gebhart/patrepeval huggingface dataset:
Novel channel materials for ballistic nanoscale MOSFETs-bandstructure effects (2006)

Performance limits of unstrained n- and p- MOSFETs with Si, Ge, GaAs and InAs channel materials are investigated using a 20 band sp <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> d <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">5</sup> s*-SO semi-empirical atomistic tight-binding model and a top-of-the-barrier seminumerical ballistic transport model. It is observed that although the deeply scaled III-V devices offer very high electron injection velocities, their very low conduction band density-of-states strongly degrades their performance. Due to the high density-of-states for both electrons and holes in Ge, nanoscale devices with Ge as channel material are found to outperform all other materials considered
Disease Course of Patients with X-linked Retinitis Pigmentosa due toRPGRGene Mutations (2007)

Patients with X-linked retinitis pigmentosa due to RPGR mutations lose visual acuity and visual field more rapidly than do patients with dominant retinitis pigmentosa due to RHO mutations.
Hydrolysis of GTP on rab11 is required for the direct delivery of transferrin from the pericentriolar recycling compartment to the cell surface but not from sorting endosomes (1998)

Rab11 is a small GTP-binding protein that in cultured mammalian cells has been shown to be concentrated in the pericentriolar endosomal recycling compartment and to play a key role in passage of the recycling transferrin receptor through that compartment [Ullrich, O., Reinsch, S., Urbé, S., Zerial, M. & Parton, R. G. (1996) J. Cell Biol. 135, 913-924]. To obtain insights into the site(s) of action of rab11 within the recycling pathway, we have now compared the effects on recycling at 37 degreesC of overexpression of wild-type rab11 and various mutant forms of this protein in cells that had been loaded with transferrin at either 37 degreesC or 16 degreesC. We show that incubation at 16 degreesC blocks passage of endocytosed transferrin into the recycling compartment and that, whereas the rab11 dominant negative mutant form (S25N) inhibits transferrin recycling after interiorization at either temperature, the wild-type rab11 and constitutively active mutant (Q70L) have no inhibitory effect on the recycling of molecules that were interiorized at 16 degreesC. This differential inhibitory effect shows that two distinct pathways for recycling are followed by the bulk of the transferrin molecules interiorized at the two different temperatures. The incapacity of the constitutively active form of rab11 (Q70L) to inhibit recycling of molecules interiorized at 16 degreesC is consistent with their recycling taking place directly from sorting endosomes, in a process that does not require hydrolysis of GTP on rab11. The fact that the dominant negative (S25N) form of rab11 inhibits recycling of molecules interiorized at both temperatures indicates that activation of rab11 by GTP is required for exit of transferrin from sorting endosomes, regardless of whether this exit is toward the recycling compartment or directly to the plasma membrane.
Multiple Signaling Pathways Converge on β-Catenin in Thyroid Cancer (2005)

The beta-catenin pathway has been conclusively demonstrated to regulate differentiation and patterning in multiple model systems. In thyroid cancer, alterations are often seen in proteins that regulate beta-catenin, including those of the RAS, PI3K/AKT, and peroxisome proliferation activated receptor-gamma (PPARgamma) pathways, and evidence from the literature suggests that beta-catenin may play a direct role in the dedifferentiation commonly observed in late-stage disease. RET/PTC rearrangements are frequent in thyroid cancer and appear to be exclusive from mutational events in RAS and BRAF. Activation of AKT by phosphatidylinositide-3 kinase (PI3K), a RAS effector, results in GSK3beta phosphorylation and deactivation and subsequent beta-catenin upregulation in thyroid cancer. Activating mutations in beta-catenin, which have been demonstrated in late-stage thyroid tumors, correlate with beta-catenin nuclear localization and poor prognosis. We hypothesize that activation of the RAS, PI3K/AKT, and PPARgamma pathways ultimately impinges upon beta-catenin. We further propose that if mutations in BRAF, RAS, and RET/PTC rearrangements are mutually exclusive in certain thyroid tumors or tumor types, as has already been shown for papillary thyroid cancer, then these interconnected pathways may cooperate in the initiation and promotion of the disease. We believe that clinical benefit for thyroid cancer patients could be derived from disrupting the middle or distal pathway effectors of these pathways, such as AKT or beta-catenin.
Sphingosine Kinase Mediates Vascular Endothelial Growth Factor-Induced Activation of Ras and Mitogen-Activated Protein Kinases (2002)

