gebhart/patrepeval huggingface dataset:
Characterization of the production of monocyte chemoattractant protein-1 and IL-8 in an allogeneic immune response. (1993)

Delayed-type hypersensitivity and allograft rejection are dependent upon the generation of Ag-specific T cell immune responses. The mixed lymphocyte reaction is a model of alloantigen-driven immunity and has provided significant insight into the mechanisms of T cell proliferation. Recently, soluble mediators, including TNF-alpha have been shown to be involved in the full expression of this response. In order to elucidate the potential mechanisms of cellular recruitment in the context of either delayed-type hypersensitivity or allograft rejection, we employed a mixed lymphocyte reaction to study the production of chemokines, monocyte chemoattractant protein-1 (MCP-1), and IL-8. Time-course experiments demonstrated that significant levels of MCP-1 and IL-8 were produced in allogeneic cultures as early as day 1, and that this relationship persisted over 6 days in culture. Northern blot analysis of chemokine mRNA confirmed the early induction of these genes in the allogeneic response. The levels of MCP-1 and IL-8 protein from mixed lymphocyte reaction supernatants as measured by specific ELISA were positively correlated with the proliferative response as measured by [3H]TdR uptake. Although significant MCP-1 and IL-8 were produced during a mixed lymphocyte reaction, these molecules did not participate in the proliferative response, as neutralizing antibodies to either MCP-1 or IL-8 had no effect on proliferation. In order to ascertain the mechanism for the induction of MCP-1 and IL-8 during the mixed lymphocyte reaction, experiments were performed in the presence of neutralizing anti-human TNF antibodies. Neutralization of TNF resulted in significant abrogation of MCP-1 and IL-8 production (75 +/- 5 and 87 +/- 2 percent, respectively). Cells isolated from the mixed lymphocyte reaction at day 6, demonstrated that MCP-1 and IL-8 Ag were localized to mononuclear phagocytes. These results demonstrate that potent chemokines, MCP-1 and IL-8, are produced during the evolution of a mixed lymphocyte reaction, and their induction is TNF-dependent.
Modeling multidimensional databases, cubes and cube operations (2002)

Online analytical processing (OLAP) is a trend in database technology, which has attracted the interest of a lot of research work. OLAP is based on the multidimensional view of data, supported either by multidimensional databases (MOLAP) or relational engines (ROLAP). We propose a model for multidimensional databases. Dimensions, dimension hierarchies and cubes are formally introduced. We also introduce cube operations (changing of levels in the dimension hierarchy, function application, navigation etc.). The approach is based on the notion of the base cube, which is used for the calculation of the results of cube operations. We focus our approach on the support of a series of operations on cubes (i.e., the preservation of the results of previous operations and the applicability of aggregate functions in a series of operations). Furthermore, we provide a mapping of the multidimensional model to the relational model and to multidimensional arrays.
Kinetic studies on decomposition of glutathione. II. Anaerobic decomposition in aqueous solution. (1980)

Kinetics studies were performed on the non-enzymatic decomposition of glutathione (GSH) in anaerobic aqueous solution. The apparent first-order rate constants of decomposition were determined in the pH range of 1-12, ionic strength 0.5, at 60° and the pH profile was constructed from the buffer-free rate constants and pH values. The decomposition of GSH took place rapidly in acidic solution, but the rate constant showed a minimum in the pH range of 5-6, a maximum at pH 8.5 and a plateau in the pH range of 10-12. The effects of ionic strength and dielectric constant were almost negligible. The apparent activation energies of decomposition of GSH were all in the range of 19-21 kcal/mol. The rate constants of decomposition were related to the mole fractions of ionic species of GSH, and could be expressed as a function of hydrogen ion activity at arbitrary pH.
Site-Directed Photosystem II Mutants with Perturbed Oxygen-Evolving Properties. 2. Increased Binding or Photooxidation of Manganese in the Absence of the Extrinsic 33-kDa Polypeptide In vivo (1994)

