gebhart/patrepeval huggingface dataset:
The Association between Abdominal Visceral Fat and Carotid Stiffness Is Mediated by Circulating Inflammatory Markers in Uncomplicated Type 2 Diabetes (2005)

Central obesity, insulin resistance, inflammation, as well as vascular changes are common in patients with type 2 diabetes. In this study we assessed the relationship among stiffness of the carotid artery, visceral fat, and circulating inflammatory markers in type 2 diabetic subjects. Carotid stiffness, quantified as the distensibility coefficient (DC), was measured by ultrasound in asymptomatic, normotensive patients with uncomplicated, well-controlled type 2 diabetes and in controls. Body fat distribution was quantified by magnetic resonance imaging. In patients, the carotid DC was inversely associated with visceral fat area (r = -0.660; P = 0.005) and plasma levels of C-reactive protein (CRP; r = -0.687; P = 0.002), but most strongly with plasma IL-6 (r = -0.766; P < 0.001). In multivariate analysis, the association between DC and visceral fat disappeared after adjustment for CRP and IL-6. Correction for age, body mass index, blood pressure, glycosylated hemoglobin, or fasting plasma glucose did not affect the association between carotid DC and inflammatory markers. Thus, carotid stiffness is associated with visceral obesity in patients with uncomplicated type 2 diabetes, but this association seems to be mediated by circulating IL-6 and CRP, of which IL-6, at least in part, originates from adipose tissue and stimulates hepatic CRP production.
Differential Transcriptional Regulation of the Two Vascular Endothelial Growth Factor Receptor Genes (1997)

Vascular endothelial growth factor (VEGF) and its two endothelial cell-specific receptor tyrosine kinases, Flk-1/KDR and Flt-1, play a key role in physiological and pathological angiogenesis. Hypoxia has been shown to be a major mechanism for up-regulation of VEGF and its receptors in vivo. When we exposed human umbilical vein endothelial cells to hypoxic conditions in vitro, we observed increased levels of Flt-1 expression. In contrast, Flk-1/KDR mRNA levels were unchanged or slightly repressed. These findings suggest a differential transcriptional regulation of the two receptors by hypoxia. To identify regulatory elements involved in the hypoxic response, promoter regions of the mouse Flt-1 and Flk-1/KDR genes were isolated and tested in conjunction with luciferase reporter gene. In transient transfection assays, hypoxia led to strong transcriptional activation of the Flt-1 promoter, whereas Flk-1/KDR transcription was essentially unchanged. Promoter deletion analysis demonstrated a 430-bp region of the Flt-1 promoter to be required for transcriptional activation in response to hypoxia. This region includes a heptamer sequence matching the hypoxia-inducible factor-1 (HIF) consensus binding site previously found in other hypoxia-inducible genes such as the VEGF gene and erythropoietin gene. We further narrowed down the element mediating the hypoxia response to a 40-base pair sequence including the putative HIF binding site. We show that this element acts like an enhancer, since it activated transcription irrespective of its location or orientation in the construct. Furthermore, mutations within the putative HIF consensus binding site lead to impaired transcriptional activation by hypoxia. These findings indicate that, unlike the KDR/Flk-1 gene, the Flt-1 receptor gene is directly up-regulated by hypoxia via a hypoxia-inducible enhancer element located at positions -976 to -937 of the Flt-1 promoter.
Wireless power transfer to a cardiac implant (2012)

We analyze wireless power transfer between a source and a weakly coupled implant on the heart. Numerical studies show that mid-field wireless powering achieves much higher power transfer efficiency than traditional inductively coupled systems. With proper system design, power sufficient to operate typical cardiac implants can be received by millimeter-sized coils.
HARMONIC DETECTION OF RESONANCE IN MICRO- AND NANO- CANTILEVERS (2006)

