gebhart/patrepeval huggingface dataset:
Structural organization of the multifunctional animal fatty‐acid synthase (1991)

The amino acid sequence of the multifunctional fatty-acid synthase has been examined to investigate the exact location of the seven functional domains. Good agreement in predicting the location of interdomain boundaries was obtained using three independent methods. First, the sites of limited proteolytic attack that give rise to relatively stable, large polypeptide fragments were identified; cryptic sites for protease attack at the subunit interface were unmasked by first dissociating the dimer into its component subunits. Second, polypeptide regions exhibiting higher-than-average rates of non-conservative mutation were identified. Third, the sizes of putative functional domains were compared with those of related monofunctional proteins that exhibit similar primary or secondary structure. Residues 1-406 were assigned to the oxoacyl synthase, residues 430-802 to the malonyl/acetyl transferase, residues 1630-1850 to the enoyl reductase, residues 1870-2100 to the oxyreductase, residues 2114-2190 to the acyl-carrier protein and residues 2200-2505 to the thioesterase. The 47-kDa transferase and 8-kDa acyl-carrier-protein domains, which are situated at opposite ends of the multifunctional subunit, were nevertheless isolated from tryptic digests as a non-covalently associated complex. Furthermore, a centrally located domain encompassing residues 1160-1545 was isolated as a nicked dimer. These findings, indicating that interactions between the head-to-tail juxtaposed subunits occur in both the polar and equatorial regions, are consistent with previously derived electron-micrograph images that show subunit contacts in these areas. The data permit refinement of the model for the fatty-acid synthase dimer and suggest that the malonyl/acetyl transferase and oxoacyl synthase of one subunit cooperate with the reductases, acyl carrier protein and thioesterase of the companion subunit in the formation of a center for fatty-acid synthesis.
Cloning and expression of the Mycobacterium bovis BCG gene for extracellular alpha antigen (1988)

The gene for the extracellular alpha antigen of Mycobacterium bovis BCG was cloned by using a single probe restricted to G or C in the third position. This technique should have great potential for the isolation of mycobacterial antigen genes. The gene analysis revealed that the alpha antigen gene encoded 323 amino acid residues, including 40 amino acids for signal peptide followed by 283 amino acids for mature protein. This is the first report on the structure of the mycobacterial signal peptide. The promoter-like sequence and ribosome-binding site were observed upstream of the open reading frame. In the coding region, the third position of the codon showed high G + C content (86%). The gene was expressed as an unfused protein in Escherichia coli by using an E. coli expression vector. This protein, which reacted with polyclonal antibody raised against alpha antigen from Mycobacterium tuberculosis, would be applicable to the immunodiagnosis of tuberculosis.
Fast neutron sensitivities of Geiger-Mueller counter gamma dosemeters (1978)

The sensitivities to 4.2 and 5.5 MeV neutrons of different types of energy-compensated Geiger-Mueller counters used in mixed field dosimetry were measured using a field produced by the 2H(d, n)3He reaction with an isotropic gamma-dose component. Further results are presented on sensitivities to 14.7 MeV neutrons.
Coseismic Deformation from the 1999 Mw 7.1 Hector Mine, California, Earthquake as Inferred from InSAR and GPS Observations (2002)

We use interferometric synthetic aperture radar (InSAR) and Global Positioning System (GPS) observations to investigate static deformation due to the 1999 M_w 7.1 Hector Mine earthquake, that occurred in the eastern California shear zone. Interferometric decorrelation, phase, and azimuth offset measurements indicate regions of surface and near-surface slip, which we use to constrain the geometry of surface rupture. The inferred geometry is spatially complex, with multiple strands. The southern third of the rupture zone consists of three subparallel segments extending about 20 km in length in a N45°W direction. The central segment is the simplest, with a single strand crossing the Bullion Mountains and a strike of N10°W. The northern third of the rupture zone is characterized by multiple splays, with directions subparallel to strikes in the southern and central. The average strike for the entire rupture is about N30°W. The interferograms indicate significant along-strike variations in strain which are consistent with variations in the ground-based slip measurements. Using a variable resolution data sampling routine to reduce the computational burden, we invert the InSAR and GPS data for the fault geometry and distribution of slip. We compare results from assuming an elastic half-space and a layered elastic space. Results from these two elastic models are similar, although the layered-space model predicts more slip at depth than does the half-space model. The layered model predicts a maximum coseismic slip of more than 5 m at a depth of 3 to 6 km. Contrary to preliminary reports, the northern part of the Hector Mine rupture accommodates the maximum slip. Our model predictions for the surface fault offset and total seismic moment agree with both field mapping results and recent seismic models. The inferred shallow slip deficit is enigmatic and may suggest that distributed inelastic yielding occurred in the uppermost few kilometers of the crust during or soon after the earthquake.
Human Immunodeficiency Virus Type 1 Attachment, Coreceptor, and Fusion Inhibitors Are Active against both Direct andtransInfection of Primary Cells (2003)

