bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Analysis and Clinical Significance of Lactobacillus spp. Recovered from Clinical Specimens Presumptively Associated with Disease
Authors: Martinez Raquel M. , Hulten Kristina G. , Bui Uyen , Clarridge Jill E.
Published: October 2013

Lactobacillus
spp. are part of the normal human flora and are generally assumed to be nonpathogenic. We determined the genotypic identification of >100
Lactobacillus
isolates from clinical specimens in the context of presumed pathogenic potential (e.g., recovered as the single/predominant isolate from a sterile site or at ≥10
5
CFU/ml from urine). This study assessed the clinical significance and the frequency of occurrence of each
Lactobacillus
sp. We identified 16 species of
Lactobacillus
by 16S rRNA gene sequence analysis, 10 of which could not be associated with disease. While
Lactobacillus rhamnosus
,
Lactobacillus gasseri
, and
Lactobacillus paracasei
were associated with infections,
L. gasseri
was also a common colonizing/contaminating species.
Lactobacillus casei
,
Lactobacillus johnsonii
, and
Lactobacillus delbrueckii
were associated with at least one infection. Species commonly used in probiotic products (e.g.,
L. rhamnosus
and
L. casei
) were identical, by 16S rRNA gene sequencing, to our isolates associated with disease. Human isolates of
Lactobacillus
spp. have differing site associations and levels of clinical significance. Knowing the niche and pathogenic potential of each
Lactobacillus
sp. can be of importance to both clinical microbiology and the food and probiotic supplement industry.
Molecular Characterization of a Catalase-Negative Methicillin-Susceptible Staphylococcus aureus subsp. aureus Strain Collected from a Patient with Cutaneous Abscess
Authors: Ellis Michael W. , Johnson Ryan C. , Crawford Katrina , Lanier Jeffrey B. , Merrell D. Scott
Published: October 2013

We describe a cutaneous abscess caused by catalase-negative methicillin-susceptible
Staphylococcus aureus
subsp.
aureus
in a patient who was concomitantly colonized with virulent USA300 methicillin-resistant
S. aureus
(MRSA). Sequencing of the
katA
gene demonstrated a thymine insertion leading to a frameshift mutation and premature truncation of catalase to 21 amino acids.
Evaluation of the BioFire FilmArray Respiratory Panel and the GenMark eSensor Respiratory Viral Panel on Lower Respiratory Tract Specimens
Authors: Ruggiero Phyllis , McMillen Tracy , Tang Yi-Wei , Babady N. Esther
Published: October 2013

We evaluated the performance characteristics of the FilmArray respiratory panel and the eSensor respiratory viral panel on clinical and spiked lower respiratory tract specimens (LRTS). The overall agreement between the two methods was 89.5% (51/57). The lower limit of detection of both assays for all targets in LRTS was comparable to that for nasopharyngeal swab specimens.
Rotavirus NSP1 Protein Inhibits Interferon-Mediated STAT1 Activation
Authors: Sen Adrish , Rott Lusijah , Phan Nguyen , Mukherjee Gourab , Greenberg Harry B.
Published: October 2013

Rotavirus (RV) replicates efficiently in intestinal epithelial cells (IECs)in vivodespite the activation of a local host interferon (IFN) response. Previously, we demonstrated that homologous RV efficiently inhibits IFN induction in single infected and bystander villous IECsin vivo. Paradoxically, RV also induces significant type I IFN expression in the intestinal hematopoietic cell compartment in a relatively replication-independent manner. This suggests that RV replication and spread in IECs must occur despite exogenous stimulation of the STAT1-mediated IFN signaling pathway. Here we report that RV inhibits IFN-mediated STAT1 tyrosine 701 phosphorylation in human IECsin vitroand identify RV NSP1 as a direct inhibitor of the pathway. Infection of human HT29 IECs with simian (RRV) or porcine (SB1A or OSU) RV strains, which inhibit IFN induction by targeting either IFN regulatory factor 3 (IRF3) or NF-κB, respectively, resulted in similar regulation of IFN secretion. By flow cytometric analysis at early times during infection, neither RRV nor SB1A effectively inhibited the activation of Y701-STAT1 in response to exogenously added IFN. However, at later times during infection, both RV strains efficiently inhibited IFN-mediated STAT1 activation within virus-infected cells, indicating that RV encodes inhibitors of IFN signaling targeting STAT1 phosphorylation. Expression of RV NSP1 in the absence of other viral proteins resulted in blockage of exogenous IFN-mediated STAT1 phosphorylation, and this function was conserved in NSP1 from simian, bovine, and murine RV strains. Analysis of NSP1 determinants responsible for the inhibition of IFN induction and signaling pathways revealed that these determinants are encoded on discrete domains of NSP1. Finally, we observed that at later times during infection with SB1A, there was almost complete inhibition of IFN-mediated Y701-STAT1 in bystander cells staining negative for viral antigen. This property segregated with the NSP1 gene and was observed in a simian SA11 monoreassortant that encoded porcine OSU NSP1 but not in wild-type SA11 or a reassortant encoding simian RRV NSP1.
The Selection of Low Envelope Glycoprotein Reactivity to Soluble CD4 and Cold during Simian-Human Immunodeficiency Virus Infection of Rhesus Macaques
Authors: McGee Kathleen , Haim Hillel , Korioth-Schmitz Birgit , Espy Nicole , Javanbakht Hassan , Letvin Norman , Sodroski Joseph
Published: October 2013

