bluuebunny/crossref_metadata_2025 huggingface dataset:
A Longitudinal Examination of the Relationship Between Perfectionism and Motivational Climate in Dance
Authors: Nordin-Bates Sanna M. , Hill Andrew P. , Cumming Jennifer , Aujla Imogen J. , Redding Emma
Published: September 2014

The present study examined the relationship between dance-related perfectionism and perceptions of motivational climate in dance over time. In doing so, three possibilities were tested: (a) perfectionism affects perceptions of the motivational climate, (b) perceptions of the motivational climate affect perfectionism, and (c) the relationship is reciprocal. Two hundred seventy-one young dancers (M = 14.21 years old, SD = 1.96) from UK Centres for Advanced Training completed questionnaires twice, approximately 6 months apart. Cross-lagged analysis indicated that perfectionistic concerns led to increased perceptions of an ego-involving climate and decreased perceptions of a task-involving climate over time. In addition, perceptions of a task-involving climate led to increased perfectionistic strivings over time. The findings suggest that perfectionistic concerns may color perceptions of training/performing environments so that mistakes are deemed unacceptable and only superior performance is valued. They also suggest that perceptions of a task-involving climate in training/performing environments may encourage striving for excellence and perfection without promoting excessive concerns regarding their attainment.
Delayed Parasite Clearance after Treatment with Dihydroartemisinin-Piperaquine in Plasmodium falciparum Malaria Patients in Central Vietnam
Authors: Thriemer Kamala , Hong Nguyen Van , Rosanas-Urgell Anna , Phuc Bui Quang , Ha Do Manh , Pockele Evi , Guetens Pieter , Van Nguyen Van , Duong Tran Thanh , Amambua-Ngwa Alfred , D'Alessandro Umberto , Erhart Annette
Published: September 2014

Reduced susceptibility of
Plasmodium falciparum
toward artemisinin derivatives has been reported from the Thai-Cambodian and Thai-Myanmar borders. Following increasing reports from central Vietnam of delayed parasite clearance after treatment with dihydroartemisinin-piperaquine (DHA-PPQ), the current first-line treatment, we carried out a study on the efficacy of this treatment. Between September 2012 and February 2013, we conducted a 42-day
in vivo
and
in vitro
efficacy study in Quang Nam Province. Treatment was directly observed, and blood samples were collected twice daily until parasite clearance. In addition, genotyping, quantitative PCR (qPCR), and
in vitro
sensitivity testing of isolates was performed. The primary endpoints were parasite clearance rate and time. The secondary endpoints included PCR-corrected and uncorrected cure rates, qPCR clearance profiles,
in vitro
sensitivity results (for chloroquine, dihydroartemisinin, and piperaquine), and genotyping for mutations in the Kelch 13 propeller domain. Out of 672 screened patients, 95 were recruited and 89 available for primary endpoint analyses. The median parasite clearance time (PCT) was 61.7 h (interquartile range [IQR], 47.6 to 83.2 h), and the median parasite clearance rate had a slope half-life of 6.2 h (IQR, 4.4 to 7.5 h). The PCR-corrected efficacy rates were estimated at 100% at day 28 and 97.7% (95% confidence interval, 91.2% to 99.4%) at day 42. At day 3, the
P. falciparum
prevalence by qPCR was 2.5 times higher than that by microscopy. The 50% inhibitory concentrations (IC
50
s) of isolates with delayed clearance times (≥72 h) were significantly higher than those with normal clearance times for all three drugs. Delayed parasite clearance (PCT, ≥72 h) was significantly higher among day 0 samples carrying the 543 mutant allele (47.8%) than those carrying the wild-type allele (1.8%;
P
= 0.048). In central Vietnam, the efficacy of DHA-PPQ is still satisfactory, but the parasite clearance time and rate are indicative of emerging artemisinin resistance. (This study has been registered at ClinicalTrials.gov under registration no. NCT01775592.)
Pharmacokinetic Interaction between Nevirapine and Nortriptyline in Rats: Inhibition of Nevirapine Metabolism by Nortriptyline
Authors: Usach Iris , Melis Virginia , Gandía Patricia , Peris José-Esteban
Published: September 2014

One of the most frequent comorbidities of HIV infection is depression, with a lifetime prevalence of 22 to 45%. Therefore, it was decided to study a potential pharmacokinetic interaction between the nonnucleoside reverse transcriptase inhibitor nevirapine (NVP) and the tricyclic antidepressant nortriptyline (NT). NVP and NT were administered to rats either orally, intraduodenally, or intravenously, and the changes in plasma levels and pharmacokinetic parameters were analyzed. Experiments with rat and human hepatic microsomes were carried out to evaluate the inhibitory effects of NT on NVP metabolism. NVP plasma concentrations were significantly higher when this drug was coadministered with NT. The maximum plasma concentrations of NVP were increased 2 to 5 times and the total plasma clearance was decreased 7-fold in the presence of NT. However, statistically significant differences in the pharmacokinetic parameters of NT in the absence and presence of NVP were not found.In vitrostudies with rat and human hepatic microsomes confirmed the inhibition of NVP hepatic metabolism by NT in a concentration-dependent way, with the inhibition being more intense in the case of rat microsomes. In conclusion, a pharmacokinetic interaction between NVP and NT was detected. This interaction was a consequence of the inhibition of hepatic metabolism of NVP by NT.In vivohuman studies are required to evaluate the effects of this interaction on the pharmacokinetics of NVP before it can be taken into account for patients receiving NVP.
Population Pharmacokinetics of Teicoplanin in Children
Authors: Ramos-Martín V. , Paulus S. , Siner S. , Scott E. , Padmore K. , Newland P. , Drew R. J. , Felton T. W. , Docobo-Pérez F. , Pizer B. , Pea F. , Peak M. , Turner M. A. , Beresford M. W. , Hope W. W.
Published: September 2014

