bluuebunny/crossref_metadata_2025 huggingface dataset:
The Arf GTPase-Activating Protein Family Is Exploited by Salmonella enterica Serovar Typhimurium To Invade Nonphagocytic Host Cells
Authors: Davidson Anthony C. , Humphreys Daniel , Brooks Andrew B. E. , Hume Peter J. , Koronakis Vassilis
Published: February 2015

To establish intracellular infections, Salmonella bacteria trigger host cell membrane ruffling and invasion by subverting cellular Arf guanine nucleotide exchange factors (GEFs) that activate Arf1 and Arf6 GTPases by promoting GTP binding. A family of cellular Arf GTPase-activating proteins (GAPs) can downregulate Arf signaling by stimulating GTP hydrolysis, but whether they do this during infection is unknown. Here, we uncovered a remarkable role for distinct Arf GAP family members in Salmonella invasion. The Arf6 GAPs ACAP1 and ADAP1 and the Arf1 GAP ASAP1 localized at Salmonella-induced ruffles, which was not the case for the plasma membrane-localized Arf6 GAPs ARAP3 and GIT1 or the Golgi-associated Arf1 GAP1. Surprisingly, we found that loss of ACAP1, ADAP1, or ASAP1 impaired Salmonella invasion, revealing that GAPs cannot be considered mere terminators of cytoskeleton remodeling. Salmonella invasion was restored in Arf GAP-depleted cells by expressing fast-cycling Arf derivatives, demonstrating that Arf GTP/GDP cycles facilitate Salmonella invasion. Consistent with this view, both constitutively active and dominant-negative Arf derivatives that cannot undergo GTP/GDP cycles inhibited invasion. Furthermore, we demonstrated that Arf GEFs and GAPs colocalize at invading Salmonella and collaborate to drive Arf1-dependent pathogen invasion. This study revealed that Salmonella bacteria exploit a remarkable interplay between Arf GEFs and GAPs to direct cycles of Arf GTPase activation and inactivation. These cycles drive Salmonella cytoskeleton remodeling and enable intracellular infections.

IMPORTANCE
To initiate infections, the Salmonella bacterial pathogen remodels the mammalian actin cytoskeleton and invades host cells by subverting host Arf GEFs that activate Arf1 and Arf6 GTPases. Cellular Arf GAPs deactivate Arf GTPases and negatively regulate cell processes, but whether they target Arfs during infection is unknown. Here, we uncovered an important role for the Arf GAP family in Salmonella invasion. Surprisingly, we found that Arf1 and Arf6 GAPs cooperate with their Arf GEF counterparts to facilitate cycles of Arf GTPase activation and inactivation, which direct pathogen invasion. This report illustrates that GAP proteins promote actin-dependent processes and are not necessarily restricted to negatively regulating cellular signaling. It uncovers a remarkable interplay between Arf GEFs and GAPs that is exploited by Salmonella to establish infection and expands our understanding of Arf GTPase-regulated cytoskeleton remodeling.
Mitochondrial Heat Shock Protein Machinery Hsp70/Hsp40 Is Indispensable for Proper Mitochondrial DNA Maintenance and Replication
Authors: Týč Jiří , Klingbeil Michele M. , Lukeš Julius
Published: February 2015

Mitochondrial chaperones have multiple functions that are essential for proper functioning of mitochondria. In the human-pathogenic protist
Trypanosoma brucei
, we demonstrate a novel function of the highly conserved machinery composed of mitochondrial heat shock proteins 70 and 40 (mtHsp70/mtHsp40) and the ATP exchange factor Mge1. The mitochondrial DNA of T. brucei, also known as kinetoplast DNA (kDNA), is represented by a single catenated network composed of thousands of minicircles and dozens of maxicircles packed into an electron-dense kDNA disk. The chaperones mtHsp70 and mtHsp40 and their cofactor Mge1 are uniformly distributed throughout the single mitochondrial network and are all essential for the parasite. Following RNA interference (RNAi)-mediated depletion of each of these proteins, the kDNA network shrinks and eventually disappears. Ultrastructural analysis of cells depleted for mtHsp70 or mtHsp40 revealed that the otherwise compact kDNA network becomes severely compromised, a consequence of decreased maxicircle and minicircle copy numbers. Moreover, we show that the replication of minicircles is impaired, although the lack of these proteins has a bigger impact on the less abundant maxicircles. We provide additional evidence that these chaperones are indispensable for the maintenance and replication of kDNA, in addition to their already known functions in Fe-S cluster synthesis and protein import.

IMPORTANCE
  Impairment or loss of mitochondrial DNA is associated with mitochondrial dysfunction and a wide range of neural, muscular, and other diseases. We present the first evidence showing that the entire mtHsp70/mtHsp40 machinery plays an important role in mitochondrial DNA replication and maintenance, a function likely retained from prokaryotes. These abundant, ubiquitous, and multifunctional chaperones share phenotypes with enzymes engaged in the initial stages of replication of the mitochondrial DNA in T. brucei.
Cost Effectiveness of Using Moxibustion to Correct Non-Vertex Presentation
Authors: García-Mochón Leticia , Martín José J , Aranda-Regules José Manuel , Rivas-Ruiz Francisco , Vas Jorge
Published: February 2015

Aims

To analyse the cost effectiveness of using the moxibustion technique to correct non-vertex presentation and to reduce the number of caesarean sections performed at term.

