gebhart/patrepeval huggingface dataset:
Structure/Function Analysis of the Murine CD95L Promoter Reveals the Identification of a Novel Transcriptional Repressor and Functional CD28 Response Element (2003)

CD28 costimulation, an important second signal for antigen-mediated T cell activation, is known to enhance expression of several genes important for the regulation of CD4+ T cell effector function including interleukin-2 and CD154. Previous studies demonstrate CD28-mediated enhancement of the transcription and expression of Fas ligand (CD95L) in T cell lines, suggesting a regulatory link between CD28 and CD95L expression. These results served as the basis for structure/function analysis of the CD95L promoter to elucidate the mechanism for CD28-mediated enhancement of CD95L. In this report, we describe a novel response element, located at -210 to -201 bp upstream of the transcription start site, that confers CD28 responsiveness to the CD95L gene. This response element is homologous to the CD28 response element (CD28RE) previously identified in the IL-2 promoter and bears structural similarities to a newly identified CD28RE in the CD154 promoter. We further demonstrate that CD28-mediated enhancement of promoter activity correlates with enhanced expression of CD95L mRNA, cell surface expression of CD95L protein, and increased apoptosis of CD95+ target cells. These results demonstrate a direct transcriptional regulatory role for CD28 in CD95L-mediated functional activity in CD4+ T cells. Mutational analysis of the CD95L promoter also reveals a novel transcriptional repressor element located approximately 60 bp 5' of the CD28RE. The repressor element bears sequence homology to an activator protein-1 element, constitutively binds c-Fos but not c-Jun, and is activation-independent.
Calpain activity increases in hepatocytes following addition of ATP. Demonstration by a novel fluorescent approach. (1993)

Our aim was to measure calpain protease activity during increases in cytosolic free calcium (Ca2+i) after addition of extracellular ATP. The calpain protease substrate t-butoxycarbonyl-Leu-Met-7-amino-4-chloromethylcoumarin was synthesized. Nonfluorescent t-butoxycarbonyl-Leu-Met-7-amino-4- chloromethyl-coumarin diffuses into the cell where it is conjugated to glutathione forming t-butoxycarbonyl-Leu-Met-7-amino-4-methylcoumarin glutathione conjugate (Boc-Leu-Met-MAC-SG). The nonfluorescent, membrane impermeant Boc-Leu-Met-MAC-SG accumulates in the cell. Intracellular proteolytic hydrolysis of Boc-Leu-Met-MAC-SG releases and unquenches the fluorescence of MAC-SG. Intracellular fluorescence of MAC-SG was quantitated in single, cultured rat hepatocytes using digitized video fluorescent microscopy. Enhancement of intracellular fluorescence generation by increases in Ca2+i and inhibition by a calpain inhibitor indicated the probe was a calpain substrate. After addition of ATP, calpain protease activity increased to 156 +/- 13% of basal concurrent with a 3-fold rise of Ca2+i for 2-4 min. Thereafter, Ca2+i decreased to values of 1.5-fold above basal and protease activity returned to normal. Incubation of cells in Ca(2+)-free buffer abolished the rise in Ca2+i and calpain protease activity. Calpain protease activity increases concomitantly with increases of Ca2+i supporting the hypothesis that calpain proteases participate in Ca(2+)-mediated signal transduction.
Identification of a Potential Role for the Adventitia in Vascular Lesion Formation After Balloon Overstretch Injury of Porcine Coronary Arteries (1996)

These data suggest that adventitial myofibroblasts contribute to the process of vascular lesion formation by proliferating, synthesizing growth factors, and possibly migrating into the neointima. Increased synthesis of alpha-smooth muscle actin observed in the adventitial cells after arterial injury may constrict the injured vessel and contribute to the process of arterial remodeling and late lumen loss after angioplasty.
A phenomenological model for systematization and prediction of doping limits in II–VI and I–III–VI2 compounds (1998)

Semiconductors differ widely in their ability to be doped. As their band gap increases, it is usually possible to dope them either n or p type, but not both. This asymmetry is documented here, and explained phenomenologically in terms of the “doping pinning rule.”
Gadolinium(III)-based blood-pool contrast agents for magnetic resonance imaging: status and clinical potential (2007)

