatory effects, the administration of recombinant hsp70 can attenuate experimental autoimmune disease. This review focuses on the immunoregulatory capacity of hsp70 and its potential therapeutic value.
HLA-haploidentical transplantation with regulatory and conventional T-cell adoptive immunotherapy prevents acute leukemia relapse (2014)

Posttransplant relapse is still the major cause of treatment failure in high-risk acute leukemia. Attempts to manipulate alloreactive T cells to spare normal cells while killing leukemic cells have been unsuccessful. In HLA-haploidentical transplantation, we reported that donor-derived T regulatory cells (Tregs), coinfused with conventional T cells (Tcons), protected recipients against graft-versus-host disease (GVHD). The present phase 2 study investigated whether Treg-Tcon adoptive immunotherapy prevents posttransplant leukemia relapse. Forty-three adults with high-risk acute leukemia (acute myeloid leukemia 33; acute lymphoblastic leukemia 10) were conditioned with a total body irradiation-based regimen. Grafts included CD34(+) cells (mean 9.7 × 10(6)/kg), Tregs (mean 2.5 × 10(6)/kg), and Tcons (mean 1.1 × 10(6)/kg). No posttransplant immunosuppression was given. Ninety-five percent of patients achieved full-donor type engraftment and 15% developed ≥grade 2 acute GVHD. The probability of disease-free survival was 0.56 at a median follow-up of 46 months. The very low cumulative incidence of relapse (0.05) was significantly better than in historical controls. These results demonstrate the immunosuppressive potential of Tregs can be used to suppress GVHD without loss of the benefits of graft-versus-leukemia (GVL) activity. Humanized murine models provided insights into the mechanisms underlying separation of GVL from GVHD, suggesting the GVL effect is due to largely unopposed Tcon alloantigen recognition in bone marrow.
Fine structure of a periciliary ridge complex of frog retinal rod cells revealed by ultrahigh resolution scanning electron microscopy (1983)

We studied the junctional region between rod inner segments (RIS) and outer segments (ROS) in frog retinas by high resolution scanning electron microscopy (SEM). Retinas of dark adapted or light exposed Rana pipiens were critical-point-dried and RIS and ROS were split and coated with ultrathin metal films of niobium and chromium--or decorated with gold--and imaged in a new SE-I imaging mode. The connecting cilium (CC) usually broke at the base of the RIS and remained attached to the ROS. The outer part of the CC plasmalemma expanded to form liplike protrusions beyond which disks evaginated with successively larger diameter until they reached the full width of the ROS. The CC rose out from an invagination of the RIS apical plasma membrane (PM). On the lateral walls of this invagination, a highly ordered complex of nine symmetrically arrayed ridges and grooves rose steeply and extended laterally approximately 0.4-1 micron on the adjacent RIS PM. On the apical plasmalemma, the ridges and grooves formed groups of three to four parallel rows that surrounded the invagination. The grooves were bridged by filaments anchored at the top edges of the ridges. This highly ordered structure we term the periciliary ridge complex (PRC). Its ninefold symmetry apparently reflects the 9 + 0 microtubule organization of the CC axoneme. The three-dimensional structure revealed by SEM was confirmed by transmission electron microscopy (TEM) of sections of Epon-embedded retinas. TEM-immunocytochemistry on thin sections of retinas embedded in glutaraldehyde cross-linked albumin suggested that the PRC and the CC may participate in opsin transport and disk morphogenesis.
Nutrition and feeding of the broodmare (2006)

