gebhart/patrepeval huggingface dataset:
Quinolone antimicrobial agents substituted with morpholines at the 7-position. Syntheses and structure-activity relationships (1993)

A series of novel 7-substituted 1-cyclopropyl-6,8-difluoro-1, 4-dihydro-4-oxo-3-quinolinecarboxylic acids have been prepared and tested for antibacterial activities and for convulsive activities in combination with nonsteroidal antiinflammatory drug. Structure-activity relationships revealed that 7-(2-(aminomethyl)morpholino) derivative 28 had a better Gram-positive activity than the reference quinolones, such as ciprofloxacin, norfloxacin, and ofloxacin. Its Gram-negative activity was equipotent with those of norfloxacin and ofloxacin but was inferior to that of ciprofloxacin. In mouse systemic infection models, 28 showed an excellent therapeutic efficacy which might result from the potent antibacterial activity and suitable physicochemical properties. Convulsive activities of 7-morpholino derivatives in combination with nonsteroidal antiinflammatory drug fenbufen or its metabolite biphenylacetic acid markedly diminished as compared to those of 7-piperazino derivatives in the electrophysiological, biochemical, and behavioral experiments. These results suggest that 28 (Y-26611) is a novel quinolone with reduced neurotoxic excitatory adverse reaction.
The role of NF-κB in the pathogenesis of glioma (2014)

Activation of NF-κB affects multiple aspects of cancer biology including cell survival and resistance to treatment. Glioblastoma (GBM) is the most common primary malignant tumor of the brain in adults and is resistant to treatment. Recent studies have reported that NF-κB activation in GBM is widespread and have elucidated the underlying regulatory mechanisms. EGFR gene amplification and mutation are among the key genetic alterations in GBM, and aberrant EGFR signaling is a key activator of NF-κB in GBM. In this review we discuss the evidence for activation of NF-κB in GBM and the key signaling pathways involved. Substantial evidence suggests a role for NF-κB in the pathogenesis of GBM and its resistance to treatment, indicating that NF-κB pathways may be useful targets for treatment.
Improvements and applications for key word recognition using hidden Markov modeling techniques (1991)

A hidden Markov model based key wordspotting algorithm developed previously can recognize key words from a predefined vocabulary list spoken in an unconstrained fashion. Improvements in the feature analysis used to represent the speech signal and modeling techniques used to train the system are explored. The authors discuss several task domain issues which influence evaluation criteria. They present results from extensive evaluations on three speaker independent databases: the 20 word vocabulary Stonehenge Road Rally database, distributed by the National Security Agency, a five word vocabulary used to automate operator-assisted calls, and a three word Spanish vocabulary that is currently being tested in Spain's telephone network. Currently, recognition accuracies range from 99.9% on the Spanish database to 74% (with 8.8 FA/H/W) on the Stonehenge task.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Laser confocal microscopy and geographic information systems in the study of dental morphology (1999)

The advent of computers has allowed the use of new analytical methods while the nature and methods of original data acquisition have seen fewer changes. Most analytical methods rely on landmark data that can be easily recorded from teeth. The choice of landmarks, however, may limit the scope of a study as decisions on data collection have to be made prior to recording the landmarks. Here we present a method to record and analyze tooth crown morphology of small teeth with almost no loss of shape information. Epoxy resin casts with eosin dye are optically sectioned with 25-100 m intervals using a laser confocal microscope with fluorescence detection. Alternatively, original specimens of Recent teeth can often be optically sectioned in reflective light mode. High-resolution digital elevation models (DEMs) of tooth crowns are produced from the image stacks using the 3Dview version of the NIH-Image software (MacOS). Digital elevation models can be transferred to Geographic Information System (GIS) software as well as interpreted by surface rendering computer programs. All traditional morphometrical measurements can be obtained from DEMs. However, the total shape data (i.e., DEMs) can be explored with GIS prior to the selection of appropriate measurements. Furthermore, as the DEMs can be stored as a museum database of tooth morphologies, the three-dimensional morphology can be accessed remotely via the Web, reducing the need to visit museum collections or borrow specimens. This confocal scanning method is well-suited for large samples of small teeth and other small fossils.
Enhanced performance of offset-gain high-barrier vertical-cavity surface-emitting lasers (1993)

The temperature dependence and power output of vertical-cavity surface-emitting lasers (VCSELs) are addressed. The peak wavelength of the quantum well has been offset from the wavelength of the device cavity mode so that they are aligned at elevated temperatures. The result of this design change is to produce an 8- mu m-diameter VCSEL capable of operation to 145 degrees C, as well as CW operation of broad-area (70- mu m diameter) heat-sunk devices to record power levels. Fiber coupling experiments were also carried out, and a record 33-mW CW power was coupled to a multimode fiber.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Hexokinase as a sugar sensor in higher plants. (1997)

