bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome Sequence of
Martelella
sp. Strain AD-3, a Moderately Halophilic Polycyclic Aromatic Hydrocarbon-Degrading Bacterium
Authors: Cui Changzheng , Li Pengpeng , Liu Gao , Tang Hongzhi , Lin Kuangfei , Luo Qishi , Liu Shanshan , Xu Ping , Liu Yongdi
Published: January 2014

Martelella
sp. strain AD-3, enriched from a petroleum-contaminated site with high salinity, can efficiently degrade polycyclic aromatic hydrocarbons. Here, we report the 4.75-Mb genome sequence of strain AD-3 with its genetic feature of helping to remediate environmental organic pollutants.
Genome Sequence Analysis of the Biogenic Amine-Degrading Strain Lactobacillus casei 5b
Authors: Ladero Victor , Herrero-Fresno Ana , Martinez Noelia , del Río Beatriz , Linares Daniel M. , Fernández María , Martín María Cruz , Alvarez Miguel A.
Published: January 2014

We here report a 3.02-Mbp annotated draft assembly of the
Lactobacillus casei
5b genome. The sequence of this biogenic amine-degrading dairy isolate may help identify the mechanisms involved in the catabolism of biogenic amines and perhaps shed light on ways to reduce the presence of these toxic compounds in food.
Draft Genome Sequence of
Blastomonas
sp. Strain CACIA 14H2, a Heterotrophic Bacterium Associated with Cyanobacteria
Authors: Lima Alex Ranieri Jerônimo , Siqueira Andrei Santos , dos Santos Bruno Garcia Simões , da Silva Fábio Daniel Florêncio , Lima Clayton Pereira , Cardoso Jedson Ferreira , Vianez-Júnior João Lídio S. G. , Nunes Márcio Roberto Teixeira , Gonçalves Evonnildo Costa
Published: January 2014

With the new methods for assembling sequence data from metagenomic samples, the genomic study of heterotrophic bacterium-cyanobacterium associations can now be improved. In this work, the draft genome sequence of
Blastomonas
sp. strain CACIA 14H2, obtained from a nonaxenic culture of a
Cyanobium
sp., is presented.
Parallel Pathways for Nitrite Reduction during Anaerobic Growth in Thermus thermophilus
Authors: Alvarez Laura , Bricio Carlos , Hidalgo Aurelio , Berenguer José
Published: January 2014

Respiratory reduction of nitrate and nitrite is encoded in
Thermus thermophilus
by the respective transferable gene clusters. Nitrate is reduced by a heterotetrameric nitrate reductase (Nar) encoded along transporters and regulatory signal transduction systems within the nitrate respiration conjugative element (NCE). The nitrite respiration cluster (
nic
) encodes homologues of nitrite reductase (Nir) and nitric oxide reductase (Nor). The expression and role of the
nirSJM
genes in nitrite respiration were analyzed. The three genes are expressed from two promoters, one (
nirSp
) producing a tricistronic mRNA under aerobic and anaerobic conditions and the other (
nirJp
) producing a bicistronic mRNA only under conditions of anoxia plus a nitrogen oxide. As for its nitrite reductase homologues, NirS is expressed in the periplasm, has a covalently bound heme
c
, and conserves the heme
d
1
binding pocket. NirJ is a cytoplasmic protein likely required for heme
d
1
synthesis and NirS maturation. NirM is a soluble periplasmic homologue of cytochrome
c
552
. Mutants defective in
nirS
show normal anaerobic growth with nitrite and nitrate, supporting the existence of an alternative Nir in the cells. Gene knockout analysis of different candidate genes did not allow us to identify this alternative Nir protein but revealed the requirement for Nar in NirS-dependent and NirS-independent nitrite reduction. As the likely role for Nar in the process is in electron transport through its additional cytochrome
c
periplasmic subunit (NarC), we concluded all the Nir activity takes place in the periplasm by parallel pathways.
Expression and Targeting of Secreted Proteins from Chlamydia trachomatis
Authors: Bauler Laura D. , Hackstadt Ted
Published: January 2014

