bluuebunny/crossref_metadata_2025 huggingface dataset:
The Contemporary Presidency Obama's Authorization Paradox: Syria and Congress's Continued Relevance in Military Affairs
Authors: Kriner Douglas L.
Published: April 2014

President Obama's decision to seek congressional authorization for a military strike against Syria caught many political observers by surprise. However, I argue that the decision was more a gambit for political gain than a sincere reevaluation of the scope of presidential war powers. Moreover, Obama's ploy reveals a larger truth about American politics: that Congress often retains considerable influence over military affairs through informal means. An original survey experiment shows that seeking authorization can bolster support for the president and his foreign policies, particularly if the decision is backed by congressional leaders. More importantly, authorization votes may pay political dividends years later by muting congressional criticism of presidential policies. A wealth of data from previous interventions in Iraq, Kosovo, Bosnia, and Lebanon suggests that members of both parties who voted to authorize the use of force are much less willing in the future to vote to curtail it or criticize it publicly than are their co‐partisan peers who did not vote for an authorization.
Measuring Multi‐Membership in Economic Integration and Its Trade Impact: A Comparative Study of ECOWAS and SADC
Authors: Afesorgbor Sylvanus Kwaku , van Bergeijk Peter A. G.
Published: April 2014

One of the intriguing aspects of African regional trade agreements (RTAs) is the extent of multi‐membership, where many African countries are members of more than one RTA. Using a gravity model for 25 countries and the years 1980‐2006, we measure the extent of multi‐membership and compare its impact in two major African regional blocs, Economic Community of West Africa States (ECOWAS) and Southern Africa Development Community (SADC). We find that the impact of multi‐membership critically depends on the characteristics of the multi‐membership of regional integration initiatives. We find a positive impact if an additional membership complements the integration process of the original regional integration initiative: overlapping memberships had a much stronger and significant positive effect on bilateral trade within ECOWAS compare with an insignificant impact within the SADC.
Factors influencing isometric exercise training‐induced reductions in resting blood pressure
Authors: Lawrence M. M. , Cooley I. D. , Huet Y. M. , Arthur S. T. , Howden R.
Published: April 2014

Hypertension is a major health concern, and current recommendations for blood pressure management (lifestyle modifications and pharmacological intervention) have not been universally successful. For two decades, isometric exercise training (IET) has become established as effective at reducing in resting BP (RBP) in a short period (4–10 weeks). The most common IET modes have comprised isometric handgrip (IHG) or isometric bilateral leg (IBL) training and 4 × 2‐min contractions at ∼20–50% maximal voluntary contraction with 1–5‐min rest between. Although this type of exercise training could have important implications, for hypertensive patients and in preventing hypertension development, little is known about the mechanisms responsible for IET‐induced RBP reductions. This uncertainty derives from a lack of understanding concerning the most effective IET programs for specific populations. Possible influential factors and mechanisms include age, sex, pre‐existing disease and medication, and IET‐induced adaptations in the exercising muscle and nervous system, which are discussed in this review. Designing effective IET programs may involve manipulation of exercise intensity, frequency, duration and mode, as well as consideration of yet discovered mechanisms for RBP reductions. We call for additional research designed to understand more about the mechanisms involved in IET‐induced RBP reductions for maximum effectiveness.
Do nonsteroidal anti‐inflammatory drugs affect the outcome of arthroscopic Bankart repair?
Authors: Blomquist J. , Solheim E. , Liavaag S. , Baste V. , Havelin L. I.
Published: April 2014

To achieve pain control after arthroscopic shoulder surgery, nonsteroidal anti‐inflammatory drugs (NSAIDs) are a complement to other analgesics. However, experimental studies have raised concerns that these drugs may have a detrimental effect on soft tissue‐to‐bone healing and, thus, have a negative effect on the outcome. We wanted to investigate if there are any differences in the clinical outcome after the arthroscopic Bankart procedure for patients who received NSAIDs prescription compared with those who did not. 477 patients with a primary arthroscopic Bankart procedure were identified in the Norwegian shoulder instability register and included in the study. 32.5% received prescription of NSAIDs post‐operatively. 370 (78%) of the patients answered a follow‐up questionnaire containing the Western Ontario Shoulder Instability index (WOSI). Mean follow‐up was 21 months. WOSI at follow‐up were 75% in the NSAID group and 74% in the control group. 12% of the patients in the NSAID group and 14% in the control group reported recurrence of instability. The reoperation rate was 5% in both groups. There were no statistically significant differences between the groups. Prescription of short‐term post‐operative NSAID treatment in the post‐operative period did not influence on the functional outcome after arthroscopic Bankart procedures.
A Reference Architecture for Mobile SOA
Authors: Sefid‐Dashti Behrouz , Habibi Jafar
Published: April 2014

Integration of mobile devices into a service‐oriented system involves the consideration of architectural design principles and trade‐offs among interdependent design decisions to cope with limitations of mobile devices in terms of resources available within a device and aspects of network connectivity. Mobile devices consume some services and provide others. A reference architecture (RA) that provides solutions, baseline and future insights is the priority in designing efficient mobile service oriented architecture (SOA). This paper discusses nuances of the concept of RA. The paper presents a survey of 26 mobile SOA patterns and proposes mobile SOA RA that extends Open Group SOA RA based on the catalogue of mobile SOA patterns proposed in this paper. Evaluations are made and discussed for both RA and its possible instantiation.
A Controller Framework for Autonomous Drifting: Design, Stability, and Experimental Validation
Authors: Hindiyeh Rami Y. , Christian Gerdes J.
Published: April 2014

