gebhart/patrepeval huggingface dataset:
Physiological disposition of verapamil in man (1976)

14C-D,L-verapamil was administered intravenously (10 mg) and orally (80 mg) to five volunteer patients. Plasma concentrations of verapamil, which were determined by mass fragmentography, declined bi-exponentially with half-lives of the chi-phase ranging from 18 to 35 min and of the beta-phase from 170 to 440 min. The apparent volume of distribution ranged from 270 to 460 litre and plasma clearance from 730 to 1980 ml/min. Following oral administration absorption was almost complete as judged from the area under the curve (AUC) of 14C-activity and cumulative urinary excretion of 14C. After intravenous infusion of verapamil about 80% of the radioactivity administered could be recovered in urine and faeces within 5 d. Despite its almost complete absorption after oral administration verapamil was shown to undergo extensive first pass metabolism as the bioavailability was only 10 to 22%. Rapid biotransformation had occurred as only a small percentage of AUC of 14C was seen to correspond to unchanged verapamil after both intravenous and oral administration.
Cerebral Activation during Vagus Nerve Stimulation: A Functional MR Study (2002)

VNS-induced thalamic and insular cortical activation during fMRI suggests that these areas may play a role in modulating cerebral cortical activity, and the observed decrease in seizure frequency in patients who are given VNS may be a consequence of this increased activation.
Design and Parametric Analysis of Axial Flux PM Motors With Minimized Cogging Torque (2009)

<para xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> This paper deals with analysis and experiment of an axial flux permanent magnet (AFPM) brushless direct current (BLDC) motor with minimized cogging torque. Recently, many optimal designs for the AFPM motor have been done by finite-element (FE) analysis, but such analysis generally is time-consuming. In this study, the equation of magnetic flux lines existing between PMs and cores is assumed mathematically and the minimum cogging torque is calculated theoretically and geometrically without FE analysis. The form of equation is assumed to be a second-order polynomial in this paper. The skew angle that makes the cogging torque minimized is calculated theoretically, and the value of minimum cogging torque is confirmed by FE analyses and experiments. In the theoretical analysis, the maximum cogging torque of a proposed AFPM motor has the smallest value approximately at a skew angle of 4<formula formulatype="inline"> <tex Notation="TeX">$^\circ$</tex></formula> and that value is about the same as those of FE analyses and experiments. Compared with the nonskewed motor, the cogging torque of the skewed motor can be decreased to over 90%, which has a value of 5% of the rated torque. Two types of stator cores, with the skew angle of 0<formula formulatype="inline"><tex Notation="TeX">$^\circ$</tex> </formula> (nonskewed) and 4<formula formulatype="inline"><tex Notation="TeX">$^\circ$</tex> </formula>(skewed optimally), are analyzed, manufactured, and tested experimentally in this paper. </para>
Hypertension is critically dependent on the carotid body input in the spontaneously hypertensive rat (2012)

The peripheral chemoreflex is known to be enhanced in individuals with hypertension. In pre-hypertensive (PH) and adult spontaneously hypertensive rats (SHRs) carotid body type I (glomus) cells exhibit hypersensitivity to chemosensory stimuli and elevated sympathoexcitatory responses to peripheral chemoreceptor stimulation. Herein, we eliminated carotid body inputs in both PH-SHRs and SHRs to test the hypothesis that heightened peripheral chemoreceptor activity contributes to both the development and maintenance of hypertension. The carotid sinus nerves were surgically denervated under general anaesthesia in 4- and 12-week-old SHRs. Control groups comprised sham-operated SHRs and aged-matched sham-operated and carotid sinus nerve denervated Wistar rats. Arterial blood pressure was recorded chronically in conscious, freely moving animals. Successful carotid sinus nerve denervation (CSD) was confirmed by testing respiratory responses to hypoxia (10% O(2)) or cardiovascular responses to i.v. injection of sodium cyanide. In the SHR, CSD reduced both the development of hypertension and its maintenance (P<0.05) and was associated with a reduction in sympathetic vasomotor tone (as revealed by frequency domain analysis and reduced arterial pressure responses to administration of hexamethonium; P<0.05 vs. sham-operated SHR) and an improvement in baroreflex sensitivity. No effect on blood pressure was observed in sham-operated SHRs or Wistar rats. In conclusion, carotid sinus nerve inputs from the carotid body are, in part, responsible for elevated sympathetic tone and critical for the genesis of hypertension in the developing SHR and its maintenance in later life.
Influence of HSiO1.5 Sol−Gel Polymer Structure and Composition on the Size and Luminescent Properties of Silicon Nanocrystals (2009)

