gebhart/patrepeval huggingface dataset:
Isolation and Properties of a Thrombin-sensitive Protein of Human Platelets (1972)

A glycoprotein of human platelets is released into the incubation medium upon treatment of the intact cells with 1 unit per ml of thrombin for 2 min. The cellular location and properties of this protein differ from those of other thrombin-labile platelet proteins such as fibrin-stabilizing factor, fibrinogen, and the contractile protein thrombosthenin. It occurs only in the particulate fraction and is released only from intact cells. Thrombin concentrations of 100 units per ml do not release this thrombin-sensitive protein from sonicated platelets. As isolated from the incubation supernatant of thrombin-treated platelets the thrombin-sensitive protein is excluded from Sephadex G-200; it has an apparent molecular weight of 190,000 in sodium dodecyl sulfate polyacrylamide gels, from which it has been purified and partially characterized. No smaller subunits have been found. It has limited solubility in the absence of detergent, and is highly sensitive to proteolytic degradation in whole platelets and after release from the cells. Membrane-bound and released forms of the thrombin-sensitive protein show no significant difference in molecular weight or amino acid and carbohydrate composition, suggesting that release does not involve proteolysis of the thrombin-sensitive protein itself by thrombin. This protein contains 3.9% sialic acid, 1.6% N-acetylglucosamine, and 25% each of acidic and nonpolar residues. Although it contains carbohydrate the thrombin-sensitive protein does not represent the major membrane glycoprotein of platelets, for it contains only 5% of the total platelet sialic acid. The thrombin-sensitive protein accounts for approximately 5% of the total protein in the particulate fraction of human platelets and represents about 20 to 30% of the protein found in the incubation supernatant after thrombin treatment.
Preventing Infectious Disease in Dynamic Populations Under Uncertainty (2018)

Treatable infectious diseases are a critical challenge for public health. Outreach campaigns can encourage undiagnosed patients to seek treatment but must be carefully targeted to make the most efficient use of limited resources. We present an algorithm to optimally allocate limited outreach resources among demographic groups in the population. The algorithm uses a novel multiagent model of disease spread which both captures the underlying population dynamics and is amenable to optimization. Our algorithm extends, with provable guarantees, to a stochastic setting where we have only a distribution over parameters such as the contact pattern between agents. We evaluate our algorithm on two instances where this distribution is inferred from real world data: tuberculosis in India and gonorrhea in the United States. Our algorithm produces a policy which is predicted to avert an average of least 8,000 person-years of tuberculosis and 20,000 person-years of gonorrhea annually compared to current policy.
Isolation of New Arabidopsis Mutants With Enhanced Disease Susceptibility to Pseudomonas syringae by Direct Screening (1998)

To identify plant defense components that are important in restricting the growth of virulent pathogens, we screened for Arabidopsis mutants in the accession Columbia (carrying the transgene BGL2-GUS) that display enhanced disease susceptibility to the virulent bacterial pathogen Pseudomonas syringae pv. maculicola (Psm) ES4326. Among six (out of a total of 11 isolated) enhanced disease susceptibility (eds) mutants that were studied in detail, we identified one allele of the previously described npr1/nim1/sai1 mutation, which is affected in mounting a systemic acquired resistance response, one allele of the previously identified EDS5 gene, and four EDS genes that have not been previously described. The six eds mutants studied in detail (npr1-4, eds5-2, eds10-1, eds11-1, eds12-1, and eds13-1) displayed different patterns of enhanced susceptibility to a variety of phytopathogenic bacteria and to the obligate biotrophic fungal pathogen Erysiphe orontii, suggesting that particular EDS genes have pathogen-specific roles in conferring resistance. All six eds mutants retained the ability to mount a hypersensitive response and to restrict the growth of the avirulent strain Psm ES4326/avrRpt2. With the exception of npr1-4, the mutants were able to initiate a systemic acquired resistance (SAR) response, although enhanced growth of Psm ES4326 was still detectable in leaves of SAR-induced plants. The data presented here indicate that eds genes define a variety of components involved in limiting pathogen growth, that many additional EDS genes remain to be discovered, and that direct screens for mutants with altered susceptibility to pathogens are helpful in the dissection of complex pathogen response pathways in plants.
Amperometric biosensors produced by immobilization of redox enzymes at polythiophene‐modified electrode surfaces (1996)

The use of polythiophene films for the immobilization of enzymes at electrodes is shown to have advantages over other conducting polymer films. Two methods by which the enzymes can be immobilized—entrapment and covalent immobilization at the surface—are described and compared. The improved stability of polythiophene against oxidation in ambient environments is expected to enable the construction of biosensors with improved sensor characteristics and lifetime.
Genomics as a Probe for Disease Biology (2003)

