gebhart/patrepeval huggingface dataset:
Cancer diagnosis using proteomic patterns (2003)

The advent of proteomics has brought with it the hope of discovering novel biomarkers that can be used to diagnose diseases, predict susceptibility and monitor progression. Much of this effort has focused upon the mass spectral identification of the thousands of proteins that populate complex biosystems such as serum and tissues. A revolutionary approach in proteomic pattern analysis has emerged as an effective method for the early diagnosis of diseases such as ovarian cancer. Proteomic pattern analysis relies on the pattern of proteins observed and does not rely on the identification of a traceable biomarker. Hundreds of clinical samples per day can be analyzed utilizing this technology, which has the potential to be a novel, highly sensitive diagnostic tool for the early detection of cancer.
Processing and trafficking of clotting factor X in the secretory pathway. Effects of warfarin (1992)

Clotting factor X undergoes several post-translational processing steps in the liver before the protein appears in blood as the mature two-chain zymogen. In this study we have followed the factor X precursor through the secretory pathway in rat liver in order to identify the site for proteolytic processing of the precursor into a two-chain form and the site for warfarin inhibition of precursor trafficking within the pathway. Isolated rat liver Golgi apparatus was shown to harbour two single-chains of factor X precursors of 70 and 74 kDa and the heavy (50 kDa) and light chains of factor X. It was demonstrated that the two-chain factor X form was produced from a late processing form of the factor X precursor, which indicated that the site for proteolytic conversion to a two-chain form was in the trans-Golgi compartment. The 70 and 74 kDa single-chain precursors and also the light chain of the two-chain form were shown to contain the factor X propeptide which is normally removed before the coagulation factor appears in blood. The data demonstrate that intra-chain cleavage of a single chain factor X precursor in the trans-Golgi compartment can precede release of the propeptide. Warfarin was shown to affect trafficking of the factor X precursor between the endoplasmic reticulum (ER) and the Golgi apparatus. The data suggest a link between vitamin K-dependent gamma-carboxylation of the precursor and its exit from the ER. Warfarin administration resulted in accumulation of factor X precursors associated with the ER membrane. These precursors appear to be stabilized from intracellular degradation while in the ER. In contrast to the large increase in the factor X precursor concentration in the ER membrane, there was no change in the prothrombin precursor concentration as a result of warfarin action on the liver. However, intracellular turnover of the microsomal prothrombin precursor pool in warfarin-treated rats resulted in a pool of less negatively charged proteins, indicating ongoing protein synthesis but inhibition of gamma-carboxylation. The data are consistent with previous findings [Wallin & Martin (1988) J. Biol. Chem. 263, 9994-10001] suggesting that prothrombin and factor X are processed differently by the vitamin K-dependent carboxylase in the ER membrane.
Inactivation of Tumor Suppressor Genes: Choice Between Genetic and Epigenetic Routes (2004)

Inactivation of tumor suppressor genes can occur via epigenetic or genetic mechanisms. The reasons underlying this choice of gene inactivation routes during tumorigenesis have not been clarified, nor have the precise roles in cancer evolution for genes which are solely affected by epigenetically mediated loss of function. Here we discuss a mouse model in which the disruption of Hic1, a gene solely involved with epigenetic silencing in human cancer, can markedly influence the disruption of the powerful tumor suppressor gene, p53, in determining malignant tumor incidence, spectrum and virulence. Furthermore, the mechanism for inactivation of Hic1 in tumors produced can be switched from an epigenetic to a genetic mode depending on how the Hic1 and p53 knockouts are localized on mouse chromosome 11. The value of such a model and the implications of the findings for choice of epigenetically versus genetically determined loss of gene function in cancer are discussed.
What’s for Dinner?: Entner-Doudoroff Metabolism in Escherichia coli (1998)

