Miracle-dz/UniFAR-FTUs huggingface dataset:
Induction of a type I interferon signature in normal human monocytes by gadolinium‐based contrast agents: comparison of linear and macrocyclic agents

The gadolinium‐based contrast agent (GdBCA) Omniscan activates human macrophages through Toll‐like receptor (TLR)‐4 and TLR‐7 signalling. To explore the mechanisms responsible we compared the ability of linear and macrocyclic GdBCA to induce a type I interferon signature and a proinflammatory/profibrotic phenotype in normal human monocytes in vitro. Expression of genes associated with type I interferon signalling and inflammation and production of their corresponding proteins were determined. Both linear and macrocyclic GdBCA stimulated expression of multiple type I interferon‐regulated genes and the expression of numerous chemokines, cytokines and growth factors in normal human peripheral blood monocytes. There was no correlation between the magnitude of the measured response and the Gd chelate used. To explore the mechanisms responsible for GdBCA induction of fibrosis in nephrogenic systemic fibrosis (NSF) in vitro, normal human dermal fibroblasts were incubated with GdBCA‐treated monocyte culture supernatants and the effects on profibrotic gene expression were examined. Supernatants from monocytes exposed to all GdBCA stimulated types I and III collagen, fibronectin and α‐smooth muscle actin (α‐SMA) expression in normal dermal fibroblasts. The results indicate that the monocyte activation induced by GdBCA may be the initial step in the development of GdBCA associated fibrosis in NSF.
Perceptions of Sedentary African-American Women About Continuous versus Intermittent Walking

ABSTRACT To meet current physical activity recommendations, a person may chose to adopt a continuous or an intermittent physical activity program, as long as they accumulate 30 minutes of moderate-intensity physical activity most days of the week. Sixty-four sedentary African-American women were surveyed to assess whether perceptions about continuous and intermittent walking programs differed. Specifically, we assessed whether perceptions of self-efficacy, outcome expectations, social support, and the environment varied with respect to walking programs. Results indicated that the women perceived higher self-efficacy for the intermittent walking program and associated this program with more favorable environmental factors (p < .05). However, they expected greater benefits from the continuous walking program (p < .05). Overall, 65% of the women reported that they would prefer to adopt the continuous walking program.
Hepatic artery and biliary complications in liver transplant recipients undergoing pretransplant transarterial chemoembolization

Liver transplantation (LT) is the treatment of choice for patients with cirrhosis and hepatocellular carcinoma (HCC) not amenable to resection. Locoregional therapies for HCC are often used to reduce tumor burden, bridge patients to LT, and down‐stage HCC so that patients are eligible for LT. We hypothesized that prior endovascular antitumor therapy may increase the risk of hepatic artery (HA) and biliary complications after LT. The aim of this study was to compare HA and biliary complications in LT recipients with HCC who received transarterial chemoembolization (TACE) before LT with complications in LT recipients with HCC who did not receive TACE before LT. This was a retrospective cohort study of HCC patients at two transplant centers. The prevalence of HA complications (HA thrombosis, stenosis, or pseudoaneurysm) and biliary complications (nonanastomotic stricture, bile leak, and diffuse injury) were compared between patients treated with or without TACE. There were 456 HCC patients with a median age of 61 years (77% were male, and 63% had hepatitis C virus), and 328 (72%) received TACE before LT. The overall prevalence of HA complications was 4.7% in the no‐TACE group and 7.9% in the TACE group (P = 0.22). All HA stenosis complications (n = 14) occurred in the TACE group (P = 0.018 versus the no‐TACE group). An older donor age and a lower albumin level significantly increased the odds of HA complications. There was a nonstatistically significant increased odds of HA complications in the TACE group versus the no‐TACE group according to an adjusted analysis (odds ratio = 2.02, 95% confidence interval = 0.79‐5.16, P = 0.14). The overall prevalence of biliary complications was 16.4% in the no‐TACE group and 19.8% in the TACE group (P = 0.40). In conclusion, a lower pre‐LT albumin level and an older donor age were significantly associated with higher odds of HA complications after LT. TACE was not associated with higher odds of overall HA complications but was associated with a higher prevalence of HA stenosis. Further studies are warranted to confirm the HA stenosis findings and elucidate the pathogenesis. Liver Transpl 20:1221‐1228, 2014. © 2014 AASLD.
Deficiency of Arginine Esterase in Cystic Fibrosis of the Pancreas: Demonstration of the Proteolytic Nature of the Activity

