bluuebunny/crossref_metadata_2025 huggingface dataset:
Purinergic receptor X7 is a key modulator of metabolic oxidative stress-mediated autophagy and inflammation in experimental nonalcoholic steatohepatitis
Authors: Das Suvarthi , Seth Ratanesh Kumar , Kumar Ashutosh , Kadiiska Maria B. , Michelotti Gregory , Diehl Anna Mae , Chatterjee Saurabh
Published: October 2013

Recent studies indicate that metabolic oxidative stress, autophagy, and inflammation are hallmarks of nonalcoholic steatohepatitis (NASH) progression. However, the molecular mechanisms that link these important events in NASH remain unclear. In this study, we investigated the mechanistic role of purinergic receptor X7 (P2X7) in modulating autophagy and resultant inflammation in NASH in response to metabolic oxidative stress. The study uses two rodent models of NASH. In one of them, a CYP2E1 substrate bromodichloromethane is used to induce metabolic oxidative stress and NASH. Methyl choline-deficient diet feeding is used for the other NASH model. CYP2E1 and P2X7 receptor gene-deleted mice are used to establish their roles in regulating metabolic oxidative stress and autophagy. Autophagy gene expression, protein levels, confocal microscopy based-immunolocalization of lysosome-associated membrane protein (LAMP)2A and histopathological analysis were performed. CYP2E1-dependent metabolic oxidative stress induced increases in P2X7 receptor expression and chaperone-mediated autophagy markers LAMP2A and heat shock cognate 70 but caused depletion of light chain 3 isoform B (LC3B) protein levels. P2X7 receptor gene deletion significantly decreased LAMP2A and inflammatory indicators while significantly increasing LC3B protein levels compared with wild-type mice treated with bromodichloromethane. P2X7 receptor-deleted mice were also protected from NASH pathology as evidenced by decreased inflammation and fibrosis. Our studies establish that P2X7 receptor is a key regulator of autophagy induced by metabolic oxidative stress in NASH, thereby modulating hepatic inflammation. Furthermore, our findings presented here form a basis for P2X7 receptor as a potential therapeutic target in the treatment for NASH.
Familial hypercholesterolemia impairs exercise-induced systemic vasodilation due to reduced NO bioavailability
Authors: de Beer Vincent J. , Merkus Daphne , Bender Shawn B. , Tharp Darla L. , Bowles Douglas K. , Duncker Dirk J. , Laughlin M. Harold
Published: October 2013

Hypercholesterolemia impairs endothelial function [e.g., the nitric oxide (NO)-cyclic GMP-phosphodiesterase 5 (PDE5) pathway], limits shear stress-induced vasodilation, and is therefore expected to reduce exercise-induced vasodilation. To assess the actual effects of hypercholesterolemia on endothelial function and exercise-induced vasodilation, we compared the effects of endothelial NO synthase (eNOS) and PDE5 inhibition in chronically instrumented Yucatan (Control) and Rapacz familial hypercholesterolemic (FH) swine, at rest and during treadmill exercise. The increases in systemic vascular conductance produced by ATP (relative to nitroprusside) and exercise were blunted in FH compared with Control swine. The vasoconstrictor response to eNOS inhibition, with nitro-l-arginine (NLA), was attenuated in FH compared with Control swine, both at rest and during exercise. Furthermore, whereas the vasodilator response to nitroprusside was enhanced slightly, the vasodilator response to PDE5 inhibition, with EMD360527, was reduced in FH compared with Control swine. Finally, in the pulmonary circulation, FH resulted in attenuated vasodilator responses to ATP, while maintaining the responses to both NLA and EMD360527. In conclusion, hypercholesterolemia reduces exercise-induced vasodilation in the systemic but not the pulmonary circulation. This reduction appears to be the principal result of a decrease in NO bioavailability, which is mitigated by a lower PDE5 activity.
Dynamic cerebral autoregulation after bed rest: effects of volume loading and exercise countermeasures
Authors: Jeong Sung-Moon , Hwang Gyu-Sam , Kim Seon-Ok , Levine Benjamin D. , Zhang Rong
Published: October 2013

This study assessed effects of head-down-tilt (HDT) bed rest on dynamic cerebral autoregulation (CA) in 21 healthy young adults with volume loading and exercise countermeasures. Of these, seven underwent an 18-day bed rest without exercise countermeasures ( sedentary group). Volume loading with dextran infusion was performed after bed rest to restore reduced plasma volume to levels before bed rest. In the other 14 subjects, supine cycling during bed rest was performed to preserve cardiac work from before bed rest ( exercise group). Volume loading was also performed in a subgroup of these subjects ( Ex+Dex, n = 7). Dynamic CA was estimated by transfer function analysis of changes in arterial pressure and cerebral blood flow (CBF) velocity in the very low (VLF, 0.02–0.07 Hz), low (LF, 0.07–0.20 Hz), and high frequency ranges (HF, 0.20–0.35 Hz). After bed rest, transfer function gain was reduced in the sedentary group (VLF, 0.93 ± 0.23 to 0.61 ± 0.23 cm−1·s−1·mmHg; P = 0.007) and in the exercise group (LF, 1.22 ± 0.43 to 0.94 ± 0.26 cm−1·s−1·mmHg; P = 0.005, HF, 1.32 ± 0.55 to 1.00 ± 0.32 cm−1·s−1·mmHg; P = 0.010). After volume loading, transfer function gain increased in the sedentary group but not in the Ex+Dex group. Taken together, these findings suggest that dynamic CA was preserved or improved after HDT bed rest in both sedentary and exercise subjects. Furthermore, increases of transfer function gain with volume loading suggest that changes in plasma volume may play an important role in CBF regulation.
Regulation of oxidative phosphorylation during work transitions results from its kinetic properties
Authors: Korzeniewski Bernard
Published: October 2013

