bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid Identification of Carbapenemase Types in Enterobacteriaceae and Pseudomonas spp. by Using a Biochemical Test
Authors: Dortet Laurent , Poirel Laurent , Nordmann Patrice
Published: October 2012

A biochemical test (Carba NP test II) was developed to identify carbapenemase production in
Enterobacteriaceae
and
Pseudomonas
spp. and to discriminate between the different types of carbapenemases (classes A, B, and D). It is based on the detection of the acidification resulting from imipenem hydrolysis, coupled with tazobactam and EDTA as inhibitors. This is an easy and reliable technique (100% sensitivity and specificity) for detection of not only carbapenemase activity but also carbapenemase types in
Enterobacteriaceae
and
Pseudomonas aeruginosa
.
Liposome-Mediated Delivery of Iminosugars Enhances Efficacy against Dengue Virus
In Vivo
Authors: Miller Joanna L. , Lachica Ruben , Sayce Andrew C. , Williams James P. , Bapat Manisha , Dwek Raymond , Beatty P. Robert , Harris Eva , Zitzmann Nicole
Published: October 2012

A key challenge faced by promising antiviral drugs, such as iminosugars, is
in vivo
delivery to achieve effective levels of drug without toxicity. Four iminosugars, all deoxynojirimycin (DNJ) derivatives—
N
-butyl DNJ (
N
B-DNJ),
N
-nonyl DNJ,
N
-(9-methoxynonyl) DNJ, and
N
-(6′-[4″-azido-2″-nitrophenylamino]hexyl)-1-DNJ (
N
AP-DNJ)—potently inhibited both the percentage of cells infected with dengue virus and release of infectious virus from primary human monocyte-derived macrophages, demonstrating their efficacy in primary cells. In a lethal antibody-dependent enhancement mouse model of dengue pathogenesis, free
N
B-DNJ significantly enhanced survival and lowered viral load in organs and serum. Liposome-mediated delivery of
N
B-DNJ, in comparison with free
N
B-DNJ, resulted in a 3-log
10
reduction in the dose of drug sufficient to enhance animal survival. The optimizing of the effective dose in this way could liberate the therapeutic potential of many cytotoxic antivirals against both dengue virus and a wide array of other viruses.
Characterization of the Polymyxin B Resistome of Pseudomonas aeruginosa
Authors: Fernández Lucía , Álvarez-Ortega Carolina , Wiegand Irith , Olivares Jorge , Kocíncová Dana , Lam Joseph S. , Martínez José Luis , Hancock Robert E. W.
Published: October 2012

Multidrug resistance in
Pseudomonas aeruginosa
is increasingly becoming a threat for human health. Indeed, some strains are resistant to almost all currently available antibiotics, leaving very limited choices for antimicrobial therapy. In many such cases, polymyxins are the only available option, although as their utilization increases so does the isolation of resistant strains. In this study, we screened a comprehensive PA14 mutant library to identify genes involved in changes of susceptibility to polymyxin B in
P. aeruginosa
. Surprisingly, our screening revealed that the polymyxin B resistome of this microorganism is fairly small. Thus, only one resistant mutant and 17 different susceptibility/intrinsic resistance determinants were identified. Among the susceptible mutants, a significant number carried transposon insertions in lipopolysaccharide (LPS)-related genes. LPS analysis revealed that four of these mutants (
galU
,
lptC
,
wapR
, and
ssg
) had an altered banding profile in SDS-polyacrylamide gels and Western blots, with three of them exhibiting LPS core truncation and lack of O-antigen decoration. Further characterization of these four mutants showed that their increased susceptibility to polymyxin B was partly due to increased basal outer membrane permeability. Additionally, these mutants also lacked the aminoarabinose-substituted lipid A species observed in the wild type upon growth in low magnesium. Overall, our results emphasize the importance of LPS integrity and lipid A modification in resistance to polymyxins in
P. aeruginosa
, highlighting the relevance of characterizing the genes that affect biosynthesis of cell surface structures in this pathogen to follow the evolution of peptide resistance in the clinic.
Ceftaroline Increases Membrane Binding and Enhances the Activity of Daptomycin against Daptomycin-Nonsusceptible Vancomycin-Intermediate Staphylococcus aureus in a Pharmacokinetic/Pharmacodynamic Model
Authors: Werth Brian J. , Sakoulas George , Rose Warren E. , Pogliano Joseph , Tewhey Ryan , Rybak Michael J.
Published: October 2012