Method

A deterministic model of decision analysis has been developed to analyse the cost of treatment in which heat is applied by moxibustion (the combustion of Artemisia vulgaris) at acupuncture point BL67 for pregnant women with non-vertex fetal position at 33–35 weeks’ gestation. This approach was compared with conventional treatment recommendations based on the knee-chest posture technique. The costs were obtained mainly from data provided by the Andalusian Public Health System. Effectiveness data for the baseline analysis were taken from a previous clinical study. A secondary analysis was performed based on a meta-analysis conducted using random effects analysis, by reference to studies published in recent systematic reviews of moxibustion versus conventional treatment, in order to make the results generalisable to other healthcare settings. Deterministic and probabilistic sensitivity analyses were performed under diverse assumptions to assess the uncertainty of the result.

Results

The baseline analysis shows that the application of moxibustion prevents 8.92% of deliveries with non-vertex presentation compared with conventional treatment, with an average cost saving of ¢107.11 per delivery, mainly due to the cost saving from avoiding the need for caesarean section. The meta-analysis revealed a relative risk of the version of non-vertex presentation at term of 0.34 (95% CI 0.16 to 0.76). The sensitivity analysis showed that moxibustion can avoid 0.34 caesarean sections, with an incremental cost per delivery ranging from ¢68 to −¢640 for moxibustion versus conventional treatment.

Conclusions

Moxibustion treatment applied at acupuncture point BL67 can avoid the need for caesarean section and achieve cost savings for the healthcare system in comparison with conventional treatment.
Selective dorsal rhizotomy: an old treatment re-emerging
Authors: Aquilina Kristian , Graham David , Wimalasundera Neil
Published: February 2015

Selective dorsal rhizotomy (SDR) is a neurosurgical technique developed to reduce spasticity and improve mobility in children with cerebral palsy (CP) and lower extremity spasticity. It involves the selective division of lumbosacral afferent (sensory) rootlets at the conus or at the intervertebral foramina under intraoperative neurophysiological guidance. First described in 1908, early procedures were effective at reducing spasticity but were associated with significant morbidity. Technical advancements over the last two decades have reduced the invasiveness of the procedure, typically from a five-level laminoplasty to a single-level laminotomy at the conus. As practised today, SDR is an effective treatment for young patients with bilateral spastic CP who are rigorously selected for surgery and for whom realistic objectives are set. SDR has therefore re-emerged as a valuable management option for spastic CP. In this article, the authors review the single-level SDR technique and its role in the management of bilateral spastic CP, with particular emphasis on patient selection and outcomes.
Predicting IVIG resistance in UK Kawasaki disease
Authors: Davies Sarah , Sutton Natalina , Blackstock Sarah , Gormley Stuart , Hoggart Clive J , Levin Michael , Herberg Jethro A
Published: February 2015

The Kobayashi score (KS) predicts intravenous immunoglobulin (IVIG) resistance in Japanese children with Kawasaki disease (KD) and has been used to select patients for early corticosteroid treatment. We tested the ability of the KS to predict IVIG resistance and coronary artery abnormalities (CAA) in 78 children treated for KD in our UK centre. 19/59 children were IVIG non-responsive. This was not predicted by a high KS (11/19 IVIG non-responders, compared with 26/40 responders, had a score ≥4; p=0.77). CAA were not predicted by KS (12/20 children with CAA vs 25/39 with normal echo had a score ≥4; p=0.78). Low albumin and haemoglobin, and high C-reactive protein were significantly associated with CAA. The KS does not predict IVIG resistance or CAA in our population. This highlights the need for biomarkers to identify children at increased risk of CAA, and to select patients for anti-inflammatory treatment in addition to IVIG.
Dietary protein-to-carbohydrate ratio and added sugar as determinants of excessive gestational weight gain: a prospective cohort study
Authors: Maslova Ekaterina , Halldorsson Thorhallur I , Astrup Arne , Olsen Sjurdur F
Published: February 2015

Objective

To examine the relation between the protein:carbohydrate (P/C) ratio and added sugar intake in pregnancy and gestational weight gain (GWG).

Design

A prebirth cohort including 103 119 pregnancies enrolled between 1996 and 2003.

Setting

All women in Denmark were eligible to participate if they spoke Danish and were planning to carry to term.The pregnant women were recruited and enrolled during their first antenatal visit (6–10 weeks of gestation).

Participants

Participants included women with live-born singletons and complete data on dietary intake and GWG, leaving 46 262 women for the analysis.

Exposure

Macronutrient intake was quantified using a validated food frequency questionnaire administered in the 25th week of gestation. The P/C ratio and added sugar intake were examined in quintiles.

Primary outcome measures

GWG was based on self-reported weight in gestational weeks 12 and 30 and defined as gain in g/week. We used multivariable linear regression, including adjusting for pre-pregnancy body mass index, to calculate relative change in GWG and 95% CI.

Results

Average GWG was 471(224) g/week. The adjusted weight gain was 16 g/week lower (95% CI 9 to 22, p for trend <0.001) in the highest (Q5) versus lowest (Q1) quintile of the P/C ratio (∼3% average reduction across the entire pregnancy). Weight gain for those with >20%E vs <12%E from protein was 36 g/week lower (95% CI 20 to 53, p for trend <0.0001; ∼8% average reduction). A high P/C ratio was inversely related to intake of added sugars. Added sugar consumption was strongly associated with GWG (Q5 vs Q1: 34, 95% CI 28 to 40 g/week, p for trend <0.0001).

