gebhart/patrepeval huggingface dataset:
Premalignant and malignant disease of the breast: the roles of the pathologist. (1998)

This review targets the current role of the pathologist in the diagnosis and management of breast disease, a responsibility that evolved along with an increasingly complex approach to human breast cancer. We will focus on the three major areas of this responsibility: premalignancy, highlighting the atypical hyperplasias; the carcinomas in situ, highlighting low grade ductal carcinoma in situ; and the stratification and prognosis of invasive carcinomas. It will be evident that with the advent of an increasingly rich menu of treatment options, the challenge to identify an optimal categorization of breast cancer and its putative precursors is not static.
Genome of the Bacterium Streptococcus pneumoniae Strain R6 (2001)

Streptococcus pneumoniae is among the most significant causes of bacterial disease in humans. Here we report the 2,038,615-bp genomic sequence of the gram-positive bacterium S. pneumoniae R6. Because the R6 strain is avirulent and, more importantly, because it is readily transformed with DNA from homologous species and many heterologous species, it is the principal platform for investigation of the biology of this important pathogen. It is also used as a primary vehicle for genomics-based development of antibiotics for gram-positive bacteria. In our analysis of the genome, we identified a large number of new uncharacterized genes predicted to encode proteins that either reside on the surface of the cell or are secreted. Among those proteins there may be new targets for vaccine and antibiotic development.
Hypothalamic ependymal‐glial cells express the glucose transporter GLUT2, a protein involved in glucose sensing (2003)

The GLUT2 glucose transporter and the K-ATP-sensitive potassium channels have been implicated as an integral part of the glucose-sensing mechanism in the pancreatic islet beta cells. The expression of GLUT2 and K-ATP channels in the hypothalamic region suggest that they are also involved in a sensing mechanism in this area. The hypothalamic glial cells, known as tanycytes alpha and beta, are specialized ependymal cells that bridge the cerebrospinal fluid and the portal blood of the median eminence. We used immunocytochemistry, in situ hybridization and transport analyses to demonstrate the glucose transporters expressed in tanycytes. Confocal microscopy using specific antibodies against GLUT1 and GLUT2 indicated that both transporters are expressed in alpha and beta tanycytes. In addition, primary cultures of mouse hypothalamic tanycytes were found to express both GLUT1 and GLUT2 transporters. Transport studies, including 2-deoxy-glucose and fructose uptake in the presence or absence of inhibitors, indicated that these transporters are functional in cultured tanycytes. Finally, our analyses indicated that tanycytes express the K-ATP channel subunit Kir6.1 in vitro. As the expression of GLUT2 and K-ATP channel is linked to glucose-sensing mechanisms in pancreatic beta cells, we postulate that tanycytes may be responsible, at least in part, for a mechanism that allows the hypothalamus to detect changes in glucose concentrations.
An Integrated Quad-Core Opteron Processor (2007)

An integrated quad-core times86 processor is implemented in a 65nm 11M SOI CMOS process. Based on an enhanced Opterontrade core, the SoC-developed processor employs power- and thermal-management techniques throughout the design. The SRAM cache designs target process variation considerations and future process scalability. A DDR2/DDR3 combo-PHY and HT3 I/Os provide high-bandwidth interfaces.
Possible involvement of inositol 1,4,5-trisphosphate receptor type 3 (IP3R3) in the peritoneal dissemination of gastric cancers. (2003)