Teicoplanin is frequently administered to treat Gram-positive infections in pediatric patients. However, not enough is known about the pharmacokinetics (PK) of teicoplanin in children to justify the optimal dosing regimen. The aim of this study was to determine the population PK of teicoplanin in children and evaluate the current dosage regimens. A PK hospital-based study was conducted. Current dosage recommendations were used for children up to 16 years of age. Thirty-nine children were recruited. Serum samples were collected at the first dose interval (1, 3, 6, and 24 h) and at steady state. A standard 2-compartment PK model was developed, followed by structural models that incorporated weight. Weight was allowed to affect clearance (CL) using linear and allometric scaling terms. The linear model best accounted for the observed data and was subsequently chosen for Monte Carlo simulations. The PK parameter medians/means (standard deviation [SD]) were as follows: CL, [0.019/0.023 (0.01)] × weight liters/h/kg of body weight; volume, 2.282/4.138 liters (4.14 liters); first-order rate constant from the central to peripheral compartment (

K
cp

), 0.474/3.876 h
−1
(8.16 h
−1
); and first-order rate constant from peripheral to central compartment (

K
pc

), 0.292/3.994 h
−1
(8.93 h
−1
). The percentage of patients with a minimum concentration of drug in serum (
C
min
) of <10 mg/liter was 53.85%. The median/mean (SD) total population area under the concentration-time curve (AUC) was 619/527.05 mg · h/liter (166.03 mg · h/liter). Based on Monte Carlo simulations, only 30.04% (median AUC, 507.04 mg · h/liter), 44.88% (494.1 mg · h/liter), and 60.54% (452.03 mg · h/liter) of patients weighing 50, 25, and 10 kg, respectively, attained trough concentrations of >10 mg/liter by day 4 of treatment. The teicoplanin population PK is highly variable in children, with a wider AUC distribution spread than for adults. Therapeutic drug monitoring should be a routine requirement to minimize suboptimal concentrations.

IMPORTANCE
(This trial has been registered in the European Clinical Trials Database Registry [EudraCT] under registration number 2012-005738-12.)
The Clinical Candidate VT-1161 Is a Highly Potent Inhibitor of Candida albicans CYP51 but Fails To Bind the Human Enzyme
Authors: Warrilow A. G. S. , Hull C. M. , Parker J. E. , Garvey E. P. , Hoekstra W. J. , Moore W. R. , Schotzinger R. J. , Kelly D. E. , Kelly S. L.
Published: September 2014

The binding and cytochrome P45051 (CYP51) inhibition properties of a novel antifungal compound, VT-1161, against purified recombinant
Candida albicans
CYP51 (
ERG11
) and
Homo sapiens
CYP51 were compared with those of clotrimazole, fluconazole, itraconazole, and voriconazole. VT-1161 produced a type II binding spectrum with
Candida albicans
CYP51, characteristic of heme iron coordination. The binding affinity of VT-1161 for
Candida albicans
CYP51 was high (dissociation constant [

K
d

], ≤39 nM) and similar to that of the pharmaceutical azole antifungals (

K
d

, ≤50 nM). In stark contrast, VT-1161 at concentrations up to 86 μM did not perturb the spectrum of recombinant human CYP51, whereas all the pharmaceutical azoles bound to human CYP51. In reconstitution assays, VT-1161 inhibited
Candida albicans
CYP51 activity in a tight-binding fashion with a potency similar to that of the pharmaceutical azoles but failed to inhibit the human enzyme at the highest concentration tested (50 μM). In addition, VT-1161 (MIC = 0.002 μg ml
−1
) had a more pronounced fungal sterol disruption profile (increased levels of methylated sterols and decreased levels of ergosterol) than the known CYP51 inhibitor voriconazole (MIC = 0.004 μg ml
−1
). Furthermore, VT-1161 weakly inhibited human CYP2C9, CYP2C19, and CYP3A4, suggesting a low drug-drug interaction potential. In summary, VT-1161 potently inhibited
Candida albicans
CYP51 and culture growth but did not inhibit human CYP51, demonstrating a >2,000-fold selectivity. This degree of potency and selectivity strongly supports the potential utility of VT-1161 in the treatment of
Candida
infections.
Evaluation of a Loop-Mediated Isothermal Amplification-Based Methodology To Detect Carbapenemase Carriage in Acinetobacter Clinical Isolates
Authors: Vergara Andrea , Zboromyrska Yuliya , Mosqueda Noraida , Morosini María Isabel , García-Fernández Sergio , Roca Ignasi , Cantón Rafael , Marco Francesc , Vila Jordi
Published: September 2014

Carbapenem-resistant
Acinetobacter baumannii
is a major source of nosocomial infections worldwide and is mainly associated with the acquisition of OXA-type carbapenemases and, to a lesser extent, metallo-β-lactamases (MBLs). In this study, 82 nonepidemiologically related
Acinetobacter
strains carrying different types of OXA or MBL enzymes were tested using the Eazyplex system, a loop-mediated isothermal amplification (LAMP)-based method to rapidly detect carbapenemase carriage. The presence/absence of carbapenem-hydrolyzing enzymes was correctly determined for all isolates in <30 min.
Role of Toll-Like Receptor 13 in Innate Immune Recognition of Group B Streptococci
Authors: Signorino Giacomo , Mohammadi Nastaran , Patanè Francesco , Buscetta Marco , Venza Mario , Venza Isabella , Mancuso Giuseppe , Midiri Angelina , Alexopoulou Lena , Teti Giuseppe , Biondo Carmelo , Beninati Concetta
Published: September 2014