The regulation of oxidative phosphorylation (OXPHOS) during work transitions in skeletal muscle and heart is still not well understood. Different computer models of this process have been developed that are characterized by various kinetic properties. In the present research-polemic theoretical study it is argued that models belonging to one group (Model A), which predict that among OXPHOS complexes complex III keeps almost all of the metabolic control over oxygen consumption (Vo2) and involve a strong complex III activation by inorganic phosphate (Pi), lead to the conclusion that an increase in Piis the main mechanism responsible for OXPHOS activation (feedback-activation mechanism). Models belonging to another group (Model B), which were developed to take into account an approximately uniform distribution of metabolic control over Vo2among particular OXPHOS complexes (complex I, complex III, complex IV, ATP synthase, ATP/ADP carrier, phosphate carrier) encountered in experimental studies in isolated mitochondria, predict that all OXPHOS complexes are directly activated in parallel with ATP usage and NADH supply by some external cytosolic factor/mechanism during rest-to-work or low-to-high work transitions in skeletal muscle and heart (“each-step-activation” mechanism). Model B demonstrates that different intensities of each-step activation can account for the very different (slopes of) phenomenological Vo2-ADP relationships observed in various skeletal muscles and heart. Thus they are able to explain the differences in the regulation of OXPHOS during work transitions between skeletal muscle (where moderate changes in ADP take place) and intact heart in vivo (where ADP is essentially constant).
A new method to detect rapid oxygen changes around cells: How quickly do calcium channels sense oxygen in cardiomyocytes?
Authors: Scaringi John A. , Rosa Angelo Oscar , Morad Martin , Cleemann Lars
Published: October 2013

Acute hypoxia is thought to trigger protective responses that, in tissues like heart and carotid body, include rapid (5–10 s) suppression of Ca2+ and K+ channels. To gain insight into the mechanism for the suppression of the cardiac l-type Ca2+ channel, we measured O2-dependent fluorescence in the immediate vicinity of voltage-clamped cardiac cells subjected to rapid exchange of solutions with different O2 tensions. This was accomplished with an experimental chamber with a glass bottom that was used as a light guide for excitation of a thin ruthenium-based O2-sensitive ORMOSIL coating. Fluorescence imaging showed that steady-state Po2 was well controlled within the entire stream from an electromagnetically controlled solution “puffer” but that changes were slower at the periphery of the stream (τ1/2 ∼ 500 ms) than immediately around the voltage-clamped myocyte (τ1/2 ∼ 225 ms) where, in turn, firmly attached cells produced an additional local delay of 50–100 ms. Performing simultaneous voltage clamp and O2 measurements, we found that acute hypoxia gradually and reversibly suppressed the Ca2+ channel (CaV1.2). Using Ba2+ as charge carrier, the suppression was significant after 1.5 s, reached ∼10% after 2.5 s, and was nearly completely reversible in 5 s. The described fluorescence measurements provide the means to check and fine tune solution puffers and suggest that changes in Po2 can be accomplished within ∼200 ms. The rapid and reversible suppression of barium current under hypoxia is consistent with the notion that the cardiac Ca2+ channel is directly modulated by O2.
Serum AMH in Physiology and Pathology of Male Gonads
Authors: Matuszczak Ewa , Hermanowicz Adam , Komarowska Marta , Debek Wojciech
Published: October 2013

AMH is secreted by immature Sertoli cells (SC) and is responsible for the regression of Müllerian ducts in the male fetus as part of the sexual differentiation process. AMH is also involved in testicular development and function. AMHs are at their lowest levels in the first days after birth but increase after the first week, likely reflecting active SC proliferation. AMH rises rapidly in concentration in boys during the first month, reaching a peak level at about 6 months of age, and then slowly declines during childhood, falling to low levels in puberty. Basal and FSH-stimulated levels of AMH, might become a useful predictive marker of the spermatogenic response to gonadotropic treatment in young patients with hypogonadotropic hypogonadism. After puberty, AMH is released preferentially by the apical pole of the SC towards the lumen of the seminiferous tubules, resulting in higher concentrations in the seminal plasma than in the serum. Defects in AMH production and insensitivity to AMH due to receptor defects result in the persistent Müllerian duct syndrome. A measurable value of AMH in a boy with bilateral cryptorchidism is predictive of undescended testes, while an undetectable value is highly suggestive of anorchia or ovaries, as would be the case in girls with female pseudohermaphroditism and pure gonadal dysgenesis. Lower serum AMH concentrations in otherwise healthy boys with cryptorchidism, who were compared with their age-matched counterparts with palpable testes, have been reported previously. AMH levels are higher in prepubertal patients with varicocele than in controls. This altered serum profile of AMH in boys with varicoceles may indicate an early abnormality in the regulation of the seminiferous epithelial function. Serum AMH is known to be valuable in assessing gonadal function. As compared to testing involving the administration of human chorionic gonadotropin, the measurement of AMH is more sensitive and equally specific. Measurement of AMH is very useful in young children, because serum gonadotropin concentrations in those who are agonadal are nondiagnostic in midchildhood and serum testosterone concentrations may fail to increase with provocative testing in children with abdominal testes.
Vibration Analysis of Cylindrical Sandwich Aluminum Shell with Viscoelastic Damping Treatment
Authors: Cheng Tai-Hong , Li Zhen-Zhe , Shen Yun-De
Published: October 2013