Several site-directed photosystem II mutants with substitutions at Asp-170 or in the carboxyterminal region of the D1 polypeptide were characterized in vivo in the absence of the extrinsic 33-kDa polypeptide. Site-directed mutations were constructed in the cyanobacterium Synechocystis sp. PCC 6803. The 33-kDa polypeptide was removed by insertional inactivation of the Synechocystis psbO gene. Mutants were characterized by measuring changes in the yield of variable chlorophyll a fluorescence following a saturating flash or brief illumination in the presence of an electron-transfer inhibitor or following each of a series of saturating flashes in the absence of inhibitor [Chu, H.-A., Nguyen, A. P., & Debus, R. J. (1994) Biochemistry (preceding paper in this issue)]. In the presence of the extrinsic 33-kDa polypeptide, many site-directed mutants contained a significant fraction of photosystem II reaction centers that lacked photooxidizable Mn ions. This fraction decreased dramatically in the absence of the extrinsic 33-kDa polypeptide, even in mutants having a significantly perturbed high-affinity Mn binding site (e.g., in the mutants D170A and D170T). These results show that, in vivo, the extrinsic 33-kDa polypeptide directly or indirectly governs the occupancy of the high-affinity Mn binding site by Mn ions or the ability of bound Mn ions to reduce YZ+.
A Glucose‐Selective Molecular Fluorescence Sensor (1994)

Low concentrations of D-fructose and D-galactose do not hinder the detection of D-glucose with the fluorescence sensor 1. The diboronic acid 1 is easy to synthesize and forms a cleft structure in which monosaccharides bind with differing selectivity. The saccharide-diboronic acid 1:1 complexes are readily detected by their fluorescence.
The transcription factor Egr-1: a potential drug in wound healing and tissue repair (2001)

In the United States, between 40 and 90 million hospital days are lost per year as a result of trauma and surgical procedures which result in the loss of functional tissue. This is estimated to cost the economy and healthcare providers in excess of US$ 500 billion, a figure that is increasing because of extending population lifespan. Tissue engineering and gene therapies are radical new treatments that are aimed at tissue regeneration ranging from dermal, osteal and occular repair to the replacement of failing tissue with entire biosynthetic organs. Over the last decade, numerous proteins have been identified that are able to direct the synthesis of new tissue. Such proteins include growth factors, cytokines and, more recently, transcription factors.
Protein Glycation (2004)

The advanced glycation end products (AGEs) are a heterogeneous class of molecules, including the following main subgroups: bis(lysyl)imidazolium cross-links, hydroimidazolones, 3-deoxyglucosone derivatives, and monolysyl adducts. AGEs are increased in diabetes, renal failure, and aging. Microvascular lesions correlate with the accumulation of AGEs, as demonstrated in diabetic retinopathy or renal glomerulosclerosis. On endothelial cells, ligation of receptor for AGE (RAGE) by AGEs induces the expression of cell adhesion molecules, tissue factor, cytokines such as interleukin-6, and monocyte chemoattractant protein-1. A chief means by which AGEs via RAGE exert their effects is by generation of reactive oxygen species, at least in part via stimulation of NADPH oxidase. Diabetes-associated vascular dysfunction in vivo can be prevented by blockade of RAGE. Thus, agents that limit AGE formation, increase the catabolism of these species, or antagonize their binding to RAGE may provide new targets for vascular protection in diabetes.
A precursor form of prostate-specific antigen is more highly elevated in prostate cancer compared with benign transition zone prostate tissue. (2000)

Prostate-specific antigen (PSA) is a widely used serum marker for prostate cancer (PCa), but in the critical diagnostic range of 4-10 ng/ml it has limited specificity for distinguishing early PCa from benign prostatic hyperplasia (BPH). PSA in serum is comprised of a variety of both "free" and "complexed" forms that have been used to improve the specificity of PSA for prostate cancer detection. We previously reported that pro PSA (pPSA), the zymogen or precursor form of PSA, is a component of free PSA in the serum of PCa patients. In the current study, we examined prostate tissues to understand the origin and specificity of pPSA. PSA was immuno-affinity purified from matched sets of prostate tissues including peripheral zone cancer (PZ-C); peripheral zone noncancer; and benign tissue from the transition zone (TZ), the primary site of BPH within the prostate. We found that pPSA is differentially elevated in PZ-C, but is largely undetectable in TZ. N-terminal sequencing revealed that the pPSA was comprised primarily of [-2]pPSA and minor levels of [-4]pPSA, containing pro leader peptides of 2 and 4 amino acids, respectively. The median value of pPSA was 3% in PZ-C and 0% (undetectable) in TZ (P < 0.0026). No pPSA was detected in 13 of 18 transition zone specimens (72%), but only 2 of the 18 matched cancer specimens (11%) contained no measurable pPSA. These results demonstrate that pPSA is more highly correlated with prostate cancer than with BPH. The pPSA in serum may represent a more cancer-specific form of PSA that could help distinguish prostate cancer from BPH.
Effects of melengestrol acetate on the inflammatory response in heifers challenged with Mannheimia haemolytica1 (2007)