Four pregnant donkeys at approximately 10-11 month of pregnancy were used. The aim of the trial was to compare the apparent digestibility of two different rations: a low quality meadow hay based diet versus a diet with hay and a cereal commercial concentrate feed (CM). Diet 1 consisted of 9 kg of meadow hay whereas in Diet 2 hay was partially replaced by the CM (70:30 hay:CM ratio). The animals were randomly divided into two groups and the trial was conducted according to a change-over design for two periods of 20d. Measurements of apparent digestibility were made on the last 6 d of each period. Size of fibre particles in faeces was evaluated too. Donkeys fed with Diet 1 consumed significantly more of DM per metabolic weight unit than animals fed with diet 2. Higher apparent digestibilities of dietary DM, energy, and fibre fractions were seen observed in donkeys fed with Diet 2. Intakes of both diets exceeded the estimated energy requirement, whereas protein needs were not satisfied by Diet 1. The percentages of different size fibre particles recovered in faeces showed no significant differences in both diets.
RNA-guided complex from a bacterial immune system enhances target recognition through seed sequence interactions (2011)

Prokaryotes have evolved multiple versions of an RNA-guided adaptive immune system that targets foreign nucleic acids. In each case, transcripts derived from clustered regularly interspaced short palindromic repeats (CRISPRs) are thought to selectively target invading phage and plasmids in a sequence-specific process involving a variable cassette of CRISPR-associated (cas) genes. The CRISPR locus in Pseudomonas aeruginosa (PA14) includes four cas genes that are unique to and conserved in microorganisms harboring the Csy-type (CRISPR system yersinia) immune system. Here we show that the Csy proteins (Csy1-4) assemble into a 350 kDa ribonucleoprotein complex that facilitates target recognition by enhancing sequence-specific hybridization between the CRISPR RNA and complementary target sequences. Target recognition is enthalpically driven and localized to a "seed sequence" at the 5' end of the CRISPR RNA spacer. Structural analysis of the complex by small-angle X-ray scattering and single particle electron microscopy reveals a crescent-shaped particle that bears striking resemblance to the architecture of a large CRISPR-associated complex from Escherichia coli, termed Cascade. Although similarity between these two complexes is not evident at the sequence level, their unequal subunit stoichiometry and quaternary architecture reveal conserved structural features that may be common among diverse CRISPR-mediated defense systems.
Mutations of PIK3CAin gastric adenocarcinoma (2005)

Our data suggested that activation of the PI3K signalling pathway in gastric cancer may be achieved through up-regulation or mutation of PIK3CA, in which the latter may be a consequence of mismatch repair deficiency.
Towards a consensus on datasets and evaluation metrics for developing B‐cell epitope prediction tools (2007)

A B-cell epitope is the three-dimensional structure within an antigen that can be bound to the variable region of an antibody. The prediction of B-cell epitopes is highly desirable for various immunological applications, but has presented a set of unique challenges to the bioinformatics and immunology communities. Improving the accuracy of B-cell epitope prediction methods depends on a community consensus on the data and metrics utilized to develop and evaluate such tools. A workshop, sponsored by the National Institute of Allergy and Infectious Disease (NIAID), was recently held in Washington, DC to discuss the current state of the B-cell epitope prediction field. Many of the currently available tools were surveyed and a set of recommendations was devised to facilitate improvements in the currently existing tools and to expedite future tool development. An underlying theme of the recommendations put forth by the panel is increased collaboration among research groups. By developing common datasets, standardized data formats, and the means with which to consolidate information, we hope to greatly enhance the development of B-cell epitope prediction tools.
Sequence and expression of the Escherichia coli K1 neuC gene product (1992)

The nucleotide sequence of the neuC gene of the Escherichia coli K1 capsule gene cluster encodes a protein with a predicted molecular weight of 44,210 containing 391 amino acids. A chimeric protein with beta-galactosidase fused to the carboxy terminus of the neuC gene product (P7) was constructed and purified. Its amino-terminal sequence confirmed the prediction from the nucleotide sequence that the neuC gene overlaps the distal end of the neuA gene by a single base pair. Both the neuA and neuC genes are coexpressed under the control of a single upstream T7 or tac promoter, suggesting that neuA and neuC are part of an operon.
Interphase FISH detection of BCL2 rearrangement in follicular lymphoma using breakpoint‐flanking probes (2000)