This paper presents the development of a controller for autonomous, steady-state cornering with rear tire saturation (“drifting”) of a rear wheel drive vehicle. The controller is designed using a three-state vehicle model intended to balance simplicity and sufficient model fidelity. The model has unstable “drift equilibria” with large rear drive forces that induce deep rear tire saturation. The rear tire saturation at drift equilibria reduces vehicle stability but enables “steering” of the rear tire force through friction circle coupling of rear tire forces. This unique stability–controllability tradeoff is reflected in the controller design, through novel usage of the rear drive force for lateral control. An analytical stability guarantee is provided for the controller through a physically insightful invariant set around a desired drift equilibrium when operating in closed-loop. When implemented on a by-wire testbed, the controller achieves robust drifts on a surface with highly varying friction, suggesting that steady cornering with rear tire saturation can prove quite effective for vehicle trajectory control under uncertain conditions.
Study of the Cavitating Instability on a Grooved Venturi Profile
Authors: Danlos Amélie , Méhal Jean-Elie , Ravelet Florent , Coutier-Delgosha Olivier , Bakir Farid
Published: April 2014

Instabilities of a partial cavity developed on a hydrofoil, a converging-diverging step, or in an interblade channel have already been investigated in many previous works. The aim of this study is to evaluate a passive control method of the sheet cavity. According to operating conditions, cavitation can be described by two different regimes: an unstable regime with a cloud cavitation shedding and a stable regime with only a pulsating sheet cavity. Avoiding cloud cavitation can limit structure damage since this regime is less aggressive. The surface condition of a converging-diverging step is here studied as a solution to control the cavitation regime. This study discusses the effect of longitudinal grooves on the developed sheet cavity. Analyzes conducted with laser Doppler velocimetry, visualizations, and pressure measurements show that the grooves geometry, and especially the groove depth act on the sheet cavity dynamics and can even suppress the cloud cavitation shedding.
Accurate measurement of dopant concentration in organic light-emitting diodes by combining high-performance liquid chromatography and TOF-SIMS
Authors: Fujimoto Hiroshi , Edura Tomohiko , Miyayama Takuya , Sanada Noriaki , Adachi Chihaya
Published: April 2014

The authors report the use of high-performance liquid chromatography (HPLC) and time-of-flight secondary ion mass spectrometry (TOF-SIMS) utilizing a gas cluster ion beam to accurately measure the dopant concentration and its depth profile in organic thin films used for organic light-emitting diodes. The total dopant concentrations estimated by HPLC for films of 4,4'-bis(carbazol-9-yl)biphenyl (CBP) doped with tris(2-phenylpyridinato)iridium(III) (Ir(ppy)3) are consistent with those measured by quartz crystal microbalances (QCMs) during the deposition. Concentrations measured for Ir(ppy)3:CBP films by HPLC and TOF-SIMS show a nearly linear relationship in the range of 1–8 wt. %. At concentrations higher than 8 wt. %, TOF-SIMS values significantly deviate because of the matrix effect. The depth profile of the dopant concentration measured by TOF-SIMS was in good agreement with that measured by QCMs during film deposition for concentrations below 8 wt. %. These methods are especially useful for comparing the dopant concentration of films deposited in different batches and equipment.
Microglial Progenitors Lie in Wait
Authors: Berndt Jason D.
Published: April 2014

CSFR1 is required for the homeostasis of microglia in the adult brain.
Sabotaging Immunosurveillance
Authors: Ferrarelli Leslie K.
Published: April 2014

Some cancer therapies may be a double-edged sword, blocking pathways that mediate tumor growth and those mediating immune recognition.
Defended by Lipids
Authors: Gough Nancy R.
Published: April 2014

Lipid signals mediate the response to mitochondrial stress.
A Conserved Hydrogen-Bonding Network of P2
bis
-Tetrahydrofuran-Containing HIV-1 Protease Inhibitors (PIs) with a Protease Active-Site Amino Acid Backbone Aids in Their Activity against PI-Resistant HIV
Authors: Yedidi Ravikiran S. , Garimella Harisha , Aoki Manabu , Aoki-Ogata Hiromi , Desai Darshan V. , Chang Simon B. , Davis David A. , Fyvie W. Sean , Kaufman Joshua D. , Smith David W. , Das Debananda , Wingfield Paul T. , Maeda Kenji , Ghosh Arun K. , Mitsuya Hiroaki
Published: April 2014

In the present study, GRL008, a novel nonpeptidic human immunodeficiency virus type 1 (HIV-1) protease inhibitor (PI), and darunavir (DRV), both of which contain a P2-
bis
-tetrahydrofuranyl urethane (
bis
-THF) moiety, were found to exert potent antiviral activity (50% effective concentrations [EC
50
s], 0.029 and 0.002 μM, respectively) against a multidrug-resistant clinical isolate of HIV-1 (HIV
A02
) compared to ritonavir (RTV; EC
50
, >1.0 μM) and tipranavir (TPV; EC
50
, 0.364 μM). Additionally, GRL008 showed potent antiviral activity against an HIV-1 variant selected in the presence of DRV over 20 passages (HIV
DRV
R
P20
), with a 2.6-fold increase in its EC
50
(0.097 μM) compared to its corresponding EC
50
(0.038 μM) against wild-type HIV-1
NL4-3
(HIV
WT
). Based on X-ray crystallographic analysis, both GRL008 and DRV showed strong hydrogen bonds (H-bonds) with the backbone-amide nitrogen/carbonyl oxygen atoms of conserved active-site amino acids G27, D29, D30, and D30′ of HIV
A02
protease (PR
A02
) and wild-type PR in their corresponding crystal structures, while TPV lacked H-bonds with G27 and D30′ due to an absence of polar groups. The P2′ thiazolyl moiety of RTV showed two conformations in the crystal structure of the PR
A02
-RTV complex, one of which showed loss of contacts in the S2′ binding pocket of PR
A02
, supporting RTV's compromised antiviral activity (EC
50
, >1 μM). Thus, the conserved H-bonding network of P2-
bis
-THF-containing GRL008 with the backbone of G27, D29, D30, and D30′ most likely contributes to its persistently greater antiviral activity against HIV
WT
, HIV
A02
, and HIV
DRV
R
P20
.
Population Pharmacokinetic Analysis of Piperacillin in Burn Patients
Authors: Jeon Sangil , Han Seunghoon , Lee Jongtae , Hong Taegon , Paek Jeongki , Woo Heungjeong , Yim Dong-Seok
Published: April 2014

