bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics and Safety of Single and Multiple Doses of ACHN-490 Injection Administered Intravenously in Healthy Subjects
Authors: Cass Robert T. , Brooks Carter D. , Havrilla Nancy A. , Tack Kenneth J. , Borin Marie T. , Young Don , Bruss Jon B. 
Published: September 2011

ABSTRACT

ACHN-490 is an aminoglycoside with activity against multidrug-resistant pathogens, including those resistant to currently used aminoglycosides. Two randomized, double-blind, placebo-controlled clinical studies investigated the pharmacokinetics (PK), safety, and tolerability of ACHN-490 injection in healthy subjects. Study 1 used a parallel-group design with escalating single (SD) and multiple doses (MD). Study 2 explored a longer duration of the highest dose tolerated in the first study. Subjects were randomly assigned to receive either ACHN-490 injection or a placebo administered by a 10-min intravenous infusion. Study 1 enrolled 39 subjects (30 active and 9 placebo) and consisted of a single dose of 1 mg/kg body weight followed by ascending SD and MD cohorts of 4, 7, 11, and 15 mg/kg for 10, 10, 5, and 3 days, respectively. Study 2 enrolled 8 subjects (6 active and 2 placebo) who received 15 mg/kg for 5 days. Safety was assessed from adverse event (AE) reporting, standard clinical laboratory procedures, and testing for renal, cochlear, and vestibular function. ACHN-490 exhibited linear and dose-proportional PK, with agreement between the studies for PK parameters assessed. The 15-mg/kg dose did not accumulate with repeated dosing over 5 days. Mean steady-state (±standard deviation) area under the concentration-time curve from 0 to 24 h (AUC
0-24
), maximum concentration of drug in serum (
C
max
), half-life (
t
1/2
), clearance, and volume of distribution at steady state (
V
ss
) for the 15-mg/kg, day 5 dose were 239 ± 45 h·mg/liter, 113 ± 17 mg/liter, 3 ± 0.3 h, 1.1 ± 0.1 ml/min/kg, and 0.24 ± 0.04 liters/kg, respectively. AEs were mild to moderate and rapidly resolved. No evidence of nephrotoxicity or ototoxicity was observed.
Wild-Type MIC Distributions and Epidemiological Cutoff Values for Amphotericin B and Aspergillus spp. for the CLSI Broth Microdilution Method (M38-A2 Document)
Authors: Espinel-Ingroff A. , Cuenca-Estrella M. , Fothergill A. , Fuller J. , Ghannoum M. , Johnson E. , Pelaez T. , Pfaller M. A. , Turnidge J. 
Published: August 2011

ABSTRACT

Although clinical breakpoints have not been established for mold testing, epidemiological cutoff values (ECVs) are available for
Aspergillus
spp. versus the triazoles and caspofungin. Wild-type (WT) MIC distributions (organisms in a species-drug combination with no acquired resistance mechanisms) were defined in order to establish ECVs for six
Aspergillus
spp. and amphotericin B. Two sets (CLSI/EUCAST broth microdilution) of available MICs were evaluated: those for
A. fumigatus
(3,988/833),
A. flavus
(793/194),
A. nidulans
(184/69),
A. niger
(673/140),
A. terreus
(545/266), and
A. versicolor
(135/22). Three sets of data were analyzed: (i) CLSI data gathered in eight independent laboratories in Canada, Europe, and the United States; (ii) EUCAST data from a single laboratory; and (iii) the combined CLSI and EUCAST data. ECVs, expressed in μg/ml, that captured 95%, 97.5%, and 99% of the modeled wild-type population (CLSI and combined data) were as follows: for
A. fumigatus
, 2, 2, and 4; for
A. flavus
, 2, 4, and 4; for
A. nidulans
, 4, 4, and 4; for
A. niger
, 2, 2, and 2; for
A. terreus
, 4, 4, and 8; and for
A. versicolor
, 2, 2, and 2. Similar to the case for the triazoles and caspofungin, amphotericin B ECVs may aid in the detection of strains with acquired mechanisms of resistance to this agent.
Draft Genome Sequence of the Marine Sediment-Derived Actinomycete Streptomyces xinghaiensis NRRL B24674T
Authors: Zhao Xinqing , Yang Tianhong 
Published: September 2011

