gebhart/patrepeval huggingface dataset:
Fibrosis and ischemia: the real risks in hypertensive heart disease (2001)

The increased cardiovascular morbidity and mortality in hypertension are related to the target organs (ie, heart, brain, kidneys) involvement from vascular disease. Left ventricular hypertrophy (LVH), the major expression of cardiac involvement, is both a structural and functional adaptation to the afterload imposed by the vascular disease. Without this adaptation, cardiac failure would result much earlier in the natural history of hypertensive heart disease (HHD). However, LVH imposes an independent risk that is even greater than the risk associated with the height of systolic or diastolic pressure. The mechanisms that explain this risk have not been defined precisely; several have been postulated. Among these are the following: 1) coronary hemodynamic alterations associated with HHD (ie, increased coronary vascular and minimal vascular resistance, reduced coronary blood flow and flow reserve, and increased blood viscosity); 2) enhanced predisposition for lethal cardiac arrhythmias, cardiac failure, and accelerated atherosclerosis of the coronary arteries (with exacerbation of the ischemia); and 3) collagen deposition and ventricular fibrosis. From the earliest controlled therapeutic trials, deaths from stroke and coronary heart disease were significantly reduced. However, more recent data have indicated that the prevalence of cardiac failure (CHF) continues to rise progressively. The nature of the CHF is no longer primarily from systolic dysfunction, but is now chiefly from diastolic dysfunction. Diastolic dysfunction occurs primarily in the elderly hypertensive patient or in the patient with ischemic heart disease, both of which are associated with increased collagen deposition. Indeed, these effects continue to be suggested by the data from the Framingham Heart Study as well as NHANES-III that indicate CHF is the most common diagnosis occurring in hospitalized patients over 65 years of age. In this report, both experimental and clinical evidence demonstrating that increased ventricular fibrosis occurs in the spontaneously hypertensive rats and in hypertensive patients are provided, and that treatment with the newer antihypertensive agents reduce ventricular hydroxyproline (ie, collagen) content while, at the same time, improve coronary hemodynamics.
Protection of erythrocytes against hemolytic agents by cyclodextrin polysulfate (1993)

Cyclodextrins generally exhibit hemolytic activity, some at concentrations as low as 1-10 mg/mL or lower. However, we found previously that a highly polysulfated cyclodextrin has no demonstrable hemolytic activity (Macarak et al., Biochem Pharmacol 42: 1502-1503, 1991). In the present study, we determined that, in fact, cyclodextrin polysulfate (CDS) actively protected erythrocytes against hemolysis induced by a wide spectrum of hemolytically active substances, ranging from pharmaceuticals, such as chlorpromazine, to solid suspensions of siliceous particles. The protective action was also effective against the hemolytic action of non-sulfated cyclodextrins. The similar kinetic responses of the erythrocytes to CDS protection against such chemically and structurally diverse hemolytic agents suggest a common mechanism involving the cell. Addition of the sulfated cyclodextrins to other cyclodextrin compounds used to solubilize poorly soluble pharmaceutical agents can extend the allowable maximum dosage without deleterious hemolytic action.
Thyroid Hormone and Adipocyte Differentiation (2008)

Thyroid hormones act as pleiotropic factors in many tissues during development, by regulating genes involved in differentiation. The adipose tissue, a target of thyroid hormones, is the main place for energy storage and acts as a regulator of energy balance, sending signals to keep metabolic control. Adipogenesis is a complex process that involves proliferation of preadipocytes and its differentiation into mature adipocytes. This process is regulated by several transcription factors (CCAAT/enhancer-binding proteins [C/EBPs], peroxisome proliferator-activated receptors [PPARs]) that act coordinately, activating adipocyte-specific genes that will provide the adipocytic phenotype. Thyroid hormones regulate many of those genes, markers of differentiation of adipocytes, those involved in lipogenesis, lipolysis, and thermogenesis in the brown adipose tissue (BAT). Triiodothyronine (T3) actions are achieved either directly through specific thyroid response elements (TREs), by regulating other key genes as PPARs, or through specific isoforms of the nuclear T3 receptors. The availability of T3 is regulated through the deiodinases D3, D2, and D1. D3 is activated by serum and mitogens during proliferation of preadipocytes, while D2 is linked to the differentiation program of adipocytes, through the C/EBPs that govern its functionality, providing the T3 required for thermogenesis and lipogenesis. The relationship between white adipose tissue (WAT) and BAT and the possible reactivation of WAT by activation of uncoupling protein-1 (UCP1) is discussed.
Gas‐holdup measurements in bubble columns using computed tomography (1997)