Over the past decade there has been an explosion in the study of cantilevered beams on the micron and submicron dimension. The applications and research that involve these structures include state-of-the-art electronic components, sensors, and more recently, studies aimed at elucidating the mechanical properties of cantilevered carbon nanotubes and semiconducting nanowires. In nanoelectro-mechanical systems (NEMS), it is desirable to develop a capacitive readout method involving only two electrodes that are fully compliant with standard CMOS technology. However, the main drawback with this method is the ability to detect resonance in the presence of parasitic capacitance, which is due to the fringing electric fields present between the electrodes (cantilever and the counter electrode). \t\t\tThe work presented in this thesis deals with the electrical actuation / detection of mechanical resonance in individual micron and sub-micron sized cantilevers. The aim is to overcome parasitic capacitance which masks the detection of resonance signal in these cantilevers thereby increasing the signal-to-background ratio (SBR). In our method, a silicon microcantilever, or cantilevered multi-walled carbon nanotube (MWNT), is placed close to a counter electrode whose potential is varied at a frequency ω. An electrical signal comes from the flow of charge on and off of the cantilever when ω equals a resonant frequency 0 of the cantilever. Higher harmonics of 0 are measured to overcome the parasitic capacitance. This technique, termed harmonic detection of resonance (HDR), allows detection at frequencies well removed from the driving frequency thereby increasing the SBR by ~3 orders of magnitude. It is shown that HDR allows the detection of resonance even in multi-walled carbon nanotubes, which have diameters on the order of 50 nm. Furthermore, superharmonics inherent to electrostatic actuation, are shown to occur at driving frequencies of ω0/n where n=1,2,3,... .
Low-power circuits and technology for wireless digital systems (2003)

As CMOS technology scales to deep-submicron dimensions, designers face new challenges in determining the proper balance between aggressive high-performance transistors and lower-performance transistors to optimize system power and performance for a given application. Determining this balance is crucial for battery-powered handheld devices in which transistor leakage and active power limit the available system performance. This paper explores these questions and describes circuit techniques for low-power communication systems which exploit the capabilities of advanced CMOS technology.
Treatment of ventricular tachycardia induced cardiogenic shock by percoronary chemical ablation (1990)

Incessant ventricular arrhythmias pose an especially challenging therapeutic dilemma. We describe the successful treatment and follow-up of a patient with refractory ventricular tachycardia-induced cardiogenic shock with percoronary chemical ablation. After endocardial mapping was used to identify the "tachycardia-related" coronary artery, temporary termination of the arrhythmia with balloon occlusion and subselective intracoronary installation of iced saline as previously advocated was unsuccessful. This was probably due to a dual arterial blood supply to the arrhythmogenic focus. However, infusion of 2 cc ethanol (99%) permanently terminated the arrhythmia. Contrary to previous experience, ethanol-induced arrhythmia termination did not result in arterial occlusion, further supporting a direct toxic effect on the myocardium as its mode of action. Use of standard angioplasty balloon inflation prevents "backwash" of distally infused ethanol and more generalized cell death. The only complication of this procedure was temporary third-degree AV block, requiring permanent pacemaker implantation.
Method for Supporting Platinum on Single-Walled Carbon Nanotubes for a Selective Hydrogenation Catalyst (2001)

We have prepared a novel material, consisting of Pt particles supported on purified single-walled carbon nanotubes (SWNTs), representing the first reported metal-loaded SWNT material. The material contains 10 wt % Pt on entangled SWNT bundles consisting of 20−100 nanotubes each. The average Pt particle size is 1−2 nm. High-resolution transmission electron microscopy (HRTEM) observations combined with electron energy-loss spectroscopy (EELS) indicate chemical bonding between Pt and the SWNT surfaces. This bonding is accomplished presumably by ion exchange on carboxylic acid sites created on the nanotube surfaces by slow wet oxidation in dilute HNO3. In addition, a simple SWNT purification scheme requiring no filtration was developed for the preparation of this material. The purification results in a well-defined structure for the metal support useful for investigating the role of this material as a heterogeneous catalyst and the effects of metal−support interactions (MSI). Preliminary kinetics measurements of the activity of this material for the selective partial hydrogenation of 3-methyl-2-butenal (prenal) to 3-methyl-2-butenol (prenol)a representative reaction important in the fine chemicals industryindicates the desired catalytic selectivity above 75 °C, demonstrating a utility of this material that can be optimized in future work.
Effect of phenylboronic acid groups in copolymers on endothelial cell differentiation into capillary structures (1998)