Previous research from our laboratory has indicated that melengestrol acetate (MGA) added to the diet during the first 35 d after arrival in the feedlot improves growth rates and tends to reduce chronic respiratory disease in heifers naturally challenged with bovine respiratory disease. The current study was conducted to provide further insight into the possible immunomodulatory effects of MGA. Crossbred heifers (n = 48; 232 +/- 5.5 kg of BW) were used in a randomized complete block design to determine the effects of MGA on lung pathology and markers of inflammation after Mannheimia haemolytica challenge. On d 0, cattle were blocked by BW and randomly assigned, within block, to diets (54% concentrate) that provided 0 or 0.5 mg of MGA per heifer daily for the duration of the experiment. Inoculum containing from 1.3 x 10(9) to 1.7 x 10(9) cfu of M. haemolytica (20 mL) was instilled at the bifurcation of the trachea on d 14. Blood samples were collected, clinical observations were made, and rectal temperatures were recorded for each animal at 0, 12, 24, 48, 72, 96, 120, and 138 h after inoculation. Heifers fed MGA had greater circulating concentrations of eosinophils and postchallenge concentrations of segmented neutrophils and white blood cells (P < 0.01) than controls, as well as elevated plasma protein, serum haptoglobin, and fibrinogen after M. haemolytica challenge (P < 0.01). Heifers fed MGA had lower plasma glucose (P < 0.01), greater plasma urea N (P = 0.02), and elevated respiratory indices (P < 0.01) compared with controls. Necropsies performed on d 6 after inoculation suggested that M. haemolytica challenge was relatively mild, because lesions were confined to a small portion of the lungs. On a 0 to 100 scale, average lung lesion scores were 3 and 1 for MGA-fed and control groups, respectively (P < 0.06). Heifers fed MGA before mild M. haemolytica challenge were more susceptible to infection, as evidenced by a greater number of heifers fed MGA exhibiting pulmonary lesions 138 h after inoculation than controls (14 out of 23 vs. 6 out of 24 for MGA and controls, respectively; P < 0.02).
Calculation of radiation doses for nonuniformly distributed β and γ radionuclides in soft tissue (1985)

In cancer radioimmunotherapy nonuniform distributions of radionuclides in geometrically irregular tumor volumes will be encountered. If the tumor is surrounded by a homogeneous layer of soft tissue, the radiation dose distribution in the tumor due to a beta‐emitting nuclide can be calculated by convolution of the appropriate Loevinger's point source dose function, J , with the nuclide concentration distribution. Computer programs using fast Fourier transform techniques have been developed to evaluate the three‐dimensional spatial convolution accurately and efficiently. Equivalent techniques have also been applied to gamma‐emitting nuclides by replacing J in the convolution by the photon point isotropic specific absorbed fraction. Illustractive results are presented for the radiation dose distribution in a 1‐ml target volume with activity distribution which is (i) uniform, (ii) limited by diffusion into the target volume, or (iii) limited by diffusion and shedding of radionuclide in the peripheral layers of the target volume. Calculations for the three cases are presented for 3 2 P, 1 3 1 I, and 15‐, 30‐, and 100‐keV photon emitters.
Integrated Cognitive-neuroscience Architectures for Understanding Sensemaking (ICArUS): Phase 2 Challenge Problem Design and Test Specification (2014)