The use of genomic techniques has led to insights into the pathobiology of both common and uncommon diseases. This last installment in the Genomic Medicine series provides a number of examples of the ways in which genomics has served as a probe for disease biology.
Lithium-induced nephrogenic diabetes insipidus: new clinical and experimental findings (2010)

Lithium (Li+) salts are widely used to treat bipolar mood disorders. Recent trials suggest a potential efficacy also in the treatment of amyotrophic lateral sclerosis and Alzheimer's disease. Li+ is freely filtered by the glomerulus and mainly reabsorbed in the proximal convoluted tubule. Reabsorption in the distal nephron becomes significant under sodium-restricted conditions. Nevertheless, the distal nephron is greatly affected by Li+ even under normal sodium intake. Polyuria, renal tubular acidosis and finally chronic renal failure are the most frequent adverse effects. The occurrence of an overt nephrogenic diabetes insipidus (NDI) limits Li+ usage and imposes suspension. The molecular mechanisms of Li+-related urinary concentration defect involve a dysregulation of the aquaporin system in principal cells of the collecting duct. ENaC is crucial as the entry route for intracellular Li+ accumulation. The basolateral exit route is not clearly identified, but some evidence suggests Na+/H+ exchanger 1 (NHE1) as a potential candidate. Li+ promotes polyuria mainly counteracting the intracellular vasopressin signaling. An additional role of the inner medullary interstitial cells and PGE-2 pathway has to be considered. The GSK3ß cascade is also regulated by Li+. GSK3ß inhibition could lead not only to the polyuria, but also to the Li+-dependent proliferative effect on principal cells. Cellular reorganization of the collecting duct and microcysts are the main pathological findings during Li+ treatment. Their relationship with the urinary concentration defect and an eventual Li+-induced ciliopathy has to been investigated. Li+-induced NDI has been a matter of investigation since the early 1970s. This manuscript reports the latest clinical and experimental findings in combination with the older fundamental results.
A microfluidic processor for gene expression profiling of single human embryonic stem cells (2007)

The gene expression of human embryonic stem cells (hESC) is a critical aspect for understanding the normal and pathological development of human cells and tissues. Current bulk gene expression assays rely on RNA extracted from cell and tissue samples with various degree of cellular heterogeneity. These 'cell population averaging' data are difficult to interpret, especially for the purpose of understanding the regulatory relationship of genes in the earliest phases of development and differentiation of individual cells. Here, we report a microfluidic approach that can extract total mRNA from individual single-cells and synthesize cDNA on the same device with high mRNA-to-cDNA efficiency. This feature makes large-scale single-cell gene expression profiling possible. Using this microfluidic device, we measured the absolute numbers of mRNA molecules of three genes (B2M, Nodal and Fzd4) in a single hESC. Our results indicate that gene expression data measured from cDNA of a cell population is not a good representation of the expression levels in individual single cells. Within the G0/G1 phase pluripotent hESC population, some individual cells did not express all of the 3 interrogated genes in detectable levels. Consequently, the relative expression levels, which are broadly used in gene expression studies, are very different between measurements from population cDNA and single-cell cDNA. The results underscore the importance of discrete single-cell analysis, and the advantages of a microfluidic approach in stem cell gene expression studies.
Deficiency of intact thrombospondin and membrane glycoprotein Ia in platelets with defective collagen-induced aggregation and spontaneous loss of disorder (1988)

Platelets from a patient with a severe lifelong bleeding tendency, which later spontaneously disappeared, lacked intact thrombospondin and glycoprotein (GP) Ia. Before disappearance of the bleeding disorder, results of coagulation studies and platelet aggregation in response to adenosine diphosphate (ADP), arachidonic acid, thrombin, A23187, epinephrine, and ristocetin were normal. In contrast, aggregation only occurred in the presence of collagen or wheat germ agglutinin at unusually high doses of these agonists. The platelets adhered normally to purified bovine and human type I collagen, and they did not spread in the presence of methylated type I collagen. No collagen-induced clot retraction was observed. Two-dimensional gel electrophoretic analyses of platelet proteins and immunologic studies showed that intact thrombospondin and GP Ia were absent. Aggregation in response to collagen could be restored by adding thrombospondin. Disappearance of the bleeding tendency occurred at the onset of menopause; subsequent analyses revealed that thrombospondin and GP Ia were present in platelets and that collagen-induced platelet aggregation was normal. These results suggest that both thrombospondin and GP Ia are essential in collagen-induced platelet aggregation. The spontaneous disappearance of the bleeding tendency may have been related to hormonal influences.
ChemInform Abstract: Synthesis of 3‐(2,4‐Dichlorophenyl)‐4‐substituted‐5‐mercapto‐1,2,4‐ triazoles and Their Derivatives. (1991)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Increase of chemokine interferon-inducible protein-10 (IP-10) in the serum of patients with autoimmune liver diseases and increase of its mRNA expression in hepatocytes (2001)

