bluuebunny/crossref_metadata_2025 huggingface dataset:
Cylinder Pressure Information-Based Postinjection Timing Control for Aftertreatment System Regeneration in a Diesel Engine—Part II: Active Diesel Particulate Filter Regeneration
Authors: Lee Hyunjun , Shin Jaesik , Han Manbae , Sunwoo Myoungho
Published: January 2016

The successful utilization of a diesel particulate filter (DPF) to reduce particulate matter (PM) in a passenger car diesel engine necessitates a periodic regeneration of the DPF catalyst without deterioration of the drivability and emission control performance. For successful active DPF regeneration, the exhaust gas temperature should be over 500 °C to oxidize the soot loaded in the DPF. Previous research increased the exhaust gas temperature by applying early and late post fuel injection with a look-up table (LUT) based feedforward control implemented into the engine management system (EMS). However, this method requires enormous calibration work to find the optimal timing and quantity of the main, early, and late post fuel injection with less certainty of accurate torque control. To address this issue, we propose a cylinder pressure based multiple fuel injection (MFI) control method for active DPF regeneration. The feedback control of the indicated mean effective pressure (IMEP), lambda, and DPF upstream temperature was applied to precisely control the injection quantity of the main, early, and late post fuel injection. To determine their fuel injection timings, a mass fraction burned 60% after location of the rate of heat release maximum (MFB60aLoROHRmax) was proposed based on the cylinder pressure information. The proposed control method was implemented in an in-house EMS and validated at several engine operating conditions. During the regeneration period, the exhaust gas temperature tracked the desired temperature, and the engine torque fluctuation was minimized with minimal PM and NOx emissions.
Sensitivity Analysis of the Crack Compliance and Layer Removal Methods for Residual Stress Measurement in GFRP Pipes
Authors: Carpenter H. W. , Reid R. G. , Paskaramoorthy R.
Published: January 2016

A comparison is presented between the sensitivity to measurement error of the crack compliance and layer removal methods of residual stress measurement when applied to glass fiber reinforced plastic (GFRP) pipes. This is done by adding random scatter to the exact strain distribution associated with a known stress distribution. This defines strain data that simulate experimental measurements. These data are used to determine the corresponding residual stress distributions. The error in the residual stress distribution when scatter is included can thereby be determined. It is shown that the layer removal and crack compliance methods are equally suitable for the measurement of axial and circumferential stresses in a pipe wound at only ±55 deg. The layer removal method, however, is shown to have significantly lower sensitivity to measurement error when the axial residual stresses in layered GFRP pipes are considered.
Identification of Fic-1 as an enzyme that inhibits bacterial DNA replication by AMPylating GyrB, promoting filament formation
Authors: Lu Canhua , Nakayasu Ernesto S. , Zhang Li-Qun , Luo Zhao-Qing
Published: January 2016

Fic-1 inhibits bacterial replication by AMPylating DNA gyrase.
Fumarate-Mediated Persistence of Escherichia coli against Antibiotics
Authors: Kim Jun-Seob , Cho Da-Hyeong , Heo Paul , Jung Suk-Chae , Park Myungseo , Oh Eun-Joong , Sung Jaeyun , Kim Pan-Jun , Lee Suk-Chan , Lee Dae-Hee , Lee Sarah , Lee Choong Hwan , Shin Dongwoo , Jin Yong-Su , Kweon Dae-Hyuk
Published: January 2016

Bacterial persisters are a small fraction of quiescent cells that survive in the presence of lethal concentrations of antibiotics. They can regrow to give rise to a new population that has the same vulnerability to the antibiotics as did the parental population. Although formation of bacterial persisters in the presence of various antibiotics has been documented, the molecular mechanisms by which these persisters tolerate the antibiotics are still controversial. We found that amplification of the fumarate reductase operon (
FRD
) in
Escherichia coli
led to a higher frequency of persister formation. The persister frequency of
E. coli
was increased when the cells contained elevated levels of intracellular fumarate. Genetic perturbations of the electron transport chain (ETC), a metabolite supplementation assay, and even the toxin-antitoxin-related
hipA7
mutation indicated that surplus fumarate markedly elevated the
E. coli
persister frequency. An
E. coli
strain lacking succinate dehydrogenase (
SDH
), thereby showing a lower intracellular fumarate concentration, was killed ∼1,000-fold more effectively than the wild-type strain in the stationary phase. It appears that
SDH
and
FRD
represent a paired system that gives rise to and maintains
E. coli
persisters by producing and utilizing fumarate, respectively.
Population Pharmacokinetic Assessment and Pharmacodynamic Implications of Pediatric Cefepime Dosing for Susceptible-Dose-Dependent Organisms
Authors: Shoji Kensuke , Bradley John S. , Reed Michael D. , van den Anker John N. , Domonoske Christine , Capparelli Edmund V.
Published: January 2016