Inhibitors of human immunodeficiency virus type 1 attachment (CD4-immunoglobulin G subclass 2), CCR5 usage (PRO 140), and fusion (T-20) were tested on diverse primary cell types that represent the major targets both for infection in vivo and for the inhibition of trans infection of target cells by virus bound to dendritic cells. Although minor cell-type-dependent differences in potency were observed, each inhibitor was active on each cell type and trans infection was similarly vulnerable to inhibition at each stage of the fusion cascade.
Transcription of hepatitis B virus in peripheral blood mononuclear cells from persistently infected patients (1997)

Hepatitis B virus (HBV) has been reported to exist in peripheral blood mononuclear cells (PBMC), but it is not clear whether it replicates there. A precondition for replication should be the formation of covalently closed viral DNA and transcription of all essential viral mRNAs. The mRNAs of HBV form a nested box with common 3' ends. In order to detect even low levels of potential replication, we developed a quantitative reverse transcription-PCR method for detection of a smaller HBV mRNA species in the presence of the larger ones. All three highly viremic patients tested so far had mRNAs for the large and the small surface proteins and the X protein of the virus within PBMC but not in the virus from their sera. Furthermore, we detected by PCR covalently closed viral DNA in their PBMC. These data suggest that HBV may be not only taken up but also replicated by mononuclear blood cells and that these cells may be an extrahepatic site of viral persistence. X mRNA was detected in the largest amount. Possibly, X protein interferes with functions of the mononuclear cells during the immune response against the virus.
Standard of Care and Promising New Agents for Triple Negative Metastatic Breast Cancer (2014)

Triple negative breast cancer (TNBC) is a cluster of heterogeneous diseases, all of them sharing the lack of expression of estrogen and progesterone receptors and HER2 protein. They are characterized by different biological, molecular and clinical features, including a poor prognosis despite the increased sensitivity to the current cytotoxic therapies. Several studies have identified important molecular features which enable further subdivision of this type of tumor. We are drawing from genomics, transcription and translation analysis at different levels, to improve our knowledge of the molecular alterations along the pathways which are activated during carcinogenesis and tumor progression. How this information should be used for the rational selection of therapy is an ongoing challenge and the subject of numerous research studies in progress. Currently, the vascular endothelial growth factor (VEGF), poly (ADP-ribose) polymerase (PARP), HSP90 and Aurora inhibitors are most used as targeting agents in metastatic setting clinical trials. In this paper we will review the current knowledge about the genetic subtypes of TNBC and their different responses to conventional therapeutic strategies, as well as to some new promising molecular target agents, aimed to achieve more tailored therapies.
Genetic and biochemical analyses of pantothenate biosynthesis in Escherichia coli and Salmonella typhimurium (1982)