Vascular endothelial growth factor (VEGF) signaling is critical to the processes of angiogenesis and tumor growth. Here, evidence is presented for VEGF stimulation of sphingosine kinase (SPK) that affects not only endothelial cell signaling but also tumor cells expressing VEGF receptors. VEGF or phorbol 12-myristate 13-acetate treatment of the T24 bladder tumor cell line resulted in a time- and dose-dependent stimulation of SPK activity. In T24 cells, VEGF treatment reduced cellular sphingosine levels while raising that of sphingosine-1-phosphate. VEGF stimulation of T24 cells caused a slow and sustained accumulation of Ras-GTP and phosphorylated extracellular signal-regulated kinase (phospho-ERK) compared with that after EGF treatment. Small interfering RNA (siRNA) that targets SPK1, but not SPK2, blocks VEGF-induced accumulation of Ras-GTP and phospho-ERK in T24 cells. In contrast to EGF stimulation, VEGF stimulation of ERK1/2 phosphorylation was unaffected by dominant-negative Ras-N17. Raf kinase inhibition blocked both VEGF- and EGF-stimulated accumulation of phospho-ERK1/2. Inhibition of SPK by pharmacological inhibitors, a dominant-negative SPK mutant, or siRNA that targets SPK blocked VEGF, but not EGF, induction of phospho-ERK1/2. We conclude that VEGF induces DNA synthesis in a pathway which sequentially involves protein kinase C (PKC), SPK, Ras, Raf, and ERK1/2. These data highlight a novel mechanism by which SPK mediates signaling from PKC to Ras in a manner independent of Ras-guanine nucleotide exchange factor.
Identification of lipoxygenase‐linoleate decomposition products by direct gas chromatography‐mass spectrometry (1980)

Lipoxygenase, prepared from Virginia-type peanuts, was used to catalyze the oxidation of linoleic acid and methyl linoleate to form the C-9 and C-13 hydroperoxides. These reactions were monitored by rapid unconventional direct gas chromatography-mass spectroscopy. An aliquot of the enzymatic reaction mixture, without prior extraction or chemical modification, was secured directly into the heated (40-70 C) or nonheated (room temperature) injection system. When the reaction mixture was analyzed at room temperature, only hexanal was found. At elevated temperatures, five major and several minor components were identified. The predominant compounds identified were pentane, hexanal, 2-pentylfuran, trans-2,cis-4-decadienal, and trans-2,trans-4-decadienal. These products originate from decomposition of either the C-9 or C-13 hydroperoxides generated by peanut lipoxygenase.
Acute and chronic blood pressure response to recurrent acoustic arousal in rats (1999)

Repetitive episodic hypoxia every 30 sec administered chronically to Sprague-Dawley (SD) rats has been shown by previous studies to cause a sustained increase in daytime blood pressure (BP). Acoustic arousal in humans during wake or sleep produces an acute BP rise. The question then arises as to whether chronic episodic acoustic arousal applied with the same frequency and duration as episodic hypoxia induces elevated BP. We exposed 14-week-old (N = 10) SD rats in individual cages to recurrent buzzer noise (500 Hz, 100 dB) 6 out of every 30 sec, 7 h/day for 35 days. Ten other rats were placed in similar cages daily but not exposed to noise, to provide a sham condition. An infrared beam with a detector was positioned at the end of each cage. This allowed us to quantify motion by registering the number of times the rat broke the beam per 7 h period. Mean intraarterial BP was measured in unrestrained conscious animals at baseline and at the end of 35 days of their respective conditions. Acute episodic acoustic stimulation caused an immediate response in BP and heart rate. Habituation occurred in that the movement response to 120 noises per hour was 75% in hour one and 20% in hours two through seven on day one. The movement response was further reduced by day 35 but remained significantly higher than in animals not stimulated by noise. The cardiovascular response to noise also showed signs of habituation. Chronic noise stimulation produced no sustained increases in BP after 35 days of exposure.
The role of the autonomic nervous system in hypertension: a bond graph model study (2008)