Conclusions

A high P/C ratio was associated with reduced GWG. This association appeared to be partly driven by a decrease in intake of added sugar. These results are consistent with randomised trials in non-pregnant participants. A dietary intervention targeting an increased P/C ratio with emphasis on reducing added sugar can contribute to reducing excessive GWG.
Validity of a PCI Bleeding Risk Score in patient subsets stratified for body mass index
Authors: Dobies David R , Barber Kimberly R , Cohoon Amanda L
Published: February 2015

Objective

An accurate tool with good discriminative for bleeding would be useful to clinicians for improved management of all their patients. Bleeding risk models have been published but not externally validated in independent clinical data set. We chose the National Cardiovascular Data Registry (NCDR) percutaneous coronary intervention (PCI) score to validate within a large, multisite community data set. The aim of the study was validation of this Bleeding Risk Score (BRS) tool among a subgroup of patients based on body mass index.

Methods

This is a large-scale retrospective analysis of a current registry utilising data from a 37-hospital health system. The central repository of patients with coronary heart disease undergoing PCI between 1 June 2009 and 30 June 2012 was utilised to validate the NCDR PCI BRS among 4693 patients. The primary end point was major bleeding. Validation analysis calculating the receiver operating characteristic curve was performed.

Results

There were 143 (3%) major bleeds. Mean BRS was 14.7 (range 3–42). Incidence of bleeding by risk category: low (0.5%), intermediate (1.7%) and high risk (7.6%). Tool accuracy was poor to fair (area-under-the curve (AUC) 0.78 heparin, 0.65 bivalirudin). Overall accuracy was 0.71 (CI 0.66 to 0.76). Accuracy did not improve when confined to just the intermediate risk group (AUC 0.58; CI 0.55 to 0.67). Tool accuracy was the lowest among the low BMI group (AUC 0.62) though they are at increased risk of bleeding following PCI.

Conclusions

Bleeding risk tools have low predictive value even among subgroups of patients at higher risk. Adjustment for anticoagulation use resulted in poor discrimination because bivalirudin differentially biases outcomes toward no bleeding. The current state of bleeding risk tools provide little support for diagnostic utility in regards to major bleeding and therefore have limited clinical applicability.
From AutoCAD to 3ds Max: An automated approach for animating heavy lifting studies
Authors: Lei Zhen , Taghaddos Hosein , Han SangHyeok , Bouferguène Ahmed , Al-Hussein Mohamed , Hermann Ulrich
Published: February 2015

Modular construction is a dominant manufacturing method for industrial construction in Alberta, Canada. Modularization requires large-capacity mobile cranes to lift heavy modules, such as piperack modules. The current practice utilizes AutoCAD to generate heavy lift studies for modular onsite installations. Heavy lift studies consist of 2D and 3D simulations of the lifting scenarios, along with the corresponding calculations (e.g., lifting capacity checking, ground bearing pressure checking). These static simulations provide snapshots of mobile cranes at pick and set configurations, but they do not represent the movements between the two configurations. For better communication among site engineers and crews, current static heavy lift studies need to be improved by animating the entire lifting process. 3ds Max is an animation tool that can visualize the lifting process, but the tedious and manual process of preparing the animation restricts efficiency and productivity. This research thus introduces a newly developed animation system that automates the transfer of heavy lift studies from AutoCAD into Autodesk 3ds Max animation. Also in this research, the kinetics of mobile cranes are studied and generic crane movements are defined. Using MAXScript, a script is written to link the crane and project database for automatic generating of animations. This research aims to provide the construction industry with a generic method for automating the animation process for heavy lifts based on AutoCAD and 3ds Max systems.
Oscillator strengths and lifetimes for Cu I
Authors: Çelik Gültekin , Ateş Şule , Erol Elmas
Published: February 2015

Electric dipole oscillator strengths and lifetimes for Cu I have been calculated within the weakest bound electron potential model theory and the quantum defect orbital theory under the assumption of the LS coupling scheme. In the calculations, many transition arrays including both multiplet and fine-structure transitions are considered. The present results are consistent with earlier theoretical calculations and experimental measurements. Some of these results are reported for the first time.
Upper thermal tolerance in anuran embryos and tadpoles at constant and variable peak temperatures
Authors: Turriago J.L. , Parra C.A. , Bernal M.H.
Published: February 2015

Anuran survival is strongly affected by exposure to high environmental temperatures. However, their upper thermal tolerances vary between species and within developmental stages. The aims of this research were to measure the median lethal temperature (LT50) of three anuran developmental stages (Gosner stages 10, 20, and 25) at a constant thermal regime, and of developing embryos (stage 10) until they became tadpoles (stage 25) exposed to daily peaks of temperatures between 1000 and 1600. Four Colombian species (Emerald-eyed Treefrog, Hypsiboas crepitans (Wied-Neuwied, 1824); Tungara Frog, Engystomops pustulosus (Cope, 1864); Rivero’s Toad, Rhinella humboldti (Gallardo, 1965); Emerald Glassfrog, Espadarana prosoblepon (Boettger, 1892)) were used in these experiments. An ontogenetic increase was observed in the upper thermal tolerance from embryos to tadpoles for all species studied. In addition, developing embryos exposed to peak temperatures showed a LT50fairly close to the mean of the maximum habitat temperatures, particularly in H. crepitans and E. pustulosus that lay egg masses exposed directly to the sun. Environmental temperatures in the microhabitat of species studied showed values remarkably higher than their experimental LT50. Therefore, we postulate that rapid increases in environmental temperatures, as result of global or local changes, might be a critical factor for anuran survival, mainly during the embryonic stages when they are more sensitive to temperature.
A complete classification of threshold properties for one-dimensional discrete Schrödinger operators
Authors: Ito Kenichi , Jensen Arne
Published: February 2015

