gebhart/patrepeval huggingface dataset:
Mechanisms and kinetics of the thermal decomposition of sodium sulphide pentahydrate under controlled water vapour pressure (1986)

The kinetics and mechanism of the thermal decomposition of sodium sulphide pentahydrate to an essentially anhydrous form was investigated, in the pressure range 3–20 Torr, using thermogravimetry and X-ray powder diffractometry under controlled temperature and water vapour pressure. A two-step dehydration reaction pathway involving an intermediate dihydrate phase was observed: Na2S·5H2O → Na2S·2H2O + 3H2O (g); Na2S·2H2O → Na2S + 2H2O (g). The latter reaction is shown to be relatively more inhibited than the first. The intermediate phase was studied by means of simultaneous thermogravimetry and X-ray powder diffraction methods. A structural transformation is proposed in terms of a topotactic process, which readily accounts for the readiness with which the first reaction takes place and which is also consistent with the overall structural transformation from the pentahydrate to the anhydrous product.
Molecular Progenitor Profiling in Human Myeloproliferative Disorders. (2005)

Abstract Myeloproliferative disorders (MPD) are clonal hematopoietic disorders characterized by a hypercellular marrow, an overabundance of distinct lineages of terminally differentiated progeny and a propensity to transform to acute myelogenous leukemia (AML). Recent reports revealed that a specific (V617F) mutation in JAK2 resulted in constitutive cytokine signaling and increased sensitivity to cytokines in a large proportion of patients with MPD. However, the stage of hematopoiesis at which this mutation occurs and whether additional mutations contribute to the evolution of MPD into AML has yet to be determined. We performed phenotypic and functional analyses of hematopoeitic stem cells (HSC), common myeloid progenitors (CMP), granulocyte-macrophage progenitors (GMP) and megakaryocyte-erythroid progenitors (MEP) in 63 MPD peripheral blood or bone marrow samples donated by patients with PV (n=15), essential thrombocythemia (ET; n=8), post-polycythemic myeloid metaplasia/myelofibrosis (PPMM/MF; n=5), chronic myelogenous leukemia (CML; n=7), atypical CML/myeloproliferative disease unspecified (aCML/UMPD; n=2), chronic eosinophilic leukemia (CEL; n=1), chronic myelomonocytic leukemia (CMML; n=13) and AML (n=12) in order to identify the stage of hematopoiesis at which mutations arose as well as to provide prognostic information on patients with a propensity to transform to AML. Of the MPD mononuclear cells sequenced, 12 of 15 PV, 2 of 5 ET, 3 of 3 post-polycythemic myeloid metaplasia, and 2 of 2 aCML samples were positive for the JAK2 V617F mutation. With regard to phenotypic changes in progenitor profiles, PV samples had an increase in CMP together with a distinctive IL-3Ra high population that distinguished it from all other MPD. Conversely, aCML, AML and proliferative CMML had a preponderance of GMP. Functional changes in progenitors were assessed using hematopoietic progenitor assays (Figure 1A and B). This methodology demonstrated that the differentiation potential of PV was already skewed toward the erythroid lineage at the HSC level in contrast to CMML, CML, aCML and AML HSC which produced a preponderance of myeloid colonies. In addition, the aberrant erythroid potential of PV HSC could be potently inhibited with a specific JAK2 inhibitor - AG490 suggesting that JAK2 plays a role in enhancing the erythroid differentiation potential of PV at the stem cell level. Finally, other molecular abnormalities were detected at the progenitor level in MPD including changes in GATA-1 and PU.1 expression, bcl-2 overexpression and beta-catenin activation that were associated with progression to AML. Thus, molecular progenitor profiling may provide prognostic information in a variety of MPD and could be a useful adjunct to current diagnostic methods. NBM versus MPD Colonies NBM versus MPD Colonies Normal BM vs PV Progenitor Colonies Normal BM vs PV Progenitor Colonies
Multipath characteristics of impulse radio channels (2002)

