gebhart/patrepeval huggingface dataset:
Cell Cycle Checkpoints: Preventing an Identity Crisis (1996)

Cell cycle checkpoints are regulatory pathways that control the order and timing of cell cycle transitions and ensure that critical events such as DNA replication and chromosome segregation are completed with high fidelity. In addition, checkpoints respond to damage by arresting the cell cycle to provide time for repair and by inducing transcription of genes that facilitate repair. Checkpoint loss results in genomic instability and has been implicated in the evolution of normal cells into cancer cells. Recent advances have revealed signal transduction pathways that transmit checkpoint signals in response to DNA damage, replication blocks, and spindle damage. Checkpoint pathways have components shared among all eukaryotes, underscoring the conservation of cell cycle regulatory machinery.
On bistable behavior and open-base breakdown of bipolar transistors in the avalanche regime-modeling and applications (1992)

In the presence of carrier multiplication in the base collector diode the I/sub c/(I/sub b/, V/sub ce/) characteristics of bipolar transistors show a bistable region of operation. This phenomenon is investigated experimentally and theoretically with the help of the extended Gummel/Poon model. Analysis of the output characteristics yields two breakdown voltages which mark the boundaries of the bistable regime on the V/sub ec/ axis. A generalization of Miller's formula is used to model the decrease of the multiplication factor with increasing transfer current, required for proper description of the input characteristics in the bistable regime. The input characteristics in the bistable regime are used for a discussion of a special BiCMOS SRAM cell that only employs two devices. Formulas for LO and HI level, as well as the switching point, are derived and used for a discussion of power dissipation, area requirements, and noise immunity of the cell.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
β-Amyloid Peptides Induce Mitochondrial Dysfunction and Oxidative Stress in Astrocytes and Death of Neurons through Activation of NADPH Oxidase (2004)

Beta-amyloid (betaA) peptide is strongly implicated in the neurodegeneration underlying Alzheimer's disease, but the mechanisms of neurotoxicity remain controversial. This study establishes a central role for oxidative stress by the activation of NADPH oxidase in astrocytes as the cause of betaA-induced neuronal death. betaA causes a loss of mitochondrial potential in astrocytes but not in neurons. The mitochondrial response consists of Ca2+-dependent transient depolarizations superimposed on a slow collapse of potential. The slow response is both prevented by antioxidants and, remarkably, reversed by provision of glutamate and other mitochondrial substrates to complexes I and II. These findings suggest that the depolarization reflects oxidative damage to metabolic pathways upstream of mitochondrial respiration. Inhibition of NADPH oxidase by diphenylene iodonium or 4-hydroxy-3-methoxy-acetophenone blocks betaA-induced reactive oxygen species generation, prevents the mitochondrial depolarization, prevents betaA-induced glutathione depletion in both neurons and astrocytes, and protects neurons from cell death, placing the astrocyte NADPH oxidase as a primary target of betaA-induced neurodegeneration.
ChemInform Abstract: Synthesis, Structure, and Reactivity of a Palladium Hydrazonato Complex: A New Type of Reductive Elimination Reaction to Form C—N Bonds and Catalytic Arylation of Benzophenone Hydrazone. (1998)

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.
Stereochemical Studies. X. Effects of Neighboring Functional Groups on 1, 2-Asymmetric Induction in the Reduction of Propiophenone Derivatives with Sodium Borohydride (1972)

Effects of neighboring functional groups on 1, 2-asymmetric induction in sodium borohydride reduction were examined with eight kinds of ketones (I-VIII) having functional groups, such as -NH2HCl, -OH, and-OCH3, at a-and/or β-positions to the carbonylgroup. It was recognized that the stereochemical course of the reduction was highlydependent on the position of these functional groups, i. e. erythro-rich products were obtained in reduction of ketones having a functional group at a-position to the carbonyl group, while threo-rich products were obtained in reduction of ketones having a functional group at β-position to the carbonyl group. A six-membered empirical model (XXXVII) was proposed for predicting the stereochemical course in the reduction of ketones having a functional group at β-position to the carbonyl group.Determinations of the relative configurations of the diastereomers (X, XI, XII, XIV, XV, and XVI) were also performed.
Gene expression analysis of lung adenocarcinoma and matched adjacent non-tumor lung tissue. (2014)

