gebhart/patrepeval huggingface dataset:
Sialoforms of dipeptidylpeptidase IV from rat kidney and liver (1999)

Dipeptidylpeptidase IV (DPP IV, CD26), a serine-type exo- and endopeptidase found in the cell surface membrane of many tissues, was employed as a model membrane glycoprotein to study the expression of sialoforms on cell surface glycoproteins. Native, enzymatically active DPP IV was purified from plasma membranes of kidney and liver by lectin affinity chromatography in conjunction with crown ether anion exchange chromatography. The enzyme was gradient-eluted in continuous fractions, all showing a single polypeptide band of about 100 kDa when separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under reducing, denaturing conditions. Analysis of the purified DPP IV by isoelectric focusing (IEF) showed that it consists of several polypeptides of different isoelectric points (IP) ranging from 5.5 to 7.0. In vitro- desialylation of the enzyme and subsequent isoelectric focusing revealed that the differences in isoelectric points were due to differences in the degree of sialylation. Differences in the degree of sialylation between the fractions were also demonstrated by SDS-PAGE under nonreducing and nondenaturing conditions. Increased sialylation of the enzyme as demonstrated by isoelectric focusing resulted in increased migration velocity in nonreducing and nondenaturing SDS-polyacrylamide gels. In vitro -desialylation of the enzyme and its resialylation confirmed that sialylation was responsible for this extraordinary migration behavior. The native enzyme was predominantly sialylated via alpha 2, 6-linkage, as shown by lectin affinity blotting employing Sambucus nigra agglutinin (SNA) and Maackia amurensis agglutinin (MAA). These findings demonstrate that a distinct membrane glycoprotein may exist in various sialoforms, distinguished from each other by a different number of sialic acid residues. Moreover, these sialoforms can be individually purified by crown ether anion exchange chromatography.
KRAS Mutation Is Associated With Elevated Myeloblastin Activity In Human Lung Adenocarcinoma (2012)

Lung cancer is the leading cause of all cancer deaths worldwide with suboptimal prognosis and treatment options. Therefore this study aimed to identify molecular characteristics with a predictive clinical utility which at the same time might represent novel therapeutic targets for human lung adenocarcinoma. Within this study mutations of v-Ki-RAS2 Kirsten rat sarcoma viral oncogene homolog (KRAS), a gene frequently mutated in lung adenocarcinoma, and their association with enzymatic activities, as assessed by activity-based proteomics, of members of the serine hydrolase (SH) superfamily, a large class of enzymes that have previously been linked to cancer was investigated. The results revealed that the activity of myeloblastin was significantly altered in the lung adenocarcinoma biopsies harboring a KRAS gene mutation. In conclusion myeloblastin is a potential therapeutic target for human lung adenocarcinoma, indicating that the combination of activity-based proteomics with mutational analysis is a valid approach for the discovery of novel biomarkers.
Thiamine biosynthesis in Escherichia coli: isolation and initial characterisation of the ThiGH complex (2003)

In Escherichia coli, two of the proteins required for the biosynthesis of the thiazole moiety of thiamine (vitamin B(1)) are ThiG and ThiH, encoded as part of the thiCEFSGH operon. In this study, a C-terminally hexahistidine-tagged ThiH (ThiH-His) was expressed in E. coli as a soluble protein from thiGH-His-tag and thiFSGH-His-tag-bearing plasmids. When isolated under anaerobic conditions, ThiG and ThiH-His co-purify as a large multimeric non-covalent complex. Electron paramagnetic resonance and UV-visible spectroscopy together with iron and sulfide analyses revealed the presence of an iron-sulfur cluster within this complex.
Transgenic Mice Overexpressing the Complement Inhibitor Crry as a Soluble Protein Are Protected from Antibody-induced Glomerular Injury (1998)

