gebhart/patrepeval huggingface dataset:
Direct profiling and imaging of peptides and proteins from mammalian cells and tissue sections by mass spectrometry (2002)

Mass spectrometry can be used to map the distribution of targeted compounds in tissue, providing important molecular information in many areas of biological research. Matrix assisted laser desorption/ionization - time of flight - mass spectrometry (MALDI-TOF-MS) is well suited for the analysis of tissue samples with a spatial resolution of about 30 microm for compounds in a mass range from 1000 to over 50 000 Da. Direct analysis of tissue sections requires spotting or coating of the tissue with a matrix compound typically sinapinic acid or other cinnamic acid analogs. A raster of this sample by the laser beam and subsequent mass analysis of the desorbed ions can record molecular intensities throughout the section. The overall process is illustrated by profiling and imaging of mouse epididymis sections where protein activity changes markedly throughout the section.
Crystal structure of mammalian α1,6-fucosyltransferase, FUT8 (2006)

Mammalian alpha1,6-fucosyltransferase (FUT8) catalyses the transfer of a fucose residue from a donor substrate, guanosine 5'-diphosphate-beta-L-fucose to the reducing terminal N-acetylglucosamine (GlcNAc) of the core structure of an asparagine-linked oligosaccharide. Alpha1,6-fucosylation, also referred to as core fucosylation, plays an essential role in various pathophysiological events. Our group reported that FUT8 null mice showed severe growth retardation and emphysema-like lung-destruction as a result of the dysfunction of epidermal growth factor and transforming growth factor-beta receptors. To elucidate the molecular basis of FUT8 with respect to pathophysiology, the crystal structure of human FUT8 was determined at 2.6 A resolution. The overall structure of FUT8 was found to consist of three domains: an N-terminal coiled-coil domain, a catalytic domain, and a C-terminal SH3 domain. The catalytic region appears to be similar to GT-B glycosyltransferases rather than GT-A. The C-terminal part of the catalytic domain of FUT8 includes a Rossmann fold with three regions that are conserved in alpha1,6-, alpha1,2-, and protein O-fucosyltransferases. The SH3 domain of FUT8 is similar to other SH3 domain-containing proteins, although the significance of this domain remains to be elucidated. The present findings of FUT8 suggest that the conserved residues in the three conserved regions participate in the Rossmann fold and act as the donor binding site, or in catalysis, thus playing key roles in the fucose-transferring reaction.
EnclaveDB: A Secure Database Using SGX (2018)

We propose EnclaveDB, a database engine that guarantees confidentiality, integrity, and freshness for data and queries. EnclaveDB guarantees these properties even when the database administrator is malicious, when an attacker has compromised the operating system or the hypervisor, and when the database runs in an untrusted host in the cloud. EnclaveDB achieves this by placing sensitive data (tables, indexes and other metadata) in enclaves protected by trusted hardware (such as Intel SGX). EnclaveDB has a small trusted computing base, which includes an in-memory storage and query engine, a transaction manager and pre-compiled stored procedures. A key component of EnclaveDB is an efficient protocol for checking integrity and freshness of the database log. The protocol supports concurrent, asynchronous appends and truncation, and requires minimal synchronization between threads. Our experiments using standard database benchmarks and a performance model that simulates large enclaves show that EnclaveDB achieves strong security with low overhead (up to 40% for TPC-C) compared to an industry strength in-memory database engine.
Chain Shuffling to Modify Properties of Recombinant Immunoglobulins (2003)

Combinatorial libraries and selection of variants from such libraries have proven to be a successful approach for identifying molecules with novel or improved properties. The importance of antibody (Ab) molecules in basic and applied research, as well as the extensive knowledge of how they interact with their antigen (Ag) targets, have made them favorite targets for modification by this approach. The binding site of Abs can be described as a set of modules that together make up the Ag-binding site. These modules may be defined either as the heavy-chain (HC) and light-chain (LC) variable domains (V H and V L, respectively) or as the six individual complementarity-determining regions (CDRs) or hypervariable loops, which act together to form this structure. The variable CDRs reside in a relatively fixed framework region (FR) that makes up the basic structure and fold of the protein.
원저 : 류마티스 관절염 환자의 활액과 활막조직에서의 IL - 6 의 활성도 (1993)

