Miracle-dz/UniFAR-FTUs huggingface dataset:
Type 2 Diabetic Rats on Diet Supplemented With Chromium Malate Show Improved Glycometabolism, Glycometabolism-Related Enzyme Levels and Lipid Metabolism

Our previous study showed that chromium malate improved the regulation of blood glucose in mice with alloxan-induced diabetes. The present study was designed to evaluate the effect of chromium malate on glycometabolism, glycometabolism-related enzymes and lipid metabolism in type 2 diabetic rats. Our results showed that fasting blood glucose, serum insulin level, insulin resistance index and C-peptide level in the high dose group had a significant downward trend when compared with the model group, chromium picolinate group and chromium trichloride group. The hepatic glycogen, glucose-6-phosphate dehydrogenase, glucokinase, Glut4, phosphor-AMPKβ1 and Akt levels in the high dose group were significantly higher than those of the model, chromium picolinate and chromium trichloride groups. Chromium malate in a high dose group can significantly increase high density lipoprotein cholesterol level while decreasing the total cholesterol, low density lipoprotein cholesterol and triglyceride levels when compared with chromium picolinate and chromium trichloride. The serum chromium content in chromium malate and chromium picolinate group is significantly higher than that of the chromium trichloride group. The results indicated that the curative effects of chromium malate on glycometabolism, glycometabolism-related enzymes and lipid metabolism changes are better than those of chromium picolinate and chromium trichloride. Chromium malate contributes to glucose uptake and transport in order to improved glycometabolism and glycometabolism-related enzymes.
Immunolocalization of cannabinoid receptor type 1 and CB2 cannabinoid receptors, and transient receptor potential vanilloid channels in pterygium

Cannabinoids, as multi-target mediators, activate cannabinoid receptors and transient receptor potential vanilloid (TRPV) channels. There is evidence to support a functional interaction of cannabinoid receptors and TRPV channels when they are coexpressed. Human conjunctiva demonstrates widespread cannabinoid receptor type 1 (CB1), CB2 and TRPV channel localization. The aim of the present study was to investigate the expression profile for cannabinoid receptors (CB1 and CB2) and TRPV channels in pterygium, an ocular surface lesion originating from the conjunctiva. Semi-serial paraffin-embedded sections from primary and recurrent pterygium samples were immunohistochemically examined with the use of specific antibodies. All of the epithelial layers in 94, 78, 96, 73 and 80% of pterygia cases, exhibited CB1, CB2, TRPV1, TRPV2 and TRPV3 cytoplasmic immunoreactivity, respectively. The epithelium of all pterygia cases (100%) showed strong, mainly nuclear, TRPV4 immunolocalization. In the pterygium stroma, scattered cells demonstrated intense CB2 immunoreactivity, whereas vascular endothelial cells were immunopositive for the cannabinoid receptors and all TRPV channels. Quantitative analyses of the immunohistochemical findings in epithelial cells demonstrated a significantly higher expression level in conjunctiva compared with primary pterygia (P=0.04) for CB1, but not for CB2 (P>0.05). Additionally, CB1 and CB2 were significantly highly expressed in primary pterygia (P=0.01), compared with recurrent pterygia. Furthermore, CB1 expression levels were significantly correlated with CB2 expression levels in primary pterygia (P=0.005), but not in recurrent pterygia (P>0.05). No significant difference was detected for all TRPV channel expression levels between pterygium (primary or recurrent) and conjunctival tissues (P>0.05). A significant correlation between the TRPV1 and TRPV3 expression levels (P<0.001) was detected independently of pterygium recurrence. Finally, TRPV channel expression was identified to be significantly higher than the expression level of cannabinoid receptors in the pterygium samples (P<0.001). The differentiated expression of cannabinoid receptors in combination with the presence of TRPV channels, in primary and recurrent pterygia, imply a potential role of these cannabinoid targets in the underlying mechanisms of pterygium.
Comparison of inhibin B and estradiol responses to intravenous FSH in women with polycystic ovary syndrome and normal women.