Copolymers (IABb) composed of N-isopropylacrylamide (I), N-(3-dimethylaminopropyl)-acrylamide (A), 3-acrylamidophenylboronic acid (B), and a hydrophobic comonomer, n-butyl methacrylate (b), were synthesized as cell culture substrata since we previously learned that bovine aortic endothelial cells (BAECs) cultured on the phenylboronic acid-containing copolymer (IAB) differentiated into capillary structures after 26 days culture. The synthesized IABb copo ymers contained higher boron and amine moieties than the IAB copolymer. The results of the dynamic contact angle measurement revealed that IABb copolymer-coated surfaces showed a relatively hydrophobic nature, changing to hydrophilic in response to the aqueous environment. BAECs cultured on the copolymer substrata developed into capillary networks after 7 days. This is probably due to the enrichment of boron and amine segments in the vicinity of the hydrophilic copolymer surface, enhancing more pronounced interaction of boronates with cell membrane glycocalyx. The introduction of n-butyl methacrylate into the polymers might enhance the diffusion of the hydrophobic segments to the bulk polymers and the concentration of relatively hydrophilic segments at the outermost polymer surfaces by contact with water. A copolymer (IAP) without boronic acid groups was also prepared using N-phenylacrylamide (P) as a comonomer instead of 3-acrylamidophenylboronic acid in the IAB copolymer to investigate the effect of boronic acid moieties on the capillary formation of the cultured cells. Although the endothelial cells seeded on the copolymer without boronic acid groups adhered during the early culture period, these cells showed neither proliferation nor differentiation and detached from the surface after 13 days. These results strongly support the opinion that the phenylboronic acid groups in the copolymers are responsible for the specific induction of tissue formation of BAECs through the interaction with glycoconjugates on the cell membranes.
Antibody-promoted dimerization bypasses the regulation of DNA binding by the heme domain of the yeast transcriptional activator HAP1. (1993)

The yeast transcriptional activator HAP1 contains a DNA-binding domain homologous to the zinc finger of GAL4 and an adjacent regulatory domain that blocks DNA binding in the absence of the inducer heme. We show that short HAP1 fragments containing the zinc finger are unable to bind to DNA but can be rescued by antibody to the HAP1 zinc finger. These fragments are missing a coiled-coil sequence similar to that within the dimerization domain of GAL4 and dimerization domains of myosin heavy chain. We surmise that the antibody promotes DNA binding by bringing together two monomers. Interestingly, the antibody will also promote DNA binding of a larger HAP1 fragment containing the DNA-binding and the heme-regulatory domains. This suggests that the regulatory domain acts by preventing dimerization of HAP1 in the absence of heme. Consistent with this view is an in vivo assay that also reveals that heme promotes HAP1 dimerization in yeast cells.
What is the best size descriptor to use for pharmacokinetic studies in the obese? (2004)

The prevalence of obesity in the western world is dramatically rising, with many of these individuals requiring therapeutic intervention for a variety of disease states. Despite the growing prevalence of obesity there is a paucity of information describing how doses should be adjusted, or indeed whether they need to be adjusted, in the clinical setting. This review is aimed at identifying which descriptors of body size provide the most information about the relationship between dose and concentration in the obese. The size descriptors, weight, lean body weight, ideal body weight, body surface area, body mass index, fat-free mass, percent ideal body weight, adjusted body weight and predicted normal body weight were considered as potential size descriptors. We conducted an extensive review of the literature to identify studies that have assessed the quantitative relationship between the parameters clearance (CL) and volume of distribution (V) and these descriptors of body size. Surprisingly few studies have addressed the relationship between obesity and CL or V in a quantitative manner. Despite the lack of studies there were consistent findings: (i) most studies found total body weight to be the best descriptor of V. A further analysis of the studies that have addressed V found that total body weight or another descriptor that incorporated fat mass was the preferred descriptor for drugs that have high lipophilicity; (ii) in contrast, CL was best described by lean body mass and no apparent relationship between lipophilicity or clearance mechanism and preference for body size descriptor was found. In conclusion, no single descriptor described the influence of body size on both CL and V equally well. For drugs that are dosed chronically, and therefore CL is of primary concern, dosing for obese patients should not be based on their total weight. If a weight-based dose individualization is required then we would suggest that chronic drug dosing in the obese subject should be based on lean body weight, at least until a more robust size descriptor becomes available.
Thrombin receptor activation causes rapid neural cell rounding and neurite retraction independent of classic second messengers. (1992)