We report the preparation of SiO2-embedded silicon nanocrystals (Si-NCs) from the thermal processing of sol−gel polymers derived from trichlorosilane (HSiCl3). Straightforward addition of water to HSiCl3 generates a cross-linked (HSiO1.5)n sol−gel polymer suitable for the generation of bulk quantities of SiO2-embedded Si-NCs. It is shown that structural differences between the present (HSiO1.5)n polymer and hydrogen silsesquioxane (HSQ) result in controllable differences in the resulting oxide-embedded Si-NCs produced from these precursors. A polymer structure/NC size relationship is further delineated through the preparation and evaluation of methyl-modified (HSiO1.5)n(CH3SiO1.5)m (m ≪ n, m + n = 1) sol−gel copolymers, in which a low concentration of methyl groups acts as a polymer network modifier and influences the formation of Si-NCs during thermal processing. Si-NC size is readily tailored by controlled variations to peak processing temperature for (HSiO1.5)n and composition (n and m) for (HSiO1.5)n(CH3SiO1.5)m. Furthermore, the present Si-NCs exhibit size-dependent photoluminescence (PL) in accordance with the principles of quantum confinement. Freestanding Si-NCs are obtained through chemical etching of the oxide matrix and exhibit tunable PL throughout the visible spectrum.
CD34+ hematopoietic progenitors from human cord blood differentiate along two independent dendritic cell pathways in response to GM-CSF+TNF alpha. (1996)

Human dendritic cells (DC) can now be generated in vitro in large numbers by culturing CD34+ hematopoietic progenitors in presence of GM-CSF+TNF alpha for 12 d. The present study demonstrates that cord blood CD34+ HPC indeed differentiate along two independent DC pathways. At early time points (day 5-7) during the culture, two subsets of DC precursors identified by the exclusive expression of CD1a and CD14 emerge independently. Both precursor subsets mature at day 12-14 into DC with typical morphology and phenotype (CD80, CD83, CD86, CD58, high HLA class II). CD1a+ precursors give rise to cells characterized by the expression of Birbeck granules, the Lag antigen and E-cadherin, three markers specifically expressed on Langerhans cells in the epidermis. In contrast, the CD14+ progenitors mature into CD1a+ DC lacking Birbeck granules, E-cadherin, and Lag antigen but expressing CD2, CD9, CD68, and the coagulation factor XIIIa described in dermal dendritic cells. The two mature DC were equally potent in stimulating allogeneic CD45RA+ naive T cells. Interestingly, the CD14+ precursors, but not the CD1a+ precursors, represent bipotent cells that can be induced to differentiate, in response to M-CSF, into macrophage-like cells, lacking accessory function for T cells. Altogether, these results demonstrate that different pathways of DC development exist: the Langerhans cells and the CD14(+)-derived DC related to dermal DC or circulating blood DC. The physiological relevance of these two pathways of DC development is discussed with regard to their potential in vivo counterparts.
The protein N-glycosylation in plants (1998)

In plants, most proteins of the extracellular compartment and the endomembrane system are glycosylated by N-linked oligosaccharides. The N-glycosylation of proteins has a great impact both on their physicochemical properties and on their biological functions. Over the last ten years, a number of laboratories have contributed considerably to the understanding of the structure, the biosynthesis and the function of plant N-linked glycans. In this review, data on this domain will be summarized and the recent results on the N-glycosylation of a vacuolar lectin, the bean phytohaemagglutinin (PHA) will also be included. This PHA, used as a model glycoprotein, was expressed in different plant systems and the N-glycosylation patterns of different recombinant PHA were compared. In addition to this study on plant-specific glycosylation, the same model glycoprotein was used to investigate whether or not N-glycosylation and N-glycan maturation is organ-specific in plants.
IL-1β-Specific Up-Regulation of Neutrophil Gelatinase-Associated Lipocalin Is Controlled by IκB-ζ (2006)