The discovery of featured genes which were significantly related to cell cycle and DNA replication has potential for use in the clinic for the diagnosis of lung adenocarcinoma in the future. However, further experiments will be needed to confirm our result.
Role for Phospholipid Interactions in the Trafficking Defect of ΔF508-CFTR (2002)

Cystic fibrosis commonly occurs as a consequence of the DeltaF508 mutation in the first nucleotide binding fold domain (NBF-1) of CFTR. The mutation causes retention of the mutant CFTR molecule in the endoplasmic reticulum, and this aberrant trafficking event is believed to be due to defective interactions between the mutant NBF-1 domain and other cellular factors in the endoplasmic reticulum. Since the NBF-1 domain has been shown to interact with membranes, we wanted to investigate whether NBF-1 and CFTR interactions with specific phospholipid chaperones might play a role in trafficking. We have found that the recombinant wild-type NBF-1 interacts selectively with phosphatidylserine (PS) rather than phosphatidylcholine (PC). By contrast, NBF-1 carrying the DeltaF508 mutation loses the ability to discriminate between these two phospholipids. In cells expressing DeltaF508-CFTR, replacement of PC by noncharged analogues results in an absolute increase in CFTR expression. In addition, we detected progressive expression of higher molecular weight CFTR forms. Thus, phospholipid chaperones may be important for CFTR trafficking, and contribute to the pathology of cystic fibrosis.
Ryanodine receptors of striated muscles: a complex channel capable of multiple interactions (1997)

The ryanodine receptor (RyR) is a high-conductance Ca2+ channel of the sarcoplasmic reticulum in muscle and of the endoplasmic reticulum in other cells. In striated muscle fibers, RyRs are responsible for the rapid release of Ca2+ that activates contraction. Ryanodine receptors are complex molecules, with unusually large cytoplasmic domains containing numerous binding sites for agents that control the state of activity of the channel-forming domain of the molecule. Structural considerations indicate that long-range interactions between cytoplasmic and intramembrane domains control channel function. Ryanodine receptors are located in specialized regions of the SR, where they are structurally and functionally associated with other intrinsic proteins and, indirectly, also with the luminal Ca2(+)-binding protein calsequestrin. Activation of RyRs during the early part of the excitation-contraction coupling cascade is initiated by the activity of surface-membrane Ca2+ channels, the dihydropyridine receptors (DHPRs). Skeletal and cardiac muscles contain different RyR and DHPR isoforms and both contribute to the diversity in cardiac and skeletal excitation-contraction coupling mechanisms. The architecture of the sarcoplasmic reticulum-surface junctions determines the types of RyR-DHPR interactions in the two muscle types.
Topics over time (2006)

This paper presents an LDA-style topic model that captures not only the low-dimensional structure of data, but also how the structure changes over time. Unlike other recent work that relies on Markov assumptions or discretization of time, here each topic is associated with a continuous distribution over timestamps, and for each generated document, the mixture distribution over topics is influenced by both word co-occurrences and the document's timestamp. Thus, the meaning of a particular topic can be relied upon as constant, but the topics' occurrence and correlations change significantly over time. We present results on nine months of personal email, 17 years of NIPS research papers and over 200 years of presidential state-of-the-union addresses, showing improved topics, better timestamp prediction, and interpretable trends.
Evaluation of the Human Melanoma Targeting Properties of Radiolabeled α-Melanocyte Stimulating Hormone Peptide Analogues (2003)