Envelope glycoprotein (Env) reactivity (ER) describes the propensity of human immunodeficiency virus type 1 (HIV-1) Env to change conformation from the metastable unliganded state in response to the binding of ligands (antibodies and soluble CD4 [sCD4]) or incubation in the cold. To investigate Env properties that favorin vivopersistence, we inoculated rhesus macaques with three closely related CCR5-tropic simian-human immunodeficiency viruses (SHIVs) that differ in ER to cold (ERcold) and ER to sCD4 (ERsCD4); these SHIVs were neutralized by antibodies equivalently and thus were similar in ERantibody. All three SHIVs achieved high levels of acute viremia in the monkeys without alteration of their Env sequences, indicating that neither ERcoldnor ERsCD4significantly influences the establishment of infection. Between 14 and 100 days following infection, viruses with high ERcoldand ERsCD4were counterselected. Remarkably, the virus variant with low ERcoldand low ERsCD4did not elicit a neutralizing antibody response against the infecting virus, despite the generation of high levels of anti-Env antibodies in the infected monkeys. All viruses that achieved persistent viremia escaped from any autologous neutralizing antibodies and exhibited low ERcoldand low ERsCD4. One set of gp120 changes determined the decrease in ERcoldand ERsCD4, and a different set of gp120 changes determined resistance to autologous neutralizing antibodies. Each set of changes contributed to a reduction in Env-mediated entry. During infection of monkeys, any Env replication fitness costs associated with decreases in ERcoldand ERsCD4may be offset by minimizing the elicitation of autologous neutralizing antibodies.
Functional Characterization of Bovine Viral Diarrhea Virus Nonstructural Protein 5A by Reverse Genetic Analysis and Live Cell Imaging
Authors: Isken Olaf , Langerwisch Ulrike , Schönherr Robert , Lamp Benjamin , Schröder Kristin , Duden Rainer , Rümenapf Tillmann H. , Tautz Norbert
Published: October 2013

Nonstructural protein 5A (NS5A) of bovine viral diarrhea virus (BVDV) is a hydrophilic phosphoprotein with RNA binding activity and a critical component of the viral replicase.In silicoanalysis suggests that NS5A encompasses three domains interconnected by two low-complexity sequences (LCSs). While domain I harbors two functional determinants, an N-terminal amphipathic helix important for membrane association, and a Zn-binding site essential for RNA replication, the structure and function of the C-terminal half of NS5A are still ill defined. In this study, we introduced a panel of 10 amino acid deletions covering the C-terminal half of NS5A. In the context of a highly efficient monocistronic replicon, deletions in LCS I and the N-terminal part of domain II, as well as in domain III, were tolerated with regard to RNA replication. When introduced into a bicistronic replicon, only deletions in LCS I and the N-terminal part of domain II were tolerated. In the context of the viral full-length genome, these mutations allowed residual virion morphogenesis. Based on these data, a functional monocistronic BVDV replicon coding for an NS5A variant with an insertion of the fluorescent protein mCherry was constructed. Live cell imaging demonstrated that a fraction of NS5A-mCherry localizes to the surface of lipid droplets. Taken together, this study provides novel insights into the functions of BVDV NS5A. Moreover, we established the first pestiviral replicon expressing fluorescent NS5A-mCherry to directly visualize functional viral replication complexes by live cell imaging.
Crystal Structures of Beta- and Gammaretrovirus Fusion Proteins Reveal a Role for Electrostatic Stapling in Viral Entry
Authors: Aydin Halil , Cook Jonathan D. , Lee Jeffrey E.
Published: October 2013

Membrane fusion is a key step in the life cycle of all envelope viruses, but this process is energetically unfavorable; the transmembrane fusion subunit (TM) of the virion-attached glycoprotein actively catalyzes the membrane merger process. Retroviral glycoproteins are the prototypical system to study pH-independent viral entry. In this study, we determined crystal structures of extramembrane regions of the TMs from Mason-Pfizer monkey virus (MPMV) and xenotropic murine leukemia virus-related virus (XMRV) at 1.7-Å and 2.2-Å resolution, respectively. The structures are comprised of a trimer of hairpins that is characteristic of class I viral fusion proteins and now completes a structural library of retroviral fusion proteins. Our results allowed us to identify a series of intra- and interchain electrostatic interactions in the heptad repeat and chain reversal regions. Mutagenesis reveals that charge-neutralizing salt bridge mutations significantly destabilize the postfusion six-helix bundle and abrogate retroviral infection, demonstrating that electrostatic stapling of the fusion subunit is essential for viral entry. Our data indicate that salt bridges are a major stabilizing force on the MPMV and XMRV retroviral TMs and likely provide the key energetics for viral and host membrane fusion.
Murine Cytomegalovirus Protein pM92 Is a Conserved Regulator of Viral Late Gene Expression
Authors: Chapa Travis J. , Perng Yi-Cheih , French Anthony R. , Yu Dong
Published: October 2013