The Clinical and Laboratory Standards Institute (CLSI) revised cefepime (CFP) breakpoints for
Enterobacteriaceae
in 2014, and MICs of 4 and 8 μg/ml were reclassified as susceptible-dose dependent (SDD). Pediatric dosing to provide therapeutic concentrations against SDD organisms has not been defined. CFP pharmacokinetics (PK) data from published pediatric studies were analyzed. Population PK parameters were determined using NONMEM, and Monte Carlo simulation was performed to determine an appropriate CFP dosage regimen for SDD organisms in children. A total of 664 CFP plasma concentrations from 91 neonates, infants, and children were included in this analysis. The median patient age was 1.0 month (interquartile range [IQR], 0.2 to 11.2 months). Serum creatinine (SCR) and postmenstrual age (PMA) were covariates in the final PK model. Simulations indicated that CFP dosing at 50 mg/kg every 8 h (q8h) (as 0.5-h intravenous [i.v.] infusions) will maintain free-CFP concentrations in serum of >4 and 8 μg/ml for >60% of the dose interval in 87.1% and 68.6% of pediatric patients (age, ≥30 days), respectively, and extending the i.v. infusion duration to 3 h results in 92.3% of patients with free-CFP levels above 8 μg/ml for >60% of the dose interval. CFP clearance (CL) is significantly correlated with PMA and SCR. A dose of 50 mg/kg of CFP every 8 to 12 h does not achieve adequate serum exposure for older children with serious infections caused by Gram-negative bacilli with a MIC of 8 μg/ml. Prolonged i.v. infusions may be useful for this population.
Pharmacokinetics of Rifampin, Isoniazid, Pyrazinamide, and Ethambutol in Infants Dosed According to Revised WHO-Recommended Treatment Guidelines
Authors: Bekker A. , Schaaf H. S. , Draper H. R. , van der Laan L. , Murray S. , Wiesner L. , Donald P. R. , McIlleron H. M. , Hesseling A. C.
Published: January 2016

There are limited pharmacokinetic data for use of the first-line antituberculosis drugs during infancy (<12 months of age), when drug disposition may differ. Intensive pharmacokinetic sampling was performed in infants routinely receiving antituberculosis treatment, including rifampin, isoniazid, pyrazinamide, and ethambutol, using World Health Organization-recommended doses. Regulatory-approved single-drug formulations, including two rifampin suspensions, were used on the sampling day. Assays were conducted using liquid chromatography-mass spectrometry; pharmacokinetic parameters were generated using noncompartmental analysis. Thirty-nine infants were studied; 14 (36%) had culture-confirmed tuberculosis. Fifteen (38%) were premature (<37 weeks gestation); 5 (13%) were HIV infected. The mean corrected age and weight were 6.6 months and 6.45 kg, respectively. The mean maximum plasma concentrations (
C
max
) for rifampin, isoniazid, pyrazinamide, and ethambutol were 2.9, 7.9, 41.9, and 1.3 μg/ml, respectively (current recommended adult target concentrations: 8 to 24, 3 to 6, 20 to 50, and 2 to 6 μg/ml, respectively), and the mean areas under the concentration-time curves from 0 to 8 h (AUC
0–8
) were 12.1, 24.7, 239.4, and 5.1 μg · h/ml, respectively. After adjusting for age and weight, rifampin exposures for the two formulations used differed in
C
max
(geometric mean ratio [GMR]
,
2.55; 95% confidence interval [CI], 1.47 to 4.41;
P
= 0.001) and AUC
0–8
(GMR, 2.52; 95% CI, 1.34 to 4.73;
P
= 0.005). HIV status was associated with lower pyrazinamide
C
max
(GMR, 0.85; 95% CI, 0.75 to 0.96;
P
= 0.013) and AUC
0–8
(GMR, 0.79; 95% CI, 0.69 to 0.90;
P
< 0.001) values. No other important differences were observed due to age, weight, prematurity, ethnicity, or gender. In summary, isoniazid and pyrazinamide concentrations in infants compared well with proposed adult target concentrations; ethambutol concentrations were lower but similar to previously reported pediatric studies. The low rifampin exposures require further investigation. (This study has been registered at ClinicalTrials.gov under registration no. NCT01637558.)
Effect of Media Modified To Mimic Cystic Fibrosis Sputum on the Susceptibility of Aspergillus fumigatus, and the Frequency of Resistance at One Center
Authors: Stevens David A. , Moss Richard B. , Hernandez Cathy , Clemons Karl V. , Martinez Marife
Published: January 2016

Studies of cystic fibrosis (CF) patient exacerbations attributed to
Pseudomonas aeruginosa
infection have indicated a lack of correlation of outcome with
in vitro
susceptibility results. One explanation is that the media used for testing do not mimic the airway milieu, resulting in incorrect conclusions. Therefore, media have been devised to mimic CF sputum.
Aspergillus fumigatus
is the leading fungal pathogen in CF, and susceptibility testing is also used to decide therapeutic choices. We assessed whether media designed to mimic CF sputa would give different fungal susceptibility results than those of classical methods, assaying voriconazole, the most utilized anti-
Aspergillus
drug in this setting, and 30 CF
Aspergillus
isolates. The frequency of marked resistance (defined as an MIC of >4 μg/ml) in our CF unit by classical methods is 7%. Studies performed with classical methods and with digested sputum medium, synthetic sputum medium, and artificial sputum medium revealed prominent differences in
Aspergillus
susceptibility results, as well as growth rate, with each medium. Clinical correlative studies are required to determine which results are most useful in predicting outcome. Comparison of MICs with non-CF isolates also indicated the CF isolates were generally more resistant.
Identification of EnvC and Its Cognate Amidases as Novel Determinants of Intrinsic Resistance to Cationic Antimicrobial Peptides
Authors: Oguri Tamiko , Yeo Won-Sik , Bae Taeok , Lee Hyunwoo
Published: January 2016