We consider the one-dimensional discrete Schrödinger operator on ℤ, and study the relation between the generalized eigenstates and the asymptotic expansion of the resolvent for the threshold 0. We decompose the generalized zero eigenspace into subspaces, some of which correspond to the bound states or the resonance states, only by their growth properties at infinity, and precisely describe the first few leading coefficients in the expansion using these subspaces. The generalized zero eigenspace we consider is the largest possible one, consisting of all solutions to the eigenequation. For the resolvent expansion, we implement the expansion scheme of Jensen–Nenciu [Rev. Math. Phys. 13 (2001) 717–754] and [Rev. Math. Phys. 16 (2004) 675–677] in its full generality.
Yang–Mills theory and jumping curves
Authors: Savelyev Yasha
Published: February 2015

We study a smooth analogue of jumping curves of a holomorphic vector bundle, and use Yang–Mills theory over S2 to show that any non-trivial, smooth Hermitian vector bundle E over a smooth simply connected manifold, must have such curves. This is used to give new examples complex manifolds for which a non-trivial holomorphic vector bundle must have jumping curves in the classical sense (when c1(E) is zero). We also use this to give a new proof of a theorem of Gromov on the norm of curvature of unitary connections, and make the theorem slightly sharper. Lastly we define a sequence of new non-trivial integer invariants of smooth manifolds, connected to this theory of smooth jumping curves, and make some computations of these invariants. Our methods include an application of the recently developed Morse–Bott chain complex for the Yang–Mills functional over S2.
Reversible elementary cellular automaton with rule number 150 and periodic boundary conditions over 𝔽p
Authors: Martín del Rey A. , Rodríguez Sánchez G.
Published: February 2015

The study of the reversibility of elementary cellular automata with rule number 150 over the finite state set 𝔽p and endowed with periodic boundary conditions is done. The dynamic of such discrete dynamical systems is characterized by means of characteristic circulant matrices, and their analysis allows us to state that the reversibility depends on the number of cells of the cellular space and to explicitly compute the corresponding inverse cellular automata.
A novel lattice traffic flow model on a curved road
Authors: Cao Jin-Liang , Shi Zhon-Ke
Published: February 2015

Due to the existence of curved roads in real traffic situation, a novel lattice traffic flow model on a curved road is proposed by taking the effect of friction coefficient and radius into account. The stability condition is obtained by using linear stability theory. The result shows that the traffic flow becomes stable with the decrease of friction coefficient and radius of the curved road. Using nonlinear analysis method, the Korteweg–de Vries (KdV) and modified Korteweg–de Vries (mKdV) equation are derived to describe soliton waves and the kink–antikink waves in the meta-stable region and unstable region, respectively. Numerical simulations are carried out and the results are consistent with the theoretical results.
MACROPRUDENTIAL POLICIES AS BUFFER AGAINST VOLATILE CROSS-BORDER CAPITAL FLOWS
Authors: AYSAN AHMET FARUK , FENDOĞLU SALIH , KILINÇ MUSTAFA
Published: February 2015

This paper investigates the effectiveness of macroprudential policies introduced by Turkey in late 2010. The unprecedented quantitative easing policies of advanced countries after the global financial crisis have presented serious financial stability concerns for most emerging countries including Turkey. To cope with these challenges, Turkey has devised new policy tools such as asymmetric interest rate corridor and reserve option mechanism. From the perspective of capital flows, the interest rate corridor works mainly through stabilizing supply of foreign funds, and the reserve option mechanism through decreasing the sensitivity of equilibrium exchange rate to shifts in the demand for foreign funds. Using a large panel of 46 countries and employing [Bruno and Shin (2013a). Capital flows, cross-border banking and Global liquidity. Working paper, Princeton university; Bruno and Shin (2013b). Assessing macroprudential policies: Case of Korea. Working paper, Princeton university] methodology, we investigate whether the new policy framework in Turkey has been successful in cushioning the economy from volatile cross-border capital flows from a comparative perspective. The results show that, after controlling for a set of domestic and external variables and relative to a group of advanced and emerging countries, cross-border capital flows to Turkey have been less sensitive to global factors after the implementation of macroprudential policies.
INTERNATIONAL LENDING AND THE SAMARITAN'S DILEMMA
Authors: MOURMOURAS ALEXANDROS , RANGAZAS PETER
Published: February 2015

We analyze how the altruism of an International Financial Institution (IFI) towards its Low-Income member Countries (LICs) alters the effectiveness of its loans. We study IFI loans to a credit-constrained LIC. The IFI's repayment policy is determined by the interplay of its concerns for the welfare of the loan recipient and its fiduciary responsibilities to creditor countries. If the IFI is unable to commit to either the size of future loans or the repayment terms on past loans, conditional loans are superior to unconditional loans. Thus, IFI altruism and the inability to commit are sufficient reasons to equip loans with conditions. Conditional loans produce an efficient allocation of resources, so altruism is not a fundamental reason that loans fail to increase welfare.
Uniqueness Conditions for A Class of ℓ0-Minimization Problems
Authors: Xu Chunlei , Zhao Yun-Bin
Published: February 2015