The purpose of this study was to evaluate the human MC1 receptor-mediated melanoma targeting properties of two metal cyclized alpha-MSH peptide analogues, (188)Re-(Arg(11))CCMSH and (188)Re-CCMSH. Initially, the presence and density of the MC1 receptor were determined on a bank of human melanoma cell lines. All eight human melanoma cell lines tested in this study displayed the MC1 receptor at a density of 900 to 5700 receptors per cell. Receptor affinity and biodistribution properties of (188)Re-(Arg(11))CCMSH and (188)Re-CCMSH were evaluated in a cultured TXM13 human melanoma-xenografted Scid mouse model. Biodistribution results demonstrated that 3.06 +/- 0.68 %ID/g of (188)Re-(Arg(11))CCMSH accumulated in the tumors 1 h postinjection and greater than 65% of the activity at 1 h postinjection remained in the tumors at 4 h after dose administration. Whole body clearance of (188)Re-(Arg(11))CCMSH was very rapid, with approximately 82% of injected dose cleared through urinary system at 4 h postinjection. There was very little activity in blood and major organs such as liver, lung, and muscle except for the kidney. (188)Re-CCMSH exhibited similar tumor uptake and retention in TXM13 human melanoma-xenografted Scid mice as (188)Re-(Arg(11))CCMSH. However, the kidney uptake value of (188)Re-CCMSH was two times higher than that of (188)Re-(Arg(11))CCMSH. The results of this study indicate that the MC1 receptor is present on the surface of a large number of human melanoma cells, which makes the MC1 receptor a good imaging or therapeutic target. Moreover, the biodistribution properties of (188)Re-(Arg(11))CCMSH and (188)Re-CCMSH highlight their potential as therapeutic agents for human melanoma.
Common Binding Sites for β-Amyloid Fibrils and Fibroblast Growth Factor-2 in Heparan Sulfate from Human Cerebral Cortex (1999)

Heparan sulfate found in the cerebral plaques of Alzheimer's disease binds to beta-amyloid (Abeta) fibrils. This interaction has been proposed to enhance fibril deposition and mediate Abeta-induced glia activation and neurotoxicity. On the other hand, heparan sulfate augments signaling of fibroblast growth factor-2 (FGF-2), a neuroprotective factor that antagonizes the neurotoxic effects of Abeta. We defined structures in heparan sulfate from human cerebral cortex that bind Abeta fibrils. The minimal binding site is found in N-sulfated hexasaccharide domains and contains critical 2-O-sulfated iduronic acid residues. By contrast, binding of Abeta monomers requires, in addition, 6-O-sulfate groups on glucosamine residues. The binding specificity of fibrillar Abeta is shared by FGF-2, and we here show that cerebral heparan sulfate domains selected for binding to Abeta-(1-40) fibrils bind also to FGF-2. These data suggest that neurotoxic and neuroprotective signals may converge by competing for the same binding sites on the heparan sulfate chain.
Novel histone deacetylase inhibitors in clinical trials as anti-cancer agents (2010)

Histone deacetylases (HDACs) can regulate expression of tumor suppressor genes and activities of transcriptional factors involved in both cancer initiation and progression through alteration of either DNA or the structural components of chromatin. Recently, the role of gene repression through modulation such as acetylation in cancer patients has been clinically validated with several inhibitors of HDACs. One of the HDAC inhibitors, vorinostat, has been approved by FDA for treating cutaneous T-cell lymphoma (CTCL) for patients with progressive, persistent, or recurrent disease on or following two systemic therapies. Other inhibitors, for example, FK228, PXD101, PCI-24781, ITF2357, MGCD0103, MS-275, valproic acid and LBH589 have also demonstrated therapeutic potential as monotherapy or combination with other anti-tumor drugs in CTCL and other malignancies. At least 80 clinical trials are underway, testing more than eleven different HDAC inhibitory agents including both hematological and solid malignancies. This review focuses on recent development in clinical trials testing HDAC inhibitors as anti-tumor agents.
cDNA array technology in melanoma: An overview (2003)

Genetic aberrations, mostly resulting in changes in gene expression, are critical events in cancer onset and progression. The advent of the cDNA array technology allows the screening and the efficient measurement of expression of thousands genes simultaneously in a wide spectrum of experimental and clinical models. This genomic scale approach is being currently used to obtain global views of human cancer gene expression and to identify genetic markers that might be important for diagnosis, prognosis, and therapy. This review discusses some recent findings obtained by means of cDNA arrays investigating the human melanoma.
Wavelength multiplexing in multimode optical fibers (1977)

The capacity of optical fiber transmission systems could be increased by multiplexing several signals at different wavelengths on each fiber. This paper considers various multiplex system designs that might be used with multimode fiber transmission systems. In each case, the required multiplexer size and material properties are calculated as functions of the basic parameters of the fiber system. For fiber systems of the type currently being tested, a compact (~2 mm in diameter x 1 cm long), rugged, three-channel multiplexer could be constructed using a blazed plane reflection grating and graded-refractive-index (GRIN) optics; and it appears that such devices could be produced using available materials and technology. Multiplexers using thick gratings or multilayer dielectric filters are larger, more complicated, and require materials at the very edge of available technology. Multiplexers using a multiple thick grating or hologram could be even smaller than the blazed-grating devices, but materials having the quired characteristics have not been demonstrated.
Minimally modified low density lipoprotein stimulates monocyte endothelial interactions. (1990)