Chlamydia trachomatis
is an obligate intracellular pathogen that replicates in a vacuole termed the inclusion. Many of the interactions of chlamydiae with the host cell are dependent upon bacterial protein synthesis and presumably exposure of these proteins to the cytosol. Because of the dearth of genetic tools for chlamydiae, previous studies examining secreted proteins required the use of heterologous bacterial systems. Recent advances in genetic manipulation of chlamydia now allow for transformation of the bacteria with plasmids. We describe here a shuttle vector system, pBOMB4, that permits expression of recombinant proteins under constitutive or conditional promoter control. We show that the inclusion membrane protein IncD is secreted in a type III-dependent manner from
Yersinia pseudotuberculosis
and also secreted from
C. trachomatis
in infected cells where it localizes appropriately to the inclusion membrane. IncD truncated of the first 30 amino acids containing the secretion signal is no longer secreted and is retained by the bacteria. Cytosolic exposure of secreted proteins can be confirmed by using CyaA, GSK, or microinjection assays. A protein predicted to be retained within the bacteria, NrdB is indeed localized to the chlamydia. In addition, we have shown that the chlamydial effector protein, CPAF, which is secreted into the host cell cytosol by a Sec-dependent pathway, also accesses the cytosol when expressed from this system. These assays should prove useful to assess the secretion of other chlamydial proteins that are potentially exposed to the cytosol of the host cell.
A Signaling Pathway Involving the Diguanylate Cyclase CelR and the Response Regulator DivK Controls Cellulose Synthesis in Agrobacterium tumefaciens
Authors: Barnhart D. Michael , Su Shengchang , Farrand Stephen K.
Published: January 2014

The production of cellulose fibrils is involved in the attachment ofAgrobacterium tumefaciensto its plant host. Consistent with previous studies, we reported recently that a putative diguanylate cyclase,celR, is required for synthesis of this polymer inA. tumefaciens. In this study, the effects ofcelRand other components of the regulatory pathway of cellulose production were explored. Mutational analysis ofcelRdemonstrated that the cyclase requires the catalytic GGEEF motif, as well as the conserved aspartate residue of a CheY-like receiver domain, for stimulating cellulose production. Moreover, a site-directed mutation within the PilZ domain of CelA, the catalytic subunit of the cellulose synthase complex, greatly reduced cellulose production. In addition, deletion ofdivK, the first gene of thedivK-celRoperon, also reduced cellulose production. This requirement fordivKwas alleviated by expression of a constitutively active form of CelR, suggesting that DivK acts upstream of CelR activation. Based on bacterial two-hybrid assays, CelR homodimerizes but does not interact with DivK. The mutation indivKadditionally affected cell morphology, and this effect was complementable by a wild-type copy of the gene, but not by the constitutively active allele ofcelR. These results support the hypothesis that CelR is a bona fide c-di-GMP synthase and that the nucleotide signal produced by this enzyme activates CelA via the PilZ domain. Our studies also suggest that the DivK/CelR signaling pathway inAgrobacteriumregulates cellulose production independent of cell cycle checkpoint systems that are controlled bydivK.
Acute gross painless transudative ascites in a patient with lupus
Authors: Erfani T , Manolios N , Howe G , Spencer D
Published: January 2014

Gross ascites is a rare presentation of lupus. Ascites in lupus may be due to lupus peritonitis or secondary to one of the complications including nephrotic syndrome. The ascites due to lupus peritonitis has been described as exudative with a serum-ascites albumin gradient (SAAG) below 11 g/L, unless associated with nephrotic syndrome. We report an unusual case of lupus ascites in a 23-year-old woman who presented with acute painless gross ascites with no constitutional, skin or musculoskeletal symptoms of a lupus flare. The ascites was a transudate with SAAG above 11 g/L with no associated nephrotic syndrome. She was treated with corticosteroids, mycophenolate mofetil and diuretics with a good response and no recurrence of her ascites.
Haemorrhagic cholecystitis: an unusual cause of upper gastrointestinal bleeding
Authors: Hicks Natalie
Published: January 2014