In this study, we report that murine cytomegalovirus (MCMV) protein pM92 regulates viral late gene expression during virus infection. Previously, we have shown that MCMV protein pM79 and its human cytomegalovirus (HCMV) homologue pUL79 are required for late viral gene transcription. Identification of additional factors involved is critical to dissecting the mechanism of this regulation. We show here that pM92 accumulated abundantly at late times of infection in a DNA synthesis-dependent manner and localized to nuclear viral replication compartments. To investigate the role of pM92, we constructed a recombinant virus SM
in
92, in which pM92 expression was disrupted by an insertional/frameshift mutation. During infection, SM
in
92 accumulated representative viral immediate-early gene products, early gene products, and viral DNA sufficiently but had severe reduction in the accumulation of late gene products and was thus unable to produce infectious progeny. Coimmunoprecipitation and mass spectrometry analysis revealed an interaction between pM92 and pM79, as well as between their HCMV homologues pUL92 and pUL79. Importantly, we showed that the growth defect of pUL92-deficient HCMV could be rescued in
trans
by pM92. This study indicates that pM92 is an additional viral regulator of late gene expression, that these regulators (represented by pM92 and pM79) may need to complex with each other for their activity, and that pM92 and pUL92 share a conserved function in CMV infection. pM92 represents a potential new target for therapeutic intervention in CMV disease, and a gateway into studying a largely uncharted viral process that is critical to the viral life cycle.
Association of inorganic arsenic exposure with type 2 diabetes mellitus: a meta-analysis
Authors: Wang Weijing , Xie Zhutian , Lin Yan , Zhang Dongfeng
Published: October 2013

Background

The association of long-term effects of inorganic arsenic (iAs) exposure with type 2 diabetes mellitus (T2DM) risk remains controversial.

Methods

A literature search was performed in PubMed, China National Knowledge Infrastructure and Web of Knowledge for relevant available articles published in English or Chinese from 1 January 1990 to 5 June 2013. Case-control, cohort or cross-sectional studies evaluating iAs and T2DM were included. The DerSimonian and Laird random effect model was adopted as the pooling method. Dose-response relationship was assessed by restricted cubic spline model and multivariate random-effect meta-regression.

Results

Of the 569 articles identified through searching databases, 17 published articles with 2 243 745 participants for iAs in drinking water and 21 083 participants for total arsenic (tAs) in urine were included for this meta-analysis. The pooled relative risk with 95% CI of T2DM for the highest versus lowest category of iAs exposure level in drinking water was 1.75 (1.20 to 2.54). After removing three studies that had a strong effect on heterogeneity, the pooled relative risk was 1.23 (1.12 to 1.36). Dose–response analysis suggested T2DM risk increased by 13% (1.13 (1.00 to 1.27)) for every 100 µg/L increment of iAs in drinking water. Significant association of T2DM risk with tAs in urine was also found 1.28 (1.14 to 1.44).

Conclusions

This meta-analysis indicates that long-term iAs exposure might be positively associated with T2DM risk.
15(S)-HETE-induced angiogenesis in adipose tissue is mediated through activation of PI3K/Akt/mTOR signaling pathway
Authors: Soumya Sasikumar J. , Binu Sheela , Helen Antony , Reddanna Pallu , Sudhakaran Perumana R.
Published: October 2013

Chronic low-grade inflammation underlies obesity and associated metabolic dysfunctions. Lipoxygenase pathways are activated in adipose tissue during obese conditions. Since adipogenesis is associated with angiogenesis, the present study was designed to examine the role of 15-lipoxygenase metabolite, 15(S)-hydroxyeicosatetraenoic acid [15(S)-HETE] on angiogenesis in adipose tissue. Results showed that 15(S)-HETE induced sprouting in fat pad stromovascular tissues, induced morphological changes relevant to angiogenesis in endothelial cells derived from adipose tissue, upregulated the production of CD31, upregulated the gene level expression and production of vascular endothelial growth factor (VEGF), indicating the pro-angiogenic effect of 15(S)-HETE. LY294002, an inhibitor of PI3K-Akt pathway, and rapamycin, inhibitor of mammalian target of rapamycin (mTOR), significantly reversed the effect of 15(S)-HETE. 15(S)-HETE also induced activation of Akt and mTOR. These observations suggest that 15(S)-HETE stimulates angiogenesis in adipose tissue through activation of PI3K/Akt/mTOR signaling.
The influence of forest composition and climate on outbreak characteristics of the spruce budworm in eastern Canada
Authors: Gray David R.
Published: October 2013

The spruce budworm (Choristoneura fumiferana Clemens) is perhaps the single most important disturbance agent in Canada’s eastern forests. Climate and forest composition are dominant factors in spruce budworm outbreak dynamics through their direct influences on the pest, its natural enemies, and its hosts, and through their influence on the multitrophic interactions that are important in outbreak dynamics. A combination of four climate variables, three forest composition variables, and one location variable explained 60% of the multivariate variability in outbreak characteristics (duration and severity) in eastern Canada. Outbreak duration was most strongly influenced by April–May accumulation of degree-days; outbreak severity was most strongly influenced by the extreme maximum temperatures of April–May. The basal area of balsam fir had a stronger influence than that of black spruce on duration and on severity. Both outbreak characteristics declined in more northerly locations. Under a projected future (2011–2040) climate scenario the largest increases in outbreak duration and severity are predicted to occur on the Gaspé Peninsula and the north shore of the St. Lawrence River (Quebec). The largest decreases in duration and severity are predicted to occur in southern Ontario and along the Bay of Fundy in New Brunswick and Nova Scotia. The predicted average change in outbreak duration is around –1.3 years. The predicted average change in outbreak severity is only slightly different from zero (around –1.5% defoliation).
QUASINORMAL FREQUENCIES OF BLACK BRANES WITH HYPERSCALING VIOLATION
Authors: BAI NAN , GAO YI-HONG , QI BU-GUAN , XU XIAO-BAO
Published: October 2013