New antimicrobial agents and novel combination therapies are needed to treat serious infections caused by methicillin-resistant
Staphylococcus aureus
(MRSA) with reduced susceptibility to daptomycin and vancomycin. The purpose of this study was to evaluate the combination of ceftaroline plus daptomycin or vancomycin in an
in vitro
pharmacokinetic/pharmacodynamic model. Simulations of ceftaroline-fosamil at 600 mg per kg of body weight every 8 h (q8h) (maximum free-drug concentration in serum [
fC
max
], 15.2 mg/liter; half-life [
t
1/2
], 2.3 h), daptomycin at 10 mg/kg/day (
f
C
max
, 11.3 mg/liter;
t
1/2
, 8 h), vancomycin at 2 g q12h (
fC
max
, 30 mg/liter;
t
1/2
, 6 h), ceftaroline plus daptomycin, and ceftaroline plus vancomycin were evaluated against a clinical, isogenic MRSA strain pair: D592 (daptomycin susceptible and heterogeneous vancomycin intermediate) and D712 (daptomycin nonsusceptible and vancomycin intermediate) in a one-compartment
in vitro
pharmacokinetic/pharmacodynamic model over 96 h. Therapeutic enhancement of combinations was defined as ≥2 log
10
CFU/ml reduction over the most active single agent. The effect of ceftaroline on the membrane charge, cell wall thickness, susceptibility to killing by the human cathelicidin LL37, and daptomycin binding were evaluated. Therapeutic enhancement was observed with daptomycin plus ceftaroline in both strains and vancomycin plus ceftaroline against D592. Ceftaroline exposure enhanced daptomycin-induced depolarization (81.7% versus 72.3%;
P
= 0.03) and killing by cathelicidin LL37 (
P
< 0.01) and reduced cell wall thickness (
P
< 0.001). Fluorescence-labeled daptomycin was bound over 7-fold more in ceftaroline-exposed cells. Whole-genome sequencing and mutation analysis of these strains indicated that change in daptomycin susceptibility is related to an
fmtC
(
mprF
) mutation. The combination of daptomycin plus ceftaroline appears to be potent, with rapid and sustained bactericidal activity against both daptomycin-susceptible and -nonsusceptible strains of MRSA.
Transferable Multiresistance Plasmids Carrying
cfr
in Enterococcus spp. from Swine and Farm Environment
Authors: Liu Yang , Wang Yang , Schwarz Stefan , Li Yun , Shen Zhangqi , Zhang Qijing , Wu Congming , Shen Jianzhong
Published: October 2012

Seventy-seven porcine
Enterococcus
isolates with florfenicol MICs of ≥16 μg of were/ml screened for the presence of the multiresistance gene
cfr
, its location on plasmids, and its genetic environment. Three isolates—
Enterococcus thailandicus
3-38 (from a porcine rectal swab collected at a pig farm),
Enterococcus thailandicus
W3, and
Enterococcus faecalis
W9-2 (the latter two from sewage at a different farm), carried the
cfr
gene. The SmaI pulsed-field gel electrophoresis patterns of the three isolates differed distinctly. In addition,
E. faecalis
W9-2 was assigned to a new multilocus sequence type ST469. Mating experiments and Southern blot analysis indicated that
cfr
is located on conjugative plasmids pW3 (∼75 kb) from
E. thailandicus
W3, p3-38 (∼72 kb) from
E. thailandicus
3-38, and pW9-2 (∼55 kb) from
E. faecalis
W9-2; these plasmids differed in their sizes, additional resistance genes, and the analysis of the segments encompassing the
cfr
gene. Sequence analysis revealed that all plasmids harbored a 4,447-bp central region, in which
cfr
was bracketed by two copies of the novel insertion sequence IS
Enfa4
located in the same orientation. The sequences flanking the central regions of these plasmids, including the partial
tra
gene regions and a ω-ε-ζ toxin-antitoxin module, exhibited >95% nucleotide sequence identity to the conjugative plasmid pAMβ1 from
E. faecalis
. Conjugative plasmids carrying
cfr
appear to play an important role in the dissemination and maintenance of the multiresistance gene
cfr
among enterococcal isolates and possibly other species of Gram-positive bacteria.
VraT/YvqF Is Required for Methicillin Resistance and Activation of the VraSR Regulon in Staphylococcus aureus
Authors: Boyle-Vavra Susan , Yin Shouhui , Jo Dae Sun , Montgomery Christopher P. , Daum Robert S.
Published: October 2012

Staphylococcus aureus
infections caused by strains that are resistant to all forms of penicillin, so-called methicillin-resistant
S. aureus
(MRSA) strains, have become common. One strategy to counter MRSA infections is to use compounds that resensitize MRSA to methicillin.
S. aureus
responds to diverse classes of cell wall-inhibitory antibiotics, like methicillin, using the two-component regulatory system VraSR (
vra
) to up- or downregulate a set of genes (the cell wall stimulon) that presumably facilitates resistance to these antibiotics. Accordingly, VraS and VraR mutations decrease resistance to methicillin, vancomycin, and daptomycin cell wall antimicrobials.
vraS
and
vraR
are encoded together on a transcript downstream of two other genes, which we call
vraU
and
vraT
(previously called
yvqF
). By producing nonpolar deletions in
vraU
and
vraT
in a USA300 MRSA clinical isolate, we demonstrate that
vraT
is essential for optimal expression of methicillin resistance
in vitro
, whereas
vraU
is not required for this phenotype. The deletion of
vraT
also improved the outcomes of oxacillin therapy in mouse models of lung and skin infection. Since
vraT
expressed in
trans
did not complement a
vra
operon deletion, we conclude that VraT does not inactivate the antimicrobial. Genome-wide transcriptional microarray experiments reveal that VraT facilitates resistance by playing a necessary regulatory role in the VraSR-mediated cell wall stimulon. Our data prove that VraTSR comprise a novel three-component regulatory system required to facilitate resistance to cell wall agents in
S. aureus
. We also provide the first
in vivo
proof of principle for using VraT as a sole target to resensitize MRSA to β-lactams.
Childhood adversities and adult-onset asthma: a cohort study
Authors: Korkeila Jyrki , Lietzen Raija , Sillanmäki Lauri H , Rautava Päivi , Korkeila Katariina , Kivimäki Mika , Koskenvuo Markku , Vahtera Jussi
Published: October 2012

Objectives

Childhood adversities may be important determinants of later illnesses and poor health behaviour. However, large-scale prospective studies on the associations between childhood adversities and the onset of asthma in adulthood are lacking.