Murine Toll-like receptor 13 (TLR13), an endosomal receptor that is not present in humans, is activated by an unmethylated motif present in the large ribosomal subunit of bacterial RNA (23S rRNA). Little is known, however, of the impact of TLR13 on antibacterial host defenses. Here we examined the role of this receptor in the context of infection induced by the model pathogen group B streptococcus (GBS). To this end, we used bacterial strains masked from TLR13 recognition by virtue of constitutive expression of the ErmC methyltransferase, which results in dimethylation of the 23S rRNA motif at a critical adenine residue. We found that TLR13-mediated rRNA recognition was required for optimal induction of tumor necrosis factor alpha and nitrous oxide in dendritic cell and macrophage cultures stimulated with heat-killed bacteria or purified bacterial RNA. However, TLR13-dependent recognition was redundant when live bacteria were used as a stimulus. Moreover, masking bacterial rRNA from TLR13 recognition did not increase the ability of GBS to avoid host defenses and replicatein vivo. In contrast, increased susceptibility to infection was observed under conditions in which signaling by all endosomal TLRs was abolished, i.e., in mice with a loss-of-function mutation in the chaperone protein UNC93B1. Our data lend support to the conclusion that TLR13 participates in GBS recognition, although blockade of the function of this receptor can be compensated for by other endosomal TLRs. Lack of selective pressure by bacterial infections might explain the evolutionary loss of TLR13 in humans. However, further studies using different bacterial species are needed to prove this hypothesis.
Mycobacterium tuberculosis MtrB Sensor Kinase Interactions with FtsI and Wag31 Proteins Reveal a Role for MtrB Distinct from That Regulating MtrA Activities
Authors: Plocinska Renata , Martinez Luis , Gorla Purushotham , Pandeeti Emmanuel , Sarva Krishna , Blaszczyk Ewelina , Dziadek Jaroslaw , Madiraju Murty V. , Rajagopalan Malini
Published: September 2014

The septal association of
Mycobacterium tuberculosis
MtrB, the kinase partner of the MtrAB two-component signal transduction system, is necessary for the optimal expression of the MtrA regulon targets, including
ripA
,
fbpB
, and
ftsI
, which are involved in cell division and cell wall synthesis. Here, we show that MtrB, irrespective of its phosphorylation status, interacts with Wag31, whereas only phosphorylation-competent MtrB interacts with FtsI. We provide evidence that FtsI depletion compromises the MtrB septal assembly and MtrA regulon expression; likewise, the absence of MtrB compromises FtsI localization and, possibly, FtsI activity. We conclude from these results that FtsI and MtrB are codependent for their activities and that FtsI functions as a positive modulator of MtrB activation and MtrA regulon expression. In contrast to FtsI, Wag31 depletion does not affect MtrB septal assembly and MtrA regulon expression, whereas the loss of MtrB increased Wag31 localization and the levels of PknA/PknB (PknA/B) serine-threonine protein kinase-mediated Wag31 phosphorylation. Interestingly, we found that FtsI decreased levels of phosphorylated Wag31 (Wag31∼P) and that MtrB interacted with PknA/B. Overall, our results indicate that MtrB interactions with FtsI, Wag31, and PknA/B are required for its optimal localization, MtrA regulon expression, and phosphorylation of Wag31. Our results emphasize a new role for MtrB in cell division and cell wall synthesis distinct from that regulating the MtrA phosphorylation activities.
A Novel, Broad-Range, CTXΦ-Derived Stable Integrative Expression Vector for Functional Studies
Authors: Das Bhabatosh , Kumari Reena , Pant Archana , Sen Gupta Sourav , Saxena Shruti , Mehta Ojasvi , Nair Gopinath Balakrish
Published: September 2014

CTXΦ, a filamentous vibriophage encoding cholera toxin, uses a unique strategy for its lysogeny. The single-stranded phage genome forms intramolecular base-pairing interactions between two inversely oriented XerC and XerD binding sites (XBS) and generates a functional phage attachment site,
attP
(
+
), for integration. The
attP
(
+
) structure is recognized by the host-encoded tyrosine recombinases XerC and XerD (XerCD), which enables irreversible integration of CTXΦ into the chromosome dimer resolution site (
dif
) of
Vibrio cholerae
. The
dif
site and the XerCD recombinases are widely conserved in bacteria. We took advantage of these conserved attributes to develop a broad-host-range integrative expression vector that could irreversibly integrate into the host chromosome using XerCD recombinases without altering the function of any known open reading frame (ORF). In this study, we engineered two different arabinose-inducible expression vectors, pBD62 and pBD66, using XBS of CTXΦ. pBD62 replicates conditionally and integrates efficiently into the
dif
of the bacterial chromosome by site-specific recombination using host-encoded XerCD recombinases. The expression level of the gene of interest could be controlled through the P
BAD
promoter by modulating the functions of the vector-encoded transcriptional factor AraC. We validated the irreversible integration of pBD62 into a wide range of pathogenic and nonpathogenic bacteria, such as
V. cholerae
,
Vibrio fluvialis
,
Vibrio parahaemolyticus
,
Escherichia coli
,
Salmonella enterica
, and
Klebsiella pneumoniae
. Gene expression from the P
BAD
promoter of integrated vectors was confirmed in
V. cholerae
using the well-studied reporter genes
mCherry
,
eGFP
, and
lacZ
.
Methylamine Utilization via the
N
-Methylglutamate Pathway in Methylobacterium extorquens PA1 Involves a Novel Flow of Carbon through C
1
Assimilation and Dissimilation Pathways
Authors: Nayak Dipti D. , Marx Christopher J.
Published: September 2014