We investigated quasinormal frequencies (QNFs) in black brane with hyperscaling violating by using the continued fractions method. We calculate QNF of massless scalar field and electromagnetic field both with zero spatial momentum, find that QNFs have negative imaginary frequency suggesting black brane with hyperscaling violation is stable under those perturbations.
ON THE MATHIEU EQUATION DESCRIBING ULTRA-RELATIVISTIC FERMIONS EVOLVING IN A TIME-HARMONIC ELECTRIC FIELD PARALLEL TO A STATIC MAGNETIC INDUCTION
Authors: DARIESCU MARINA-AURA , DARIESCU CIPRIAN
Published: October 2013

The present work is studying the behavior of relativistic fermions in parallel electric and magnetic fields, oriented along Oz. As expected, in the particular case of static field intensities, the temporal part of the wave function is expressed in terms of the parabolic cylinder functions. When the static electric field is replaced by a time-harmonic one, the ultra-relativistic particles are described by a Mathieu-type equation, of purely imaginary parameter. Below the first branching point, which imposes a maximum value for the electric intensity, one may use a series expansion of the Mathieu's functions to derive the corresponding wave functions and the conserved current density components. Finally, we obtain a nontrivial quantization law of the longitudinal momentum, pz.
EFFECT OF ISOSPIN DEGREE OF FREEDOM ON TRANSVERSE MOMENTUM SPECTRA
Authors: KAUR SUKHJIT , SWATI
Published: October 2013

We study the effect of isospin degree of freedom, incident energy as well as system mass on the behavior of transverse momentum spectra, dN/ptdpt, of neutrons and protons. We find that most of the nucleons suffer soft collisions. The effect of isospin degree of freedom on transverse spectra diminishes with the increase in the incident energy. In Fermi energy region, transverse momentum spectra of both protons and neutrons show sensitivity toward the density dependence of symmetry energy.
EFFICIENT QUANTUM RANDOM NUMBER GENERATION USING QUANTUM INDISTINGUISHABILITY
Authors: SHENOY H. AKSHATA , SRIKANTH R. , SRINIVAS T.
Published: October 2013

In this paper, we propose a quantum method for generation of random numbers based on bosonic stimulation. Randomness arises through the path-dependent indeterministic amplification of two competing bosonic modes. We show that the process provides an efficient method for macroscopic extraction of microscopic randomness.
ssDNA TRANSLOCATION WITH CARBOXYL-MODIFIED TRANSMEMBRANE SINGLE-WALLED CARBON NANOTUBE
Authors: REN Y. X. , NG T. Y. , LI HUA
Published: October 2013

Functionalized transmembrane carbon nanotube (CNT) interactions are of significant importance in CNT-based drug delivery systems and biomedical devices. In this work, an all-atom molecular dynamics simulation is applied to study the encapsulation of a short single-stranded DNA (ssDNA) oligonucleotide in functionalized carbon nanotube (f-CNT) channels. We show that while the van der Waals (vdW) interaction between the ssDNA and the f-CNT induces a spontaneous encapsulation of the molecule within the nanotube channel, the vdW interaction between the ssDNA and biomembrane counteract the encapsulation. However, the vdW attraction due to the f-CNT is stronger than that from the membrane lipid bilayer, leading to the final encapsulation. In particular, we obtain the vdW interaction force between the ssDNA, biomembrane and the f-CNT analytically through a general mathematical model. This interaction force is found to play a dominate role in the adsorption process. The analytically obtained vdW force and potential fields show good correspondence with the adsorption conditions and the adsorption behavior of the ssDNA obtained numerically via the all-atom molecular dynamics simulation.
Assessing the seismic AVA detectability of CO
2
storage sites using novel time-lapse attributes
Authors: Jafargandomi Arash , Curtis Andrew
Published: October 2013

Monitoring of stored carbon dioxide (CO
2
) in subsurface reservoirs is fundamental to operation and management of the storage site, and is a requirement of some national and international legislation. As a consequence, effectiveness of monitorability (the ability to observe the evolving location of subsurface CO
2
) for any given level of investment in monitoring technology is a significant investment uncertainty that must be assessed along other components of the storage-site selection criteria (e.g. capacity, injectivity and storage economies). We develop a workflow to assess the time-lapse seismic detectability of changes in subsurface aquifer reservoirs by analysing expected changes in seismic amplitude variation with angle (AVA) in the field. Laboratory measurements are used to calculate the seismic response of the reservoir at different saturations and pressures. We include the scattering effect of material above and below the reservoir by using a finite-difference, full-waveform modelling approach AVA analysis then assimilates local site effects into the detectability assessment. We show that performing waveform modelling which includes local geological heterogeneities above and below the reservoir interval is essential to assess the storage site monitroability. In order to quantify expected time-lapse changes in the seismic response, we introduce a new set of robust time-lapse attributes based on time–frequency decomposition. The attributes effectively separate amplitude and phase changes (time-shifts) of time-lapse seismic records, and allow us to quantify their repeatability against the background noise. Furthermore, the frequency-dependent nature of the attributes provides a quantification of the frequency–domain effects of time-lapse changes. The approach is employed to assess the detectability of supercritical CO
2
in two analogue storage sites in the near-shore UK North Sea. Analysis of laboratory measurements and AVA responses indicate the contrasting monitorability of the two sites, which helps decision making about further site investigation and development. Application of the approach to hydrocarbon reservoir monitoring is straightforward.
Analyzing System-Level Information’s Correlation to FPGA Placement
Authors: Gharibian Farnaz , Shannon Lesley , Jamieson Peter , Chung Kevin
Published: October 2013