Our previous study using cDNA microarray showed that differentially expressed genes among gastric cancer cells involved in peritoneal dissemination could be positively identified. One of these genes, which is overexpressed, is inositol 1,4,5-trisphosphate receptor type 3 (IP3R3). IP3R3 is responsible for the intracellular Ca2+ release channel and for mobilizing stored Ca2+. Three different receptor types have been molecularly cloned and their genes have been classified into a family. However, the role of the IP3 signaling pathway in the peritoneal dissemination of gastric cancer is still unclear. In the study presented here, the IP3R3 is showed to be overexpressed in gastric cancer cell lines established from malignant ascites, but weakly expressed in a gastric cancer cell line established from primary tumor as well as normal gastric epithelial cells. IP3R1 and 2 are only weakly or not expressed in these cells. The antagonist of IP3R, 2APB, inhibited cell proliferation and induced apoptosis in gastric cancer cells from malignant ascites at concentrations of 100 nM to 100 microM in a dose-dependent manner. On the other hand, 2APB showed a weak effect on other gastric cancer cells established from primary tumors (SNU1), lymph node metastases or liver metastases (MKN1 or 74), methothelial cell lines Met5A and myeloid leukemia HL60 cells. This suggests that this inhibitory effect depends on the level of IP3R3 expression. As cells which express IP3R3 mRNA (i.e. pancreas ascinar cells) are known to have a secretory function in which IP3/Ca2+ signaling has been shown to be involved, IP3R3 may be a prerequisite for secretion of an enzyme, such as protease, in gastric cancer cells. These results indicate that IP3R3 may be specifically involved in gastric cancer peritoneal dissemination and that IP3R3 may be a molecular target of the peritoneal dissemination of gastric cancer. Its antagonist, 2APB, may thus be useful for the specific treatment of peritoneal dissemination of gastric cancer.
Remnant lipoprotein metabolism: key pathways involving cell-surface heparan sulfate proteoglycans and apolipoprotein E (1999)

The plasma clearance of intestinally derived remnant lipoproteins by the liver is a process that likely involves three steps. Our model suggests that the initial rapid clearance by the liver begins with sequestration of the remnants within the space of Disse, where apolipoprotein E secreted by hepatocytes enhances remnant binding and uptake. Heparan sulfate proteoglycans (HSPG), which are also abundant in the space of Disse, mediate this enhanced binding. Next, the remnants undergo further processing in the space of Disse by hepatic and lipoprotein lipases, which may also serve as ligands mediating remnant uptake. The final step, endocytosis by hepatocytes, appears to be mediated, at least in part, by the low density lipoprotein (LDL) receptor and by the LDL receptor-related protein (LRP). Cell-surface HSPG play a critical role in remnant uptake, not only in the important initial sequestration or capture step in the space of Disse, but also as an essential or integral component of the HSPG-LRP pathway. In addition, HSPG appear to function alone as a receptor and display unique handling properties for specific isoforms of apolipoprotein E.
Monte Carlo Simulation of Interlayer Molecular Structure in Swelling Clay Minerals. 1. Methodology (1995)

Abstract Monte Carlo (MC) simulations of molecular structure in the interlayers of 2:1 Na-saturated clay minerals were performed to address several important simulation methodological issues. Investigation was focused on monolayer hydrates of the clay minerals because these systems provide a severe test of the quality and sensitivity of MC interlayer simulations. Comparisons were made between two leading models of the water-water interaction in condensed phases, and the sensitivity of the simulations to the size or shape of the periodically-repeated simulation cell was determined. The results indicated that model potential functions permitting significant deviations from the molecular environment in bulk liquid water are superior to those calibrated to mimic the bulk water structure closely. Increasing the simulation cell size or altering its shape from a rectangular 21.12 Å × 18.28 Å × 6.54 Å cell (about eight clay mineral unit cells) had no significant effect on the calculated interlayer properties.
Open Fractures: Evaluation and Management (2003)

Open fractures are complex injuries that involve both the bone and surrounding soft tissues. Management goals are prevention of infection, union of the fracture, and restoration of function. Achievement of these goals requires a careful approach based on detailed assessment of the patient and injury. The classification of open fractures is based on type of fracture, associated soft-tissue injury, and bacterial contamination present. Tetanus prophylaxis and intravenous antibiotics should be administered immediately. Local antibiotic administration is a useful adjunct. The open fracture wound should be thoroughly irrigated and debrided, although the optimal method of irrigation remains uncertain. Controversy also exists regarding the optimal timing and technique of wound closure. Extensive soft-tissue damage may necessitate the use of local or free muscle flaps. Techniques of fracture stabilization depend on the anatomic location of the fracture and characteristics of the injury.
[Demonstration of a central hypotensive action of lysine vasopressin in the dog]. (1981)