To clarify the role of IP-10 in autoimmune liver diseases, we studied the serum levels of IP-10 in 14 patients with autoimmune hepatitis (AIH), 23 patients with primary biliary cirrhosis (PBC), and 65 patients with chronic viral hepatitis (20 type B and 45 type C). The hepatic expression of IP-10 mRNA and the correlation between the serum levels of IP-10 and clinical parameters were also evaluated. In addition to 20 healthy controls, 16 rheumatoid arthritis (RA) patients were included as an extrahepatic inflammatory disease. The serum level of IP-10 was significantly (P < 0.02) higher in patients with AIH, PBC, and chronic hepatitis B and C than in healthy controls, and it was significantly correlated (P < 0.05) with the serum levels of aspartate aminotransferase and alanine aminotransferase in patients with AIH, PBC, and chronic hepatitis B and C. The serum level of IP-10 was not elevated in RA patients. After successful treatment of AIH and chronic hepatitis C, the serum level of IP-10 decreased to the same level as in healthy volunteers. As we previously showed in cases with chronic hepatitis B or C, in situ hybridization in both AIH and PBC cases demonstrated the expression of IP-10 mRNA in hepatocytes around focal or lobular necrosis surrounded by infiltrating mononuclear cells, whereas IP-10 mRNA was not expressed in areas around the damaged bile ducts in PBC cases. The present results suggest that IP-10 is specifically produced by hepatocytes in inflammatory areas irrespective of the aetiology of hepatitis, and that IP-10 may help to recruit T cells to the hepatic lesions in autoimmune liver diseases as well as in chronic viral hepatitis.
Platinum(II)-Catalyzed Generation and [3+2] Cycloaddition Reaction of α,β-Unsaturated Carbene Complex Intermediates for the Preparation of Polycyclic Compounds (2010)

Pt(II)-catalyzed generation of unsaturated carbene complex intermediates from various propargyl ether derivatives based on electrophilic activation of alkynes was realized. These in situ generated unsaturated carbene complexes undergo [3+2] cycloaddition reaction with various vinyl ethers, leading to efficient formation of indoles, naphthols, and benzofuran fused with a five-membered ring in high yields.
Human chorionic gonadotropin (HCG) in the treatment of obesity: a critical assessment of the Simeons method. (1977)

A common practice in toughening semicrystalline polymers is to blend them with second-phase rubber particles. A multiscale numerical model is used to investigate the effect of a specific microstructural morphology on the mechanical behavior of particle-dispersed systems. A polycrystalline model is used for the polymer matrix material. The basic structural element in this model is a layered two-phase composite inclusion, comprising both a crystalline and an amorphous domain. The averaged fields of an aggregate of composite inclusions, having either random or preferential orientations, form the constitutive response of the polymeric matrix material. Transcrystallized orientations are found to have a limited effect on matrix shear yielding and alter the triaxial stress field.
Towards automatic visual obstacle avoidance (1977)

This report describes ongoing research on a working system which drives a vehicle through cluttered environments under computer control, guided by images perceived through an onboard television camera. The emphasis is on reliable and fast low level visual techniques which determine the existence and location of objects in the world, but do not identify them
HSP90 is a therapeutic target in JAK2-dependent myeloproliferative neoplasms in mice and humans (2010)

JAK2 kinase inhibitors were developed for the treatment of myeloproliferative neoplasms (MPNs), following the discovery of activating JAK2 mutations in the majority of patients with MPN. However, to date JAK2 inhibitor treatment has shown limited efficacy and apparent toxicities in clinical trials. We report here that an HSP90 inhibitor, PU-H71, demonstrated efficacy in cell line and mouse models of the MPN polycythemia vera (PV) and essential thrombocytosis (ET) by disrupting JAK2 protein stability. JAK2 physically associated with both HSP90 and PU-H71 and was degraded by PU-H71 treatment in vitro and in vivo, demonstrating that JAK2 is an HSP90 chaperone client. PU-H71 treatment caused potent, dose-dependent inhibition of cell growth and signaling in JAK2 mutant cell lines and in primary MPN patient samples. PU-H71 treatment of mice resulted in JAK2 degradation, inhibition of JAK-STAT signaling, normalization of peripheral blood counts, and improved survival in MPN models at doses that did not degrade JAK2 in normal tissues or cause substantial toxicity. Importantly, PU-H71 treatment also reduced the mutant allele burden in mice. These data establish what we believe to be a novel therapeutic rationale for HSP90 inhibition in the treatment of JAK2-dependent MPN.
Liquid Chromatography–High Resolution Mass Spectrometry Analysis of Fatty Acid Metabolism (2011)

