gebhart/patrepeval huggingface dataset:
Nonbiased identification of DNA sequences that bind thyroid hormone receptor alpha 1 with high affinity. (1993)

Thyroid hormone receptors are transcription factors that bind to specific DNA sequences and regulate gene expression in a ligand-dependent manner. Although thyroid hormone receptors are known to bind to the hexamer 5'-AGGTCA, it is not known if this represents the optimal binding site. Therefore, a nonbiased strategy was used to identify DNA sequences which bind thyroid hormone receptor alpha 1 with high affinity. Such DNA sequences were isolated from a pool of random sequences using a strategy combining an electrophoretic mobility shift assay with the polymerase chain reaction. It was found that thyroid hormone receptor alpha 1 binds with highest affinity to the octamer 5'-TAAGGTCA. Mutation of the two 5'-nucleotides decreased the affinity of thyroid hormone receptor alpha 1 for this DNA sequence approximately 5-fold, and the importance of those nucleotides in receptor binding was confirmed by DNA footprinting. A single copy of the octamer sequence (but not the hexamer AGGTCA) could impart T3 responsiveness to a heterologous promoter in a transient transfection assay. The results indicate that the optimal binding site for thyroid hormone receptor alpha 1 is 2 base pairs larger than previously thought, and that a single binding site can function as a response element. In addition, we speculate that the optimal binding sites for thyroid hormone, vitamin D, and retinoic acid receptors may not be identical, as had previously been thought.
Oral extended-release products (1999)

The use of extended-release products offers some potential advantages in patient convenience/compliance and therapeutic outcomes.
Differential inactivation of Escherichia coli membrane dehydrogenases by a myeloperoxidase-mediated antimicrobial system (1990)

Neutrophil myeloperoxidase, hydrogen peroxide, and chloride constitute a potent antimicrobial system with multiple effects on microbial cytoplasmic membranes. Among these is inhibition of succinate-dependent respiration mediated, principally, through inactivation of succinate dehydrogenase. Succinate-dependent respiration is inhibited at rates that correlate with loss of microbial viability, suggesting that loss of respiration might contribute to the microbicidal event. Because respiration in Escherichia coli can be mediated by dehydrogenases other than succinate dehydrogenase, the effects of the myeloperoxidase system on other membrane dehydrogenases were evaluated by histochemical activity stains of electrophoretically separated membrane proteins. Two bands of succinate dehydrogenase activity proved the most susceptible to inactivation with complete loss of staining activity within 20 min, under the conditions employed. A group with intermediate susceptibility, consisting of lactate, malate, glycerol-3-phosphate, and dihydroorotate dehydrogenases as well as three bands of glucose-6-phosphate dehydrogenase, was almost completely inactivated within 30 min. The relatively resistant group, including the dehydrogenases for glutamate, NADH, and NADPH and the remaining bands of glucose-6-phosphate dehydrogenase, retained substantial amounts of diaphorase activity for up to 60 min of incubation with the myeloperoxidase system. The differential effects of myeloperoxidase on dehydrogenase inactivation could not be correlated with published enzyme contents of flavin or iron-sulfur centers, potential targets of myeloperoxidase-derived oxidants. Despite the relative resistance of NADH dehydrogenase/diaphorase activity to myeloperoxidase-mediated inactivation, electron transport particles prepared from E. coli incubated for 20 min with the myeloperoxidase system lost 55% of their NADH oxidase activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Synthesis and Evaluation of Nitroheterocyclic Phosphoramidates as Hypoxia-Selective Alkylating Agents (2000)

A series of novel nitroheterocyclic phosphoramidates has been prepared, and the cytotoxicity of these compounds has been evaluated in clonogenic assays against B16, wild-type and cyclophosphamide-resistant MCF-7, and HT-29 cells under aerobic conditions and HT-29 cells under hypoxic conditions. All compounds were comparable in toxicity to wild-type and resistant MCF-7 cells and were also selectively toxic to HT-29 cells under hypoxic conditions (selectivity ratios 1.7 to >20). Analogues lacking the nitro group were not cytotoxic. Electron-withdrawing substituents increased cytotoxicity under aerobic conditions and thereby decreased hypoxic selectivity. In contrast, an electron-donating substituent markedly decreased both aerobic and hypoxic cytotoxicity but enhanced hypoxic selectivity. Chemical reduction of the nitro group resulted in rapid expulsion of the cytotoxic phosphoramide mustard. The most potent of these compounds show significant cytotoxicity under both aerobic and hypoxic conditions.
Neutrophil elastase inhibitors as treatment for COPD (2002)