Abstract A computed tomographic scanner was developed for imaging gas‐holdup distributions in two‐phase flow systems such as bubble columns and fluidized beds. The scanner has been used to study the effects of various operating parameters (such as column diameter, superficial gas velocity, and distributor type) on the gas holdup and its distribution in an air–water bubble column. The experimental investigation shows that the column dimensions have no significant effect on the void fraction when the column diameter is greater than 0.15 m. Differences in the holdup distribution due to the kind of distributor used are significant only at low gas flow rates. Surface tension of the liquid has a profound influence on the gas holdup and its distribution.
Ketohexokinase: Expression and Localization of the Principal Fructose-metabolizing Enzyme (2009)

Ketohexokinase (KHK, also known as fructokinase) initiates the pathway through which most dietary fructose is metabolized. Very little is known about the cellular localization of this enzyme. Alternatively spliced KHK-C and KHK-A mRNAs are known, but the existence of the KHK-A protein isoform has not been demonstrated in vivo. Using antibodies to KHK for immunohistochemistry and Western blotting of rodent tissues, including those from mouse knockouts, coupled with RT-PCR assays, we determined the distribution of the splice variants. The highly expressed KHK-C isoform localized to hepatocytes in the liver and to the straight segment of the proximal renal tubule. In both tissues, cytoplasmic and nuclear staining was observed. The KHK-A mRNA isoform was observed exclusively in a range of other tissues, and by Western blotting, the presence of endogenous immunoreactive KHK-A protein was shown for the first time, proving that the KHK-A mRNA is translated into KHK-A protein in vivo, and supporting the suggestion that this evolutionarily conserved isoform is physiologically functional. However, the low levels of KHK-A expression prevented its immunohistochemical localization within these tissues. Our results highlight that the use of in vivo biological controls (tissues from knockout animals) is required to distinguish genuine KHK immunoreactivity from experimental artifact.
Noncontact imaging photoplethysmography to effectively access pulse rate variability (2012)

Noncontact imaging photoplethysmography (PPG) can provide physiological assessment at various anatomical locations with no discomfort to the patient. However, most previous imaging PPG (iPPG) systems have been limited by a low sample frequency, which restricts their use clinically, for instance, in the assessment of pulse rate variability (PRV). In the present study, plethysmographic signals are remotely captured via an iPPG system at a rate of 200 fps. The physiological parameters (i.e., heart and respiration rate and PRV) derived from the iPPG datasets yield statistically comparable results to those acquired using a contact PPG sensor, the gold standard. More importantly, we present evidence that the negative influence of initial low sample frequency could be compensated via interpolation to improve the time domain resolution. We thereby provide further strong support for the low-cost webcam-based iPPG technique and, importantly, open up a new avenue for effective noncontact assessment of multiple physiological parameters, with potential applications in the evaluation of cardiac autonomic activity and remote sensing of vital physiological signs.
Relaxivity‐iron calibration in hepatic iron overload: Probing underlying biophysical mechanisms using a Monte Carlo model (2010)

Iron overload is a serious condition for patients with β-thalassemia, transfusion-dependent sickle cell anemia, and inherited disorders of iron metabolism. MRI is becoming increasingly important in noninvasive quantification of tissue iron, overcoming the drawbacks of traditional techniques (liver biopsy). Effective transverse relaxation rate (1/effective transverse relaxation time) rises linearly with iron while transverse relaxation rate (1/T2) has a curvilinear relationship in human liver. Although recent work has demonstrated clinically valid estimates of human liver iron, the calibration varies with MRI sequence, field strength, iron chelation therapy, and organ imaged, forcing recalibration in patients. To understand and correct these limitations, a thorough understanding of the underlying biophysics is of critical importance. Toward this end, a Monte Carlo-based approach, using human liver as a "model" tissue system, was used to determine the contribution of particle size and distribution on MRI signal relaxation. Relaxivities were determined for hepatic iron concentrations ranging from 0.5 to 40 mg iron per gram dry tissue weight. Model predictions captured the linear and curvilinear relationship of effective transverse relaxation rate and transverse relaxation rate with hepatic iron concentrations, respectively, and were within in vivo confidence bounds; contact or chemical exchange mechanisms were not necessary. A validated and optimized model will aid understanding and quantification of iron-mediated relaxivity in tissues where biopsy is not feasible (heart and spleen).
Logic Partitioning for Minimizing Gate Arrays (1983)