A bond graph model of the cardiovascular system with embedded autonomic nervous regulation was developed for a better understanding of the role of the autonomic nervous system (ANS) in hypertension. The model is described by a pump model of the heart and a detailed representation of the head and neck, pulmonary, coronary, abdomen and extremity circulation. It responds to sympathetic and parasympathetic activities by modifying systemic peripheral vascular resistance, heart rate, ventricular end-systolic elastance and venous unstressed volumes. The impairment of ANS is represented by an elevation of the baroreflex set point. The simulation results show that, compared with normotensive, in hypertension the systolic and diastolic blood pressure (SBP/DBP) rose from 112/77 mmHg to 144/94 mmHg and the left ventricular wall thickness (LVWT) increased from 10 mm to 12.74 mm. In the case that ANS regulation was absent, both the SBP and DBP further increased by 8 mmHg and the LVWT increased to 13.22 mm. The results also demonstrate that when ANS regulation is not severely damaged, e.g. the baroreflex set point is 97 mmHg, it still has an effect in preventing the rapid rise of blood pressure in hypertension; however, with the worsening of ANS regulation, its protective role weakens. The results agree with human physiological and pathological features in hemodynamic parameters and carotid baroreflex function curves, and indicate the role of ANS in blood pressure regulation and heart protection. In conclusion, the present model may provide a valid approach to study the pathophysiological conditions of the cardiovascular system and the mechanism of ANS regulation.
Thermodynamics and kinetics of single residue replacements in avian ovomucoid third domains: effect on inhibitor interactions with serine proteinases (1982)

Sequence determinations in our laboratory have yielded the primary structures of ovomucoid third domains from 35 avian species. From that list, 12 sequences could be arranged into a contiguous set such that each sequence differs from a second by a single amino acid replacement. For this set of domains and for five additional domains of special interest, we report here the association equilibrium constants for their binding with bovine alpha-chymotrypsin, elastase I, and subtilisin Carlsberg. The results are interpreted with the aid of the three-dimensional structure of highly homologous Japanese quail ovomucoid third domain and of computer-generated models of the complexes of the inhibitor with the respective enzymes. The results show that (i) changes in inhibitor residues other than the primary recognition residue (P1) even sequentially far from the reactive site, may exert large effects on association equilibrium constant values provided these residues make contact with the enzyme, (ii) changes in residues other than P1 often exert large differential effects toward the different enzymes, i.e., the same change can make the inhibitor stronger for one enzyme and weaker for another, (iii) the sign and to some extent the magnitude of the changes can be rationalized from the known structures of the inhibitor and the enzyme, (iv) changes in surface residues which do not contact the enzyme in complex are virtually without effect, and (v) glycosylated and nonglycosylated inhibitors have the same constants. For confirmation of the validity of the equilibrium constant comparisons in a few cases, the rate constants kon and kd were determined and the resultant calculated equilibrium constant values compared to the directly determined numbers. An additional test of validity is provided by experiments where a glycosylated domain of one species is allowed to compete with an unglycosylated domain of another for the same enzyme.
Controlled lysis of bacterial cells utilizing mutants with defective synthesis of D-alanine (1988)

An alanine racemase (EC 5.1.1.1) mutant (Dal-) of Bacillus subtilis required small amounts of D-alanine to synthesize an osmotically stable cell wall in certain growth media. Investigation of the conditions which caused lysis in hypotonic media revealed that in addition to complex media, such as nutrient broth and acid-hydrolyzed casein, glycine inhibited stable cell wall formation. D-Alanine prevented the glycine inhibition. Up to 99% lysis occurred in both dilute and dense cell suspensions (optical densities up to 110) within 2.5 h after adding 1% glycine to late log phase cultures. Intracellular enzymes recovered from the lysate were as active as those from lysozyme-disrupted cells. No amino acid tested other than glycine induced lysis. Dal- mutants can be used for controlled lysis of bacterial cells to facilitate the isolation of normal intracellular constituents and bioengineered products from fermentation processes. Cell walls of most bacteria contain D-alanine; thus, this strategy should be applicable to a wide variety of microorganisms.
Directed selection of a conformational antibody domain that prevents mature amyloid fibril formation by stabilizing Aβ protofibrils (2007)