Chronic obstructive pulmonary disease, characterised by a slowly progressive, irreversible airways limitation, is a major worldwide cause of chronic morbidity and mortality. The imbalance between human neutrophil elastase and endogenous antiproteases may cause excess human neutrophil elastase in pulmonary tissues, which may be considered a major pathogenic factor in chronic obstructive pulmonary disease. Great effort has been devoted to finding a method to restore the balance, resulting in the discovery of potent two-typed small-molecular-weight human neutrophil elastase inhibitors. In the application of chronic obstructive pulmonary disease therapy, the human neutrophil elastase inhibitors mainly focused upon include ONO-5046, MR-889, L-694,458, CE-1037, GW-311616 and TEI-8362 as the acyl-enzyme inhibitors; and ONO-6818, AE-3763, FK-706, ICI-200,880, ZD-0892 and ZD-8321 as the transition-state inhibitors. In this review, various problems that remain to be solved in the clinical use of human neutrophil elastase inhibitors are discussed.
Identification of Annexin II Heterotetramer as a Plasmin Reductase (2002)

Annexin II heterotetramer (AIIt) is a Ca(2+)- and phospholipid-binding protein that consists of two copies of a p36 and p11 subunit. AIIt regulates the production and autoproteolysis of plasmin at the cell surface. In addition to its role as a key cellular protease, plasmin also plays a role in angiogenesis as the precursor for antiangiogenic proteins. Recently we demonstrated that the primary antiangiogenic plasmin fragment, called A(61) (Lys(78)-Lys(468)) was released from cultured cells. In the present study we report for the first time that AIIt possesses an intrinsic plasmin reductase activity. AIIt stimulated the reduction of the plasmin Cys(462)-Cys(541) bond in a time- and concentration-dependent manner, which resulted in the release of A(61) from plasmin. Mutagenesis of p36 C334S and either p11 C61S or p11 C82S inactivated the plasmin reductase activity of the isolated subunits, suggesting that specific cysteinyl residues participated in the plasmin reductase activity of each subunit. Furthermore, we demonstrated that the loss of AIIt from the cell surface of HT1080 cells transduced with a retroviral vector encoding p11 antisense dramatically reduced the cellular production of A(61) from plasminogen. This is the first demonstration that AIIt regulates the cellular production of the antiangiogenic plasminogen fragment, A(61).
[Study on the correlation between acute lymphoblastic leukemia and HLA genes in southern China Han population]. (2005)

To study the correlation between acute lymphoblastic leukemia (ALL) and HLA-A, B and DRB1 gene in southern Chinese Han population and to investigate the susceptible HLA gene to ALL, a total of 4707 healthy volunteer bone marrow donors from southern Chinese Han population were used as a control group, 201 patients diagnosed as patient group from southern Han individuals were genotyped at HLA-A, B and DRB1 loci by PCR-SSP, PCR-SSOP and SBT. HLA allele frequency and its distribution of ALL patient group were compared with the control group by using chi(2) test, and calculated the statistic value of relative risk (RR), pathogenicity score (EF) and preventive score (PF). The results showed that in comparison with the control group, the gene frequence of HLA-A26, B56 and DR9 increased significantly, but the gene frequence of HLA-A30, A33 and B58 allele frequency decreased significantly for patients with ALL. It is concluded that HLA-A26, B56 and DR9 gene have a high correlation with ALL and seem to contribute the genetic susceptibility to ALL in southern Chinese Han populations. However, HLA-A30, A33 and B58 gene seem to have protective role for southern Han individuals suffered from ALL.
Electrophysiological and Morphological Characterization of Rat Embryonic Motoneurons in a Defined System (2003)