One popular placement algorithms for Field-Programmable Gate Arrays (FPGAs) is called Simulated Annealing (SA). This algorithm tries to create a good quality placement from a flattened design that no longer contains any high-level information related to the original design hierarchy. Placement is an NP-hard problem, and as the size and complexity of designs implemented on FPGAs increases, SA does not scale well to find good solutions in a timely fashion. In this article, we investigate if system-level information can be reconstructed from a flattened netlist and evaluate how that information is realized in terms of its locality in the final placement. If there is a strong relationship between good quality placements and system-level information, then it may be possible to divide a large design into smaller components and improve the time needed to create a good quality placement. Our preliminary results suggest that the locality property of the information embedded in the system-level HDL structure (i.e. “module”, “always”, and “if” statements) is greatly affected by designer HDL coding style. Therefore, a reconstructive algorithm, called Affinity Propagation, is also considered as a possible method of generating a meaningful coarse-grain picture of the design.
Distinguishing Users By Pointing Performance in Laboratory and Real-World Tasks
Authors: Hurst Amy , Hudson Scott E. , Mankoff Jennifer , Trewin Shari
Published: October 2013

Accurate pointing is an obstacle to computer access for individuals who experience motor impairments. One of the main barriers to assisting individuals with pointing problems is a lack of frequent and low-cost assessment of pointing ability. We are working to build technology to automatically assess pointing problems during every day (or real-world) computer use. To this end, we have gathered and studied real-world pointing use from individuals with motor impairments and older adults. We have used this data to develop novel techniques to analyze pointing performance. In this article, we present learned statistical models that distinguish between pointing actions from diverse populations using real-world pointing samples. We describe how our models could be used to support individuals with different abilities sharing a computer, or one individual who experiences temporary pointing problems. Our investigation contributes to a better understanding of real-world pointing. We hope that these techniques will be used to develop systems that can automatically adapt to users’ current needs in real-world computing environments.
UNTANGLED
Authors: Mehta Gayatri , Crawford Carson , Luo Xiaozhong , Parde Natalie , Patel Krunalkumar , Rodgers Brandon , Sistla Anil Kumar , Yadav Anil , Reisner Marc
Published: October 2013

The problem of creating efficient mappings of dataflow graphs onto specific architectures (i.e., solving theplace and routeproblem) is incredibly challenging. The difficulty is especially acute in the area of Coarse-Grained Reconfigurable Architectures (CGRAs) to the extent that solving the mapping problem may remove a significant bottleneck to adoption. We believe that the next generation of mapping algorithms will exhibit pattern recognition, the ability to learn from experience, and identification of creative solutions, all of which are human characteristics. This manuscript describes our game UNTANGLED, developed and fine-tuned over the course of a year to allow us to capture and analyze human mapping strategies. It also describes our results to date. We find that the mapping problem can be crowdsourced very effectively, that players can outperform existing algorithms, and that successful player strategies share many elements in common. Based on our observations and analysis, we make concrete recommendations for future research directions for mapping onto CGRAs.
Test-and-adapt
Authors: Denaro Giovanni , Pezzè Mauro , Tosi Davide
Published: October 2013

Service-oriented applications do not fully benefit from standard APIs yet, and many applications fail to use interchangeably all the services that implement a standard service API. This article presents an approach to develop adaptation strategies that improve service interchangeability for service-oriented applications based on standard APIs. In our approach, an adaptation strategy consists of sets of parametric adaptation plans (called test-and-adapt plans), which execute test cases to reveal the occurrence of interchangeability problems, and activate runtime adaptors according to the test results. Throughout this article, we formalize the structure of the parametric test-and-adapt plans and of their execution semantics, present an algorithm for identifying correct execution orders through sets of test-and-adapt plans, provide empirical evidence of the occurrence of interchangeability problems for sample applications and services, and discuss the effectiveness of the approach in terms of avoided failures, runtime overheads and development costs.
A methodology for testing CPU emulators
Authors: Martignoni Lorenzo , Paleari Roberto , Reina Alessandro , Roglia Giampaolo Fresi , Bruschi Danilo
Published: October 2013

A CPU emulator is a software system that simulates a hardware CPU. Emulators are widely used by computer scientists for various kind of activities (e.g., debugging, profiling, and malware analysis). Although no theoretical limitation prevents developing an emulator that faithfully emulates a physical CPU, writing a fully featured emulator is a very challenging and error prone task. Modern CISC architectures have a very rich instruction set, some instructions lack proper specifications, and others may have undefined effects in corner cases. This article presents a testing methodology specific for CPU emulators, based on fuzzing. The emulator is “stressed” with specially crafted test cases, to verify whether the CPU is properly emulated or not. Improper behaviors of the emulator are detected by running the same test case concurrently on the emulated and on the physical CPUs and by comparing the state of the two after the execution. Differences in the final state testify defects in the code of the emulator. We implemented this methodology in a prototype (named as EmuFuzzer), analyzed five state-of-the-art IA-32 emulators (QEMU, Valgrind, Pin, BOCHS, and JPC), and found several defects in each of them, some of which can prevent proper execution of programs.
Monitoring the Corrosion Inhibition of Nitrogen-Containing Heterocyclic Compounds in Dye Sensitized Solar Cells
Authors: Wragg David A , Watson Trystan M.
Published: October 2013