Rearrangement of the BCL2 gene is an important parameter for the differential diagnosis of non-Hodgkin lymphomas. Although a relatively large proportion of breakpoints is clustered, many are missed by standard PCR. A FISH assay is therefore desired. Up to now, a lack of probes flanking the BCL2 gene has limited the possibilities for a FISH assay to an approach based on colocalization of probes for BCL2 and the immunoglobulin heavy chain (IGH) locus. Intrinsically high rates of false positive nuclei and high interobserver variability make such assays unsuitable for use on lymphoma tissue samples, where tumor cells often form only a minority of the cell population. Using YAC end cloning techniques and screening of a PAC library, we have isolated PAC clones flanking the BCL2 gene. Using these PACs, and several cosmid clones in the second BCL2 intron, we developed a segregation-based interphase FISH assay with two probe combinations enabling separate detection of 5′ and 3′ (mbr/mcr) breakpoints. The assay was applied to a series of 40 follicular lymphomas. To evaluate the results, the same lymphomas were analyzed by DNA fiber FISH with a 600-kb set of BCL2 DNA clones labeled in alternating colors in combination with a color barcode covering the IGH locus. This approach allowed precise mapping of BCL2 breakpoints, and simultaneously showed juxtaposition of IGH genes to BCL2. Comparison of the results of interphase and fiber FISH showed complete correlation. Five cases were negative with both FISH techniques as well as with Southern blotting. Interestingly, all of these 5 cases lacked BCL2 overexpression as determined by immunohistochemistry, against 3 of 35 rearrangement-positive follicular lymphomas. Furthermore, absence of t(14;18) seemed to be correlated with a higher histologic grade (grades 2 and 3 according to Berard). These data indicate that the segregation-based interphase FISH assay detects 100% of BCL2 rearrangements. Because interpretation of the results is straightforward and requires no extensive experience, this assay may be the best available diagnostic test for BCL2 rearrangement. Genes Chromosomes Cancer 27:85–94, 2000. © 2000 Wiley-Liss, Inc.
Current knowledge and perspectives of Paenibacillus: a review (2016)

Isolated from a wide range of sources, the genus Paenibacillus comprises bacterial species relevant to humans, animals, plants, and the environment. Many Paenibacillus species can promote crop growth directly via biological nitrogen fixation, phosphate solubilization, production of the phytohormone indole-3-acetic acid (IAA), and release of siderophores that enable iron acquisition. They can also offer protection against insect herbivores and phytopathogens, including bacteria, fungi, nematodes, and viruses. This is accomplished by the production of a variety of antimicrobials and insecticides, and by triggering a hypersensitive defensive response of the plant, known as induced systemic resistance (ISR). Paenibacillus-derived antimicrobials also have applications in medicine, including polymyxins and fusaricidins, which are nonribosomal lipopeptides first isolated from strains of Paenibacillus polymyxa. Other useful molecules include exo-polysaccharides (EPS) and enzymes such as amylases, cellulases, hemicellulases, lipases, pectinases, oxygenases, dehydrogenases, lignin-modifying enzymes, and mutanases, which may have applications for detergents, food and feed, textiles, paper, biofuel, and healthcare. On the negative side, Paenibacillus larvae is the causative agent of American Foulbrood, a lethal disease of honeybees, while a variety of species are opportunistic infectors of humans, and others cause spoilage of pasteurized dairy products. This broad review summarizes the major positive and negative impacts of Paenibacillus: its realised and prospective contributions to agriculture, medicine, process manufacturing, and bioremediation, as well as its impacts due to pathogenicity and food spoilage. This review also includes detailed information in Additional files 1, 2, 3 for major known Paenibacillus species with their locations of isolation, genome sequencing projects, patents, and industrially significant compounds and enzymes. Paenibacillus will, over time, play increasingly important roles in sustainable agriculture and industrial biotechnology.
Context and orientation in hypermedia networks (1989)