Piperacillin in combination with tazobactam, a β-lactamase inhibitor, is a commonly used intravenous antibiotic for the empirical treatment of infection in intensive care patients, including burn patients. The purpose of this study was to develop a population pharmacokinetic (PK) model for piperacillin in burn patients and to predict the probability of target attainment (PTA) using MICs and concentrations simulated from the PK model. Fifty burn patients treated with piperacillin-tazobactam were enrolled. Piperacillin-tazobactam was administered via infusion for approximately 30 min at a dose of 4.5 g (4 g piperacillin and 0.5 g tazobactam) every 8 h. Blood samples were collected just prior to and at 1, 2, 3, 4, and 6 h after the end of the infusion at steady state. The population PK model of piperacillin was developed using NONMEM. A two-compartment first-order elimination PK model was finally chosen. The covariates included were creatinine clearance (CL
CR
), day after burn injury (DAI), and sepsis. The final PK parameters were clearance (liters/h) (equal to 16.6 × [CL
CR
/132] + DAI × [−0.0874]), central volume (liters) (equal to 25.3 + 14.8 × sepsis [0 for the absence or 1 for the presence of sepsis]), peripheral volume (liters) (equal to 16.1), and intercompartmental clearance (liters/h) (equal to 0.636). The clearance and volume of piperacillin were higher than those reported in patients without burns, and the terminal half-life and PTA decreased with the increased CL
CR
. Our PK model suggests that higher daily doses or longer durations of infusion of piperacillin should be considered, especially for burn patients with a CL
CR
of ≥160 ml/min.
Copper Complexation Screen Reveals Compounds with Potent Antibiotic Properties against Methicillin-Resistant Staphylococcus aureus
Authors: Haeili Mehri , Moore Casey , Davis Christopher J. C. , Cochran James B. , Shah Santosh , Shrestha Tej B. , Zhang Yaofang , Bossmann Stefan H. , Benjamin William H. , Kutsch Olaf , Wolschendorf Frank
Published: April 2014

Macrophages take advantage of the antibacterial properties of copper ions in the killing of bacterial intruders. However, despite the importance of copper for innate immune functions, coordinated efforts to exploit copper ions for therapeutic interventions against bacterial infections are not yet in place. Here we report a novel high-throughput screening platform specifically developed for the discovery and characterization of compounds with copper-dependent antibacterial properties toward methicillin-resistant
Staphylococcus aureus
(MRSA). We detail how one of the identified compounds, glyoxal-bis(N4-methylthiosemicarbazone) (GTSM), exerts its potent strictly copper-dependent antibacterial properties on MRSA. Our data indicate that the activity of the GTSM-copper complex goes beyond the general antibacterial effects of accumulated copper ions and suggest that, in contrast to prevailing opinion, copper complexes can indeed exhibit species- and target-specific activities. Based on experimental evidence, we propose that copper ions impose structural changes upon binding to the otherwise inactive GTSM ligand and transfer antibacterial properties to the chelate. In turn, GTSM determines target specificity and utilizes a redox-sensitive release mechanism through which copper ions are deployed at or in close proximity to a putative target. According to our proof-of-concept screen, copper activation is not a rare event and even extends to already established drugs. Thus, copper-activated compounds could define a novel class of anti-MRSA agents that amplify copper-dependent innate immune functions of the host. To this end, we provide a blueprint for a high-throughput drug screening campaign which considers the antibacterial properties of copper ions at the host-pathogen interface.
In Vitro
and
In Vivo
Biological Effects of Novel Arylimidamide Derivatives against Trypanosoma cruzi
Authors: Timm Bruno Lisboa , da Silva Patrícia Bernadino , Batista Marcos Meuser , da Silva Francisca Hildemagna Guedes , da Silva Cristiane França , Tidwell Richard R. , Patrick Donald A. , Jones Susan Kilgore , Bakunov Stanislav A. , Bakunova Svetlana M. , Soeiro Maria de Nazaré C.
Published: April 2014