Methylotrophs grow on reduced single-carbon compounds like methylamine as the sole source of carbon and energy. In
Methylobacterium extorquens
AM1, the best-studied aerobic methylotroph, a periplasmic methylamine dehydrogenase that catalyzes the primary oxidation of methylamine to formaldehyde has been examined in great detail. However, recent metagenomic data from natural ecosystems are revealing the abundance and importance of lesser-known routes, such as the
N
-methylglutamate pathway, for methylamine oxidation. In this study, we used
M. extorquens
PA1, a strain that is closely related to
M. extorquens
AM1 but is lacking methylamine dehydrogenase, to dissect the genetics and physiology of the ecologically relevant
N
-methylglutamate pathway for methylamine oxidation. Phenotypic analyses of mutants with null mutations in genes encoding enzymes of the
N
-methylglutamate pathway suggested that γ-glutamylmethylamide synthetase is essential for growth on methylamine as a carbon source but not as a nitrogen source. Furthermore, analysis of
M. extorquens
PA1 mutants with defects in methylotrophy-specific dissimilatory and assimilatory modules suggested that methylamine use via the
N
-methylglutamate pathway requires the tetrahydromethanopterin (H
4
MPT)-dependent formaldehyde oxidation pathway but not a complete tetrahydrofolate (H
4
F)-dependent formate assimilation pathway. Additionally, we present genetic evidence that formaldehyde-activating enzyme (FAE) homologs might be involved in methylotrophy. Null mutants of FAE and homologs revealed that FAE and FAE2 influence the growth rate and FAE3 influences the yield during the growth of
M. extorquens
PA1 on methylamine.
Unique Genomic Arrangements in an Invasive Serotype M23 Strain of Streptococcus pyogenes Identify Genes That Induce Hypervirulence
Authors: Bao Yunjuan , Liang Zhong , Booyjzsen Claire , Mayfield Jeffrey A. , Li Yang , Lee Shaun W. , Ploplis Victoria A. , Song Hui , Castellino Francis J.
Published: September 2014

The first genome sequence of a group A
Streptococcus pyogenes
serotype M23 (
emm23
) strain (M23ND), isolated from an invasive human infection, has been completed. The genome of this opacity factor-negative (SOF
−
) strain is composed of a circular chromosome of 1,846,477 bp. Gene profiling showed that this strain contained six phage-encoded and 24 chromosomally inherited well-known virulence factors, as well as 11 pseudogenes. The bacterium has acquired four large prophage elements, ΦM23ND.1 to ΦM23ND.4, harboring genes encoding streptococcal superantigen (
ssa
), streptococcal pyrogenic exotoxins (
speC
,
speH
, and
speI
), and DNases (
spd1
and
spd3
), with phage integrase genes being present at one flank of each phage insertion, suggesting that the phages were integrated by horizontal gene transfer. Comparative analyses revealed unique large-scale genomic rearrangements that result in genomic rearrangements that differ from those of previously sequenced GAS strains. These rearrangements resulted in an imbalanced genomic architecture and translocations of chromosomal virulence genes. The
covS
sensor in M23ND was identified as a pseudogene, resulting in the attenuation of
speB
function and increased expression of the genes for the chromosomal virulence factors multiple-gene activator (
mga
), M protein (
emm23
), C5a peptidase (
scpA
), fibronectin-binding proteins (
sfbI
and
fbp54
), streptolysin O (
slo
), hyaluronic acid capsule (
hasA
), streptokinase (
ska
), and DNases (
spd
and
spd3
), which were verified by PCR. These genes are responsible for facilitating host epithelial cell binding and and/or immune evasion, thus further contributing to the virulence of M23ND. In conclusion, strain M23ND has become highly pathogenic as the result of a combination of multiple genetic factors, particularly gene composition and mutations, prophage integrations, unique genomic rearrangements, and regulated expression of critical virulence factors.
Charge Requirements of Lipid II Flippase Activity in Escherichia coli
Authors: Butler Emily K. , Tan Wee Boon , Joseph Hildy , Ruiz Natividad
Published: September 2014

Peptidoglycan (PG) is an extracytoplasmic glycopeptide matrix essential for the integrity of the envelope of most bacteria. The PG building block is a disaccharide-pentapeptide that is synthesized as a lipid-linked precursor called lipid II. The translocation of the amphipathic lipid II across the cytoplasmic membrane is required for subsequent incorporation of the disaccharide-pentapeptide into PG. In
Escherichia coli
, the essential inner membrane protein MurJ is the lipid II flippase. Previous studies showed that 8 charged residues in the central cavity region of MurJ are crucial for function. Here, we completed the functional analysis of all 57 charged residues in MurJ and demonstrated that the respective positive or negative charge of the 8 aforementioned residues is required for proper MurJ function. Loss of the negative charge in one of these residues, D39, causes a severe defect in MurJ biogenesis; by engineering an intragenic suppressor mutation that restores MurJ biogenesis, we found that this charge is also essential for MurJ function. Because of the low level of homology between MurJ and putative orthologs from Gram-positive bacteria, we explored the conservation of these 8 charged residues in YtgP, a homolog from
Streptococcus pyogenes
. We found that only 3 positive charges are similarly positioned and essential in YtgP; YtgP possesses additional charged residues within its predicted cavity that are essential for function and conserved among Gram-positive bacteria. From these data, we hypothesize that some charged residues in the cavity region of MurJ homologs are required for interaction with lipid II and/or energy coupling during transport.
Characterization of Five β-Glycoside Hydrolases from Cellulomonas fimi ATCC 484
Authors: Gao Juan , Wakarchuk Warren
Published: September 2014