BACKGROUND Inhibin B (Inh B) is produced by pre-antral and early antral follicles whereas estradiol (E(2)) is a product of follicles undergoing antrum formation. This temporal distinction is evident in the patterns of Inh B and E(2) release earlier and later during the follicular phase of the menstrual cycle, respectively. However, in previous studies of women with polycystic ovary syndrome (PCOS) and normal controls, release of these granulosa cell (GC) products appears to be simultaneous in response to FSH stimulation. In order to reconcile these disparate findings, we conducted dose-response studies in both PCOS women and normal controls to determine whether GC product responses were due to the amount of FSH administered. In addition, we compared FSH-stimulated responses in PCOS women at various stages of recovery following ovarian suppression with a long-acting GnRH agonist to examine whether Inh B and E(2) responses reflected the level of ovarian follicle activity (i.e. circulating E(2) levels). METHODS Women with PCOS, 18-35 years (n = 23), and normal ovulatory controls, 18-35 years (n = 10) were recruited for study. Dose-responses were assessed over 24 h following intravenous administration of 0 (saline), 37.5, 75 and 150 IU of recombinant human FSH (r-hFSH) in PCOS and normal women. In addition, E(2) and Inh B responses to 150 IU of r-hFSH were assessed at baseline and 4, 6 and 8 weeks following suppression of ovarian steroidogenesis by a long-acting GnRH agonist in PCOS women. RESULTS In PCOS women and normal controls, serum Inh B and E(2) exhibit similar and simultaneous dose-responsiveness to FSH stimulation. During recovery from ovarian suppression, basal and stimulated Inh B release appear to be restored earlier than that of E(2) in PCOS women. CONCLUSIONS These findings are consistent with the notion that, in PCOS women, the level of ovarian follicle activity largely determines the earlier release of Inh B compared with E(2).
Mitochondrion as a Novel Site of Dichloroacetate Biotransformation by Glutathione Transferase ζ1

Dichloroacetate (DCA) is a potential environmental hazard and an investigational drug. Repeated doses of DCA result in reduced drug clearance, probably through inhibition of glutathione transferase ζ1 (GSTZ1), a cytosolic enzyme that converts DCA to glyoxylate. DCA is known to be taken up by mitochondria, where it inhibits pyruvate dehydrogenase kinase, its major pharmacodynamic target. We tested the hypothesis that the mitochondrion was also a site of DCA biotransformation. Immunoreactive GSTZ1 was detected in liver mitochondria from humans and rats, and its identity was confirmed by liquid chromatography/tandem mass spectrometry analysis of the tryptic peptides. Study of rat submitochondrial fractions revealed GSTZ1 to be localized in the mitochondrial matrix. The specific activity of GSTZ1-catalyzed dechlorination of DCA was 2.5- to 3-fold higher in cytosol than in whole mitochondria and was directly proportional to GSTZ1 protein expression in the two compartments. Rat mitochondrial GSTZ1 had a 2.5-fold higher AppKm for glutathione than cytosolic GSTZ1, whereas the AppKm values for DCA were identical. Rats administered DCA at a dose of 500 mg/kg/day for 8 weeks showed reduced hepatic GSTZ1 activity and expression of ∼10% of control levels in both cytosol and mitochondria. We conclude that the mitochondrion is a novel site of DCA biotransformation catalyzed by GSTZ1, an enzyme colocalized in cytosol and mitochondrial matrix.
A Design-Oriented Combined Approach for Bifurcation Prediction in Switched-Mode Power Converters

In this brief, two different approaches are combined for studying the stability of a buck switching power dc-dc converter and for predicting its bifurcations. Instability indexes derived from both approaches are combined to get a complete design-oriented perspective of bifurcation analysis in terms of practical circuit parameter and to show the effect of each parameter on the system behavior. The first approach is based on the conventional Routh-Hurwitz criterion applied to the averaged converter dynamics, and it is suitable for detecting low-frequency oscillations but is unsuitable for predicting fast-scale period-doubling instabilities. Complementarily, the second approach considers the ripple component before the pulsewidth modulator to quantitatively predict the occurrence of subharmonic oscillations. The usefulness of the combined approach is shown by analytically deriving inequalities that compress the complete design space into simple instability indexes, which, used complementarily, allow a division of the design space into the different instability regions (both period-doubling or fast-scale instability, and Hopf or slow-scale instability). Comparison of the design-oriented complete map obtained combining both methods and their related stability indexes with the results obtained both from time-domain numerical simulations of the exact switched state equations, as well as the stability border obtained from discrete recurrent maps, corroborates the approach.
Spectral balancing techniques application to CDMA and UWB signaling