Complement receptor 1-related gene/protein y (Crry) is a potent murine membrane complement regulator that inhibits classical and alternative pathway C3 convertases. In nephrotoxic serum (NTS) nephritis, injected antibodies (Abs) bind to glomeruli, leading to complement activation and subsequent glomerular injury and albuminuria. To study the phenotypic effects of continuous complement pathway blockade, transgenic mice were created that express recombinant soluble (rs) Crry directed by the broadly active and heavy metal-inducible metallothionein-I promoter. One transgenic line expressing high levels of rsCrry was propagated. Serum rsCrry levels were 18.7 +/- 2.7 microg/ml (n = 5) at basal level and increased to 118.1 +/- 20.6 microg/ml 4 d after addition of zinc to the drinking water. By reverse transcription polymerase chain reaction (RT-PCR), transgene messenger (m)RNA was present in liver, kidney, brain, lung, and spleen, but not in heart. By in situ RT-PCR analysis of kidneys, transgene mRNA was widely expressed both in renal glomeruli and tubules. Urinary excretion of rsCrry was 113.4 +/- 22.4 microg/ml with a fractional excretion relative to creatinine of 13.2 +/- 2.7%, consistent with local renal production of rsCrry and secretion into urine. The founder and all transgene positive adult animals have remained healthy with no mortality or apparent phenotypic abnormalities, including infection or immune complex disease. To determine whether rsCrry blocked complement-mediated injury, NTS nephritis was induced by injection of NTS immunoglobulin (Ig)G, followed by an 18-h urine collection to quantitate the excretion of albumin as a measure of glomerular injury. In transgene-negative littermates (n = 15), transgene-positive animals (n = 10), and transgene-positive animals fed zinc (n = 10), albuminuria was 4,393 +/- 948, 1,783 +/- 454, and 1,057 +/- 277 microg/mg creatinine, respectively (P < 0.01 by ANOVA). Glomerular C3 was evident by immunofluorescence staining in 12/15 transgene-negative animals, but in none of the transgene-positive animals fed zinc. Thus, we have produced the first transgenic animals that overexpress a soluble C3 convertase inhibitor. rsCrry expression markedly ameliorates an Ab-induced disease model in vivo. These results support the hypothesis that continuous complement inhibition at the C3 convertase step is feasible and effective in complement-mediated injury states.
Integration of commercial routing with flood search routing (2002)

Integration of commercial personal communications services (PCS) technology with tactical communication systems portends to offer tremendous advantages to the warfighter, not the least of which are improved quality wireless access, and light weight and portable phones. Integration of the two systems will require conversion of signaling and routing protocols. This paper addresses the routing issues for integration of a code division multiple access (CDMA) digital PCS system with the mobile subscriber equipment (MSE) army tactical communications system. The over the air standard for the next generation digital cellular CDMA system defines the signaling protocol and message formats for mobile station (MS) to base station (BS) interoperability. Part of this standard describes the MS registration process. Subscribers register with the CDMA system through the use of a variety of different registration types. These registration types are required so that a mobile may wander over the coverage area of the system, and into coverage areas of other system providers utilizing the same standard. Users' position and profile data base information is exchanged through the use of home and visitor location registers, which communicate as the mobile subscriber wanders throughout the system. Thus, switches can route calls appropriately. MSE, on the other hand uses saturation routing, i.e. flood search routing to complete calls. A subscriber affiliation process unambiguously registers the user and all profile information associated with the user to one switch. Flood search routing is used in the system to locate the subscriber and the trunk between switches are marked for call connection between the parties. Integration of PCS registration messaging and MSE flood search routing will provide means for incorporation of CDMA technology into the MSE system.
In Vivo Optical Imaging of Interscapular Brown Adipose Tissue with 18F-FDG via Cerenkov Luminescence Imaging (2013)

CLI with (18)F-FDG is a feasible and reliable method for imaging BAT in mice. Compared to PET imaging, CLI is significantly cheaper, faster for 2D planar imaging and easier to use. We believe that this method could be used as an important tool for researchers investigating BAT.
Processivity of proteolytically modified forms of T7 RNA polymerase (1988)

Two proteolytically modified forms of T7 RNA polymerase have been characterized with respect to transcription initiation and processivity. One species, denoted 80K-20K, is singly cleaved within the region of the polypeptide chain between amino acids 172 and 180. The second species, denoted 80K, is generated by extensive proteolysis of the N-terminal 20K domain by trypsin. The 80K-20K form is fully active in initiation and escape from abortive cycling. It is deficient only in processivity on long DNA templates. Likewise, the 80K species shows initiation kinetics and abortive product synthesis similar to those of the native enzyme. This latter species, however, is unable to escape abortive cycling and shows no synthesis of transcripts longer than about eight bases. Studies of RNA and DNA binding to the three different forms of the enzyme by gel retention assays reveal that the native (98K), the 80K-20K, and the 80K species all form specific complexes with promoter-containing DNA. In addition, the native enzyme binds nonspecifically to double-stranded DNA, while the 80K-20K and 80K enzymes do not. The native enzyme also binds RNA. This RNA binding is reduced in the 80K-20K enzyme and is absent in the 80K species. We suggest a model for T7 RNA polymerase wherein the 20K N-terminal domain of the protein or a shared region between the N- and the C-terminal domains of the protein forms a nonspecific polynucleotide binding site.(ABSTRACT TRUNCATED AT 250 WORDS)
Gentamicin nucleotidyltransferase. Stereochemical inversion at phosphorus in enzymatic 2'-deoxyadenylyl transfer to tobramycin. (1986)