Background: Interleukin-6 (IL-6), previously known as B cell stimulatory factor 2 (BSF-2) is a multifunctional cytokine that is produced by a various cells and plays an important role in the host defence mechanism such as regulation of immune response, acute phase reaction and hematopoiesis. Recent investigations have demonstrated that unregulated expression of IL-6 gene and overproducion of lL-6 were involved in the pathogenesis of cardiac myxoma, Castleman's disease, autoimmune disease, proliferative glomerulonephritis and certain lymphoid malignancies, especially plasmacytoma/multiple myelomas. We tried to evaluate the regulatory effect of IL 6 an the pathogenesis of rheumatoid arthritis (RA) which is characterized by hyperactivation of 8 cells, presence of various autoantibodies and increase in acute phase proteins and platelets. Methods: The IL-6 activity was measured by bioassay using the murine IL-6 dependent hybridoma cell lines (MH60. BSF2), ELISA method and immunohistochemical analysis. Results: 1) IL-6 activity was significantly elevated m synovial fluid from patients with rheumatoid arthritis (RA, n= 25) as compared with osteoarthrits (OA, n=6) and seronegative arthritis (SNA, n=4) (p<0.05). 2) IL-6 activity was also elevated in serum from patients with RA as compared with other disease (P <0.01). 3) High IL-6 activity and destructive changes in affected joints had a tendency to be correlated (r=0.716), And positive correlations between IL-6 activity and C-reactive proteins in serum were observed in patients with RA (r=0.752). 4) Immunohistachemical analysis demonstrated that positive-staining cells were located on the perivascular space. Conclusion: The results suggest that unregulated production of IL-6 may play an important role in the pathogenesis of RA and could explain local as well as generalized symptoms of RA. However, it is not known whether excessive production of IL-6 is a primary event in the disease process, or secondary consequence.
Susceptibility of Antibiotic-Susceptible and Antibiotic-Resistant Hospital Bacteria to Disinfectants (1997)

OBJECTIVE: To evaluate whether hospital strains of antibiotic-resistant bacteria exhibited altered susceptibility to disinfectants. DESIGN: Antibiotic-susceptible bacteria were obtained from American Type Culture Collection: Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Klebsiella pneumoniae, Salmonella choleraesuis, and Pseudomonas aeruginosa. Hospital strains of antibiotic-resistant bacteria were obtained from clinical isolates, including: S aureus, S epidermidis, E coli, Enterococcus species, K pneumoniae, and P aeruginosa. The Association of Official Analytical Chemist's use-dilution method was used to test these 12 strains of 7 bacterial pathogens for their susceptibility to a phenol and a quaternary ammonium compound. For five pathogens, we tested a susceptible and a more resistant strain in 20 comparative trials (5 pathogens, 2 disinfectants, 2 dilutions per disinfectant). RESULTS: In our 20 comparative trials, the antibiotic-resistant strains exhibited an increased resistance to the disinfectant in only a single instance. CONCLUSIONS: Our data demonstrate that the development of antibiotic resistance does not appear to be correlated to increased resistance to disinfectants.
An epoxygenase metabolite of arachidonic acid 5,6 epoxy-eicosatrienoic acid mediates angiotensin-induced natriuresis in proximal tubular epithelium. (1991)

Several laboratories have documented that angiotensin II (AII) induces natriuresis in proximal tubular epithelium by a mechanism that has as yet not been disclosed. The present studies were designed to test the hypothesis that cytochrome P450-dependent metabolites of arachidonic acid mediate this effect. In cultured rabbit proximal tubule a ketoconazole-sensitive product comigrating with 5,6-epoxy-eicosatrienoic acid (5,6-EET) on reverse phase and normal phase HPLC was stimulated two-fold by AII. We employed cultures of early S1 segments on a modified Ussing chamber as a bioassay to evaluate the effects of AII and 5,6-EET on unidirectional 22Na (apical to basolateral) flux (JNa). AII inhibited JNa, an effect that was abolished by ketoconazole. Furthermore, 5,6-EET decreased JNa in a manner analogous to AII, and the effect was potentiated by inhibition of endogenous 5,6-EET production. Employing the Ca2(+)-sensitive fluorescent probe, Fura 2, we observed a dose-dependent increase in [Ca2+]i with nM to microM 5,6-EET, effects that were abolished by depletion of extracellular Ca2+ and voltage-sensitive Ca-channel blockers. These observations support the hypothesis that 5,6-EET represents the second messenger that mediates AII-induced natriuresis via stimulation of Ca2+ influx through voltage-sensitive channels.
A selective CVD tungsten local interconnect technology (2003)

