gebhart/patrepeval huggingface dataset:
Columnar Specificity of Microvascular Oxygenation and Volume Responses: Implications for Functional Brain Mapping (2004)

Cortical neurons with similar properties are grouped in columnar structures and supplied by matching vascular networks. The hemodynamic response to neuronal activation, however, is not well described on a fine spatial scale. We investigated the spatiotemporal characteristics of microvascular responses to neuronal activation in rat barrel cortex using optical intrinsic signal imaging and spectroscopy. Imaging was performed at 570 nm to provide functional maps of cerebral blood volume (CBV) changes and at 610 nm to estimate oxygenation changes. To emphasize parenchymal rather than large vessel contributions to the functional hemodynamic responses, we developed an ANOVA-based statistical analysis technique. Perfusion-based maps were compared with underlying neuroanatomy with cytochrome oxidase staining. Statistically determined CBV responses localized accurately to individually stimulated barrel columns and could resolve neighboring columns with a resolution better than 400 microm. Both CBV and early oxygenation responses extended beyond anatomical boundaries of single columns, but this vascular point spread did not preclude spatial specificity. These results indicate that microvascular flow control structures providing targeted flow increases to metabolically active neuronal columns also produce finely localized changes in CBV. This spatial specificity, along with the high contrast/noise ratio, makes the CBV response an attractive mapping signal. We also found that functional oxygenation changes can achieve submillimeter specificity not only during the transient deoxygenation ("initial dip") but also during the early part of the hyperoxygenation. We, therefore, suggest that to optimize hemodynamic spatial specificity, appropriate response timing (using < or =2-3 sec changes) is more important than etiology (oxygenation or volume).
Octamer and Sox Elements Are Required for Transcriptional cis Regulation of Nanog Gene Expression (2005)

The pluripotential cell-specific gene Nanog encodes a homeodomain-bearing transcription factor required for maintaining the undifferentiated state of stem cells. However, the molecular mechanisms that regulate Nanog gene expression are largely unknown. To address this important issue, we used luciferase assays to monitor the relative activities of deletion fragments from the 5'-flanking region of the gene. An adjacent pair of highly conserved Octamer- and Sox-binding sites was found to be essential for activating pluripotential state-specific gene expression. Furthermore, the 5'-end fragment encompassing the Octamer/Sox element was sufficient for inducing the proper expression of a green fluorescent protein reporter gene even in human embryonic stem (ES) cells. The potential of OCT4 and SOX2 to bind to this element was verified by electrophoretic mobility shift assays with extracts from F9 embryonal carcinoma cells and embryonic germ cells derived from embryonic day 12.5 embryos. However, in ES cell extracts, a complex of OCT4 with an undefined factor preferentially bound to the Octamer/Sox element. Thus, Nanog transcription may be regulated through an interaction between Oct4 and Sox2 or a novel pluripotential cell-specific Sox element-binding factor which is prominent in ES cells.
Sympathetic reactivity during a yohimbine challenge test in essential hypertension. (1991)

Systemic administration of yohimbine augments sympathetic outflow and blocks presynaptic alpha 2-adrenergic receptors, releasing the sympathetic neurotransmitter norepinephrine (NE) into the bloodstream. The present study examined sympathoadrenal and hemodynamic responses to yohimbine in 19 patients with essential hypertension and 19 normotensive control subjects. Baseline mean values for arterial NE, epinephrine, dihydroxyphenylglycol (the main intraneuronal metabolite of NE), spillover of NE into arterial plasma, and corticotropin did not differ between the hypertensive and normotensive groups. Yohimbine (0.125 mg/kg i.v. bolus followed by 0.001 mg/kg/min infusion for a total of 15 minutes) increased mean arterial pressure in all but one subject (by 13 +/- 2% [SEM] in the normotensive and 17 +/- 2% in the hypertensive group) and increased arterial NE levels in all subjects (by 253 +/- 50 pg/ml in the normotensive and 312 +/- 51 pg/ml in the hypertensive group). Among hypertensive patients, pressor, cardiac, output, and arterial NE responses were distributed bimodally. Patients with large hemodynamic and NE responses to yohimbine typically reported a history of anxiety, depression, or other psychopathology and of marked pressor or tachycardic episodes during emotional stress. In the hypertensive and normotensive groups, baseline arterial NE concentrations predicted the magnitude of pressor responses to yohimbine (r = 0.59, r = 0.54,p less than 0.01), whereas baseline mean arterial pressure was unrelated to the pressor response. A yohimbine challenge test can identify patients with pressor hyperresponsiveness and can distinguish patients with pressor hyperresponsiveness due to excessive sympathoadrenal reactivity from patients with enhanced postsynaptic responsiveness to endogenous NE.
Colonization outwith the colon: plants as an alternative environmental reservoir for human pathogenic enterobacteria (2008)