Gentamicin nucleotidyltransferase-catalyzed reaction of (Sp)-[alpha-17O]dATP with tobramycin produced 2"-(2'-deoxyadenosine 5'-[17O]phosphoryl)tobramycin. The configuration at phosphorus in this product was shown to be Rp by chemical degradation to chiral [17O, 18O]dAMP using a stereochemically defined procedure, and determination of the configuration at phosphorus in this product. Periodate-base treatment of 2"-(2'-deoxyadenosine 5'-[17O]phosphoryl)tobramycin followed by NaBH4 reduction produced (2-glyceryl)-[17O]dAMP, which upon snake venom phosphodiesterase-catalyzed hydrolysis in H(2)18O produced [17O,18O] dAMP. The configuration at phosphorus in this product was shown to be S by enzymatic phosphorylation to [17O,18O]dATP, adenylylcyclase (Bordetella pertussis)-catalyzed cyclization to 3',5'-cyclic [17O,18O]dAMP, and 31P NMR analysis of the ethyl esters. Since snake venom phosphodiesterase-catalyzed hydrolyses proceed with retention of configuration at phosphorus, (Sp)-[17O,18O]dAMP must have been produced from (Rp)-(2-glyceryl)-[17O]dAMP; and since the chemical degradation to the latter compound did not involve cleavage of any bonds to phosphorus, the initial enzymatic product must have been (Rp)-2"-(2'-deoxyadenosine 5'-[17O]phosphoryl)tobramycin. Therefore, nucleotidyl transfer catalyzed by gentamicin nucleotidyl-transferase proceeds with inversion of configuration at phosphorus, and the reaction mechanism involves an uneven number of phosphotransfer steps. Inasmuch as this is an uncomplicated two-substrate group transfer reaction, the mechanism probably involves direct nucleotidyl transfer from the nucleoside triphosphate to the aminoglycoside. The B. pertussis adenylylcyclase reaction was shown to proceed with inversion at phosphorus, as has been established for other adenylylcyclases.
Home photovoltaic systems for physicists (2008)

Installing a modest photovoltaic system and using it to run a suite of appliances can be educational and immensely satisfying. This brief how-to guide will help get you started.
ADME and Safety Aspects of Non-cleavable Linkers in Drug Discovery and Development (2018)

Non-cleavable linkers are used in a number of different modalities for various reasons, such as linking an active drug moiety to half-life extending molecules, to groups that enable a specific tissue or cell targeting or to facilitate active uptake into target cells. Non-cleavable linkers do not have a designated weak point in their structure that can lead to cleavage by proteases, hydrolases or chemically by pH changes. Consequently, when designing a conjugate, the choice of a non-cleavable over a cleavable linker is usually a consequence of pursuing a certain mode of action where the stability of the complex is more important than a fast liberation of the active moiety. Linkers of various length, polarity, stability and flexibility are used for different types of conjugates and the linker design is mostly driven by the particular purpose and desired mode of action. This article reviews non-cleavable linkers applied predominantly in Antibody Drug Conjugates (ADCs), and how they influence these conjugates in terms of ADME properties (absorption, distribution, metabolism and elimination) and safety.
The Sensitivity of Developing Cardiac Myofibrils to Cytochalasin-B (1972)

Developing cardiac muscle cells of 11- to 13-somite chick embryos are sensitive to cytochalasin-B. In cultured chick embryos, ranging in development from 11 to 13 somites, hearts stop beating in the presence of this agent. Both polarized light and electron microscopic examination show that cytochalasin-B disrupts existing myofibrils and inhibits the formation of new ones. Discrete Z-bands are not present in treated heart cells and thick, presumably myosin, filaments are found in disarray. These effects are reversible; after cytochalasin-B is removed from the medium, heartbeat recovers and myofibrils with discrete Z-bands reappear. Fibrillar sensitivity appears to be a function of age since fibrils in hearts of embryos having from 22 to 28 pairs of somites are more resistant.
PAI‐1 inhibits urokinase‐induced chemotaxis by internalizing the urokinase receptor (2001)