A novel local interconnect technology utilizing polysilicon strapped with selective CVD (chemical vapor deposition) tungsten (W) has been developed for advanced CMOS applications. Problems associated with etching of a local interconnect material do not exist, since the local interconnects are of polysilicon and defined at the same level as the gate electrodes. CVD W deposited on the polysilicon serves as a very attractive gate shunt and local interconnect because of its low resistivity and ability to carry a high-density current reliably. Both n- and p-channel MOSFETs have been successfully fabricated with this technology. An alternate version of this technology utilizing a second polysilicon layer for the formation of the local interconnects is also discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
SERS: Materials, applications, and the future (2012)

Surface enhanced Raman spectroscopy (SERS) is a powerful vibrational spectroscopy technique that allows for highly sensitive structural detection of low concentration analytes through the amplification of electromagnetic fields generated by the excitation of localized surface plasmons. SERS has progressed from studies of model systems on roughened electrodes to highly sophisticated studies, such as single molecule spectroscopy. We summarize the current state of knowledge concerning the mechanism of SERS and new substrate materials. We highlight recent applications of SERS including sensing, spectroelectrochemistry, single molecule SERS, and real-world applications. We also discuss contributions to the field from the Van Duyne group. This review concludes with a discussion of future directions for this field including biological probing with UV-SERS, tip-enhanced Raman spectroscopy, and ultrafast SERS.
Phosphorylation of Streptococcus salivarius Lactose Permease (LacS) by HPr(His∼P) and HPr(Ser-P)(His∼P) and Effects on Growth (2003)

The oral bacterium Streptococcus salivarius takes up lactose via a transporter called LacS that shares 95% identity with the LacS from Streptococcus thermophilus, a phylogenetically closely related organism. S. thermophilus releases galactose into the medium during growth on lactose. Expulsion of galactose is mediated via LacS and stimulated by phosphorylation of the transporter by HPr(His approximately P), a phosphocarrier of the phosphoenolpyruvate:sugar phosphotransferase transport system (PTS). Unlike S. thermophilus, S. salivarius grew on lactose without expelling galactose and took up galactose and lactose concomitantly when it is grown in a medium containing both sugars. Analysis of the C-terminal end of S. salivarius LacS revealed a IIA-like domain (IIA(LacS)) almost identical to the IIA domain of S. thermophilus LacS. Experiments performed with purified proteins showed that S. salivarius IIA(LacS) was reversibly phosphorylated on a histidine residue at position 552 not only by HPr(His approximately P) but also by HPr(Ser-P)(His approximately P), a doubly phosphorylated form of HPr present in large amounts in rapidly growing S. salivarius cells. Two other major S. salivarius PTS proteins, IIAB(L)(Man) and IIAB(H)(Man), were unable to phosphorylate IIA(LacS). The effect of LacS phosphorylation on growth was studied with strain G71, an S. salivarius enzyme I-negative mutant that cannot synthesize HPr(His approximately P) or HPr(Ser-P)(His approximately P). These results indicated that (i) the wild-type and mutant strains had identical generation times on lactose, (ii) neither strain expelled galactose during growth on lactose, (iii) both strains metabolized lactose and galactose concomitantly when grown in a medium containing both sugars, and (iv) the growth of the mutant was slightly reduced on galactose.
Polyclonal B-cell activation reveals antibodies against human immunodeficiency virus type 1 (HIV-1) in HIV-1-seronegative individuals. (1990)