Extract: Proteolytic activity, defined as the hydrolysis of peptide bonds involving the carboxyl group of L-arginine, in plasma of patients with cystic fibrosis, heterozygotes, and control subjects has been assayed using a fluorometric method with protamine as the substrate and fluorescamine as the reagent. The mean total proteolytic activity in plasma of patients with cystic fibrosis was approximately one-half the mean total activity in control subjects and heterozygotes. The mean proteolytic activity inhibited by soybean trypsin inhibitor in plasma of patients with cystic fibrosis was approximately one-third that of control subjects and heterozygotes.The relationship of arginine esterase activity to proteolytic activity was investigated. The pH optimum and action of reversible and irreversible inhibitors were similar for both activities, suggesting that the arginine esterase activity and proteolytic activity represent similar catalytic entities. These findings are consistent with our hypothesis that the basic defect in cystic fibrosis may reside in the deficiency of a proteolytic enzyme which results in the accumulation of the various cationic macromolecular “factors” described by other investigators in serum of patients with cystic fibrosis.Speculation: The demonstration of a deficiency of proteolytic activity as assayed by the hydrolysis of protamine, a cationic polypeptide, could explain the presence of ciliotoxic cationic protein or polypeptide factors in serum of patients with cystic fibrosis and may, in some unknown manner, be related to the clinical manifestations of the disease.
Long-term consequence of elevated thyroglobulin in differentiated thyroid cancer.

BACKGROUND Serum thyroglobulin (Tg) is the most sensitive biomarker for recurrence of differentiated thyroid cancer (DTC). We have assessed the changing pattern of stimulated Tg (sTg) and the clinical course of patients with no structural evidence of disease (NSED), based on imaging studies such as neck ultrasonography (US), fluorodeoxyglucose positron emission tomography, and/or chest computed tomogram (CT). We sought to determine if, in patients with DTC who had been treated with bilateral thyroidectomy and remnant ablation with radioactive iodine, sTg 1 year (sTg1) after initial treatment and repeated sTg measurements, 1-2 years after sTg1, helped predict the long-term outcome with respect to structural recurrence and biochemical remission (BR), which is defined as sTg <1 ng/mL. METHODS We retrospectively assessed the records of patients with DTC who had been treated with bilateral thyroidectomy and remnant ablation with radioactive iodine between 1995 and 2004. The study included 186 patients who had NSED with sTg1 ≥2 ng/mL and subsequent sTg measurements (sTg2) without additional treatment. Patients were classified into three groups based on their sTg1 measurements: Group A, 2-4.9 ng/mL; Group B, 5-19.9 ng/mL; and Group C, ≥20 ng/mL. Patients were also classified into two groups based on whether sTg2, 1-2 years after sTg1, had decreased by ≥50% (Group 1) or had either decreased by <50% or increased (Group 2). sTg was measured every 1-2 years until structural recurrence or BR. RESULTS Patients remaining in NSED showed a decrease in serial sTg. Of patients in Groups A, B, and C, 41%, 17%, and 1%, respectively, achieved BR, and there was a significant difference in the BR rate between Groups 1 and 2 (p<0.001). In patients with structural recurrence, serial sTg generally did not decrease from sTg1. There was a significant difference in the recurrence rate among Groups A, B, and C (p=0.005) and between Groups 1 and 2 (p<0.001). CONCLUSIONS We found that 41% of patients with sTg1 in the range 2-5 ng/mL achieved BR, and that sTg1 and percent change of subsequent sTg were predictive of BR. Repeated sTg measurements are useful for predicting patient prognosis in patients with DTC.
Pressure and Shear Differentially Alter Human Articular Chondrocyte Metabolism: A Review