Chagas disease (CD), a neglected tropical disease caused by
Trypanosoma cruzi
, remains a serious public health problem in several Latin American countries. The available chemotherapies for CD have limited efficacy and exhibit undesirable side effects. Aromatic diamidines and arylimidamides (AIAs) have shown broad-spectrum activity against intracellular parasites, including
T. cruzi
. Therefore, our aim was to evaluate the biological activity of eight novel AIAs (16DAP002, 16SAB079, 18SAB075, 23SMB022, 23SMB026, 23SMB054, 26SMB070, and 27SMB009) against experimental models of
T. cruzi
infection
in vitro
and
in vivo
. Our data show that none of the compounds induced a loss of cellular viability up to 32 μM. Two AIAs, 18SAB075 and 16DAP002, exhibited good
in vitro
activity against different parasite strains (Y and Tulahuen) and against the two relevant forms of the parasite for mammalian hosts. Due to the excellent selective indexes of 18SAB075, this AIA was moved to
in vivo
tests for acute toxicity and parasite efficacy; nontoxic doses (no-observed-adverse-effect level [NOAEL], 50 mg/kg) were employed in the tests for parasite efficacy. In experimental models of acute
T. cruzi
infection, 18SAB075 reduced parasitemia levels only up to 50% and led to 40% protection against mortality (at 5 mg/kg of body weight), being less effective than the reference drug, benznidazole.
Plasmid Carriage of
bla
NDM-1
in Clinical Acinetobacter baumannii Isolates from India
Authors: Jones Lim S. , Toleman Mark A. , Weeks Janis L. , Howe Robin A. , Walsh Timothy R. , Kumarasamy Karthikeyan K.
Published: April 2014

NDM-1 probably emerged in
Acinetobacter
species prior to its dissemination among
Enterobacteriaceae
, and NDM-1-like enzymes are increasingly reported in
Acinetobacter
species. Here, we report on the genetic context of
bla
NDM-1
in the earliest known NDM-1-producing organisms, clinical isolates of
Acinetobacter
from India in 2005. These strains harbor
bla
NDM-1
plasmids of different sizes. The gene is associated with the remnants of the Tn
125
transposon normally associated with
bla
NDM-1
in
Acinetobacter
spp. The transposon has been disrupted by the IS
26
insertion and subsequent movement events.
Relationship between Time to Clinical Response and Outcomes among Pneumonia Outcomes Research Team (PORT) Risk Class III and IV Hospitalized Patients with Community-Acquired Pneumonia Who Received Ceftriaxone and Azithromycin
Authors: Zasowski Evan , Butterfield Jill M. , McNutt Louise-Ann , Cohen Jason , Cosler Leon , Pai Manjunath P. , Gottwald Joseph , Chen Wen Zhen , Lodise Thomas P.
Published: April 2014

Recent Food and Drug Administration (FDA) guidance endorses the use of an early clinical response endpoint as the primary outcome for community-acquired bacterial pneumonia (CABP) trials. While antibiotics will now be approved for CABP, in practice they will primarily be used to treat patients with community-acquired pneumonia (CAP). More importantly, it is unclear how achievement of the new FDA CABP early response endpoint translates into clinically applicable real-world outcomes for patients with CAP. To address this, a retrospective cohort study was conducted among adult patients who received ceftriaxone and azithromycin for CAP of Pneumonia Outcomes Research Team (PORT) risk class III and IV at an academic medical center. The clinical response was defined as clinical stability for 24 h with improvement in at least one pneumonia symptom and with no symptom worsening. A classification and regression tree (CART) was used to determine the delay in response time, measured in days, associated with the greatest risk of a prolonged hospital length of stay (LOS) and adverse outcomes (in-hospital mortality or 30-day CAP-related readmission). A total of 250 patients were included. On average, patients were discharged 2 days following the achievement of a clinical response. In the CART analysis, adverse clinical outcomes were higher among day 5 nonresponders than those who responded by day 5 (22.4% versus 6.9%,
P
= 0.001). The findings from this study indicate that time to clinical response, as defined by the recent FDA guidance, is a reasonable prognostic indictor of real-world effectiveness outcomes among hospitalized PORT risk class III and IV patients with CAP who received ceftriaxone and azithromycin.
Activity of Potent and Selective Host Defense Peptide Mimetics in Mouse Models of Oral Candidiasis
Authors: Ryan Lisa K. , Freeman Katie B. , Masso-Silva Jorge A. , Falkovsky Klaudia , Aloyouny Ashwag , Markowitz Kenneth , Hise Amy G. , Fatahzadeh Mahnaz , Scott Richard W. , Diamond Gill
Published: April 2014

There is a strong need for new broadly active antifungal agents for the treatment of oral candidiasis that not only are active against many species of
Candida
, including drug-resistant strains, but also evade microbial countermeasures which may lead to resistance. Host defense peptides (HDPs) can provide a foundation for the development of such agents. Toward this end, we have developed fully synthetic, small-molecule, nonpeptide mimetics of the HDPs that improve safety and other pharmaceutical properties. Here we describe the identification of several HDP mimetics that are broadly active against
C. albicans
and other species of
Candida
, rapidly fungicidal, and active against yeast and hyphal cultures and that exhibit low cytotoxicity for mammalian cells. Importantly, specificity for
Candida
over commensal bacteria was also evident, thereby minimizing potential damage to the endogenous microbiome which otherwise could favor fungal overgrowth. Three compounds were tested as topical agents in two different mouse models of oral candidiasis and were found to be highly active. Following single-dose administrations, total
Candida
burdens in tongues of infected animals were reduced up to three logs. These studies highlight the potential of HDP mimetics as a new tool in the antifungal arsenal for the treatment of oral candidiasis.
IS
1R
-Mediated Plasticity of IncL/M Plasmids Leads to the Insertion of
bla
OXA-48
into the Escherichia coli Chromosome
Authors: Beyrouthy R. , Robin F. , Delmas J. , Gibold L. , Dalmasso G. , Dabboussi F. , Hamzé M. , Bonnet R.
Published: April 2014