We investigate the multipath characteristics of the impulse radios (IR) which have drawn much attention for future high-speed wireless communication services. For this objective, we observe the characteristics of bit error rates through computer simulations for the deterministic two-path model and the statistical indoor multipath model of Saleh and Valenzuela (1987). The simulation results indicate that the performance of the IR system depends on the time-delay differences between the multipath components, the path gains, the time interval in the PPM, and the reference signal waveform. It is also observed that the reference signal waveform used in the AWGN channel can not be applicable to the multipath channel.
CD8+ T‐cell memory in tumor immunology and immunotherapy (2006)

The cellular and molecular mechanisms underlying the formation of distinct central, effector, and exhausted CD8+ T-cell memory subsets were first described in the setting of acute and chronic viral diseases. The role of these T-cell memory subsets are now being illuminated as relevant to the tumor-bearing state. The generation and persistence of productive CD8+ T-cell memory subsets is determined, in part, by antigen clearance, costimulation, responsiveness to homeostatic cytokines, and CD4+ T-helper cells. By contrast, chronic exposure to antigen, negative costimulation, and immunomodulation by CD4+ T regulatory cells corrupt productive CD8+ T memory formation. It has become clear from human and mouse studies that the mere generation of CD8+ T-cell memory is not a 'surrogate marker' for cancer vaccine efficacy. Some current cancer vaccine strategies may fail because they amplify, rather than correct or reset, the corrupted CD8+ memory population. Thus, much of the present effort in the development of vaccines for cancer and chronic infectious diseases is aimed at creating effective memory responses. Therapeutic vaccines for cancer and chronic infectious diseases may achieve consistent efficacy by ablation of the dysfunctional immune state and the provision of newly generated, non-corrupted memory cells by adoptive cell transfer.
Levels of Nicotinamide Adenine Dinucleotide and Reduced Nicotinamide Adenine Dinucleotide in Facultative Bacteria and the Effect of Oxygen (1972)

Nicotinamide adenine dinucleotide (NAD) and reduced NAD (NADH) levels have been measured in bacterial cultures. The cofactors were assayed by using the very sensitive cycling assay described previously by Cartier. Control experiments showed that the level of total NAD(H) falls during harvesting, and so samples were taken quickly from growing cultures and extracted immediately without separating the cells from the medium. Total NAD(H) ranged from 4.0 to 11.7 mumoles/g of dry cells for three facultative organisms, Klebsiella aerogenes, Escherichia coli, and Staphylococcus albus. NADH was remarkably constant in these bacteria; only one out of ten series of determinations was outside the range 1.4 to 1.9 mumoles/g of dry cells. NAD(+) showed much greater variation. An anaerobe (Clostridium welchii) had significantly more total NAD(H) whereas an aerobe Pseudomonas aeruginosa had about as much NAD(H) as the facultative organisms. NAD and NADH were measured during growth: once more NADH was much more constant than NAD. During change-over between aerobiosis and anaerobiosis, NADH showed a temporary increase but then returned to a constant level, whereas NAD changed from high aerobically to low anaerobically. These results are discussed in terms of the control mechanisms that may be involved.
Electron transfer in ruthenium-modified proteins (1992)

The electron-transfer (ET) reactions of metalloproteins&#13;\nare potentially far more complex than those of small molecules. The structural intricacies of proteins are largely responsible for the added complexity. Reactive centers are surrounded by polypeptide matrices that shield these sites from solvent and separate them from their redox partners. The nonuniform charge distributions on the protein surfaces create anisotropic interactions between redox partners, confounding the interpretation of bimolecular reactions. Covalent or electrostatic coupling of redox partners can be exploited to simplify the problem but does not eliminate all of the complicating factors in metalloprotein ET reactions. The energetics and dynamics&#13;\nof nuclear reorientations accompanying protein ET reactions continue to be a source of inquiry. Multiple conformational states in the polymer surrounding the redox sites create the potential for "gating" and directional electron transfer. The peptide matrix also separates the redox sites, leading to questions of how protein ET can be efficient over such long (&gt; 10 Å) distances. One line of research aimed at addressing many of the fundamental issues in protein ET involves the use of proteins modified by the coordination of Ru complexes to surface amino acid residues.
Surface tension induced by dipalmitoyl lecithin in vitro under physiological conditions (1979)