Blood-pool MRI contrast agents have enormous potential to aid sensitive magnetic resonance detection and yield definitive diagnostic data of cancer and diseases of the cardiovascular system. Many attempts have been initiated to design macromolecular gadolinium (Gd[III]) complexes as magnetic resonance imaging blood-pool contrast agents, as macromolecules do not readily diffuse across healthy vascular endothelium, and remain intravascular. Although extremely efficacious in detecting and characterizing pathologic tissue, clinical development of these agents has been limited by potential toxicity concerns from incomplete Gd(III) clearance. Recent innovative technologies, such as reversible protein-binding contrast agents and biodegradable macromolecular contrast agents, may be valuable alternatives that combine the effective imaging characteristics of an intravascular contrast agent and the safety of clinically approved low-molecular-weight Gd(III) chelates.
Coordination of Copper(II) to Polyaminopolycarboxylic Acids in Aqueous Solution (1992)

Abstract The formation of copper(II) complexes in aqueous solution has been followed by EPR and electronic absorption spectroscopy for a series of polyaminopolycarboxylic ligands, namely ethylenediaminotetra-acetic (EDTA), N-(2-hydroxyethyl)ethylenediamino-N,N′,N′-triacetic (HEDTA), ethylenediaminodiacetic (EDDA), iminodiacetic (IDA), and nitrilotriacetic (NTA) acids. The species in complex formation have been identified and structures proposed by previous studies have been examined and discussed on the basis of the spectroscopic data. Key Words: Coppermultidentates speciationstability constants
<i>Pneumocystis carinii</i>Cytochrome b Mutations Are Associated with Atovaquone Exposure in Patients with AIDS (2001)

This retrospective cohort study was conducted to determine whether Pneumocystis carinii cytochrome b gene mutations in patients with AIDS and P. carinii pneumonia (PCP) are associated with atovaquone exposure. Portions of the P. carinii cytochrome b genes that were obtained from 60 patients with AIDS and PCP from 6 medical centers between 1995 and 1999 were amplified and sequenced by using polymerase chain reaction. Fifteen patients with previous atovaquone prophylaxis or treatment exposure were matched with 45 patients with no atovaquone exposure. Cytochrome b coenzyme Q binding site mutations were observed in 33% of isolates from patients exposed to atovaquone, compared with 6% from those who were not (P=.018). There was no difference in survival 1 month after treatment between patients with or without cytochrome b mutations (P=.14). Thus, cytochrome b mutations are significantly more common in patients with AIDS and PCP with atovaquone exposure, but the clinical significance of these mutations remains unknown.
Novel findings on the metabolic effects of the low glycaemic carbohydrate isomaltulose (Palatinose™) (2010)

The slow digestible disaccharide isomaltulose (iso; Palatinose) is available as novel functional carbohydrate ingredient for manufacturing of low glycaemic foods and beverages. Although basically characterised, various information on physiological effects of iso are still lacking. Thus, the objective of the present study was to expand scientific knowledge of physiological characteristics of iso by a set of three human intervention trials. Using an ileostomy model, iso was found to be essentially absorbed, irrespective of the nature of food (beverage and solid food). Apparent digestibility of 50 g iso from two different meals was 95.5 and 98.8 %; apparent absorption was 93.6 and 96.1 %, respectively. In healthy volunteers, a single dose intake of iso resulted in lower postprandial blood glucose and insulin responses than did sucrose (suc), while showing prolonged blood glucose delivery over 3 h test. In a 4-week trial with hyperlipidaemic individuals, regular consumption of 50 g/d iso within a Western-type diet was well tolerated and did not affect blood lipids. Fasting blood glucose and insulin resistance were lower after the 4-week iso intervention compared with baseline. This would be consistent with possible beneficial metabolic effects as a consequence of the lower and prolonged glycaemic response and lower insulinaemic burden. However, there was no significant difference at 4 weeks after iso compared with suc. In conclusion, the study shows that iso is completely available from the small intestine, irrespective of food matrix, leading to a prolonged delivery of blood glucose. Regular iso consumption is well tolerated also in subjects with increased risk for vascular diseases.
Tigecycline Efflux as a Mechanism for Nonsusceptibility in <i>Acinetobacter baumannii</i> (2007)