The OXA-48 carbapenemase is mainly encoded by ∼62-kb IncL/M plasmids. However, chromosome-mediated genes have been observed in
Escherichia coli
isolates. In this work, we investigated the genetic environment of OXA-48 in members of the family
Enterobacteriaceae
(
n
= 22) to understand how the OXA-48-encoding gene is transferred into the
E. coli
chromosome. The OXA-48-encoding gene was located within intact Tn
1999.2
transposons in the ∼62-kb plasmids or within a truncated variant of Tn
1999.2
for the OXA-48-encoding genes located in the chromosomes of
E. coli
bacteria. The analysis of the Tn
1999.2
genetic environment revealed an inverted orientation of the transposon in five ∼62-kb plasmids (5/14 [35%]) and in all chromosome inserts (
n
= 8). The sequencing of pRA35 plasmid showed that this orientation of Tn
1999.2
and the acquisition of an IS
1R
insertion sequence generated a 21.9-kb IS
1R
-based composite transposon encoding OXA-48 and designated Tn
6237
. The sequencing of a chromosomal insert encoding OXA-48 also revealed this new transposon in the
E. coli
chromosome. PCR mapping showed the presence of this element in all strains harboring an OXA-48-encoding chromosomal insert. However, different insertion sites of this transposon were observed in the
E. coli
chromosome. Overall, these findings indicate a plasticity of the OXA-48 genetic environment mediated by IS
1R
insertion sequences. The insertion sequences can induce the transfer of the OXA-encoding gene into
E. coli
chromosomes and thereby promote its persistence and expression at low levels.
Emergence of Clinical Salmonella enterica Serovar Typhimurium Isolates with Concurrent Resistance to Ciprofloxacin, Ceftriaxone, and Azithromycin
Authors: Wong Marcus Ho Yin , Yan Meiying , Chan Edward Wai Chi , Biao Kan , Chen Sheng
Published: April 2014

Salmonella
infection is an important public health issue for which the needs of antimicrobial treatment are increasing. A total of 546 human clinical
S. enterica
serovar Typhimurium isolates were recovered from patients in hospitals in China during the period of 2005 to ∼2011. Twenty percent of the isolates exhibited resistance to ciprofloxacin, and 4% were resistant to ceftriaxone. Importantly, for the first time, 12 (2%)
S
. Typhimurium isolates resistant to both ciprofloxacin and ceftriaxone were recovered; among these 12 isolates, two were also resistant to azithromycin, and one was resistant to all other drugs tested. The combined effects of various transferrable extended-spectrum β-lactamase determinants and a novel efflux-based ciprofloxacin resistance mechanism encoded by the mobile efflux gene
oqxAB
were responsible for the emergence of these extremely (highly) drug-resistant (XDR)
S
. Typhimurium isolates. The dissemination of resistance genes, such as those encoding ESBLs and the OqxAB pump, among
Salmonella
organisms will speed up the selection of XDR
Salmonella
, posing a huge threat to public health and
Salmonella
infection control.
Complete Nucleotide Sequence of Two Multidrug-Resistant IncR Plasmids from Klebsiella pneumoniae
Authors: Compain Fabrice , Frangeul Lionel , Drieux Laurence , Verdet Charlotte , Brisse Sylvain , Arlet Guillaume , Decré Dominique
Published: April 2014

We report here the complete nucleotide sequence of two IncR replicons encoding multidrug resistance determinants, including β-lactam (
bla
DHA-1
,
bla
SHV-12
), aminoglycoside (
aphA1
,
strA
,
strB
), and fluoroquinolone (
qnrB4
,
aac6′-1b-cr
) resistance genes. The plasmids have backbones that are similar to each other, including the replication and stability systems, and contain a wide variety of transposable elements carrying known antibiotic resistance genes. This study confirms the increasing clinical importance of IncR replicons as resistance gene carriers.
Strain Types and Antimicrobial Resistance Patterns of Clostridium difficile Isolates from the United States, 2011 to 2013
Authors: Tickler Isabella A. , Goering Richard V. , Whitmore Joseph D. , Lynn Ashley N. W. , Persing David H. , Tenover Fred C.
Published: April 2014

We determined the PCR ribotypes and antimicrobial susceptibility patterns of 508 toxigenic
Clostridium difficile
isolates collected between 2011 and 2013 from 32 U.S. hospitals. Of the 29 PCR ribotypes identified, the 027 strain type was the most common (28.1%), although the rates varied by geographic region. Ribotype 014/020 isolates appear to be emerging. Clindamycin and moxifloxacin resistances (36.8% and 35.8%, respectively) were the most frequent resistance phenotypes observed. Reduced susceptibility to vancomycin was observed in 39.1% of 027 isolates.
Akt Inhibitor MK2206 Prevents Influenza pH1N1 Virus Infection
In Vitro
Authors: Denisova Oxana V. , Söderholm Sandra , Virtanen Salla , Von Schantz Carina , Bychkov Dmitrii , Vashchinkina Elena , Desloovere Jens , Tynell Janne , Ikonen Niina , Theisen Linda L. , Nyman Tuula A. , Matikainen Sampsa , Kallioniemi Olli , Julkunen Ilkka , Muller Claude P. , Saelens Xavier , Verkhusha Vladislav V. , Kainov Denis E.
Published: April 2014

The influenza pH1N1 virus caused a global flu pandemic in 2009 and continues manifestation as a seasonal virus. Better understanding of the virus-host cell interaction could result in development of better prevention and treatment options. Here we show that the Akt inhibitor MK2206 blocks influenza pH1N1 virus infection
in vitro
. In particular, at noncytotoxic concentrations, MK2206 alters Akt signaling and inhibits endocytic uptake of the virus. Interestingly, MK2206 is unable to inhibit H3N2, H7N9, and H5N1 viruses, indicating that pH1N1 evolved specific requirements for efficient infection. Thus, Akt signaling could be exploited further for development of better therapeutics against pH1N1 virus.
Cysteine Protease Activity of Feline Tritrichomonas foetus Promotes Adhesion-Dependent Cytotoxicity to Intestinal Epithelial Cells
Authors: Tolbert M. K. , Stauffer S. H. , Brand M. D. , Gookin J. L.
Published: April 2014