The Entner-Doudoroff (ED) pathway was first discovered in 1952 in Pseudomonas saccharophila (21) and several years later was shown to be present in Escherichia coli (23). Although generally considered to be restricted to gram-negative bacteria, the ED pathway is present in all three phylogenetic domains, including the most deeply rooted Archaea (18). The ubiquity of the ED pathway suggests that it is of far greater importance in nature than was previously recognized. In fact, a recent essay on the evolution of glycolytic pathways suggested that the ED pathway predates the Embden-Meyerhof-Parnas pathway (60). E. coli is generally recognized as a member of the normal gastrointestinal microbiota and is extremely versatile, with the ability to grow on many of the nutrients that can be found there (45). But what exactly are the nutrients preferred by E. coli to support its growth in the intestine? And what about growth of E. coli outside of the intestine? Certainly E. coli spends periods of time in aquatic, aerobic habitats when it is in between host intestinal tracts. Mounting evidence suggests that sugar acid metabolism via the ED pathway is important for growth of E. coli in both intestinal and aquatic habitats. The role of the ED pathway, especially with regard to colonization of the mammalian large intestine, will be discussed below. The biochemistry and physiology of sugar acid metabolism in E. coli are very well understood, and several newly discovered genes encoding sugar acid transporters, associated regulatory proteins, and a novel pathway for sugar acid catabolism have been identified as a result of the E. coli genome project (12). Homology searches reveal that the genes of the ED pathway are present on several other genomes (Table 1), and it is becoming clear that there will be additional, perhaps even novel, sugar acid catabolic pathways revealed by analysis of these genomes. OVERVIEW OF THE ED PATHWAY The ED pathway can be properly considered as one of three pathways found in nature, in addition to the Embden-Meyerhof-Parnas and pentose phosphate pathways, that feed into the “bottom half” of glycolysis, which is central to all of intermediary metabolism (18, 28). The overall schemes of the ED and Embden-Meyerhof-Parnas pathways are quite similar: 6-carbon sugars are primed by phosphorylation and subsequently cleaved by aldolase enzymes into two 3-carbon intermediates (Fig. 1). The primary distinction between the two pathways lies in the nature of the 6-carbon metabolites that serve as substrates for aldol cleavage: for the ED pathway this intermediate is 2-keto-3-deoxy-6-phosphogluconate (KDPG). The first of the two key enzymes is unique to the ED pathway, 6-phosphogluconate dehydratase (Edd), which catalyzes a dehydration of 6-phosphogluconate to form KDPG. The second enzyme of the ED pathway, KDPG aldolase (Eda), catalyzes an aldol cleavage of KDPG to form pyruvate and glyceraldehyde3-phosphate. The triose phosphate intermediate is further metabolized by the glycolytic pathway and provides energy via substrate-level phosphorylation.
Update: Peptide Motifs for Insertion of Radiolabeled Biomolecules into Cells and Routing to the Nucleus for Cancer Imaging or Radiotherapeutic Applications (2008)

Intracellular compartments, in particular the cytoplasm or nucleus, have generally been poorly accessible or inaccessible to radiolabeled biomolecules (e.g., monoclonal antibodies [mAbs], peptides, or oligonucleotides [ODNs]). However, recently cell-penetrating peptides (CPPs) and nuclear localizing peptide sequences (NLSs) have been shown to have the capability of inserting biomolecules into cells and transporting them to the cell nucleus. This discovery now presents intriguing new opportunities to design radiopharmaceuticals that could potentially probe, through imaging, the expression of key intracellular or intranuclear regulatory proteins that define the tumor phenotype, predict outcome, or act as sensitive reporters of response or resistance to treatment. CPPs could also more efficiently internalize radiolabeled antisense ODNs or peptide nucleic acids (PNAs) into tumor cells to enhance the sensitivity of imaging gene expression at the mRNA level. Perhaps one of the most exciting new developments to emerge is the use of NLS to route mAbs and peptides conjugated to nanometer-micrometer range Auger-electron-emitting radionuclides (e.g., (111)In) to the nucleus of cancer cells following their receptor-mediated internalization. In the nucleus, these electrons are highly potent in causing lethal DNA strand breaks. In some cases, NLSs are present naturally in peptide growth factors or their receptors, where they function to deliver internalized ligands to the nucleus, or alternatively, they can be introduced synthetically. This update reviews the properties of CPPs and NLS and focuses on their use for inserting radiolabeled biomolecules into cancer cells for imaging or targeted Auger electron radiotherapy of malignancies.
5'-[4-(Pivaloyloxy)-1,3,2-dioxaphosphorinan-2-yl]-2'-deoxy-5-fluorouridine: A Membrane-Permeating Prodrug of 5-Fluoro-2'-deoxyuridylic Acid (FdUMP) (1995)