The Gram-positive bacterium
Cellulomonas fimi
produces a large array of carbohydrate-active enzymes. Analysis of the collection of carbohydrate-active enzymes from the recent genome sequence of
C. fimi
ATCC 484 shows a large number of uncharacterized genes for glycoside hydrolase (GH) enzymes potentially involved in biomass utilization. To investigate the enzymatic activity of potential β-glucosidases in
C. fimi
, genes encoding several GH3 enzymes and one GH1 enzyme were cloned and recombinant proteins were expressed in
Escherichia coli
. Biochemical analysis of these proteins revealed that the enzymes exhibited different substrate specificities for
para
-nitrophenol-linked substrates (
p
NP), disaccharides, and oligosaccharides. Celf_2726 encoded a bifunctional enzyme with β-
d
-xylopyranosidase and α-
l
-arabinofuranosidase activities, based on
p
NP-linked substrates (CfXyl3A). Celf_0140 encoded a β-
d
-glucosidase with activity on β-1,3- and β-1,6-linked glucosyl disaccharides as well as
p
NP-β-Glc (CfBgl3A). Celf_0468 encoded a β-
d
-glucosidase with hydrolysis of
p
NP-β-Glc and hydrolysis/transglycosylation activities only on β-1,6-linked glucosyl disaccharide (CfBgl3B). Celf_3372 encoded a GH3 family member with broad aryl-β-
d
-glycosidase substrate specificity. Celf_2783 encoded the GH1 family member (CfBgl1), which was found to hydrolyze
p
NP-β-Glc/Fuc/Gal, as well as cellotetraose and cellopentaose. CfBgl1 also had good activity on β-1,2- and β-1,3-linked disaccharides but had only very weak activity on β-1,4/6-linked glucose.
Role of Adaptor TrfA and ClpPC in Controlling Levels of SsrA-Tagged Proteins and Antitoxins in Staphylococcus aureus
Authors: Donegan Niles P. , Marvin Jonathan S. , Cheung Ambrose L.
Published: September 2014

Staphylococcus aureusresponds to changing extracellular environments in part by adjusting its proteome through alterations of transcriptional priorities and selective degradation of the preexisting pool of proteins. InBacillus subtilis, the proteolytic adaptor protein MecA has been shown to play a role in assisting with the proteolytic degradation of proteins involved in competence and the oxidative stress response. However, the targets of TrfA, the MecA homolog inS. aureus, have not been well characterized. In this work, we investigated how TrfA assists chaperones and proteases to regulate the proteolysis of several classes of proteins inS. aureus. By fusing the last 3 amino acids of the SsrA degradation tag to Venus, a rapidly folding yellow fluorescent protein, we obtained both fluorescence-based and Western blot assay-based evidence that TrfA and ClpCP are the adaptor and protease, respectively, responsible for the degradation of the SsrA-tagged protein inS. aureus. Notably, the impact of TrfA on degradation was most prominent during late log phase and early stationary phase, due in part to a combination of transcriptional regulation and proteolytic degradation of TrfA by ClpCP. We also characterized the temporal transcriptional regulation governing TrfA activity, wherein Spx, a redox-sensitive transcriptional regulator degraded by ClpXP, activatestrfAtranscription while repressing its own promoter. Finally, the scope of TrfA-mediated proteolysis was expanded by identifying TrfA as the adaptor that works with ClpCP to degrade antitoxins inS. aureus. Together, these results indicate that the adaptor TrfA adds temporal nuance to protein degradation by ClpCP inS. aureus.
Relationships of North American members ofRhodiola(Crassulaceae)
Authors: Olfelt Joel P. , Freyman William A.
Published: September 2014

Taxa of Rhodiola L. (Crassulaceae) generally grow in arctic or alpine habitats. Some Rhodiola species are used medicinally, one taxon, Rhodiola integrifolia Raf. subsp. leedyi (Rosend. & J.W.Moore) Moran, (Leedy’s roseroot), is rare and endangered, and the group’s biogeography in North America is intriguing because of distributional disjunctions and the possibility that Rhodiola rhodantha (A.Gray) H.Jacobsen (2n = 7II) and Rhodiola rosea L. (2n = 11II) hybridized to form Rhodiola integrifolia Raf. (2n = 18II). Recent studies of the North American Rhodiola suggest that the group’s current taxonomy is misleading. We analyzed nuclear and chloroplast DNA sequences (internal transcribed spacer (ITS), trnL intron, trnL–trnF spacer, trnS–trnG spacer) from the North American Rhodiola taxa. We combined our data with GenBank sequences from Asian Rhodiola species, performed parsimony, maximum likelihood (ML), and Bayesian phylogenetic analyses, and applied a Bayesian clock model to the ITS data. Our analyses reveal two major Rhodiola clades, suggest that hybridization between R. rhodantha and R. rosea lineages was possible, show two distinct clades within R. integrifolia, and demonstrate that a Black Hills, South Dakota, Rhodiola population should be reclassified as Leedy’s roseroot. We recommend that R. integrifolia be revised, and that the Black Hills Leedy’s roseroot population be managed as part of that rare and endangered taxon.
Gravitational and topological effects on $\sqrt{-F^2}$ confinement dynamics
Authors: Vasihoun Mahary , Guendelman Eduardo
Published: September 2014