Design

Prospective cohort study with 7-year follow-up.

Setting

Nationally representative study. Data were collected from the Health and Social Support (HeSSup) survey and national registers.

Participants

The participants represent the Finnish population from the following age groups: 20–24, 30–34, 40–44, and 50–54 years at baseline in 1998 (24 057 survey participants formed the final cohort of this study). The occurrence of childhood adversities was assessed at baseline with a six-item survey scale. The analyses were adjusted for sociodemographic characteristics, behavioural health risks and common mental disorders.

Primary and secondary outcomes

The survey data were linked to data from national health registers on incident asthma during a 7-year follow-up to define new-onset asthma cases with verified diagnoses.

Results

A total of 12 126 (59%) participants reported that they encountered a childhood adversity. Of them 3677 (18% of all) endured three to six adversities. During a follow-up of 7 years, 593 (2.9%) participants were diagnosed with incident asthma. Those who reported three or more childhood adversities had a 1.6-fold (95% CI 1.31 to 2.01) greater risk of asthma compared to those without childhood adversities. This hazard attenuated but remained statistically significant after adjustment for conventional risk factors (HR 1.33; 95% CI 1.06 to 1.67).

Conclusions

Adults who report having encountered adversities in childhood may have an increased risk of developing asthma.
SCALAR FIELD COSMOLOGY II: SUPERFLUIDITY, QUANTUM TURBULENCE, AND INFLATION
Authors: HUANG KERSON , LOW HWEE-BOON , TUNG ROH-SUAN
Published: October 2012

We generalize the big bang model in a previous paper by extending the real vacuum scalar field to a complex vacuum scalar field, within the FLRW framework. The phase dynamics of the scalar field, which makes the universe a superfluid, is described in terms of a density of quantized vortex lines, and a tangle of vortex lines gives rise to quantum turbulence. We propose that all the matter in the universe was created in the turbulence, through reconnection of vortex lines, a process necessary for the maintenance of the vortex tangle. The vortex tangle grows and decays, and its lifetime is the era of inflation. These ideas are implemented in a set of closed cosmological equations that describe the cosmic expansion driven by the scalar field on the one hand, and the vortex–matter dynamics on the other. We show how these two aspects decouple from each other, due to a vast difference in energy scales. The model is not valid beyond the inflation era, but the universe remains a superfluid afterwards. This gives rise to observable effects in the present universe, including dark matter, galactic voids, nonthermal filaments, and cosmic jets.
LASER ENHANCED MOBILITY IN WIDE BAND GAP SEMICONDUCTOR CRYSTALS
Authors: AHLAWAT DHARAMVIR SINGH
Published: October 2012

Laser enhanced mobility in the case of PbI 2 single crystal has been investigated on the basis of the experimental results of photoconductivity measurements using high power Nd : YAG laser. Its dependence on energy area density/photon density and charge carrier concentration has been studied. The obtained results of PbI 2 have been compared with that of CdI 2 and ZnS crystals studied under similar experimental conditions. The laser enhanced mobility has also been compared with the theoretical study in the case of GaAs crystal using CO 2 laser.
COMPLEX MATTER AND NONLINEAR KINETICS: CRYSTAL SIZE DISTRIBUTION DUE TO SELF-ORGANIZATION
Authors: BASIOS VASILEIOS
Published: October 2012

Crystallization processes in nanophase materials, a form of complex matter, exhibit self-organization steps highlighting the importance of nonstandard kinetic and structural factors, and therefore, requires a fresh look at the nature of their underlying mechanisms. The resulting crystallite size distribution signifies an important departure from the classical one, essentially exponential, and reveals the presence of correlations. The emergence of a characteristic crystal size for this distribution is the signature of the underlying nonlinear kinetics and the nonequilibrium constraints imposed by the initial conditions. The whole process can be elucidated within the framework, insights and conceptual tools, furnished by nonlinear science and complexity.
MATRIX QUANTIZATION OF TURBULENCE
Authors: FLORATOS EMMANUEL
Published: October 2012

Based on our recent work on Quantum Nambu Mechanics [Axenides & Floratos 2009], we provide an explicit quantization of the Lorenz chaotic attractor through the introduction of noncommutative phase space coordinates as Hermitian N × N matrices in R3. For the volume preserving part, they satisfy the commutation relations induced by one of the two Nambu Hamiltonians, the second one generating a unique time evolution. Dissipation is incorporated quantum mechanically in a self-consistent way having the correct classical limit without the introduction of external degrees of freedom. Due to its volume phase space contraction, it violates the quantum commutation relations. We demonstrate that the Heisenberg–Nambu evolution equations for the Matrix Lorenz system develop fast decoherence to N independent Lorenz attractors. On the other hand, there is a weak dissipation regime, where the quantum mechanical properties of the volume preserving nondissipative sector survive for long times.
QUANTUM VORTICES AND TRAJECTORIES IN PARTICLE DIFFRACTION
Authors: DELIS N. , EFTHYMIOPOULOS C. , CONTOPOULOS G.
Published: October 2012

