Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacokinetic–pharmacodynamic analysis of the arrhythmogenic potency of a novel antiallergic agent, ebastine, in rats

Ebastine (EBS), a novel nonsedative antiallergic agent, is similar to terfenadine in its chemical structure. However, clinical arrhythmogenicity of EBS remains controversial. In this study, we evaluated the possible arrhythmogenic potency of EBS as assessed by QT prolongation from a pharmacokinetic–pharmacodynamic viewpoint in comparison with that of terfenadine. EBS was intravenously infused into anesthetized rats at a rate of 3.0 or 10 mg/kg/h for 60 min, and electrocardiographic effects were continuously monitored from lead II. The plasma concentrations of EBS and its major metabolite, carebastine, were also measured under the same conditions. When intravenously administered, EBS exhibited QT prolongation in an infusion rate‐dependent manner, with a lag time. Pharmacokinetic–pharmacodynamic analysis of EBS based on the effect‐compartment model revealed values of EC50, Emax and EC10 ms (where 10 ms of QT prolongation was evoked) of 0.73 μg/mL, 12.5 ms and 2.90 μg/mL, respectively. The EC10 ms value of EBS was five times higher than that of terfenadine reported previously (Ohtani et al., J. Pharm. Pharmacol., 49, 458–462 (1997)). In conclusion, EBS was suggested to be less arrhythmogenic than terfenadine. Copyright © 1999 John Wiley & Sons, Ltd.
Changes in gut mucosal nitric oxide synthase (NOS) activity after thermal injury and its relation with barrier failure.

This study was designed to investigate changes in mucosal NOS activity after burns and its relation to barrier failure. In Experiment 1, female specific pathogen free (SPF) Sprague-Dawley rats underwent 35% total body surface area (TBSA) burn. One to six days after burn, intestinal permeability was determined from the plasma leakage of fluorescein isothiocyanate (FITC)-dextran 4400, intestinal mucosal cNOS and iNOS activity were assayed using Griess' reagent, and the cellular localization of iNOS was examined using immunostaining. In Experiment 2, S-methylisothiourea (SMT) was given (5 mg/kg, i.p. every 12 h) for 2 days to suppress inducible NOS (iNOS) activity after thermal injury. On postburn Day 2, the effect of SMT on gut mucosal NOS activity, intestinal permeability, and barrier function were evaluated. The activity of iNOS increased 24 h after the injury and up to a maximum of twofold on postburn Day 2, and decreased thereafter. The increase in iNOS activity in gut mucosa correlated well with the increase in intestinal permeability, an index for barrier failure (r = .776, p = .0002). Results from iNOS immunostaining showed that changes in mucosal iNOS activity after the burn occurred mainly in the enterocytes rather than in the macrophages. Administration of SMT decreased mucosal iNOS activity, intestinal permeability, and bacterial translocation incidence to mesenteric lymph node concurrently. In conclusion, thermal injury induces intestinal mucosal iNOS, which is principally in the enterocytes. The increased intestinal iNOS activity was closely related to barrier failure. SMT inhibited intestinal mucosal iNOS activity and prevented barrier failure as demonstrated by a decrease in BT occurrence and intestinal permeability.
TCAD simulations of double gate junctionless tunnel field effect transistor with spacer

In this paper, we proposed a double gate junction-less tunnel field effect transistor (DGJL-TFET) with the spacer. The performance parameters of the device are figured as in terms of ON-state to the OFF-state current ratio(ION/ Ioff), sub-threshold swing (SS) and output transconductance(gd). By using dielectric as a spacer, we can observed that the ON-state current of the device increase and consequently making the device more versatile. However, the OFF-state current is just slightly influenced by rising dielectric constant of the spacer. In this paper, we compare the proposed device with DGJL-TFET and observe that the proposed device have the better candidate for the low power device.
A Novel, Orally Bioavailable Nociceptin Receptor Antagonist, LY2940094, Reduces Ethanol Self-Administration and Ethanol Seeking in Animal Models.