We present a review, of recent developments on nonlinear gauge theory containing a [Formula: see text] term coupled to gravity. We start by showing some of the confining features of this theory in flat space–time. We then consider the coupling, of this nonlinear term, to gravity and discuss two types of spherically symmetric solutions. One of them has a tube topology, that is [Formula: see text], or of the Levi-Civita–Bertotti–Robinson (LCBR) type, where the metric coefficient gθθ is a constant. The other type of solutions, Reissner–Nordström–de Sitter (RNdS), with gθθ = r2, where r is a radial variable allowed to have all values from zero to infinity. Next we consider the matching of these solutions via lightlike, and subsequently, timelike membranes and show the topologically induced effects of "hiding of charge," where a charged particle can appear neutral to an external observer looking at it from the RNdS region and the "confining of charge" in a wormhole throat, where two opposite charges are at the opposite sides of a wormhole throats. We proceed with some applications to extended theories of general relativity, in the form of quadratic gravity model (F(R)), then wormholes arise naturally from the nonlinear electromagnetic field rather than requiring exotic matter to generate a predesigned wormhole geometry (Morris–Thorne approach), in another model considered here we have, in addition to quadratic gravity, a dilaton field (ϕ), where we find wormhole solutions with de Sitter asymptotics and confinement–deconfinement transition effects as function of the dilaton vacuum expectation value. The last application we present is to the "Two Measure Theory," where in addition to the metric volume element, [Formula: see text], we consider a new, metric independent, volume element Φ. Finally we conclude and summarize our findings.
A Novel Arc Segmentation Approach for Document Image Processing
Authors: Zhang Zili , Wang Xuan , Han Kai , Jiang Zoe L.
Published: September 2014

In document image processing, arc segmentation plays an important role in vectorization and graphic recognition. Moreover, the unsatisfactory results of several recent arc segmentation contests indicate that conventional methods are inadequate. This paper proposes a new arc segmentation algorithm called SymCAve (an acronym for Symmetry axis, Circle fitting and Average distribution points). First, we locate several seed points and adopt three strategies to ensure that the seed points are proper; then we calculate the center and radius utilizing the seed points. Second, the coordinates of the center and radius are adjusted by employing symmetry axes. Third, the average distribution points method is used to verify whether the points on the circumference are all black pixels. It is a complete circle if all of the points are black pixels. Otherwise, it is a partial circle if some of the points are black pixels and are continuous. Based on this information, the start and end angles of the partial circle can be determined. Finally, these arcs are verified to ensure that the results are accurate. Images and the evaluation tool were obtained from the GREC Workshop's Arc Segmentation contests, to test the systematic performance of the SymCAve algorithm. The experiments demonstrate that the proposed method can provide promising results. However, the algorithm has some drawbacks: it cannot detect a line with width of one pixel, small angles, and any large radius arcs. It is suited for segmenting images with appropriate symmetry axes.
Vibration and Dynamic Stability of Pre-Twisted Thick Cantilever Beam Made of Functionally Graded Material
Authors: Mohanty Sukesh Chandra , Dash Rati Ranjan , Rout Trilochan
Published: September 2014

In the present work, the vibration and dynamic stability of functionally graded ordinary (FGO) pre-twisted cantilever Timoshenko beam has been investigated. Finite element shape functions are established from differential equations of static equilibrium. Expressions for element stiffness and mass matrices are obtained from energy considerations. Floquet's theory is used to establish the stability boundary. The material properties along the thickness of the beam are assumed to vary according to the power law. The effects of power law index and pre-twist angle on the natural frequencies and dynamic stability of the beam have been investigated. Increase in pre-twist angle enhances the stability of the beam for first mode whereas it makes the beam more prone to parametric instability for the second mode. The increase in power law index is found to have a detrimental effect on the stability of the beam. The chance of parametric instability is enhanced with the increase in static load factor.
Byte weight enumerators and modular forms of genus r
Authors: Sharma Anuradha , Sharma Amit K.
Published: September 2014

For a positive integer m, let R be either the ring ℤ2m of integers modulo 2m or the quaternionic ring Σ2m = ℤ2m + αℤ2m + βℤ2m + γℤ2m with α = 1 + î, β = 1 + ĵ and [Formula: see text], where [Formula: see text] are elements of the ring ℍ of real quaternions satisfying [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text]. In this paper, we obtain Jacobi forms (or Siegel modular forms) of genus r from byte weight enumerators (or symmetrized byte weight enumerators) in genus r of Type I and Type II codes over R. Furthermore, we derive a functional equation for partial Epstein zeta functions, which are summands of classical Epstein zeta functions associated with quadratic forms.
Rings whose modules have maximal or minimal subprojectivity domain
Authors: Durğun Yılmaz
Published: September 2014

Given modules M and N, M is said to be N-subprojective if for every epimorphism g : B → N and homomorphism f : M → N, there exists a homomorphism h : M → B such that gh = f. For a module M, the subprojectivity domain of M is defined to be the collection of all modules N such that M is N-subprojective. As an alternative perspective on the projectivity of a module, a module M is said to be p-indigent if its subprojectivity domain is smallest possible, namely, consisting of exactly the projective modules. Properties of subprojectivity domains and of p-indigent modules are studied. For various classes of modules (such as simple and singular), necessary and sufficient conditions for the existence of p-indigent modules of those types are studied. We characterize the rings over which every (simple) module is projective or p-indigent. In addition, we use our results to provide a characterization of a special class of QF-rings in which the subinjectivity and subprojectivity domains of all modules coincide. As the projective analog of indigent modules, p-indigent modules were introduced by Holston, López-Permouth, Mastromatteo and Simental-Rodriguez. The paper is inspired by similar ideas and problems in papers by Aydoğdu and López-Permouth and by Alizade, Büyükaşık and Er, where an injective version of p-indigent modules is introduced and studied.
Algebras with only finitely many subalgebras
Authors: Kosters Michiel
Published: September 2014