5'-[4-(Pivaloyloxy)-1,3,2-dioxaphosphorinan-2-yl]-2'-deoxy-5 -fluorouridine (1c) was designed as a potential membrane-permeable prodrug of 2'-deoxy-5-fluorouridine 5'-monophosphate (FdUMP), a putative active metabolite of the antitumor drug 5-fluorouracil (FU). It was anticipated that 1c would be hydrolyzed in vivo by carboxylate esterase (E.C. 3.1.1.1) to the labile 4-hydroxy analogue 2a, which should penetrate cells by passive diffusion and ring open to the aldehyde 3a. Spontaneous elimination of acrolein from 3a would then generate the free nucleotide, FdUMP. 1c might also penetrate cells directly and undergo the same degradation sequence after hydrolysis by cellular esterases. 1c was prepared by condensing 2-hydroxy-2-oxo-4-(pivaloyloxy)-1,3,2-dioxaphosphorinane with 2'-deoxy-5-fluorouridine (FUdR) in the presence of triphenylphosphine and diethyl azodicarboxylate. 1c was moderately stable in aqueous buffers over the pH range 1-7.4 (T1/2 > 30 h). In the presence of carboxylate esterase, however, it was degraded, in a concentration-dependent manner, to FdUMP. No intermediates were detected in the incubation mixture. In mouse plasma, 1c was degraded first to FdUMP and then to FUdR. The latter is presumably formed by dephosphorylation of FdUMP by plasma 5'-nucleotidases or phosphatases. 1c and FU inhibited the growth of Chinese hamster ovary (CHO) cells in culture at a concentration of 5 x 10(-6) M. 1c was equally potent against a CHO variant that was 20-fold resistant to FU. Administered intraperitoneally for 5 consecutive days, 1c was as effective as FU at prolonging the life span of mice bearing P-388 leukemia. In the presence of 2-mercaptoehtanesulfonic acid, an acrolein scavenger, 1c was equally effective against a P-388 mutant cell line that was resistant to FU. Collectively, these data suggest that 1c acts as a membrane-permeable prodrug of FdUMP. This prodrug strategy may be generally useful for introducing dianionic phosphates and phosphonates into cells.
Routine Phenotypic Identification of Bacterial Species of the Family Pasteurellaceae Isolated from Animals (2008)

Pasteurellaceae are bacteria with an important role as primary or opportunistic, mainly respiratory, pathogens in domestic and wild animals. Some species of Pasteurellaceae cause severe diseases with high economic losses in commercial animal husbandry and are of great diagnostic concern. Because of new data on the phylogeny of Pasteurellaceae, their taxonomy has recently been revised profoundly, thus requiring an improved phenotypic differentiation procedure to identify the individual species of this family. A new and simplified procedure to identify species of Actinobacillus, Avibacterium, Gallibacterium, Haemophilus, Mannheimia, Nicoletella, and Pasteurella, which are most commonly isolated from clinical samples of diseased animals in veterinary diagnostic laboratories, is presented in the current study. The identification procedure was evaluated with 40 type and reference strains and with 267 strains from routine diagnostic analysis of various animal species, including 28 different bacterial species. Type, reference, and field strains were analyzed by 16S ribosomal RNA (rrs) and rpoB gene sequencing for unambiguous species determination as a basis to evaluate the phenotypic differentiation schema. Primary phenotypic differentiation is based on beta-nicotinamide adenine dinucleotide (beta-NAD) dependence and hemolysis, which are readily determined on the isolation medium. The procedure divides the 28 species into 4 groups for which particular biochemical reactions were chosen to identify the bacterial species. The phenotypic identification procedure allowed researchers to determine the species of 240 out of 267 field strains. The procedure is an easy and cost-effective system for the rapid identification of species of the Pasteurellaceae family isolated from clinical specimens of animals.
Bicyclic compounds as ring-constrained inhibitors of protein-tyrosine kinase p56lck (1993)

A study was undertaken to prepare inhibitors of the lymphocyte protein-tyrosine kinase p56lck. Using the known p56lck inhibitor 3,4-dihydroxy-alpha-cyanocinnamamide (4) as a lead compound, bicyclic analogues were designed as conformationally constrained mimetics in which the phenyl ring and vinyl side chain of the cinnamamide are locked into a coplanar orientation. Such planarity was rationalized to be an important determinant for binding within a putative flat, cleftlike catalytic cavity. Bicyclic analogues were prepared using the naphthalene, quinoline, isoquinoline, and 2-iminochromene ring systems and examined for their ability to inhibit autophosphorylation of immunopurified p56lck. The most potent analogues were methyl 7,8-dihydroxyisoquinoline-3-carboxylate (12) (IC50 = 0.2 microM) and 7,8-dihydroxyisoquinoline-3-carboxamide (13) (IC50 = 0.5 microM). Inhibition by 12 was not competitive with respect to ATP. These compounds may represent important new structural motifs for the development of p56lck inhibitors.
Evaluation of an automatic segmentation algorithm for definition of head and neck organs at risk (2014)