In chloralose-anaesthetized dogs intravenous infection of lysine-vasopressin (0.01 to 100 mU/kg) induced a dose-dependent increase in blood pressure and a decrease in heart rate. The same dosis injected by central (intracisternal) route induced a constant decrease in blood pressure. These results suggest the involvement of vasopressin in central cardiovascular control and in pathogenesis of some varieties of arterial hypertension.
Differential nitros(yl)ation of blood and tissue constituents during glyceryl trinitrate biotransformation in vivo (2004)

Nitric oxide (NO)-derived products may modify tissue constituents, forming S- and N-nitroso adducts and metal nitrosyls implicated in NO signaling. Nitrovasodilator drugs have been in widespread use for more than a century, yet their biotransformation pathways to NO and their effects as NO donors across tissues remain ill defined. By using a metabonomics approach (termed "NObonomics") for detailing the global NO-related metabolism of the cornerstone nitrovasodilator, glyceryl trinitrate (GTN; 0.1-100 mg/kg), in the rat in vivo, we find that GTN biotransformation elicits extensive tissue nitros(yl)ation throughout all major organ systems. The corresponding reaction products remained detectable hours after administration, and vascular tissue was not a major nitros(yl)ation site. Extensive heart and liver modifications involved both S- and N-nitrosation, and RBC S-nitrosothiol formation emerged as a sensitive indicator of organic nitrate metabolism. The dynamics of GTN-derived oxidative NO metabolites in blood did not reflect the nitros(yl)ation patterns in the circulation or in tissues, casting doubt on the usefulness of plasma nitrite/nitrate as an index of NO/NO-donor biodynamics. Target-tissue NO metabolites varied in amount and type with GTN dose, suggesting a dose-sensitive shift in the prevailing routes of GTN biotransformation ("metabolic shunting") from thiol nitrosation to heme nitrosylation. We further demonstrate that GTN-induced nitros(yl)ation is modulated by a complex, tissue-selective interplay of enzyme-catalyzed pathways. These findings provide insight into the global in vivo metabolism of GTN at pharmacologically relevant doses and offer an additional experimental paradigm for the NObonomic analysis of NO-donor metabolism and signaling.
Electroluminescence in a Terbium Complex (1990)

Abstract Electroluminescent devises consisted of two layers, a hole injecting diamine layer and an emitting Tb3+ complex of acetylacetonate layer, were fabricated by vacuum deposition. The EL cells exhibited characteristic bright Tb3+ luminescence with high efficiency at low drive voltage.
The 3′-Untranslated Region of the α2C-Adrenergic Receptor mRNA Impedes Translation of the Receptor Message (1997)

We report that two subtypes of alpha2-adrenergic receptors (alpha2A/D- and alpha2C-AR) are ectopically expressed with dramatically different efficiencies and that this difference is due to a 288-nucleotide (nt) segment in the 3'-untranslated region (3'-UTR) of the alpha2C-AR mRNA that impairs translational processing. NIH-3T3 fibroblasts were transfected with receptor constructs (coding region plus 552 nt, alpha2C-AR; coding region plus 1140 nt, alpha2A/D-AR) and a vector conferring G418 resistance. Transcription was driven by the murine sarcoma virus promoter element, and the receptor gene segment was upstream of an SV40 polyadenylation cassette. Drug-resistant transfectants were evaluated for expression of receptor mRNA and protein. 90% of the NIH-3T3 alpha2C-AR transfectants expressed receptor mRNA, but only 14% of the clonal cell lines expressed receptor protein. In contrast, 90% of the NIH-3T3 alpha2A/D-AR transfectants expressed receptor protein (200-5000 fmol/mg). Similar results were obtained following transfection of DDT1MF-2 cells with the two receptor constructs. The role of the 3'-UTR of the alpha2C-AR in mRNA processing was determined by generating new constructs in which the 3'-UTR was progressively truncated from 552 to 470, 182, 143, or 74 nt 3' to the stop codon. Truncation of the 3'-UTR resulted in the expression of receptor protein in the G418-resistant transfectants (nt 74, 100%; nt 143, 80%; nt 182, 50%). The level of mRNA in the transfectants expressing the receptor protein was not greater than that in nonexpressing clones, and the differences in protein expression did not reflect altered mRNA stability in the truncated construct. The alpha2C-AR mRNA with the longer 3'-UTR underwent translational initiation as it was found in the polysome fraction, indicating that the lack of receptor protein was due to impaired translational elongation or termination. These data suggest that translational efficiency is a key mechanism for regulating alpha2C-AR expression and associated signaling events.
In vitrotranscription analysis of the role of flanking sequence on the DNA sequence specificity of Adriamycin (1989)