BACKGROUND The nociceptin/orphanin-FQ (or opioid receptor-like [ORL1]) receptor (NOP) is localized in the mesolimbic reward pathway and has been suggested to play a role in feeding, mood, stress, and addiction. Since its deorphanization in 1995, there has been a clear dichotomy in the literature regarding whether an agonist or antagonist would provide therapeutic benefit. Specifically, the literature reports indicate that NOP receptor antagonists produce efficacy in animal models of hyperphagia and antidepressant-like activity, whereas NOP agonists produce anxiolytic-like effects and dampen reward/addiction behaviors including ethanol consumption. METHODS We characterize here the potent, orally bioavailable NOP antagonist, LY2940094, in rodent models of ethanol consumption, including ethanol self-administration, progressive ratio operant self-administration, stress-induced reinstatement of ethanol seeking, and in vivo microdialysis in the nucleus accumbens. RESULTS LY2940094 dose dependently reduced homecage ethanol self-administration in Indiana alcohol-preferring (P) and Marchigian Sardinian alcohol-preferring (msP) rats, without affecting food/water intake or locomotor activity. Reduced ethanol intake in P rats did not show significant tolerance over 4 days of subchronic dosing. LY2940094 attenuated progressive ratio operant responding and break points for ethanol in P rats. Moreover, stress-induced reinstatement of ethanol seeking in msP rats was completely blocked by LY2940094. Furthermore, LY2940094 blocked ethanol-stimulated dopamine release in response to ethanol challenge (1.1 g/kg, intraperitoneally). CONCLUSIONS Our findings demonstrate for the first time that blockade of NOP receptors attenuates ethanol self-administration and ethanol-motivated behaviors, stress-induced ethanol seeking, and ethanol-induced stimulation of brain reward pathways in lines of rats that exhibit excessive ethanol consumption. Results suggest that LY2940094 may have potential therapeutic utility in treating alcohol addiction.
Separation of the Monotone NC Hierarchy

, for the monotone depth of functions in monotone-P. As a result we achieve the separation of the following classes. 1. monotone-NC ≠ monotone-P. 2. For every i≥1, monotone-≠ monotone-. 3. More generally: For any integer function D(n), up to (for some ε>0), we give an explicit example of a monotone Boolean function, that can be computed by polynomial size monotone Boolean circuits of depth D(n), but that cannot be computed by any (fan-in 2) monotone Boolean circuits of depth less than Const·D(n) (for some constant Const). Only a separation of monotone- from monotone- was previously known. Our argument is more general: we define a new class of communication complexity search problems, referred to below as DART games, and we prove a tight lower bound for the communication complexity of every member of this class. As a result we get lower bounds for the monotone depth of many functions. In particular, we get the following bounds: 1. For st-connectivity, we get a tight lower bound of . That is, we get a new proof for Karchmer–Wigderson's theorem, as an immediate corollary of our general result. 2. For the k-clique function, with , we get a tight lower bound of Ω(k log n). This lower bound was previously known for k≤ log n [1]. For larger k, however, only a bound of Ω(k) was previously known.
Dynamics of intestinal metabolites and morphology in response to necrotic enteritis challenge in broiler chickens

ABSTRACT Despite the relatively small contribution to metabolizable energy that volatile fatty acids (VFAs) provide in chickens, these organic acids have been reported to play beneficial roles in the gastrointestinal tract (GIT) of birds, for example, inhibition of the growth of some pathogenic bacteria. However, information regarding the dynamics of these metabolites in the GIT of chickens is still scarce, especially under disease conditions such as necrotic enteritis (NE). Here, we investigated the dynamics of VFAs and lactic acid, and intestinal morphology in response to NE predisposing factors, that is, excessive dietary fishmeal and Eimeria inoculation, and causative agent Clostridium perfringens producing NetB toxin. The experiment was designed in a 2 × 2 × 2 factorial arrangement of treatments with or without: fishmeal feeding, Eimeria inoculation and C. perfringens challenge. The results showed that these factors significantly influenced composition and concentration of VFAs and lactic acids, pH and histomorphometry in one way or another. These changes may be important for the onset of NE or only the synergetic responses to micro environmental stress. Eimeria appeared to be more important than fishmeal in predisposing birds to NE, thus the application of Eimeria in NE challenge provides more consistent success in inducing the disease. The metabolic responses to various adverse factors such as excessive dietary fishmeal and Eimeria infection are complex. Thus, intensive efforts are required to better understand NE so as to achieve the control of the disease in the absence of antibiotics.
Modeling and realization of GaN-based dual-gate HEMTs and HPA MMICs for Ku-band applications