PAI-1 (plasminogen activator inhibitor-1) binds the urokinase-type plasminogen activator (uPA) and causes its degradation via its receptor uPAR and low-density lipoprotein receptor-related protein (LRP). While both uPA and PAI-1 are chemoattractants, we find that a preformed uPA-PAI-1 complex has no chemotactic activity and that PAI-1 inhibits uPA-induced chemotaxis. The inhibitory effect of PAI-1 on uPA-dependent chemotaxis is reversed when uPAR internalization is inhibited by the 39 kDa receptor-associated protein or by anti-LRP antibodies. Under the same conditions, the uPA-PAI-1 complex is turned into a chemoattractant causing cytoskeleton reorganization and extracellular-regulated kinase/mitogen-activated protein kinases activation. Thus, uPAR internalization by PAI-1 regulates cell migration.
Synthesis, Assembly, and Biofunctionalization of Silica‐Coated Gold Nanorods for Colorimetric Biosensing (2006)

Abstract An efficient silica coating process using an improved Stöber method has been used to prepare silica‐coated gold nanorods (Au rod @SiO 2 ). The resulting pure and clean silica surface of the gold nanorods (GNRs) is important for the facile self‐assembly of Au rod @SiO 2 films on poly(4‐vinylpyridine) (PVP) modified quartz substrates and offers versatile functional groups, such as the amino group, for the immobilization of biomolecules by well‐established silica surface modification protocols. The subsequent covalent bioconjugation of amino‐functionalized Au rod @SiO 2 films with goat anti‐human‐immunoglobulin G (anti‐h‐IgG) is successfully employed for the colorimetric detection of h‐IgG in a model reaction based on the specific binding affinity between the proteins. Significantly, the protein‐recognition event on the Au rod @SiO 2 films can not only be monitored by changes in the absorption of light, but is also observable by the naked eye.
Efficient record-level wrapper induction (2009)

Web information is often presented in the form of record, e.g., a product record on a shopping website or a personal profile on a social utility website. Given a host webpage and related information needs, how to identify relevant records as well as their internal semantic structures is critical to many online information systems. Wrapper induction is one of the most effective methods for such tasks. However, most traditional wrapper techniques have issues dealing with web records since they are designed to extract information from a page, not a record. We propose a record-level wrapper system. In our system, we use a novel ``broom'' structure to represent both records and generated wrappers. With such representation, our system is able to effectively extract records and identify their internal semantics at the same time. We test our system on 16 real-life websites from four different domains. Experimental results demonstrate 99\% extraction accuracy in terms of F1-Value.
Conjunctive Visual Processing Appears Abnormal in Autism (2019)

Face processing in autism spectrum disorder (ASD) is thought to be atypical, but it is unclear whether differences in visual conjunctive processing are specific to faces. To address this, we adapted a previously established eye-tracking paradigm which modulates the need for conjunctive processing by varying the degree of feature ambiguity in faces and objects. Typically-developed (TD) participants showed a canonical pattern of conjunctive processing: High-ambiguity objects were processed more conjunctively than low-ambiguity objects, and faces were processed in an equally conjunctive manner regardless of ambiguity level. In contrast, autistic individuals did not show differences in conjunctive processing based on stimulus category, providing evidence that atypical visual conjunctive processing in ASD is the result of a domain general lack of perceptual specialization.
Permeability characteristics of the human nail plate (1983)

Synopsis The permeation of chemicals across the nail plate and their consequent effects are discussed in relation to cosmetic toxicity and possible clinical efficacy. The reviewed data are then assessed and placed in context with recent observations on the direct assessment of permeability of the human nail plate. Although marked differences between the diffusional barrier characteristics of nail and stratum corneum are shown, a reasonably unified picture of nail plate permeability is drawn from the collective observations. The cosmetic and clinical implications of chemical penetration of the nail plate are briefly outlined and places where knowledge needs to be strengthened are identified.
Erlotinib Plus Gemcitabine Compared With Gemcitabine Alone in Patients With Advanced Pancreatic Cancer: A Phase III Trial of the National Cancer Institute of Canada Clinical Trials Group (2007)