The core of hypermedia's power lies in the complex networks of links that can be created within and between documents. However, these networks frequently overwhelm the user and become a source of confusion. Within Intermedia, we have developed the Web View-a tool for viewing and navigating such networks with a minimum of user confusion and disorientation. The key factors in the Web View's success are a display that combines a record of the user's path through the network with a map of the currently available links; a scope line that summarizes the number of documents and links in the network; and a set of commands that permit the user to open documents directly from the Web View.
Characteristics of a Highly Labile Human Type 5 17β-Hydroxysteroid Dehydrogenase1 (1999)

17Beta-hydroxysteroid dehydrogenases (17betaHSDs) play an essential role in the formation of active intracellular sex steroids. Six types of 17betaHSD have been described to date, which only share approximately 20% homology. Human type 5 17betaHSD complementary DNA is unique among the 17betaHSDs because it belongs to the aldo-keto reductase family, whereas the others are members of the short chain alcohol dehydrogenases. The characteristics of human type 5 17betaHSD were investigated in human embryonic (293) cells stably transfected with human and mouse type 5 17betaHSD, as well as human type 3 3alphaHSD. Using intact transfected cells, type 5 17betaHSD shows a substrate specificity pattern comparable to those of human type 3 17betaHSD and mouse type 5 17betaHSD. These enzymes catalyze more efficiently the transformation of androstenedione (4-dione) to testosterone, whereas the transformation of dihydrotestosterone to 5alpha-androstane-3alpha,17beta-diol is much lower. In contrast, type 3 3alphaHSD catalyzes more efficiently the transformation of dihydrotestosterone to 5alpha-androstane-3alpha,17beta-diol, whereas the transformation of 4-dione to testosterone represents only 7% of the 3alphaHSD activity. However, upon homogenization, human type 5 17betaHSD activity decreases to approximately 10% of the activity in intact cells and remains stable at this level together with the 3alphaHSD activity. Under the same conditions, however, the mouse enzyme is not altered by homogenization. Indeed, using purified human 17betaHSD overexpressed in Escherichia coli, we could confirm that a much greater amount of protein is required to produce activity similar to the enzymatic activity measured in intact transfected cells. The present data provide the answer to the question of why previous researchers could hardly detect type 5 17betaHSD activity. Indeed, all previous publications used cell or tissue homogenates or purified enzymes. Under such conditions, only the low level, but stable, 3alphaHSD and 17betaHSD activities could be measured, whereas the high level, but highly unstable, 17betaHSD activity could not be measured. As type 5 17betaHSD shares 84%, 86%, and 88% amino acid identity with types 1 and 3 3alphaHSD and 20alphaHSDs, respectively, Northern blot analysis used in previous studies could not provide unequivocal information. In this report, we used a more specific ribonuclease protection assay and could thus show that human type 5 17betaHSD is expressed in the liver, adrenal, and prostate; in prostatic cancer cell lines DU-145 and LNCaP; as well as in bone carcinoma (MG-63) cells. By analogy with type 3 17betaHSD, which is responsible for the formation of androgens in the testis, the expression of type 5 17betaHSD in the prostate and bone cells suggests that this enzyme is involved in the formation of active intracellular androgens in these tissues.
Emerging Resistance, New Antimicrobial Agents  …  but No Tests! The Challenge of Antimicrobial Susceptibility Testing in the Current US Regulatory Landscape (2016)

Accurate and timely performance of antimicrobial susceptibility testing (AST) by the clinical laboratory is paramount to combating antimicrobial resistance. The ability of laboratories in the United States to effectively perform ASTs is challenged by several factors. Some, such as new resistance mechanisms and the associated evolution of testing recommendations and breakpoints, are inevitable. Others are entirely man-made. These include unnecessarily strict US Food and Drug Administration (FDA) limitations on how commercial AST systems can be used for diagnostic testing, the absence of up-to-date performance data on these systems, and the lack of commercially available FDA-cleared tests for newer antimicrobial agents or for older agents with updated breakpoints. This viewpoint will highlight contemporary AST challenges faced by the clinical laboratory, and propose some solutions.
Compositional and structural analysis of camel milk proteins with emphasis on protective proteins (1998)