The protease thrombin is a potent activator of various cell types. Thrombin cleaves and thereby activates its own seven-transmembrane-domain receptor which couples to G proteins. Thrombin also can inhibit neuronal differentiation, supposedly by degrading components of the extracellular matrix. Here we report that active thrombin induces immediate cell rounding and neurite retraction in differentiating N1E-115 and NG108-15 neural cells in serum-free culture. Serum (0.5-5% vol/vol) evokes similar responses, but the cell-rounding and neurite-retracting activity of serum is not attributable to thrombin. Neural cell rounding is transient, subsiding after 10-15 min, and subject to homologous desensitization, whereas retracted neurites rapidly degenerate. Thrombin action is inhibited by cytochalasin, but not colchicine. A novel 14-amino acid peptide agonist of the thrombin receptor fully mimics thrombin's morphoregulatory activity, indicating that thrombin-induced shape changes are receptor-mediated and not secondary to extracellular matrix degradation. Although thrombin receptors couple to phosphoinositide hydrolysis and Ca2+ mobilization, thrombin-induced shape changes appear to depend neither on the Ca2+/protein kinase C- nor the cyclic nucleotide-mediated signal transduction pathways; however, the morphological response to thrombin is blocked by pervanadate, an inhibitor of tyrosine phosphatases, and by broad-specificity kinase inhibitors. Our results suggest that the thrombin receptor communicates to an as-yet-uncharacterized effector to reorganize the actin cytoskeleton and to reverse the differentiated phenotype of neural cells.
Mapping epitopes of human Fc gamma RII (CDw32) with monoclonal antibodies and recombinant receptors (1993)

Fc gamma RII is a low affinity FcR for IgG with two Ig-like extracellular domains (D1 gamma and D2 gamma), a transmembrane domain, and a cytoplasmic domain. The production, characterization, and epitope analysis of four anti-human Fc gamma RII mAb (8.2, 8.7, 8.26, and 7.30) are detailed, and the mAb are compared with two defined CDw32 mAb, IV.3 and CIKM5. Reactivity of all mAb with Fc gamma RII was demonstrated by (a) specific binding to Fc gamma RII+ L cells (produced after transfection of L cells with human Fc gamma RIIa cDNA, HFc3.0), by using flow cytometry, (b) inhibition of the binding of SRBC sensitized with rabbit antibody (EA) to Fc gamma RII+ L cells, and (c) immunoprecipitation and SDS-PAGE, which detected a 42-kDa protein on K562 and U937 cells and a single 45-kDa protein on Fc gamma RII+ L cells. The mAb were able to detect different forms of Fc gamma RII, by flow cytometry, on Daudi cells (8.7 and 7.30) and U937 cells (8.2, IV.3, and CIKM5); 8.26 stained Daudi cells with intermediate fluorescence and U937 cells with the highest fluorescence, relative to the remaining mAb. Binding to transiently expressed isoforms of Fc gamma RII (a and b1) and four allelic variants of Fc gamma RIIa in COS-7 cells did not distinguish the mAb epitopes. Further mapping of the mAb epitopes was determined by (a) EA inhibition assays, (b) mAb blocking studies, and (c) the binding of the mAb to segments of human Fc gamma RIIa by using genetically engineered chimeric receptors. Chimeric receptors expressing either D1 gamma linked to domain 2 of Fc epsilon RI or domain 1 of Fc epsilon RI linked to D2 gamma were produced by exchanging homologous, but antigenically different, regions of Fc gamma RIIa and the high affinity receptor for IgE. Four clusters of mAb were identified, each mapping to discrete epitopes of Fc gamma RII. Cluster I (mAb 8.2 and CIKM5) defines a combinatorial epitope with determinants in D1 gamma and D2 gamma distant from the IgG Fc binding site, inasmuch as F(ab')2 fragments of 8.2 and CIKM5 do not inhibit the binding of EA to Fc gamma RII. The epitopes of clusters 2 (mAb 8.26), 3 (mAb IV.3), and 4 (mAb 8.7 and 7.30) are located entirely in D2 gamma and all involve the IgG Fc binding region, because F(ab')/F(ab')2 fragments of the mAb inhibit EA binding to Fc gamma RII. Thus, all mAb that inhibit the binding of EA map totally to D2 gamma; it is likely the IgG Fc binding region is also contained in D2 gamma.
[Correction of morphology and indicators of atrial function using long-term physiologic cardiac pacing in patients with prior chronic atrioventricular dissociation or VVI pacing]. (1999)

The authors provided evidence of the reversibility of the morphological and functional atrial damage and the favourable effect of atrioventricular synchronization on left ventricular function.
Monoclonal antibody analysis of keratin expression in epidermal diseases: a 48- and 56-kdalton keratin as molecular markers for hyperproliferative keratinocytes. (1984)