This paper has applied the constrained viscoelastic layer damping treatments to a cylindrical aluminum shell using layerwise displacement theory. The transverse shear, the normal strains, and the curved geometry are exactly taken into account in the present layerwise shell model, which can depict the zig-zag in-plane and out-of-plane displacements. The damped natural frequencies, modal loss factors, and frequency response functions of cylindrical viscoelastic aluminum shells are compared with those of the base thick aluminum panel without a viscoelastic layer. The thickness and damping ratio of the viscoelastic damping layer, the curvature of proposed cylindrical aluminum structure, and placement of damping layer of the aluminum panel were investigated using frequency response function. The presented results show that the sandwiched viscoelastic damping layer can effectively suppress vibration of cylindrical aluminum structure.
Current Treatment of Heart Failure with Preserved Ejection Fraction: Should We Add Life to the Remaining Years or Add Years to the Remaining Life?
Authors: Li Jia , Becher Peter Moritz , Blankenberg Stefan , Westermann Dirk
Published: October 2013

According to the ejection fraction, patients with heart failure may be divided into two different groups: heart failure with preserved or reduced ejection fraction. In recent years, accumulating studies showed that increased mortality and morbidity rates of these two groups are nearly equal. More importantly, despite decline in mortality after treatment in regard to current guideline in patients with heart failure with reduced ejection fraction, there are still no trials resulting in improved outcome in patients with heart failure with preserved ejection fraction so far. Thus, novel pathophysiological mechanisms are under development, and other new viewpoints, such as multiple comorbidities resulting in increased non-cardiac deaths in patients with heart failure and preserved ejection fraction, were presented recently. In this review, we will focus on the tested as well as the promising therapeutic options that are currently studied in patients with heart failure with preserved ejection fraction, along with a brief discussion of pathophysiological mechanisms and diagnostic options that are helpful to increase our understanding of novel therapeutic strategies.
Delay Bound: Fractal Traffic Passes through Network Servers
Authors: Li Ming , Zhao Wei , Cattani Carlo
Published: October 2013

Delay analysis plays a role in real-time systems in computer communication networks. This paper gives our results in the aspect of delay analysis of fractal traffic passing through servers. There are three contributions presented in this paper. First, we will explain the reasons why conventional theory of queuing systems ceases in the general sense when arrival traffic is fractal. Then, we will propose a concise method of delay computation for hard real-time systems as shown in this paper. Finally, the delay computation of fractal traffic passing through severs is presented.
Effects of Carbon Nanotubes Acid Treated or Annealed and Manganese Nitrate Thermally Decomposed on Capacitive Characteristics of Electrochemical Capacitors
Authors: Lin Chuen-Chang , Kuo Chung-Lun
Published: October 2013

Carbon nanotubes (CNTs) directly grown on aluminum foil or nanoporous alumina templates by chemical vapor deposition are treated with acid for different times or annealed at different temperatures. Then, the CNTs are immersed into a manganese nitrate aqueous solution and then manganese oxides are formed by thermally decomposing the manganese nitrate at different temperatures. The longer the time that the CNTs are treated with the acid, the slower the decreasing rate of the specific capacitance. Also, the higher the annealing temperature of the CNTs, the slower the decreasing rate of the specific capacitance. Furthermore, the electrochemical stability for thermally decomposing manganese nitrate at 400°C is better than that at 200 or 300°C and the operational stability with nanoporous alumina templates as a substrate is better than that with Al foil as a substrate.
Maternal and Foetal Cardiovascular Effects of the Anaesthetic Alfaxalone in 2‐Hydroxypropyl‐β‐cyclodextrin in the Pregnant Ewe
Authors: Andaluz Anna , Santos Laura , García Félix , Ferrer Rosa I. , Fresno Laura , Moll Xavier
Published: October 2013

The objective of this study was to determine the pharmacodynamics effects of the anaesthetic alfaxalone in 2‐hydroxypropyl‐β‐cyclodextrin in pregnant sheep after the intravenous injection of a 2 mg/kg weight dose. Six pregnant Ripollesa sheep, weighing 47.1 ± 4.4 kg, were used. Twenty‐four hours after instrumentation, sheep were anaesthetized with intravenous alfaxalone in cyclodextrin. Time to standing from anaesthesia was 30.0 ± 10.81 min. Foetal heart rate increased significantly during the first 5 min after alfaxalone administration. Significant differences were observed in maternal diastolic arterial blood pressure between minute 10 and minutes 90, 120, 150, 180, 210, and 240. Significant differences were observed for foetal systolic arterial blood pressure between 5 and 30 min after alfaxalone administration. Significant differences in foetal pH were detected during the entire study period, whereas maternal pH returned to baseline values by 60 min after alfaxalone administration. The present study indicated that alfaxalone in 2‐hydroxypropyl‐β‐cyclodextrin administered as an intravenous bolus at 2 mg/kg body weight produced minimal adverse effects and an uneventful recovery from anaesthesia in pregnant sheep and their foetus.
Cortex Moutan Induces Bladder Cancer Cell Death via Apoptosis and Retards Tumor Growth in Mouse Bladders
Authors: Lin Mei-Yi , Lee Ying-Ray , Chiang Su-Yin , Li Yi-Zhen , Chen Yueh-Sheng , Hsu Cheng-Da , Liu Yi-Wen
Published: October 2013

