gebhart/patrepeval huggingface dataset:
Lysine 2,3‐Aminomutase and the Mechanism of the Interconversion of Lysine and β‐Lysine (1993)

Introduction Properties of Lysine 2,3-aminomutase The Role of S-Adenosylmethionine in Hydrogen Transfer The Formation of Substrate Radicals as Intermediates The Role of Pyridoxal Phosphate in Amino Group Migration The Importance of Iron-Sulfur Clusters and Cobalt Adenosylcobalamin-dependent Aminomutases Adenosyl-cofactors as Evolutionary Predecessors of Adenosylcobalamin
Blockwise Approach to Fragments of the O-Specific Polysaccharide of Shigella flexneri Serotype 2a:  Convergent Synthesis of a Decasaccharide Representative of a Dimer of the Branched Repeating Unit1 (2004)

The D'A'B'(E')C'DAB(E)C decasaccharide representative of a dimer of a frame-shifted pentasaccharide repeating unit of the O-specific polysaccharide of Shigella flexneri 2a was synthesized as its methyl glycoside by condensing a pentasaccharide donor (D'A'B'(E')C') and a pentasaccharide acceptor (DAB(E)C-OMe). Several convergent routes to these two building blocks, involving either the AB linkage or the BC linkage as the disconnection site, were evaluated in comparison to the linear strategy. The latter was preferred. It is based on the use of the trichloroacetimidate chemistry. The target branched oligosaccharide was designed to probe the recognition at the molecular level of the natural polysaccharide by protective monoclonal antibodies.
Essential functions of amino-terminal domains in the yeast telomerase catalytic subunit revealed by selection for viable mutants (1999)

Telomerase is a ribonucleoprotein complex that adds telomeric DNA repeats to the ends of most eukaryotic chromosomes. The reverse transcriptase subunit of telomerase (TERT) differs from retroviral reverse transcriptases in having a long basic amino-terminal extension. We made a large library containing random mutations in the amino terminus of the EST2 gene, which encodes the Saccharomyces cerevisiae TERT, and selected functional alleles by their ability to rescue senescence of telomerase-negative cells. Through analysis of 265 mutations, the amino terminus of Est2p was found to contain at least four essential regions. This domain structure was verified by a combination of deletion and alanine-block mutations. Mutations within two essential domains of the protein reduced RNA binding, suggesting that the amino terminus of Est2p makes important contacts with the intrinsic RNA component of telomerase. A mutant close to the amino terminus retained RNA binding and in vitro enzymatic activity but was defective in vivo, suggesting a role in interaction with other macromolecular components of telomerase.
Human genes involved in cholesterol metabolism: chromosomal mapping of the loci for the low density lipoprotein receptor and 3-hydroxy-3-methylglutaryl-coenzyme A reductase with cDNA probes. (1985)

Cellular cholesterol metabolism is regulated primarily through the coordinate expression of two proteins, the low density lipoprotein (LDL) receptor and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (EC 1.1.1.34). We have used cDNA probes for the human genes encoding these proteins to determine the precise chromosomal location of the two loci. By in situ hybridization we have regionally mapped the LDL receptor gene, LDLR, to the short arm of chromosome 19 in bands p13.1-p13.3. This result concurs with and extends a previous study in which LDLR was mapped to chromosome 19 by screening somatic cell hybrids with a species-specific monoclonal antibody. We have assigned the HMG-CoA reductase gene, HMGCR, to chromosome 5 by Southern blotting of DNA from a somatic cell hybrid panel and to bands 5q13.3-q14 by in situ hybridizations of the cDNA probe to human metaphase cells with normal and rearranged chromosomes.
A clinical, noninvasive, MR imaging-monitored ultrasound surgery method (1996)

A noninvasive method of tissue ablation that is guided and monitored with magnetic resonance (MR) imaging has been developed. The method uses sharply focused ultrasound transducers of different focal lengths to induce a localized temperature elevation during a short exposure (1-20 seconds). A hydraulic, computer-controlled positioning device moves the transducer in an MR imager. The positioner is built into a standard cradle in the imager. The system includes cavitation detection and power monitoring circuitry for patient safety. The target volume is outlined with cross-sectional MR images obtained immediately before sonication. By means of the software, the focus is moved to ablate the volume defined with the images. The temperature elevation during the exposure is monitored by means of the proton resonance frequency shift with fast gradient-echo sequences, and the necrosed volume is demonstrated with T2-weighted fast spin-echo images. This method has been extensively tested in in vivo animal experiments and is now undergoing clinical trial.
Murine Cytomegalovirus Open Reading Frame M27 Plays an Important Role in Growth and Virulence in Mice (2001)