This paper reports on linear and nonlinear modeling and realization of AlGaN/GaN dual-gate HEMTs and high power amplifier (HPA) MMICs for Ku-band applications. A method to describe the extrinsic and intrinsic parts of the dual-gate structure separated from each other using a distributed modeling approach is demonstrated. A small-signal model based on this approach was developed. A scalable nonlinear model was obtained through enhancing the small-signal model by an intrinsic large-signal state-space kernel. The excellent capabilities of both the linear and nonlinear models are demonstrated on fabricated dual-gate HEMTs with 0.25 µm gate length and a total gate width between 0.3mm and 0.8mm with a varying number of fingers. A 14–18 GHz, 2.5W high power amplifier was designed and realized to illustrate the suitability of the developed models for MMIC design.
Ćuk-based universal converters in discontinuous conduction mode of operation

This paper introduces an open-loop control scheme for Ćuk-based universal converters that have recently been proposed by the author. Ćuk-based universal converters extend the principles of the operation a dc-dc Ćuk converter to systems with single-phase or multi-phase ac sources and/or loads. These power converters can provide galvanic isolation by adding a single-phase high frequency transformer to the link. This eliminates the need for low frequency transformers that have large volume and weight. Being single-stage, the Ćuk-based universal converters do not require decoupling components, and a small capacitor is used for transferring the power from input towards output. This eliminates the need for large electrolytic capacitors that have high failure rates. In prior works, a closed-loop control system was used for the Ćuk-based universal converters. These converters were controlled such that they always operate at the boundary of continuous and discontinuous conduction modes, which leads to a variable switching frequency and a large voltage ripple across the link capacitor. The closed-loop operation along with variable switching frequency result in a complex control algorithm, which can limit the maximum switching frequency of the converter. This paper proposes an open-loop control scheme that allows the converter operate in discontinuous conduction mode and with a fixed switching frequency. Implementation of the proposed control scheme is simpler than the closed-loop control method. This paper presents details of the proposed method and evaluates its effectiveness.
Non-protected carotid artery stent without angioplasty in high-risk patients with carotid and coronary artery disease undergoing cardiac surgery

Abstract Hemodynamic depression (HD) is a frequent complication related to carotid endartherectomy or carotid artery stenting (CAS), often not well tolerated in patients with coronary artery disease. The purpose of this study is to assess whether CAS without angioplasty is beneficial in patients with severe carotid artery disease before coronary revascularization surgery (CABG) regarding the occurrence of HD. Between October 2002 and August 2006, 39 CAS were performed in 35 patients before cardiac surgery. Outcome measures, including periprocedural and 30-day post stenting and cardiac surgery complications, were assessed. Twenty-seven patients underwent CABG and eight combined CABG and valve replacement. During or immediately after CAS there was no episode of bradycardia or hypotension necessitating medical treatment. In the period between CAS-CABG, there was no case of HD. We also found no myocardial infarction. There were five neurological complications, two of them in the period between CAS-CABG (one transitory ischemic attack (TIA) and one minor stroke) and three after CABG (one TIA and two strokes). Three of them were discharged symptom-free. CAS without angioplasty can be a safe alternative to treat patients with coexistence of carotid and cardiac disease, since does not produce hemodynamic depression, therefore diminishing the cardiac complications.
Ghrelin does not modulate angiogenesis in matrigel plug in normal and diet-induced obese mice