Members of the Enterobacteriaceae have the capacity to adapt to a wide variety of environments and can be isolated from a range of host species across biological kingdoms. Bacteria that are pathogenic to animals, in particular humans, are increasingly found to be transmitted through the food chain by fruits and vegetables. Rather than simply contaminating plant surfaces, there is a growing body of evidence to show that these bacteria actively interact with plants and can colonize them as alternative hosts. This review draws together evidence from studies that investigate proven and potential mechanisms involved in colonization of plants by human pathogenic enterobacteria.
Epipolythiodiketopiperazine Alkaloids: Total Syntheses and Biological Activities (2011)

Abstract Epipolythiodiketopiperazine (ETP) alkaloids are structurally characterized by the presence of diketopiperazine rings having sensitive (poly)sulfide bridges, and most of them are classified as fungal secondary metabolites. Various biological activities have been reported for members of this family, including cytotoxic, antibacterial, antimicrobial, antiviral, antitumor, antiallergic, and antimalarial activities. Notably, some of the molecules were reported to show specific inhibitory activities against certain critical enzymes. Since the supply of these compounds from natural sources is quite limited, efficient chemical syntheses of ETP alkaloids would be useful for biological studies. However, total syntheses of ETP alkaloids remain a formidable challenge in current synthetic organic chemistry because of their structural complexity. In this review article, we present an overview of synthetic approaches to the ETP alkaloids during the past 50 years, and discuss significant milestones. We also summarize the biological activities of these compounds, focusing on the molecular mechanisms.
Epoxidation of bacterial polyesters with unsaturated side chains. II. Rate of epoxidation and polymer properties (1998)

Poly(3-hydroxyoctanoate-co-3-hydroxy-10-undecenoate)s (PHOUs) with controlled amounts of unsaturated repeating units were epoxidized to various extents with m-chloroperbenzoic acid (MCPBA) in homogeneous solution. The epoxidation reaction was second order, with an initial rate constant of 1.1 × 10−3Lmol−1.s−1 at 20°C, regardless of the unsaturated unit content in PHOU. No substantial change in either molecular weight or molecular weight distribution occurred as a result of epoxidation, but the melt transition temperature and enthalpy of melting both decreased as the unsaturated groups were increasingly converted into epoxide groups. In contrast, the glass transition temperature (Tg) increased by approximately 0.25°C for each 1 mol % of epoxidation, irrespective of the composition of the PHOU. © 1998 John Wiley & Sons, Inc. J. Polym. Sci. A Polym. Chem. 36: 2381–2387, 1998
Local thrombolytic therapy: bridging the "generation gap" (1983)

Local thrombolytic therapy: bridging the "generation gap"GJ BeckerAudio Available | Share
A new approach to sequence comparison: normalized sequence alignment (2001)

The Smith-Waterman algorithm for local sequence alignment is one of the most important techniques in computational molecular biology. This ingenious dynamic programming approach was designed to reveal the highly conserved fragments by discarding poorly conserved initial and terminal segments. However, the existing notion of local similarity has a serious flaw: it does not discard poorly conserved intermediate segments. The Smith-Waterman algorithm finds the local alignment with maximal score but it is unable to find local alignment with maximum degree of similarity (e.g. maximal percent of matches). Moreover, there is still no efficient algorithm that answers the following natural question: do two sequences share a (sufficiently long) fragment with more than 70% of similarity? As a result, the local alignment sometimes produces a mosaic of well-conserved fragments artificially connected by poorly-conserved or even unrelated fragments. This may lead to problems in comparison of long genomic sequences and comparative gene prediction as recently pointed out by Zhang et al. (Bioinformatics, 15, 1012-1019, 1999). In this paper we propose a new sequence comparison algorithm (normalized local alignment ) that reports the regions with maximum degree of similarity. The algorithm is based on fractional programming and its running time is O(n2log n). In practice, normalized local alignment is only 3-5 times slower than the standard Smith-Waterman algorithm.
MediaView (1991)