We investigate the phenomenon of the diffraction of charged particles by thin material targets using the method of the de Broglie–Bohm quantum trajectories. The particle wave function can be modeled as a sum of two terms ψ = ψingoing+ ψoutgoing. A thin separator exists between the domains of prevalence of the ingoing and outgoing wavefunction terms. The structure of the quantum-mechanical currents in the neighborhood of the separator implies the formation of an array of quantum vortices. The flow structure around each vortex displays a characteristic pattern called "nodal point–X point complex". The X point gives rise to stable and unstable manifolds. We find the scaling laws characterizing a nodal point–X point complex by a local perturbation theory around the nodal point. We then analyze the dynamical role of vortices in the emergence of the diffraction pattern. In particular, we demonstrate the abrupt deflections, along the direction of the unstable manifold, of the quantum trajectories approaching an X-point along its stable manifold. Theoretical results are compared to numerical simulations of quantum trajectories. We finally calculate the times of flight of particles following quantum trajectories from the source to detectors placed at various scattering angles θ, and thereby propose an experimental test of the de Broglie–Bohm formalism.
EFFICIENT INTEGRATION OF THE VARIATIONAL EQUATIONS OF MULTIDIMENSIONAL HAMILTONIAN SYSTEMS: APPLICATION TO THE FERMI–PASTA–ULAM LATTICE
Authors: GERLACH ENRICO , EGGL SIEGFRIED , SKOKOS CHARALAMPOS
Published: October 2012

We study the problem of efficient integration of variational equations in multidimensional Hamiltonian systems. For this purpose, we consider a Runge–Kutta-type integrator, a Taylor series expansion method and the so-called "Tangent Map" (TM) technique based on symplectic integration schemes, and apply them to the Fermi–Pasta–Ulam β (FPU-β) lattice of N nonlinearly coupled oscillators, with N ranging from 4 to 20. The fast and accurate reproduction of well-known behaviors of the Generalized Alignment Index (GALI) chaos detection technique is used as an indicator for the efficiency of the tested integration schemes. Implementing the TM technique — which shows the best performance among the tested algorithms — and exploiting the advantages of the GALI method, we successfully trace the location of low-dimensional tori.
ESTIMATING HYPERBOLICITY OF CHAOTIC BIDIMENSIONAL MAPS
Authors: SALA MATTEO , MANCHEIN CESAR , ARTUSO ROBERTO
Published: October 2012

We apply to bidimensional chaotic maps the numerical method proposed by Ginelli et al. [2007] to approximate the associated Oseledets splitting, i.e. the set of linear subspaces spanned by the so-called covariant Lyapunov vectors (CLV) and corresponding to the Lyapunov spectrum. These subspaces are the analog of linearized invariant manifolds for nonperiodic points, so the angles between them can be used to quantify the degree of hyperbolicity of generic orbits; however, such splitting being noninvariant under smooth transformations of phase space, it is interesting to investigate the properties of transversality when coordinates change, e.g. to study it in distinct dynamical systems. To illustrate this issue on the Chirikov–Taylor standard map, we compare the probability densities of transversality for two different coordinate systems; these are connected by a linear transformation that deforms splitting angles through phase space, changing also the probability density of almost-zero angles although complete tangencies are in fact invariant. This is completely due to the PDF transformation law and strongly suggests that any statistical inference from such distributions must be generally taken with care.
EFFICIENT CONTROL OF ACCELERATOR MAPS
Authors: BOREUX JEHAN , CARLETTI TIMOTEO , SKOKOS CHARALAMPOS , PAPAPHILIPPOU YANNIS , VITTOT MICHEL
Published: October 2012

Recently, the Hamiltonian Control Theory was used in [Boreux et al., 2012] to increase the dynamic aperture of a ring particle accelerator having a localized thin sextupole magnet. In this paper, these results are extended by proving that a simplified version of the obtained general control term leads to significant improvements of the dynamic aperture of the uncontrolled model. In addition, the dynamics of flat beams based on the same accelerator model can be significantly improved by a reduced controlled term applied in only one degree of freedom.
DETECTION OF DIRECT CAUSAL EFFECTS AND APPLICATION TO EPILEPTIC ELECTROENCEPHALOGRAM ANALYSIS
Authors: PAPANA ANGELIKI , KUGIUMTZIS DIMITRIS , LARSSON PÅL G.
Published: October 2012

An extension of transfer entropy, called partial transfer entropy (PTE), is proposed to detect causal effects among observed interacting systems, and particularly to distinguish direct from indirect causal effects. PTE is compared to a linear direct causality measure, the Partial Directed Coherence (PDC), on known linear stochastic systems and nonlinear deterministic systems. PTE performs equally well as PDC on the linear systems and better than PDC on the nonlinear systems, both being dependent on the selection of the measure specific parameters. PTE and PDC are applied to electroencephalograms of epileptic patients during the preictal, ictal and postictal states, and PTE turns out to detect better changes of the strength of the direct causality at specific pairs of electrodes and for the different states.
FUNCTIONAL ANALYSIS FOR PARAMETRIC FAMILIES OF FUNCTIONAL DATA
Authors: DE SANCTIS ANGELA , DI BATTISTA TONIO
Published: October 2012

Assuming a Parametric Family of Functional Data, the problem of computing summary statistics of the same functional form is investigated. The central idea is to compile the statistics on the parameters instead of on the functions themselves. With the hypothesis of a monotonic dependence from parameters, we highlight the special features of this statistics.
BIFURCATIONS IN A FREQUENCY-WEIGHTED KURAMOTO OSCILLATORS NETWORK
Authors: WANG HANQING , LI XIANG
Published: October 2012