We consider a class of ℓ0-minimization problems, which is to search for the partial sparsest solution to an underdetermined linear system with additional constraints. We introduce several concepts, including lp-induced quasi-norm (0 < p < 1), maximal scaled spark and scaled mutual coherence, to develop several new uniqueness conditions for the partial sparsest solution to this class of ℓ0-minimization problems. A further improvement of some of these uniqueness criteria has been also achieved through the so-called concepts such as maximal scaled (sub)coherence rank.
Safe Approximations for Distributionally Robust Joint Chance Constrained Program
Authors: Wu Chenchen , Xu Dachuan , Zhang Jiawei
Published: February 2015

In this paper, we present a bilinear second-order cone programming safe approximation for the distributionally robust chance constrained program (DRCCP), assuming that the support of the uncertain parameters, and the first and second marginal moments of the probability with respect to the interval constraint imposed on the sum of the uncertain parameters are given. If we further know the covariance matrix, we can obtain a bilinear semi-definite programming safe approximation. Preliminary numerical tests indicate that the proposed models are competitive.
Achieving Better Solutions for Vehicle Routing Problem Involving Split Deliveries and Pickups Using a Competitive Decision Algorithm
Authors: Wang Kefeng , Ye Chunming , Ning Aibing
Published: February 2015

This paper discusses vehicle routing problem involving split deliveries and pickups, in which the customer has pickup and delivery demands that can exceed the capacity of the vehicle, and one customer can be visited by no more than one vehicle or by one vehicle for no more than one time. The objective of the problem is to minimize total travel cost. A new heuristic algorithm, the competitive decision algorithm, is proposed to solve the problem. Computational experiments on the benchmark provided by Mitra are performed to evaluate our algorithm against the previously proposed method. The experiment shows that our algorithm provides the best solutions to a total of 110 problems whether or not the number of vehicles used is restricted to the minimum.
The concept of physical surface in nuclear matter
Authors: Mazilu Nicolae , Agop Maricel
Published: February 2015

The main point of a physical definition of surface forces in the matter in general, especially in the nuclear matter, is that the curvature of surfaces and its variation should be physically defined. The forces are therefore just the vehicles of introducing physics. The problem of mathematical definition of a surface in term of the curvature parameters thus naturally occurs. The present work addresses this problem in terms of the asymptotic directions of a surface in a point. A physical meaning of these parameters is given, first in terms of inertial forces, then in terms of a differential theory of colors, whereby the space of curvature parameters is identified with the color space. The work concludes with an image of the evolution of a local portion of a surface.
B-meson production in the Parton Reggeization Approach at Tevatron and the LHC
Authors: Karpishkov A. V. , Nefedov M. A. , Saleev V. A. , Shipilova A. V.
Published: February 2015

We study the inclusive hadroproduction of B0, B+and [Formula: see text] mesons at leading order in the Parton Reggeization Approach using the universal fragmentation functions extracted from the combined e+e-annihilation data from CERN LEP1 and SLAC SLC colliders. We have described B-meson transverse momentum distributions measured in the central region of rapidity by the CDF Collaboration at Fermilab Tevatron and CMS Collaboration at LHC within uncertainties and without free parameters, applying Kimber–Martin–Ryskin unintegrated gluon distribution function in a proton. The forward B-meson production (2.0<y<4.5) measured by the LHCb Collaboration also has been studied and expected disagreement between our theoretical predictions and data has been obtained.
A microscopic approach to quark and lepton masses and mixings
Authors: Lampe Bodo
Published: February 2015

In recent papers, a microscopic model for the SM Higgs mechanism has been proposed, and an idea how to determine the 24 quark and lepton masses of all three generations has emerged in that framework. This idea is worked out in detail here by accommodating the fermion masses and mixings to microscopic parameters. The top quark mass can be given in terms of the Fermi scale and of certain exchange couplings of isospin vectors obeying a tetrahedral symmetry. The observed hierarchy in the family spectrum is attributed to a natural hierarchy in the microscopic couplings. The neutrinos will be shown to vibrate within the potential valleys of the system, thus retaining very tiny masses. This is related to a Goldstone effect inside the internal dynamics. A discussion of the quark and lepton mixing matrices is also included. The mixing angles of the PMNS matrix are calculated for an example set of parameters, and a value for the CP-violating phase is given.
Locality and nonlinear quantum mechanics
Authors: Ho Chiu Man , Hsu Stephen D. H.
Published: February 2015

Nonlinear modifications of quantum mechanics generically lead to nonlocal effects which violate relativistic causality. We study these effects using the functional Schrödinger equation for quantum fields and identify a type of nonlocality which causes nearly instantaneous entanglement of spacelike separated systems. We describe a simple example involving widely separated wave packet (coherent) states, showing that nonlinearity in the Schrödinger evolution causes spacelike entanglement, even in free field theory.
Energy Harvesting and Management in Wireless Networks for Perpetual Operations
Authors: Abbas Muhammad Mazhar , Muhammad Zia , Saleem Khalid , Saqib Nazar Abbas , Mahmood Hasan
Published: February 2015

