gebhart/patrepeval huggingface dataset:
Elevation of iron storage in humans attenuates the pulmonary vascular response to hypoxia (2016)

Sustained hypoxia over several hours induces a progressive rise in pulmonary artery systolic pressure (PASP). Administration of intravenous iron immediately prior to the hypoxia exposure abrogates this effect, suggesting that manipulation of iron stores may modify hypoxia-induced pulmonary hypertension. Iron (ferric carboxymaltose) administered intravenously has a plasma half-life of 7-12 h. Thus any therapeutic use of intravenous iron would require its effect on PASP to persist long after the iron-sugar complex has been cleared from the blood. To examine this, we studied PASP during sustained (6 h) hypoxia on 4 separate days (days 0, 1, 8, and 43) in 22 participants. On day 0, the rise in PASP with hypoxia was well matched between the iron and saline groups. On day 1, each participant received either 1 g of ferric carboxymaltose or saline in a double-blind manner. After administration of intravenous iron, the rise in PASP with hypoxia was attenuated by ∼50%, and this response remained suppressed on both days 8 and 43 (P < 0.001). Following administration of intravenous iron, values for ferritin concentration, transferrin saturation, and hepcidin concentration rose significantly (P < 0.001, P < 0.005, and P < 0.001, respectively), and values for transferrin concentration fell significantly (P < 0.001). These changes remained significant at day 43 We conclude that the attenuation of the pulmonary vascular response to hypoxia by elevation of iron stores persists long after the artificial iron-sugar complex has been eliminated from the blood. The persistence of this effect suggests that intravenous iron may be of benefit in some forms of pulmonary hypertension.
New Palladium(II) and Platinum(II) Complexes with 9-Aminoacridine: Structures, Luminiscence, Theoretical Calculations, and Antitumor Activity (2008)

The new complexes [Pd(dmba)( N10-9AA)(PPh 3)]ClO 4 ( 1), [Pt(dmba)( N9-9AA)(PPh 3)]ClO 4 ( 2), [Pd(dmba)( N10-9AA)Cl] ( 3), and [Pd(C 6F 5)( N10-9AA)(PPh 3)Cl] ( 4) (9-AA = 9-aminoacridine; dmba = N,C-chelating 2-(dimethylaminomethyl)phenyl) have been prepared. The crystal structures have been established by X-ray diffraction. In complex 2, an anagostic C-H...Pt interaction is observed. All complexes are luminescent in the solid state at room temperature, showing important differences between the palladium and platinum complexes. Complex 2 shows two structured emission bands at high and low energies in the solid state, and the lifetimes are in agreement with excited states of triplet parentage. Density functional theory and time-dependent density functional theory calculations for complex 2 have been done. Values of IC 50 were also calculated for the new complexes 1- 4 against the tumor cell line HL-60. All of the new complexes were more active than cisplatin (up to 30-fold in some cases). The DNA adduct formation of the new complexes synthesized was followed by circular dichroism and electrophoretic mobility. Atomic force microscopy images of the modifications caused by the complexes on plasmid DNA pB R322 were also obtained.
Construction of Polyclonal Antibody Libraries Using Phage Display (2003)

Polyclonal antibody libraries (PCALs) are standardized mixtures of antibodies (Abs) specific for an antigen (Ag) or multi-Ag target (a poly-Ag). As the immunoglobulin (Ig) genes are cloned, the mixtures can be perpetuated, amplified, and modified as desired. Poly-Ags of special interest are microbes and tumor cells, with potential for both therapeutic and diagnostic applications. PCALs combine the advantages of serum-derived polyclonal Abs with the perpetuity of monoclonal antibodies (MAbs). Like serum-derived polyclonal Abs, PCALs target multiple epitopes on poly-Ags, resulting in high-avidity binding, low likelihood of Ag “escape variants” emerging, and efficient triggering of effector functions (1). A PCAL is not merely a collection of Ag-specific MAbs: the PCAL is selected in mass for binding to a target poly-Ag, and is, thereafter, perpetuated without isolation or characterization of individual library members. Thus, a PCAL contains Abs specific for the target poly-Ag, and Abs that crossreact with other poly-Ags (e.g., normal cells). However, the Ag profile of the target poly-Ag differs qualitatively and quantitatively from the Ag profile of any other poly-Ag, enabling the PCAL to recognize the target poly-Ag with a high signal: noise ratio. This concept is illustrated schematically in Fig. 1. Because effector functions are inefficient at low Ab density, low-level crossreactivity with normal tissue will probably be tolerated in therapeutic applications.
Expression of interleukin‐12 in synovial tissue from patients with rheumatoid arthritis (1998)