Cationic antimicrobial peptides (CAMPs) are an essential part of the innate immune system. Some Gram-negative enteric pathogens, such as
Salmonella enterica
, show intrinsic resistance to CAMPs. However, the molecular basis of intrinsic resistance is poorly understood, largely due to a lack of information about the genes involved. In this study, using a microarray-based genomic technique, we screened the Keio collection of 3,985
Escherichia coli
mutants for altered susceptibility to human neutrophil peptide 1 (HNP-1) and identified
envC
and
zapB
as novel genetic determinants of intrinsic CAMP resistance. In CAMP killing assays, an
E. coli
Δ
envC
Ec
or Δ
zapB
Ec
mutant displayed a distinct profile of increased susceptibility to both LL-37 and HNP-1. Both mutants, however, displayed wild-type resistance to polymyxin B and human β-defensin 3 (HBD3), suggesting that the intrinsic resistance mediated by EnvC or ZapB is specific to certain CAMPs. A corresponding
Salmonella
Δ
envC
Se
mutant showed similarly increased CAMP susceptibility. The
envC
mutants of both
E. coli
and
S. enterica
displayed increased surface negativity and hydrophobicity, which partly explained the increased CAMP susceptibility. However, the Δ
envC
Ec
mutant, but not the Δ
envC
Se
mutant, was defective in outer membrane permeability, excluding this defect as a common factor contributing to the increased CAMP susceptibility. Animal experiments showed that the
Salmonella
Δ
envC
Se
mutant had attenuated virulence. Taken together, our results indicate that the role of
envC
in intrinsic CAMP resistance is likely conserved among Gram-negative enteric bacteria, demonstrate the importance of intrinsic CAMP resistance for full virulence of
S. enterica
, and provide insight into distinct mechanisms of action of CAMPs.
Azithromycin Dose To Maximize Efficacy and Suppress Acquired Drug Resistance in Pulmonary Mycobacterium avium Disease
Authors: Deshpande Devyani , Pasipanodya Jotam G. , Gumbo Tawanda
Published: January 2016

Mycobacterium avium
complex is now the leading mycobacterial cause of chronic pneumonia in the United States. Macrolides and ethambutol form the backbone of the regimen used in the treatment of pulmonary disease. However, therapy outcomes remain poor, with microbial cure rates of 4% in cavitary disease. The treatment dose of azithromycin has mostly been borrowed from that used to treat other bacterial pneumonias; there are no formal dose-response studies in pulmonary
M. avium
disease and the optimal dose is unclear. We utilized population pharmacokinetics and pharmacokinetics/pharmacodynamics-derived azithromycin exposures associated with optimal microbial kill or resistance suppression to perform 10,000 patient Monte Carlo simulations of dose effect studies for daily azithromycin doses of 0.5 to 10 g. The currently recommended dose of 500 mg per day achieved the target exposures in 0% of patients. Exposures associated with optimal kill and resistance suppression were achieved in 87 and 54% of patients, respectively, only by the very high dose of 8 g per day. The azithromycin susceptibility breakpoint above which patients failed therapy on the very high doses of 8 g per day was an MIC of 16 mg/liter, suggesting a critical concentration of 32 mg/liter, which is 8-fold lower than the currently used susceptibility breakpoint of 256 mg/liter. If the standard dose of 500 mg a day were used, then the critical concentration would fall to 2 mg/liter, 128-fold lower than 256 mg/liter. The misclassification of resistant isolates as susceptible could explain the high failure rates of current doses.
Garcinol Inhibits GCN5-Mediated Lysine Acetyltransferase Activity and Prevents Replication of the Parasite Toxoplasma gondii
Authors: Jeffers Victoria , Gao Hongyu , Checkley Lisa A. , Liu Yunlong , Ferdig Michael T. , Sullivan William J.
Published: January 2016

Lysine acetylation is a critical posttranslational modification that influences protein activity, stability, and binding properties. The acetylation of histone proteins in particular is a well-characterized feature of gene expression regulation. In the protozoan parasite
Toxoplasma gondii
, a number of lysine acetyltransferases (KATs) contribute to gene expression and are essential for parasite viability. The natural product garcinol was recently reported to inhibit enzymatic activities of GCN5 and p300 family KATs in other species. Here we show that garcinol inhibits TgGCN5b, the only nuclear GCN5 family KAT known to be required for
Toxoplasma
tachyzoite replication. Treatment of tachyzoites with garcinol led to a reduction of global lysine acetylation, particularly on histone H3 and TgGCN5b itself. We also performed transcriptome sequencing (RNA-seq), which revealed increasing aberrant gene expression coincident with increasing concentrations of garcinol. The majority of the genes that were most significantly affected by garcinol were also associated with TgGCN5b in a previously reported chromatin immunoprecipitation assay with microarray technology (ChIP-chip) analysis. The dysregulated gene expression induced by garcinol significantly inhibits
Toxoplasma
tachyzoite replication, and the concentrations used exhibit no overt toxicity on human host cells. Garcinol also inhibits
Plasmodium falciparum
asexual replication with a 50% inhibitory concentration (IC
50
) similar to that for
Toxoplasma
. Together, these data support that pharmacological inhibition of TgGCN5b leads to a catastrophic failure in gene expression control that prevents parasite replication.
Uncovering an Important Role for YopJ in the Inhibition of Caspase-1 in Activated Macrophages and Promoting Yersinia pseudotuberculosis Virulence
Authors: Schoberle Taylor J. , Chung Lawton K. , McPhee Joseph B. , Bogin Ben , Bliska James B.
Published: January 2016