This paper focuses on the origin of rich dynamics in a frequency-weighted Kuramoto-oscillator network, which embeds the periodical activity patterns of human beings to understand the collective behaviorial dynamics in human population. We present analytical results of the dynamics of the model by reducing the N-dimensional system to solvable low-dimensional equations. The bifurcation analysis reveals that there exist supercritical Hopf bifurcation and infinite-period saddle-node bifurcation, which explain the rich dynamics including the incoherent, oscillatory, and synchronous states observed in this model.
CHAOTIFYING CONTINUOUS-TIME NONLINEAR AUTONOMOUS SYSTEMS
Authors: YU SIMIN , CHEN GUANRONG
Published: October 2012

Based on the principle of chaotification for continuous-time autonomous systems, which relies on two basic properties of chaos, i.e. being globally bounded with necessary positive-zero-negative Lyapunov exponents, this paper derives a feasible and unified chaotification method for designing a general chaotic continuous-time autonomous nonlinear system. For a system consisting of a linear and a nonlinear subsystems, chaotification is achieved using separation of state variables, which decomposes the system into two open-loop subsystems interacting through mutual feedback resulting in an overall closed-loop nonlinear feedback system. Under the condition that the nonlinear feedback control output is uniformly bounded where the nonlinear function is of bounded-input/bounded-output, it is proved that the resulting system is chaotic in the sense of being globally bounded with a required placement of Lyapunov exponents. Several numerical examples are given to verify the effectiveness of the theoretical design. Since linear systems are special cases of nonlinear systems, the new method is also applicable to linear systems in general.
OPTIMAL BINARY SPACE PARTITIONS FOR SEGMENTS IN THE PLANE
Authors: DE BERG MARK , KHOSRAVI AMIRALI
Published: October 2012

An optimal BSP for a set S of disjoint line segments in the plane is a BSP for S that produces the minimum number of cuts. We study optimal BSPs for three classes of BSPs, which differ in the splitting lines that can be used when partitioning a set of fragments in the recursive partitioning process: free BSPs can use any splitting line, restricted BSPs can only use splitting lines through pairs of fragment endpoints, and auto-partitions can only use splitting lines containing a fragment. We obtain the following two results:

• It is NP-hard to decide whether a given set of segments admits an auto-partition that does not make any cuts.

• An optimal restricted BSP makes at most 2 times as many cuts as an optimal free BSP for the same set of segments.
GHOST CHIMNEYS
Authors: CHARLTON DAVID , DEMAINE ERIK D. , DEMAINE MARTIN L. , DUJMOVIĆ VIDA , MORIN PAT , UEHARA RYUHEI
Published: October 2012

A planar point set S is an (i, t)set of ghost chimneys if there exist lines H0, H1,…,Ht-1 such that the orthogonal projection of S onto Hj consists of exactly i + j distinct points. We give upper and lower bounds on the maximum value of t in an (i, t) set of ghost chimneys, showing that it is linear in i.
Nonlinear Adjustments of Volatility Expectations to Forecast Errors: Evidence from Markov-Regime Switches in Implied Volatility
Authors: Nishina Kazuhiko , Maghrebi Nabil , Holmes Mark J.
Published: October 2012

This paper tests for nonlinearities in the behavior of volatility expectations based on model-free implied volatility indices. Using Markov regime-switching models, the empirical evidence from the German, Japanese and U.S. markets suggests that there are indeed regime-specific levels of volatility expectations. Whereas the regimes seem to be governed by the degree of serial correlation and adjustment to forecast errors, there is no evidence of significant leverage effects. The frequency of regime shifts in volatility expectations is affected by the onset of financial crises, which have the effect of increasing the likelihood of regimes driven by lower autoregressive effects and faster speeds of adjustment. The evidence suggests that despite the heterogeneous beliefs of market participants, implied volatility indices provide a measure of consensus expectations that can be useful in understanding the nonlinear behavior of volatility expectations during periods of financial instability.
EDITORIAL
Authors: Phua Kok Khoo
Published: October 2012

In this issue of Asia Pacific Physics Newsletter (APPN), we especially commemorate the birth centennial of Madame Chien-Shiung Wu.
Spin-Orbit Coupled Quantum Gases
Authors: Zhai Hui
Published: October 2012

Spin-orbit coupling is an important effect in many areas of physics, for instance, it plays an important role in determining atomic and nuclei structure and it gives birth to topological insulators. However, for long time spinorbit coupling was not discussed in the physics of ultracold atomic gases, because there is no spin-orbit coupling for the motion of neutral atoms. Recently, there are many proposals of generating various types of spin-orbit coupling in cold atom systems, and in particular, in 2011, Ian Speilman's group in NIST has realized one of these proposals experimentally in Rb-87 Bose condensate. These progresses generate a lot of interests and many good results have been published in the last couple years. Spin-orbit coupled quantum gases have now become one of the hottest research directions in cold atom physics. This review article reviews most recent theoretical and experimental progresses on this direction.
Time-Shift in the OPERA Setup: Proof against Superluminal Neutrinos without the need of knowing the CERN-LNGS distance and Reminiscences on the Origin of the Gran Sasso Lab, of the Third Neutrino and of the "Teramo Anomaly"
Authors: Zichichi Antonino
Published: October 2012