Tigecycline has an extended spectrum of in vitro antimicrobial activities, including that against multidrug-resistant Acinetobacter. After identifying bloodstream isolates of Acinetobacter with reduced susceptibilities to tigecycline, we performed a study to assess tigecycline efflux mediated by the resistance-nodulation-division-type transporter AdeABC. After exposure of two tigecycline-nonsusceptible isolates to the efflux pump inhibitor phenyl-arginine-beta-naphthylamide (PABN), a fourfold reduction in the tigecycline MIC was observed. Both tigecycline-susceptible and -nonsusceptible isolates were found to carry the gene coding for the transmembrane component of the AdeABC pump, adeB, and the two-component regulatory system comprising adeS and adeR. Previously unreported point mutations were identified in the regulatory system in tigecycline-nonsusceptible isolates. Real-time PCR identified 40-fold and 54-fold increases in adeB expression in the two tigecycline-nonsusceptible isolates compared to that in a tigecycline-susceptible isolate. In vitro exposure of a tigecycline-susceptible clinical strain to tigecycline caused a rapid rise in the MIC of tigecycline from 2 microg/ml to 24 microg/ml, which was reversible with PABN. A 25-fold increase in adeB expression was observed in a comparison between this tigecycline-susceptible isolate and its isogenic tigecycline-nonsusceptible mutant. These results indicate that an efflux-based mechanism plays a role in reduced tigecycline susceptibility in Acinetobacter.
[Differences in the arrangement and morphometric characteristics of the umbilical blood vessels]. (1999)

On the cross histotopographic sections of 76 cords individual differences in the location of two arteries and veins of cord have been studied. The data are obtained on the changes of morphometric parameters of cord in normal and complicated pregnancy (obesity, neurocirculatory dystonia in hypertension type and miscarriages).
A Chart for Sequentially Testing Observed Arithmetic Means from Lognormal Populations Against a Given Standard (1968)

The aim of this paper is to illustrate how the arithmetic mean can be used for sequentially testing hypotheses about the mean of a lognormal distribution. It is suggested that this can be satisfactorily done as long as the coefficient of variation of the original observations is less than 50%. For coefficients of variation of more than 50% the approximation on which the result is based becomes progressively less realistic.
[Hospitals in Nantes during the revolution]. (1993)

La periode de la Revolution francaise fut difficile pour les hopitaux de Nantes, frappes par la crise economique et l'impact de la desorganisation politique. Cependant, malgre cette situation critique, l'organisation des hopitaux progressa grâce au personnel medical, aux etudiants et aux regles d'hygiene qui permirent de dimimuer la contagion et la mortalite
An atmospheric perspective on North American carbon dioxide exchange: CarbonTracker (2007)

We present an estimate of net CO(2) exchange between the terrestrial biosphere and the atmosphere across North America for every week in the period 2000 through 2005. This estimate is derived from a set of 28,000 CO(2) mole fraction observations in the global atmosphere that are fed into a state-of-the-art data assimilation system for CO(2) called CarbonTracker. By design, the surface fluxes produced in CarbonTracker are consistent with the recent history of CO(2) in the atmosphere and provide constraints on the net carbon flux independent from national inventories derived from accounting efforts. We find the North American terrestrial biosphere to have absorbed -0.65 PgC/yr (1 petagram = 10(15) g; negative signs are used for carbon sinks) averaged over the period studied, partly offsetting the estimated 1.85 PgC/yr release by fossil fuel burning and cement manufacturing. Uncertainty on this estimate is derived from a set of sensitivity experiments and places the sink within a range of -0.4 to -1.0 PgC/yr. The estimated sink is located mainly in the deciduous forests along the East Coast (32%) and the boreal coniferous forests (22%). Terrestrial uptake fell to -0.32 PgC/yr during the large-scale drought of 2002, suggesting sensitivity of the contemporary carbon sinks to climate extremes. CarbonTracker results are in excellent agreement with a wide collection of carbon inventories that form the basis of the first North American State of the Carbon Cycle Report (SOCCR), to be released in 2007. All CarbonTracker results are freely available at http://carbontracker.noaa.gov.
Oxidative Stress‐Induced Depolymerization of Microtubules and Alteration of Mitochondrial Mass in Human Cells (2005)