Homeostasis of articular cartilage depends in part on mechanical loads generated during daily activity whereas inappropriate joint loads result in focal degeneration of cartilage, as occurs in osteoarthritis. We will review results of a series of questions regarding the effects of two types of mechanical loads—intermittent hydrostatic pressure and shear stress—on adult human articular chondrocytes in high-density monolayer culture. Intermittent hydrostatic pressure increased aggrecan and Type II collagen gene expression in normal chondrocytes and induced changes in the cell-associated proteins of normal and osteoarthritic chondrocytes. Hydrostatic pressure also counteracted inhibitory effects of bacterial lipopolysaccharide on matrix protein expression by cultured chondrocytes. Application of shear stress to osteoarthritic chondrocytes increased the release of the proinflammatory mediator, nitric oxide, decreased aggrecan and Type II collagen expression, and induced molecular changes associated with apoptosis whereas hydrostatic pressure increased matrix macromolecule expression. The findings show that the types of load comprising the mechanical loading environment of articular cartilage considerably alter chondrocyte metabolism and suggest that mechanical stimulation may be used for in vitro or in vivo approaches for cartilage engineering.
Electro-Optical Characterization of SiPMs With Green Bandpass Dichroic Filters

There is an increasing interest to use silicon photomultipliers (SiPMs) in medical applications like Photoplethysmography or Functional Near Infrared Spectroscopy, allowing the monitoring of physiological signs through non-invasive equipment. The use of large area SiPMs with embedded color filters for environmental light rejection could bring relevant advantages in these applications in terms of higher signal-to-noise ratio of the measurements. Here, we report on the first electro-optical characterization results obtained on n-on-p SiPMs with green interference bandpass filters glued on the top side of the detector SMD package. We will show how the use of the filter considerably increases, especially for large overvoltage values, the SiPM dark noise rate, due to the significant amplification of optical cross-talk effects (up to 150% of dark current increase at 50%-OV). This makes necessary a careful evaluation of the SiPMs performances in order to define the best operating conditions and layout characteristics of the detectors that will be used in the final applications.
The Nuclear Factor-κB Engages CBP/p300 and Histone Acetyltransferase Activity for Transcriptional Activation of the Interleukin-6 Gene Promoter*

Expression of the pleiotropic cytokine interleukin (IL)-6 can be stimulated by the proinflammatory cytokine tumor necrosis factor (TNF) and the microbial alkaloid staurosporine (STS). In this report, the transcriptional mechanisms were thoroughly investigated. Whereas transcription factors binding to the activator protein-1-, cAMP-responsive element-, and CAAT enhancer-binding protein-responsive sequences are necessary for gene activation by STS, nuclear factor (NF)-κB alone is responsible and sufficient for inducibility by TNF, which reveals distinct signaling pathways for both compounds. At the cofactor level, cAMP-responsive element-binding protein-binding protein (CBP) or p300 potentiate basal and induced IL-6 promoter activation via multiple protein-protein interactions with all transcription factors bound to the promoter DNA. However, the strongest promoter activation relies on the p65 NF-κB subunit, which specifically engages CBP/p300 for maximal transcriptional stimulation by its histone acetyltransferase activity. Moreover, treatment of chromatin-integrated promoter constructions with the histone deacetylase inhibitor trichostatin A exclusively potentiates TNF-dependent (i.e. NF-κB-mediated) gene activation, while basal or STS-stimulated IL-6 promoter activity remains completely unchanged. Similar observations were recorded with other natural NF-κB-driven promoters, namely IL-8 and endothelial leukocyte adhesion molecule (ELAM). We conclude that, within an “enhanceosome-like” structure, NF-κB is the central mediator of TNF-induced IL-6 gene expression, involving CBP/p300 and requiring histone acetyltransferase activity.
Neuroprotective effects of ganoderma lucidum polysaccharides against oxidative stress-induced neuronal apoptosis