Abstract : Phase 2 of the IARPA program ICArUS (Integrated Cognitive-neuroscience Architectures for Understanding Sensemaking) requires a research problem that poses cognitive challenges of spatial-temporal sensemaking (BAA, 2010). The problem serves as a challenge for performers who are building integrated cognitive-neuroscience models, and as a tool for obtaining data from human experiments. This document describes the challenge problem, and outlines the T&E(Test & Evaluation( approach for evaluating models in Comparative Performance Assessment and Cognitive Fidelity Assessment (BAA, 2010). Normative (Bayesian) solutions to the challenge problem are derived, as needed to support the assessment of human and model performance. Opportunities are also identified for transition of the challenge problem design and results to the geospatial Intelligence Community.
Catalytic Asymmetric Addition of β‐Ketoesters to Various Imines by Using Chiral Palladium Complexes (2005)

A highly enantioselective Mannich-type reaction of β-ketoesters was developed using a catalytic amount of the Pd–aqua complexes 1 (see scheme; PG=protecting group). A variety of imines derived from glyoxylate, as well as simple aromatic and α,β-unsaturated aldehydes were successfully used. The corresponding Mannich adducts were obtained in high yield with excellent enantioselectivity. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2005/z462202_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Chemical Interrogation of the Malaria Kinome (2014)

Malaria, an infectious disease caused by eukaryotic parasites of the genus Plasmodium, afflicts hundreds of millions of people every year. Both the parasite and its host utilize protein kinases to regulate essential cellular processes. Bioinformatic analyses of parasite genomes predict at least 65 protein kinases, but their biological functions and therapeutic potential are largely unknown. We profiled 1358 small-molecule kinase inhibitors to evaluate the role of both the human and the malaria kinomes in Plasmodium infection of liver cells, the parasites' obligatory but transient developmental stage that precedes the symptomatic blood stage. The screen identified several small molecules that inhibit parasite load in liver cells, some with nanomolar efficacy, and each compound was subsequently assessed for activity against blood-stage malaria. Most of the screening hits inhibited both liver- and blood-stage malaria parasites, which have dissimilar gene expression profiles and infect different host cells. Evaluation of existing kinase activity profiling data for the library members suggests that several kinases are essential to malaria parasites, including cyclin-dependent kinases (CDKs), glycogen synthase kinases, and phosphoinositide-3-kinases. CDK inhibitors were found to bind to Plasmodium protein kinase 5, but it is likely that these compounds target multiple parasite kinases. The dual-stage inhibition of the identified kinase inhibitors makes them useful chemical probes and promising starting points for antimalarial development.
Analysis of Receptor Tyrosine Kinase ROS1-Positive Tumors in Non–Small Cell Lung Cancer: Identification of a FIG-ROS1 Fusion (2012)

NSCLC tumors with ROS1 rearrangements are uncommon in the Chinese population and represent a distinct entity of carcinomas. The ROS1 IHC assay described here is a valuable tool for identifying patients expressing mutant ROS1 and could be routinely applied in clinical practice to detect lung cancers that may be responsive to targeted therapies.
Adaptive RED: An Algorithm for Increasing the Robustness of RED's Active Queue Management (2001)

The RED active queue management algorithm allows network operators to simultaneously achieve high throughput and low average delay. However, the resulting average queue length is quite sensitive to the level of congestion and to the RED parameter settings, and is therefore not predictable in advance. Delay being a major component of the quality of service delivered to their customers, network operators would naturally like to have a rough a priori estimate of the average delays in their congested routers; to achieve such predictable average delays with RED would require constant tuning of the parameters to adjust to current traffic conditions. Our goal in this paper is to solve this problem with minimal changes to the overall RED algorithm. To do so, we revisit the Adaptive RED proposal of Feng et al. from 1997 [6, 7]. We make several algorithmic modifications to this proposal, while leaving the basic idea intact, and then evaluate its performance using simulation. We find that this revised version of Adaptive RED, which can be implemented as a simple extension within RED routers, removes the sensitivity to parameters that affect RED’s performance and can reliably achieve a specified target average queue length in a wide variety of traffic scenarios. Based on extensive simulations, we believe that Adaptive RED is sufficiently robust for deployment in routers.
Vaccine-Induced Env V1-V2 IgG3 Correlates with Lower HIV-1 Infection Risk and Declines Soon After Vaccination (2014)