Background: The reciprocal interaction between adipocytes and angiogenesis is considered as an essential component in the development and expansion of adipose tissue. The aim of this study was to evaluate the effect of ghrelin on angiogenic response using in vivo angiogenesis assay of matrigel plug and its correlation with serum leptin levels in normal and diet-induced obese mice. Materials and Methods: This experimental study has been done on 24 male C57BL/6 mice which were randomly divided into four groups: Normal diet (ND) or control, ND + ghrelin, high-fat-diet (HFD) or obese and HFD + ghrelin (n = 6/group). Obese and control groups received HFD or standard diet for 14 weeks. Then, growth factor reduced matrigel plug (500 μl) containing bFGF (basic fibroblast growth factor; 100 ng) with or without ghrelin (100 μg/kg) was injected subcutaneously in the mid-ventral abdominal region of each mice. After 10 days, blood samples were taken and matrigel plugs were removed under anesthesia and angiogenic response was assessed by immunohisochemical staining. Results: HFD significantly increased angiogenesis in matrigel plug as expressed as the number of CD31-positive cells than standard diet (43 ± 5 vs. 13 ± 2.5 CD31+ cells/field). Ghrelin did not alter angiogenesis in matrigel plug in both obese and control groups. There was a strong positive correlation between the number of CD31-positive cells and serum leptin concentration (r = 0.91). Conclusion: Leptin as an angiogenic factor has a positive correlation with angiogenesis in matrigel plug model of angiogenesis and ghrelin could not alter angiogenesis.
A Pilot Study of Citalopram Treatment in Preventing Relapse of Depressive Episode after Acute Treatment.

PURPOSE To examine the benefit of continuation treatment with citalopram in adolescents 13 to 18 years of age with major depression using a multi-site randomized placebo controlled discontinuation design. METHODS Subjects with depression who responded to open label treatment with citalopram in 12-week acute phase were randomized to continued treatment with citalopram or placebo for 24 weeks. RESULTS Twenty five subjects were randomized to either continued treatment with citalopram (n = 12) versus placebo (n = 13). Seventy-five percent of subjects on citalopram (75%) remained well as compared to placebo (62%). Time to relapse was compared between groups using the log rank test and was not found to be significantly different (χ(2)(1) = 0.35, P = 0.55). A Cox proportional hazards model including drug assignment (hazard ratio (HR = 0.51, 95% CI 0.11 to 2.36, P = 0.39), gender (HR = 0.58, 95% CI 0.14 to 2.37, P = 0.44), or HAM-score at entry to continuation phase (HR = 1.33, 95% CI 0.90 to 1.95, P = 0.95) was not significant. CONCLUSION Although we did not find statistically significant differences between citalopram and placebo, the findings suggest a possible benefit of continued treatment with citalopram over placebo. A larger clinical trial with adequate power is required to confirm or disconfirm these findings.
Point‐by‐Point Radiofrequency Ablation Versus the Cryoballoon or a Novel Combined Approach: A Randomized Trial Comparing 3 Methods of Pulmonary Vein Isolation for Paroxysmal Atrial Fibrillation (The Cryo Versus RF Trial)

Catheter ablation of paroxysmal AF using the Cryoballoon (CRYO) has yielded similar success rates to conventional wide encirclement using radiofrequency catheter ablation (RFCA), but randomized data are lacking. Pilot data suggested a high success rate with a combined approach (COMBINED) using wide encirclement with RFCA followed by 2 CRYO applications to each vein. We compared these 3 strategies in a randomized controlled trial.
Prediction of FSS radome performane using simple design equation