The polypeptide composition of epidermal keratin varies in disease. To better understand the biological meaning of these variations, we have analyzed keratins from a number of human epidermal diseases by the immunoblot technique using AE1 and AE3 monoclonal antikeratin antibodies. The results reveal a continuous spectrum of keratin expression ranging from one closely resembling the normal in vivo pattern to one almost identical to cultured epidermal keratinocytes. Specifically, a 50-kilodalton (kd) (AE1-positive) and a 58-kd (AE3-positive) keratin are present in all diseases, supporting the concept that they represent "permanent" markers for keratinocytes. A 56.5-kd (AE1) and a 65-67-kd (AE3) keratin, previously shown to be markers for keratinization, are expressed only by lesions retaining a keratinized morphology. A 48-kd (AE1) and a 56-kd (AE3) keratin are present in all hyperproliferative (para- or nonkeratinized) disorders, but not in normal abdominal epidermis or in ichthyosis vulgaris which is a nonhyperproliferative disease. These two keratins have previously been found in various nonepidermal keratinocytes undergoing hyperproliferation, suggesting that these keratins are not epidermis-specific and may represent markers for hyperproliferative keratinocytes in general. In various epidermal diseases, there is a reciprocal expression of the (keratin) markers for hyperproliferation and keratinization, supporting the mutual exclusiveness of the two cellular events. Moreover, our results indicate that, as far as keratin expression is concerned, cultured human epidermal cells resemble and thus may be regarded as a model for epidermal hyperplasia. Finally, the apparent lack of any major, disease-specific keratin changes in the epidermal disorders studied so far implies that keratin abnormalities probably represent the consequence, rather than the cause, of these diseases.
Isolation of a Natural Inhibitor of Human Malignant Glial Cell Invasion: Inter α-Trypsin Inhibitor Heavy Chain 2 (2006)

Malignant central nervous system (CNS) tumors, such as glioblastoma multiforme, invade the brain and disrupt normal tissue architecture, making complete surgical removal virtually impossible. Here, we have developed and optimized a purification strategy to isolate and identify natural inhibitors of glioma cell invasion in a three-dimensional collagen type I matrix. Inter alpha-trypsin inhibitor heavy chain 2 (ITI H2) was identified from the most inhibitory fractions and its presence was confirmed both as a single protein and in a bikunin-bound form. Stable overexpression in U251 glioma cells validated ITI H2's strong inhibition of human glioma cell invasion together with significant inhibition of cell proliferation and promotion of cell-cell adhesion. Analysis of primary human brain tumors showed significantly higher levels of ITI H2 in normal brain and low-grade tumors compared with high-grade gliomas, indicating an inverse correlation with malignancy. The phosphatidylinositol 3-kinase/Akt signaling cascade seemed to be one of the pathways involved in the effect of ITI H2 on U251 cells. These findings suggest that reduction of ITI H2 expression correlates with brain tumor progression and that targeting factors responsible for its loss or restoring the ITI supply exogenously may serve as potential therapeutic strategies for a variety of CNS tumors.
Stereochemistry of the hydrolysis of adenosine 5'-thiophosphate catalyzed by venom 5'-nucleotidase (1980)

The stereochemical problem involving a pro-pro-prochiral phosphorus center, the hydrolysis of adenosine 5'-monophosphate to adenosine and inorganic phosphate catalyzed by the venom 5'-nucleotidase, has been studied by use of chiral [16O, 17O, 18O]thiophosphates (Psi). (Rp)- and (Sp)-[alpha-18O1]Adenosine 5'-thiophosphates (AMPS) were synthesized by a combined chemical and biochemical procedure. Hydrolysis of (Rp)- and (Sp)-[alpha-18O1]AMPS in H217O by 5'-nucleotidase gave two enantiomers of chiral Psi of unknown configuration. A 31P NMR method based on the combination of the quadrupolar effect of 17O [Tsai, M.-D. (1979) Biochemistry 18, 1468-1472] and the 18O isotope shift [Cohn, M., & Hu. A. (1978) Proc. Natl. Acad. Sci. U.S.A. 75, 200-203] has been developed to analyze the configuration of chiral Pso. The results indicate that hydrolysis of (Rp)- and (Sp)-[alpha-18O1]AMPS in H217O gave (R)- and (S)- [16O, 17O, 18O]Psi, respectively. Therefore the hydrolysis of AMPS catalyze by the venom 5'-nucleotidase must proceed with inversion of configuration at phosphorus, which suggests that the reaction is most likely an "in line" single displacement without involving a phosphoryl-enzyme intermediate and without pseudorotation.