Pathogenic
Yersinia
species utilize a type III secretion system to translocate Yop effectors into infected host cells. Yop effectors inhibit innate immune responses in infected macrophages to promote
Yersinia
pathogenesis. In turn,
Yersinia-
infected macrophages respond to translocation of Yops by activating caspase-1, but different mechanisms of caspase-1 activation occur, depending on the bacterial genotype and the state of phagocyte activation. In macrophages activated with lipopolysaccharide (LPS) prior to
Yersinia pseudotuberculosis
infection, caspase-1 is activated by a rapid inflammasome-dependent mechanism that is inhibited by translocated YopM. The possibility that other effectors cooperate with YopM to inhibit caspase-1 activation in LPS-activated macrophages has not been investigated. Toward this aim, epistasis analysis was carried out in which the phenotype of a
Y. pseudotuberculosis
yopM
mutant was compared to that of a
yopJ yopM
,
yopE yopM
,
yopH yopM
,
yopT yopM
, or
ypkA yopM
mutant. Activation of caspase-1 was measured by cleavage of the enzyme, release of interleukin-1β (IL-1β), and pyroptosis in LPS-activated macrophages infected with wild-type or mutant
Y. pseudotuberculosis
strains. Results show enhanced activation of caspase-1 after infection with the
yopJ yopM
mutant relative to infection by any other single or double mutant. Similar results were obtained with the
yopJ
,
yopM
, and
yopJ yopM
mutants of
Yersinia pestis
. Following intravenous infection of mice, the
Y. pseudotuberculosis
yopJ
mutant was as virulent as the wild type, while the
yopJ yopM
mutant was significantly more attenuated than the
yopM
mutant. In summary, through epistasis analysis this work uncovered an important role for YopJ in inhibiting caspase-1 in activated macrophages and in promoting
Yersinia
virulence.
Interleukin-13 Receptor α1-Dependent Responses in the Intestine Are Critical to Parasite Clearance
Authors: Sun Rex , Urban Joseph F. , Notari Luigi , Vanuytsel Tim , Madden Kathleen B. , Bohl Jennifer A. , Ramalingam Thirumalai R. , Wynn Thomas A. , Zhao Aiping , Shea-Donohue Terez
Published: January 2016

Nematode infection upregulates interleukin-4 (IL-4) and IL-13 and induces STAT6-dependent changes in gut function that promote worm clearance. IL-4 and IL-13 activate the type 2 IL-4 receptor (IL-4R), which contains the IL-13Rα1 and IL-4Rα chains. We used mice deficient in IL-13Rα1 (IL-13Rα1−/−) to examine the contribution of IL-13 acting at the type 2 IL-4R to immune and functional responses to primary (Hb1) and secondary (Hb2) infections with the gastrointestinal nematode parasiteHeligmosomoides bakeri. There were differences between strains in the IL-4 and IL-13 expression responses to Hb1 but not Hb2 infection. Following Hb2 infection, deficient mice had impaired worm expulsion and higher worm fecundity despite normal production of Th2-derived cytokines. The upregulation of IL-25 and IL-13Rα2 in Hb1- and Hb2-infected wild-type (WT) mice was absent in IL-13Rα1−/−mice. Goblet cell numbers and resistin-like molecule beta (RELM-β) expression were attenuated significantly in IL-13Rα1−/−mice following Hb2 infections. IL-13Rα1 contributes to the development of alternatively activated macrophages, but the type 1 IL-4R is also important. Hb1 infection had no effects on smooth muscle function or epithelial permeability in either strain, while the enhanced mucosal permeability and changes in smooth muscle function and morphology observed in response to Hb2 infection in WT mice were absent in IL-13Rα1−/−mice. Notably, the contribution of claudin-2, which has been linked to IL-13, does not mediate the increased mucosal permeability following Hb2 infection. These results show that activation of IL-13Rα1 is critical for key aspects of the immune and functional responses to Hb2 infection that facilitate expulsion.
Trk2 Potassium Transport System in Streptococcus mutans and Its Role in Potassium Homeostasis, Biofilm Formation, and Stress Tolerance
Authors: Binepal Gursonika , Gill Kamal , Crowley Paula , Cordova Martha , Brady L. Jeannine , Senadheera Dilani B. , Cvitkovitch Dennis G.
Published: January 2016

Potassium (K
+
) is the most abundant cation in the fluids of dental biofilm. The biochemical and biophysical functions of K
+
and a variety of K
+
transport systems have been studied for most pathogenic bacteria but not for oral pathogens. In this study, we establish the modes of K
+
acquisition in
Streptococcus mutans
and the importance of K
+
homeostasis for its virulence attributes. The
S. mutans
genome harbors four putative K
+
transport systems that included two Trk-like transporters (designated Trk1 and Trk2), one glutamate/K
+
cotransporter (GlnQHMP), and a channel-like K
+
transport system (Kch). Mutants lacking Trk2 had significantly impaired growth, acidogenicity, aciduricity, and biofilm formation. [K
+
] less than 5 mM eliminated biofilm formation in
S. mutans
. The functionality of the Trk2 system was confirmed by complementing an
Escherichia coli
TK2420 mutant strain, which resulted in significant K
+
accumulation, improved growth, and survival under stress. Taken together, these results suggest that Trk2 is the main facet of the K
+
-dependent cellular response of
S. mutans
to environment stresses.