In an attempt to integrate biological components with silicon-based devices and systems, artificial silane surfaces have been successfully used to grow motoneurons in a defined environment. In this study we characterized the morphology and electrophysiology of purified rat embryonic (E14) motoneurons grown on a self-assembled monolayer (SAM) of N-1[3-(trimethoxysilyl)propyl]diethylenetriamine (DETA) versus that on ornithine/laminin surfaces in serum-free media. On DETA motoneurons were flat and grew more processes, whereas on ornithine/laminin they tended to aggregate. The membrane time constant, a characteristic associated with electrotonic compactness, was significantly longer for motoneurons grown on DETA. Other electrophysiological parameters were similar for the motoneurons on the different surfaces. This is the first study where purified ventral horn motoneurons were cultured in a completely defined (nonbiological surface, serum-free) environment.
Dynamic International Prognostic Scoring System (DIPSS) predicts progression to acute myeloid leukemia in primary myelofibrosis (2010)

Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) with a high propensity to develop acute myeloid leukemia, named at this stage blast phase (BP) of PMF. 1 Oncogenic JAK2 signaling is an important event in MPN, but transformation process into BP, although not completely understood, often involves additional genomic lesions. 2 Several models have been developed to predict survival in PMF. 3-5 Concerning BP occurrence, leukocyte count more than 30 10 9 /L, 5 blast cell count more than 10%, 6 platelet count below 50 10 9 /L, 6 red blood cell transfusion dependency, 7 selected cytogenetic abnormalities, 6,8 low JAK2(V617F) allele burden 9 have been reported to shorten BP-free survival.
Long-Term Pioglitazone Treatment for Patients With Nonalcoholic Steatohepatitis and Prediabetes or Type 2 Diabetes Mellitus (2016)

Burroughs Wellcome Fund and American Diabetes Association.
Induction of siderophore activity in Anabaena spp. and its moderation of copper toxicity (1987)

Growth of Anabaena sp. strain 7120 (in the absence of chelators or added iron) was inhibited by the addition of 2.1 to 6.5 microM copper and was abolished by copper concentration of 10 microM or higher. When the copper was chelated to schizokinen (the siderophore produced by this organism in response to iron starvation), the toxic effects were eliminated. Analysis of culture filtrates showed that the cupric schizokinen remains in the medium, thereby lowering the amount of copper taken up by the cells. Although this organism actively transports ferric schizokinen, it apparently does not recognize the cupric complex. Thus, Anabaena sp. is protected from copper toxicity under conditions in which siderophore is being produced. For cells grown in low iron, the accumulation of extracellular schizokinen was observed to parallel cell growth and continue well into stationary phase. The actual iron status of the organism was monitored by using iron uptake velocity as an assay. Cultures grown on 0.1 microM added iron were found to be severely iron limited upon reaching stationary phase, thus explaining the continued production of schizokinen. These data show that the siderophore system in Anabaena spp. has developed primarily as a response to iron starvation and that additional functions such as alleviation of copper toxicity or allelopathic inhibition of other algal species are merely secondary benefits.
Inhalation Exposure Methodology (1984)

Modern man is being confronted with an ever-increasing inventory of potentially toxic airborne substances. Exposures to these atmospheric contaminants occur in residential and commercial settings, as well as in the workplace. In order to study the toxicity of such materials, a special technology relating to inhalation exposure systems has evolved. The purpose of this paper is to provide a description of the techniques which are used in exposing laboratory subjects to airborne particles and gases. The various modes of inhalation exposure (whole body, head only, nose or mouth only, etc.) are described at length, including the advantages and disadvantages inherent to each mode. Numerous literature citations are included for further reading. Among the topics briefly discussed are the selection of appropriate animal species for toxicological testing, and the types of inhalation studies performed (acute, chronic, etc.).
Electrical Methods For Precision Stepper Column Optimization (1986)

This paper presents a quick and accurate method for determining optical column misalignment and degree of telecentricity of a precision wafer stepper using computerized electrical techniques. The trend toward increasingly difficult device design rules has driven the present demand for ultimate stepper performance, which requires the optimization of column alignment and telecentricity, along with the routine monitoring of standard parameters including translation, rotation, magnification, trapezoid and distortion. Device designs using a full-lens field and requiring complex processing, involving large topographical steps, are especially demanding.
Expression of the neuronal form of pp60c-src in neuroblastoma in relation to clinical stage and prognosis. (1990)