Let R be a commutative ring. A not necessarily commutative R-algebra A is called futile if it has only finitely many R-subalgebras. In this paper, we relate the notion of futility to familiar properties of rings and modules. We do this by first reducing to the case where A is commutative. Then we refine the description of commutative futile algebras from Dobbs, Picavet and Picavet-L'Hermite.
On p-supersolubility and solubility of finite groups
Authors: Mao Yuemei , Guo Wenbin , Li Baojun
Published: September 2014

Let 𝔉 be a class of groups. A subgroup H of G is said to be weakly 𝔉s-quasinormal in G if G has an S-quasinormal subgroup T such that HT is S-quasinormal in G and (H ∩ T) HG/HG ≤ Z𝔉(G/HG), where Z𝔉(G/HG) is the 𝔉-hypercenter of G/HG. In this paper, we investigate further the influence of weakly 𝔉s-quasinormality of some subgroups on the structure of finite groups. Some new characterizations about p-supersolubility and solubility of finite groups are obtained.
Commutative nil clean group rings
Authors: McGovern Warren Wm. , Raja Shan , Sharp Alden
Published: September 2014

In [A. J. Diesl, Classes of strongly clean rings, Ph.D. Dissertation, University of California, Berkely (2006); Nil clean rings, J. Algebra383 (2013) 197–211], a nil clean ring was defined as a ring for which every element is the sum of a nilpotent and an idempotent. In this short paper, we characterize nil clean commutative group rings.
Water Dispersible Graphene Sheets Produced from Unassembled Graphene–Polyaniline Nanohybrids
Authors: Li Qi , Li Denian , Dong Lijie , Sun Fan , Huang Jing , Xie Haian , Xiong Chuanxi
Published: September 2014

We present an efficient process for producing water dispersible graphene sheets from unassembled graphene–polyaniline nanohybrids. The result of atomic force microscopy reveals that over 80% of thus-prepared graphitic sheets are single layers with typical thickness of approximately 0.8 nm. The proportion of modifying molecules in the product is found to be as low as 3.0 wt.%, as determined by elemental analysis. Along with its fascinating water dispersibility and remarkably high electrical conductivity, such material is anticipated to be very promising for use in graphene-based nanoelectronics and high-performance composites.
Origin of the high tunability of BaTiSnO3 thin films deposited by sol–gel
Authors: Mascot Manuel , Carru Jean-Claude , Fasquelle Didier
Published: September 2014

Ba ( Sn 0.02 Ti 0.98) O 3 thin films (BTS) were prepared by sol–gel route and deposited by spin-coating on commercial Pt / Ti / SiO 2/ Si substrates. By modifying the annealing conditions from 750°C at 1 h to 950°C at 15 min, the relative tunability nr at 100°C in the paraelectric state increased from 45 to 70% while the DC dielectric permittivity ε′(0) increased as well. The evolutions of ε′(E) and nr(E) are explained from Devonshire thermodynamic formalism. The very high value of tunability of 70% is explained by the grain size increase of our BTS thin films and the decrease of the dead layer effect when the annealing conditions are optimized.
Trade and Investment Liberalization in India: Implications for Productivity Gains
Authors: Das Ram Upendra
Published: September 2014

Since 1991, India has witnessed wide-ranging economic reforms in its policies governing international trade and foreign direct investment (FDI) flows which has consequently led to a dramatic rise in both trade and FDI flows since then. Using firm-level panel data, this paper investigates whether these trends have contributed to significant productivity improvements since 2000, as measured by total factor productivity (TFP). In addition, the paper also examines the determinants of TFP across a range of different industry categories. The results suggest the existence of significant productivity improvements since 2000 and also identify variables such as imports of raw materials and capital goods, size of operation, quality of employment captured by wage rates, and technology imports as crucial determinants of productivity.
A New Regime of SME Finance in Emerging Asia: Enhancing Access to Growth Capital and Policy Implications
Authors: Shinozaki Shigehiro
Published: September 2014

While finance is critical for small and medium-sized enterprises (SMEs) to survive and grow, most SMEs suffer from poor access to finance. Given the pronounced global financial uncertainty, stable access to appropriate funding sources has become even more difficult for SMEs to attain. Lessons from the global financial crisis have motivated many countries to consider SME access to finance beyond conventional bank credit and to diversify their domestic financial systems. This paper uses empirical analysis to point out the limitations of traditional bank lending to SMEs and suggests possible policy approaches facilitating them to access growth capital.
Physical-layer encryption on the public internet: A stochastic approach to the Kish-Sethuraman cipher
Authors: Gunn Lachlan J. , Chappell James M. , Allison Andrew , Abbott Derek
Published: September 2014

While information-theoretic security is often associated with the one-time pad and quantum key distribution, noisy transport media leave room for classical techniques and even covert operation. Transit times across the public internet exhibit a degree of randomness, and cannot be determined noiselessly by an eavesdropper. We demonstrate the use of these measurements for information-theoretically secure communication over the public internet.
The 1970 eruption on Deception Island (Antarctica): eruptive dynamics and implications for volcanic hazards
Authors: Pedrazzi Dario , Aguirre-Díaz Gerardo , Bartolini Stefania , Martí Joan , Geyer Adelina
Published: September 2014

In the southern winter of 1970, a phreatomagmatic eruption occurred in the northern part of Deception Island (South Shetland Archipelago, Antarctic Peninsula). The eruption, with no eye-witnesses to the event, occurred in the same general area as the 1967 eruption, but with new, more widely distributed vents. Two contrasting groups of craters were formed in the 1970 eruption, showing that different active fissures and eruptive dynamics were operating. One group consists of ‘maar-like’ craters, whereas the other comprises conical edifices. The 1970 eruption can be classified as volcanic explosivity index (VEI) 3, with mainly phreatomagmatic phases that generated a bulk volume of about 0.1 km
3
of pyroclastic material and an eruptive column at least 10 km high, from which fallout deposits are recognized more than 100 km to the NE. The 1970 eruption was similar to that of 1967 and together these two eruptive events show how eruption dynamics can be controlled by the uppermost part of the volcano substrate and the width and orientation of the eruptive fissure. These influence magma–water interaction and hence may imply different eruptive phases and associated volcanic hazards.