Using a Tn3-based transposon mutagenesis approach, we have generated a pool of murine cytomegalovirus (MCMV) mutants. In this study, one of the mutants, RvM27, which contained the transposon sequence at open reading frame M27, was characterized both in tissue culture and in immunocompetent BALB/c mice and immunodeficient SCID mice. Our results suggest that the M27 carboxyl-terminal sequence is dispensable for viral replication in vitro. Compared to the wild-type strain and a rescued virus that restored the M27 region, RvM27 was attenuated in growth in both BALB/c and SCID mice that were intraperitoneally infected with the viruses. Specifically, the titers of RvM27 in the salivary glands, lungs, spleens, livers, and kidneys of the infected SCID mice at 21 days postinfection were 50- to 500-fold lower than those of the wild-type virus and the rescued virus. Moreover, the virulence of the mutant virus appeared to be attenuated, because no deaths occurred among SCID mice infected with RvM27 for up to 37 days postinfection, while all the animals infected with the wild-type and rescued viruses died within 27 days postinfection. Our observations provide the first direct evidence to suggest that a disruption of M27 expression results in reduced viral growth and attenuated viral virulence in vivo in infected animals. Moreover, these results suggest that M27 is a viral determinant required for optimal MCMV growth and virulence in vivo and provide insight into the functions of the M27 homologues found in other animal and human CMVs as well as in other betaherpesviruses.
Pathways of Glucose Metabolism in Candida 107, a Lipid-accumulating Yeast (1977)

Phosphofructokinase was not detected in extracts of Candida 107 prepared in a variety of ways but was highly active in cells treated with toluene. Disruption of these cells destroyed activity of phosphofructokinase indicating that the enzyme is extremely labile. As patterns of labelling from [I-14C]glucose and [6-14C]glucose showed that 60% of glucose was metabolized via the pentose cycle, augmentation of this cycle is necessary to account for the high molar growth yields of this yeast. Phosphoketolases, reacting with xylulose 5-phosphate and fructose 6-phosphate, were found but the extent to which they contribute to glucose metabolism was not assessed.
Nonlinear and two-photon-induced fluorescence (1997)

The Theory of Two-Photon Induced Fluorescence Anisotropy P.R. Callis. Anisotropy Decays Induced by Two-Photon Excitation C.K. Johnson, C. Wan. Multiphoton Excitation of Biochemical Fluorophores J.R. Lakowicz, I. Gryczynski. Two-Photon Excitation and Anisotropy Decays in Membranes and Oriented Systems W. van der Meer, S.-Y.S. Chen. Two-Photon Induced Fluorescence of Proteins b. Kierdaszuk, et al. Fluorescence and Multiwave Mixing Induced by Photon Absorption of Excited Molecules V. Bogdanov. Ultrafast Stimulated Emission Spectroscopy G.J. Blanchard. Fluorescence Quenching by Stimulated Emission J.R. Lakowicz, I. Gryczynski. Increasing the Resolution of Far-Field Fluorescence Light Microscopy by Point Spread Functional Engineering S.W. Hell. Time-Resolved Stimulated-Emission and Transient-Absorption Microscopy and Spectroscopy P.T.C. So, et al. Index.
Regulation and Accreditation in Cellular Therapy (2009)

This chapter contains sections titled: Introduction Haemopoietic stem cell transplant activity The structure of SCT programmes European Union directives and legislation The Human Tissue Act 2004 The US Food and Drug Administration Non-governmental (voluntary) accreditation Conclusions: how do HSCT programmes respond to the challenge? Key points Further reading
Myocardial microvascular permeability, interstitial oedema, and compromised cardiac function (2010)