Neutrophil gelatinase-associated lipocalin (NGAL) is a siderophore-binding protein that exerts a bacteriostatic effect by sequestering iron. Strong induction of NGAL synthesis has been observed in inflamed epithelium of the lungs and colon. Expression of NGAL is up-regulated in the lung epithelial cell line A549 by IL-1beta, but not by TNF-alpha, despite an induction of NF-kappaB binding to the NGAL promoter by both cytokines. In this study, we present evidence that the IL-1beta specificity is caused by a requirement of the NGAL promoter for the NF-kappaB-binding cofactor IkappaB-zeta for transcriptional activation. Up-regulation of NGAL expression in A549 cells following IL-1beta stimulation was dependent on de novo protein synthesis and was greatly diminished by a small interfering against IkappaB-zeta mRNA. Cotransfection of A549 cells with a plasmid expressing IkappaB-zeta made TNF-alpha capable of inducing NGAL transcription, indicating that IkappaB-zeta induction is the only factor discriminating between IL-1beta and TNF-alpha in their ability to induce NGAL expression. Coexpression of the cofactor Bcl-3, which is closely related to IkappaB-zeta, did not enable TNF-alpha to induce NGAL transcription. A functional NF-kappaB site of the NGAL promoter was required for IkappaB-zeta to exert its effect. The human beta defensin 2 gene also required IkappaB-zeta for its IL-1beta-specific induction in A549 cells. Our findings indicate that a common regulatory mechanism has evolved to control expression of a subset of antimicrobial proteins expressed in epithelial cells.
Statistical analysis of the Bacterial Carbohydrate Structure Data Base (BCSDB): Characteristics and diversity of bacterial carbohydrates in comparison with mammalian glycans (2008)

For the first time a systematic database analysis of the bacterial glycome has been performed. This study summarizes the current knowledge of bacterial glycan architecture and diversity and reveals putative targets for the rational design and development of therapeutic intervention strategies by comparing bacterial and mammalian glycans.
Negative regulation of ErbB family receptor tyrosine kinases (2004)

Receptors of the EGF receptor or ErbB family of growth factor receptor tyrosine kinases are frequently overexpressed in a variety of solid tumours, and the aberrant activation of their tyrosine kinase activities is thought to contribute to tumour growth and progression. Much effort has been put into developing inhibitors of ErbB receptors, and both antibody and small-molecule approaches have exhibited clinical success. Recently, a number of endogenous negative regulatory proteins have been identified that suppress the signalling activity of ErbB receptors in cells. These include intracellular RING finger E3 ubiquitin ligases such as cbl and Nrdp1 that mediate ErbB receptor degradation, and may include a wide variety of secreted and transmembrane proteins that suppress receptor activation by growth factor ligands. It will be of interest to determine the extent to which tumour cells suppress these pathways to promote their progression, and whether restoration of endogenous receptor-negative regulatory pathways may be exploited for therapeutic benefit.
FIERY1 encoding an inositol polyphosphate 1-phosphatase is a negative regulator of abscisic acid and stress signaling in Arabidopsis (2001)

The plant hormone abscisic acid (ABA) plays a wide range of important roles in plant growth and development, including embryogenesis, seed dormancy, root and shoot growth, transpiration, and stress tolerance. ABA and various abiotic stresses also activate the expression of numerous plant genes through undefined signaling pathways. To gain insight into ABA and stress signal transduction, we conducted a genetic screen based on ABA- and stress-inducible gene transcription. Here we report the identification of an Arabidopsis mutation, fiery1 (fry1), which results in super-induction of ABA- and stress-responsive genes. Seed germination and postembryonic development of fry1 are more sensitive to ABA or stress inhibition. The mutant plants are also compromised in tolerance to freezing, drought, and salt stresses. Map-based cloning revealed that FRY1 encodes an inositol polyphosphate 1-phosphatase, which functions in the catabolism of inositol 1, 4, 5-trisphosphate (IP(3)). Upon ABA treatment, fry1 mutant plants accumulated more IP(3) than did the wild-type plants. These results provide the first genetic evidence indicating that phosphoinositols mediate ABA and stress signal transduction in plants and their turnover is critical for attenuating ABA and stress signaling.
Analysis of viral and cellular gene expression during progression and suppression of the transformed phenotype in type 5 adenovirus-transformed rat embryo cells. (1991)