A challenge facing the successful commercialization of dye sensitized solar cells (DSCs) is in the choice of substrates used in their construction. Previous studies have shown that titanium is the current best choice for mass produced liquid state DSC due to the corrosive nature of the electrolyte, however this is an expensive material for use in large scale production. Other industrial metal substrates such as steel, nickel or aluminium have been shown previously to be prone to corrosion by the aggressive triiodide species contained in the electrolyte. In this study we show that nitrogen containing heterocyclics (NHCs) present in the electrolyte for enhancement of photovoltaic performance can also provide an additional effect of inhibiting corrosion on certain metal substrates.
Electrochemical Cells for In-Situ XRD Studies of Insertion and Extraction Mechanisms of Lithium in Anode Materials for Lithium Ion Batteries Tested at Aluminum Model Electrodes
Authors: Bach Philipp , Seemayer Andreas , Rütt Uta , Gutowski Olof , Renner Frank Uwe
Published: October 2013

Lithium ion batteries (LIBs) are already widely used in a variety of different applications in daily life and are now facing new applications with new challenges requiring significant enhancement of power, lifetime, cost, safety and flexibility. Our aim with regard to purposeful improvement of LIBs is to get insight on the atomic scale into the mechanisms during charging and discharging. Applying in-situ X-ray diffraction (in-situ XRD) using synchrotron light we studied the alloy phase evolution during galvanostatic electrochemical lithiation (charging) and delithiation (discharging) of an Al model anode. We found the alloy phase Li1Al1 to be formed and dissolved, respectively, reproducibly and reversibly. To perform in-situ XRD we constructed two electrochemical cells penetrable for X-ray radiation which can be operated on top of the diffractometer at synchrotron radiation facilities. With this approach it is possible to correlate electrochemistry, phase evolution and crystallographic orientation.
The Oxygen Evolution Reaction at Manganese Oxide Films in Base: Kinetics and Mechanism
Authors: Browne Michelle , Cullen Ronan J. , Doyle Richard L. , Colavita Paula E , Lyons Michael E.G.
Published: October 2013

Various manganese oxide type Dimensionally Stable Anode (DSA) electrodes were prepared though a simple thermal decomposition technique at different annealing temperatures for their effect on the oxygen evolution reaction (OER). Along with the change in different annealing temperatures, the effects of different metal substrates were also explored. Cyclic Voltammetry was used to analysis the redox transitions of all annealing temperatures on the nickel and titanium substrates. Steady state polarization curves (also known as Tafel Plots) were used to determine tafel slopes, Open Circuit Potential decay analysis was also used to determine tafel slopes. Reaction orders of the 350°C nickel MnxOy electrode were determined and calculated as a half reaction order. A mechanism for this electrode is also proposed. SEM-EDX and FTIR analysis are also reported on some MnxOy films and powders.
Application of Alginate Binders to Graphite Electrodes and Characterization of Their Lithium-Ion Battery Performance
Authors: Soeda Kazunari , Matsui Yukiko , Yamagata Masaki , Ishikawa Masashi
Published: October 2013

Alginate salts (Alg-salt) were used as binders for graphite electrodes in both ionic liquid (IL)- and organic-electrolyte-based lithium-ion batteries (LIBs). Two different types of Alg-salt were used in this study: Alg-Na and Alg-Mg. According to the cyclic voltammograms and charge–discharge measurements, a graphite negative electrode with the Alg-Na binder in both IL and conventional organic electrolytes exhibited reversible and high C-rate capability compared with an electrode with an SBR binder. This implies that the high affinity of Alg for graphite electrode active materials decreases the electrode/electrolyte interfacial resistance. We also fabricated full cells composed of the prepared graphite electrode with Alg-salt and LiNi1/3Co1/3Mn1/3O2 (NMC/C+Alg-X, X = Na+ or Mg2+). During high-voltage (3.0–4.5 V) operation, NMC/C+Alg-Mg showed the most stable cycle performance with high coulombic efficiency. These results suggest that the Alg-salt binder, especially the Alg-Mg binder, can be used in the fabrication of high-performance LIBs with either an IL- or organic-based electrolyte.
Attenuated thermoregulatory, metabolic, and liver acute phase protein response to heat stroke in TNF receptor knockout mice
Authors: Leon Lisa R. , Dineen Shauna , Blaha Michael D. , Rodriguez-Fernandez Maria , Clarke David C.
Published: October 2013

Tumor necrosis factor (TNF) is considered an adverse mediator of heat stroke (HS) based on clinical studies showing high serum levels. However, soluble TNF receptors (sTNFR; TNF antagonists) were higher in survivors than nonsurvivors, and TNFR knockout (KO) mice showed a trend toward increased mortality, suggesting TNF has protective actions for recovery. We delineated TNF actions in HS by comparing thermoregulatory, metabolic, and inflammatory responses between B6129F2(wild type, WT) and TNFR KO mice. Before heat exposure, TNFR KO mice showed ∼0.4°C lower core temperature (Tc; radiotelemetry), ∼10% lower metabolic rate (Mr; indirect calorimetry), and reduced plasma interleukin (IL)-1α and sIL-1RI than WT mice. KO mice selected warmer temperatures than WT mice in a gradient but remained hypothermic. In the calorimeter, both genotypes showed a similar heating rate, but TNFR KO maintained lower Tcand Mrthan WT mice for a given heat exposure duration and required ∼30 min longer to reach maximum Tc(42.4°C). Plasma IL-6 increased at ∼3 h of recovery in both genotypes, but KO mice showed a more robust sIL-6R response. Higher sIL-6R in the KO mice was associated with delayed liver p-STAT3 protein expression and attenuated serum amyloid A3 (SAA3) gene expression, suggesting the acute phase response (APR) was attenuated in these mice. Our data suggest that the absence of TNF signaling induced a regulated hypothermic state in the KO mice, TNF-IL-1 interactions may modulate Tcand Mrduring homeostatic conditions, and TNF modulates the APR during HS recovery through interactions with the liver IL-6-STAT3 pathway of SAA3 regulation.
Role of an excitatory preoptic-raphé pathway in febrile vasoconstriction of the rat's tail
Authors: Tanaka Mutsumi , McKinley Michael J. , McAllen Robin M.
Published: October 2013