We propose a design equation for the resonant frequency of FSS radome due to the dielectric cover effect. The FSS radome structure is composed of the single layer arrays of square loop symmetrically embedded in a dielectric layer. This equation was obtained through the curve fitting method based on FSS radome's fullwave simulation for various thickness and different permittivity. To validate the proposed equation, the FSS radomes having various thicknesses were fabricated and measured for prediction of their performance. From the obtained results, we also present the dielectric thickness range of FSS radome that the proposed equation can be applied. We believe that the proposed equation is very useful to design FSS radome and can be applied to various communication and electrical instruments.
Lysophosphatidic Acid and Platelet-Derived Growth Factor Synergistically Stimulate Growth of Cultured Rat Mesangial Cells

Abstract Lysophosphatidic acid (LPA) is a structurally simple, platelet-derived phospholipid, capable of eliciting a variety of physiological responses. We have demonstrated previously that LPA elicited a marked contractile response in rat mesangial cells (Inoue CN, Forster HG, Epstein M. Circ Res 77:888-896, 1995). In the present study, we examined the potential of this vasoactive substance to induce mesangial cell proliferation. Serum-starved quiescent rat mesangial cells were incubated with either LPA or in combination with platelet-derived growth factor (PDGF). DNA synthesis was assessed by [3H]thymidine incorporation after 24 hr, and cell numbers were determined at 0, 4, and 7 days. LPA- (1 nM-30 μM) stimulated mesangial cell DNA synthesis in a dose-dependent manner. The DNA synthesis stimulated by PDGF (1-100 ng/ml) was characterized by a bell-shaped response curve with a maximum at 40 ng/ml PDGF. The ability of LPA (30 μM) to synergize PDGF was observed over the entire range of PDGF concentrations (1-100 ng/ml). Under optimal concentrations of LPNPDGF (30 μM40 ng/ml, respectively), mesangial cells displayed a 67-fold increase in [3H]thymidine incorporation, and a 1.9-fold (Day 4) and 2.5-fold (Day 7) increase in cell number as compared with that of quiescent mesangial cells. With an in vitro assay with myelin basic protein as the substrate, both LPA and PDGF induced stimulation of mitogen-activated protein (MAP) kinase activity. In addition, LPA augmented PDGF-induced increase in MAP kinase activity. In summary, these results demonstrate that LPA is mitogenic alone and also acts synergistically in combination with PDGF to promote mesangial cell proliferation. We postulate that these actions of LPA have the potential to play a crucial role in the mitogenic response of mesangial cells seen in a wide array of inflammatory and thrombotic glomerular disorders.
New malignant diseases after allogeneic marrow transplantation for childhood acute leukemia.

PURPOSE To determine the incidence of and risk factors for second malignancies after allogeneic bone marrow transplantation (BMT) for childhood leukemia. PATIENTS AND METHODS We studied a cohort of 3, 182 children diagnosed with acute leukemia before the age of 17 years who received allogeneic BMT between 1964 and 1992 at 235 centers. Observed second cancers were compared with expected cancers in an age- and sex-matched general population. Risks factors were evaluated using Poisson regression. RESULTS Twenty-five solid tumors and 20 posttransplant lymphoproliferative disorders (PTLDs) were observed compared with 1.0 case expected (P <.001). Cumulative risk of solid cancers increased sharply to 11.0% (95% confidence interval, 2.3% to 19.8%) at 15 years and was highest among children at ages younger than 5 years at transplantation. Thyroid and brain cancers (n = 14) accounted for most of the strong age trend; many of these patients received cranial irradiation before BMT. Multivariate analyses showed increased solid tumor risks associated with high-dose total-body irradiation (relative risk [RR] = 3.1) and younger age at transplantation (RR = 3.7), whereas chronic graft-versus-host disease was associated with a decreased risk (RR = 0.2). Risk factors for PTLD included chronic graft-versus-host disease (RR = 6.5), unrelated or HLA-disparate related donor (RR = 7. 5), T-cell-depleted graft (RR = 4.8), and antithymocyte globulin therapy (RR = 3.1). CONCLUSION Long-term survivors of BMT for childhood leukemia have an increased risk of solid cancers and PTLDs, related to both transplant therapy and treatment given before BMT. Transplant recipients, especially those given radiation, should be monitored closely for second cancers.