MediaView is a multimedia digital publication system that was designed to be flexible and free from restrictions. It was also designed to take maximum advantage of the media-rich hardware and software capabilities of the NeXT [5] computer, especially the features of the NeXTdimension [17] subsystem. Rather than emphasize the work that is almost always paired with multimedia, presentation, MediaView emphasizes communication. The system does not tacitly impose the “publisher's” agenda on the reader, but structure and sequencing can be overlaid if appropriate. The result is a very general system—free of artificial structure and inconvenient metaphors.
Electropolymerization of o‐phenylenediamine on Pt‐electrode from aqueous acidic solution: Kinetic, mechanism, electrochemical studies and characterization of the polymer obtained (2009)

Abstract Electropolymerization of O ‐phenylenediamine ( o‐ PD) on Pt‐electrode from a deoxygenated aqueous acid medium was carried out using cyclic voltammetry technique. The kinetic parameters were calculated by means of electrochemical data. The experimentally obtained kinetic equation was R P , E = k E [monomer] 1.19 [acid] 1.23 [electrolyte] 0.87 from the value of the anodic current density using cyclic voltammetry technique. The apparent activation energy ( E a ) is found to be 28.34 kJ mol −1 . The polymer films obtained have been characterized by X‐ray diffraction, elemental analysis, scanning electron microscopy, 1 H‐NMR, 13 C‐NMR, UV‐visible, and IR spectroscopy. The mechanism of the electrochemical polymerization reaction has been discussed. TGA is used to confirm the proposed structure and determination of the number of water molecules in the polymeric chain unit. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Direct Synthesis of Well-Defined Alcohol-Functionalized Polymers via Acyclic Diene Metathesis (ADMET) Polymerization (1998)

Because of its robust nature, Grubbs' ruthenium benzylidene catalyst RuCl2(CHPh)(PCy3)2 promotes the successful acyclic diene metathesis (ADMET) bulk polymerization of alcohol-functionalized dienes, thus providing a method for the direct synthesis of linear polymers containing hydroxy groups. Primary, secondary, and tertiary alcohol functional groups can be placed at precise intervals along an unsaturated hydrocarbon backbone. Exhaustive hydrogenation of the secondary alcohol homologue produces a well-defined ethylene−vinyl alcohol copolymer. Only the unsaturated and saturated secondary alcohol polymers crystallize, a phenomenon likely attributed to the enhanced packing propensity of these macromolecules in comparison with those of their primary and tertiary analogues.
Association of Preoperative Plasma Levels of Insulin-Like Growth Factor I and Insulin-Like Growth Factor Binding Proteins-2 and -3 With Prostate Cancer Invasion, Progression, and Metastasis (2002)

PURPOSE: We tested the hypothesis that preoperative plasma levels of insulin-like growth factor (IGF) binding protein (BP)-2 or IGFBP-3 would predict cancer stage and prognosis in patients undergoing radical prostatectomy. MATERIAL AND METHODS: Plasma levels of IGF-I, IGFBP-2, and IGFBP-3 were measured preoperatively in 120 consecutive patients who underwent radical prostatectomy for clinically localized disease, postoperatively in 51 of these patients, in 44 healthy men, in 19 patients with metastases to regional lymph nodes, and in 10 patients with bone metastases. RESULTS: Plasma IGFBP-3 levels were lowest in patients with bone metastases (P ≤ .043). IGFBP-2 levels were elevated in prostate cancer patients compared with healthy subjects (P ≤ .006). However, within the group of prostatectomy patients, preoperative plasma IGFBP-2 levels were lower in patients with advanced disease (P ≤ .033), were inversely correlated with prostatic tumor volume (P = .037), and declined after prostate removal (P = .044). Lower preoperative IGFBP-2 and IGFBP-3 levels and biopsy Gleason score were independent predictors of biochemical progression (P = .043, P = .040, and P = .020, respectively). In patients with disease progression, preoperative plasma IGFBP-3 levels were lower in those with aggressive than in those with nonaggressive failure (P = .042). CONCLUSION: Elevation of plasma IGFBP-2 levels in prostate cancer patients apparently is due to increased release directly from the prostate. For patients with clinically localized prostate cancer, preoperative plasma IGFBP-2 levels are inversely associated with biologically aggressive disease and disease progression. Preoperative plasma IGFBP-3 levels were decreased in patients with prostate cancer metastases and were an independent predictor of biochemical progression after surgery, presumably because of an association with occult metastatic disease present at the time of radical prostatectomy.
32-Channel Full Customized CMOS Biosensor Chip for Extracellular Neural Signal Recording (2005)