Trichomonads are obligate protozoan parasites most renowned as venereal pathogens of the reproductive tract of humans and cattle. Recently, a trichomonad highly similar to bovine venerealTritrichomonas foetusbut having a unique tropism for the intestinal tract was recognized as a significant cause of colitis in domestic cats. Despite a high prevalence, worldwide distribution, and lack of consistently effective drugs for treatment of the infection, the cellular mechanisms ofT. foetuspathogenicity in the intestinal tract have not been examined. The aims of this study were to determine the pathogenic effect of felineT. foetuson porcine intestinal epithelial cells, the dependence ofT. foetuspathogenicity on adhesion ofT. foetusto the intestinal epithelium, and the identity of mediators responsible for these effects. Using anin vitrococulture approach to model felineT. foetusinfection of the intestinal epithelium, these studies demonstrate thatT. foetuspromotes a direct contact-dependent activation of intestinal epithelial cell apoptosis signaling and progressive monolayer destruction. Moreover, these pathological effects were demonstrated to be largely dependent onT. foetuscell-associated cysteine protease activity. Finally,T. foetuscysteine proteases were identified as enabling cytopathic effects by promoting adhesion ofT. foetusto the intestinal epithelium. The present studies are the first to examine the cellular mechanisms of pathogenicity ofT. foetustoward the intestinal epithelium and support further investigation of the cysteine proteases as virulence factorsin vivoand as potential therapeutic targets for ameliorating the pathological effects of intestinal trichomonosis.
Mechanism of Asp24 Upregulation in Brucella abortus Rough Mutant with a Disrupted O-Antigen Export System and Effect of Asp24 in Bacterial Intracellular Survival
Authors: Tian Mingxing , Qu Jing , Han Xiangan , Ding Chan , Wang Shaohui , Peng Daxin , Yu Shengqing
Published: April 2014

We previously showed thatBrucella abortusrough mutant strain 2308 ΔATP(called the ΔrfbEmutant in this study) exhibits reduced intracellular survival in RAW264.7 cells and attenuated persistence in BALB/c mice. In this study, we performed microarray analysis to detect genes with differential expression between the ΔrfbEmutant and wild-type strain S2308. Interestingly, acid shock protein 24 gene (asp24) expression was significantly upregulated in the ΔrfbEmutant compared to S2308, as confirmed by quantitative reverse transcription-PCR (qRT-PCR) and Western blotting. Further studies using additional strains indicated that the upregulation ofasp24occurred only in rough mutants with disrupted O-antigen export system components, including the ATP-binding protein generfbE(bab1_0542) and the permease generfbD(bab1_0543), while the ΔwboArough mutant (which lacks an O-antigen synthesis-related glycosyltransferase) and the RB51 strain (a vaccine strain with the rough phenotype) showed no significant changes inasp24expression compared to S2308. In addition, abolishing the intracellular O-antigen synthesis of the ΔrfbEmutant by deleting thewboAgene (thereby creating the ΔrfbEΔwboAdouble-knockout strain) recoveredasp24expression. These results indicated thatasp24upregulation is associated with intracellular O-antigen synthesis and accumulation but not with the bacterial rough phenotype. Further studies indicated thatasp24upregulation in the ΔrfbEmutant was associated neither with bacterial adherence and invasion nor with cellular necrosis on RAW264.7 macrophages. However, proper expression of theasp24gene favors intracellular survival ofBrucellain RAW264.7 cells and HeLa cells during an infection. This study reveals a novel mechanism forasp24upregulation inB. abortusmutants.
The numerical calculation of quantum field theory in hadron spectroscopy
Authors: Sun M. Z. , Cao Y. , Hu B. T. , Zhang Y. , Chen X. R.
Published: April 2014

In this paper, we introduced QFT++, a C++ toolkit for numerical calculation of quantum field theory. By comparing the result from QFT++ with the traditional calculation result of the Feynman amplitude [Formula: see text], the validity of QFT++ was demonstrated. Furthermore, the toolkit was optimized in a fixed convention, in which a significant improvement of performance was found. The optimized version will be used in the partial wave analysis (PWA) of hadron spectroscopy, where the computation speed is a crucial bottleneck in most cases.
Fabrication of Microchannels in Ceramics (Quartz) Using Electrochemical Spark Micromachining (ECSMM)
Authors: Jain V. K. , Priyadarshini D.
Published: April 2014

Electrochemical Machining (ECM) and Electric Discharge Machining (EDM) processes have high potential when applied in micro regimes for good accuracy and shape reproduction. But they have a limitation that only electrically conducting materials can be machined by them. To overcome this limitation, a combination of ECM and EDM processes has been conceived, and it is known as "electrochemical spark machining" (ECSM). ECSM is slowly gaining popularity in machining of non-conductive materials. Here, an attempt is made to perform machining at micro-level on quartz. It is piezoelectric in nature, and made up of a lattice of silica ( SiO 2) tetrahedral. For micromachining of quartz, the optimal value of voltage and work piece feed are found out. The depth of microchannel is increased to increase the aspect ratio of the microchannels to make them more useful to make the component such as a micromixer. Microchannels of different shapes are also generated. Finally, the microchannels of minimum width of 144 μm are obtained.
Examining Investment Strategies of Venture Capitalists in Open Source Software
Authors: Schaarschmidt Mario , von Kortzfleisch Harald
Published: April 2014