This paper presents techniques for generating orthogonal bases of signals with jointly optimized spectra, in the sense that they are made as close as possible. To this end, we propose new criteria, the minimization of which leads to signals with close energy inside a set of prescribed subbands. We present a first algorithm that performs this spectrum balancing and that we apply to Walsh-Hadamard codes. As an example, we build balanced Walsh codes in CDMA comunications. Alternatively, we propose another way to perform spectrum balancing in two steps and that makes use of joint diagonalization techniques. As an example application, we show how balancing of Prolate Spheroidal Wave Functions (PSWFs) can be used to build orthogonal families of brief impulses with flat spectra that are of potential interest for Ultra Wide Band (UWB) communications.
A decade of direct-to-consumer advertising of prescription drugs.

BACKGROUND Evidence suggests that direct-to-consumer advertising of prescription drugs increases pharmaceutical sales and both helps to avert underuse of medicines and leads to potential overuse. Concern about such advertising has increased recently owing to the withdrawal from the market of heavily advertised drugs found to carry serious risks. Moreover, the Food and Drug Administration (FDA) has been criticized for its weak enforcement of laws regulating such advertising. METHODS We examined industry-wide trends in spending by pharmaceutical companies on direct-to-consumer advertising and promotion to physicians during the past decade. We characterized the drugs for which such advertising is used and assessed the timing of advertising after a drug is introduced. Finally, we examined trends in the FDA's regulation of drug advertising. RESULTS Total spending on pharmaceutical promotion grew from $11.4 billion in 1996 to $29.9 billion in 2005. Although during that time spending on direct-to-consumer advertising increased by 330%, it made up only 14% of total promotional expenditures in 2005. Direct-to-consumer campaigns generally begin within a year after the approval of a product by the FDA. In the context of regulatory changes requiring legal review before issuing letters, the number of letters sent by the FDA to pharmaceutical manufacturers regarding violations of drug-advertising regulations fell from 142 in 1997 to only 21 in 2006. CONCLUSIONS Spending on direct-to-consumer advertising has continued to increase in recent years in spite of the criticisms leveled against it. Our findings suggest that calls for a moratorium on such advertising for new drugs would represent a dramatic departure from current practices.
Hypothyroidism in coronary heart disease and its relation to selected risk factors

Introduction Hypothyroidism (HT) has been found a predictor of cardiovascular diseases. We aimed to ascertain the prevalence of HT in patients with manifest coronary heart disease (CHD), and to establish its association with conventional risk factors. Methods 410 patients, 6–24 months after hospitalization for acute coronary syndrome, and/or revascularization, were included into the cross-sectional study. Results The prevalence of thyroid dysfunction was found in males and females as follows: overt HT, ie, thyroid stimulating hormone (TSH) > 3.65 mIU/L and free thyroxine (fT4) < 9 pmol/L and/or L-thyroxine substitution, in 2.6% and 8.4%, respectively; subclinical HT (TSH >3.65, fT4 9–23 and no substitution) in 4.3% and 15.0%, respectively. Higher prevalence of HT was found in females with hypercholesterolemia, and in males and females with concomitant positive thyroid peroxydase antibodies. Hypothyroid subjects had higher total homocysteine in both genders and von Willebrand factor in males only. Hypothyroid females had higher total and LDL cholesterol, and were more often treated for diabetes. Conclusions HT was found highly prevalent in patient with clinical coronary heart disease, mainly in females, and was associated with several cardiovascular risk factors.
Fermentation kinetics of Zymomonas mobilis at high ethanol concentrations: Oscillations in continuous cultures