In this paper we present a full-customized CMOS biosensor integrated circuit (IC) design, layout, and implementation techniques for extracellular multichannel action potential recording applications. Schematics and simulation data for each of the sub-circuit macros are presented which includes contact sensors, unity gain buffer, variable gain amplifier and logic control unit. The chip provides a satisfactory signal-to-noise ratio for neural signals with amplitudes in the range of 50-500 muV and frequency spectrum in the range of 20-2000 Hz. The prototype IC was fabricated by MOSIS using AMI'S 1.5 mum, double poly, double level metal CMOS technology
Testosterone Deficiency Accelerates Neuronal and Vascular Aging of SAMP8 Mice: Protective Role of eNOS and SIRT1 (2012)

Oxidative stress and atherosclerosis-related vascular disorders are risk factors for cognitive decline with aging. In a small clinical study in men, testosterone improved cognitive function; however, it is unknown how testosterone ameliorates the pathogenesis of cognitive decline with aging. Here, we investigated whether the cognitive decline in senescence-accelerated mouse prone 8 (SAMP8), which exhibits cognitive impairment and hypogonadism, could be reversed by testosterone, and the mechanism by which testosterone inhibits cognitive decline. We found that treatment with testosterone ameliorated cognitive function and inhibited senescence of hippocampal vascular endothelial cells of SAMP8. Notably, SAMP8 showed enhancement of oxidative stress in the hippocampus. We observed that an NAD(+)-dependent deacetylase, SIRT1, played an important role in the protective effect of testosterone against oxidative stress-induced endothelial senescence. Testosterone increased eNOS activity and subsequently induced SIRT1 expression. SIRT1 inhibited endothelial senescence via up-regulation of eNOS. Finally, we showed, using co-culture system, that senescent endothelial cells promoted neuronal senescence through humoral factors. Our results suggest a critical role of testosterone and SIRT1 in the prevention of vascular and neuronal aging.
Glucose Availability Regulates IFN-γ Production and p70S6 Kinase Activation in CD8+ Effector T Cells (2005)

Differentiation of CD8+ T cells from the naive to the effector state is accompanied by changes in basal gene expression profiles that parallel the acquisition of effector functions. Among these are metabolism genes, and we now show that 2C TCR transgenic effector CD8+ T cells express higher levels of glycolytic enzymes and display greater glucose uptake, a higher glycolytic rate, and increased lactate production compared with naive cells. To determine whether glucose was required for effector T cell functions, we regulated glucose availability in vitro. Glucose deprivation strongly inhibited IFN-gamma gene expression, whereas IL-2 production was little affected. Inhibition correlated with diminished phosphorylation of p70S6 kinase and eIF4E binding protein 1 and a requirement for de novo protein synthesis, whereas other signaling pathways known to regulate IFN-gamma expression were unaffected. Together, our data reveal that optimal induction of IFN-gamma transcription is a glucose-dependent process, indicate that there are undefined factors that influence IFN-gamma expression, and have implications for regulation of the effector phase of CD8+ T cell responses in tissue microenvironments.
The Use of Microwave Heating To Promote Organic Reactions (1995)

This study documents the usefulness of microwave heating for the preparation of a wide variety of organic compounds using a commercial microwave system equipped with a built-in pressure unit and an external temperature monitoring device. The results of control experiments conducted under conventional heating conditions are also provided for each reaction. Most of the reactions studied showed drastically reduced reaction times compared with conventional heating, due to the higher temperatures attained. These results show that microwave heating is useful for preparative organic chemistry.
Detection of surgical pathogens by in vitro DNA amplification. Part I. Rapid identification of Candida albicans by in vitro amplification of a fungus-specific gene. (1990)