Mitochondrial biogenesis is a biological process that has been intensively studied over the past few years. However, the detailed molecular mechanism underlying this increase in mitochondria remains unclear. To investigate the mechanism of such a mitochondrial proliferation, we examined alterations in mitochondria of human osteosarcoma 143B cells that had been treated with 100 to 500 microM hydrogen peroxide (H2O2) for 48 h. The results showed that mitochondrial mass of the cell was increased with the increase of the concentration of H2O2. On the other hand, by using real-time PCR techniques, we observed the changes of mitochondrial DNA (mtDNA) content in the cells exposed to oxidative stress. The copy number of mtDNA was increased by treatment with a low dose of H2O2 but was drastically decreased after treatment with H2O2 higher than 300 microM. Transmission electron microscopic images revealed that mitochondria were abnormally proliferated in cells exposed to oxidative stress. Moreover, we found that the percentage of 143B cells arrested at the G2/M phase increased upon treatment with H2O2. Immunostaining and microtubule fractionation assay revealed that microtubules were depolymerized in the cells that had been treated with H2O2. To understand the effect of microtubules depolymerization on the mitochondrial mass, we treated the cells with several kinds of microtubule-active drugs, which arrest cultured cells at the G2/M phase. The results showed that mitochondrial mass and mtDNA copy number all were increased after such treatments. Taking these findings together, we suggest that oxidative stress-induced microtubule derangement is one of the molecular events involved in the increase of mitochondrial mass upon treatment of human cells with H2O2.
Phenotypic Change Caused by Transcriptional Bypass of Uracil in Nondividing Cells (1999)

Cytosine deamination to uracil occurs frequently in cellular DNA. In vitro, RNA polymerase efficiently inserts adenine opposite to uracil, resulting in G to A base substitutions. In vivo, uracil could potentially alter transcriptional fidelity, resulting in production of mutant proteins. This study demonstrates that in nondividing Escherichia coli cells, a DNA template base replaced with uracil in a stop codon in the firefly luciferase gene results in conversion of inactive to active luciferase. The level of transcriptional base substitution is dependent on the capacity to repair uracil. These results provide evidence for a DNA damage-dependent, transcription-driven pathway for generating mutant proteins in nondividing cells.
A Fluorescent, Shape-Persistent Dendritic Host with Photoswitchable Guest Encapsulation and Intramolecular Energy Transfer (2011)

A fluorescent and photoresponsive host based on rigid polyphenylene dendrimers (PPDs) has been synthesized. The key building block for the divergent dendrimer buildup is a complex tetracyclone 12 containing azobenzenyl, pyridyl, and ethynyl entities. The rigidity of polyphenylenes is of crucial importance for a site-specific placement of different functions: eight azobenzene (AB) moieties into the rigid scaffold, a fluorescent perylenetetracarboxdiimide (PDI) into the core, and eight pyridin functions into the interior cavities. AB moieties of host-1 undergo reversible cis-trans photoisomerization and are photostable, as confirmed by various techniques: UV-vis, (1)H NMR, size exclusion chromatography, and fluorescence correlation (FCS). In this system, AB moieties act as photoswitchable hinges and enable control over (i) molecular size, (ii) intramolecular energy transfer between AB and PDI, and (iii) encapsulation and release of guest molecules. The presence of PDI allows not only following the effect of cis-trans photoisomerization on molecular size with highly sensitive FCS but also monitoring the efficiency of the intramolecular energy transfer process (from AB to PDI) by time-resolved optical spectroscopy. Pyridyl functions were incorporated to facilitate guest uptake via hydrogen bonds between the host and guests. Also, we have demonstrated that the photoswitchability of the host can be utilized to actively encapsulate guest molecules into its interior cavities. This novel, light-driven encapsulation mechanism could enable the design of new drug delivery systems.
Digital Camera Detection and Image Disruption Using Controlled Intentional Electromagnetic Interference (2012)

Photography is becoming more and more an end-user capability, with many people having digital cameras on their mobile phones. In general, digital cameras are phasing out traditional film-based equipment. The advantages of digital photography are many: the compactness of the cameras, high reliability, ease of image processing, and transmission of the images via the internet or multimedia messaging. These processes emphasize a big problem which is the ability to photograph an object without the approval of its owner. This unsolved problem has many aspects: the right to privacy, paparazzi, industrial intelligence, and the need to protect objects which have high security sensitivity. This paper describes a method of sensing and then disrupting digital imaging by using a controlled radio frequency transmission. This method can be used in order to create a system that causes a localized malfunction of a digital camera in a specified area so that it will degrade photographic recording done by the digital camera. This method is composed of two stages: coupling the digital camera to a source of intentional electromagnetic interference and generating electromagnetic waves in a specific frequency to interfere with the correct functioning of at least one electronic component of the digital camera.
Distribution, diversity, evolution, and survival of <i>Helitrons</i> in the maize genome (2009)