Cortex Moutan is the root bark ofPaeonia suffruticosaAndr. It is the herbal medicine widely used in Traditional Chinese Medicine for the treatment of blood-heat and blood-stasis syndrome. Furthermore, it has been reported that Cortex Moutan has anticancer effect. In this study, the Cortex Moutan extract was evaluated in bladder cancer therapy in vitro and in vivo. Cortex Moutan extract reduces cell viability with IC50between 1~2 mg/ml in bladder cancer cells, and it has lower cytotoxicity in normal urotheliums. It arrests cells in G1 and S phase and causes phosphatidylserine expression in the outside of cell membrane. It induces caspase-8 and caspase-3 activation and poly(ADP-ribose) polymerase degradation. The pan caspase inhibitor z-VAD-fmk reverses Cortex Moutan-induced cell death. Cortex Moutan also inhibits cell invasion activity in 5637 cells. In mouse orthotopic bladder cancer model, intravesical application of Cortex Moutan decreases the bladder tumor size without altering the blood biochemical parameters. In summary, these results demonstrate the antiproliferation and anti-invasion properties of Cortex Moutan in bladder cancer cells and its antibladder tumor effect in vivo. Cortex Moutan may provide an alternative therapeutic strategy for the intravesical therapy of superficial bladder cancer.
Budd-Chiari Syndrome with Multiple Thrombi due to a Familial Arg42Ser Mutation in the Protein C Gene
Authors: Muratsu Jun , Morishima Atsuyuki , Mizoguchi Kazuhiro , Ataka Keiji , Yamamoto Hiroshi , Fan Xinping , Miyata Toshiyuki , Sakaguchi Katsuhiko
Published: October 2013

A 34-year-old Japanese woman was admitted to our hospital complaining of developing bilateral pedal edema. Imaging studies led to a diagnosis of Budd-Chiari syndrome combined with internal jugular vein thrombus. We investigated the cause of thrombosis and found that the anticoagulant activity of protein C was decreased. Genetic analysis showed the presence of a c.125C>A (Arg42Ser) substitution in the protein C gene (PROC) of the proband, which generates an Arg42Ser mutation that replaces the scissile bond Arg42-Ala43 normally cleaved by a furin-like processing protease. Her father and younger brother also carried this mutation, although they had no evidence of thrombosis.
Optical Characterization of Porous Sputtered Silver Thin Films
Authors: Carton Olivier , Ghaymouni Jaouad , Lejeune Michaël , Zeinert Andreas
Published: October 2013

The optical properties of various porous silver films, grown with a commercial DC sputter coater, were investigated and compared for different plasma parameters. Effective Drude models were successfully used for those films whose spectra did not show particular resonance peaks. For the other films, neither an effective Drude model nor effective medium models (Maxwell Garnett, Bruggeman, and Looyenga) can describe the optical properties. It turns out that a more general approach like the Bergman representation describes the optical data of these films accurately adopting porosity values consistent with physical measurements.
Contribution to Analysis of Co/Cu Substituted Ni-Zn Ferrites
Authors: Choudary G. S. V. R. K. , Prameela P. , Varma M. Chaitanya , Kumar A. Mahesh , Rao K. H.
Published: October 2013

In this communication, Co/Cu substituted Ni-Zn ferrites processed through sol-gel synthesis using polyethylene glycol (PEG) as a chelating agent are studied, intending to aid in understanding and choosing the optimum ferrite material for high frequency applications. Lattice constant and average crystallite size have been estimated from FWHM of the X-ray diffraction peaks, and these parameters are understood by considering the ionic radii of the substituted as well as the replacing ions. Observed variations in saturation magnetization and initial permeability for these ferrites have been explained on the basis of anisotropy contribution for cobalt and segregation of copper at grain boundaries evident from scanning electron micrographs.
Subclass of Multivalent Harmonic Functions Defined by Wright Generalized Hypergeometric Functions
Authors: Aouf M. K. , Moustafa A. O. , Adwan E. A.
Published: October 2013

We introduce a new class of multivalent harmonic functions defined by Wright generalized hypergeometric function. Coefficient estimates, extreme points, distortion bounds, and convex combination for functions belonging to this class are obtained.
Fabrication of Silicon Nitride Ion Sensitive Field‐Effect Transistor for pH Measurement and DNA Immobilization/Hybridization
Authors: Hashim U. , Chong Soon Weng , Liu Wei-Wen
Published: October 2013

The fabrication of ion sensitive field‐effect transistor (ISFET) using silicon nitride (Si3N4) as the sensing membrane for pH measurement and DNA is reported. For the pH measurement, the Ag/AgCl electrode was used as the reference electrode, and different pH values of buffer solution were used in the ISFET analysis. The ISFET device was tested with pH buffer solutions of pH2, pH3, pH7, pH8, and pH9. The results show that the IV characteristic of ISFET devices is directly proportional and the device’s sensitivity was 43.13 mV/pH. The ISFET is modified chemically to allow the integration with biological element to form a biologically active field‐effect transistor (BIOFET). It was found that the DNA immobilization activities which occurred on the sensing membrane caused the drain current to drop due to the negatively charged backbones of the DNA probes repelled electrons from accumulating at the conducting channel. The drain current was further decreased when the DNA hybridization took place.
ZnO Nanoparticles as an Efficient, Heterogeneous, Reusable, and Ecofriendly Catalyst for Four‐Component One‐Pot Green Synthesis of Pyranopyrazole Derivatives in Water
Authors: Sachdeva Harshita , Saroj Rekha
Published: October 2013

An extremely efficient catalytic protocol for the synthesis of a series of pyranopyrazole derivatives developed in a one‐pot four‐component approach in the presence of ZnO nanoparticles as heterogeneous catalyst using water as a green solvent is reported. Greenness of the process is well instituted as water is exploited both as reaction media and medium for synthesis of catalyst. The ZnO nanoparticles exhibited excellent catalytic activity, and the proposed methodology is capable of providing the desired products in good yield (85–90%) and short reaction time. After reaction course, ZnO nanoparticles can be recycled and reused without any apparent loss of activity which makes this process cost effective and hence ecofriendly. All the synthesized compounds have been characterized on the basis of elemental analysis, IR, 1H NMR, and 13C NMR spectral studies.
Dendritic Cell-Based Approaches for Therapeutic Immune Regulation in Solid-Organ Transplantation
Authors: Vassalli Giuseppe
Published: October 2013