The management of candidemia and disseminated candidiasis depends on rapid, unambiguous identification of Candida. Such identification is retarded by the slow growth of Candida from clinical specimens. Administration of effective but potentially toxic antifungal therapy is often withheld pending identification. To circumvent this slow growth and thus to expedite diagnosis and therapy, the polymerase chain reaction (PCR) was used to amplify a segment of fungal DNA coding for the cytochrome P450L1A1 (lanosterol-14 alpha-demethylase) in vitro. The technique provides unambiguous evidence of C. albicans in as few as 6 hours with a detection threshold of 10 organisms in a 100 mu specimen. Clinical specimens of urine (n = 4), sputum (n = 6), wound fluid (n = 1, and blood (n = 2) were collected from patients, and C. albicans was conventionally documented at these sites; in each case, PCR was confirmed. Of 17 additional specimens that were culture negative, PCR suggested the presence of yeast in two of the specimens. PCR-based detection of surgical pathogens may have broad application in rapid screening for the presence of organisms either indigenous to a particular surgical intensive care unit or peculiar to selected patient populations.
The Enteric Nervous System III: A Target for Pharmacological Treatment (2003)

Abstract: The past decade has seen major advances in the pharmacological understanding of the nervous system of the gastrointestinal tract, the enteric nervous system, and its importance for gut functions in several states of disease. Indeed, the enteric nervous system has become a promising target in the treatment of many gastrointestinal symptoms and disorders. Some of these new therapeutic concepts, such as botulinum toxin for achalasia and serotonergic drugs for functional bowel diseases, are already in clinical use. This paper is part 3 of three Minireviews in Pharmacology &amp; Toxicology , and presents the neurogastrointestinal pharmacological therapeutic options in gastrointestinal pain, functional gastrointestinal disorders, inflammatory bowel diseases, cancer and related conditions with focus on future drug targets. The diagnosis of gastrointestinal neuropathy, the role of serotonin and related neuroendocrine transmitters, serotonergic drugs, and neurotrophic factors in neurogastrointestinal pharmacology will be addressed in this context.
Regulation of intracellular protein degradation in IMR‐90 human diploid fibroblasts (1983)

Human diploid fibroblasts (IMR-90) regulate their overall rates of proteolysis in response to the composition of the culture medium and the ambient temperature. The magnitude and, in some cases, the direction of the response depend on the half-lives of the cellular proteins that are radioactively labeled and the time chosen for measurements of protein degradation. Fetal calf serum, insulin, fibroblast growth factor, epidermal growth factor, and amino acids selectively regulate catabolism of long-lived proteins without affecting degradation of short-lived proteins. Fetal calf serum reduces degradative rates of long-lived proteins and is maximally effective at a concentration of 20%, but the effect of serum on proteolysis is evident only for the first 24 hr. Insulin inhibits degradation of long-lived proteins in the presence or absence of glucose and amino acids in the medium, but is maximally effective only at high concentrations (10(-5) M). Amino acid deprivation increases degradative rates of long-lived proteins for the first 6 hr, but then decreases their catabolism for the subsequent 20 hr. Lowered temperature is the only condition tested that significantly alters degradative rates of short-lived proteins. Although cells incubated at 27 degrees C have reduced rates of degradation for both short-lived and long-lived proteins compared to cells at 37 degrees C, lowered temperature reduces catabolism of long-lived proteins to a greater extent.
The Human Body (1983)

US News Books is providing an excellent science resource library for the general reading public (including persons trained in the medical arts and teachers and students of the psychological and biologic sciences) through the publication of its series<i>The Human Body</i>. This service has already been acknowledged by the American Heart Association, which only recently awarded its Blakeslee Prize for "outstanding achievement in the area of educating the public on the heart, its functions and dysfunctions," to the publisher for its book<i>The Heart</i>. Other volumes currently available are<i>The Skeleton, Blood, Reproduction, The Eye, The Brain, Muscles</i>, and<i>Skin</i>. The books are published approximately every three to four months. Some 20 are anticipated in the complete set, and future titles will include<i>The Cell, Digestive System, Genetics and Heredity</i>, and<i>Wonders of the Ear</i>. A historical survey, covering the particular subject at hand, begins each approximately 165-page text. This