Heat dissipation from the rat's tail is reduced in response to cold and during fever. The sympathetic premotor neurons for this mechanism, located in the medullary raphé, are under tonic inhibitory control from the preoptic area. In parallel with the inhibitory pathway, an excitatory pathway from the rostromedial preoptic region (RMPO) to the medullary raphé mediates the vasoconstrictor response to cold skin. Whether this applies also to the tail vasoconstrictor response in fever is unknown. Single- or a few-unit tail sympathetic nerve activity (SNA) was recorded in urethane-anesthetized, artificially ventilated rats. Experimental fever was induced by PGE2injected into the lateral cerebral ventricle (50 ng in 1.5 μl icv) or into the RMPO (0.2 ng in 60 nl); in both cases, there was a robust increase in tail SNA and a delayed rise in core temperature. Microinjection of glutamate receptor antagonist kynurenate (50 mM, 120 nl) into the medullary raphé completely reversed the tail SNA response to intracerebroventricular or RMPO PGE2injection. Inhibiting RMPO neurons by microinjecting glycine (0.5 M, 60 nl) or the GABAAreceptor agonist, muscimol (2 mM, 30–60 nl), reduced the tail SNA response to PGE2injected into the same site by approximately half. Vehicle injections into the medullary raphé or RMPO were without effect. These results suggest that the tail vasoconstrictor response during experimental fever depends on a glutamatergic excitatory synaptic relay in the medullary raphé and that an excitatory output signal from the RMPO contributes to the tail vasoconstrictor response during fever.
Neural correlates of motion processing through echolocation, source hearing, and vision in blind echolocation experts and sighted echolocation novices
Authors: Thaler L. , Milne J. L. , Arnott S. R. , Kish D. , Goodale M. A.
Published: October 2013

We have shown in previous research (Thaler L, Arnott SR, Goodale MA. PLoS One 6: e20162, 2011) that motion processing through echolocation activates temporal-occipital cortex in blind echolocation experts. Here we investigated how neural substrates of echo-motion are related to neural substrates of auditory source-motion and visual-motion. Three blind echolocation experts and twelve sighted echolocation novices underwent functional MRI scanning while they listened to binaural recordings of moving or stationary echolocation or auditory source sounds located either in left or right space. Sighted participants' brain activity was also measured while they viewed moving or stationary visual stimuli. For each of the three modalities separately (echo, source, vision), we then identified motion-sensitive areas in temporal-occipital cortex and in the planum temporale. We then used a region of interest (ROI) analysis to investigate cross-modal responses, as well as laterality effects. In both sighted novices and blind experts, we found that temporal-occipital source-motion ROIs did not respond to echo-motion, and echo-motion ROIs did not respond to source-motion. This double-dissociation was absent in planum temporale ROIs. Furthermore, temporal-occipital echo-motion ROIs in blind, but not sighted, participants showed evidence for contralateral motion preference. Temporal-occipital source-motion ROIs did not show evidence for contralateral preference in either blind or sighted participants. Our data suggest a functional segregation of processing of auditory source-motion and echo-motion in human temporal-occipital cortex. Furthermore, the data suggest that the echo-motion response in blind experts may represent a reorganization rather than exaggeration of response observed in sighted novices. There is the possibility that this reorganization involves the recruitment of “visual” cortical areas.
Movement speed is biased by prior experience
Authors: Hammerbeck Ulrike , Yousif Nada , Greenwood Richard , Rothwell John C. , Diedrichsen Jörn
Published: October 2013

How does the motor system choose the speed for any given movement? Many current models assume a process that finds the optimal balance between the costs of moving fast and the rewards of achieving the goal. Here, we show that such models also need to take into account a prior representation of preferred movement speed, which can be changed by prolonged practice. In a time-constrained reaching task, human participants made 25-cm reaching movements within 300, 500, 700, or 900 ms. They were then trained for 3 days to execute the movement at either the slowest (900-ms) or fastest (300-ms) speed. When retested on the 4th day, movements executed under all four time constraints were biased toward the speed of the trained movement. In addition, trial-to-trial variation in speed of the trained movement was significantly reduced. These findings are indicative of a use-dependent mechanism that biases the selection of speed. Reduced speed variability was also associated with reduced errors in movement amplitude for the fast training group, which generalized nearly fully to a new movement direction. In contrast, changes in perpendicular error were specific to the trained direction. In sum, our results suggest the existence of a relatively stable but modifiable prior of preferred movement speed that influences the choice of movement speed under a range of task constraints.
Respiration-related discharge of hyoglossus muscle motor units in the rat
Authors: Powell Gregory L. , Rice Amber , Bennett-Cross Seres J. , Fregosi Ralph F.
Published: October 2013