IMPORTANCE
Biofilm formation and stress tolerance are important virulence properties of caries-causing
Streptococcus mutans
. To limit these properties of this bacterium, it is imperative to understand its survival mechanisms. Potassium is the most abundant cation in dental plaque, the natural environment of
S. mutans
. K
+
is known to function in stress tolerance, and bacteria have specialized mechanisms for its uptake. However, there are no reports to identify or characterize specific K
+
transporters in
S. mutans
. We identified the most important system for K
+
homeostasis and its role in the biofilm formation, stress tolerance, and growth. We also show the requirement of environmental K
+
for the activity of biofilm-forming enzymes, which explains why such high levels of K
+
would favor biofilm formation.
SagB Glucosaminidase Is a Determinant of Staphylococcus aureus Glycan Chain Length, Antibiotic Susceptibility, and Protein Secretion
Authors: Chan Yvonne G. Y. , Frankel Matthew B. , Missiakas Dominique , Schneewind Olaf
Published: January 2016

The envelope of
Staphylococcus aureus
is comprised of peptidoglycan and its attached secondary polymers, teichoic acid, capsular polysaccharide, and protein. Peptidoglycan synthesis involves polymerization of lipid II precursors into glycan strands that are cross-linked at wall peptides. It is not clear whether peptidoglycan structure is principally determined during polymerization or whether processive enzymes affect cell wall structure and function, for example, by generating conduits for protein secretion. We show here that
S. aureus
lacking SagB, a membrane-associated
N
-acetylglucosaminidase, displays growth and cell-morphological defects caused by the exaggerated length of peptidoglycan strands. SagB cleaves polymerized glycan strands to their physiological length and modulates antibiotic resistance in methicillin-resistant
S. aureus
(MRSA). Deletion of
sagB
perturbs protein trafficking into and across the envelope, conferring defects in cell wall anchoring and secretion, as well as aberrant excretion of cytoplasmic proteins.

IMPORTANCE
Staphylococcus aureus
is thought to secrete proteins across the plasma membrane via the Sec pathway; however, protein transport across the cell wall envelope has heretofore not been studied. We report that
S. aureus sagB
mutants generate elongated peptidoglycan strands and display defects in protein secretion as well as aberrant excretion of cytoplasmic proteins. These results suggest that the thick peptidoglycan layer of staphylococci presents a barrier for protein secretion and that SagB appears to extend the Sec pathway across the cell wall envelope.
Electroacupuncture Protects against Articular Cartilage Erosion by Inhibiting Mitogen-Activated Protein Kinases in a Rat Model of Osteoarthritis
Authors: Liao Ying , Li Xinhong , Li Neng , Zhou Jun
Published: January 2016

Objective

The therapeutic effects of electroacupuncture (EA) on osteoarthritis (OA) are well documented; however, the precise mechanisms of action have not yet been fully elucidated. The present study aimed to investigate the effect of EA on cartilage in an experimental animal model of OA induced by anterior cruciate ligament transection (ACLT) and to examine for concomitant changes in the expression of mitogen-activated protein kinases (MAPKs) in the articular cartilage.

Methods

Thirty-three-month-old male Sprague Dawley rats were randomly divided into the following three groups (n=10 each): sham operated group (Control group), ACLT without treatment (ACLT group), and ACLT with EA treatment (ACLT+EA group). One week after ACLT, rats in the ACLT+EA group received 12 weeks of EA treatment. Histological analysis and quantitative real-time PCR were used to investigate the effects of EA on cartilage morphology (quantified using modified Mankin scores) and expression of MAPKs (p38, c-Jun N-terminal kinase (c-Jun), and extracellular signal-regulated kinase (ERK)1), respectively.

Results

ACLT produced coarse cartilage surfaces, fibrous degeneration, and fissuring, all of which were suppressed by EA treatment. Although Mankin scores in the ACLT+EA group were significantly higher compared to the Control group (p<0.01), they were significantly lower than the (untreated) ACLT group (p<0.01). The increase in mRNA expression of p38, c-Jun, ERK1, and matrix metalloproteinase (MMP)-13 observed in cartilage after ACLT was significantly inhibited by EA.

Conclusions

EA appears to prevent the degeneration of articular cartilage, at least partly through regulation of MMP-13 and inhibition of MAPKs in the cartilage of rats with ACLT-induced OA.
ONE APPROACH TO RESOLVE THE EXCHANGE RATE PUZZLE: RESULTS USING DATA FROM THE UNITED KINGDOM AND THE UNITED STATES
Authors: ARIFF MOHAMED , ZAREI ALIREZA
Published: January 2016

We approach a significant research topic in international economics by restating the test procedures in a novel manner consistent with monetary theorems with controls using monetary variables and applying an appropriate econometric methodology to re-examine three aspects of exchange rate behavior. (i) Does the inflation (price) factor affect Nominal Exchange Rate (NER)? (ii) Do relative interest rates between countries affect a country’s exchange rate? (iii) Do the price and interest rate effects hold if controls for non-parity factors are embedded in tests? The data series for this study are taken over 55 years covering pre-and-post-Bretton Woods era: a second test was done over the post-Bretton Woods period only using 30 years of data. Also, the traditional factors of parity conditions are extended in this research to take into account recently theorized and tested non-parity factors related to cash flows. The resulting evidence affirms clearly that both the parity factors (prices and interest rates) and the non-parity factors affect exchange rates significantly over the long run, also over the 30-year period. In our view, these findings extend our knowledge of how currency behavior is consistent with parity and non-parity theorems.
Gravitational waves: Classification, methods of detection, sensitivities and sources
Authors: Kuroda Kazuaki , Ni Wei-Tou , Pan Wei-Ping
Published: January 2016

After giving a brief introduction and presenting a complete classification of gravitational waves (GWs) according to their frequencies, we review and summarize the detection methods, the sensitivities and the sources. We notice that real-time detections are possible above 300 pHz. Below 300 pHz, the detections are possible on GW imprints or indirectly. We are on the verge of detection. The progress in this field will be promising and thriving. We will see improvement of a few orders to several orders of magnitude in the GW detection sensitivities over all frequency bands in the next hundred years.
SIMULATION OF MUSCLE ACTIVATION WITH COUPLED NONLINEAR FE MODELS
Authors: LI FAN , LI HONGGENG , HU WEI , SU SICHENG , WANG BINGYU
Published: January 2016