Transformation of secondary Sprague-Dawley rat embryo (RE) cells with type 5 adenovirus (Ad5) results in morphologically transformed cells which can undergo a series of sequential changes resulting in enhanced expression of the transformed phenotype, a process termed progression. Selection for a progressed phenotype often occurs after growth in agar or tumor formation in nude mice, and this process is reversible following treatment of cells with 5-azacytidine. In the present study we have analyzed a series of clonal populations of Ad5-transformed RE cells representing different stages in a defined progression lineage. Progression was not associated with alterations in the steady-state levels of mRNA produced by the viral transforming genes, E1A and E1B, or the cellular gene, c-myc. In addition, the tumor-promoting agent 12-O-tetradecanoyl-phorbol-13-acetate (TPA), which induces expression of a progressed phenotype in Ad5-transformed RE cells, did not significantly alter the RNA transcription rates of the Ad5 E1A or E1B genes, the TPA-inducible gene TPA-S1 or the TPA-responsive genes Pro1 or protein kinase C. TPA did, however, increase by 1 h the steady-state level of c-fos mRNA, but this effect was similar in both progressed and unprogressed cells. Progression also did not involve a change in the RNA transcription rate of a number of cellular and viral genes, including actin, c-Ha-ras, c-myc, v-fos, erbB, TGF-alpha, TGF-beta, Pro-2, transin, TPA-R1, v-myb and c-mos, or other adenovirus genes in addition to E1A and E1B, including E2A and E4. Immunoblotting analysis using E1B polyclonal antiserum further indicated that progression was not associated with changes in the levels of an Mr 21,000 polypeptide encoded by E1B. Similarly, immunoprecipitation analysis with an Ad2 E1A monoclonal antibody indicated similar levels of the Mr 55,000 and 48,000 E1A polypeptides, as well as coprecipitated proteins of Mr 300,000, 107,000 and 105,000 [which is the retinoblastoma (Rb) protein], in E11 and E11-NMT cells. Immunoprecipitation of cell lysates with a monoclonal antibody specific for the Mr 105,000 Rb protein further demonstrated that progression also was not associated with a change in the level or state of phosphorylation of the Rb protein. However, transfection of a human Rb gene (also containing a neomycin resistance gene) into Ad5-transformed RE cells was more inhibitory, with respect to formation of G418-resistant colonies, in unprogressed than in progressed Ad5-transformed RE cells.(ABSTRACT TRUNCATED AT 400 WORDS)
Processor Design in 3D Die-Stacking Technologies (2007)

Three-dimensional integration is an emerging fabrication technology that vertically stacks multiple integrated chips. The benefits include an increase in device density; much greater flexibility in routing signals, power, and clock; the ability to integrate disparate technologies; and the potential for new 3D circuit and microarchitecture organizations. This article provides a technical introduction to the technology and its impact on processor design. Although our discussions here primarily focus on high-performance processor design, most of the observations and conclusions apply to other microprocessor market segments.
Volumetric navigators for prospective motion correction and selective reacquisition in neuroanatomical MRI (2011)

We introduce a novel method of prospectively compensating for subject motion in neuroanatomical imaging. Short three-dimensional echo-planar imaging volumetric navigators are embedded in a long three-dimensional sequence, and the resulting image volumes are registered to provide an estimate of the subject's location in the scanner at a cost of less than 500 ms, ~ 1% change in contrast, and ~3% change in intensity. This time fits well into the existing gaps in sequences routinely used for neuroimaging, thus giving a motion-corrected sequence with no extra time required. We also demonstrate motion-driven selective reacquisition of k-space to further compensate for subject motion. We perform multiple validation experiments to evaluate accuracy, navigator impact on tissue intensity/contrast, and the improvement in final output. The complete system operates without adding additional hardware to the scanner and requires no external calibration, making it suitable for high-throughput environments.
Multiple sclerosis: B- and T-cell responses to the extracellular domain of the myelin oligodendrocyte glycoprotein (1999)