Although respiratory muscle motor units have been studied during natural breathing, simultaneous measures of muscle force have never been obtained. Tongue retractor muscles, such as the hyoglossus (HG), play an important role in swallowing, licking, chewing, breathing, and, in humans, speech. The HG is phasically recruited during the inspiratory phase of the respiratory cycle. Moreover, in urethane anesthetized rats the drive to the HG waxes and wanes spontaneously, providing a unique opportunity to study motor unit firing patterns as the muscle is driven naturally by the central pattern generator for breathing. We recorded tongue retraction force, the whole HG muscle EMG and the activity of 38 HG motor units in spontaneously breathing anesthetized rats under low-force and high-force conditions. Activity in all cases was confined to the inspiratory phase of the respiratory cycle. Changes in the EMG were correlated significantly with corresponding changes in force, with the change in EMG able to predict 53–68% of the force variation. Mean and peak motor unit firing rates were greater under high-force conditions, although the magnitude of discharge rate modulation varied widely across the population. Changes in mean and peak firing rates were significantly correlated with the corresponding changes in force, but the correlations were weak ( r2 = 0.27 and 0.25, respectively). These data indicate that, during spontaneous breathing, recruitment of HG motor units plays a critical role in the control of muscle force, with firing rate modulation playing an important but lesser role.
Phase I Trial of Preoperative Chemoradiation plus Sorafenib for High-Risk Extremity Soft Tissue Sarcomas with Dynamic Contrast-Enhanced MRI Correlates
Authors: Meyer Janelle M. , Perlewitz Kelly S. , Hayden James B. , Doung Yee-Cheen , Hung Arthur Y. , Vetto John T. , Pommier Rodney F. , Mansoor Atiya , Beckett Brooke R. , Tudorica Alina , Mori Motomi , Holtorf Megan L. , Afzal Aneela , Woodward William J. , Rodler Eve T. , Jones Robin L. , Huang Wei , Ryan Christopher W.
Published: October 2013

Purpose: We conducted a phase I trial of the addition of sorafenib to a chemoradiotherapy regimen in patients with high-risk (intermediate/high grade, >5 cm) extremity soft tissue sarcoma undergoing limb salvage surgery. We conducted a correlative study of quantitative dynamic contrast-enhanced MRI (DCE-MRI) to assess response to treatment.

Experimental Design: Patients were treated at increasing dose levels of sorafenib (200 mg daily, 400 mg daily, 400 mg twice daily) initiated 14 days before three preoperative and three postoperative cycles of epirubicin/ifosfamide. Radiation (28 Gy) was administered during cycle 2 with epirubicin omitted. The primary objective was to determine the maximum tolerated dose (MTD) of sorafenib. DCE-MRI was conducted at baseline, after 2 weeks of sorafenib, and before surgery. The imaging data were subjected to quantitative pharmacokinetic analyses.

Results: Eighteen subjects were enrolled, of which 16 were evaluable. The MTD of sorafenib was 400 mg daily. Common grade 3–4 adverse events included neutropenia (94%), hypophosphatemia (75%), anemia (69%), thrombocytopenia (50%), and neutropenic fever/infection (50%). Of note, 38% developed wound complications requiring surgical intervention. The rate of ≥95% histopathologic tumor necrosis was 44%. Changes in DCE-MRI biomarker ΔKtrans after 2 weeks of sorafenib correlated with histologic response (R2 = 0.67, P = 0.012) at surgery.

Conclusion: The addition of sorafenib to preoperative chemoradiotherapy is feasible and warrants further investigation in a larger trial. DCE-MRI detected changes in tumor perfusion after 2 weeks of sorafenib and may be a minimally invasive tool for rapid assessment of drug effect in soft tissue sarcoma. Clin Cancer Res; 19(24); 6902–11. ©2013 AACR.
Discrete Molecular Classes of Ovarian Cancer Suggestive of Unique Mechanisms of Transformation and Metastases
Authors: Gardi Nilesh L. , Deshpande Tejaswini U. , Kamble Swapnil C. , Budhe Sagar R. , Bapat Sharmila A.
Published: October 2013

Purpose: Tumor heterogeneity and subsistence of high-grade serous ovarian adenocarcinoma (HGSC) classes can be speculated from clinical incidences suggesting passive tumor dissemination versus active invasion and metastases.

Experimental Design: We explored this theme toward tumor classification through two approaches of gene expression pattern clustering: (i) derivation of a core set of metastases-associated genes and (ii) resolution of independent weighted correlation networks. Further identification of appropriate cell and xenograft models was carried out for resolution of class-specific biologic functions.

Results: Both clustering approaches achieved resolution of three distinct tumor classes, two of which validated in other datasets. Networks of enriched gene modules defined biologic functions of quiescence, cell division-differentiation-lineage commitment, immune evasion, and cross-talk with niche factors. Although deviant from normal homeostatic mechanisms, these class-specific profiles are not totally random. Preliminary validation of these suggests that Class 1 tumors survive, metastasize in an epithelial–mesenchymal transition (EMT)-independent manner, and are associated with a p53 signature, aberrant differentiation, DNA damage, and genetic instability. These features supported by association of cell-specific markers, including PAX8, PEG3, and TCF21, led to the speculation of their origin being the fimbrial fallopian tube epithelium. On the other hand, Class 2 tumors activate extracellular matrix–EMT–driven invasion programs (Slug, SPARC, FN1, THBS2 expression), IFN signaling, and immune evasion, which are prospectively suggestive of ovarian surface epithelium associated wound healing mechanisms. Further validation of these etiologies could define a new therapeutic framework for disease management. Clin Cancer Res; 20(1); 87–99. ©2013 AACR.