Improvements in accuracy of automatic segmentation for head and neck OARs would be worthwhile and are required before its routine clinical implementation.
Polysaccharide Hydrolase Folds Diversity of Structure and Convergence of Function (1997)

Polysaccharide glycosyl hydrolases are a group of enzymes that hydrolyze the glycosidic bond between carbohydrates or between a carbohydrate and a noncarbohydrate moiety. Here we illustrate that traditional schemes for grouping enzymes, such as by substrate specificity or by organism of origin, are not appropriate when thinking of structure—function relationships and protein engineering. Instead, sequence comparisons and structural studies reveal that enzymes with diverse specificities and from diverse organisms can be placed into groups among which mechanisms are largely conserved and insights are likely to be transferrable. In particular, we illustrate how enzymes have been grouped using protein sequence alignment algorithms and hydrophobic cluster analysis. Unfortunately for those who seek to improve cellulase function by design, cellulases are distributed throughout glycosyl hydrolase Families 1,5,6,7,9, and 45. These cellulase families include members from widely different fold types, i.e., the TIM-barrel, βαβ-barrel variant (a TIM-barrel-like structure that is imperfectly superimposable on the TIM-barrel template), β-sandwich, and α-helix circular array. This diversity in cellulase fold structure must be taken into account when considering the transfer and application of design strategies between various cellulases.
Numerical Simulation of Steady and Unsteady Meso-scale Eddies (1989)

Eddy circulation in numerical hydrodynamic models is examined to show how eddies with diameters of the order of 102 metres can be adequately simulated. The results demonstrate the techniques which produce fast eddy circulation, while providing insight into the processes operating physically. By utilising a third order finite difference approximation for the non-linear terms and by judicious selection of the horizontal eddy viscosity coefficient, large increases (more than an order of magnitude) in the eddy strength can be achieved. These results are demonstrated numerically using the schematized bathymetry of flow past a rectangular step and examples of eddy circulation in natural environments, the latter selected from simulations of a variety of locations on Australia's Great Barrier Reef. A 'phase eddy parameter' is proposed which describes the potential for eddy formation in natural unsteady flows.
Design of compact pinhole SPECT system based on flat panel PMT (2003)

The present development of new gamma imagers has allowed to realize detectors with ultra high spatial resolution and very compact size for PET as well as for SPET application. In this paper we analyze and discuss the possible design of new pinhole SPECT scanners based on heads which consist of flat panel PSPMT and different design of scintillation arrays like NaI(Tl), 1 mm pixel size, and CsI(Tl) multi layers array, mounted in off centered configuration to improve the intrinsic spatial resolution of the imagers. The results show that an array configuration 2/spl times/2 Hamamatsu flat panel PSPMTs coupled to NaI(Tl) scintillation array with 1 mm pixel size, represents the best trade off between compactness and spatial resolution of pinhole SPET scanner. The use of off centered CsI(Tl) scintillation array coupled to a single flat panel PSPMT allows to arrange a high sensitivity and very compact pinhole SPET scanner at very low cost only worsening of 50% spatial resolution than an Anger gamma camera pinhole SPECT.
Optoelectronic Tweezers as a Tool for Parallel Single-Cell Manipulation and Stimulation (2009)

Optoelectronic tweezers (OET) is a promising approach for the parallel manipulation of single cells for a variety of biological applications. By combining the manipulation capabilities of OET with other relevant biological techniques (such as cell lysis and electroporation), one can realize a true parallel, single-cell diagnostic and stimulation tool. Here, we demonstrate the utility of the OET device by integrating it onto single-chip systems capable of performing in-situ, electrode-based electroporation/lysis, individual cell, light-induced lysis, and light-induced electroporation.
Reduction of 1-beta-D-arabinofuranosylcytosine and adriamycin cytotoxicity following cell cycle arrest by anguidine. (1981)