The LVD time stability allows one to establish a time-shift in the OPERA experiment, thus providing the first proof against superluminal neutrinos, using the horizontal muons of the "Teramo Anomaly." This proof is particularly interesting because it does not need the knowledge of the distance between the location at which the neutrinos are produced (CERN) and the location they are detected (LNGS). Since the superluminal neutrinos generated in the physics community a vivid interest in good and bad behavior in physics research, the author thought it was appropriate to recall the origin of the Gran Sasso Lab, of the third neutrino, of the horizontal muons due to the "Teramo Anomaly" and of the oscillation between leptonic flavors, when the CERN-Gran Sasso neutrino beam was included in the project for the most powerful underground laboratory in the world.
IUCAA (Inter-University Centre for Astronomy and Astrophysics, Pune, India): A Brief Description
Authors: Kembhavi Ajit
Published: October 2012

The Inter-University Centre for Astronomy and Astrophysics (IUCAA), located in the city of Pune in India, is an autonomous institution under the University Grants Commission (UGC). It is a centre of excellence for research in astronomy and astrophysics (A&A) and related areas. It also serves as a platform for the entire university community in the country for work in A&A. IUCAA has a vibrant environment for research and development and attracts hundreds of national and international visitors every year who use its facilities, benefit from the interaction with the faculty and provide their own expertise to the centre.
Information Technology research challenges for healthcare
Authors: Graham Susan , Estrin Deborah , Horvitz Eric , Kohane Isaac , Mynatt Elizabeth , Sim Ida
Published: October 2012

This whitepaper is a reprint from the Computing Community Consortium (http://www.cra.org/ccc/), first printed on May 25, 2010. This paper is an outgrowth of the workshop, "Discovery and Innovation in Health IT," sponsored by the National Science Foundation, the Office of the National Coordinator for Health Information Technology, the National Institute of Standards and Technology, the National Library of Medicine, the Agency for Healthcare Research and Quality, the Computing Community Consortium, and the American Medical Informatics Association. The workshop was held at the Parc 55 Hotel in San Francisco on October 29 and 30, 2009.
ACM International Health Informatics Symposium (IHI 2010) symposium report
Authors: Andrade Henrique
Published: October 2012

The first meeting of the ACM International Health Informatics Symposium took place in Arlington, Virginia during the period of November 11 and 12, 2010. This international forum focused on the application of computer and information science principles and information and communication technology to problems in healthcare, public health, the delivery of healthcare services and consumer health as well as the related social and ethical issues.
34th Annual Symposium on Biomedical and Health Informatics (AMIA 2010) conference report
Authors: Lai Albert M.
Published: October 2012

This conference report summarizes events and activities of the 34th AMIA Annual Symposium on Biomedical and Health Informatics held in Washington, DC, November 13--17, 2010. This conference is the premier educational event AMIA presents each year. The review process for the conference includes peer review from at least 3 reviewers. There were 958 submissions. 192 papers, 364 posters, and 66 panels were presented over 102 sessions. There were approximately 2,400 attendees. The next AMIA Annual Symposium will be held in Washington, DC, October 22--26, 2011.
How to Improve Security?
Authors: Neville-Neil George
Published: October 2012

We recently had a security compromise at work, and now the whole IT department is scrambling to improve security. One problem this whole episode has brought to light is that so much security advice is generic. It’s like being told to lock your door when you go out at night, without saying what kind of lock you ought to own or how many are enough to protect your house. I think by now most people know they need to lock their doors, so why aren’t there more specific guidelines for securing systems?
Abstraction in Hardware System Design
Authors: Nikhil Rishiyur S.
Published: October 2012

The history of software engineering is one of continuing development of abstraction mechanisms designed to tackle ever-increasing complexity. Hardware design, however, is not as current. For example, the two most commonly used HDLs date back to the 1980s. Updates to the standards lag behind modern programming languages in structural abstractions such as types, encapsulation, and parameterization. Their behavioral semantics lag even further. They are specified in terms of event-driven simulators running on uniprocessor von Neumann machines.
Scheduling of stream-based real-time applications for heterogeneous systems
Authors: Virlet Bruno , Zhou Xing , Giacalone Jean Pierre , Kuhn Bob , Garzaran Maria J. , Padua David
Published: October 2012

Designers of mobile devices face the challenge of providing the user with more processing power while increasing battery life. Heterogeneous systems offer some opportunities to solve this challenge. In an heterogeneous system, multiple classes of processors with dynamic voltage and frequency scaling functionality are embedded in the mobile device. With such a system it is possible to maximize performance while minimizing power consumption if tasks are mapped to the class of processors where they execute the most efficiently.