Muscle activation plays an important role in head–neck dynamic response in vehicle accidents, especially in low speed impacts. The aim of the present study was to analyze the mechanical characteristics and dynamic stability of the muscle using coupled non-linear finite element model, which could be further applied for biomechanical study of head–neck system in car crash accidents. A rabbit tibialis anterior (TA) geometry model was developed. Two finite element models of TA were developed with coupled constitutive models. One coupled model was developed combining quasi-linear viscoelastic (QLV) elements and Hill type elements, and the other was developed combining hyperelastic rubber elements and Hill type elements, representing the passive behavior and active behavior, respectively. The models were validated via eccentric contractions tests under different strain rates published by Myers et al. Isometric Contraction and axial compression were also simulated via both models to evaluate the computational stability. The results showed that the coupled constitutive muscle models had a good biofidelity for the simulation of muscle activation. Both muscle models can fulfill the requirement of neck muscle system modeling for biomechanical study.
Towards Anomalous Diffusion Sources Detection in a Large Network
Authors: Zhang Peng , He Jing , Long Guodong , Huang Guangyan , Zhang Chengqi
Published: January 2016

Witnessing the wide spread of malicious information in large networks, we develop an efficient method to detect anomalous diffusion sources and thus protect networks from security and privacy attacks. To date, most existing work on diffusion sources detection are based on the assumption that network snapshots that reflect information diffusion can be obtained continuously. However, obtaining snapshots of an entire network needs to deploy detectors on all network nodes and thus is very expensive. Alternatively, in this article, we study the diffusion sources locating problem by learning from information diffusion data collected from only a small subset of network nodes. Specifically, we present a new regression learning model that can detect anomalous diffusion sources by jointly solving five challenges, that is, unknown number of source nodes, few activated detectors, unknown initial propagation time, uncertain propagation path and uncertain propagation time delay. We theoretically analyze the strength of the model and derive performance bounds. We empirically test and compare the model using both synthetic and real-world networks to demonstrate its performance.
Lessons from the tech transfer trenches
Authors: Chandra Satish , Thummalapenta Suresh , Sinha Saurabh
Published: January 2016

Moving from the research realm to real-world business application.
The verification of a distributed system
Authors: McCaffrey Caitie
Published: January 2016

A practitioner's guide to increasing confidence in system correctness.
Schema.org
Authors: Guha R. V. , Brickley Dan , Macbeth Steve
Published: January 2016

Big data makes common schemas even more necessary.
Revealing the API ecosystem and enterprise strategy via visual analytics
Authors: Evans Peter C. , Basole Rahul C.
Published: January 2016

Seeking better understanding of digital transformation.
Pinocchio
Authors: Parno Bryan , Howell Jon , Gentry Craig , Raykova Mariana
Published: January 2016

To instill greater confidence in computations outsourced to the cloud, clients should be able to
verify
the correctness of the results returned. To this end, we introduce Pinocchio, a built system for efficiently verifying general computations while relying only on cryptographic assumptions. With Pinocchio, the client creates a public evaluation key to describe her computation; this setup is proportional to evaluating the computation once. The worker then evaluates the computation on a particular input and uses the evaluation key to produce a proof of correctness. The proof is only 288 bytes, regardless of the computation performed or the size of the IO. Anyone can check the proof using a public verification key.

Crucially, our evaluation on seven applications demonstrates that Pinocchio is efficient in practice too. Pinocchio's verification time is a fixed 10 ms plus 0.4--15 μs per IO element: 5--7 orders of magnitude less than previous work; indeed Pinocchio is the first general-purpose system to demonstrate verification cheaper than native execution (for some apps). The worker's proof effort is still expensive, but Pinocchio reduces it by 19×--60× relative to prior work. As an additional feature, Pinocchio allows the worker to include private inputs in the computation and prove that she performed the computation correctly without revealing any information about the private inputs to the client. Finally, to aid development, Pinocchio provides an end-to-end toolchain that compiles a subset of C into programs that implement the verifiable computation protocol.
Hardening an L4 Microkernel Against Soft Errors by Aspect-Oriented Programming and Whole-Program Analysis
Authors: Borchert Christoph , Spinczyk Olaf
Published: January 2016

Transient hardware faults in computer systems have become widespread as shrinking structures and low supply voltages reduce the amount of energy needed to trigger a fault. This paper describes the latest improvements of a software-based fault-tolerance mechanism called Generic Object Protection (GOP). It is based on Aspect-Orientied Programming in AspectC++ and has been used in a case study to harden the L4/Fiasco.OC microkernel. As a result, the improved GOP avoids 60% of kernel failures at an acceptable overhead of 19% code size and less than 1% runtime. The GOP improvements use static whole-program analysis and have been implemented in a prototypical manner. As an outlook, the paper presents envisioned language extensions providing whole-program control-flow and data-flow analyses in future AspectC++ versions.
Sudden Drop in the Battery Level?
Authors: Hoque Mohammad A. , Tarkoma Sasu
Published: January 2016