The effect of minimally modified LDL (MM-LDL) on the ability of large vessel endothelial cells (EC) to interact with monocytes and neutrophils was examined. These LDL preparations, obtained by storage or by mild iron oxidation, were indistinguishable from native LDL to the LDL receptor and were not recognized by the scavenger receptor. Treatment of EC with as little as 0.12 micrograms/ml MM-LDL caused a significant increase in the production of chemotactic factor for monocytes (sevenfold) and increased monocyte binding (three- to fivefold). Monocyte binding was maximal after 4 h of EC exposure to MM-LDL, persisted for 48 h, and was inhibited by cycloheximide. In contrast, neutrophil binding was not increased after 1-24 h of exposure. Activity in the MM-LDL preparations was found primarily in the polar lipid fraction. MM-LDL was toxic for EC from one rabbit but not toxic for the cells from another rabbit or any human umbilical vein EC. The resistant cells became sensitive when incubated with lipoprotein in the presence of cycloheximide, whereas the sensitive strain became resistant when preincubated with sublethal concentrations of MM-LDL. We conclude that exposure of EC to sublethal levels of MM-LDL enhances monocyte endothelial interactions and induces resistance to the toxic effects of MM-LDL.
RELATIONSHIP BETWEEN INSTRUMENTAL AND SENSORY MEASUREMENTS OF CHEESE TEXTURE (1999)

ABSTRACT The relationship between sensory and instrumental texture measurements of natural and processed cheeses was studied. A descriptive analysis panel evaluated seven mouth‐evaluated and five hand‐evaluated texture terms. Instrumental measurements included texture profile analysis (TPA), frequency sweeps, and creep. Multivariate analyses showed that many of the sensory and instrumental analyses were highly correlated. Principal component analysis showed similarities and differences in how the cheeses were differentiated by sensory and instrumental techniques. TPA and fundamental rheological tests worked equally well at predicting sensory attributes of the cheeses, but TPA was better at predicting sensory attributes when cheeses were divided into two groups, natural and processed. Instrumental measurements predicted sensory attributes of processed cheeses better than natural cheeses. While fundamental rheological tests reveal important information on network structure and molecular arrangement, these results indicate that empirical texture evaluations work equally well or better at predicting sensory texture properties.
Differentiation in vitro: Effects of Sephadex Fractions of Chick Embryo Extract (1966)

Chicken embryo extract has been fractionated into high-and low-molecular-weight components on Sephadex G-25. Media supplemented with the low-molecular-weight fraction (L) support full differentiation in clones of cartilage and of pigmented retina cells from chicken embryos. Growth rates of such cultures in L-supplemented media are greater than in media without embryo extract, and plating efficiencies are higher than in media with or without whole embryo extract. The high-molecular-weight fraction (H) in low concentrations also stimulates growth and plating efficiency, but inhibits the expression of differentiation.
Nonprogressive transgene-related callosal and hippocampal changes in PDAPP mice (2006)

We have previously shown that homozygous PDAPP mice, a transgenic model of Alzheimer's-like amyloidosis, have abnormal corpus callosi and anterior hippocampi. Now, we investigated the extent to which these morphological abnormalities are correlated with mutant gene dose in a larger, independent, and substantially younger cohort. Homozygous and heterozygous PDAPP mice had significantly smaller callosal commissure length and anterior hippocampal area than controls. Reductions correlated with mutant APP gene dose, with homozygotes showing the greatest reduction, and were present at 2 months of age. These findings and previous work with APP knockouts suggest that PDAPP mice have impaired white matter development due to interference with native murine APP.
Cyclins and Cyclin–Dependent Kinases: Comparative Study of Hepatocellular Carcinoma Versus Cirrhosis (2003)