The heart, perhaps more than any other organ, is exquisitely sensitive to increases in microvascular permeability and the accumulation of myocardial interstitial oedema fluid. Whereas some organs can cope with profound increases in the interstitial fluid volume or oedema formation without a compromise in function, heart function is significantly compromised with only a few percent increase in the interstitial fluid volume. This would be of little consequence if myocardial oedema were an uncommon pathology. On the contrary, myocardial oedema forms in response to many disease states as well as clinical interventions such as cardiopulmonary bypass and cardioplegic arrest common to many cardiothoracic surgical procedures. The heart's inability to function effectively in the presence of myocardial oedema is further confounded by the perplexing fact that the resolution of myocardial oedema does not restore normal cardiac function. We will attempt to provide some insight as to how microvascular permeability and myocardial oedema formation compromise cardiac function and discuss the acute changes that might take place in the myocardium to perpetuate compromised cardiac function following oedema resolution. We will also discuss compensatory changes in the interstitial matrix of the heart in response to chronic myocardial oedema and the role they play to optimize myocardial function during chronic oedemagenic disease.
The Efficient Catabolism of Thrombin-Protease Nexin 1 Complexes Is a Synergistic Mechanism That Requires Both the LDL Receptor-related Protein and Cell Surface Heparins (1997)

Protease nexin 1 (PN1) is a serine protease inhibitor (SERPIN) that acts as a suicide substrate for thrombin (Th) and urokinase-type plasminogen activator (uPA). PN1 forms 1:1 stoichiometric complexes with these proteases, which are then rapidly bound, internalized, and degraded. The low density lipoprotein receptor-related protein (LRP) is the receptor responsible for the internalization of protease-PN1 complexes. However, we found that the LRP is not significantly involved in the initial cell surface binding of thrombin-PN1, leading us to investigate what cellular component was responsible for this initial interaction. Since Th-PN1 complexes retain a high-affinity for heparin after complex formation, unlike several of the other SERPINs, we tested the possibility that cell surface heparins were involved in initial complex binding. Soluble heparin was found to be a potent inhibitor of the binding of Th-PN1 to the cell surface and greatly facilitated the dissociation of Th-PN1 complexes pre-bound in the absence of soluble heparin. To ascertain the role of cell surface heparins, further studies were done using complexes of thrombin and PN1(K7E), a variant of PN1 in which the heparin binding site was rendered non-functional. When added at equal initial concentrations of complexes, Th-PN1(K7E) was catabolized 5- to 10-fold less efficiently than Th-PN1, a direct result of the greatly diminished initial binding of the Th-PN1(K7E) complexes. These data demonstrate the sizable contribution of cell surface heparins to Thrombin-PN1 complex binding and support a model in which these heparins act to concentrate the complexes at the cell surface facilitating their subsequent LRP-dependent endocytosis.
Abstractions for Recursive Pointer Data Structures: Improving the Analysis of Imperative Programs. (1992)

The aims of this study were to describe rheumatoid arthritis patients' compliance with continued exercise after participation in a 2-year supervised high-intensity exercise program and to investigate if the initially achieved effectiveness and safety were sustained. Data were gathered by follow-up of the participants who completed the 2-year high-intensity intervention in a randomized controlled trial (Rheumatoid Arthritis Patient In Training study). Eighteen months thereafter, measurements of compliance, aerobic capacity, muscle strength, functional ability, disease activity, and radiological damage of the large joints were performed. Seventy-one patients were available for follow-up at 18 months, of whom 60 (84%) were still exercising (exercise group: EG), with average similar intensity but at a lower frequency as the initial intervention. Eleven patients (16%) reported low intensity or no exercises (no-exercise group: no-EG). Patients in the EG had better aerobic fitness and functional ability, lower disease activity, and higher attendance rate after the initial 2-year intervention. At follow-up, both groups showed a deterioration of aerobic fitness and only patients in the EG were able to behold their muscle strength gains. Functional ability, gained during the previous participation in high-intensity exercises, remained stable in both groups. Importantly, no detrimental effects on disease activity or radiological damage of the large joints were found in either group. In conclusion, the majority of the patients who participated in the 24-month high-intensity exercise program continued exercising in the ensuing 18 months. In contrast to those who did not continue exercising, they were able to preserve their gains in muscle strength without increased disease activity or progression of radiological damage.
Antibody Responses To Toxic-Shock-Syndrome (TSS) Toxin by Patients with TSS and by Healthy Staphylococcal Carriers (1984)