Ganoderma lucidum polysaccharides have protective effects against apoptosis in neurons exposed to ischemia/reperfusion injury, but the mechanisms are unclear. The goal of this study was to investigate the underlying mechanisms of the effects of ganoderma lucidum polysaccharides against oxidative stress-induced neuronal apoptosis. Hydrogen peroxide (H2O2) was used to induce apoptosis in cultured cerebellar granule cells. In these cells, ganoderma lucidum polysaccharides remarkably suppressed H2O2-induced apoptosis, decreased expression of caspase-3, Bax and Bim and increased that of Bcl-2. These findings suggested that ganoderma lucidum polysaccharides regulate expression of apoptosis-associated proteins, inhibit oxidative stress-induced neuronal apoptosis and, therefore, have significant neuroprotective effects.
Metabolic Syndrome, C-Reactive Protein and Increased Arterial Stiffness in Japanese Subjects

The aim of this study was to investigate whether the metabolic syndrome (MS) was associated with an elevated level of C-reactive protein (CRP) and increased arterial stiffness, and to clarify whether combined MS and CRP data had a stronger relation to arterial stiffness than did MS data alone. Brachial-ankle pulse wave velocity (baPWV), CRP, and conventional risk factors were evaluated in 3,412 men and 854 women. Adjusted mean values of baPWV in men with 0, 1, 2, and ≥3 components were 1,309, 1,372, 1,422, and 1,462 cm/s, respectively (p for trend <0.001). Adjusted mean values of baPWV in women with 0, 1, 2, and ≥3 components were 1,212, 1,292, 1,357, and 1,391 cm/s, respectively (p for trend <0.001). Adjusted geometric mean concentrations of CRP in men with 0, 1, 2, and ≥3 components were 0.036, 0.049, 0.059, and 0.076 mg/dl, respectively (p for trend <0.001). Adjusted geometric mean concentrations of CRP in women with 0, 1, 2, and ≥3 components were 0.023, 0.030, 0.057, and 0.077 mg/dl, respectively (p for trend <0.001). In analyses of adjusted mean values of baPWV according to the number of MS components and according to CRP levels within or without top quartile levels, the p value for the trend was significant (<0.001) in both men and women but, in post hoc analyses, comparing high and low CRP levels in each MS component–number group, no significant difference was found. These results suggest that, for prediction of increased arterial stiffness, combining MS and CRP data has little additive effect compared to the use of MS data alone.
Understanding the suppressed charge trapping in relaxed- and strained-Ge/SiO2/HfO2 pMOSFETs and implications for the screening of alternative high-mobility substrate/dielectric CMOS gate stacks

We study charge trapping in a variety of Ge-based pMOS and nMOS technologies, either with Si passivation and conventional SiO2/HfO2 gate stack, or with GeOx/high-k gate stacks. A general model for understanding this phenomenon in alternative substrate/dielectric systems is proposed. We discuss two different approaches to pursue a reduction of charge trapping in alternative material systems, which will be necessary for achieving reliable high-mobility devices.
A tetrahedral intermediate in the EPSP synthase reaction observed by rapid quench kinetics.

Direct evidence for an enzyme-bound intermediate in the EPSP synthase reaction pathway has been obtained by rapid chemical quench-flow studies. The transient-state kinetic analysis has led to the following complete scheme: (formula; see text) Values for all 12 rate constants were obtained. Substrate trapping experiments in the forward and reverse reactions established the kinetically preferred order of binding and release of substrates and products and showed that shikimate 3-phosphate (S3P) and 5-enolpyruvoylshikimate 3-phosphate (EPSP) dissociate at rates greater than turnover in each direction. Pre-steady-state bursts of product formation were observed in the reaction in each direction indicating a rate-limiting step following catalysis. Single turnover experiments with enzyme in excess over substrate demonstrated the formation of a transient intermediate in both the forward and reverse reactions. In these experiments, the enzymatic reaction was observed by employing a radiolabel in the enol moiety of either phosphoenol pyruvate (PEP) or EPSP. The separation and quantitation of reaction products were accomplished by HPLC monitoring radioactivity. The intermediate was observed as the transient production of radiolabeled pyruvate, formed due to the breakdown of the intermediate in the acid quench used to stop the reaction. The intermediate was observed within 5-10 ms after the substrates were mixed with enzyme and decayed in a reaction paralleling the formation of product in each direction. Thus, the kinetics demonstrate directly the kinetic competence of the presumed intermediate. No pyruvate was formed, on a time scale which is relevant to catalysis, after incubation of the enzyme with dideoxy-S3P and PEP or with EPSP in the absence of phosphate; and so, the intermediate does not accumulate under these conditions. The intermediate broke down to form PEP and EPSP in addition to pyruvate when the reaction was quenched with base rather than acid; therefore, the intermediate must contain the elements of each product. Other experiments were designed to measure directly the phosphate binding rate and further constrain the PEP binding rate. The overall solution equilibrium constant in the forward direction was determined to be 180 by quantitation of radiolabeled reactants and products in equilibrium after incubation with a low enzyme concentration. The internal, active site equilibrium constant was obtained by incubation of radiolabeled S3P with excess enzyme and high concentrations of phosphate and PEP to provide the ratio of [EPSP]/[S3P] = 2.3, which is largely a measure of K4. (ABSTRACT TRUNCATED AT 250 WORDS)
Maintenance of Intermediolateral Spinal Cord Neurons by Fibroblast Growth Factor Administered to the Medullectomized Rat Adrenal Gland: Dependence on Intact Adrenal Innervation and Cellular Organization of Implants