To avoid immune rejection, allograft recipients require drug-based immunosuppression, which has significant toxicity. An emerging approach is adoptive transfer of immunoregulatory cells. While mature dendritic cells (DCs) present donor antigen to the immune system, triggering rejection, regulatory DCs interact with regulatory T cells to promote immune tolerance. Intravenous injection of immature DCs of either donor or host origin at the time of transplantation have prolonged allograft survival in solid-organ transplant models. DCs can be treated with pharmacological agents before injection, which may attenuate their maturationin vivo. Recent data suggest that injected immunosuppressive DCs may inhibit allograft rejection, not by themselves, but through conventional DCs of the host. Genetically engineered DCs have also been tested. Two clinical trials in type-1 diabetes and rheumatoid arthritis have been carried out, and other trials, including one trial in kidney transplantation, are in progress or are imminent.
Trends in Breast Cancer Incidence Rates by Age and Stage at Diagnosis in Gharbiah, Egypt, over 10 Years (1999–2008)
Authors: Hirko Kelly A. , Soliman Amr S. , Hablas Ahmed , Seifeldin Ibrahim A. , Ramadan Mohamed , Banerjee Mousumi , Harford Joe B. , Chamberlain Robert M. , Merajver Sofia D.
Published: October 2013

Background. This study was undertaken to evaluate trends in breast cancer incidence in Egypt from 1999 to 2008 and to make projections for breast cancer occurrence for the years 2009–2015.Patients and Methods. We utilized joinpoint regression and average annual percent change (AAPC) measures with 95% confidence intervals (CI) to describe the trends in breast cancer incidence rates from the Gharbiah Cancer Registry by age and stage at diagnosis and to estimate expected breast cancer caseloads for 2009–2015.Results. From 1999 to 2008, the AAPC in breast cancer incidence rates in Gharbiah significantly increased among women 50 years and older and among localized tumors (AAPC %, 95% CI, 3.1% to 8.0%). Our results predict a significant increase in breast cancer caseloads from 2009 to 2015 among women aged 30–39 (AAPC %, 95% CI, 0.9% to 1.1%) and among women aged 40–49 years (AAPC %, 95% CI, 1.0% to 2.6%).Conclusion. These results have important implications for allocating limited resources, managing treatment needs, and exploring the consequences of prior interventions and/or changing risk factors in Egypt and other developing countries at the same stages of demographic and health transitions.
Chemical Effect on Wellbore Instability of Nahr Umr Shale
Authors: Yu Baohua , Yan Chuanliang , Nie Zhen
Published: October 2013

Wellbore instability is one of the major problems that hamper the drilling speed in Halfaya Oilfield. Comprehensive analysis of geological and engineering data indicates that Halfaya Oilfield features fractured shale in the Nahr Umr Formation. Complex accidents such as wellbore collapse and sticking emerged frequently in this formation. Tests and theoretical analysis revealed that wellbore instability in the Halfaya Oilfield was influenced by chemical effect of fractured shale and the formation water with high ionic concentration. The influence of three types of drilling fluids on the rock mechanical properties of Nahr Umr Shale is tested, and time‐dependent collapse pressure is calculated. Finally, we put forward engineering countermeasures for safety drilling in Halfaya Oilfield and point out that increasing the ionic concentration and improving the sealing capacity of the drilling fluid are the way to keep the wellbore stable.
Common Fixed Point Theorems for a Rational Inequality in Complex Valued Metric Spaces
Authors: Kumar Pankaj , Kumar Manoj , Kumar Sanjay
Published: October 2013

We prove a common fixed point theorem for a pair of mappings. Also, we prove a common fixed point theorem for pairs of self-mappings along with weakly commuting property.
An Intact Immune System Is Required for the Anticancer Activities of Histone Deacetylase Inhibitors
Authors: West Alison C. , Mattarollo Stephen R. , Shortt Jake , Cluse Leonie A. , Christiansen Ailsa J. , Smyth Mark J. , Johnstone Ricky W.
Published: October 2013

Cell-intrinsic effects such as induction of apoptosis and/or inhibition of cell proliferation have been proposed as the major antitumor responses to histone deacetylase inhibitors (HDACi). These compounds can also mediate immune-modulatory effects that may contribute to their anticancer effects. However, HDACi can also induce anti-inflammatory, and potentially immunosuppressive, outcomes. We therefore sought to clarify the role of the immune system in mediating the efficacy of HDACi in a physiologic setting, using preclinical, syngeneic murine models of hematologic malignancies and solid tumors. We showed an intact immune system was required for the robust anticancer effects of the HDACi vorinostat and panobinostat against a colon adenocarcinoma and two aggressive models of leukemia/lymphoma. Importantly, although HDACi-treated immunocompromised mice bearing established lymphoma succumbed to disease significantly earlier than tumor bearing, HDACi-treated wild-type (WT) mice, treatment with the conventional chemotherapeutic etoposide equivalently enhanced the survival of both strains. IFN-γ and tumor cell signaling through IFN-γR were particularly important for the anticancer effects of HDACi, and vorinostat and IFN-γ acted in concert to enhance the immunogenicity of tumor cells. Furthermore, we show that a combination of vorinostat with α-galactosylceramide (α-GalCer), an IFN-γ–inducing agent, was significantly more potent against established lymphoma than vorinostat treatment alone. Intriguingly, B cells, but not natural killer cells or CD8+ T cells, were implicated as effectors of the vorinostat antitumor immune response. Together, our data suggest HDACi are immunostimulatory during cancer treatment and that combinatorial therapeutic regimes with immunotherapies should be considered in the clinic. Cancer Res; 73(24); 7265–76. ©2013 AACR.
Clinical Significance of Immunoglobulin E Responses to Staphylococcal Superantigens in Patients with Aspirin-Exacerbated Respiratory Disease
Authors: Yoo Hye-Soo , Shin Yoo-Seob , Liu Jing Nan , Kim Mi-Ae , Park Hae-Sim
Published: October 2013