The protein synthesis inhibitor anguidine induced a frozen cell cycle state in exponentially growing Chinese hamster ovary cells, as demonstrated by serial DNA flow cytometric measurements in the absence and presence of Colcemid as a stathmokinetic agent. The minimally effective concentration of anguidine for induction of cell cycle arrest was 0.1 microgram/ml. As demonstrated by tritiated thymidine labeling index and DNA flow cytometric investigations in the presence of Colcemid, a 4-hr exposure of Chinese hamster ovary cells to greater than or equal to 4 micrograms of anguidine per ml effected a greater than or equal to 12-hr cycle perturbation at no cytotoxic expense. Preincubation of exponentially growing Chinese hamster ovary cells for 4 hr with 5 micrograms of anguidine per ml reduced the cytotoxicity from Adriamycin (1 hr; 0.1 to 10 micrograms/ml) and from 1-beta-D-arabinofuranosylcytosine treatment (18 hr; 5 to 50 micrograms/ml) by 10- to 100-fold. Further investigation of the concentration dependence and time course of this protective effect of anguidine revealed a plateau at 1 microgram of anguidine per ml and lack of protection in case of anguidine exposure subsequent to Adriamycin and 1-beta-D-arabinofuranosylcytosine treatment. Prolongation of the treatment-free interval between initial anguidine exposure and 1-hr Adriamycin treatment demonstrated partial recovery of DNA synthesis associated with some loss in cytoprotection. Our results indicate that the largely indiscriminate interference with cycle progression by anguidine under noncytotoxic conditions affords significant protection against 1-beta-D-arabinofuranosylcytosine and Adriamycin-related cytotoxicity, the degree of which appears to be related to the extent of reduction in cycle traverse rate. Thus, anguidine may serve as a useful probe to study in detail drug-induced lethal injury as a function of cycle traverse rate.
VAP-1: a new anti-inflammatory target? (2004)

HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY

Polymorphonuclear leukocyte (PMN) migration through the endothelium to sites of tissue inflammation is regulated by a complex network of signals involving adhesion molecules and chemotactic cytokines. The first stage of the extravasation cascade involves
Characterization and Biological Properties of A Hepatitis B Virus Isolated From A Patient Without Hepatitis B Virus Serologic Markers (1990)

We have developed a rapid method to characterize genomic diversity of low-level hepatitis B and related viral agents after their identification in serum by high-affinity HBsAg-antibody monoclonal antibody capture and subsequent polymerase chain reaction amplification. Serum from an individual with chronic liver disease and without hepatitis B virus serological markers but reactive by monoclonal antibody capture/polymerase chain reaction amplification was inoculated into a chimpanzee. After inoculation, an acute hepatitis B virus-like hepatitis developed in the chimpanzee. Analysis of serial liver biopsy samples showed the persistence of hepatitis B virus DNA for more than 17 mo after resolution of acute hepatitis and seroconversion. Applying the technique of restriction enzyme fragment analysis to serial chimpanzee liver biopsy samples and acute-phase sera, along with the serum inoculum, we established that all hepatitis B virus DNA sequences are derived from the same viral agent. We present evidence that the viral DNA persisted as a nonreplicating episomal form in the nucleus of hepatocytes. This study demonstrates that after clinical and serological recovery from an acute hepatitis, there may be persistence of low-level hepatitis B virus-related genome in the liver despite the presence of antibodies to HBsAg. Such persistence of viral genome may be a natural sequela of infection and may serve as a source of viral latency and possible reactivation. Finally, cloning and complete nucleic-acid sequencing of this virus have demonstrated multiple nucleotide and amino acid changes compared with all known hepatitis B virus subtypes. These changes may have contributed in part to a different antigenic composition or immunological reactivity of the host to this hepatitis B virus isolate.
Anatomical Frames of Reference and Biomechanics (1980)

For dynamic simulation of human movement, segment axis systems are often defined by the inertial tensor unique to each simulated body segment. When empirical three-dimensional data are sought that describe either the mass distribution or the kinematic properties of the human body, anatomical frames of reference are needed for the sake of measurement methodology and data comparability. Anatomical axis systems are based on anatomical landmarks that must represent functional and stable features in the skeletal geometry. The role of anthropometric landmarks used in defining anatomical coordinate axis systems is discussed with examples from current research regarding the kinematics of the hip joint and mass distribution of the whole body. The use of anatomical frames of reference will improve the correspondence between computer simulations of the human body and the biological structure.