Objective To examine the importance of interleukin-12 (IL-12) as a factor in the interferon-γ (IFNγ)-dominant T cell cytokine response in the synovial tissue of patients with rheumatoid arthritis (RA). Methods The expression of IL-12 in synovial tissue samples from patients with chronic RA (≥2 years) was compared with that in samples from osteoarthritis (OA) patients by detection of IL-12 p40 messenger RNA (mRNA) using reverse transcriptase-polymerase chain reaction, measurement of IL-12 p70 protein in culture supernatants of tissue cells by immunoassay, and immunostaining of tissue sections with anti-IL-12 p70. The production of IFNγ by RA synovial tissue cells cultured with or without IL-12 was determined. In addition, T cells were obtained 14 days after culturing RA synovial tissue cells with IL-2 alone or with IL-2 plus IL-12, neutralizing anti-IL-12, or IL-4, and cytokine patterns (i.e., IFNγ and IL-4 levels) were determined by stimulating cells for 24 hours with anti-CD3 plus phorbol myristate acetate. Results Synovial tissues from RA patients more strongly expressed IL-12 p40 mRNA than did OA tissues. Dissociated tissue cells from 21 of 37 RA patients spontaneously released detectable amounts of IL-12 p70 (≥12.5 pg/ml) in culture, whereas production of IL-12 by OA tissues was limited. By immunohistochemical analysis, IL-12-producing cells were localized mainly in the sublining layer of RA synovium, and mostly expressed the CD68 antigen. Levels of IFNγ production by RA synovial tissue cells were potently and selectively enhanced by IL-12. The ability of IL-2-expanding synovial T cells to produce IFNγ was augmented by costimulation with IL-12 and diminished by anti-IL-12, while it was not affected by IL-4. Conclusion These data suggest that IL-12, produced mainly by macrophage-lineage cells, may be involved in IFNγ-dominant cytokine production by infiltrating T cells in joints with chronic RA.
Increased expression of platelet IgG Fc receptors in immune heparin- induced thrombocytopenia (1993)

Our previous finding that heparin-dependent antibodies in heparin- induced thrombocytopenia (HIT) bind to platelets via platelet IgG Fc receptors (FcRs) prompted this study. Platelet FcRs in 16 patients with HIT, 23 control patients, and 42 normal subjects were studied. Patients with HIT had substantially increased platelet FcRs during the acute illness. Those who suffered serious thrombotic complications or died shortly after diagnosis had significantly more FcRs per platelet than those with milder disease. Consistent with their increased FcRs, platelets of patients with HIT showed increased aggregation reactivity to aggregated IgG and heparin-dependent antibodies. Platelet FcRs in patients with HIT remained elevated for 1 to 3 months after the acute illness then stabilized to a mean value not significantly different from either control group. The increased expression of FcRs on HIT platelets and their increased reactivity to heparin-dependent antibodies may contribute to the pathogenesis of thrombocytopenia and thrombosis in HIT.
Preclinical evaluation of a new, stabilized neurotensin(8--13) pseudopeptide radiolabeled with (99m)tc. (2002)

The changes that were introduced stabilized the molecule against enzymatic degradation without affecting binding properties. Moreover, the increase in stability enhanced tumor uptake, making this derivative a promising candidate for clinical use.
Label-free oxygen-metabolic photoacoustic microscopy in vivo (2011)

