LTLf satisfiability checking

We consider here Linear Temporal Logic (LTL) formulas interpreted over \emph{finite} traces. We denote this logic by LTLf. The existing approach for LTLf satisfiability checking is based on a reduction to standard LTL satisfiability checking. We describe here a novel direct approach to LTLf satisfiability checking, where we take advantage of the difference in the semantics between LTL and LTLf. While LTL satisfiability checking requires finding a \emph{fair cycle} in an appropriate transition system, here we need to search only for a finite trace. This enables us to introduce specialized heuristics, where we also exploit recent progress in Boolean SAT solving. We have implemented our approach in a prototype tool and experiments show that our approach outperforms existing approaches

Fast LTL Satisfiability Checking by SAT Solvers

Satisfiability checking for Linear Temporal Logic (LTL) is a fundamental step in checking for possible errors in LTL assertions. Extant LTL satisfiability checkers use a variety of different search procedures. With the sole exception of LTL satisfiability checking based on bounded model checking, which does not provide a complete decision procedure, LTL satisfiability checkers have not taken advantage of the remarkable progress over the past 20 years in Boolean satisfiability solving. In this paper, we propose a new LTL satisfiability-checking framework that is accelerated using a Boolean SAT solver. Our approach is based on the variant of the \emph{obligation-set method}, which we proposed in earlier work. We describe here heuristics that allow the use of a Boolean SAT solver to analyze the obligations for a given LTL formula. The experimental evaluation indicates that the new approach provides a a significant performance advantage

Resection Cavity Contraction Effects in the Use of Radioactive Sources (1-25 versus Cs-131) for Intra-Operative Brain Implants.

Background and Objectives Intra-parenchymal brain surgical resection cavities usually contract in volume following low dose rate (LDR) brachytherapy implants. In this study, we systematically modeled and assessed dose variability resulting from such changes for I-125 versus Cs-131 radioactive sources. Methods Resection cavity contraction was modeled based on 95 consecutive patient cases, using surveillance magnetic resonance (MR) images. The model was derived for single point source geometry and then fully simulated in 3D where I-125 or Cs-131 seeds were placed on the surface of an ellipsoidal resection cavity. Dose distribution estimated via TG-43 calculations and biological effective dose (BED) calculations were compared for both I-125 and Cs-131, accounting for resection cavity contractions. Results Resection cavity volumes were found to contract with an effective half-life of approximately 3.4 months (time to reach 50% of maximum volume contraction). As a result, significant differences in dose distributions were noted between I-125 and Cs-131 radioactive sources. For example, when comparing with static volume, assuming no contraction effect, I-125 exhibited a 31.8% and 30.5% increase in D90 and D10 values (i.e., the minimal dose to 90% and 10% of the volume respectively) in the peripheral target areas over the follow-up period of 20.5 months. In contrast, Cs-131 seeds only exhibited a 1.44% and 0.64% increase in D90 and D10 values respectively. Such discrepancy is likewise similar for BED calculations. Conclusion Resection cavity contractions affects Cs-131 dose distribution significantly less than that of I-125 for permanent brain implants. Care must be taken to account for cavity contractions when prescribing accumulative doses of a radioactive source in performing the brain implant procedures