Background: Previous studies have reported a higher prevalence of immunoglobulin E (IgE) specific for staphylococcal superantigens (SAg) in the nasal mucosa of patients with aspirin-exacerbated respiratory disease (AERD), associated with eosinophilic inflammation and leukotriene production. However, the role of SAg-specific IgE in the pathogenesis of AERD is not well understood. We evaluated the clinical significance of serum IgE specific for three types of SAg, namely staphylococcal enterotoxins A and B (SEA and SEB) and toxic shock syndrome toxin-1 (TSST-1) in AERD. Methods: We enrolled 147 patients with AERD confirmed by a lysine-acetyl salicylic acid bronchoprovocative test and compared them with 147 patients with aspirin-tolerant asthma (ATA) and 141 healthy controls (NC). The levels of serum total IgE and SAg-specific IgE were measured using an ImmunoCAP system. Other clinical parameters were analyzed retrospectively. Results: The prevalences of SEA-, SEB- and TSST-1-specific IgE in the AERD and ATA groups were significantly higher than those in the NC group (p < 0.05, respectively). The total IgE level was significantly higher in patients with AERD with high levels of SEA-specific IgE than in those with lower levels (p < 0.05), with significant positive correlations between total and SAE-specific IgE levels (p < 0.05). The PC20 methacholine level was significantly lower in patients with AERD with high levels of SEA-specific IgE, while a significantly higher eosinophil count was noted in patients with AERD with high levels of SEB-specific IgE (p < 0.05, respectively). Conclusions: Specific IgE responses to SAg may increase the serum total IgE level, airway hyperresponsiveness and eosinophil activation, leading to more severe clinical symptoms in AERD.
Rationale and Clinical Pearls for Primary Care Doctors Referring Patients for Deep Brain Stimulation
Authors: Martinez-Ramirez Daniel , Okun Michael S.
Published: October 2013

Background: Deep brain stimulation (DBS) is a surgical treatment involving the implantation of a brain lead connected to a chest-based neurostimulator similar to a cardiac pacemaker. The device can be programmed to deliver electrical impulses to neuromodulate abnormal brain circuitry in disorders such as Parkinson's disease (PD), essential tremor (ET), and dystonia. As the number of patients receiving DBS surgery increases, it will be important for primary care doctors to identify reasonable DBS candidates for referral to an experienced center. Objective: To provide primary care physicians with a rationale and also to provide clinically useful pearls for referral of potential DBS candidates. Methods: A complete PubMed review of the literature. Results: This review will be focused on PD and ET and will address the following issues: what are the common motor and nonmotor symptoms? What is the evidence supporting the use of DBS in PD and ET? What is the importance of a multi- or interdisciplinary DBS team for patient selection? What can be done to improve success in identifying and referring potential DBS candidates? Conclusion: DBS is a highly effective therapy for select candidates with PD and ET. The most important factor influencing DBS outcome is proper patient selection. It will be critical as DBS continues to be more commonly employed for primary care doctors to select candidates from their practices as appropriate referrals to specialized centers.
CCL5/RANTES, sVCAM-1, and sICAM-1 in Chronic Spontaneous Urticaria
Authors: Puxeddu Ilaria , Panza Filomena , Pratesi Federico , Bartaloni Debora , Casigliani Rabl Sara , Rocchi Valeria , Del Corso Isabella , Migliorini Paola
Published: October 2013

Background: Chronic urticaria (CU) is a common disease characterized by recurrent itchy wheals and/or angioedema for more than 6 weeks. We aimed to investigate the potential involvement of chemotactic mediators and soluble adhesion molecules as markers of endothelial dysfunction in the pathogenesis of chronic spontaneous urticaria (CSU). The potential relevance of these soluble mediators in the evaluation of disease activity was also investigated. Methods: We measured the levels of CCL5/RANTES, CXCL8/IL-8, sVCAM-1, and sICAM-1 in the sera of 87 patients with CSU and 61 normal healthy subjects (NHS) using ELISA assays. According to the results of autologous serum skin tests (ASST), CSU patients were classified into ASST-positive and ASST-negative subgroups. Furthermore, we investigated in 4 patients whether H1-antihistamine therapy decreases sVCAM-1 and sICAM-1 levels. Results: We detected a significantly higher concentration of CCL5/RANTES (p < 0.0001) but not of CXCL8/IL-8 in CSU patients compared to NHS. The serum levels of sICAM-1 and sVCAM-1 were significantly increased in CSU patients compared to NHS (p = 0.0121 and p = 0.0043, respectively). No difference in chemokine or soluble adhesion molecule levels was detected between the ASST-positive and ASST-negative subgroups. A positive correlation was found between sICAM-1 and sVCAM-1 (p = 0.0022) but not between these and CCL5/RANTES. After H1-antihistamine therapy, sVCAM-1 and sICAM-1 levels did not decrease in the 4 CSU patients tested. Conclusions: Our study suggests that CCL5/RANTES, sICAM-1, and sVCAM-1 play a potential role in the pathogenesis of CSU but they do not parallel disease activity and are not predictive of the response to H1-antihistamine therapy.
The Relevance of Basophil Allergen Sensitivity Testing to Distinguish between Severe and Mild Peanut-Allergic Children
Authors: Homšak Matjaž , Šilar Mira , Berce Vojko , Tomazin Maja , Skerbinjek-Kavalar Maja , Čelesnik Nina , Košnik Mitja , Korošec Peter
Published: October 2013