Almost all diseases, especially cancer and diabetes, manifest abnormal oxygen metabolism. Accurately measuring the metabolic rate of oxygen (MRO(2)) can be helpful for fundamental pathophysiological studies, and even early diagnosis and treatment of disease. Current techniques either lack high resolution or rely on exogenous contrast. Here, we propose label-free metabolic photoacoustic microscopy (mPAM) with small vessel resolution to noninvasively quantify MRO(2) in vivo in absolute units. mPAM is the unique modality for simultaneously imaging all five anatomical, chemical, and fluid-dynamic parameters required for such quantification: tissue volume, vessel cross-section, concentration of hemoglobin, oxygen saturation of hemoglobin, and blood flow speed. Hyperthermia, cryotherapy, melanoma, and glioblastoma were longitudinally imaged in vivo. Counterintuitively, increased MRO(2) does not necessarily cause hypoxia or increase oxygen extraction. In fact, early-stage cancer was found to be hyperoxic despite hypermetabolism.
PA-RISC 2.0 architecture (1995)

1. Overview. Traditional RISC Characteristics of PA-RISC. PA-RISC-The Genius is in the Details. A Critical Calculus: Instruction Pathlength. Multimedia Support: The Precision Process Illustrated. Integrated CPU. Extensibility and Longevity. System Organization. 2. Processing Resources. Non-Privileged Software-Accessible Registers. Privileged Software-Accessible Registers. Unused Registers and Bits. Data Types. Byte Ordering (Big Endian/Little Endian). 3. Addressing and Access Control. Physical and Absolute Addressing. Virtual Addressing. Pointers and Address Specification. Address Resolution and the TLB. Access Control. 4. Page Table Structure. Caches. Control Flow. Branching. Nullification. Instruction Execution. Instruction Pipelining. 5. Interruptions. Interrupt Classes. Interruption Handling. Instruction Recoverability. Masking and Nesting of Interruptions. Interruption Priorities. Return from Interruption. Interruption Descriptions. 6. Instruction Set Overview. Computation Instructions. Multimedia Instructions. Memory Reference Instructions. Long Immediate Instructions. Branch Instructions. System Control Instructions. Assist Instructions. Conditions and Control Flow. Additional Notes on the Instruction Set. 7. Instruction Descriptions. 8. Floating-point Coprocessor. The IEEE Standard. The Instruction Set. Coprocessor Registers. Data Registers. Data Formats. Floating-Point Status Register. Floating-Point Instruction Set. 9. Floating-Point Instruction Set. 10. Floating-Point Exceptions. Exception Registers. Interruptions and Exceptions. Saving and Restoring State. 11. Performance Monitor Coprocessor. Performance Monitor Instructions. Performance Monitor Interruptions. Monitor Units. Glossary. Appendix B. Instruction Formats. Appendix C. Operation Codes. Appendix D. Conditions. Appendix E. Instruction Notation Control Structures. Appendix F. TLB and Cache Control. Appendix G. Memory Ordering Model. Appendix H. Address Formation Details. Appendix I. Programming Notes. Appendix J. PA-RISC 2 Instruction Completers & Pseudo-Ops.
Materials Science of Synthetic Membranes (1985)

Material science aspects of synthetic polymeric membranes are presented in this survey. The objective is to place each of the subsequent chapters of this volume into proper perspective. Therefore, frequent reference is made to the accompanying chapters and, where necessary, to alternative information sources. By way of introduction, this chapter considers in turn: material selection, material characterization and evaluation, membrane preparation, membrane characterization and membrane evaluation. Membrane module design and manufacture, transport phenomena and process performance are introduced in the discussion only as they pertain to membrane materials science. Following this introduction, the various chapters of this volume are previewed.
Myristoylation Is Required for Human Immunodeficiency Virus Type 1 Gag-Gag Multimerization in Mammalian Cells (2007)