A growing body of literature has explored the motivation of firms to take part in open source software (OSS) development, yet the role of venture capitalists and their role in OSS projects is largely unattached. Based on information from publicly available data, we investigated the investment behavior of 37 VCs investing in 45 OSS projects. To understand how these venture capitalists try to reduce their perception of uncertainty and risk, we developed a 2 × 2 matrix of different investment approaches. While the X-axis represents the average age of a community/OSS product at the time of investment, the Y-axis reflects the average round of a venture capitalist's entry. This exploratory study illustrates how venture capitalists limit the level of risk inherent in certain OSS investments and results in a number of implications for communities seeking for external funds as well as for investing firms.
ALTERATIONS OF DNA TOPOISOMERASES OF RIEMERELLA ANATIPESTIFER WITH IN VITRO-REDUCED SUSCEPTIBILITY TO QUINOLONES
Authors: Chen Yen-Ping , Tseng Chun-Hsien , Lee Shu-Hwae , Chou Chung-Hsi , Tsai Hsiang-Jung
Published: April 2014

To elucidate on a potential association between mutations of topoisomerases and quinolone resistance in Riemerella anatipestifer, mutants of reduced quinolones susceptibility were generated from the four clinical isolates by serial passages in the presence of increased concentrations of nalidixic acid, ofloxacin, enrofloxacin and ciprofloxacin. Eleven alterations at eight positions (81, 82, 83, 84, 87, 117, 119, and 181) in GyrA and five different alterations at four (431, 452, 470, and 471) positions in GyrB were induced within mutants, resulting in various levels of resistance to different quinolones. The most frequent alteration was at Ser83 in GyrA, which concurred with that of previous clinical studies. To our best knowledge, alterations at Ala183 in GyrA and at Arg452 as well as Glu471 in GyrB were firstly reported. The study demonstrated that alterations of GyrA and GyrB are the prior mechanisms by which R. anatipestifer develops its resistance to quinolones. Expanding the quinolone-resistance determining region for R. anatipestifer is suggested as well.
Algorithm 941
Authors: Kressner Daniel , Tobler Christine
Published: April 2014

The hierarchical Tucker format is a storage-efficient scheme to approximate and represent tensors of possibly high order. This article presents a
Matlab
toolbox, along with the underlying methodology and algorithms, which provides a convenient way to work with this format. The toolbox not only allows for the efficient storage and manipulation of tensors in hierarchical Tucker format but also offers a set of tools for the development of higher-level algorithms. Several examples for the use of the toolbox are given.
Beyond Lamport's
Happened-before
Authors: Ben-Zvi Ido , Moses Yoram
Published: April 2014

The coordination of a sequence of actions, to be performed in a linear temporal order in a distributed system, is studied. While in asynchronous message-passing systems such ordering of events requires the construction of message chains based on Lamport's happened-before relation, this is no longer true in the presence of time bounds on message delivery. Given such bounds, the mere passage of time can provide information about the occurrence of events at remote sites, without the need for explicit confirmation. A new causal structure called the centipede is introduced, and it is shown that centipedes must exist in every execution where linear ordering of actions is ensured. Centipedes capture the subtle interplay between the explicit information obtained via message chains, and the indirectly derived information gained by the passage of time, given the time bounds. Centipedes are defined using two relations. One is called syncausality, a slight generalisation of the happened-before relation. The other is a novel bound guarantee relation among events, that is based on the bounds on message transmission. In a precise sense, centipedes play a role in the synchronous setting analogous to that played by message chains in asynchronous systems. Our study is based on a knowledge-based analysis of distributed coordination. Temporally linear coordination is reduced to nested knowledge (knowledge about knowledge). Obtaining nested knowledge of a spontaneous event is, in turn, shown to require the existence of an appropriate centipede.
Undecidability of Propositional Separation Logic and Its Neighbours
Authors: Brotherston James , Kanovich Max
Published: April 2014

In this article, we investigate the logical structure of memory models of theoretical and practical interest. Our main interest is in “the logic behind a fixed memory model”, rather than in “a model of any kind behind a given logical system”. As an effective language for reasoning about such memory models, we use the formalism of separation logic. Our main result is that for any concrete choice of heap-like memory model, validity in that model is
undecidable
even for purely propositional formulas in this language.

The main novelty of our approach to the problem is that we focus on validity in specific, concrete memory models, as opposed to validity in general classes of models.

Besides its intrinsic technical interest, this result also provides new insights into the nature of their decidable fragments. In particular, we show that, in order to obtain such decidable fragments, either the formula language must be severely restricted or the valuations of propositional variables must be constrained.

In addition, we show that a number of propositional systems that approximate separation logic are undecidable as well. In particular, this resolves the open problems of decidability for Boolean BI and Classical BI.

Moreover, we provide one of the simplest undecidable propositional systems currently known in the literature, called “Minimal Boolean BI”, by combining the purely positive implication-conjunction fragment of Boolean logic with the laws of multiplicative *-conjunction, its unit and its adjoint implication, originally provided by intuitionistic multiplicative linear logic. Each of these two components is individually decidable: the implication-conjunction fragment of Boolean logic is co-NP-complete, and intuitionistic multiplicative linear logic is NP-complete.