Effects of Isoproterenol on IhERG during K+ changes in HEK293 cells

noIntroduction:The human ether-a-go-go related gene (hERG) encodes the pore forming protein which mediates the rapid delayed rectifier K+ current in the heart (IKr). Together with other ion channels hERG determines the cardiac action potential and regulates the heart beating. Dysfuction of the hERG ion channel will lead to acquired long QT syndrome (LQTS). Therefore, new drug candidates must pass the test for a potential inhibitory effect on the hERG current as a first step in a nonclinical testing strategy. Arrhythmias in patients with LQTS are typically triggered during physical or emotional stress, suggesting a link between sympathetic stimulation and arrhythmias. It is well known that potassium level can affect the QT interval through affecting IhERG both in vivo and in vitro.In this study, we try to find out whether the trigger effect still exist when K+ changes violently in a short time period. In other words, whether the risk of TdP aggravate when patients suffer from acute water electrolyte balance disorder, which is a common symptom in hot weather. Methods: HEK293 Cell line stably expressing hERG channel were cultured in DMEM supplemented with 10% of fetal bovine serum.Whole-cell patch-clamp method was applied for ionic current recordings. The compositions of pipette was (in mM) 125 KCl, 5 MgCl2, 5 EGTA-K, 10 HEPES-K and 5 Na-ATP adjusted to pH 7.2 with KOH. The bath solutions for recording the IhERG currents was 136 NaCl, 4 KCl, 1 MgCl2, 10 HEPES-Na, 1.8 CaCl2 and 10 glucose, pH 7.4 with NaOH. The low extracellular K+ solution was 115 KCl, 5 MgCl2, 5 EGTA-K, 10 HEPES-K and 10 Na-ATP adjusted to pH 7.2 with NaOH. Patch-clamp experiments were performed at room temperature (22 ± 1°C). The recording of low K+ current was carried out immediately after the original normal K+ solution has been totally replaced. Isoproterenol (ISO) 100nM was added into both kinds of K+ solution to apply the effect of β1-AR stimulation. Results: We found that low K+ solution increased IhERG from 907.39±18.68to 1620.08±249.44pA(n=30,P<0.05); Low K+also shifted the I-V curve to the left. IC50 in control is 10.31±5.52 mV, low K+ is -6.15±1.58 mV. When adding ISO 100nM to extracellular solution, same effects were shown for both groups.ISO decreased Imax for both group. In control group, Imax reduced from 907.39±18.68to493.16±54.41pA (n=30, P<0.01), while in low K+ group, I max decreased Imax from 1620.08±29.44to 488.48±81.87pA(n=30,P<0.05). At the same time, ISO shifts the I-V curve to the right for the control group and shift the curve to the left for low K+ group. IC50 in control when added ISO is 22.25±3.80 mV, while IC50 in low K+ group after adding 100nM ISO is -31.00±5.73 mV. Conclusion: The results from this study is contradict to those in our previous study where low K+ combined with ISO can lead to temporarily increase of QT interval in vivo.It is reported that an increase in net outward repolarizing current, due to a relatively large increase of IKs, is responsible for the changes of QT interval in response to beta-adrenergic stimulation in vivo(2). Therefore future studies need to co-transfect IKs channel to confirm this. References: 1. Guo J, Massaeli H, Xu J, Jia Z, Wigle JT, Mesaeli N, et al. Extracellular K+ concentration controls cell surface density of IKr in rabbit hearts and of the HERG channel in human cell lines. The Journal of clinical investigation. 2009;119(9):2745- 57. 2. Shimizu W, Antzelevitch C. Differential effects of beta-adrenergic agonists and antagonists in LQT1, LQT2 and LQT3 models of the long QT syndrome. Journal of the American College of Cardiology. 2000;35(3):778-86

The Determination of Degradation Products of Lewisite and/or Mustard Gas in Water by High Performance Liquid Chromatography

Lewisite (L) and mustard gas (HD) are highly toxic vesicant warfare agents that are very sparingly soluble in water and thereby converted quantitatively to the stable and soluble degradation products 2-chlorovinylarsonous acid (CVAA), 2-chloro vinylarsonic acid (CVAOA), 2,2’-dihydroxyethyl sulphide and 2,2’-dichlorodiethyl sulphoxide. A new method based on reversed-phase high performance liquid chromatography (RP-HPLC) has been developed for the simultaneous detection of CVAOA, CVAA, 2,2’-dichlorodiethyl sulphoxide, 2,2’-dihydroxyethyl sulphide. The effects of eluent and pH on the separation efficiency were studied. UV spectra of CVAOA, CVAA, 2,2’-dichlorodiethyl sulphoxide and 2,2’-dihydroxyethyl sulphide were recorded. Good separation was achieved by HPLC using a 250 × 4.6 mm column with 5 μm ODS C18 after optimization of all relevant parameters. The calibration curves ofCVAOA,CVAA, 2,2’-dichlorodiethyl sulphoxide and 2,2’-dihydroxyethyl sulphide showed high linearity over a concentration range of 5–500, 2–500, 5–500, 50–1000 mg L–1, respectively. The detection limits at a signal-to-noise ratio of 3 were 0.001, 0.2, 2, 20mgL–1. The method may be beneficial for studying the distribution of lewisite-and/or mustard gas and their degradation products in the environment.Keywords: High performance liquid chromatography, 2-chlorovinylarsonic acid, -chlorovinylarsonous acid, 2,2’-dichlorodiethylsulphoxide, 2,2’-dihydroxyethyl sulphide