This paper describes a procedure for partitioning logic to minimize the number of gate arrays required to implement the logic. The procedure consists of three algorithms to perform initial, iterative, and interactive logic partitioning. Results are presented using three different logic circuits ranging in size from 14 000 gates to 26 000 gates.
Correlation of cathodoluminescence inhomogeneity with microstructural defects in epitaxial GaN grown by metalorganic chemical-vapor deposition (1997)

We discuss the relationship between microstructure and luminescence efficiency for heteroepitaxial films of GaN grown on c-axis sapphire substrates by metalorganic chemical-vapor deposition. We directly characterize the correlation between threading dislocations as observed by transmission electron microscopy, surface morphology as observed by atomic force microscopy, and wavelength-resolved cathodoluminescence imaging. We show that the inhomogeneity in the luminescence intensity of these films near band edge can be accounted for by a simple model where nonradiative recombination at threading dislocations causes a deficiency of minority carriers and results in dark regions of the epilayer. An upper bound for average diffusion length is estimated to be 250 nm.
Long-Term Exposure of Human Blood Vessels to HIV gp120, Morphine, and Anandamide Increases Endothelial Adhesion of Monocytes: Uncoupling of Nitric Oxide Release (1998)

Acute exposure of human saphenous vein or internal thoracic artery endothelium to either morphine [27.4 +/- 3.7 and 35.4 +/- 4.1 nM nitric oxide (NO), respectively] or anandamide (18.3 +/- 2.2 and 24.3 +/- 3.0 nM, respectively) results in NO release, whereas exposure to the human immunodeficiency virus envelope protein gp120 does not. After the short-term exposure of the vessel endothelium, monocyte adherence is diminished with morphine and anandamide treatment (jointly by -80%), whereas it is enhanced with that of gp120 (approximately 40%), indicating that gp120 enhances the ability of the endothelium to adhere monocytes. Long-term or continuous exposure of the endothelia to all agents results in a significant enhancement of monocyte adherence (p < 0.05), which is further increased when exposed to either morphine and anandamide plus gp120. This is caused by a desensitization of the endothelium to further NO release after the initial exposure to either anandamide or morphine. The results serve to indicate that in individuals abusing opiates and or cannabinoids, a tissue [i.e., central nervous system (CNS)] viral load may be higher, and acquired immunodeficiency syndrome (AIDS) may progress more rapidly because monocyte adherence and mobility is significantly increased, indicating a higher level of transmembrane migration.
Termination of immediate-early gene expression after stimulation by parathyroid hormone or isoproterenol (2002)

cAMP/PKA signaling transiently stimulates mRNA expression of immediate-early genes, including IL-6 and c-fos. We confirmed that these mRNAs are transiently stimulated by parathyroid hormone (PTH) in ROS 17/2.8 osteoblastic cells. Consistent with the role for cAMP/PKA signaling in this response, PTH induces transient cAMP elevation, PKA activation, and cAMP-responsive element-binding protein (CREB) phosphorylation. Our goal was to determine whether termination of immediate-early gene expression is due to receptor desensitization or cAMP degradation. The approaches used were 1) inhibition of PTH receptor desensitization with G protein-coupled receptor kinase 2 (GRK2) antisense oligonucleotides or antisense plasmids, 2) sustained activation of adenyl cyclase with forskolin, and 3) inhibition of cAMP degradation with 3-isobutyl-1-methylxanthine. These experiments show that mechanisms downstream of receptor desensitization and cAMP degradation are primarily responsible for termination of PKA activity, CREB phosphorylation, and immediate-early gene expression. Similar conclusions were also obtained in response to PTH in a second osteoblastic cell line (MC3T3-E1) and in response to isoproterenol in NIH3T3 fibroblasts. This conclusion may therefore reflect a general mechanism for termination of immediate-early gene expression after induction by cAMP/PKA.
Renal Denervation Prevents and Reverses Hyperinsulinemia-Induced Hypertension in Rats (1998)