Substrate‐limited continuous culture results at 47 g/L ethanol show that the maintenance factor and the yield factor of an unstructured maintenance model are lower compared to the values at 23 g/L ethanol. Computing the results according to a structured two‐compartment model predicts an enhanced turnover rate of the K‐compartment (RNA fraction) by ethanol, resulting in a lower steady‐state amount of K‐compartment. This is in agreement with experimentally determined RNA fractions. The parameters of both models respond qualitatively in the same way to elevation of the ethanol concentration as to elevation of the temperature. In product‐inhibited continuous cultures, at ethanol concentrations above 55 g/L, nearly sustained oscillations in biomass, substrate, and products were observed. The maximum ethanol concentration achieved in these continuous cultures was 70 g/L. The oscillations could be described by a structured mathematical model, in which ethanol inhibits the maximum specific growth rate indirectly by inhibiting the synthesis of an internal growth‐rate‐determining compound.
The Effect of Mesh Resolution on Convective Boundary Layer Statistics and Structures Generated by Large-Eddy Simulation

AbstractA massively parallel large-eddy simulation (LES) code for planetary boundary layers (PBLs) that utilizes pseudospectral differencing in horizontal planes and solves an elliptic pressure equation is described. As an application, this code is used to examine the numerical convergence of the three-dimensional time-dependent simulations of a weakly sheared daytime convective PBL on meshes varying from 323 to 10243 grid points. Based on the variation of the second-order statistics, energy spectra, and entrainment statistics, LES solutions converge provided there is adequate separation between the energy-containing eddies and those near the filter cutoff scale. For the convective PBL studied, the majority of the low-order moment statistics (means, variances, and fluxes) become grid independent when the ratio zi/(CsΔf) > 310, where zi is the boundary layer height, Δf is the filter cutoff scale, and Cs is the Smagorinsky constant. In this regime, the spectra show clear Kolmogorov inertial subrange scaling.
Generation of dendritic cell‐like antigen‐presenting cells in long‐term mixed leucocyte culture: phenotypic and functional studies

The mechanisms contributing to the proliferation and differentiation of antigen‐presenting cell (APC) precursors upon antigen stimulation or tissue injury are poorly understood. Herein, we report the induction of a population of dendritic cell‐like cells (DLC) with potent antigen‐presentation function from unfractionated spleen cells by means of repetitive allostimulation in long‐term mixed leucocyte cultures (LT‐MLC). Initially, only a few adherent DLC were observed. By 4–6 weeks, however, there were large numbers of DLC which survived persistently. Features of these DLC are closely related to dendritic cells (DC), including: (1) dendritic, veiled or spiny‐processed morphology; (2) expression of a wide array of leucocyte surface markers including DC‐associated or restricted antigens: 33D1, NLDC‐145, CD11c (N418), heat‐stable antigen (HSA), CD44, B7‐1 and B7‐2; (3) ability to migrate to draining lymph nodes and white pulp area of spleen; (4) expression of high level of major histocompatability complex (MHC) class II molecules and (5) more potent mixed leucocyte reaction (MLR)‐stimulating capacity than peritoneal macrophages and APC‐enriched spleen cells. DLC‐stimulated MLR was inhibited by monoclonal antibodies (mAbs) to B7‐1, B7‐2, intracellular adhesion molecule‐1 (ICAM‐1), vascular cell adhesion molecule‐1 (VCAM‐1), leucocyte‐function associated antigen‐1 (LFA‐1) or very‐late activation antigen‐4 (VLA‐4) by 30–55%. When maintained for more than 2 months, the DLC did not lose their MLR‐stimulating activity, but many surface markers were down‐regulated except for Mac‐2 and VCAM‐1, which remained stable or were up‐regulated, respectively. In short‐term culture, the addition of granulocyte–macrophage colony‐stimulating factor (GM‐CSF) or interleukin (IL)‐2 enhanced proliferation of DLC, while tumour necrosis factor‐α (TNF‐α) and IL‐4 did not. IL‐4 suppressed not only ‘spontaneous’, but also GM‐CSF‐enhanced proliferation, suggesting that cytokines play a differential role in DLC proliferation. These results confirm that professional APC can proliferate in response to repetitive antigen stimulation, and their proliferation is differentially regulated by cytokines. A comparison study of DLC with typical DC is being carried out in our laboratory.
Robust statistical modelling using the multivariate skew t distribution with complete and incomplete data