Pantothenate (pan) auxotrophs of Escherichia coli K-12 and Salmonella typhimurium LT2 were characterized by enzymatic and genetic analyses. The panB mutants of both organisms and the pan-6 ("panA") mutant of S. typhimurium are deficient in ketopantoate hydroxymethyltransferase, whereas the panC mutants lack pantothenate synthetase. panD mutants of E. coli K-12 were previously shown to be deficient in aspartate 1-decarboxylase. All mutants showed only a single enzyme defect. The finding that the pan-6 mutant was deficient in ketopantoate hydroxymethyltransferase indicates that the genetic lesion is a panB allele. The pan-6 mutant therefore is deficient in the utilization of alpha-ketoisovalerate rather than the synthesis of alpha-ketoisovalerate, as originally proposed. The order of the pan genes of E. coli K-12 was determined by phage P1-mediated three-factor crosses. The clockwise order was found to be aceF panB panD panC tonA on the genetic map of E. coli K-12. The three-factor crosses were greatly facilitated by use of a closely linked Tn10 transposon as the outside marker. We also found that supplementation of E. coli K-12 auxotrophs with a high concentration of pantothenate or beta-alanine increased the intracellular coenzyme A level two- to threefold above the normal level. Supplementation with pantoate or ketopantoate resulted in smaller increases.
Mucoepidermoid carcinoma of the salivary gland: A clinicopathological study (2012)

1995年から2010年までに当科で加療した唾液腺原発粘表皮癌12例（男性6例，女性6例，平均年齢59.3歳）に対して臨床病理学的検討を行ったので報告する。Goode分類による病理組織学的悪性度は低悪性度8例，高悪性度4例であった。年齢と病理組織学的悪性度との関連は，低悪性度の平均年齢は55.1歳，高悪性度は67.5歳で年齢差を認めなかった。性別との関連では，低悪性度は女性が多く，高悪性度は男性に多かった。頸部リンパ節転移との関連では，低悪性度はN0が多く，高悪性度はN1-3が多かった。臨床病期分類との関連では，低悪性度はstage Iが多く，高悪性度はstage IVAが多かった。原発巣制御率との関連では，低悪性度75.0%に対して高悪性度の制御率は25.0%と低下していた。生存率は，低悪性度の5年死因特異的累積生存率87.5%に対して高悪性度は25.0%と不良であった。同様に5年無病累積生存率も低悪性度72.9%に対して高悪性度は22.0%と不良であった。Goode分類は粘表皮癌の予後予測として有用な病理組織学的悪性度分類であると思われた。
Environmental and Economic Costs of Pesticide Use (1992)

W orldwide, approximately 2.5 million tons of pesticides are applied each year with a purchase price of $20 billion (Pesticide News 1990). In the United States, approximately 500,000 tons of 600 different types of pesticides are used annually at a cost of $4.1 billion, including application costs (Pimentel et al. 1991). Pesticides make a significant contribution to maintaining world food production. In general, each dollar invested in pesticide control returns approximately $4 in crops saved. Estimates are that losses to pests would increase 10% if no pesticides were used at all; specific crop losses would range from zero to nearly 100%. Despite the widespread use of pesticides in the United States, pests (principally insects, plant pathogens, and weeds) destroy 37% of all potential food and fiber crops (Pimentel 1990). Although pesticides are generally profitable, their use does not always decrease crop losses. For example, even with the tenfold increase in insecticide use in the United States from 1945 to 1989, total crop losses from insect damage have nearly doubled from 7% to 13% (Pimentel et al. 1991). This rise in crop losses to in-
Distributed and Collaborative Visualization (2004)

Abstract Visualization is a powerful tool for analyzing data and presenting results in science, engineering and medicine. This paper reviews ways in which it can be used in distributed and/or collaborative environments. Distributed visualization addresses a number of resource allocation problems, including the location of processing close to data for the minimization of data traffic. The advent of the Grid Computing paradigm and the link to Web Services provides fresh challenges and opportunities for distributed visualization—including the close coupling of simulations and visualizations in a steering environment. Recent developments in collaboration have seen the growth of specialized facilities (such as Access Grid) which have supplemented traditional desktop video conferencing using the Internet and multicast communications. Collaboration allows multiple users—possibly at remote sites—to take part in the visualization process at levels which range from the viewing of images to the shared control of the visualization methods. In this review, we present a model framework for distributed and collaborative visualization and assess a selection of visualization systems and frameworks for their use in a distributed or collaborative environment. We also discuss some examples of enabling technology and review recent work from research projects in this field.
Degradable polymers for site‐specific drug delivery (1992)