To our knowledge, this randomized phase III trial is the first to demonstrate statistically significantly improved survival in advanced pancreatic cancer by adding any agent to gemcitabine. The recommended dose of erlotinib with gemcitabine for this indication is 100 mg/d.
Collaborative prediction and ranking with non-random missing data (2009)

A fundamental aspect of rating-based recommender systems is the observation process, the process by which users choose the items they rate. Nearly all research on collaborative filtering and recommender systems is founded on the assumption that missing ratings are missing at random. The statistical theory of missing data shows that incorrect assumptions about missing data can lead to biased parameter estimation and prediction. In a recent study, we demonstrated strong evidence for violations of the missing at random condition in a real recommender system. In this paper we present the first study of the effect of non-random missing data on collaborative ranking, and extend our previous results regarding the impact of non-random missing data on collaborative prediction.
The T4 Glycoprotein Is a Cell-surface Receptor for the AIDS Virus (1986)

Taken together, our studies suggest a mechanism of AIDS virus infection that initially involves the specific association of the AIDS virus with T4 molecules on the cell surface. This association does not require additional T-cell-specific molecules and can be demonstrated on both B lymphocytes and epithelial cell lines. The T4-AIDS virus complex is likely to be internalized in endosomes via receptor-mediated endocytosis. The virus can then fuse with the vacuolar membrane, releasing the viral nucleocapsid into the cytoplasm to undergo uncoating. Viral replication does not appear to require the environment of a T lymphocyte because active infection is also observed in human T4+ B lymphocytes and epithelial cell lines. Moreover, the T4 gene is expressed in the brain as well as in lymphocytes, providing an explanation for the dual neurotropic and lymphotropic character of the virus. In this manner, a T-lymphocyte surface protein thought to be important in mediating effector cell-target cell interactions has been exploited by a human lymphotropic virus to target the AIDS virus specifically to populations of T4+ cells.
Escherichia coli aromatic amino acid aminotransferase: Characterization and comparison with aspartate aminotransferase (1993)

Aromatic amino acid aminotransferase (ArAT) from Escherichia coli was overexpressed in E. coli cells, purified, and characterized. The enzyme was similar to aspartate aminotransferase (AspAT) of E. coli in many aspects, such as gross protein structure and spectroscopic properties. The reactions of pyridoxal 5'-phosphate-form ArAT with amino acids and pyridoxamine 5'-phosphate-form ArAT with oxo acids were investigated using stopped-flow spectrophotometric techniques. The kinetic parameters for these "half" reactions could excellently explain the ArAT-catalyzed overall transamination reactions at pH 8.0. Reactions of ArAT with aspartate and tryptophan which had been deuterated at position 2 showed isotope effects of 2.5 and 6.0 in the kcat values of the half-reactions, showing that the proton-transfer step is at least partially rate-limiting for these reactions. ArAT and AspAT showed overlapping substrate specificity. Both ArAT and AspAT were active toward dicarboxylic substrates. ArAT showed, however, 10(3)-fold higher activity toward aromatic substrates than AspAT. This high activity toward aromatic substrates was in part ascribed to the active site hydrophobicity of ArAT, which was suggested to be about 1.4 times as large as that of AspAT. In addition to dicarboxylic substrate analogs, aromatic substrate analogs such as carboxylic acids, 2-methyl amino acids, and 3-hydroxy amino acids caused characteristic changes in the absorption spectra of ArAT, while these aromatic analogs did not significantly change the spectra of AspAT. In particular, the erythro-3-hydroxy analogs of phenylalanine and aspartate caused a prominent absorption of ArAT at around 500 nm, which is generally ascribed to the accumulation of quinonoid intermediates. The threo forms of these 3-hydroxy analogs acted as substrates for ArAT. The erythro and threo forms of 3-hydroxyaspartate reacted with AspAT similarly as they reacted with ArAT; however, both forms of 3-phenylserine were poor substrates for AspAT, although phenylalanine was a fairly good substrate for AspAT. The observations on the two erythro-3-hydroxy amino acids show the similar orientation of these analogs in the active site of ArAT, probably through a hydrogen-bonding network involving the hydroxy groups of the analogs and Tyr70, and suggest that the aromatic binding pocket is near or even overlaps the side-chain-carboxylate-binding site for dicarboxylic substrates.