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Strategy for Comprehensive Identification of Post-translational Modifications in Cellular Proteins, Including Low Abundant Modifications: Application to Glyceraldehyde-3-phosphate Dehydrogenase (2008)

Post-translational modifications (PTMs) play key roles in the regulation of biological functions of proteins. Although some progress has been made in identifying several PTMs using existing approaches involving a combination of affinity-based enrichment and mass spectrometric analysis, comprehensive identification of PTMs remains a challenging problem in proteomics because of the dynamic complexities of PTMs in vivo and their low abundance. We describe here a strategy for rapid, efficient, and comprehensive identification of PTMs occurring in biological processes in vivo. It involves a selectively excluded mass screening analysis (SEMSA) of unmodified peptides during liquid chromatography-electrospray ionization-quadrupole-time-of-flight tandem mass spectrometry (LC-ESI-q-TOF MS/MS) through replicated runs of a purified protein on two-dimensional gel. A precursor ion list of unmodified peptides with high mass intensities was obtained during the initial run followed by exclusion of these unmodified peptides in subsequent runs. The exclusion list can grow as long as replicate runs are iteratively performed. This enables the identifications of modified peptides with precursor ions of low intensities by MS/MS sequencing. Application of this approach in combination with the PTM search algorithm MODi to GAPDH protein in vivo modified by oxidative stress provides information on multiple protein modifications (19 types of modification on 42 sites) with >92% peptide coverage and the additional potential for finding novel modifications, such as transformation of Cys to Ser. On the basis of the information of precursor ion m/z, quantitative analysis of PTM was performed for identifying molecular changes in heterogeneous protein populations. Our results show that PTMs in mammalian systems in vivo are more complicated and heterogeneous than previously reported. We believe that this strategy has significant potential because it permits systematic characterization of multiple PTMs in functional proteomics.
Pharmacological characteristics and side effects of a new galenic formulation of propofol without soyabean oil* (2003)

We compared the pharmacokinetics, pharmacodynamics and safety profile of a new galenic formulation of propofol (AM149 1%), which does not contain soyabean oil, with a standard formulation of propofol (Disoprivan 1%). In a randomised, double-blind, cross-over study, 30 healthy volunteers received a single intravenous bolus injection of 2.5 mg.kg-1 propofol. Plasma propofol levels were measured for 48 h following drug administration and evaluated according to a three-compartment model. The pharmacodynamic parameters assessed included induction and emergence times, respiratory and cardiovascular effects, and pain on injection. Patients were monitored for side effects over 48 h. Owing to a high incidence of thrombophlebitis, the study was terminated prematurely and only the data of the two parallel treatment groups (15 patients in each group) were analysed. Plasma concentrations did not differ significantly between the two formulations. Anaesthesia induction and emergence times, respiratory and cardiovascular variables showed no significant differences between the two treatment groups. Pain on injection (80 vs. 20%, p < 0.01) and thrombophlebitis (93.3 vs. 6.6%, p < 0.001) occurred more frequently with AM149 than with Disoprivan. Although both formulations had similar pharmacokinetic and pharmacodynamic profiles the new formulation is not suitable for clinical use due to the high incidence of thrombophlebitis produced.
Large in-memory cyber-physical security-related analytics via scalable coherent shared memory architectures (2011)

Cyber-physical security-related queries and analytics run on traditional relational databases can take many hours to return. Furthermore, programming analytics on distributed databases requires great skill, and there is a shortage of such talent worldwide. In this talk on computational intelligence within cyber security, we will review developments of processing large datasets in-memory using a coherent shared memory approach. The coherent shared memory approach allows programmers to view a cluster of servers as a system with a single large RAM. By hiding the actual system architecture under a software layer, we proffer a more intuitive programming model. Furthermore, the design of applications is “timeless” since hardware upgrades require no changes to the software. The advantages of shared memory are countered by some disadvantages in that race conditions can occur; however, in many of these cases, we can provide models that protect us against such problems. Exemplars include sensemaking of Twitter feeds, the processing of Smart Meter datasets, and the large scale simulation of the caching of files at disparate points around the globe.