In this paper, we study the scheduling of tasks in a real-time context on a heterogeneous system-on-chip that has dynamic voltage and frequency scaling functionality. We develop a heuristic scheduling algorithm which minimizes the energy while still meeting the deadline. We introduce the concept of cross-platform task heterogeneity and model sets of tasks to conduct extensive experiments. The experimental results show that our heuristic has a much higher success rate than existing state of the art heuristics and derives a solution whose energy requirements are close to those of the optimal solution.
Task-level analysis for a language with async/finish parallelism
Authors: Albert Elvira , Arenas Puri , Genaim Samir , Zanardini Damiano
Published: October 2012

The task level of a program is the maximum number of tasks that can be available (i.e., not finished nor suspended) simultaneously during its execution for any input data. Static knowledge of the task level is of utmost importance for understanding and debugging parallel programs as well as for guiding task schedulers. We present, to the best of our knowledge, the first static analysis which infers safe and precise approximations on the task level for a language with async-finish parallelism. In parallel languages, async and finish are basic constructs for, respectively, spawning tasks and waiting until they terminate. They are the core of modern, parallel, distributed languages like X10. Given a (parallel) program, our analysis returns a task-level upper bound, i.e., a function on the program's input arguments that guarantees that the task level of the program will never exceed its value along any execution. Our analysis provides a series of useful (over)-approximations, going from the total number of tasks spawned in the execution up to an accurate estimation of the task level.
Precise and efficient parametric path analysis
Authors: Althaus Ernst , Altmeyer Sebastian , Naujoks Rouven
Published: October 2012

Hard real-time systems require tasks to finish in time. To guarantee the timeliness of such a system, static timing analyses derive upper bounds on the worst-case execution time (WCET) of tasks. There are two types of timing analyses: numeric and parametric. A numeric analysis derives a numeric timing bound and, to this end, assumes all information such as loop bounds to be given a priori. If these bounds are unknown during analysis time, a parametric analysis can compute a timing formula parametric in these variables. A performance bottleneck of timing analyses, numeric and especially parametric, is the so-called path analysis, which determines the path in the analyzed task with the longest execution time bound.

In this paper, we present a new approach to path analysis. This approach exploits the often rather regular structure of software for hard real-time and safety-critical systems. As we show in the evaluation of this paper, we strongly improve upon former techniques in terms of precision and runtime in the parametric case. Even in the numeric case, the approach competes with state-of-the-art techniques and may be an alternative to commercial tools employed for path analysis.
Global productiveness propagation
Authors: Bhagat Indu , Gibert Enric , Sánchez Jesús , González Antonio
Published: October 2012

This paper proposes a unique hardware-software collaborative strategy to remove useless work at 16-bit data-width granularity. The underlying motivation is to design a low power execution platform by exploiting 'narrow' computations. The proposal uses a strictly narrow bit-wide microarchitecture (16-bit integer datapath), which realizes the goal of a low cost, low hardware complexity, low power execution engine. Software dynamically maps the 64-bit computations by translating them into an equivalent 16-bit instruction stream and optimizing them.

In this paper, we propose an optimization technique, called Global Productiveness Propagation (GPP), which is a dynamic, profile-based optimization technique that infers the minimum required dataflow by pruning narrow computations that are most-probably useless (non-productive). More precisely, GPP speculatively prunes the static backward slices of selected narrow computations: computations that result in the same value (in their respective storage location) as that at the input of the region. This speculative optimization technique is formulated around the concept of 'narrow' computations because the same allow a finer granularity to distinguish between useful (productive) and useless (non-productive) work. GPP has been evaluated on an in-order narrow bit-wide execution core, achieving an average dynamic instruction stream reduction of 6.6%, while improving overall performance by 4.2%.
The safety of Electronic Medical Record (EMR) systems
Authors: Weber-Jahnke Jens H. , Mason-Blakley Fieran
Published: October 2012

Information and communication technology is rapidly transforming modern health care systems. Electronic Medical Records (EMRs) systems have replaced traditional forms of storing, processing, interpreting and exchanging patient health in many health care organizations. However, an increasing number of concerns are raised about the quality of EMR systems and industry regulators are pondering ways to ensure safer health information technologies. This paper discusses fundamental concepts associated with the safety of EMR systems, describes current approaches to regulating the industry, and discusses limitations of traditional safety engineering methods with respect to their application to EMR systems. We then present a domain-specific adaptation of Leveson's system-theoretic model STAMP for safety engineering of EMR systems and demonstrate its application with a real-world case study.
Underspecified harnesses and interleaved bugs
Authors: Joshi Saurabh , Lahiri Shuvendu K. , Lal Akash
Published: October 2012

Static assertion checking of open programs requires setting up a precise harness to capture the environment assumptions. For instance, a library may require a file handle to be properly initialized before it is passed into it. A harness is used to set up or specify the appropriate preconditions before invoking methods from the program. In the absence of a precise harness, even the most precise automated static checkers are bound to report numerous false alarms. This often limits the adoption of static assertion checking in the hands of a user.

In this work, we explore the possibility of automatically filtering away (or prioritizing) warnings that result from imprecision in the harness. We limit our attention to the scenario when one is interested in finding bugs due to concurrency. We define a warning to be an interleaved bug when it manifests on an input for which no sequential interleaving produces a warning. As we argue in the paper, limiting a static analysis to only consider interleaved bugs greatly reduces false positives during static concurrency analysis in the presence of an imprecise harness.

We formalize interleaved bugs as a differential analysis between the original program and its sequential version and provide various techniques for finding them. Our implementation CBugs demonstrates that the scheme of finding interleaved bugs can alleviate the need to construct precise harnesses while checking real-life concurrent programs.
Higher-order functional reactive programming in bounded space
Authors: Krishnaswami Neelakantan R. , Benton Nick , Hoffmann Jan
Published: October 2012

Functional reactive programming (FRP) is an elegant and successful approach to programming reactive systems declaratively. The high levels of abstraction and expressivity that make FRP attractive as a programming model do, however, often lead to programs whose resource usage is excessive and hard to predict. In this paper, we address the problem of space leaks in discrete-time functional reactive programs. We present a functional reactive programming language that statically bounds the size of the dataflow graph a reactive program creates, while still permitting use of higher-order functions and higher-type streams such as streams of streams. We achieve this with a novel linear type theory that both controls allocation and ensures that all recursive definitions are well-founded.