Battery State of Charge (SOC) estimation is a fundamental component of today's smartphones that affects the internal processes and observable behavior of the devices. This article systematically investigates and analyzes the SOC estimation techniques in smartphones. First, we discover that the voltage curve of a given smartphone implicitly captures the usable capacity of the battery while charging the mobile device. Second, we observe that today's SOC estimation techniques do not model battery capacity loss sufficiently to accurately capture the usable capacity. Finally, we report findings based on battery analytics of 2077 devices that validate the relationship between battery voltage and the usable capacity of a device. The presented results enable the development of more accurate battery gauges and metering solutions thus resulting in better power-saving decisions, recommendations for the users, and most importantly more reliable system.
Novel Aerial 3D Mapping System Based on UAV Platforms and 2D Laser Scanners
Authors: Roca David , Martínez-Sánchez Joaquín , Lagüela Susana , Arias Pedro
Published: January 2016

The acquisition of 3D geometric data from an aerial view implies a high number of advantages with respect to terrestrial acquisition, the greatest being that aerial view allows the acquisition of information from areas with no or difficult accessibility, such as roofs and tops of trees. If the aerial platform is copter-type, other advantages are present, such as the capability of displacement at very low-speed, allowing for a more detailed acquisition. This paper presents a novel Aerial 3D Mapping System based on a copter-type platform, where a 2D laser scanner is integrated with a GNSS sensor and an IMU for the generation of georeferenced 3D point clouds. The accuracy and precision of the system are evaluated through the measurement of geometries in the point clouds generated by the system, as well as through the geolocation of target points for which the real global coordinates are known.
Norfloxacin and N-Donor Mixed-Ligand Copper(II) Complexes: Synthesis, Albumin Interaction, and Anti-Trypanosoma cruziActivity
Authors: Martins Darliane A. , Gouvea Ligiane R. , Muniz Gabriel S. Vignoli , Louro Sonia R. W. , Batista Denise da Gama Jaen , Soeiro Maria de Nazaré C. , Teixeira Letícia R.
Published: January 2016

Copper(II) complexes with the first-generation quinolone antibacterial agent norfloxacin containing a nitrogen donor heterocyclic ligand 2,2′-bipyridine (bipy) or 1,10-phenanthroline (phen) were prepared and characterized by IR, EPR spectra, molar conductivity, and elemental analyses. The experimental data suggest that norfloxacin was coordinated to copper(II) through the carboxylato and ketone oxygen atoms. The interaction of the copper(II) complexes with bovine serum albumin (BSA) and human serum albumin (HSA) was investigated using fluorescence quenching of the tryptophan residues and copper(II) EPR spectroscopy. The results of fluorescence titration revealed that copper(II) complexes have a moderate ability to quench the intrinsic fluorescence of the albumins through a static quenching mechanism. EPR experiments showed that BSA and HSA Cu(II) sites compete with NOR for Cu(II)-bipy and Cu(II)-phen to form protein mixed-ligand complexes. Copper(II) complexes, together with the corresponding ligands, were evaluated for their trypanocidal activityin vitroagainstTrypanosoma cruzi, the causative agent of Chagas disease. The tests performed using bloodstream trypomastigotes showed that the Cu(II)-N-donor precursors and the metal complexes were more active than the free fluoroquinolone.
Antimicrobial Properties of Mesenchymal Stem Cells: Therapeutic Potential for Cystic Fibrosis Infection, and Treatment
Authors: Sutton Morgan T. , Fletcher David , Ghosh Santosh K. , Weinberg Aaron , van Heeckeren Rolf , Kaur Sukhmani , Sadeghi Zhina , Hijaz Adonis , Reese Jane , Lazarus Hillard M. , Lennon Donald P. , Caplan Arnold I. , Bonfield Tracey L.
Published: January 2016

Cystic fibrosis (CF) is a genetic disease in which the battle between pulmonary infection and inflammation becomes the major cause of morbidity and mortality. We have previously shown that human MSCs (hMSCs) decrease inflammation and infection in the in vivo murine model of CF. The studies in this paper focus on the specificity of the hMSC antimicrobial effectiveness using Pseudomonas aeruginosa (gram negative bacteria) and Staphylococcus aureus (gram positive bacteria). Our studies show that hMSCs secrete bioactive molecules which are antimicrobial in vitro against Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pneumonia, impacting the rate of bacterial growth and transition into colony forming units regardless of the pathogen. Further, we show that the hMSCs have the capacity to enhance antibiotic sensitivity, improving the capacity to kill bacteria. We present data which suggests that the antimicrobial effectiveness is associated with the capacity to slow bacterial growth and the ability of the hMSCs to secrete the antimicrobial peptide LL‐37. Lastly, our studies demonstrate that the tissue origin of the hMSCs (bone marrow or adipose tissue derived), the presence of functional cystic fibrosis transmembrane conductance regulator (CFTR: human, Cftr: mouse) activity, and response to effector cytokines can impact both hMSC phenotype and antimicrobial potency and efficacy. These studies demonstrate, the unique capacity of the hMSCs to manage different pathogens and the significance of their phenotype in both the antimicrobial and antibiotic enhancing activities.
Residential Environment Induced Preference Heterogeneity for River Ecosystem Service Improvements: A Comparison between Urban and Rural Households in the Wei River Basin, China
Authors: Shi Hengtong , Zhao Minjuan , Aregay Fanus Asefaw , Zhao Kai , Jiang Zhide
Published: January 2016