We present a liquid chromatography/mass spectrometry (LC/MS) method for long-chain and very-long-chain fatty acid analysis and its application to (13)C-tracer studies of fatty acid metabolism. Fatty acids containing 14 to 36 carbon atoms are separated by C(8) reversed-phase chromatography using a water-methanol gradient with tributylamine as ion pairing agent, ionized by electrospray and analyzed by a stand-alone orbitrap mass spectrometer. The median limit of detection is 5 ng/mL with a linear dynamic range of 100-fold. Ratios of unlabeled to (13)C-labeled species are quantitated precisely and accurately (average relative standard deviation 3.2% and deviation from expectation 2.3%). In samples consisting of fatty acids saponified from cultured mammalian cells, 45 species are quantified, with average intraday relative standard deviations for independent biological replicates of 11%. The method enables quantitation of molecular ion peaks for all labeled forms of each fatty acid. Different degrees of (13)C-labeling from glucose and glutamine correspond to fatty acid uptake from media, de novo synthesis, and elongation. To exemplify the utility of the method, we examined isogenic cell lines with and without activated Ras oncogene expression. Ras increases the abundance and alters the labeling patterns of saturated and monounsaturated very-long-chain fatty acids, with the observed pattern consistent with Ras leading to enhanced activity of ELOVL4 or an enzyme with similar catalytic activity. This LC/MS method and associated isotope tracer techniques should be broadly applicable to investigating fatty acid metabolism.
Sparse initial entrapment of systemically injected Salmonella typhimurium leads to heterogeneous accumulation within tumors. (2003)

Blood-borne therapeutics, which rely on diffusion and convection for delivery, often do not accumulate in effective concentrations distant from vasculature and are therefore unable to eradicate all cells within a tumor. Motile bacteria have the potential to overcome the diffusion and pressure gradients that prevent passive materials from penetrating into poorly perfused regions of tumors. Here, we test several proposed mechanisms of Salmonella typhimurium accumulation in tumors, including: (a) entrapment in the chaotic vasculature of tumors; (b) attraction to specific tumor microenvironments; and (c) preferential replication within specific microenvironments. After systemic injection of S. typhimurium into tumor-bearing mice, we used intravital microscopy and histological techniques to quantify their interaction with tumor vasculature. Immediately after injection, few S. typhimurium (<4 in 10,000) adhered to tumor vasculature; most remained passively suspended in the blood. Despite this low initial adhesion, approximately 10,000-fold more S. typhimurium accumulated in tumors than any other organ 1 week after the injection, thus demonstrating their specificity. However, within the tumors, we found that most bacteria were located in necrotic tissue as large colonies far (750 micro m) from functional vasculature. Together, these results suggest that S. typhimurium has limited ability to adhere to tumor vasculature and migrate within tumors and only survives in tissue that becomes necrotic. Although S. typhimurium is a promising delivery vehicle because of its tumor specificity, increasing its intra-tumoral motility should improve its therapeutic effectiveness.
Crystalline Structure and Properties of EP and EB Copolymers by Solid-State NMR, DSC, and WAXS (2002)

The crystalline structures of ethylene−propylene (EP) and ethylene−butene (EB) copolymers have been investigated using a combination of solid-state NMR, WAXS, and DSC. In high-propylene (>20 mol %) EP copolymers, the α methylene exhibits different isotropic chemical shifts in the crystalline and amorphous regions. This indicates the presence of the methyl branch in the crystalline region and that the branch point has a trans conformation. As a result of the incorporation, on increasing branch content, the orthorhombic lattice expands in the EP copolymers. Then they exhibit a first-order transition from orthorhombic to a rotator (hexagonal) phase in which chains rotate about the chain axes. In the rotator crystals, about 5% of the carbons are methyl groups. At lower propylene comonomer contents, the crystal structure is orthorhombic, although with a larger area per chain and lower-field isotropic chemical shift value than observed for HDPE. It is proposed that the pattern of change of lattice constants and eventual transition into the rotator phase upon increasing branch content are closely related to the dynamics of the crystalline chains. In EB copolymers, in contrast, even at high comonomer concentrations, the crystal structure is still orthorhombic. The measured expansion coefficient of the rotator phase is much less than that of the same phase in n-alkanes, likely due to temperature-dependent branch incorporation.
Vegetative Insecticidal Proteins (2010)

The field of plant genetic engineering has arisen from the laboratory and into the market place as a technology to provide farmers and consumers with improved crops. 1996 marks a turning point as the first genetically engineered crops to control agronomically important pests are registered for commercial sale. In most cases it has taken over a decade to develop commercially viable products. This book serves both as an update of current technologies that have been proven successful for engineering insect tolerant crops and an overview of new technologies that are being pursued for the development of new genetically engineered crops in the future. The book includes an introductory chapter on the world wide importance of insect problems in crops and the advantages of genetically engineered crops over traditional breeding; reviews insect control principles that are being develpoed for genetically engineered crops; and provides an overview of many new areas that wil lead to new insect control agents in the next decade.