The formation of amyloid fibrils is a common biochemical characteristic that occurs in Alzheimer's disease and several other amyloidoses. The unifying structural feature of amyloid fibrils is their specific type of beta-sheet conformation that differentiates these fibrils from the products of normal protein folding reactions. Here we describe the generation of an antibody domain, termed B10, that recognizes an amyloid-specific and conformationally defined epitope. This antibody domain was selected by phage-display from a recombinant library of camelid antibody domains. Surface plasmon resonance, immunoblots, and immunohistochemistry show that this antibody domain distinguishes Abeta amyloid fibrils from disaggregated Abeta peptide as well as from specific Abeta oligomers. The antibody domain possesses functional activity in preventing the formation of mature amyloid fibrils by stabilizing Abeta protofibrils. These data suggest possible applications of B10 in the detection of amyloid fibrils or in the modulation of their formation.
Pronounced Effects of Acute Endurance Exercise on Gene Expression in Resting and Exercising Human Skeletal Muscle (2012)

Regular physical activity positively influences whole body energy metabolism and substrate handling in exercising muscle. While it is recognized that the effects of exercise extend beyond exercising muscle, it is unclear to what extent exercise impacts non-exercising muscles. Here we investigated the effects of an acute endurance exercise bouts on gene expression in exercising and non-exercising human muscle. To that end, 12 male subjects aged 44-56 performed one hour of one-legged cycling at 50% W(max). Muscle biopsies were taken from the exercising and non-exercising leg before and immediately after exercise and analyzed by microarray. One-legged cycling raised plasma lactate, free fatty acids, cortisol, noradrenalin, and adrenalin levels. Surprisingly, acute endurance exercise not only caused pronounced gene expression changes in exercising muscle but also in non-exercising muscle. In the exercising leg the three most highly induced genes were all part of the NR4A family. Remarkably, many genes induced in non-exercising muscle were PPAR targets or related to PPAR signalling, including PDK4, ANGPTL4 and SLC22A5. Pathway analysis confirmed this finding. In conclusion, our data indicate that acute endurance exercise elicits pronounced changes in gene expression in non-exercising muscle, which are likely mediated by changes in circulating factors such as free fatty acids. The study points to a major influence of exercise beyond the contracting muscle.
Testosterone Deficiency and Replacement (2001)

In the human male, testosterone is the major circulating androgen. More than 95% of circulating testosterone is secreted by the testis with a production rate of 6-7 mg/day. The clinical effects of androgens are numerous, and testosterone deficiency is associated with a number of clinical abnormalities. Overt hypogonadism results in reductions in bone mineral density, alterations in body composition and effects on mood, aggressive behaviour, cognitive function, sexual function and several factors important for cardiovascular risk. Androgen replacement in this context is clearly beneficial, and numerous studies have demonstrated improvements in bone and muscle mass, reductions in body fat, and positive effects on quality of life following treatment. The benefits of therapy in men with milder degrees of hypogonadism, and elderly men with "physiological" testosterone deficiency, are less clear-cut, and the appropriate biochemical cut-off below which replacement should be offered has not been clearly defined. Several options are available for androgen replacement in adult men. Oral testosterone, intramuscular injections, subcutaneous implants and transdermal therapy have all been used. Each mode of delivery has advantages and drawbacks and the choice between them will often depend on patient reference. Recent advances include the development of longer-acting intramuscular preparations, which offer more stable androgen levels with fairly infrequent injections, and testosterone gel which appears to provide transdermal replacement without a high incidence of skin reactions. This article will examine the evidence concerning the impact of male hypogonadism and the response to androgen therapy. The question of who to treat will be addressed with particular reference to mild hypogonadism and hypogonadism in the elderly. Finally, an overview of the different modes of replacement therapy will be presented.
Tunnel conductance of Watson–Crick nucleoside–base pairs from telegraph noise (2009)