Background: Peanut sensitization is common in children. However, it is difficult to assess which children will react mildly and which severely. This study evaluated the relevance of basophil allergen sensitivity testing to distinguish the severity of peanut allergy in children. Methods: Twenty-seven peanut-sensitized children with symptoms varying from mild symptoms to severe anaphylaxis underwent peanut CD63 dose-response curve analysis with the inclusion of basophil allergen sensitivity calculation (CD-sens) and peanut component immunoglobulin E (IgE) testing. Results: Eleven children who had experienced anaphylaxis to peanuts showed a markedly higher peanut CD63 response at submaximal allergen concentrations and CD-sens (median 1,667 vs. 0.5; p < 0.0001) than 16 children who experienced a milder reaction. Furthermore, a negative or low CD-sens to peanuts unambiguously excluded anaphylactic peanut allergy. Children with anaphylaxis have higher levels of Ara h 1, 2, 3 and 9 IgE, but comparable levels of IgE to Ara h 8 and whole-peanut extract. The diagnostic specificity calculated with a receiver operating characteristic analysis reached 100% for CD-sens and 73% for Ara h 2. Conclusions: We demonstrated that severe peanut allergy is significantly associated with higher basophil allergen sensitivity. This cellular test should facilitate a more accurate diagnosis of peanut allergy.
Forme Fruste Keratoconus Imaging and Validation via Novel Multi-Spot Reflection Topography
Authors: Kanellopoulos Anastasios John , Asimellis George
Published: October 2013

Background/Aims: This case report aims to evaluate safety, efficacy and applicability of anterior surface imaging in a patient with forme fruste keratoconus (FFKC) based on a novel multi-spot, multicolor light-emitting-diode (LED) tear film-reflection imaging technology Case Description: A 45-year-old male patient, clinically diagnosed with FFKC, with highly asymmetric manifestation between his eyes, was subjected to the multicolor-spot reflection topography. We investigated elevation and sagittal curvature maps comparatively with the multicolor-spot reflection topographer, a Placido topographer and a Scheimpflug imaging system. For the right eye, steep and flat keratometry values were 41.92 and 41.05 D with the multicolor spot-reflection topographer, 42.30 and 42.08 D with the Placido, and 41.95 and 41.19 D with the Scheimpflug system. For the left eye, steep and flat keratometry values were 41.86 and 41.19 D with the multicolor spot-reflection topographer, 42.06 and 41.66 D with the Placido topographer, and 41.96 and 41.66 D with the Scheimpflug camera. Average repeatability of the keratometry measurements was ±0.35 D for the multicolor spot-reflection topographer, ±0.30 D for the Placido, and ±0.25 D for the Scheimpflug camera. Very good agreement between the instruments was demonstrated on the elevation and curvature maps. Conclusion: The ease of use and the comparable results offered by the multicolor spot-reflection topographer, in comparison to established Placido and Scheimpflug imaging, as well as the increased predictability that may be offered by the multicolor spot-reflection topographer, may hold promise for wider clinical application, such as screening of young adults for early keratoconus and, in a much wider perspective, potential candidates for laser corneal refractive surgery.
Globotriaosylceramide Induces Lysosomal Degradation of Endothelial K
Ca
3.1 in Fabry Disease
Authors: Choi Shinkyu , Kim Ji Aee , Na Hye-Young , Cho Sung-Eun , Park Seonghee , Jung Sung-Chul , Suh Suk Hyo
Published: October 2013

Objective—

Globotriaosylceramide (Gb3) induces K
Ca
3.1 downregulation in Fabry disease (FD). We investigated whether Gb3 induces K
Ca
3.1 endocytosis and degradation.

Approach and Results—

K
Ca
3.1, especially plasma membrane–localized K
Ca
3.1, was downregulated in both Gb3-treated mouse aortic endothelial cells (MAECs) and human umbilical vein endothelial cells. Gb3-induced K
Ca
3.1 downregulation was prevented by lysosomal inhibitors but not by a proteosomal inhibitor. Endoplasmic reticulum stress–inducing agents did not induce K
Ca
3.1 downregulation. Gb3 upregulated the protein levels of early endosome antigen 1 and lysosomal-associated membrane protein 2 in MAECs. Compared with MAECs from age-matched wild-type mice, those from aged α-galactosidase A (Gla)-knockout mice, an animal model of FD, showed downregulated K
Ca
3.1 expression and upregulated early endosome antigen 1 and lysosomal-associated membrane protein 2 expression. In contrast, no significant difference was found in early endosome antigen 1 and lysosomal-associated membrane protein 2 expression between young Gla-knockout and wild-type MAECs. In aged Gla-knockout MAECs, clathrin was translocated close to the cell border and clathrin knockdown recovered K
Ca
3.1 expression. Rab5, an effector of early endosome antigen 1, was upregulated, and Rab5 knockdown restored K
Ca
3.1 expression, the current, and endothelium-dependent relaxation.

Conclusions

—Gb3 accelerates the endocytosis and lysosomal degradation of endothelial K
Ca
3.1 via a clathrin-dependent process, leading to endothelial dysfunction in FD.
RyR-NCX-SERCA Local Cross-Talk Ensures Pacemaker Cell Function at Rest and During the Fight-or-Flight Reflex
Authors: Maltsev Anna V. , Yaniv Yael , Stern Michael D. , Lakatta Edward G. , Maltsev Victor A.
Published: October 2013

Rationale:

A recent study published in
Circulation Research
by Gao et al used sinoatrial node (SAN)–targeted, incomplete Ncx1 knockout in mice to explore the role of the Na
+
/Ca
2+
exchanger (NCX) in cardiac pacemaker. The authors concluded that NCX is required for increasing sinus rates, but not for maintaining resting heart rate. This conclusion was based, in part, on numeric model simulations performed by Gao et al that reproduced their experimental results of unchanged action potentials in the knockout SAN cells. The authors, however, did not simulate the NCX current (I
NCX
), that is, the subject of the study.