ABSTRACTActinobacteria are a rich source of novel natural products. We recently characterizedStreptomyces xinghaiensisNRRL B24674Tas a novel species of marine origin. Here we report the draft genome sequence of this species. This is the first validly published marine streptomycete for which a genome sequence has been presented.
Complete Genome Sequence of “Candidatus Tremblaya princeps” Strain PCVAL, an Intriguing Translational Machine below the Living-Cell Status
Authors: López-Madrigal Sergio , Latorre Amparo , Porcar Manuel , Moya Andrés , Gil Rosario 
Published: September 2011

ABSTRACT

The sequence of the genome of “
Candidatus
Tremblaya princeps” strain PCVAL, the primary endosymbiont of the citrus mealybug
Planococcus citri
, has been determined. “
Ca
. Tremblaya princeps” presents an unusual nested endosymbiosis and harbors a gammaproteobacterial symbiont within its cytoplasm in all analyzed mealybugs. The genome sequence reveals that “
Ca
. Tremblaya princeps” cannot be considered an independent organism but that the consortium with its gammaproteobacterial symbiotic associate represents a new composite living being.
Draft Genome Sequence of Nesterenkonia sp. Strain F, Isolated From Aran-Bidgol Salt Lake in Iran
Authors: Sarikhan Sajjad , Azarbaijani Reza , Yeganeh Laleh Parsa , Fazeli Abolhassan Shahzadeh , Amoozegar Mohammad Ali , Salekdeh Ghasem Hosseini 
Published: September 2011

ABSTRACT

The draft genome of the aerobic, Gram-positive, halophilic chemoorganotroph
Nesterenkonia
sp. strain F consists of a 2,812,133-bp chromosome. This study is the first to report the shotgun-sequenced draft genome of a member of the genus
Nesterenkonia
.
Genome Sequence of the Ruminal Bacterium Megasphaera elsdenii
Authors: Marx Hans , Graf Alexandra Bettina , Tatto Nadine Elpida , Thallinger Gerhard Günther , Mattanovich Diethard , Sauer Michael 
Published: September 2011

ABSTRACT

Megasphaera elsdenii
is a Gram-negative ruminal bacterium. It is being investigated as a probiotic supplement for ruminants as it may provide benefits for energy balance and animal productivity. Furthermore, it is of biotechnological interest due to its capability of producing various volatile fatty acids. Here we report the complete genome sequence of
M. elsdenii
DSM 20460, the type strain for the species.
A botulinum toxin A treatment algorithm for de novo management of torticollis and laterocollis
Authors: Hefter Harald , Kupsch Andreas , Müngersdorf Martina , Paus Sebastian , Stenner Andrea , Jost Wolfgang 
Published: September 2011

ObjectivesFew studies have investigated the injection patterns for botulinum toxin type A for the treatment of heterogeneous forms of cervical dystonia (CD). This large, prospective, open-label, multicentre study aimed to evaluate the effectiveness and safety of 500 U botulinum toxin A for the initial treatment according to a standardised algorithm of the two most frequent forms of CD, predominantly torticollis and laterocollis.DesignPatients (aged ≥18 years) with CD not previously treated with botulinum neurotoxin therapy were given one treatment with 500 U Dysport, according to a defined intramuscular injection algorithm based on clinical assessment of direction of head deviation, occurrence of shoulder elevation, occurrence of tremor (all evaluated using the Tsui rating scale) and hypertrophy of the sternocleidomastoid muscle.ResultsIn this study, 516 patients were enrolled, the majority of whom (95.0%) completed treatment. Most patients had torticollis (78.1%). At week 4, mean Tsui scores had significantly decreased by −4.01, −3.76 and −4.09 points in the total, torticollis and laterocollis populations, respectively. Symptom improvement was equally effective between groups. Tsui scores remained significantly below baseline at week 12 in both groups. Treatment was well tolerated; the most frequent adverse events were muscular weakness (13.8%), dysphagia (9.9%) and neck pain (6.6%).ConclusionsDysport 500 U is effective and well tolerated for the de novo management of a range of heterogeneous forms of CD, when using a standardised regimen that allows tailored dosing based on individual symptom assessment.Clinical trials information(NCT00447772;clinicaltrials.gov)
High prevalence of macrolide resistantTreponema pallidumstrains in a London centre: Table 1
Authors: Tipple Craig , McClure Myra O , Taylor Graham P 
Published: September 2011