1. The surface tension of 161 films of DPL have been measured on a Langmuir trough using a Wilhelmy balance under conditions controlled to simulate the state of the alveolar lining in vivo.2. The parameters controlled were temperature (maintained at 37 degrees C), humidity (100% at 37 degrees C), surfactant concentrations (encompassing the best available estimates), area changes (consistent with normal respiration), frequency adaptation to continuous cycling and composition and pH of the aqueous hypophase.3. Simultaneously maintaining all of these parameters within the best estimates of physiological limits, the relationships between surface tension and surface area showed appreciable differences from previous studies, our results showing higher minimum values of surface tension, appreciably less change in surface tension with compression and far less hysteresis between surface tension and surface area.4. The higher minimum values are consistent with original estimates of alveolar surface tension made by von Neergaard, namely 35-41 dyne cm(-1).5. Although appreciably smaller than hitherto reported, the change in surface tension with change in area is still adequate to impart alveolar stability.6. The reversibility between surface tension and surface area under physiological conditions is discussed in connection with compliance hysteresis which is considered to be more dependent upon geometric irreversibility of the alveolar surface than upon any intrinsic property of the surfactant.
Reductions in log P Improved Protein Binding and Clearance Predictions Enabling the Prospective Design of Cannabinoid Receptor (CB1) Antagonists with Desired Pharmacokinetic Properties (2013)

Several strategies have been employed to reduce the long in vivo half-life of our lead CB1 antagonist, triazolopyridazinone 3, to differentiate the pharmacokinetic profile versus the lead clinical compounds. An in vitro and in vivo clearance data set revealed a lack of correlation; however, when compounds with <5% free fraction were excluded, a more predictable correlation was observed. Compounds with log P between 3 and 4 were likely to have significant free fraction, so we designed compounds in this range to give more predictable clearance values. This strategy produced compounds with desirable in vivo half-lives, ultimately leading to the discovery of compound 46. The progression of compound 46 was halted due to the contemporaneous marketing and clinical withdrawal of other centrally acting CB1 antagonists; however, the design strategy successfully delivered a potent CB1 antagonist with the desired pharmacokinetic properties and a clean off-target profile.
The Human Ortholog of Granulocyte Macrophage Colony-Stimulating Factor and Interleukin-2 Fusion Protein Induces Potent Ex vivo Natural Killer Cell Activation and Maturation (2009)

Natural killer (NK) cells are appealing cellular pharmaceuticals for cancer therapy because of their innate ability to recognize and kill tumor cells. Therefore, the development of methods that can enhance the potency in their anticancer effect would be desirable. We have previously shown that a murine granulocyte macrophage colony-stimulating factor (GM-CSF)/interleukin 2 (IL-2) fusion protein displays novel antitumor properties in vivo compared with both cytokines in combination due to recruitment of NK cells. In the present work, we have found that human ortholog of the GM-CSF/IL-2 fusion protein (a.k.a. hGIFT2) induces robust NK cell activation ex vivo with significant secretion of RANTES and a 37-fold increase in IFNgamma production when compared with either IL-2 or GM-CSF single cytokine treatment or their combination. Moreover, hGIFT2 upregulates the expression of NK cell activating receptors NKp44, NKp46, and DNAM-1 (CD226), as well as CD69, CD107a, and IL-2Rbeta expression. In addition, hGIFT2 promotes NK cell maturation, based on the downregulation of CD117 expression and upregulation of CD11b. This phenotype correlates with significantly greater cytotoxicity against tumor cells. At the molecular level, hGIFT2 leads to a potent activation of Janus-activated kinases (JAK) downstream of both IL-2 and GM-CSF receptors (JAK1 and JAK2, respectively) and consequently leads to a hyperphosphorylation of signal transducers and activators of transcription (STAT)1, STAT3, and STAT5. In conclusion, hGIFT2 fusokine possesses unique biochemical properties distinct from IL-2 and GM-CSF, constitutes a novel and potent tool for ex vivo NK cell activation and maturation, and may be of use for cancer cell immunotherapy.
BCAS1 expression defines a population of early myelinating oligodendrocytes in multiple sclerosis lesions (2017)