The Gag protein of human immunodeficiency virus type 1 directs the virion assembly process. Gag proteins must extensively multimerize during the formation of the spherical immature virion shell. In vitro, virus-like particles can be generated from Gag proteins that lack the N-terminal myristic acid modification or the nucleocapsid (NC) protein. The precise requirements for Gag-Gag multimerization under conditions present in mammalian cells, however, have not been fully elucidated. In this study, a Gag-Gag multimerization assay measuring fluorescence resonance energy transfer was employed to define the Gag domains that are essential for homomultimerization. Three essential components were identified: protein-protein interactions contributed by residues within both the N- and C-terminal domains of capsid (CA), basic residues in NC, and the presence of myristic acid. The requirement of myristic acid for multimerization was reproduced using the heterologous myristoylation sequence from v-src. Only when a leucine zipper dimerization motif was placed in the position of NC was a nonmyristoylated Gag protein able to multimerize. These results support a three-component model for Gag-Gag multimerization that includes membrane interactions mediated by the myristoylated N terminus of Gag, protein-protein interactions between CA domains, and NC-RNA interactions.
Persons and their underpinnings (2000)

Abstract I defend a conception of the relationship between the personal and sub‐personal levels as interaction withoutreduction.There are downward inferences from the personal to the sub‐personal level but we find upward explanatory gaps when we try to construct illuminating accounts of personal level conditions using just sub‐personal level notions. This conception faces several serious challenges but the objection that I consider in this paper says that, when theories support downward inferences from the personal to the sub‐personal level, this is the product of an unacceptably • mechanistic view of persons. According to this objection, if we were to focus on persons as conscious rational thinkers and agents then the support for putative downward inferences would be undermined. I consider and reject developments of this objection in response to two arguments for downward inferences.
Electrophilic methyl groups present in the diet ameliorate pathological states induced by reductive and oxidative stress: a hypothesis (2001)

Reductive stress, characterised by an increased NADH:NAD+ ratio, may be as common and as important a consequence of redox imbalance as oxidative stress. It may also be an important predisposing cause of the generation of reactive oxygen species. Considerable experimental and indirect clinical evidence suggests that protection against reductive stress depends on biomolecules with electrophilic methyl groups (EMG) such as S-adenosylmethionine, betaine, carnitine and phosphatidylcholine. Pathological processes leading to reductive stress and their relief by such protective agents is reviewed and the proposed molecular mechanism is outlined. These and other EMG-containing biomolecules are part of the daily diet and may represent an important control system for redox balance.
Materials Science Measurement of in vivo Corrosion Rates in Baboons, and Correlation with in vitro Tests (1980)

The Linear Polarization Technique was used to determine the polarization resistances and corrosion currents of various dental restorative and implant alloys and amalgams placed in the teeth of animals, and as laboratory samples in artificial saliva. Gold- and chromium-containing alloys corroded the least, and amalgams generated the highest corrosion currents. There was good agreement between measurements made in vivo and in vitro. This is the first time that corrosion currents have been measured in the mouth repeatedly over a long time span. These methods may be developed into useful predictive tests of in vivo corrosion.
Supporting Collaboration in Mobile-Aware Groupware (1998)

This paper builds on the experiences gained from the extensive work carried out during the MOST project [MOST,95]. This project investigated the use of mobile technologies to support multimedia collaboration between highly mobile field engineers in the safety critical domain of the U.K. power distribution industry. The MOST team developed a prototype distributed groupware application which was arguably the first collaborative mobile application ever built that was capable of adaption in a mobile environment [Cheverst,94]. The application was designed as an expandable toolkit comprising a number of modules including a shared GIS module. This module enabled groups of field engineers to perform spatially-aware collaboration by supporting the display and annotation of network schematics across groups. The MOST application was evaluated by real end-users in a trial scenario using the GSM service for communications. This evaluation provided a valuable set of implications regarding the development of distributed groupware in conjunction with mobile technologies. The main argument of this paper concerns the need for a new type of awareness, i.e. mobileawareness, that provides group members with relevant information concerning the effect that the
Binding of pRNA to the N-terminal 14 amino acids of connector protein of bacteriophage phi29 (2005)