The use of tunneling signals to sequence DNA is presently hampered by the small tunnel conductance of a junction spanning an entire DNA molecule. The design of a readout system that uses a shorter tunneling path requires knowledge of the absolute conductance across base pairs. We have exploited the stochastic switching of hydrogen-bonded DNA base-nucleoside pairs trapped in a tunnel junction to determine the conductance of individual molecular pairs. This conductance is found to be sensitive to the geometry of the junction, but a subset of the data appears to come from unstrained molecular pairs. The conductances determined from these pairs are within a factor of two of the predictions of density functional calculations. The experimental data reproduces the counterintuitive theoretical prediction that guanine-deoxycytidine pairs (3 H-bonds) have a smaller conductance than adenine-thymine pairs (2 H-bonds). A bimodal distribution of switching lifetimes shows that both H-bonds and molecule-metal contacts break.
PROGRAMMED CELL DEATH SIGNALING VIA CELL-SURFACE EXPRESSION OF A SINGLE-CHAIN ANTIBODY TRANSGENE (2000)

Cell surface anchorage of scFv thus provides effective delivery of immune modulatory signals, which may be manipulated for various therapeutic strategies.
Describing Textures in the Wild (2014)

Patterns and textures are key characteristics of many natural objects: a shirt can be striped, the wings of a butterfly can be veined, and the skin of an animal can be scaly. Aiming at supporting this dimension in image understanding, we address the problem of describing textures with semantic attributes. We identify a vocabulary of forty-seven texture terms and use them to describe a large dataset of patterns collected "in the wild". The resulting Describable Textures Dataset (DTD) is a basis to seek the best representation for recognizing describable texture attributes in images. We port from object recognition to texture recognition the Improved Fisher Vector (IFV) and Deep Convolutional-network Activation Features (DeCAF), and show that surprisingly, they both outperform specialized texture descriptors not only on our problem, but also in established material recognition datasets. We also show that our describable attributes are excellent texture descriptors, transferring between datasets and tasks, in particular, combined with IFV and DeCAF, they significantly outperform the state-of-the-art by more than 10% on both FMD and KTH-TIPS-2b benchmarks. We also demonstrate that they produce intuitive descriptions of materials and Internet images.
[Potential interest in powerful and specific ligands for the histamine H3 receptor]. (1988)

In contrast to cerebral histamine H1 and H2-receptors, histamine H3-receptors are presynaptically located on histamine-synthesizing nerve terminals (autoreceptors) and control the synthesis and release of the amine in cerebral neurons. Two imidazole derivatives were designed to interact at H3-receptors: (R) alpha-methylhistamine (alpha-MeHA), a chiral agonist, and thioperamide, a competitive antagonist derived from imidazolyl piperidine, both display high selectivity and potency at nanomolar concentrations in vitro. (R) alpha-MeHA, being about 15 times as potent as histamine itself, constitutes, when tritiated, a suitable probe for the radioassay of H3-receptors. Outside the brain, H3-receptor sites could be detected in the lung. The availability of new ligands made it possible to assess in vivo the physiological role of central and peripheral H3-receptors. The agonist and the antagonist modified in opposite directions histamine synthesis in the lung as in the brain, confirming the presence of H3-receptors in this peripheral organ. A large part of lung histamine being present within mast-cells, it is likely that these cells are endowed with H3-receptors controlling the amine synthesis and, possibly, release. Therefore, the novel agents may be of great practical interest in the field of allergy and inflammation.
The Bioactivity of Saponins: Triterpenoid and Steroidal Glycosides (2000)

Triterpenoid and steroidal glycosides, referred to collectively as saponins, are bioactive compounds present naturally in many plants. They have considerable potential as pharmaceutical and/or nutraceutical agents in natural or synthetic form. Saponins, from a variety of sources, have been shown to have hypocholesterolemic, anti-coagulant, anticarcinogenic, hepatoprotective, hypoglycemic, immunomodulatory, neuroprotective, anti-inflammatory and anti-oxidant activity. This paper reviews saponin research of the last decade, focussing on developments in understanding their mechanism of action and structure-activity relationships. Virtually all of this work has used animal and in vitro models. To date there are very few human data.
Superresolving filters in confocally scanned imaging systems (1986)

The limitations of superresolving filters in imaging systems are investigated. The constraints on such filters in the nonscanning imaging mode are discussed. The possible advantages of such filters in confocal scanning imaging are highlighted. It is shown theoretically and verified experimentally that simply designed complex-amplitude filters can be used effectively to double the exit pupil of a confocal imaging system and thus improve resolution. Superresolution can be achieved with acceptable energy losses and manufacturing tolerances.