Ad hoc wireless networks are self-generating and self-organizing networks consisting of mobile and static nodes, which are small and have limited power resources. In a typical setup, these nodes communicate with each other through wireless medium and may act as source, destination and/or relaying nodes. As the power of the remote nodes is depleted very quickly, it is important to have a renewable energy source to support the network operations and increase lifetime. The availability of energy from the environment is unpredictable, random and uncertain, therefore energy harvesting with appropriate management plays an important role in continuous operations of ad hoc networks. In this paper, an energy harvesting and management model is presented for ad hoc networks. Along with harvesting energy, the proposed model ensures the connectivity requirements of the network for its perpetual operation.
Collective molecular dissipation on Navier–Stokes macroscopic scales: Accretion disc viscous modeling in SPH
Authors: Lanzafame Giuseppe
Published: February 2015

In the nonlinear Navier–Stokes viscous flow dynamics, physical damping is mathematically accomplished by a braking term in the momentum equation, corresponding to a heating term in the energy equation, both responsible of the conversion of mechanical energy into heat. In such two terms, it is essential the role of the viscous stress tensor, relative to contiguous macroscopic moving flow components, depending on the macroscopic viscosity coefficient ν. A working formulation for ν can always be found analytically, tuning some arbitrary parameters in the current known formulations, according to the geometry, morphology and physics of the flow. Instead, in this paper, we write an alternative hybrid formulation for ν, where molecular parameters are also included. Our expression for ν has a more physical interpretation of the internal damping in dilute gases because the macroscopic viscosity is related to the small scale molecular dissipation, not strictly dependent on the flow morphology, as well as it is free of any arbitrary parameter. Results for some basic 2D tests are shown in the smoothed particle hydrodynamics (SPH) framework. An application to the 3D accretion disc modeling for low mass cataclysmic variables is also discussed. Consequences of the macroscopic viscosity coefficient reformulation in a more strictly physical terms on the thermal conductivity coefficient for dilute gases are also discussed.
Generalized Ehrenfest's equations and phase transition in black holes
Authors: Poshteh Mohammad Bagher Jahani , Mirza Behrouz , Oboudiat Fatemeh
Published: February 2015

In this paper, we generalize Ehrenfest's equations to systems having two work terms, i.e. systems with three degrees of freedom. For black holes with two work terms we obtain nine equations instead of two to be satisfied at the critical point of a second-order phase transition. We finally generalize this method to a system with an arbitrary number of degrees of freedom and found there is [Formula: see text] equations to be satisfied at the point of a second-order phase transition where N is number of work terms in the first law of thermodynamics.
PSOVina: The hybrid particle swarm optimization algorithm for protein–ligand docking
Authors: Ng Marcus C. K. , Fong Simon , Siu Shirley W. I.
Published: February 2015

Protein–ligand docking is an essential step in modern drug discovery process. The challenge here is to accurately predict and efficiently optimize the position and orientation of ligands in the binding pocket of a target protein. In this paper, we present a new method called PSOVina which combined the particle swarm optimization (PSO) algorithm with the efficient Broyden–Fletcher–Goldfarb–Shannon (BFGS) local search method adopted in AutoDock Vina to tackle the conformational search problem in docking. Using a diverse data set of 201 protein–ligand complexes from the PDBbind database and a full set of ligands and decoys for four representative targets from the directory of useful decoys (DUD) virtual screening data set, we assessed the docking performance of PSOVina in comparison to the original Vina program. Our results showed that PSOVina achieves a remarkable execution time reduction of 51–60% without compromising the prediction accuracies in the docking and virtual screening experiments. This improvement in time efficiency makes PSOVina a better choice of a docking tool in large-scale protein–ligand docking applications. Our work lays the foundation for the future development of swarm-based algorithms in molecular docking programs. PSOVina is freely available to non-commercial users at http://cbbio.cis.umac.mo .
Free fatty acid availability is closely related to myocardial lipid storage and cardiac function in hypoglycemia counterregulation
Authors: Winhofer Yvonne , Krššák Martin , Wolf Peter , Anderwald Christian-Heinz , Geroldinger Angelika , Heinze Georg , Baumgartner-Parzer Sabina , Marculescu Rodrig , Stulnig Thomas , Wolzt Michael , Trattnig Siegfried , Luger Anton , Krebs Michael
Published: February 2015