Serum samples taken from women with toxic-shock syndrome (TSS) and from women without a history of TSS were examined for the presence of antibodies to toxic-shock-syndrome toxin (TST). Serum samples from 38 women with TSS and from 70 women with no history of TSS were analyzed by radioimmunoassay (RIA) and by an enzyme-linked immunoadsorbent assay (ELISA). Antitoxin titers obtained by the assays were highly correlated. Antibody levels in sera of women with TSS, or a history of TSS, were significantly lower than levels in sera of women with no prior evidence of TSS. The mean level of antitoxin titers in the total sample of acute, convalescent, and recovered TSS groups was significantly lower than that of the control groups, which consisted of 31 carriers of genital Staphylococcus aureus and a similar number of age- and race-matched noncarriers. Although a trend toward elevated antitoxin titers was apparent after recovery, no vigorous immunologic response to TST was noted. In contrast, the majority of healthy women demonstrated measurable antitoxin titers, a finding indicative of current or prior colonization with TST-producing strains of S. aureus. The data suggest that absence of antibodies to the TSS toxin may be a predisposing factor in the development of clinical disease.
Cosolvent effect of alkyl acrylates on the phase behaviour of poly(alkyl acrylates)–supercritical CO2 mixtures (1998)

Cloud-point data to 220°C and 2000 bar are presented for ternary mixtures of poly(butyl acrylate)–CO2–butyl acrylate (BA) and poly(ethyl hexyl acrylate)–CO2–ethyl hexyl acrylate (EHA). The addition of either BA or EHA to the respective polymer–solvent mixtures decreases the cloud-point pressures by as much as 1000 bar and changes the pressure–temperature slope of the cloud-point curves from negative to positive which significantly increases the single-phase region. Both BA and EHA provide favourable polar interactions with the acrylate groups in the backbone of the polymer and they densify the solvent mixture. However, the effect of these cosolvents on the location of the cloud-point curves diminishes as the amount added to the solution increases.
Biliary elimination of ticarcillin plus clavulanic acid (Claventin): experimental and clinical study. (1989)

The aim of the present study was to assess the biliary elimination and disposition of Claventin, a combination of clavulanic acid (CA), a beta-lactamase inhibitor, with ticarcillin (TIC), resulting in an enhancement of the activity of the antibiotic and broadening of its antibacterial spectrum. This work was done experimentally and in humans. Assays of both molecules were performed by HPLC. During a 3 h perfusion of five isolated rabbit liver preparations, 1.3 +/- 0.2% and 0.4 +/- 0.1% of TIC and CA added to the circulating blood were eliminated in the bile. At the same time, 31.8% of TIC and 50.5% of CA were submitted to a hepatic biotransformation. In healthy subjects (n = 5), after a single i.v. injection of 3.2 g of Claventin (TIC: 3 g + CA: 0.2 g) mean peak concentrations of 66.8 +/- 31.9 micrograms/ml (TIC 4th h) and 0.3 +/- 0.1 microgram/ml (CA, 2nd h) were observed in the aspirated duodenal fluid where 0.07% and 0.01%, respectively, of the administered dose were recovered during the 4 h investigation period. In cholecystectomized patients (n = 10) provided with a T-tube, i.v. administration of Claventin, 3.2 g, resulted in biliary maximal levels of 177 +/- 49 micrograms/ml (TIC: 2nd h) and 2.7 +/- 0.5 microgram/ml (CA 1st h). Total amount of each derivative eliminated in bile over 12 h averaged 0.28% (TIC) and 0.05% (CA) of the given dose. Hepatobiliary clearance was 20.5 ml/h (TIC) and 4.4 ml/h (CA). In intra-operative simultaneously sampled specimens of serum, choledochal bile, gallbladder bile and gallbladder wall, the following concentrations were measured 1 h after i.v. administration of Claventin: TIC: 105 +/- 10; 386 +/- 66; 72 +/- 20 micrograms/ml and 36 +/- 11 micrograms/g, CA: 3.5 +/- 0.7; 5.9 +/- 1.5; 0.3 +/- 0.3 microgram/ml and 0.1 +/- 0.1 microgram/g. The biliary pharmacokinetics determined in humans makes it possible to consider favourably the prophylactic use of Claventin in surgery of the biliary tree and constitute a good prerequisite for a possible beneficial treatment of biliary tract infections.
Nonclassical IL-1β Secretion Stimulated by P2X7 Receptors Is Dependent on Inflammasome Activation and Correlated with Exosome Release in Murine Macrophages (2007)