An in vitro transcription assay has been used to define twelve high occupancy transcriptional blockage sites in 260 bp of heterogenous DNA on three promoter-containing DNA fragments. Transcription proceeded to immediately upstream of CpA sequences in nine of these sites, and this defines the most preferred intercalation site as CpA. In almost all cases, this sequence was flanked by T on the 5' end. The consensus sequence for the highest affinity Adriamycin site is therefore 5'-TCA, with some evidence for preference of AT base pairs flanking both ends of this trinucleotide [i.e., (t)TCA(a.t)(a.t)]. In contrast, lower occupancy CpA sites were flanked on the 5' end by a GC base pair, with a preference for up to three GC base pairs on the 3' end. The low affinity consensus sequence is therefore (G.C)CA(g.c)(g.c)(g.c).
Mineralized polysaccharide capsules as biomimetic microenvironments for cell, gene and growth factor delivery in tissue engineering (2006)

This paper presents an overview of our recent studies on mineralized polysaccharide capsules and their potential as multifunctional scaffolds for the organisation and delivery of human cell types, DNA and growth factors. Microcapsules containing these encapsulates are readily produced at room temperature in the form of alginate beads that are stabilized by an outer shell consisting of an ultra thin chitosan-calcium phosphate membrane. Modulation of the shell thickness and composition influences the rates of release and diffusion of encapsulated cells, growth factors and genes to produce microcapsules with tailored spatial and temporal properties that offer significant potential as novel biomimetic delivery systems in tissue engineering applications such as skeletal tissue repair and regeneration. We demonstrate the use of mineralized microcapsules to enable regeneration from encapsulated human mesenchymal populations, functional quantities of growth factor capture, and gene transfection. Significantly, we highlight the ability to fabricate integrated capsules consisting of spatially separated multiple components in nested combination that may provide phased temporal release of appropriate growth factors, analogous to the natural regeneration process.
Total Body Irradiation and Acute Graft-Versus-Host Disease: The Role of Gastrointestinal Damage and Inflammatory Cytokines (1997)

The influence of bone marrow transplantation (BMT) conditioning regimens on the incidence and severity of graft-versus-host disease (GVHD) has been suggested in clinical BMT. Using murine BMT models, we show here an increase in GVHD severity in several donor-recipient strain combinations after intensification of the conditioning regimen by increasing the total body irradiation (TBI) dose from 900 cGy to 1,300 cGy. Increased GVHD was mediated by systemic increases in tumor necrosis factor alpha (TNF alpha). Histologic analysis of gastrointestinal tracts showed synergistic damage by increased TBI and allogeneic donor cells that permitted increased translocation of lipopolysacharide (LPS) into the systemic circulation. In vitro, LPS triggered excess TNF alpha from macrophages primed by the GVH reaction. In addition, macrophages isolated within 4 hours of conditioning were primed in proportion to the TBI dose itself to secrete TNF alpha. Thus, the higher TBI dose increased macrophage priming and increased gut damage after allogeneic BMT, causing higher systemic levels of inflammatory cytokines and subsequent severe GVHD. These data highlight the importance of conditioning in GVHD pathophysiology and suggest that interventions to prevent LPS stimulation of primed macrophages may limit the severity of GVHD after intensive conditioning for allogeneic BMT.
Akt Protein Kinase Inhibits Non-apoptotic Programmed Cell Death Induced by Ceramide (2002)