HIV-1-specific immunoglobulin G (IgG) subclass antibodies bind to distinct cellular Fc receptors. Antibodies of the same epitope specificity but of a different subclass therefore can have different antibody effector functions. The study of IgG subclass profiles between different vaccine regimens used in clinical trials with divergent efficacy outcomes can provide information on the quality of the vaccine-induced B cell response. We show that HIV-1-specific IgG3 distinguished two HIV-1 vaccine efficacy studies (RV144 and VAX003 clinical trials) and correlated with decreased risk of HIV-1 infection in a blinded follow-up case-control study with the RV144 vaccine. HIV-1-specific IgG3 responses were not long-lived, which was consistent with the waning efficacy of the RV144 vaccine. These data suggest that specific vaccine-induced HIV-1 IgG3 should be tested in future studies of immune correlates in HIV-1 vaccine efficacy trials.
Detection of colonies of Anaplasma marginale in salivary glands of three Dermacentor spp infected as nymphs or adults (1989)

Salivary glands from males of 3 Dermacentor species (D andersoni, D variabilis and D occidentalis) that were infected with either the Virginia or Idaho isolate of Anaplasma marginale as nymphs or adults were examined for colonies of A marginale by use of light and electron microscopy. Prior to dissection of salivary glands, exposed ticks were held at 25 C for 15 to 18 days, followed by a 3-day incubation at 37 C. Ticks of 2 species transmitted A marginale to calves; the third tick species was confirmed infected by demonstration of typical colonies in tick gut cells, but transmission was not attempted; Colonies of A marginale were seen with light microscopy in salivary glands of all 3 species of ticks; they were located in acinar cells that contained simple granules. Colonies varied morphologically from small, compact ones to larger structures that contained distinct organisms and often were adjacent to the host cell nucleus. Electron microscopy confirmed that the colonies were rickettsial organisms. Morphologic features of A marginale varied and included reticulated forms, forms with electron-dense centers, and small particles; these various forms were similar to those described previously in midgut epithelial cells of ticks. We believe that the organism seen within tick salivary glands may replicate in the glands before its transmission to the vertebrate host.
A Nonclinical Safety Assessment of MnTE-2-PyP, a Manganese Porphyrin (2013)

Manganese (III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin (MnTE-2-PyP or BMX-010; CASRN 219818-60-7) is a manganese porphyrin compound developed as a potential drug substance for use as a radioprotective and for the ex vivo treatment of cells, tissues, and organs intended for transplantation. In preparation for an investigational new drug filing, a full good laboratory practice nonclinical safety assessment was conducted in order to evaluate the safety of MnTE-2-PyP and included the performance of in vitro genotoxicity studies, local tissue tolerance evaluation, safety pharmacology core battery studies, and single- and repeat-dose intravenous (iv) toxicity studies in mice and monkeys. The MnTE-2-PyP was determined not to be genotoxic or hemolytic, did not demonstrate flocculation or elicit adverse pharmacologic effects on respiration, the central nervous system (CNS), and had limited transitory effects on the cardiovascular system only at levels well above the therapeutic target dose. The intended iv clinical solution did not cause venous irritation in rabbits. The no observed adverse effect level (NOAEL) in mice was determined to be 10 mg/kg/day after 18 consecutive days of bolus iv dosing once daily in the morning. The NOAEL in monkeys after 14 days of bolus iv dosing in the morning was determined to be 5 mg/kg/day. At doses relevant to clinical use in humans, neither study revealed any indication of any specific target organ toxicity, including the classic heme porphyrin kidney, liver, CNS, or cardiac toxicities, or manganese toxicity. Mortality seen shortly after dosing in individual animals at higher doses was not accompanied by any organ or clinical pathology indications, suggesting a functional pharmacological-mediated effect. Based on the results of these studies, a conservative safe initial starting clinical dose of 5.0 mg (0.083 mg/kg in a 60 kg adult) was proposed for the initiation of human trials. Because of patent life issues, use of MnTE-2-PyP as a transplantation aid or radioprotective agent is not currently being pursued past the preclinical stages. It serves as a model for the clinical development of this class of drugs.