Missing data is inevitable in many situations that could hamper data analysis for scientific investigations. We establish flexible analytical tools for multivariate skew t models when fat-tailed, asymmetric and missing observations simultaneously occur in the input data. For the ease of computation and theoretical developments, two auxiliary indicator matrices are incorporated into the model for the determination of observed and missing components of each observation that can effectively reduce the computational complexity. Under the missing at random assumption, we present a Monte Carlo version of the expectation conditional maximization algorithm, which is performed to estimate the parameters and retrieve each missing observation with a single value. Additionally, a Metropolis–Hastings within Gibbs sampler with data augmentation is developed to account for the uncertainty of parameters as well as missing outcomes. The methodology is illustrated through two real data sets.
Wide-field motion tuning in nocturnal hawkmoths

Nocturnal hawkmoths are known for impressive visually guided behaviours in dim light, such as hovering while feeding from nectar-bearing flowers. This requires tight visual feedback to estimate and counter relative motion. Discrimination of low velocities, as required for stable hovering flight, is fundamentally limited by spatial resolution, yet in the evolution of eyes for nocturnal vision, maintenance of high spatial acuity compromises absolute sensitivity. To investigate these trade-offs, we compared responses of wide-field motion-sensitive neurons in three species of hawkmoth: Manduca sexta (a crepuscular hoverer), Deilephila elpenor (a fully nocturnal hoverer) and Acherontia atropos (a fully nocturnal hawkmoth that does not hover as it feeds uniquely from honey in bees' nests). We show that despite smaller eyes, the motion pathway of D. elpenor is tuned to higher spatial frequencies and lower temporal frequencies than A. atropos, consistent with D. elpenor's need to detect low velocities for hovering. Acherontia atropos, however, presumably evolved low-light sensitivity without sacrificing temporal acuity. Manduca sexta, active at higher light levels, is tuned to the highest spatial frequencies of the three and temporal frequencies comparable with A. atropos. This yields similar tuning to low velocities as in D. elpenor, but with the advantage of shorter neural delays in processing motion.
Metabolic syndrome, diabetes, and cardiovascular disease in an elderly Caucasian cohort: the Italian Longitudinal Study on Aging.

BACKGROUND The metabolic syndrome (MetS) is represented by a cluster of risk factors for cardiovascular diseases (CVDs). In spite of its high frequency and strong association with morbidity and mortality in the adult population, little is known about its magnitude in elderly persons. METHODS We assessed the prevalence of MetS by diabetic status and sex in the participants in the Italian Longitudinal Study on Aging (ILSA), a population-based study on a sample of 5632 individuals 65-84 years old at baseline (1992). We measured the association of MetS with stroke, coronary heart disease, and diabetes at baseline and with CVD mortality at 4-year follow-up. RESULTS The prevalence of MetS was 25.9% in nondiabetic men and 55.2% in nondiabetic women; in diabetic individuals it was 64.9% and 87.1% in men and women, respectively. At baseline, in both men and women there was a significant association with stroke (odds ratio [OR]=1.67, 95% confidence interval [CI], 1.02-2.75 in men and OR=1.72, CI, 1.01-2.93 in women) and diabetes (OR=4.58, CI, 3.12-6.74 in men and OR=5.15, CI, 3.23-8.20 in women). A significant association with chronic heart disease was found in men only (OR=1.40; CI, 1.02-1.97). During the approximately 4-year follow-up, nondiabetic men with MetS had a risk of CVD mortality 12% higher compared to those without MetS, whereas no significant differences were found in women. CONCLUSIONS MetS is very common in aged Italians, and it is associated with stroke and diabetes in both sexes, and with chronic heart disease in men. In men, it increases significantly the risk of CVD mortality.