Hypoglycemia, a major side effect of intensive glucose-lowering therapy, was recently linked to increased cardiovascular risk in patients with diabetes. Whether increased circulating free fatty acids (FFA) owing to catecholamine-induced lipolysis affect myocardial energy metabolism and thus link hypoglycemia to cardiac vulnerability is unclear. Therefore, this study investigated the impact of hypoglycemia counterregulation (± inhibition of lipolysis) on myocardial lipid content (MYCL) and left ventricular function in healthy subjects. Nine healthy men were studied in randomized order: 1) insulin/hypoglycemia test (IHT; ins+/aci−), 2) IHT during inhibition of adipose tissue lipolysis by acipimox (ins+/aci+), 3) normoglycemia with acipimox (ins−/aci+), and 4) normoglycemia with placebo (ins−/aci−). MYCL and cardiac function were assessed by employing magnetic resonance spectroscopy/imaging at baseline and at 2 and 6 h. In response to acute hypoglycemia, plasma FFA ( P < 0.0001) and ejection fraction (EF; from 63.2 ± 5.5 to 69.6 ± 6.3%, P = 0.0001) increased significantly and were tightly correlated with each other ( r = 0.68, P = 0.0002); this response was completely blunted by inhibition of adipose tissue lipolysis. In the presence of normoglycemia, inhibition of lipolysis was associated with a drop in EF (from 59.2 ± 5.5 to 53.9 ± 6.9%, P = 0.005) and a significant decrease in plasma FFA, triglycerides, and MYCL (by 48.5%, P = 0.0001). The present data indicate that an intact interorgan cross-talk between adipose tissue and the heart is a prerequisite for catecholamine-mediated myocardial contractility and preservation of myocardial lipid stores in response to acute hypoglycemia.
Skeletal muscle insulin resistance in zebrafish induces alterations in β-cell number and glucose tolerance in an age- and diet-dependent manner
Authors: Maddison Lisette A. , Joest Kaitlin E. , Kammeyer Ryan M. , Chen Wenbiao
Published: February 2015

Insulin resistance creates an environment that promotes β-cell failure and development of diabetes. Understanding the events that lead from insulin resistance to diabetes is necessary for development of effective preventional and interventional strategies, and model systems that reflect the pathophysiology of disease progression are an important component toward this end. We have confirmed that insulin enhances glucose uptake in zebrafish skeletal muscle and have developed a zebrafish model of skeletal muscle insulin resistance using a dominant-negative IGF-IR. These zebrafish exhibit blunted insulin signaling and glucose uptake in the skeletal muscle, confirming insulin resistance. In young animals, we observed an increase in the number of β-cells and normal glucose tolerance that was indicative of compensation for insulin resistance. In older animals, the β-cell mass was reduced to that of control with the appearance of impaired glucose clearance but no elevation in fasting blood glucose. Combined with overnutrition, the insulin-resistant animals have an increased fasting blood glucose compared with the control animals, demonstrating that the β-cells in the insulin-resistant fish are in a vulnerable state. The relatively slow progression from insulin resistance to glucose intolerance in this model system has the potential in the future to test cooperating genes or metabolic conditions that may accelerate the development of diabetes and provide new therapeutic targets.
The Cell Birth Marker BrdU Does Not Affect Recruitment of Subsequent Cell Divisions in the Adult Avian Brain
Authors: Cattan Anat , Ayali Amir , Barnea Anat
Published: February 2015

BrdU is commonly used to quantify neurogenesis but also causes mutation and has mitogenic, transcriptional, and translational effects. In mammalian studies, attention had been given to its dosage, but in birds such examination was not conducted. Our previous study suggested that BrdU might affect subsequent cell divisions and neuronal recruitment in the brain. Furthermore, this effect seemed to increase with time from treatment. Accordingly, we examined whether BrdU might alter neurogenesis in the adult avian brain. We compared recruitment of [3H]-thymidine+neurons in brains of zebra finches (Taeniopygia guttata) when no BrdU was involved and when BrdU was given 1 or 3 months prior to [3H]-thymidine. In nidopallium caudale, HVC, and hippocampus, no differences were found between groups in densities and percentages of [3H]-thymidine+neurons. The number of silver grains per [3H]-thymidine+neuronal nucleus and their distribution were similar across groups. Additionally, time did not affect the results. The results indicate that the commonly used dosage of BrdU in birds has no long-term effects on subsequent cell divisions and neuronal recruitment. This conclusion is also important in neuronal replacement experiments, where BrdU and another cell birth marker are given, with relatively long intervals between them.
Couple Stress Squeeze Films with VPD in a Curved Circular Geometry
Authors: Ponnuswamy Vimala , Govindaraj Sumathi
Published: February 2015

The problem of couple stress squeeze films considering viscosity pressure dependence (VPD) has been analysed in a curved circular geometry. Using Stokes microcontinuum theory and the Barus formula, the Reynolds type equation has been derived. The approximate analytical expressions for the squeeze film pressure and load carrying capacity are obtained using a perturbation technique. The numerical solutions for the squeeze film pressure and load carrying capacity are presented for the sinusoidal motion of the upper curved disk, assuming an exponential form for the curvature. The effects of curvature, the non-Newtonian couple stresses, and VPD and their combined effects are investigated through the squeeze film pressure and the load carrying capacity of the squeeze film.
Polycystic Ovary Syndrome: Aggressive or Protective Factor for the Retina? Evaluation of Macular Thickness and Retinal Nerve Fiber Layers Using High-Definition Optical Coherence Tomography
Authors: Souza-Júnior José Edvan de , Garcia Carlos Alexandre de Amorim , Soares Elvira Maria Mafaldo , Maranhão Técia Maria Oliveira , Lemos Telma Maria Araújo Moura , Azevedo George Dantas
Published: February 2015