The expression of the protooncogene c-src has been studied in specimens of childhood tumors with special reference to neuroblastoma and other tumors of neuronal origin. For comparison c-src gene expression was studied in seven neuroblastoma and neuroepithelioma cell lines. The structurally distinct neuronal product of the gene, pp60c-srN, expressed during normal development in neuroblasts and neurons, was identified by immunoblotting technique together with the fibroblast form, pp60c-src. While pp60c-src was found in most tumors studied, the neuronal form was restricted to neuroblastomas (23 of 27) and retinoblastomas (3 of 3) and could not be detected in the other childhood tumors. A dominance of the neuronal form, pp60c-srcN, was exclusively found in the infant cases of neuroblastoma (9 of 12), estimated to have good prognosis. These results indicate that pp60c-srcN might be a diagnostic marker in primitive childhood tumors. When expressed in higher amounts than pp60c-src, pp60c-srcN may be a positive prognostic marker in neuroblastoma, especially useful in the evaluation of infants. In addition, lack of pp60c-srcN seems to be incompatible with low stage neuroblastoma.
Destruction of pancreatic beta cells in rats by complete Freund's adjuvant combined with non-diabetogenic doses of streptozotocin. (1987)

Non-specific activation of the immune system by complete Freund's adjuvant (CFA) in combination with non-diabetogenic doses of streptozotocin (STZ) was used to study autoimmune reactions against pancreatic islets. Male Lewis RT1a rats received either CFA (0.5 ml/kg) 24 hr prior to the injection of STZ (25 mg/kg), or CFA or STZ alone. The injections of CFA followed by STZ, but not CFA or STZ alone, produced a 69% (p less than 0.01) reduction in pancreatic insulin content associated with necrosis and a decrease of the relative volume density of insulin-immunoreactive cells without affecting other islet cells. Two injections of CFA and STZ induced hyperglycemia. This was associated with a depletion of pancreatic insulin and a significant reduction in the relative volume density of insulin-immunoreactive cells (p less than 0.01) and in the mean islet area (p less than 0.01). On day 20, after treatment with 3 injections of CFA and STZ, the animals developed persistent hyperglycemia. The pancreata in these rats contained less than 12% B-cells, and the insulin content was reduced by 96% (p less than 0.01). The main components of the remaining atrophic islets were glucagon- and somatostatin-immunoreactive cells. No significant lymphocytic infiltration into the islets was detectable, but the exocrine parenchyma exhibited severe inflammatory lesions. Degranulation and vacuolation of B-cells was evident by ultra-structural analysis. The volume densities of insulin containing cells and islet area were not changed after 3 injections of either CFA or STZ alone, although the pancreatic insulin content decreased by 61% (p less than 0.01) and 39% (p less than 0.05), respectively. These treatments did not produce an increase in plasma glucose. The present results demonstrate that CFA in combination with non-diabetogenic doses of the beta cytotoxic agent STZ induces B-cell destruction without significant insulitis. Our observations support the hypothesis that activation of the immune system by CFA allows an anti-B-cell immune reaction to develop following exposure to STZ.
Optical header extraction and recognition by discrete time stretch technique (2005)

We demonstrate low latency discrete time optical header extraction and recognition. 8-bits of 10 Gb/s header is extracted and slowed down to /spl sim/590 Mb/s by discrete time stretch technique. Optical Q values of > 19 dBQ are measured.
Optimizing Platelet P2Y12 Inhibition for Patients Undergoing PCI (2007)