Experiments were performed to evaluate the role of the renal nerves in hyperinsulinemia-induced hypertension. Male Sprague-Dawley rats were made hyperinsulinemic by insulin infusion via osmotic minipumps implanted subcutaneously (3.0 mU/kg per minute for 6 weeks). Rats with vehicle infusion served as controls. Bilateral renal denervation was performed either at the beginning of or 4 weeks after insulin infusion. The systolic blood pressure was measured by the tail-cuff method twice a week. Food and water intake and urine flow were measured daily. The results showed that sustained insulin infusion significantly increased plasma insulin concentrations from 277.7+/-25.8 pmol/L to 609.9+/-22.2 and 696.7+/-23.0 pmol/L by the end of weeks 4 and 6, respectively (P<0.05). Systolic blood pressure was significantly increased from 135+/-3 to 157+/-3 and 159+/-2 mm Hg (P<0.05) at the corresponding time points. There was a significant increase in the plasma norepinephrine concentration after insulin infusion, whereas no significant changes in plasma triglyceride and glucose concentrations, water intake, urine flow, sodium excretion, sodium gain, and body weight gain were observed. Bilateral renal denervation depleted renal norepinephrine stores and prevented the development of hyperinsulinemia-induced hypertension. After hyperinsulinemia-induced hypertension had been fully established (from 134+/-2 to 157+/-2 mm Hg), bilateral renal denervation reversed the elevated systolic blood pressure to normotensive levels within 2 weeks. Transient denervated diuresis and natriuresis were observed. These results indicate that chronic hyperinsulinemia-induced hypertension requires the presence of intact renal nerves in rats.
Histone Deacetylase Inhibitors in Cancer Therapy: Latest Developments, Trends and Medicinal Chemistry Perspective (2007)

Regulation of gene expression is mediated by several mechanisms such as DNA methylation, ATP-dependent chromatin remodeling, and post-translational modifications of histones. The latter mechanism includes dynamic acetylation and deacetylation of epsilon-amino groups of lysine residues present in the tail of the core histones. Enzymes responsible for the reversible acetylation/deacetylation processes are histone acetyltransferases (HATs) and histone deacetylases (HDACs), respectively. There are three mammalian HDAC families, namely HDACs I, II and III based on their sequence homology. Inhibitors of HDACs induce hyperacetylation of histones that modulate chromatin structure and gene expression resulting in growth arrest, cell differentiation, and apoptosis of tumor cells. In addition, HDAC inhibitors enhance efficacy of anticancer agents that target DNA. Several formidable challenges associated with their development include non-specific toxicity and poor PK properties, including cell permeability. In this review, we comment on the current progress in design, discovery, in vitro/ex vivo activity and clinical potential of the synthetic modulators of HDACs.
Synthesis of a Perylene Diimide Dimer with Pyrrolic N–H Bonds and N‐Functionalized Derivatives for Organic Field‐Effect Transistors and Organic Solar Cells (2018)

This study reports on the new and optimized synthesis of an N‐annulated perylene diimide dimer with functional N–H moieties. The presence of two N–H moieties renders the dimer relatively insoluble in most organic solvents. The dimer is easily functionalized with electron donating hexyl chains or electron withdrawing tert ‐butyloxycarbonyl (tBOC) groups to yield highly soluble materials. The tBOC groups can be thermally cleaved in the thin film to give the parent dimer. The N–H bonds are acidic and interact with volatile organic bases. Deprotonation results in a color change from red to blue. All compounds have utility as electron transport materials in organic field‐effect transistors and green solvent, air processed organic solar cells. Electron mobilities were on the order of about 2–7 × 10 –6 cm 2 /V s. Solar cell power conversion efficiency reached 2 % for those using the tBOC functionalized dimer, 3 % for those using the H‐atom functionalized dimer, and 6 % for those using the hexyl chain functionalized dimer. The performance of the latter is quite impressive considering the simple materials synthesis and greener solar cell processing.
Oxytricha telomere-binding protein: separable DNA-binding and dimerization domains of the alpha-subunit. (1993)