Investigations into brain function and disease depend on the precise classification of neural cell types. Cells of the oligodendrocyte lineage differ greatly in their morphology, but accurate identification has thus far only been possible for oligodendrocyte progenitor cells and mature oligodendrocytes in humans. We find that breast carcinoma amplified sequence 1 (BCAS1) expression identifies an oligodendroglial subpopulation in the mouse and human brain. These cells are newly formed, myelinating oligodendrocytes that segregate from oligodendrocyte progenitor cells and mature oligodendrocytes and mark regions of active myelin formation in development and in the adult. We find that BCAS1<sup>+</sup> oligodendrocytes are restricted to the fetal and early postnatal human white matter but remain in the cortical gray matter until old age. BCAS1<sup>+</sup> oligodendrocytes are reformed after experimental demyelination and found in a proportion of chronic white matter lesions of patients with multiple sclerosis (MS) even in a subset of patients with advanced disease. Our work identifies a means to map ongoing myelin formation in health and disease and presents a potential cellular target for remyelination therapies in MS.
Characterization of Phenylpyruvate Decarboxylase, Involved in Auxin Production of Azospirillum brasilense (2007)

Azospirillum brasilense belongs to the plant growth-promoting rhizobacteria with direct growth promotion through the production of the phytohormone indole-3-acetic acid (IAA). A key gene in the production of IAA, annotated as indole-3-pyruvate decarboxylase (ipdC), has been isolated from A. brasilense, and its regulation was reported previously (A. Vande Broek, P. Gysegom, O. Ona, N. Hendrickx, E. Prinsen, J. Van Impe, and J. Vanderleyden, Mol. Plant-Microbe Interact. 18:311-323, 2005). An ipdC-knockout mutant was found to produce only 10% (wt/vol) of the wild-type IAA production level. In this study, the encoded enzyme is characterized via a biochemical and phylogenetic analysis. Therefore, the recombinant enzyme was expressed and purified via heterologous overexpression in Escherichia coli and subsequent affinity chromatography. The molecular mass of the holoenzyme was determined by size-exclusion chromatography, suggesting a tetrameric structure, which is typical for 2-keto acid decarboxylases. The enzyme shows the highest kcat value for phenylpyruvate. Comparing values for the specificity constant kcat/Km, indole-3-pyruvate is converted 10-fold less efficiently, while no activity could be detected with benzoylformate. The enzyme shows pronounced substrate activation with indole-3-pyruvate and some other aromatic substrates, while for phenylpyruvate it appears to obey classical Michaelis-Menten kinetics. Based on these data, we propose a reclassification of the ipdC gene product of A. brasilense as a phenylpyruvate decarboxylase (EC 4.1.1.43).
Biosynthesis of Glutamate, Aspartate, Asparagine, L -Alanine, and D -Alanine (2004)

Glutamate, aspartate, asparagine, L-alanine, and D-alanine are derived from intermediates of central metabolism, mostly the citric acid cycle, in one or two steps. While the pathways are short, the importance and complexity of the functions of these amino acids befit their proximity to central metabolism. Inorganic nitrogen (ammonia) is assimilated into glutamate, which is the major intracellular nitrogen donor. Glutamate is a precursor for arginine, glutamine, proline, and the polyamines. Glutamate degradation is also important for survival in acidic environments, and changes in glutamate concentration accompany changes in osmolarity. Aspartate is a precursor for asparagine, isoleucine, methionine, lysine, threonine, pyrimidines, NAD, and pantothenate; a nitrogen donor for arginine and purine synthesis; and an important metabolic effector controlling the interconversion of C3 and C4 intermediates and the activity of the DcuS-DcuR two-component system. Finally, L- and D-alanine are components of the peptide of peptidoglycan, and L-alanine is an effector of the leucine responsive regulatory protein and an inhibitor of glutamine synthetase (GS). This review summarizes the genes and enzymes of glutamate, aspartate, asparagine, L-alanine, and D-alanine synthesis and the regulators and environmental factors that control the expression of these genes. Glutamate dehydrogenase (GDH) deficient strains of E. coli, K. aerogenes, and S. enterica serovar Typhimurium grow normally in glucose containing (energy-rich) minimal medium but are at a competitive disadvantage in energy limited medium. Glutamate, aspartate, asparagine, L-alanine, and D-alanine have multiple transport systems.
Wellbore Heat Losses and Pressure Drop In Steam Injection (1972)