Supplementary material:

Granulometric and component histograms of the samples that are not shown in Figure 4 are available at
http://www.geolsoc.org.uk/SUP18761
.
On Palaeozoic–Mesozoic brittle normal faults along the SW Barents Sea margin: fault processes and implications for basement permeability and margin evolution
Authors: Indrevær Kjetil , Stunitz Holger , Bergh Steffen G.
Published: September 2014

Palaeozoic–Mesozoic brittle normal faults onshore along the SW Barents Sea passive margin off northern Norway give valuable insight into fault and fluid flow processes from the lower brittle crust. Microstructural evidence suggests that Late Permian–Early Triassic faulting took place during multiple phases, with initial fault movement at minimum
P–T
conditions of
c
. 300 °C and
c
. 240 MPa (
c
. 10 km depth), followed by later fault movement at minimum
P–T
conditions of
c
. 275 °C and
c
. 220 MPa (
c
. 8.5 km depth). The study shows that pore pressures locally reached lithostatic levels (240 MPa) during faulting and that faulting came to a halt during early (deep) stages of rifting along the margin. Fault permeability has been controlled by healing and precipitation processes through time, which have sealed off the core zone and eventually the damage zones after faulting. A minimum average exhumation rate of
c
. 40 m Ma
−1
since the Late Permian is estimated. It implies that the debated Late Cenozoic uplift of the margin may be explained by increased erosion rates in the coastal regions owing to climate detoriation, which caused subsequent isostatic recalibration and uplift of the marginal crust. The studied faults may be used as analogues of basement-involved fault complexes offshore, revealing details about the offshore nature of faulting, including past and present basement and fault zone permeability.
Trial of Zolpidem, Eszopiclone, and Other GABA Agonists in a Patient with Progressive Supranuclear Palsy
Authors: Chang Andrew Young , Weirich Erica
Published: September 2014

Progressive supranuclear palsy (PSP) is a progressive, debilitating neurodegenerative disease of the Parkinson-plus family of syndromes. Unfortunately, there are no pharmacologic treatments for this condition, as most sufferers of the classic variant respond poorly to Parkinson medications such as levodopa. Zolpidem, a gamma aminobutyric acid (GABA) agonist specific to theα-1 receptor subtype, has been reported to show improvements in symptoms of PSP patients, including motor dysfunction, dysarthria, and ocular disturbances. We observed a 73-year-old woman with a six-year history of PSP, who, upon administration of a single 12.5 mg dose of sustained-release zolpidem, exhibited marked enhancements in speech, facial expressions, and fine motor skills for five hours. These results were reproduced upon subsequent clinic visits. In an effort to find a sustainable medication that maximized these beneficial effects while minimizing side effects and addressing some of her comorbid neuropsychological conditions, a trial of five other GABA receptor agonists was performed with the patient’s consent, while she and her caregivers were blinded to the specific medications. She and her caretakers subsequently reported improvements, especially visual, while on eszopiclone, and, to a lesser degree, temazepam and flurazepam.
The Role of the Dominant Modes of Precipitation Variability over Eastern Africa in Modulating the Hydrology of Lake Victoria
Authors: Smith Kara A. , Semazzi Fredrick H. M.
Published: September 2014

Previous water budget studies over Lake Victoria basin have shown that there is near balance between rainfall and evaporation and that the variability of Lake Victoria levels is determined virtually entirely by changes in rainfall since evaporation is nearly constant. The variability of rainfall over East Africa is dominated by El Niño-Southern Oscillation (ENSO); however, the second and third most dominant rainfall climate modes also account for significant variability across the region. The relationship between ENSO and other significant modes of precipitation variability with Lake Victoria levels is nonlinear. This relationship should be studied to determine which modes need to be accurately modeled in order to accurately model Lake Victoria levels, which are important to the hydroelectric industry in East Africa. The objective of this analysis is to estimate the relative contributions of the dominant modes of annual precipitation variability to the modulation of Lake Victoria levels for the present day (1950–2012). The first mode of annual rainfall variability accounts for most of the variability in Lake Victoria levels, while the effects of the second and third modes are negligible even though these modes are also significant over the region.
Therapeutic Use of MicroRNAs in Lung Cancer
Authors: Fortunato Orazio , Boeri Mattia , Verri Carla , Moro Massimo , Sozzi Gabriella
Published: September 2014

Lung cancer is a leading cause of cancer deaths worldwide. Although the molecular pathways of lung cancer have been partly known, the high mortality rate is not markedly changed. MicroRNAs (miRNAs) are small noncoding RNAs that actively modulate cell physiological processes as apoptosis, cell-cycle control, cell proliferation, DNA repair, and metabolism. Several studies demonstrated that miRNAs are involved in the pathogenesis of lung diseases including lung cancer and they negatively regulate gene and protein expression by acting as oncogenes or tumor suppressors. In this review we summarize the current knowledge on the role of miRNAs and their target genes in lung tumorigenesis and evaluate their potential use as therapeutic agents in lung cancer. In particular, we describe methodological approaches such as inhibition of oncogenic miRNAs or replacement of tumor suppressor miRNAs, both inin vitroandin vivoassays. Furthermore we discuss new strategies to achievein vivotissue specific delivery, potential off-target effects, and safety of miRNAs systemic delivery.