Several mechanistically distinct models of nonclassical secretion, including exocytosis of secretory lysosomes, shedding of plasma membrane microvesicles, and direct efflux through plasma membrane transporters, have been proposed to explain the rapid export of caspase-1-processed IL-1 beta from monocytes/macrophages in response to activation of P2X7 receptors (P2X7R) by extracellular ATP. We compared the contribution of these mechanisms to P2X7R-stimulated IL-1 beta secretion in primary bone marrow-derived macrophages isolated from wild-type, P2X7R knockout, or apoptosis-associated speck-like protein containing a C-terminal CARD knockout mice. Our experiments revealed the following: 1) a novel correlation between IL-1 beta secretion and the release of the MHC-II membrane protein, which is a marker of plasma membranes, recycling endosomes, multivesicular bodies, and released exosomes; 2) a common and absolute requirement for inflammasome assembly and active caspase-1 in triggering the cotemporal export of IL-1 beta and MHC-II; and 3) mechanistic dissociation of IL-1 beta export from either secretory lysosome exocytosis or plasma membrane microvesicle shedding on the basis of different requirements for extracellular Ca(2+) and differential sensitivity to pharmacological agents that block activation of caspase-1 inflammasomes. Thus, neither secretory lysosome exocytosis nor microvesicle shedding models constitute the major pathways for nonclassical IL-1 beta secretion from ATP-stimulated murine macrophages. Our findings suggest an alternative model of IL-1 beta release that may involve the P2X7R-induced formation of multivesicular bodies that contain exosomes with entrapped IL-1 beta, caspase-1, and other inflammasome components.
Altered Regulation of Cyclin G in Human Breast Cancer and Its Specific Localization at Replication Foci in Response to DNA Damage in p53+/+ Cells (1999)

Cyclin G, a recent addition to the cyclin family, was initially identified in screens for new src kinase family members and soon thereafter by differential screening for transcriptional targets of the tumor suppressor gene, p53. We have identified cyclin G as being overexpressed in breast and prostate cancer cells using differential display polymerase chain reaction screening. We demonstrate here that cyclin G is overexpressed in human breast and prostate cancer cells and in cancer cells in situ from tumor specimens. Cyclin G expression was tightly regulated throughout the cell cycle in normal breast cells, peaking at the S and G2/M phases of the cell cycle with lower levels in G1. The cell cycle-dependent expression was absent in breast cancer cells. Following DNA damage in normal p53+/+ cells, cyclin G is triggered to cluster in discrete nuclear DNA replication foci that contain replication-associated proteins such as proliferating cell nuclear antigen (PCNA). While p53-/- cells displayed a faint cyclin G nuclear staining pattern, there was no increased expression and no change in distribution of the staining pattern after DNA damage. The specific subcellular localization of cyclin G at DNA replication foci provides an additional link between p53-mediated growth arrest and cell cycle regulation and suggests that cyclin G may act as an effector of p53-mediated events by functional association with replication foci protein(s).
Electronic aspects of organic photochemistry (1990)

Photophysical and Photochemical Processes Location of Minima, Funnels and Barriers on Surfaces ELEMENTARY PHOTOCHEMICAL STEPS Two-Center Reactions: One Active Orbital per Atom Cyclic Multicenter Reactions: One Active Orbital per Atom Linear Multicenter Reactions: One Active Orbital per Atom Reactions with More than One Active Orbital per Atom Epilogue Appendices Index.
Astrocytes Block Axonal Regeneration in Mammals by Activating the Physiological Stop Pathway (1987)

Regenerating sensory axons in the dorsal roots of adult mammals are stopped at the junction between the root and spinal cord by reactive astrocytes. Do these cells stop axonal elongation by activating the physiological mechanisms that normally operate to stop axons during development, or do they physically obstruct the elongating axons? In order to distinguish these possibilities, the cytology of the axon tips of regenerating axons that were stopped by astrocytes was compared with the axon tips that were physically obstructed at a cul-de-sac produced by ligating a peripheral nerve. The terminals of the physically obstructed axon tips were distended with neurofilaments and other axonally transported structures that had accumulated when the axons stopped elongating. By contrast, neurofilaments did not accumulate in the tips of regenerating axons that were stopped by spinal cord astrocytes at the dorsal root transitional zone. These axo-glial terminals resembled the terminals that axons make on target neurons during normal development. On the basis of these observations, astrocytes appear to stop axons from regenerating in the mammalian spinal cord by activating the physiological stop pathway that is built into the axon and that normally operates when axons form stable terminals on target cells.