Objective. To compare macular thickness (MT) and retinal nerve fiber layers (RNFL) between women with polycystic ovary syndrome (PCOS) and healthy women.Materials and Methods. The study included 45 women with PCOS and 47 ovulatory women undergoing clinical-gynecological and ophthalmic evaluations, including measurement of MT, RNFL, and optic disc parameters using optical coherence tomography.Results. The superior RNFL around the optic nerve was significantly thicker in PCOS than in healthy volunteers (P=0.036). After stratification according to insulin resistance, the temporal inner macula (TIM), the inferior inner macula (IIM), the nasal inner macula (NIM), and the nasal outer macula (NOM) were significantly thicker in PCOS group than in control group (P<0.05). Both the presence of obesity associated with insulin resistance (P=0.037) and glucose intolerance (P=0.001) were associated with significant increase in the PC1 mean score, relative to MT. A significant increase in the PC2 mean score occurred when considering the presence of metabolic syndrome (P<0.0001). There was a significant interaction between obesity and inflammation in a decreasing mean PC2 score relative to macular RNFL thickness (P=0.034).Conclusion. Decreased macular RNFL thickness and increased total MT are associated with metabolic abnormalities, while increased RNFL thickness around the optic nerve is associated with hormonal changes inherent in PCOS.
Reduced Serum Butyrylcholinesterase Activity Indicates Severe Systemic Inflammation in Critically Ill Patients
Authors: Zivkovic Aleksandar R. , Schmidt Karsten , Sigl Annette , Decker Sebastian O. , Brenner Thorsten , Hofer Stefan
Published: February 2015

Systemic inflammation is an immune response to a nonspecific insult of either infectious or noninfectious origin and remains a challenge in the intensive care units with high mortality rate. Cholinergic neurotransmission plays an important role in the regulation of the immune response during inflammation. We hypothesized that the activity of butyrylcholinesterase (BChE) might serve as a marker to identify and prognose systemic inflammation. By using a point‐of‐care‐testing (POCT) approach we measured BChE activity in patients with severe systemic inflammation and healthy volunteers. We observed a decreased BChE activity in patients with systemic inflammation, as compared to that of healthy individuals. Furthermore, BChE activity showed an inverse correlation with the severity of the disease. Although hepatic function has previously been found essential for BChE production, we show here that the reduced BChE activity associated with systemic inflammation occurs independently of and is thus not caused by any deficit in liver function in these patients. A POCT approach, used to assess butyrylcholinesterase activity, might further improve the therapy of the critically ill patients by minimizing time delays between the clinical assessment and treatment of the inflammatory process. Hence, assessing butyrylcholinesterase activity might help in early detection of inflammation.
Tetramethylpyrazine Enhances Vascularization and Prevents Osteonecrosis in Steroid-Treated Rats
Authors: Jiang Yini , Liu Chunfang , Chen Weiheng , Wang Hui , Wang Chao , Lin Na
Published: February 2015

Steroid-induced osteonecrosis of the femoral head (steroid-induced ONFH) is an avascular necrosis disease of bone. Tetramethylpyrazine (TMP), with significant vascular protective properties, has been widely used for the treatments of ischemic neural disorders and cardiovascular diseases. However, its role in the treatment of steroid-induced ONFH has not been evaluated. In this study, our results showed that TMP significantly decreased the ratio of empty lacuna, adipose tissue area, and adipocyte perimeter in steroid-induced ONFH rats histopathologically. TMP also reduced the levels of serum lipid dramatically by haematological examination. According to the micro-CT quantification, TMP could improve the microstructure of the trabecular bone and increases bone mineral density in steroid-induced ONFH rats. Moreover, TMP significantly increased the vessel volume, vessel surface, percentage of vessel volume, and vessel thickness of the femoral heads by micro-CT. Interestingly, the downregulation of VEGF and FLK1 proteins in the sera and necrotic femoral heads could be reversed by TMP treatment, and this was true for their mRNA expressions in femoral heads. In conclusion, these findings suggest for the first time that TMP may prevent steroid-induced ONFH and also enhance femoral head vascularization by inhibiting the effect of steroid on VEGF/FLK1 signal pathway.
Polyploidy Analysis and Attenuation of Oxidative Stress in Hepatic Tissue of STZ-Induced Diabetic Rats Treated with an Aqueous Extract ofVochysia rufa
Authors: Moraes Izabela Barbosa , Manzan-Martins Camilla , de Gouveia Neire Moura , Calábria Luciana Karen , Hiraki Karen Renata Nakamura , Moraes Alberto da Silva , Espindola Foued Salmen
Published: February 2015

Diabetes mellitus (DM) is characterized by hyperglycemia and alterations in the metabolism of lipids, carbohydrates, and proteins. Due to its hypoglycemic effectVochysia rufais frequently used in Uberlandia, Brazil, to treat DM. Despite its popularity, there is little information about its effect on hepatic tissue. Therefore, we evaluated the histoarchitecture, oxidative stress parameters, and polyploidy of liver tissue from streptozotocin- (STZ-) induced diabetic rats treated with aqueous extract ofVochysia rufa(AEV). Histology was determined by fixing the livers, processing, and staining with HE. Oxidative stress was determined by evaluating CAT, GPx, and SOD activity in liver homogenates and hepatic mitochondria fraction and by measuring GST, GSH levels and lipid peroxidation (MDA). Polyploidy was determined by subjecting isolated hepatocyte nuclei to flow cytometry. In the diabetic group, GST activity and GSH rates decreased whereas liver homogenate analysis showed that GPx, SOD activity and MDA increased. AEV treatment restored all parameters to normal levels. The oxidative stress analysis of hepatic mitochondria fraction showed similar results. Lower polyploid cell populations were found in the diabetic rat livers, even after glibenclamide treatment. Thus, AEV treatment efficiently reduced hepatic oxidative stress caused by STZ-induced diabetes and produced no morphological changes in the histological analysis.