Size dependent effects of gold nanoparticles in ISO-induced hyperthyroid rats

YesIn this study, we applied different sizes of gold nanoparticles (Au-NPs) to isoproterenol (ISO)-induced hyperthyroid heart disease rats (HHD rats). Single dose of 5, 40, 100 nm Au-NPs were injected intravenously. Cardiac safety tests were evaluated by cardiac marker enzymes in serum and cardiac accumulation of Au-NPs were measured by ICP-MS. Our results showed that size-dependent cardiac effects of Au-NPs in ISO-induced hyperthyroid rats. 5 nm Au-NPs had some cardiac protective effect but little accumulation in heart, probably due to smaller size Au-NPs can adapt to whole body easily in vivo. Histological analysis and TUNEL staining showed that Au-NPs can induce pathological alterations including cardiac fibrosis, apoptosis in control groups, however they can protect HHD groups from these harmful effects. Furthermore, transmission electron microscopy and western blotting employed on H9C2 cells showed that autophagy presented in Au-NPs treated cells and that Au-NPs can decrease LC3 II turning to LC3 I and decrease APG7 and caspase 12 in the process in HHD groups, while opposite effects on control groups were presented, which could be an adaptive inflammation reacts. As there are few animal studies about using nanoparticles in the treatment of heart disease, our in vivo and in vitro studies would provide valuable information before they can be considered for clinical use in general

Electronic correlations in the iron pnictides

In correlated metals derived from Mott insulators, the motion of an electron is impeded by Coulomb repulsion due to other electrons. This phenomenon causes a substantial reduction in the electron's kinetic energy leading to remarkable experimental manifestations in optical spectroscopy. The high-Tc superconducting cuprates are perhaps the most studied examples of such correlated metals. The occurrence of high-Tc superconductivity in the iron pnictides puts a spotlight on the relevance of correlation effects in these materials. Here we present an infrared and optical study on single crystals of the iron pnictide superconductor LaFePO. We find clear evidence of electronic correlations in metallic LaFePO with the kinetic energy of the electrons reduced to half of that predicted by band theory of nearly free electrons. Hallmarks of strong electronic many-body effects reported here are important because the iron pnictides expose a new pathway towards a correlated electron state that does not explicitly involve the Mott transition.Comment: 10 page

The Sixth Transmembrane Segment Is a Major Gating Component of the TMEM16A Calcium-Activated Chloride Channel.

Calcium-activated chloride channels (CaCCs) formed by TMEM16A or TMEM16B are broadly expressed in&nbsp;the nervous system, smooth muscles, exocrine glands, and other tissues. With two calcium-binding sites and a pore within each monomer, the dimeric CaCC exhibits voltage-dependent calcium sensitivity. Channel activity also depends on the identity of permeant anions. To understand how CaCC regulates neuronal signaling and how CaCC is, in turn, modulated by neuronal activity, we examined the molecular basis of CaCC gating. Here, we report&nbsp;that voltage modulation of TMEM16A-CaCC involves voltage-dependent occupancy of calcium- and anion-binding site(s) within the membrane electric field as well as a voltage-dependent conformational change intrinsic to the channel protein. These gating modalities all critically depend on the sixth transmembrane segment