ObjectivesMacrolide resistantTreponema pallidumstrains, caused by mutations in the 23S ribosomal RNA (23S rRNA) gene, are widespread and increasingly prevalent. The authors aimed to establish the strain types ofT pallidumisolated from patients in a London sexual health centre and to determine the frequency of macrolide resistance.MethodsT pallidumDNA from blood and ulcer samples were subjected to strain typing and mutation analysis using previously described methods.Results18 samples were tested and a 23S rRNA point mutation conferring macrolide resistance was found in 66.6%. All resistant strains were collected from men who have sex with men and both the A2058G and the A2059G mutations were found. Two strain types were identified (14d/g and 14d/f); the predominant strain type was 14d/g and an association was noted betweentp0548type g and macrolide resistance.ConclusionsHigh levels ofT pallidummacrolide resistance are present in London, UK, and this has clear implications for national treatment guidelines.
THE KARDAR–PARISI–ZHANG EQUATION AND UNIVERSALITY CLASS
Authors: CORWIN IVAN 
Published: September 2011

Brownian motion is a continuum scaling limit for a wide class of random processes, and there has been great success in developing a theory for its properties (such as distribution functions or regularity) and expanding the breadth of its universality class. Over the past 25 years a new universality class has emerged to describe a host of important physical and probabilistic models (including one-dimensional interface growth processes, interacting particle systems and polymers in random environments) which display characteristic, though unusual, scalings and new statistics. This class is called the Kardar–Parisi–Zhang (KPZ) universality class and underlying it is, again, a continuum object — a non-linear stochastic partial differential equation — known as the KPZ equation.The purpose of this survey is to explain the context for, as well as the content of a number of mathematical breakthroughs which have culminated in the derivation of the exact formula for the distribution function of the KPZ equation started with narrow wedge initial data. In particular we emphasize three topics: (1) The approximation of the KPZ equation through the weakly asymmetric simple exclusion process; (2) The derivation of the exact one-point distribution of the solution to the KPZ equation with narrow wedge initial data; (3) Connections with directed polymers in random media.As the purpose of this article is to survey and review, we make precise statements but provide only heuristic arguments with indications of the technical complexities necessary to make such arguments mathematically rigorous.
Verticillin A Overcomes Apoptosis Resistance in Human Colon Carcinoma through DNA Methylation-Dependent Upregulation of BNIP3
Authors: Liu Feiyan , Liu Qianqian , Yang Dafeng , Bollag Wendy B. , Robertson Keith , Wu Ping , Liu Kebin 
Published: September 2011

Abstract
Drug resistance is a major cause of failure in cancer chemotherapy. Therefore, identification and combined use of adjuvant compounds that can overcome drug resistance may improve the efficacy of cancer therapy. We screened extracts of Verticillium species-infected mushrooms for antitumor compounds and identified the compound Verticillin A as an inducer of hepatoma cell apoptosis in vitro and an inhibitor of tumor xenograft growth in vivo. Verticillin A exhibited a potent apoptosis-sensitizing activity in human colon carcinoma cells exposed to TRAIL or Fas in vitro. Furthermore, Verticillin A effectively sensitized metastatic human colon carcinoma xenograft to TRAIL-mediated growth inhibition in vivo. At the molecular level, we observed that Verticillin A induces cell-cycle arrest in the G2 phase of the cell cycle in human colon carcinoma cells, markedly upregulating BNIP3 in both hepatoma and colon carcinoma cells. Notably, silencing BNIP3 decreased the sensitivity of tumor cells to Verticillin A–induced apoptosis in the absence or presence of TRAIL. We found that the BNIP3 promoter is methylated in both human hepatoma and colon carcinoma cells and tumor specimens. Verticillin A upregulated the expression of a panel of genes known to be regulated at the level of DNA methylation, in support of the concept that Verticillin A may act by demethylating the BNIP3 promoter to upregulate BNIP3 expression. Taken together, our findings identify Verticillin A as a potent apoptosis sensitizer with great promise for further development as an adjuvant agent to overcome drug resistance in human cancer therapy. Cancer Res; 71(21); 6807–16. ©2011 AACR.
Mortality and Neurologic Injury After Surgical Repair With Hypothermic Circulatory Arrest in Acute and Chronic Proximal Thoracic Aortic Pathology
Authors: Czerny Martin , Krähenbühl Eva , Reineke David , Sodeck Gottfried , Englberger Lars , Weber Alberto , Schmidli Jürg , Kadner Alexander , Erdoes Gabor , Schoenhoff Florian , Jenni Hansjörg , Stalder Mario , Carrel Thierry 
Published: August 2011

Background—
The goal of this study was to determine whether advanced age affects mortality and incidence of neurological injury in patients undergoing surgical repair with hypothermic circulatory arrest in acute and chronic thoracic aortic pathology.