A telomere-binding protein heterodimer of 56-kD (alpha) and 41-kD (beta) subunits binds to the single-stranded (T4G4)2 terminus of each Oxytricha nova macronuclear DNA molecule. The alpha-subunit by itself binds to telomeric DNA. The beta-subunit alone does not bind to DNA specifically but interacts with the alpha-subunit to form a very stable ternary complex. We show that the formation of alpha-beta-DNA ternary complex is extremely cooperative. Furthermore, the binary complex (alpha-DNA) has a dissociation half-life of much less than 1 min; addition of the beta-subunit increases the half-life to approximately 100 hrs. Libraries of plasmids with random deletions of the open reading frame for the alpha-subunit were introduced into Escherichia coli, and extracts were subsequently checked for both protein expression and DNA-binding activity with or without added beta-subunit. The alpha-subunit was found to contain two structurally separable domains with distinct functions. The amino-terminal two-thirds is necessary and sufficient for sequence-specific DNA binding. The carboxy-terminal one-third is responsible for alpha/beta-subunit interactions. When expressed separately in E. coli, purified, and mixed together, these two domains reconstitute the activity of the wild-type alpha-subunit (trans-complementation in vitro). The amino-terminal two-thirds of the beta-subunit is necessary and sufficient both for alpha/beta-subunit interactions and for ternary complex formation. We conclude that the alpha-subunit of the telomere-binding protein, like many transcription factors, has separable DNA-binding and protein-protein interaction domains.
Pharmacological and toxicological properties of Nigella sativa (2003)

The seeds of Nigella sativa Linn. (Ranunculaceae), commonly known as black seed or black cumin, are used in folk (herbal) medicine all over the world for the treatment and prevention of a number of diseases and conditions that include asthma, diarrhoea and dyslipidaemia. This article reviews the main reports of the pharmacological and toxicological properties of N. sativa and its constituents. The seeds contain both fixed and essential oils, proteins, alkaloids and saponin. Much of the biological activity of the seeds has been shown to be due to thymoquinone, the major component of the essential oil, but which is also present in the fi ed oil. The pharmacological actions of the crude extracts of the seeds (and some of its active constituents, e.g. volatile oil and thymoquinone) that have been reported include protection against nephrotoxicity and hepatotoxicity induced by either disease or chemicals. The seeds/oil have antiinflammatory, analgesic, antipyretic, antimicrobial and antineoplastic activity. The oil decreases blood pressure and increases respiration. Treatment of rats with the seed extract for up to 12 weeks has been reported to induce changes in the haemogram that include an increase in both the packed cell volume (PCV) and haemoglobin (Hb), and a decrease in plasma concentrations of cholesterol, triglycerides and glucose. The seeds are characterized by a very low degree of toxicity. Two cases of contact dermatitis in two individuals have been reported following topical use. Administration of either the seed extract or its oil has been shown not to induce significant adverse effects on liver or kidney functions. It would appear that the beneficial effects of the use of the seeds and thymoquinone might be related to their cytoprotective and antioxidant actions, and to their effect on some mediators of inflammation.
CMOS front end components for micropower RF wireless systems (1998)

New applications have recently appeared for a low power, low cost, “embedded radio”. These wireless interfaces for handheld mobile nodes and Wireless Integrated Network Sensors (WINS) must provide spread spectrum signaling for multi-user operation at 902-928 MHz. Cost considerations motivate the development of complete micropower CMOS RF systems operating at previously unexplored low power levels. Micropower CMOS VCO and mixer circuits, developed for these emerging narrow-band communication systems, are reported here. Design methods combining high-Q inductors and weak inversion MOSFET operation enable the lowest reported operating power for RF front end components including a voltage-controlled oscillator (VCO) and mixer operating at frequencies of 400 MHz — 1 GHz. In addition, the VCO, by virtue of its high-Q inductive components, displays the lowest reported phase noise for 1 GHz CMOS VCO system for any power dissipation.