Identification of human immunodeficiency virus type 1 (HIV-1)-infected individuals is of paramount importance for the control of the spread of AIDS worldwide. Currently, the vast majority of screening centers throughout the world rely on serological techniques. As such, clinically asymptomatic but HIV-infected, seronegative individuals are rarely identified. In this report we show that 18% (30/165) of seronegative individuals who were considered to be a unique cohort of patients at high risk for HIV infection had circulating B cells that, upon in vitro polyclonal activation with pokeweed mitogen, produced antibodies reactive with HIV. Furthermore, polymerase chain reaction analysis of DNA obtained from aliquots of the peripheral blood mononuclear cells from these seronegative but pokeweed mitogen assay-positive individuals tested revealed the presence of HIV-specific sequences in a significant number of samples. In addition, depletion of CD8+ T cells from peripheral blood mononuclear cells of HIV-1-seronegative individuals prior to in vitro culture with pokeweed mitogen resulted in increased sensitivity for detecting HIV-reactive antibodies. This assay has obvious epidemiological implications, especially in the case of high-risk groups, and also provides a simple technique to enhance detection of HIV-infected individuals. Of further interest is the determination of the mechanisms related to the lack of HIV-specific antibodies in the serum of these infected individuals.
Infective Endocarditis Due to Staphylococcus aureus (1999)

Our results suggest that in left-sided S aureus IE anticoagulant therapy is closely associated with death due to neurologic damage. According to our data, as soon as the clinical diagnosis of S aureus IE is indicated the use of anticoagulant therapy should be immediately stopped until the septic phase of the disease is overcome.
Synthesis of esters of phosphonoformic acid and their antiherpes activity (1983)

Aliphatic and aromatic mono-, di-, and triesters of phosphonoformic acid (foscarnet) were synthesized. The triesters were prepared by the Michaelis-Arbuzov reaction and were hydrolyzed to di- and monoesters. The compounds were tested for antiviral activity on isolated herpes simplex virus type 1 (HSV-1) DNA polymerase, in a HSV-1 plaque reduction assay, and on a cutaneous HSV-1 infection in guinea pigs. None of the esters inhibited the activity of isolated HSV-1 polymerases. Monoesters with a free carboxylic group and diesters with an aromatic carboxylic ester function were active against the cutaneous herpes infection. Mono- and diesters with an aromatic phosphonic ester group also showed activity in the plaque-reduction assay. However, mono- and diesters with an aromatic phosphonic ester group also showed activity in the plaque-reduction assay. However, mono- and diesters with aliphatic carboxylic ester groups were inactive in all test systems. The results show that all three acidic groups of phosphonoformic acid must be free in order to get antiviral activity at the enzyme level. However, certain esters of this acid may be biotransformed to the acid itself to give antiherpes activity.
Amplification of the Streptococcus faecalis proton-translocating ATPase by a decrease in cytoplasmic pH (1984)

When Streptococcus faecalis was grown in the presence of protonophores , an ATPase activity of the membrane was increased at a pH below 8.0 but not at a pH above 8.0. Characteristics of this increased ATPase were identical to those of a proton-translocating ATPase (H+-ATPase) located on the membrane of normal cells. The cytoplasmic pH was regulated at 7.6 to 7.8 but was not regulated in the presence of protonophores . The increase in the H+-ATPase was observed when the cytoplasmic pH was lowered to less than 7.6 by the addition of protonophores and was not related to the dissipation of the proton motive force. Thus, we suggest that the H+-ATPase of the membrane is amplified when the cytoplasmic pH is lowered below the pH at which it is regulated under normal conditions.
Precise Measurement of the G+C Content of Deoxyribonucleic Acid by High-Performance Liquid Chromatography (1989)