Methods and Results—

A university center audit was done of 523 consecutive patients (median age, 64 years; interquartile range, 56–71 years) between 2005 and 2010. Mortality in acute type A aortic dissection (207 patients) was 9.7%, and in chronic ascending aortic aneurysms (316 patients) was 2.2% (
P
<0.001). Neurological injury was observed in 16.9% of patients with acute type A aortic dissection (chronic ascending aortic aneurysms, 7.9%;
P
=0.002). Multivariable regression analysis revealed hypothermic circulatory arrest >40 minutes (odds ratio [OR], 4.21; 95% confidence interval [CI], 1.60–11.06;
P
=0.004) and redo surgery (OR, 3.44; 95% CI, 1.11–10.64;
P
=0.03) but not age (OR, 1.98; 95% CI, 0.73–5.38;
P
=0.18) as independent predictor of mortality. Emergency surgery (OR, 3.27; 95% CI, 1.31–8.15;
P
=0.01) and extracardiac arteriopathy (OR, 2.38; 95% CI, 1.26–4.50;
P
=0.008) but not age (OR, 1.80; 95% CI, 0.93–3.48;
P
=0.08) were independent predictors of neurological injury.

Conclusions—
Age is not associated with increased risk for mortality and neurological injury in patients undergoing surgical repair for acute and chronic thoracic aortic pathology with hypothermic circulatory arrest. Extended hypothermic circulatory arrest times, reflecting the extent of disease, and redo surgery predict mortality, whereas emergency surgery and extracardiac arteriopathy predict neurological injury.
Thermodynamic Scaling of the Hydrological Cycle of the Last Glacial Maximum
Authors: Boos William R. 
Published: September 2011

Abstract
In climate models subject to greenhouse gas–induced warming, vertically integrated water vapor increases at nearly the same rate as its saturation value. Previous studies showed that this increase dominates circulation changes in climate models, so that precipitation minus evaporation (P − E) decreases in the subtropics and increases in the tropics and high latitudes at a rate consistent with a Clausius–Clapeyron scaling. This study examines whether the same thermodynamic scaling describes differences in the hydrological cycle between modern times and the last glacial maximum (LGM), as simulated by a suite of coupled ocean–atmosphere models. In these models, changes in water vapor between modern and LGM climates do scale with temperature according to Clausius–Clapeyron, but this thermodynamic scaling provides a poorer description of the changes in P − E. While the scaling is qualitatively consistent with simulations in the zonal mean, predicting higher P − E in the subtropics and lower P − E in the tropics and high latitudes, it fails to account for high-amplitude zonal asymmetries. Large horizontal gradients of temperature change, which are often neglected when applying the scaling to next-century warming, are shown to be important in large parts of the extratropics. However, even with this correction the thermodynamic scaling provides a poor quantitative fit to the simulations. This suggests that circulation changes play a dominant role in regional hydrological change between modern and LGM climates. Changes in transient eddy moisture transports are shown to be particularly important, even in the deep tropics. Implications for the selection and interpretation of climate proxies are discussed.
Sensitivity of Atlantic Meridional Overturning Circulation Variability to Parameterized Nordic Sea Overflows in CCSM4
Authors: Yeager Stephen , Danabasoglu Gokhan 
Published: September 2011