Objective:

We extended numeric examinations to simulate I
NCX
in their incomplete knockout SAN cells that is crucial to interpret the study results.

Methods and Results:

I
NCX
and Ca
2+
dynamics were simulated using different contemporary numeric models of SAN cells. We found that minimum diastolic Ca
2+
levels and I
NCX
amplitudes generated by remaining NCX molecules (only 20% of control) remained almost unchanged. Simulations using a new local Ca
2+
control model indicate that these powerful compensatory mechanisms involve complex local cross-talk of Ca
2+
cycling proteins and NCX. Specifically, lower NCX expression facilitates Ca
2+
-induced Ca
2+
release and larger local Ca
2+
releases that stabilize diastolic I
NCX
. Further reduction of NCX expression results in arrhythmia and halt of automaticity.

Conclusions:

Remaining NCX molecules in the incomplete knockout model likely produce almost the same diastolic I
NCX
as in wild-type cells. I
NCX
contribution is crucially important for both basal automaticity of SAN cells and during the fight-or-flight reflex.
Investigational Analysis Reveals a Potential Role for Neutrophils in Giant-Cell Arteritis Disease Progression
Authors: Nadkarni Suchita , Dalli Jesmond , Hollywood Jane , Mason Justin C. , Dasgupta Bhaskar , Perretti Mauro
Published: October 2013

Rationale:

Giant-cell arteritis (GCA) is a large-vessel vasculitis characterized by immune cell infiltration, yet the potential involvement of neutrophils has rarely been studied.

Objective:

We investigated whether alterations in neutrophil reactivity occurred in the pathogenesis of GCA or during its clinical management with a canonical glucocorticoid dose regimen during a 6-month period.

Methods and Results:

Blood samples were taken within 48 hours of therapy commencement and at weeks 1, 4, and 24 after glucocorticoid dose. Flow cytometric analysis revealed 3 distinct neutrophil populations and phenotypes. Within 48 hours of steroid treatment, neutrophils displayed an AnxA1
hi
CD62L
lo
CD11b
hi
phenotype, whereas week 1 neutrophils were AnxA1
hi
CD62L
lo
CD11b
lo
and displayed minimal adhesion to endothelial monolayers under flow, and week 24 (ie, lowest glucocorticoid dose) neutrophils were AnxA1
hi
CD62L
hi
CD11b
hi
with increased endothelial adhesion under flow. Week 24 plasma analyses showed high levels of C-X-C motif chemokine ligand 5, interleukin (IL) 8, IL-17, and IL-6. Importantly, comparison of week 1 and week 24 samples revealed a suppressive neutrophil effect on T-cell proliferation at the former time point only. Finally, in vitro incubation of naive neutrophils with concentrations of IL-6 and IL-17 quantified in GCA plasma at weeks 1 and 24 replicated this differential modulation of lymphocyte proliferation.

Conclusions:

This translational study highlights a novel clinical manifestation of GCA, with evidence for a neutrophil component and an escaped proinflammatory phenotype when glucocorticoid therapy is tapered. These results indicate potential involvement of neutrophils in GCA pathogenesis.
Dietary Patterns Are Associated With Incident Stroke and Contribute to Excess Risk of Stroke in Black Americans
Authors: Judd Suzanne E. , Gutiérrez Orlando M. , Newby P.K. , Howard George , Howard Virginia J. , Locher Julie L. , Kissela Brett M. , Shikany James M.
Published: October 2013

Background and Purpose—

Black Americans and residents of the Southeastern United States are at increased risk of stroke. Diet is one of many potential factors proposed that might explain these racial and regional disparities.

Methods—

Between 2003 and 2007, the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort study enrolled 30 239 black and white Americans aged ≥45 years. Dietary patterns were derived using factor analysis and foods from food frequency data. Incident strokes were adjudicated using medical records by a team of physicians. Cox-proportional hazards models were used to examine risk of stroke.

Results—

During 5.7 years, 490 incident strokes were observed. In a multivariable-adjusted analysis, greater adherence to the plant-based pattern was associated with lower stroke risk (hazard ratio, 0.71; 95% confidence interval, 0.56–0.91;
P
trend
=0.005). This association was attenuated after addition of income, education, total energy intake, smoking, and sedentary behavior. Participants with a higher adherence to the Southern pattern experienced a 39% increased risk of stroke (hazard ratio, 1.39; 95% confidence interval, 1.05, 1.84), with a significant (
P
=0.009) trend across quartiles. Including Southern pattern in the model mediated the black–white risk of stroke by 63%.

Conclusions—

These data suggest that adherence to a Southern style diet may increase the risk of stroke, whereas adherence to a more plant-based diet may reduce stroke risk. Given the consistency of finding a dietary effect on stroke risk across studies, discussing nutrition patterns during risk screening may be an important step in reducing stroke.
The Interpretation of Prosody in Disjunctive Questions
Authors: Pruitt Kathryn , Roelofsen Floris
Published: October 2013

Alternative questions differ prosodically from identically worded disjunctive yes/no questions in their accentual characteristics and their final pitch contour. Alternative questions are canonically pronounced with a final fall and with pitch accents on all disjuncts, while disjunctive yes/no questions are canonically pronounced with a final rise and generally without pitch accents on every disjunct. This article presents an experiment investigating the importance of these prosodic features in disambiguation. The experiment shows that the final contour is the most informative prosodic feature. Accentual characteristics also play a significant role, but, contrary to what is often assumed in the literature, cannot force an alternative question interpretation or a yes/no question interpretation on their own. Several theories of disjunctive questions are discussed in the light of these experimental results.