The mechanisms by which higher plants recognize and respond to sugars are largely unknown. Here, we present evidence that the first enzyme in the hexose assimilation pathway, hexokinase (HXK), acts as a sensor for plant sugar responses. Transgenic Arabidopsis plants expressing antisense hexokinase (AtHXK) genes are sugar hyposensitive, whereas plants overexpressing AtHXK are sugar hypersensitive. The transgenic plants exhibited a wide spectrum of altered sugar responses in seedling development and in gene activation and repression. Furthermore, overexpressing the yeast sugar sensor YHXK2 caused a dominant negative effect by elevating HXK catalytic activity but reducing sugar sensitivity in transgenic plants. The result suggests that HXK is a dual-function enzyme with a distinct regulatory function not interchangeable between plants and yeast.
ChemInform Abstract: Synthesis and Reactions of 2‐(α‐Phenylimido‐β‐o‐ chlorophenyl)vinyl‐4(H)‐3,1‐benzoxazin‐4‐one. (1995)

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.
Reduced Pancreatic Polypeptide Secretion in Obese Subjects* (1980)

In this work we have compared the human pancreatic polypeptide (hPP) response to a protein-rich meal (70 g smoked pork loin and 20 g white bread) in 21 healthy obese [overweight by 53 ± 2.5% (SEM)] and 28 control volunteers of similar ages. The mean fasting hPP concentration of the obese group was lower than that of the normal volunteers (32 ± 7 vs. 55 ± 7 pg/ml; P = 0.031). The hPP secretion evoked by the meal also was smaller in the obese than in the control individuals, with differences between the mean values of both groups ranging from 74–140 pg/ml throughout the experimental period. Furthermore, the hPP response, as expressed by the area above the basal value, was smaller in the obese than in the control subjects (15.60 ± 3.56 and 29.67 ± 4.64, respectively; p = 0.028). Compared to the normal individuals, the overweight subjects displayed elevated mean plasma insulin and glucose levels both in the basal state and after food ingestion. Mean fasting FFA values also were higher in the obese group than in the control subjects. The hPP hyposecretion observed in our obese subjects may be a consequence of their elevated circulating glucose and FFA levels, since the injection of these substrates in normal subjects has been shown to reduce basal hPP plasma concentrations as well as the secretory response of this hormone to food ingestion. On the other hand, the reduction of plasma hPP found in overweight individuals is in agreement with the decrease in plasma PP levels reported for New Zealand obese mice and with the diminution in the islet number of PP-secreting cells observed i n Jackson ob/ob mice. Although the causal relationship between obesity and lowered hPP secretion remains to be elucidated, our data are compatible with the concept that hPP is involved in the control of appetite by acting as an inhibitor.
Supra-additive Growth Inhibition by a Celecoxib Analogue and Carboxyamido-triazole Is Primarily Mediated through Apoptosis (2005)

Combination studies of celecoxib and chemotherapeutic agents suggest that combining cyclooxygenase-2 inhibitors with other agents may have supra-additive or synergistic effects on tumor growth inhibition. Carboxyamido-triazole (CAI), a voltage-independent calcium channel inhibitor, has been shown to induce growth inhibition and apoptosis in cancer cells. We found that continuous exposure to cytostatic doses of CAI and LM-1685, a celecoxib analogue, reduced the proliferation and survival of seven human cancer cell lines by at least one log (P < or = 0.001) over either agent alone. To explore the mechanism of action of this combination, we further studied the effects of LM-1685/CAI on CCL-250 colorectal carcinoma cells. We found that the supra-additive antiproliferative effects occurred throughout a range of LM-1685 doses (5-25 micromol/L) and paralleled a decrease in COX-2 activity as measured by prostaglandin E2 production. In these cells, treatment with LM-1685/CAI suppressed the extracellular signal-regulated kinase pathway within the first hour but ultimately results in high, sustained activation of ERK over a 9-day period (P = 0.0005). Suppression of cyclin D1 and phospho-AKT, and cleavage of caspase-3 and PARP were concomitant with persistent ERK activation. Addition of PD98059, a MEK-1 inhibitor, suppressed ERK activation and significantly but incompletely reversed these signaling events and apoptosis. Flow cytometry experiments revealed that the CAI/LM-1685 combination induced a 3-fold increase in apoptosis over control (P = 0.005) in 3 days. We show that the combination of CAI and LM-1685 produces a cytotoxic effect by suppressing proliferation and triggering apoptosis.
Identification of five allelic variants of the sheep PrP gene and their association with natural scrapie (1995)