We also give a denotational semantics for our language by combining recent work on metric spaces for the interpretation of higher-order causal functions with length-space models of space-bounded computation. The resulting category is doubly closed and hence forms a model of the logic of bunched implications.
Constraints as control
Authors: Köksal Ali Sinan , Kuncak Viktor , Suter Philippe
Published: October 2012

We present an extension of Scala that supports constraint programming over bounded and unbounded domains. The resulting language, Kaplan, provides the benefits of constraint programming while preserving the existing features of Scala. Kaplan integrates constraint and imperative programming by using constraints as an advanced control structure; the developers use the monadic 'for' construct to iterate over the solutions of constraints or branch on the existence of a solution. The constructs we introduce have simple semantics that can be understood as explicit enumeration of values, but are implemented more efficiently using symbolic reasoning. Kaplan programs can manipulate constraints at run-time, with the combined benefits of type-safe syntax trees and first-class functions. The language of constraints is a functional subset of Scala, supporting arbitrary recursive function definitions over algebraic data types, sets, maps, and integers.

Our implementation runs on a platform combining a constraint solver with a standard virtual machine. For constraint solving we use an algorithm that handles recursive function definitions through fair function unrolling and builds upon the state-of-the art SMT solver Z3. We evaluate Kaplan on examples ranging from enumeration of data structures to execution of declarative specifications. We found Kaplan promising because it is expressive, supporting a range of problem domains, while enabling full-speed execution of programs that do not rely on constraint programming.
Defining code-injection attacks
Authors: Ray Donald , Ligatti Jay
Published: October 2012

This paper shows that existing definitions of code-injection attacks (e.g., SQL-injection attacks) are flawed. The flaws make it possible for attackers to circumvent existing mechanisms, by supplying code-injecting inputs that are not recognized as such. The flaws also make it possible for benign inputs to be treated as attacks. After describing these flaws in conventional definitions of code-injection attacks, this paper proposes a new definition, which is based on whether the symbols input to an application get used as (normal-form) values in the application's output. Because values are already fully evaluated, they cannot be considered "code" when injected. This simple new definition of code-injection attacks avoids the problems of existing definitions, improves our understanding of how and when such attacks occur, and enables us to evaluate the effectiveness of mechanisms for mitigating such attacks.
Analysis of recursively parallel programs
Authors: Bouajjani Ahmed , Emmi Michael
Published: October 2012

We propose a general formal model of isolated hierarchical parallel computations, and identify several fragments to match the concurrency constructs present in real-world programming languages such as Cilk and X10. By associating fundamental formal models (vector addition systems with recursive transitions) to each fragment, we provide a common platform for exposing the relative difficulties of algorithmic reasoning. For each case we measure the complexity of deciding state-reachability for finite-data recursive programs, and propose algorithms for the decidable cases. The complexities which include PTIME, NP, EXPSPACE, and 2EXPTIME contrast with undecidable state-reachability for recursive multi-threaded programs.
Playing in the grey area of proofs
Authors: Hoder Krystof , Kovacs Laura , Voronkov Andrei
Published: October 2012

Interpolation is an important technique in verification and static analysis of programs. In particular, interpolants extracted from proofs of various properties are used in invariant generation and bounded model checking. A number of recent papers studies interpolation in various theories and also extraction of smaller interpolants from proofs. In particular, there are several algorithms for extracting of interpolants from so-called local proofs. The main contribution of this paper is a technique of minimising interpolants based on transformations of what we call the "grey area" of local proofs. Another contribution is a technique of transforming, under certain common conditions, arbitrary proofs into local ones.

Unlike many other interpolation techniques, our technique is very general and applies to arbitrary theories. Our approach is implemented in the theorem prover Vampire and evaluated on a large number of benchmarks coming from first-order theorem proving and bounded model checking using logic with equality, uninterpreted functions and linear integer arithmetic. Our experiments demonstrate the power of the new techniques: for example, it is not unusual that our proof transformation gives more than a tenfold reduction in the size of interpolants.
Resource-sensitive synchronization inference by abduction
Authors: Botincan Matko , Dodds Mike , Jagannathan Suresh
Published: October 2012

We present an analysis which takes as its input a sequential program, augmented with annotations indicating potential parallelization opportunities, and a sequential proof, written in separation logic, and produces a correctly-synchronized parallelized program and proof of that program. Unlike previous work, ours is not an independence analysis; we insert synchronization constructs to preserve relevant dependencies found in the sequential program that may otherwise be violated by a naive translation. Separation logic allows us to parallelize fine-grained patterns of resource-usage, moving beyond straightforward points-to analysis. Our analysis works by using the sequential proof to discover dependencies between different parts of the program. It leverages these discovered dependencies to guide the insertion of synchronization primitives into the parallelized program, and to ensure that the resulting parallelized program satisfies the same specification as the original sequential program, and exhibits the same sequential behaviour. Our analysis is built using frame inference and abduction, two techniques supported by an increasing number of separation logic tools.