During assembly, bacterial virus phi29 utilizes a motor to insert genomic DNA into a preformed protein shell called the procapsid. The motor contains one twelve-subunit connector with a 3.6 nm central channel for DNA transportation, six viral-encoded RNA (packaging RNA or pRNA) and a protein, gp16, with unknown stoichiometry. Recent DNA-packaging models proposed that the 5-fold procapsid vertexes and 12-fold connector (or the hexameric pRNA ring) represented a symmetry mismatch enabling production of a force to drive a rotation motor to translocate and compress DNA. There was a discrepancy regarding the location of the foothold for the pRNA. One model [C. Chen and P. Guo (1997) J. Virol., 71, 3864-3871] suggested that the foothold for pRNA was the connector and that the pRNA-connector complex was part of the rotor. However, one other model suggested that the foothold for pRNA was the 5-fold vertex of the capsid protein and that pRNA was the stator. To elucidate the mechanism of phi29 DNA packaging, it is critical to confirm whether pRNA binds to the 5-fold vertex of the capsid protein or to the 12-fold symmetrical connector. Here, we used both purified connector and purified procapsid for binding studies with in vitro transcribed pRNA. Specific binding of pRNA to the connector in the procapsid was found by photoaffinity crosslinking. Removal of the N-terminal 14 amino acids of the gp10 protein by proteolytic cleavage resulted in undetectable binding of pRNA to either the connector or the procapsid, as investigated by agarose gel electrophoresis, SDS-PAGE, sucrose gradient sedimentation and N-terminal peptide sequencing. It is therefore concluded that pRNA bound to the 12-fold symmetrical connector to form a pRNA-connector complex and that the foothold for pRNA is the connector but not the capsid protein.
5-Arylthiopyrimidines. IV. Spectrophotometric Determination of Successive Acid Dissociation Constants Differing by Less Than Two pK Units (1965)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT5-Arylthiopyrimidines. IV. Spectrophotometric Determination of Successive Acid Dissociation Constants Differing by Less Than Two pK UnitsBarbara Roth and J. F. BunnettCite this: J. Am. Chem. Soc. 1965, 87, 2, 334–339Publication Date (Print):January 1, 1965Publication History Published online1 May 2002Published inissue 1 January 1965https://doi.org/10.1021/ja01080a034Request reuse permissionsArticle Views71Altmetric-Citations12LEARN 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 InReddit PDF (571 KB) Get e-Alertsclose Get e-Alerts
5-Thio-D-Glucose Selectively Potentiates Hyperthermic Killing of Hypoxic Tumor Cells (1978)

To investigate the mechanisms by which heat affects cancer cells, we used 5-thio-D-glucose, an inhibitor of glycolysis in HeLa S-3 cells, under aerobic and hypoxic conditions at temperatures ranging from 37 degrees to 43 degrees C. Drug alone or heat alone killed a minimum number of cells under aerobic or hypoxic conditions. Exposure to drug and hyperthermia selectively increased the number of cells killed under hypoxic conditions at temperatures as low as 40.5 degrees C but had little effect on cells incubated under aerobic conditions. These results suggest that the glycolytic pathways is a primary site of hyperthermic damage leading to cell death.
Orally Administered Lactoferrin Exerts an Antimetastatic Effect and Enhances Production of IL-18 in the Intestinal Epithelium (2000)

The effects of oral administration of bovine lactoferrin (bLF) and its hydrolysate on the lung colonization by colon 26 carcinoma were investigated. At doses of 100 or 300 mg/kg/day for seven successive days, bLFs demonstrated a significant inhibitory effect on experimental metastasis, which indicated effectiveness before and after tumor implantation. Oral administration of bLFs augmented CD4+, CD8+, and asialoGM1+ cells in the spleen and peripheral blood. Their cytotoxic activities against Yac-1 and colon 26 carcinoma were enhanced by bLF. In the small intestinal epithelium, CD4+ and CD8+ cells were markedly increased, and, simultaneously, enhanced production of interleukin-18 (IL-18) was confirmed in the intestinal epithelial cells. In this model, intravenous injection of murine IL-18 showed significant inhibition of the lung colonization by colon 26 carcinoma. These results suggested that inhibition of experimental metastasis by oral administration of bLF and pepsin hydrolysate of bLF might be due to enhanced cellular immunity, presumably mediated by enhanced IL-18 production in the intestinal epithelium.