A growing body of evidence now suggests that programmed cell death (PCD) occurs via non-apoptotic mechanisms as well as by apoptosis. In contrast to apoptosis, however, the molecular mechanisms involved in the regulation of non-apoptotic PCD remain only poorly understood. Here we show that ceramide induces a non-apoptotic PCD with a necrotic-like morphology in human glioma cells. Characteristically, the cell death was not accompanied by loss of the mitochondrial transmembrane potential, cytosolic release of cytochrome c from mitochondria, or the activation of the caspase cascade. Consistent with these characteristics, this ceramide-induced cell death was inhibited neither by the overexpression of Bcl-xL nor by the pan-caspase inhibitor zVAD-fmk. However, strikingly, the ceramide-induced non-apoptotic cell death was inhibited by the activation of the Akt/protein kinase B pathway through the expression of a constitutively active version of Akt. The results for the first time indicate that the Akt kinase, known to play an essential role in survival factor-mediated inhibition of apoptotic cell death, is also involved in the regulation of non-apoptotic PCD.
Efficiency of conversion of α-linolenic acid to long chain n-3 fatty acids in man (2002)

Alpha-linolenic acid (18:3n-3) is the major n-3 (omega 3) fatty acid in the human diet. It is derived mainly from terrestrial plant consumption and it has long been thought that its major biochemical role is as the principal precursor for long chain polyunsaturated fatty acids, of which eicosapentaenoic (20:5n-3) and docosahexaenoic acid (22:6n-3) are the most prevalent. For infants, n-3 long chain polyunsaturated fatty acids are required for rapid growth of neural tissue in the perinatal period and a nutritional supply is particularly important for development of premature infants. For adults, n-3 long chain polyunsaturated fatty acid supplementation is implicated in improving a wide range of clinical pathologies involving cardiac, kidney, and neural tissues. Studies generally agree that whole body conversion of 18:3n-3 to 22:6n-3 is below 5% in humans, and depends on the concentration of n-6 fatty acids and long chain polyunsaturated fatty acids in the diet. Complete oxidation of dietary 18:3n-3 to CO2 accounts for about 25% of 18:3n-3 in the first 24 h, reaching 60% by 7 days. Much of the remaining 18:3n-3 serves as a source of acetate for synthesis of saturates and monounsaturates, with very little stored as 18:3n-3. In term and preterm infants, studies show wide variability in the plasma kinetics of 13C n-3 long chain polyunsaturated fatty acids after 13C-18:3n-3 dosing, suggesting wide variability among human infants in the development of biosynthetic capability to convert 18:3n-3 to 22:6n3. Tracer studies show that humans of all ages can perform the conversion of 18:3n-3 to 22:6n3. Further studies are required to establish quantitatively the partitioning of dietary 18:3n-3 among metabolic pathways and the influence of other dietary components and of physiological states on these processes.
Iron Acquisition and Transcriptional Regulation (2009)

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTIron Acquisition and Transcriptional RegulationCraig D. Kaplan† and Jerry Kaplan*‡View Author Information Department of Biochemistry and Biophysics, Texas A&M University, and Department of Pathology, School of Medicine, University of Utah* Corresponding author.†Texas A&M University.‡University of Utah.Cite this: Chem. Rev. 2009, 109, 10, 4536–4552Publication Date (Web):August 25, 2009Publication History Received28 April 2009Published online25 August 2009Published inissue 14 October 2009https://pubs.acs.org/doi/10.1021/cr9001676https://doi.org/10.1021/cr9001676review-articleACS PublicationsCopyright © 2009 American Chemical SocietyRequest reuse permissionsArticle Views3905Altmetric-Citations234LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Cells,Fungi,Genetics,Iron,Peptides and proteins Get e-Alerts