This mathematical model of the mechanics of flow of wet and saturated steam down the wellbore during steam injection takes into account the variation of steam temperature and pressure due to friction, as well as heat losses by radiation, conduction, and convection. It consists of two coupled nonlinear equations that are solved iteratively. Introduction Chekalyuk et al., Moss and White, and Fokeev and Kepyrin, investigated wellbore heat losses during injection of a hot or cold fluid down the casing. Ramey made a comprehensive study of the injection of liquids and gases down casing or tubing. Squier et al. presented a complete analytical treatment of hot water injection down the wellbore. Satter extended Ramey's treatment to the case of steam injection. Huygen and Huitt, presented results of a theoretical and experimental treatment of wellbore heat losses during steam injection, and pointed out the importance of the radiation heat loss. Holst and Flock as well as Earlougher extended the above treatments by including, steam pressure calculations. Eickmeier et al. considered the early transient performance, using a finite-difference model. performance, using a finite-difference model. Apart from these studies, Leutwyler gave a comprehensive treatment of casing temperature behavior, and Willhite presented a complete calculation of the over-all heat presented a complete calculation of the over-all heat transfer coefficients. The chief objective of our work was to formulate a comprehensive mathematical model of steam injection into a reservoir to include simultaneous calculation of steam pressure and quality. The model took into account the variation of steam temperature and pressure due to friction, as well as heat losses by pressure due to friction, as well as heat losses by radiation, conduction, and convection, and consisted of two coupled nonlinear differential equations that were solved iteratively. The model results were compared with those predicted by several of the above-mentioned approaches. Formulation of the Model Steam at a constant injection pressure, constant mass flow rate, and constant quality (at the surface) is injected through the tubing into the wellbore. The complete system consists of the fluid, the tubing, the annular space containing low-pressure air, the casing, the cement, and the formation. We propose to compute the pressure and the quality of steam as functions of depth and time. An energy balance and a momentum balance can be written for the flowing fluid as follows: Energy balance ..........(1) Momentum balance ..............................(2) The term dQ is given by,...................(3) where the rate of heat transfer to the formation is (4) dq = , JPT P. 139
A Panel of Artificial APCs Expressing Prevalent HLA Alleles Permits Generation of Cytotoxic T Cells Specific for Both Dominant and Subdominant Viral Epitopes for Adoptive Therapy (2009)

Adoptive transfer of virus-specific T cells can treat infections complicating allogeneic hematopoietic cell transplants. However, autologous APCs are often limited in supply. In this study, we describe a panel of artificial APCs (AAPCs) consisting of murine 3T3 cells transduced to express human B7.1, ICAM-1, and LFA-3 that each stably express one of a series of six common HLA class I alleles. In comparative analyses, T cells sensitized with AAPCs expressing a shared HLA allele or autologous APCs loaded with a pool of 15-mer spanning the sequence of CMVpp65 produced similar yields of HLA-restricted CMVpp65-specific T cells; significantly higher yields could be achieved by sensitization with AAPCs transduced to express the CMVpp65 protein. T cells generated were CD8(+), IFN-gamma(+), and exhibited HLA-restricted CMVpp65-specific cytotoxicity. T cells sensitized with either peptide-loaded or transduced AAPCs recognized epitopes presented by each HLA allele known to be immunogenic in humans. Sensitization with AAPCs also permitted expansion of IFN-gamma(+) cytotoxic effector cells against subdominant epitopes that were either absent or in low frequencies in T cells sensitized with autologous APCs. This replenishable panel of AAPCs can be used for immediate sensitization and expansion of virus-specific T cells of desired HLA restriction for adoptive immunotherapy. It may be of particular value for recipients of transplants from HLA-disparate donors.
The Synthesis of Optically Active Thiazoline and Thiazole Derived Peptides from N-Protected α-Amino Acids (1995)

The scope and limitations of the available methods for the synthesis of optically active thiazoline and thiazole-derived amino acids and peptides are compared and contrasted.