Increasing evidence has indicated that perturbation of cyclins is one of the major factors leading to cancer. The aim of this study was not only to investigate various cell cycle-related kinase activities in hepatocellular carcinoma (HCC), but also to analyze the difference of cell cycle-related kinase activity levels between hepatitis C virus (HCV)-induced HCC and HCV-induced cirrhosis. The protein levels of cyclins D1, E, A, and H, and of cyclin dependent kinase 1 (Cdk1), Cdk2, Cdk4, Cdk6, and Cdk7 in HCC and in surrounding nontumorous cirrhosis were determined by Western blot. The enzymatic activities of cyclins D1, E, A, Cdk1, Cdk4, Cdk6, Cdk7, and Wee1 were measured using in vitro kinase assays. Protein levels and kinase activities of cyclin D1, Cdk4, cyclin E, cyclin A, and Wee1 were significantly elevated in HCC compared with surrounding cirrhotic tissues. The enhanced cyclin D1-related kinase activity in HCC was accompanied by the up-regulation of Cdk4 activity, but not Cdk6 activity. The kinase activities of Cdk6, Cdk7, and Cdk1 did not differ between HCC and surrounding cirrhotic tissues. In addition, the protein levels and kinase activities of cyclin D1, Cdk4, and cyclin E were higher in poorly differentiated HCC and advanced HCC. In conclusion, the increases of cyclin D1, Cdk4, cyclin E, cyclin A, and Wee1 play an important role in the development of HCC from cirrhosis. Cyclin D1, Cdk4, and cyclin E activation may be closely related to the histopathologic grade and progression of HCC.
[Preparation and evaluation of self-microemulsifying drug delivery systems containing atorvastatin]. (2005)

The results indicated the potential use of SMEDDS for the delivery of atorvastatin to increase its oral bioavailability.
Cell Wall Integrity Signaling inSaccharomyces cerevisiae (2005)

The yeast cell wall is a highly dynamic structure that is responsible for protecting the cell from rapid changes in external osmotic potential. The wall is also critical for cell expansion during growth and morphogenesis. This review discusses recent advances in understanding the various signal transduction pathways that allow cells to monitor the state of the cell wall and respond to environmental challenges to this structure. The cell wall integrity signaling pathway controlled by the small G-protein Rho1 is principally responsible for orchestrating changes to the cell wall periodically through the cell cycle and in response to various forms of cell wall stress. This signaling pathway acts through direct control of wall biosynthetic enzymes, transcriptional regulation of cell wall-related genes, and polarization of the actin cytoskeleton. However, additional signaling pathways interface both with the cell wall integrity signaling pathway and with the actin cytoskeleton to coordinate polarized secretion with cell wall expansion. These include Ca(2+) signaling, phosphatidylinositide signaling at the plasma membrane, sphingoid base signaling through the Pkh1 and -2 protein kinases, Tor kinase signaling, and pathways controlled by the Rho3, Rho4, and Cdc42 G-proteins.
[Comparative study of the effects of metoclopramide and metopimazine on the duodenojejunal motility during the interdigestive period: a manometric study in healthy subjects]. (1988)

The objective of this paper was to compare the effects of metoclopramide (MTC) and of metopimazine (MTP) on intestinal motility in normal subjects in the period between digestion by injecting these two agents at a well-defined time of the migrating motor complex (MMC). Duodenojejunal motility was recorded by manometry (four microperfused catheters; study segment: 30 cm) during the period between phases of digestion (fasting greater than 12 hrs), for 4.6 hrs on average (3, 4, 6 hrs). 14 normal volunteer subjects (6 males, and 8 females 19 to 49 years of age) were randomly assigned to 2 study groups and were given MTC (10 mg) or MTP (10 mg) in slow IV injection (5 mins.) at a controlled rate, performed 25 mins after onset of a phase 3 (P3) in the study segment. As a reference, results obtained in a control group of seven subjects recorded under the same conditions are reported, in addition. Changes in MMC were evaluated in each group by the mean number of P3 hourly and the percent of subjects presenting a P3 within the two hours following injection of the test drug. Variations in phase 2 type motility (P2) were measured using motility indices (MI): the sum of the amplitudes, number of waves, per 5 minute interval. The number of hourly P3 was 0.40 for MTC vs 0.28 for MTP (control 0.47); 90 minutes after an injection, the first P3 appeared in 71% of patients in the MTC groups vs. 14% in the MTP group (control 57%). P3 recorded following injection were not different from the preceding in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)