High-performance liquid chromatography is a promising alternative for determining the G+C content of bacterial deoxyribonucleic acid (DNA). The method which we evaluated involves enzymatic degradation of the DNA to nucleosides by PI nuclease and bovine intestinal mucosa alkaline phosphatase, separation of the nucleosides by high-performance liquid chromatography, and calculation of the G+C content from the apparent ratios of deoxyguanosine and thymidine. Because the nucleosides are released from the DNA at different rates, incomplete degradation produces large errors in the apparent G+C content. For partially purified DNA, salts are a major source of interference in degradation. However, when the salts are carefully removed, the preparation and degradation of DNA contribute little error to the determination of G+C content. This method also requires careful selection of the chromatographic conditions to ensure separation of the major nucleosides from the nucleosides of modified bases and precise control of the flow rates. Both of these conditions are achievable with standard equipment and C18 reversed-phase columns. Then the method is precise, and the relative standard deviations of replicate measurements are close to 0.1%. It is also rapid, and a single measurement requires about 15 min. It requires small amounts of sample, and the G+C content can be determined from DNA isolated from a single bacterial colony. It is not affected by contamination with ribonucleic acid. Because this method yields a direct measurement, it may also be more accurate than indirect methods, such as the buoyant density and thermal denaturation methods. In addition, for highly purified DNA, the extent of modification can be determined.
Atypical Hemolytic Uremic Syndrome: Update on the Complement System and What Is New (2010)

Atypical hemolytic uremic syndrome (aHUS) is a rare disease of microangiopathic hemolytic anemia, thrombocytopenia, and predominant renal impairment. It is characterized by the absence of Shiga toxin-producing bacteria as a triggering factor. During the last decade, aHUS has been demonstrated to be a disorder of the complement alternative pathway dysregulation, as there is a growing list of mutations and polymorphisms in the genes encoding the complement regulatory proteins that alone or in combination may lead to aHUS. Approximately 60% of aHUS patients have so-called 'loss-of-function' mutations in the genes encoding the complement regulatory proteins, which normally protect host cells from complement activation: complement factor H (CFH), factor I (CFI) and membrane cofactor protein (MCP or CD46), or have 'gain-of-function' mutations in the genes encoding the complement factor B or C3. In addition, approximately 10% of aHUS patients have a functional CFH deficiency due to anti-CFH antibodies. Recent advances in understanding the pathogenesis of aHUS have led to a revised classification of the syndrome. Normal plasma levels of CFH and CFI do not preclude the presence of a mutation in these genes. Further, genotype-phenotype correlations of aHUS have clinical significance in predicting renal recovery and transplant outcome. Therefore, it is important to make a comprehensive analysis and perform genetic screening of the complement system in patients with aHUS to allow a more precise approach, especially before transplantation. This may also provide opportunities for more specific treatments in the near future, as complement inhibition could represent a therapeutic target in these patients who have a considerably poor prognosis in terms of both mortality and progression to end-stage renal disease and a great risk of disease recurrence after transplantation.
Cross-reactivity between HLA-A2-restricted FLU-M1:58–66 and HIV p17 GAG:77–85 epitopes in HIV-infected and uninfected individuals (2003)

BACKGROUND: The matrix protein of the influenza A virus and the matrix and capsid proteins of the human immunodeficiency virus (HIV) share striking structural similarities which may have evolutionary and biological significance. These similarities led us to hypothesize the existence of cross-reactivity between HLA-A2-restricted FLU-M1:58-66 and HIV-1 p17 GAG:77-85 epitopes. METHODS: The hypothesis that these two epitopes are cross-reactive was tested by determining the presence and extent of FLU/GAG immune cross-reactivity in lymphocytes from HIV-seropositive and seronegative HLA-A2+ donors by cytotoxicity assays and tetramer analyses. Moreover, the molecular basis for FLU/GAG cross-reactivity in HIV-seropositive and seronegative donors was studied by comparing lymphocyte-derived cDNA sequences corresponding to the TCR-beta variable regions, in order to determine whether stimulation of lymphocytes with either peptide results in the expansion of identical T-cell clonotypes. RESULTS: Here, we report evidence of cross-reactivity between FLU-M1:58-66 and HIV-1 p17 GAG:77-85 epitopes following in vitro stimulation of PBMC derived from either HIV-seropositive or seronegative HLA-A2+ donors as determined by cytotoxicity assays, tetramer analyses, and molecular clonotyping. CONCLUSION: These results suggest that immunity to the matrix protein of the influenza virus may drive a specific immune response to an HLA-A2-restricted HIV gag epitope in HIV-infected and uninfected donors vaccinated against influenza.