Guidelines recommend that dual antiplatelet therapy using aspirin and clopidogrel should be administered to the majority of patients with acute coronary syndromes, including those undergoing percutaneous coronary intervention (PCI). However, the results of a large randomized, placebo-controlled study suggest that a 300-mg loading dose of clopidogrel must be administered at least 15 h prior to PCI in order to achieve a significant reduction in peri-PCI thrombotic events. Other data suggest that 2 h of pretreatment may be sufficient if a 600-mg loading dose is used. Since it is often difficult to achieve an adequate pretreatment goal with clopidogrel in clinical practice, more rapid achievement of platelet P2Y(12) inhibition may improve patient outcomes. Prasugrel, [6-[2-(3,4-diflurophenyl) cyclopropyl1-1-y1] amino-2-propylthio-9-D-ribofuranosyl-9H-purine (AZD6140), and cangrelor are platelet P2Y(12) receptor antagonists currently in development that offer faster acting inhibition of adenosine diphosphate (ADP)--induced platelet aggregation. These agents act upon the same platelet receptor as clopidogrel, but are distinguished by their routes of administration, reversibility, and pharmacodynamic properties. Prasugrel is an orally administered agent that provides faster, higher, and more consistent inhibition of platelet aggregation than clopidogrel. The results of Phase II testing suggest that the risk of bleeding is similar in prasugrel- and clopidogrel-treated patients. AZD6140 is another orally administered platelet inhibitor with rapid and reversible action. Again, Phase II testing suggests similar bleeding risk for clopidogrel. Preliminary evidence suggests that clinical outcomes may be better in prasugrel- and AZD6140-treated patients than in clopidogrel-treated patients. Cangrelor is an intravenously administered, reversible, short-acting agent with a rapid onset of activity. Bleeding risk and clinical outcomes data are similar in cangrelor- and abciximab-treated patients. The results of ongoing Phase III clinical trials involving more than 40,000 patients will demonstrate whether these agents fulfill their potential to improve outcomes in PCI-treated patients by providing faster, higher, and more consistent inhibition of platelet aggregation.
IL-12 receptor regulation in IL-12-deficient BALB / c and C57BL / 6 mice (2000)

Immunization with protein antigen in complete Freund's adjuvant (CFA) induces Th1 cells in BALB/c and C57BL/6 (B6) mice. Pretreatment with the same protein in soluble form induces Th2 cells in BALB/c but not in B6 mice and inhibits Th1 cell development in both. We have previously shown that inhibition of Th1 in BALB/c mice correlates with the down-regulation of transcripts encoding the IL-12 receptor beta2 (IL-12Rbeta2) chain, which is required for IL-12 signaling and Th1 cell development. We now demonstrate that IL-12-deficient BALB/c mice, when primed with antigen in CFA, mount a Th2 instead of the Th1 response which develops in wild-type mice. Conversely, IL-12-deficient B6 mice fail to develop Th2 cells. Thus, a default Th2 development is induced by antigen priming in IL-12-deficient BALB/c but not B6 mice. IL-12Rbeta2 transcripts are still expressed in antigen-restimulated CD4(+) T cells from IL-12-deficient BALB/c and B6 mice and they are similarly reduced by pretreatment with soluble antigen, suggesting that intrinsic strain differences in IL-12R regulation do not account for the differential polarization to the Th2 pathway. IL-4 is not required for down-regulation of IL-12Rbeta2 transcripts and inhibition of Th1 development in mice pretreated with soluble protein, as shown by their reduction in IL-4-deficient BALB/c mice.
Principles of adaptive filters and self-learning systems (2006)

How can a signal be processed for which there are few or no a priori data?

Professor Zaknich provides an ideal textbook for one-semester introductory graduate or senior undergraduate courses in adaptive and self-learning systems for signal processing applications. Important topics are introduced and discussed sufficiently to give the reader adequate background for confident further investigation. The material is presented in a progression from a short introduction to adaptive systems through modelling, classical filters and spectral analysis to adaptive control theory, nonclassical adaptive systems and applications.
A new method for estimation of velocity vectors (1998)

The paper describes a new method for determining the velocity vector of a remotely sensed object using either sound or electromagnetic radiation. The movement of the object is determined from a field with spatial oscillations in both the axial direction of the transducer and in one or two directions transverse to the axial direction. By using a number of pulse emissions, the inter-pulse movement can be estimated and the velocity found from the estimated movement and the time between pulses. The method is based on the principle of using transverse spatial modulation for making the received signal influenced by transverse motion. Such a transverse modulation can be generated by using apodization on individual transducer array elements together with a special focusing scheme. A method for making such a field is presented along with a suitable two-dimensional velocity estimator. An implementation usable in medical ultrasound is described, and simulated results are presented. Simulation results for a flow of 1 m/s in a tube rotated in the image plane at specific angles (0, 15, 35, 55, 75, and 90 degrees) are made and characterized by the estimated mean value, estimated angle, and the standard deviation in the lateral and longitudinal direction. The average performance of the estimates for all angles is: mean velocity 0.99 m/s, longitudinal S.D. 0.015 m/s, and lateral S.D. 0.196 m/s. For flow parallel to the transducer the results are: mean velocity 0.95 m/s, angle 0.10, longitudinal S.D. 0.020 m/s, and lateral S.D. 0.172 m/s.