We report a comparative study of the B- and T-cell responses to the extracellular immunoglobulin (Ig)-like domain of human myelin-oligodendrocyte glycoprotein (MOG(Igd)) in the blood of patients with multiple sclerosis and healthy controls using a bacterial recombinant human protein (rhMOG(Igd)). The frequency of anti-rhMOG(Igd)-seropositive samples, as determined by Western blotting, was significantly higher in the multiple sclerosis group (54%) than in normal random controls (excluding laboratory workers exposed to MOG) (22%; P = 0.02). In contrast, there was no difference in rhMOG(Igd)-induced proliferation indices of peripheral blood T cells between patients and controls. To characterize the rhMOG(Igd)-reactive T-cell repertoire, we isolated a panel of MOG-specific CD4(+) T-cell lines from multiple sclerosis patients and normal subjects, and these revealed a heterogeneous response with respect to epitope specificity, cytokine response, MHC (major histocompatibility complex) restriction and T-cell receptor Vbeta-chain usage. The majority of the T-cell lines recognized epitopes in the N-terminal region of MOG (amino acids 1-60). One epitope (represented by peptide 27-50) was exclusively recognized by T-cell lines from normal controls. Forty per cent of the MOG-specific T-cell lines analysed displayed a Th-2 or Th-0 cytokine profile and could therefore act as helper T cells in vivo.
Metabolism of Tryptophan by Pseudomonas aureofaciens and Its Relationship to Pyrrolnitrin Biosynthesis (1980)

Studies on the metabolism of tryptophan in Pseudomonas aureofaciens ATCC 15926 revealed different metabolic routes for the L- and D-isomer besides the biosynthetic pathway for pyrrolnitrin synthesis. L-Tryptophan catabolism follows the aromatic route via anthranilic acid. Tryptophan 2,3-dioxygenase were induced by L-tryptophan. Kynureninase and anthranilate 1,2-dioxygenase were induced by L-tryptophan, L-kynurenine and anthranilic acid. Anthranilate 1,2-dioxygenase was absent from a mutant strain of P. aureofaciens ATCC 19526 which produced about 30-fold increased amounts of pyrrolnitrin. The Km values of tryptophan 2,3-dioxygenase and kynureninase did not differ substantially between the two strains. Kynurenine 3-monooxygenase, 3-hydroxyanthranilate 3,4-dioxygenase, tryptophanase and indolyl-3-alkane alpha-hydroxylase activities were not detected. D- and L-tryptophan were converted to indole-3-acetic acid. This additional catabolic pathway was well as tryptophan racemase activity was constitutive and present in both strains.
GABAergic Neurons and Their Role in Cortical Plasticity in Primates (1993)

GABA neurons and GABA receptors are conspicuous elements of cerebral cortical organization. They serve to shape the stimulus-response properties of neurons in the sensory areas and undoubtedly play a comparable role in the nonsensory areas as well. Although non-GABAergic local circuit neurons exist in the cerebral cortex, the variety of forms adopted by the GABAergic neurons and their important functional role have served to focus attention on the latter in investigations of local cortical circuitry. In primate neocortex, GABAergic neurons constitute approximately 25-30% of the neuronal population. In addition to their known or postulated functions in shaping neuronal receptive fields and response profiles, some of which are still controversial (Sillito, 1984; Ferster, 1986), their transmitter, GABA, and the major class of receptor upon which it acts are regulated in an activity-dependent manner even in the adult (Jones, 1990). In this, there is a potential mechanism for the plasticity of representational maps that is demonstrable in somatic sensory, motor, auditory, and visual cortex (Merzenich et al., 1983; Sanes et al., 1988; Robertson and Irvine, 1989; Kaas et al., 1990).
In vivocerebrovascular measurement combining diffuse near-infrared absorption and correlation spectroscopies (2001)

We combine two near-infrared diffuse optical techniques to study variations of blood flow, haemoglobin concentration, and blood oxygen saturation in the functioning rat brain. Diffuse correlation spectroscopy (or flowmetry) monitors changes in the cerebral blood flow, without the use of the principles of tracer clearance, by measuring the optical phase-shifts caused by moving blood cells. Near-infrared absorption spectroscopy concurrently measures tissue absorption at two wavelengths to determine haemoglobin concentration and blood oxygen saturation in this same tissue volume. This optical probe is non-invasive and was employed through the intact skull. The utility of the technique is demonstrated in vivo by measuring the temporal changes in the regional vascular dynamics of rat brain during hypercapnia. Temporal and spatial variations of cerebral blood flow, haemoglobin concentration and blood oxygen saturation during hypercapnia are compared with other measurements in the literature, and a quantitative analysis demonstrating the self-consistency of our combined observations of vascular response is presented.