This paper assesses residential environment induced preference heterogeneity regarding ecosystem services improvements of a river basin by comparing urban and rural residents’ welfare estimates. In a choice experiment, the ecological improvements are described in terms of several observable ecological indicators set in an experimental design. Given the fact that economic and environmental conditions differ for urban and rural residents in China, the utility they derive from ecological restoration is hypothesized to differ. The urban and rural residents’ survey data were modeled separately using mixed logit models. The results reveal that water quality and water quantity, measured by unit of level improvement and percentage improvement, respectively, hold the highest marginal utility values in all respondents’ models. Urban and rural residents have the same preference regarding expanding soil erosion control areas and landscape improvement. However, they have statistically significant different utility for water quality, water quantity, forest coverage, ecotourism improvements, and reducing soil erosion intensity. Generally, urban residents express a higher implicit price for most of the ecological indicators. The findings imply that policy makers should take existing preference heterogeneity into account in designing ecosystem payment schemes and allocating resources.
Prevalence of Methicillin Resistant Staphylococcal Bioaerosols in and around Residential Houses in an Urban Area in Central India
Authors: Kumar P. , Goel A. K.
Published: January 2016

Methicillin resistant staphylococci (MRS) commonly found in clinical samples or associated environment pose a major health challenge globally. The carriage rate of MRS in human population is high, especially in India but research on airborne distribution of MRS is scanty. The present study aimed to evaluate the prevalence of MRS in indoor and outdoor environment of residential houses. Air samples were collected using impactor air sampler. The total counts of viable bacteria, staphylococci, and MRS along with the particles of various sizes were determined from indoor and outdoor environment of 14 residential houses. MRS bacteria were identified as methicillin resistantS. aureus(MRSA) or coagulase negative staphylococci (CNS) employing biochemical and PCR assays. The average concentration of MRS inside and outside of the houses was 5.9% and 4.6% of the total bacteria, respectively. The maximum correlation of total indoor and outdoor bacteria with particulate matter was 10 μm (r=0.74) and 5 μm (r=0.84), respectively. Statistically, significant positive correlation of staphylococci and MRS was found with particles of 10–25 μm inside the houses. Molecular surveillance, antibiotic stewardship programme, and infection control policies can help to manage increasing MRS burden in developing countries.
Mini Tracheostomy for Obstructive Sleep Apnea: An Evidence Based Proposal
Authors: Camacho Macario , Zaghi Soroush , Chang Edward T. , Song Sungjin A. , Szelestey Blake , Certal Victor
Published: January 2016

Objective. To search for articles evaluating the use of tracheostomies (either permanent stomas or tracheostomy tubes) in adult obstructive sleep apnea (OSA) patients and to evaluate the potential for the use of mini tracheostomies as treatment for OSA.Study Design. Systematic review.Methods. Nine databases were searched from inception through July 21, 2015.Results. The overall tracheostomy search yielded 516 articles, of which eighteen studies provided polysomnographic data. No study was identified (empty review) for the use of mini tracheostomies for treating OSA. The mini tracheostomy search yielded ninety-five articles which describe findings for either mini tracheostomy kits (inner cannula diameter of 4 mm) or the performance of mini tracheotomies. Six articles described the use of mini tracheostomies as a temporary procedure to relieve acute upper airway obstruction and none described the use for OSA. For tracheostomy stomal sites, suturing the skin directly to the tracheal rings with defatting can minimize stomal site collapse. The smallest tracheostomy stomal size that can successfully treat OSA has not been described.Conclusion. Mini tracheostomies as small as 4 mm have been successfully used in the short term to relieve upper airway obstruction. Given that polysomnography data are lacking, additional research is needed.
Endoscopically Assisted Resection of a Rare Mass: Intra-Articular Osteochondroma of Shoulder Originated from Scapula
Authors: Sarikaya Baran , Suluova Fatih , Cetin Baki Volkan , Sarikaya Zeynep Bekin
Published: January 2016

Osteochondromas are the most common benign bone tumors which are mostly seen in the metaphysis of distal femur, proximal tibia, and proximal humerus. As arising from flat bones such as scapula is a rare case, intra-articular osteochondroma is also rare. When the literature is searched it appeared that the scapula and shoulder joint are an uncommon site for osteochondroma. We present a case in which a patient had an osteochondroma placed in shoulder joint and originated from scapula which is a rare situation determined in the literature.
Can the Neutrophil to Lymphocyte Ratio Be Used to Determine Gastric Cancer Treatment Outcomes? A Systematic Review and Meta-Analysis
Authors: Sun Jingxu , Chen Xiaowan , Gao Peng , Song Yongxi , Huang Xuanzhang , Yang Yuchong , Zhao Junhua , Ma Bin , Gao Xinghua , Wang Zhenning
Published: January 2016

The prognostic role of neutrophil to lymphocyte ratio (NLR) in gastric cancer remains controversial. We aimed to quantify the prognostic role of peripheral blood NLR in gastric cancer. A literature search was conducted in PubMed, EMBASE, and Cochrane databases. The results for overall survival (OS) and progression-free survival (PFS)/disease-free survival (DFS) are expressed as hazard ratios (HRs) with 95% confidence intervals (CIs). 19 studies with 5431 patients were eligible for final analysis. Elevated NLRs were associated with a significantly poor outcome for OS (HR = 1.98; 95% CI: 1.75–2.24,p<0.001) and PFS (HR = 1.58; 95% CI: 1.32–1.88,p<0.001) compared with patients who had normal NLRs. The NLR was higher for patients with late-stage compared with early-stage gastric cancer (OR = 2.76; 95% CI: 1.36–5.61,p=0.005). NLR lost its predictive role for patients with stage IV gastric cancer who received palliative surgery (HR = 1.73; 95% CI: 0.85–3.54,p=0.13). Our results also indicated that prognoses might be influenced by the NLR cutoff values. In conclusion, elevated pretreatment NLRs are associated with poor outcome for patients with gastric cancer. The ability to use the NLR to evaluate the status of patients may be used in the future for personalized cancer care.