Scrapie is a fatal neurodegenerative disease of sheep that belongs to the group of prion diseases found in humans and animals. The host encoded prion protein (PrP) plays a central role in the disease process. In the PrP genes of man, mice and sheep, polymorphisms have been found that are associated with disease susceptibility and pathogenesis. We have used denaturing gradient gel electrophoresis (DGGE) to detect polymorphisms in the sheep PrP gene. In addition to the already described polymorphisms at codons 136, 154 and 171, we identified a hitherto unknown G --> T transition at codon 171. This transition is responsible for a glutamine to histidine substitution. An arginine to glutamine substitution at this position has been described previously. DGGE allowed us to identify five different combinations of these polymorphisms within the PrP gene representing five allelic variants, which were cloned and sequenced. Based on the triplet sequences present at codons 136, 154 and 171 these allelic variants were designated PrPVRQ, PrPARR, PrPARQ, PrPARH and PrPAHQ. To determine the association of these allelic variants with natural scrapie, we screened 34 scrapie affected and 91 healthy control sheep of the Texel breed for the presence of these allelic variants. In these two groups, the five variants gave rise to 13 different genotypes. The distribution of the allelic variants among both groups showed marked differences. The PrPVRQ variant was present with high frequency in scrapie affected sheep, whereas the PrPARR variant was almost exclusively present in the healthy group. Two other variants, PrPARQ and PrPARH, were found in both groups with equal frequencies. The data obtained suggest modulation of disease susceptibility in these Texel sheep by at least five different PrP allelic variants, with the PrPVRQ and PrPARR alleles acting in a dominant, but opposite fashion over the PrPARQ and PrPARH alleles. The frequency of the PrPAHQ variant was too low to draw any conclusions.
Analytical modeling and simulation of a CMOS-MEMS cantilever based CO2 sensor for medical applications (2013)

Capnometers measure the concentration of CO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> in exhaled breath which could prevent serious problems in all areas of healthcare, from pre-hospital to extended care, and everywhere in between. Presently, high cost, big size and high power usage limit the scope of the conventional capnometers and their adaption. To overcome these issues, a CMOS MEMS micro-cantilever has been proposed for capnometric applications. Analytical modeling and simulation of the microcantilever sensor is carried out to determine its resonance frequency and sensitivity. According to the developed analytical model and simulation results, the sensor has 1% difference in the resonance frequency. The sensitivity of the sensor is determined analytically at different thicknesses of the polymer coating layer. The sensitivity of the sensor is 3.18 Hz/100ppm at 5 μm polymer layer thickness.
Modeling Discharge Behavior of Multicell Battery (2010)

Multicell battery has been widely used in various electrical and electronics devices. To achieve the optimal multicell battery design, accurately modeling battery discharge behavior of multicell battery is crucial. However, modeling discharge behavior of multicell battery is very challenging due to the nonlinear battery effects, nonuniform cell quality, and various cell connections. In this paper, we develop a circuit-based multicell battery model to accurately model the multicell battery discharge behavior in terms of available capacity, output voltage, and internal resistance with consideration of nonlinear battery effect and nonuniform cell quality. It also characterizes the cell discharge current distribution of cell strings in parallel connection. The proposed multicell battery model has been validated by extensive simulation and experimental results under various load conditions.
Biochemical and biologic characterization of lymphocyte regulatory molecules. VIII. Purification of interleukin 2 from a human T cell leukemia. (1981)

A cloned murine T cell line, LBRM-33 5A4, growing in culture can be activated by phytohemagglutinin (PHA) to secrete Interleukin 2 (IL-2) activity. In the absence of PHA, LBRM cells do not produce IL-2. The chemical and biologic properties of LBRM-derived IL-2 are compared to those of murine spleen-derived IL-2. The fractionation of culture supernatants from PHA-activated LBRM cells by ion-exchange chromatography, gel filtration, and isoelectric focusing (IEF) reveals that IL-2 activity is contained in a class of molecules indistinguishable in size (30,000) and charge (pI 4.3-4.7 and 4.9-5.1) from murine spleen IL-2. LBRM-derived IL-2 also exhibits the entire spectrum of biologic activities exhibited by spleen IL-2, stimulating the growth of established T cell lines in culture, the generation of cytotoxic T lymphocytes in thymocyte cultures and the induction of antibody responses in nude spleen cultures. Both LBRM and splenic-derived IL-2 activities exhibit similar properties after digestion with proteases, and various chemical and temperature treatments. Since IL-2 is derived from a cloned cell line, it is likely these lymphocyte assays are detecting a single class of molecules that act directly on activated T cells. The use of LBRM cells as a source of IL-2 should greatly facilitate studies on the molecular characterization and biologic activity of this class of lymphocyte regulatory molecules.
Patterns of epidermal growth factor receptor amplification in malignant gliomas. (1996)