Abstract
The inclusion of parameterized Nordic Sea overflows in the ocean component of the Community Climate System Model version 4 (CCSM4) results in a much improved representation of the North Atlantic tracer and velocity distributions compared to a control CCSM4 simulation without this parameterization. As a consequence, the variability of the Atlantic meridional overturning circulation (AMOC) on decadal and longer time scales is generally lower, but the reduction is not uniform in latitude, depth, or frequency–space. While there is dramatically less variance in the overall AMOC maximum (at about 35°N), the reduction in AMOC variance at higher latitudes is more modest. Also, it is somewhat enhanced in the deep ocean and at low latitudes (south of about 30°N). The complexity of overturning response to overflows is related to the fact that, in both simulations, the AMOC spectrum varies substantially with latitude and depth, reflecting a variety of driving mechanisms that are impacted in different ways by the overflows. The usefulness of reducing AMOC to a single index is thus called into question. This study identifies two main improvements in the ocean mean state associated with the overflow parameterization that tend to damp AMOC variability: enhanced stratification in the Labrador Sea due to the injection of dense overflow waters and a deepening of the deep western boundary current. Direct driving of deep AMOC variance by overflow transport variations is found to be a second-order effect.
A Japanese form of social anxiety (taijin kyofusho): Frequency and correlates in two generations of the same family
Authors: Essau Cecilia A. , Sasagawa Satoko , Ishikawa Shin-ichi , Okajima Isa , O’Callaghan Jean , Bray Diane 
Published: September 2011

Background: One specific type of social anxiety, occurring primarily in Japanese culture, is called taijin kyofusho. Taijin kyofusho is characterized by an intense fear that one’s body parts or functions displease, embarrass or are offensive to others. Aim: The main aim of the present study was to compare the frequency and correlates of taijin kyofusho symptoms (TKS) in Japanese adolescents and their parents. Method: The sample included 351 adolescents, aged 12 to 17 years, and one of their parents/guardians. These adolescents were recruited from secondary schools in Miyazaki, Japan. All participants completed a set of questionnaires that were used to measure TKS, DSM-IV anxiety disorder symptoms, general difficulties and positive attributes, self-construals and social support. Results: Adolescents reported significantly more TKS than their parent/guardians. In each generational sample high TKS was significantly associated with high levels of anxiety symptoms, the strongest correlation being with social phobia. The pattern of the relationship between self-construal and TKS differed across the two generations. Among adolescents, independent self-construal was associated with lower TKS, whereas among parents, interdependent self-construal was associated with lower evaluative concerns from others. Conclusion: The present study illustrates the importance of the diverse roles that self-construals play in TKS across different generations of the same family constellation in contemporary Japanese culture.
Modeling of a Nonlinear Euler-Bernoulli Flexible Beam Actuated by Two Active Shape Memory Alloy Actuators
Authors: Zakerzadeh M.R. , Salehi H. , Sayyaadi H. 
Published: September 2011

There are two different ways of using shape memory alloy (SMA) wire as an actuator for shape control of flexible structures: it can be either embedded within the composite laminate or externally attached to the structure. As the actuator can be placed at different offset distances from the beam, external actuators produce more bending moment and, consequently, considerabnle shape changes with the same magnitude of actuation force compared with the embedded type. Such a configuration also provides faster heat transfer rate owing to convection, which is very important in shape control applications that require a highfrequency response of SMA actuators. Although combination and physics-based modeling of externally attached SMA actuator wires and strips have been considered by many researchers, these studies have some drawbacks, which, if neglected, result in a number of errors in the theoretical results compared with experimental results. These shortcomings are considering the linear Euler-Bernoulli beam theory, not deriving the actuation force of the SMA from the constitutive equations, and taking into account the effect of only one SMA wire actuation force on, for example, the structure. These assumptions may lead to erroneous theoretical modeling results compared with experimental results. In this study, the aforementioned difficulties of attaching SMA actuators to the smart structures have been addressed. In other words, instead of linear beam theory, nonlinear beam theory is used in system modeling and, therefore, the proposed method and results are valid in large deflection and rotation behavior of beam. Also, in comparison to many other analyses that the effect of only one SMA wire is investigated, in the present research the effect of all active and inactive SMA wires is considered. Accordingly, the result of this paper can easily be generalized to the structure with several SMA wire actuations. Moreover, with the purpose of having practical applications in modeling and control, the heat transfer equations of all SMA wires are considered in the analysis and, as a result, the control inputs of the presented model are SMA wire electric currents rather than SMA temperatures. First, a flexible beam actuated by two active SMA actuators is modeled. Then, the Brinson constitutive equations and thermoelectric equations for SMA materials are coupled with the nonlinear beam behavior, and the coupled system of equations is numerically solved for some particular practical cases. Finally, the numerical results of the model simulation are verified against the experimental results using a test setup to validate the proposed model prediction. The implemented method used in this paper can be easily extended to the more complex smart structure with numerous externally attached SMA wires.