All of our undecidability results are obtained by means of a direct encoding of Minsky machines.
Avoiding Three Consecutive Blocks of the Same Size and Same Sum
Authors: Cassaigne Julien , Currie James D. , Schaeffer Luke , Shallit Jeffrey
Published: April 2014

We show that there exists an infinite word over the alphabet {0, 1, 3, 4} containing no three consecutive blocks of the same size and the same sum. This answers an open problem of Pirillo and Varricchio from 1994.
Public policies and multilingualism in HCI
Authors: Normand Loïc Martínez , Paternò Fabio , Winckler Marco
Published: April 2014

Public policy plays an influential role in the work we do as HCI researchers, interaction designers, and practitioners. "Public policy," a broad term, includes both government policy and policy within non-governmental organizations. This forum focuses on topics at the intersection of human-computer interaction and public policy. ---
Jonathan Lazar, Editor
A Wiener-Hopf Dynamical System for Mixed Equilibrium Problems
Authors: Suhel Farhat , Srivastava S. K. , Khan Suhel Ahmad
Published: April 2014

We suggest and analyze dynamical systems associated with mixed equilibrium problems by using the resolvent operator technique. We show that these systems have globally asymptotic property. The concepts and results presented in this paper extend and unify a number of previously known corresponding concepts and results in the literature.
Global Analysis of Almost Periodic Solution of a Discrete Multispecies Mutualism System
Authors: Zhang Hui , Jing Bin , Li Yingqi , Fang Xiaofeng
Published: April 2014

This paper discusses a discrete multispecies Lotka-Volterra mutualism system. We first obtain the permanence of the system. Assuming that the coefficients in the system are almost periodic sequences, we obtain the sufficient conditions for the existence of a unique almost periodic solution which is globally attractive. In particular, for the discrete two-species Lotka-Volterra mutualism system, the sufficient conditions for the existence of a unique uniformly asymptotically stable almost periodic solution are obtained. An example together with numerical simulation indicates the feasibility of the main result.
Entamoeba histolyticaandE. disparCalreticulin: Inhibition of Classical Complement Pathway and Differences in the Level of Expression in Amoebic Liver Abscess
Authors: Ximénez Cecilia , González Enrique , Nieves Miriam E. , Silva-Olivares Angélica , Shibayama Mineko , Galindo-Gómez Silvia , Escobar-Herrera Jaime , García de León Ma del Carmen , Morán Patricia , Valadez Alicia , Rojas Liliana , Hernández Eric G. , Partida Oswaldo , Cerritos René
Published: April 2014

The role of calreticulin (CRT) in host-parasite interactions has recently become an important area of research. Information about the functions of calreticulin and its relevance to the physiology ofEntamoebaparasites is limited. The present work demonstrates that CRT of both pathogenicE. histolyticaand nonpathogenicE. disparspecies specifically interacted with human C1q inhibiting the activation of the classical complement pathway. Using recombinantEhCRT protein, we demonstrate that CRT interaction site and human C1q is located at the N-terminal region ofEhCRT. The immunofluorescence and confocal microscopy experiments show that CRT and human C1q colocalize in the cytoplasmic vesicles and near to the surface membrane of previously permeabilized trophozoites or are incubated with normal human serum which is known to destroy trophozoites. In the presence of peripheral mononuclear blood cells, the distribution ofEhCRT and C1q is clearly over the surface membrane of trophozoites. Nevertheless, the level of expression of CRTin situin lesions of amoebic liver abscess (ALA) in the hamster model is different in bothEntamoebaspecies; this molecule is expressed in higher levels inE. histolyticathan inE. dispar. This result suggests thatEhCRT may modulate some functions during the early moments of the host-parasite relationship.
Carbon Nanofibers Modified Graphite Felt for High Performance Anode in High Substrate Concentration Microbial Fuel Cells
Authors: Shen Youliang , Zhou Yan , Chen Shuiliang , Yang Fangfang , Zheng Suqi , Hou Haoqing
Published: April 2014

Carbon nanofibers modified graphite fibers (CNFs/GF) composite electrode was prepared for anode in high substrate concentration microbial fuel cells. Electrochemical tests showed that the CNFs/GF anode generated a peak current density of 2.42 mA cm−2at a low acetate concentration of 20 mM, which was 54% higher than that from bare GF. Increase of the acetate concentration to 80 mM, in which the peak current density of the CNFs/GF anode greatly increased and was up to 3.57 mA cm−2, was seven times as that of GF anode. Morphology characterization revealed that the biofilms in the CNFs/GF anode were much denser than those in the bare GF. This result revealed that the nanostructure in the anode not only enhanced current generation but also could tolerate high substrate concentration.
Computation of Gram Matrix and Its Partial Derivative Using Precise Integration Method for Linear Time-Invariant Systems
Authors: Li Sulan , Ren Yuanhao , Bao Hong , Zhang Wei
Published: April 2014

Gram matrix is an important tool in system analysis and design as it provides a description of the input-output behavior for system; its partial derivative matrix is often required in some numerical algorithms. It is essential to study computation of these matrices. Analytical methods only work in some special circumstances; for example, the system matrix is diagonal matrix or Jordan matrix. In most cases, numerical integration method is needed, but there are two problems when compute using traditional numerical integration method. One is low accuracy: as high accuracy requires extremely small integration step, it will result in large amount of computation; and another is stability and stiffness issues caused by the dependence on the property of system matrix. In order to overcome these problems, this paper proposes an efficient numerical method based on the key idea of precise integration method (PIM) for the Gram matrix and its partial derivative of linear time-invariant systems. Since matrix inverse operation is not required in this method, it can be used with high precision no matter the system is normal or singular. The specific calculation algorithm and block diagram are also given. Finally, numerical examples are given to demonstrate the correctness and validity of this method.