Abstract The present article was aimed to review the properties and applications of the actually available biodegradable polymers that have been used as targetable drug carriers and site‐specific delivery systems. We have mainly focused on microparticulate or carrier‐based drug delivery systems with little emphasis on implants as site‐specific delivery systems. The review was divided into two major sections. The first section includes a brief description of the properties and applications of the existing biodegradable polymers for site‐specific drug delivery classified in two main categories: synthetic biopolymers (as polyesters, polyanhydrides, polyorthoesters, polyphosphazenes, polycaprolactones), and natural biomaterials (as collagen, albumin and gelatin), which still remains an active area of research in spite of the extensive development of new biodegradable polymers. The second section discusses the mechanistic approaches for the selection of polymeric carriers. General guidelines for the ideal drug carrier complex were summarized. The importance of knowing and understanding the physicochemical properties of the polymer for the optimization of the final formulation and its eventual application were emphasized. The factors governing the effective drug concentration at the specific target site were reviewed. Some of the equations describing the release kinetics of a drug from a polymeric matrix were also examined. The last section of the review describes the preparation and use of polymeric macromolecular prodrugs. A diagrammatic representation of possible polymeric prodrug systems for use in site‐specific delivery was described. The basic requirements from a polymeric prodrug system were also discussed. Finally, clinical applications of polymeric prodrugs as for cancer therapy and colonic delivery were considered.
Real-Time DNA Sequencing from Single Polymerase Molecules (2008)

We present single-molecule, real-time sequencing data obtained from a DNA polymerase performing uninterrupted template-directed synthesis using four distinguishable fluorescently labeled deoxyribonucleoside triphosphates (dNTPs). We detected the temporal order of their enzymatic incorporation into a growing DNA strand with zero-mode waveguide nanostructure arrays, which provide optical observation volume confinement and enable parallel, simultaneous detection of thousands of single-molecule sequencing reactions. Conjugation of fluorophores to the terminal phosphate moiety of the dNTPs allows continuous observation of DNA synthesis over thousands of bases without steric hindrance. The data report directly on polymerase dynamics, revealing distinct polymerization states and pause sites corresponding to DNA secondary structure. Sequence data were aligned with the known reference sequence to assay biophysical parameters of polymerization for each template position. Consensus sequences were generated from the single-molecule reads at 15-fold coverage, showing a median accuracy of 99.3%, with no systematic error beyond fluorophore-dependent error rates.
Understanding the Biochemistry and Physiology of the Gamma Carbonic Anhydrases in Methanosarcina thermophila (2007)

To date, there are five independently evolved classes (ƒN-, ƒO-, ƒ×-, ƒO-, and ƒe-) of carbonic anhydrases (CAs) participating in many physiological functions. Although the ƒ×-class is widely distributed, only one CA (Cam from a methanoarchaeon Methano-sarcina thermophila) has been characterized while no physiological function has yet been documented. The work presented in this thesis contributes to the general understanding of the biochemistry of CAs by kinetically investigating Cam, the prototypic ƒ×-class CA. In these studies, Cam was shown to utilize a hydrogen bond network analogously to the hydrogen bond network described for the ƒN- and ƒO-class CAs that involves Cam active site residues Gln75 and Asn73. In addition, Cam residue Asn202 may orient and polarize the incoming carbon dioxide molecule much like the backbone amide of ƒN-class residue Thr199. Therefore, the ƒN-, ƒO-, and ƒ×-class CA, Cam, each independently evolved variations of a fundamental functions that are essential for catalysis. This thesis also presents the initial characterization of the newly identified second ƒ×-class isozyme, CamH, thus significantly increasing the understanding of the ƒ×-class. CamH possesses several properties significantly different from Cam. Contrary to Cam, CamH does not possess a signal peptide, suggesting CamH is cytosolic whereas Cam is located at the membrane. Preliminary kinetic analyses reveal the rate of CO2 hydration in CamH (kcat/Km =104 M-1s-1) is two-fold lower than observed in Cam (kcat/Km =10 6 M-1s-1). Despite the kinetic differences, both CamH and Cam are up-regulated during aceticlastic methanogenesis. Therefore, a model was proposed based on this information outlining roles for Cam and CamH in acetate uptake in Methanosarcina species.
A Review of Therapeutic and Hemolytic Effects of Dapsone (1967)