We have previously shown that basic fibroblast growth factor (bFGF; 2 μg), when administered in gelfoams implanted to medullectomized adult rat adrenal glands, maintains target‐deprived preganglionic neurons located in the intermediolateral column (IML) of the spinal cord. We show now that administration of 600 or 60 ng/implant/organ of the biologically active recombinant protein also maintains IML‐neurons. The effects depend on an intact organ nerve supply since administration of bFGF‐implants to the medullectomized and denervated (splanchnicotomized) organ abolishes the maintenance effects for IML‐neurons. A possible regeneration of cholinergic nerve fibres was assessed by quantitative determination of choline acetyltransferase (ChAT)‐activity and ultrastructurally under various treatments. When compared to a cytochrome‐(Cyto)‐C treatment, bFGF significantly increased ChAT‐activity in the innervated adrenal gland after 4 weeks, suggesting that sprouting of cholinergic nerve fibres and/or recovery of enzyme activity had occurred. Electron microscopically, unmyelinated axons associated with Schwann cells were only found in bFGF, but not in Cyto‐C‐implants. We conclude that exogenous bFGF or a yet unidentified trophic molecule possibly induced by bFGF in the adrenal gland acts as a retrogradely transported messenger serving for the maintenance of spinal cord IML‐neurons in vivo. By stimulating axonal sprouting, bFGF might facilitate access of trophic material to nerve fibres.
Effects of iodide on the coupling between ATP hydrolysis and motile activity in axonemal dynein

Dynein transduces the chemical energy of ATP hydrolysis into mechanical work through conformational changes. To identify the factors governing the coupling between the ATPase activity and the motile activity of the dynein molecule, we examined the effects of potassium iodide, which can unfold protein tertiary structures, on dynein activity in reactivated sea urchin sperm flagella. The presence of low concentrations of KI (0.05–0.1 M) in the reactivating solution did not influence the stable beating of demembranated flagella at 0.02–1 mM ATP, when the total concentration of potassium was kept at 0.15 M by adding K‐acetate. However, double‐reciprocal plots of ATP concentration and beat frequency showed a mixed type of inhibition by KI, indicating the possibility that KI inhibits the ATP hydrolysis and decreases the maximum sliding velocity. The ATPase activity of 21S dynein with or without microtubules did not decrease with the KI concentration. In the elastase‐treated axonemes, KI decreased the velocity of sliding disintegration, while it increased the frequency of occurrence of axonemes showing no sliding. This may be related to some defect in the coordination of dynein activities. On 21S dynein adsorbed on a glass surface, however, the velocity of microtubule sliding was increased by KI, while KI lowered the dynein‐microtubule affinity. The velocity further increased under lower salt conditions enhancing the dynein‐microtubule interactions. The results suggest the importance of organized regulation of the dynamic states of dynein‐microtubule interactions through the stalk for the coupling between the ATPase activity and the motile activity of dynein in beating flagella. © 2011 Wiley‐Liss, Inc.