Homology and structure-based approaches were used to identify Helitrons in the genome of maize inbred B73. A total of 1,930 intact Helitrons from eight families (62 subfamilies) and >20,000 Helitron fragments were identified, accounting for approximately 2.2% of the B73 genome. Transposition of at least one of these families is ongoing, but the most prominent burst of amplification activity was approximately 250,000 years ago. Sixty percent of maize Helitrons were found to have captured fragments of nuclear genes ( approximately 840 different fragment acquisitions, with tens of thousands of predicted gene fragments inside Helitrons within the B73 assembly). Most acquired gene fragments are undergoing random drift, but 4% were calculated to be under purifying selection, whereas another 4% exhibit apparent adaptive selection, suggesting beneficial effects for the host or Helitron transposition/retention. Gene fragment capture is frequent in some Helitron subfamilies, with as many as 10 unlinked genes providing DNA inserts within a single element. Gene fragment acquisition appears to positively influence element survival and/or ability of the Helitron to acquire additional gene fragments. Helitrons with gene fragment captures in the antisense orientation have a lesser chance of survival. Helitron distribution in maize exhibits severe biases, including preferential accumulation in relatively gene-rich regions. Insertions, however, are not usually found inside genes. Rather, Helitrons preferentially insert near (but not into) other Helitrons. This biased accumulation is not caused by a preference for cis or nearby transposition, suggesting a specific association between Helitron integration functions and unknown chromatin characteristics that specifically mark Helitrons.
Determinants of 4α-Phorbol Sensitivity in Transmembrane Domains 3 and 4 of the Cation Channel TRPV4 (2007)

TRPV4, a Ca(2+)-permeable member of the vanilloid subgroup of the transient receptor potential (TRP) channels, is activated by cell swelling and moderate heat (>27 degrees C) as well as by diverse chemical compounds including synthetic 4 alpha-phorbol esters, the plant extract bisandrographolide A, and endogenous epoxyeicosatrienoic acids (EETs; 5,6-EET and 8,9-EET). Previous work identified a tyrosine residue located in the first half of putative transmembrane segment 3 (TM3) as a crucial determinant for the activation of TRPV4 by its most specific agonist 4 alpha-phorbol 12,13-didecanoate (4 alpha-PDD), suggesting that 4 alpha-PDD interacts with the channel through its transmembrane segments. To obtain insight in the 4 alpha-PDD-binding site and in the mechanism of ligand-dependent TRPV4 activation, we investigated the consequences of specific point mutations in TM4 on the sensitivity of the channel to different chemical and physical stimuli. Mutations of two hydrophobic residues in the central part of TM4 (Leu(584) and Trp(586)) caused a severe reduction of the sensitivity of the channel to 4 alpha-PDD, bisandrographolide A, and heat, whereas responses to cell swelling, arachidonic acid, and 5,6-EET remained unaffected. In contrast, mutations of two residues in the C-terminal part of TM4 (Tyr(591) and Arg(594)) affected channel activation of TRPV4 by all stimuli, suggesting an involvement in channel gating rather than in interaction with agonists. Based on a comparison of the responses of WT and mutant TRPV4 to 4 alpha-PDD and different 4 alpha-phorbol esters, we conclude that the length of the fatty acid moiety determines the ligand binding affinity and propose a model for the interaction between 4 alpha-phorbol esters and the TM3/4 region of TRPV4.
Ambiguity and Innovation: Implications for the Genesis of the Culture Broker<sup>1</sup> (1969)

Essential to the function of an innovator—particularly a group‐straddling one such as a “marginal man” or “culture broker”—is the manner in which others view him and the genesis of his mandate to innovate. An account of the genesis of a culture broker in a Yucatan peasant community suggests that ambiguity during the development of the innovator role may allow novel behavior while retarding negative sanction. The case described may help us understand the manner in which culture‐straddling brokers arise and receive permission to innovate.