CLINICIANS in the army and in civilian practice will probably use sulfone drugs with increasing frequency. After extensive use of sulfones for the past 25 years, dapsone (DDS), the parent sulfone, remains foremost in the therapy of leprosy throughout the world.<sup>1</sup>Introduction of dapsone into dermatologic practice in the United States<sup>2,3</sup>followed reports describing the salutary effects of the sulfone on certain chronic skin diseases.<sup>4,5</sup>Recently, the emergence of falciparum malaria resistant to chloroquine and other synthetic antimalarial drugs<sup>6,7</sup>led to an evaluation of dapsone in the therapy of these refractory strains.<sup>8</sup>Results of field trials have encouraged the US Army to add dapsone to their regimen for malaria prophylaxis.<sup>9</sup> A consideration of this effective but potentially toxic drug seems timely in view of its rapidly increasing use in civilian and military practice. Since extensive reviews of sulfones have appeared in the literature,<sup>1,10-14</sup>
Interbody Lumbar Fusion Using a Carbon Fiber Cage Implant Versus Allograft Bone (1994)

Interbody fusion using a carbon cage implant packed with autologous bone achieved a quicker and more reliable fusion compared with ethylene oxide-sterilized allograft bone. There were no adverse effects from the implant material.
Severe, Uncontrolled Hypertension and Adult‐Onset Seizures: A Case‐Control Study in Rochester, Minnesota (1996)

In the absence of clinically detected stroke, left ventricular hypertrophy without diuretic use may increase the risk of unprovoked seizures, and diuretic treatment may protect against this increased risk.
Effects of aging on the neuroglial cells and pericytes within area 17 of the rhesus monkey cerebral cortex (1991)

An electron microscopic analysis has been carried out to compare the neuroglial cells and pericytes within the primary visual cortex, area 17, of young (5-6 years) and old (25-35 years) rhesus monkeys. All of the neuroglial cell types accumulate inclusions within their cytoplasm as they age, and the inclusions within the astrocytes and oligodendrocytes are essentially characteristic of those cell types. The astrocytes probably acquire their inclusions by phagocytosis, and it is suggested that the inclusions in the oligodendrocytes are caused by an age-related degeneration of the myelin sheaths they produce. The inclusions within the microglia are very heterogeneous. They are more massive than in the other neuroglial cells, so that their inclusions may almost fill the microglia. Pericytes also accumulate inclusions with age and there is evidence to suggest that they empty the contents of their inclusions vacuoles directly into the capillaries. On the basis of counts of the numbers of profiles of neuroglial cells displaying nuclei in thin sections, the only cells to increase in number with age are the microglia. They show an increase of about 44% when the cortices of young and old monkeys are compared.
Development of Gene Expression–Based Score to Predict Sensitivity of Multiple Myeloma Cells to DNA Methylation Inhibitors (2012)

Multiple myeloma is a plasma cell cancer with poor survival, characterized by the clonal expansion of multiple myeloma cells (MMC), primarily in the bone marrow. Novel compounds are currently tested in this disease, but partial or minor patients' responses are observed for most compounds used as a single agent. The design of predictors for drug efficacy could be most useful to better understand basic mechanisms targeted by these drugs and design clinical trials. In the current study, we report the building of a DNA methylation score (DM score) predicting the efficacy of decitabine, an inhibitor of DNA methyltransferase (DNMT), targeting methylation-regulated gene expression. DM score was built by identifying 47 genes regulated by decitabine in human myeloma cell lines and the expression of which in primary MMCs of previously untreated patients is predictive for overall survival. A high DM score predicts patients' poor survival, and, of major interest, high sensitivity of primary MMCs or human myeloma cell lines to decitabine in vitro. Thus, DM score could be useful to design novel treatments with DMNT inhibitor in multiple myeloma and has highlighted 47 genes, the gene products of which could be important for multiple myeloma disease development.