Amplification of the gene for epidermal growth factor receptor (EGFR) is a common finding in malignant gliomas. We found that 18 of 29 grade 3 and grade 4 gliomas had EGFR amplification when assayed using fluorescence in situ hybridization. The amplification pattern suggests that the amplicon is contained within double minute chromosomes in most cases. EGFR copy number can differ by 20-fold in amplified cells within a single case. Polysomy 7 occurs frequently in both EGFR-amplified and -unamplified cells. More than one-third of the cases had < or = 10 percent of cells with amplified EGFR, and it is likely that these cases would not have been identified by methods that do not examine DNA on a cell by cell basis.
Predominant Hematopoietic Origin of Cell-free DNA in Plasma and Serum after Sex-mismatched Bone Marrow Transplantation (2002)

After bone marrow transplantation, the DNA in plasma and serum is predominantly hematopoietic in origin. Apart from the biological implications of this observation, this finding suggests that plasma and serum can be used as alternative materials for the study of postbone marrow transplantation chimerism.
Ultra-fast photonic curing of electrically conductive adhesives fabricated from vinyl ester resin and silver micro-flakes for printed electronics (2014)

Electrically conductive vinyl ester resin–silver micro-flake adhesives, combined with intense pulsed light, present ultra-fast photonic curing within a second.
Visual Compression of Workflow Visualizations with Automated Detection of Macro Motifs (2013)

This paper is concerned with the creation of 'macros' in workflow visualization as a support tool to increase the efficiency of data curation tasks. We propose computation of candidate macros based on their usage in large collections of workflows in data repositories. We describe an efficient algorithm for extracting macro motifs from workflow graphs. We discovered that the state transition information, used to identify macro candidates, characterizes the structural pattern of the macro and can be harnessed as part of the visual design of the corresponding macro glyph. This facilitates partial automation and consistency in glyph design applicable to a large set of macro glyphs. We tested this approach against a repository of biological data holding some 9,670 workflows and found that the algorithmically generated candidate macros are in keeping with domain expert expectations.
Activated oncogenes in human tumors. (1990)

The search for the genetic targets responsible for tumorigenesis has led to the identification of a number of cancer genes or cellular oncogenes (c-oncogenes). The oncogenes are activated forms of the proto-oncogenes, which are normal cellular genes and are scattered throughout the cellular genome. The number of known cellular proto-oncogenes and associated oncogenes now exceeds 30. There are different proto-oncogene families and their products have different functions and cellular localisation. They may function in normal cells in the process of proliferation, regulation of cellular metabolism through signal transfer, or cell differentiation. Activation of proto-oncogenes in man is now assumed to be due to: 1) point mutation; 2) overexpression or 3) gene rearrangement. The observation that in some tumors multiple oncogenes are altered could be interpreted in terms of a multigene hypothesis. However, in some cases, a single properly-activated oncogene may be able to trigger the whole process of malignant conversion. It is difficult to correlate, without ambiguity, tumor induction to specific types of DNA lesions in human tumors. Xeroderma pigmentosum (XP), a rare recessive autosomal skin disorder characterized biochemically as a DNA repair-deficient disease, is the first example in which unrepaired UV-induced DNA lesions are directly responsible for tumorigenesis. In two independent XP skin tumors, isolated from the same patient, we have detected several (N-ras, c-myc, Ha-ras) altered oncogenes in the same tumor. We postulate that the modifications we have found in these tumors are primarily due to the presence of unrepaired UV-adducts. Long term treatment of human tumoral cell lines bearing an activated ras oncogene, with Interferon-alpha (IFN), showed that IFN can affect the phenotype of the tumor cells without altering the expression of the activated ras gene. IFN may have the capacity to affect diverse cellular pathways. Consequently, the nature of the biological response of a given type of tumor cell to IFN may depend on its inherent properties.
High incidence of cholesterol gallstone disease in type 1 Gaucher disease: characterizing the biliary phenotype of type 1 Gaucher disease (2010)

Our results point to a metabolic syndrome in GD1 consisting of a propensity to cholesterol GS, low high-density lipoprotein (HDL) cholesterol, LDL cholesterol, and body mass index (BMI) associated with abnormal biliary lipid secretion.
Class IA phosphatidylinositol 3-kinase: from their biologic implication in human cancers to drug discovery (2008)

In spite of the progress made over the past few years, more studies are still needed to better understand the biology of this pathway, its interaction(s) with other signaling cascades, and the role of the individual paralogs and PI3Kalpha mutants in human cancer. From a drug discovery perspective, medicinal chemistry efforts have led to the discovery of new pan-PI3K and isoform selective inhibitors with improved specificity, potency and pharmaceutical properties. Phase I clinical studies have been initiated with some of these PI3K inhibitors and the efficacy and therapeutic index of this new generation of anticancer agents is eagerly awaited.