Haemorrhagic cholecystitis is a rare cause of upper gastrointestinal bleeding and is a difficult diagnosis to make. This case report describes an orthopaedic patient, who developed deranged liver function tests and anaemia after a hemiarthroplasty of the hip. The patient had upper abdominal pain and black stools which clinically appeared to be melaena. An ultrasound scan of the abdomen was inconclusive, and therefore a CT was performed and the potential diagnosis of haemorrhagic cholecystitis was raised. An endoscopic evaluation of the upper gastrointestinal tract showed no evidence of other causes of upper gastrointestinal bleeding. Following an emergency laparotomy and cholecystectomy, she recovered well. This report aims to increase awareness about the uncommon condition of haemorrhagic cholecystitis, and to educate regarding clinical and radiological signs which lead to this diagnosis.
Social supply of alcohol to Korean high school students: a cross-sectional International Alcohol Control Study
Authors: Asante Lydia S , Chun Sungsoo , Yun Mieun , Newell Maxine
Published: January 2014

Purpose

Underage drinking is strictly prohibited by law, nevertheless, adolescents report having access through social supply from family, friends and other members of the society. The aim of this study was to determine the primary suppliers of alcohol to Korean teenagers.

Design

Cross-sectional study.

Setting

Data were collected from 21 high schools in geographically diverse regions in South Korea from June to July 2012 as part of the International Alcohol Control Study.

Participants

Data were analysed from 247 high schoolers aged 16–18 years old as part of the International Alcohol Control Study.

Primary and secondary outcome measures

Social supply to high school students.

Results

More than 56% of high schoolers who participated in the International Alcohol Control Survey had been supplied alcohol at least once. Of this number, approximately 59% were males. Parents (especially fathers) and friends were the main suppliers, with friends contributing greater volumes (205 g) of alcohol. Of the number of students provided by mothers, 52% of them were females while 73% of respondents provided by friends were males. The most significant place for alcohol supply was at special events. Males were at higher odds for risky drinking.

Conclusions

These results support previous findings about the role of parents and friends in underage drinking in South Korean high school drinkers.
Lean thinking in hospitals: is there a cure for the absence of evidence? A systematic review of reviews
Authors: Andersen Hege , Røvik Kjell Arne , Ingebrigtsen Tor
Published: January 2014

Objective

Lean interventions aim to improve quality of healthcare by reducing waste and facilitate flow in work processes. There is conflicting evidence on the outcomes of lean thinking, with quantitative and qualitative studies often contradicting each other. We suggest that reviewing the literature within the approach of a new contextual framework can deepen our understanding of lean as a quality-improvement method. This article theorises the concept of context by establishing a two-dimensional conceptual framework acknowledging lean as complex social interventions, deployed in different organisational dimensions and domains. The specific aim of the study was to identify factors facilitating intended outcomes from lean interventions, and to understand when and how different facilitators contribute.

Design

A two-dimensional conceptual framework was developed by combining Shortell'sDimensions of capabilitywith Walshes’Domains of an intervention. We then conducted a systematic review of lean review articles concerning hospitals, published in the period 2000–2012. The identified lean facilitators were categorised according to the intervention domains and dimensions of capability provided by the framework.

Results

We provide a framework emphasising context by relating facilitators to domains and dimensions of capability. 23 factors enabling a successful lean intervention in hospitals were identified in the systematic review, where management and a supportive culture, training, accurate data, physicians and team involvement were most frequent.

Conclusions

In the absence of evidence, the two-dimensional framework, incorporating the context, may prove useful for future research on variation in outcomes from lean interventions. Findings from the review suggest that characteristics and local application of lean, in addition to strategic and cultural capability, should be given further attention in healthcare quality improvement.
Unsafe riding practice among electric bikers in Suzhou, China: an observational study
Authors: Yang Jie , Hu Yihe , Du Wei , Powis Brent , Ozanne-Smith Joan , Liao Yilan , Li Ning , Wu Ming
Published: January 2014

Background

Electric bike (E-bike)-related deaths have been increasing rapidly in China and such injuries may be partly attributable to unsafe riding practice.

Objectives

To describe potentially unsafe riding behaviours among electric bikers (E-bikers) and to investigate factors influencing these practices in China.

Methods

In September 2012, a cross-sectional observation study including a speed measurement component was conducted in Wuzhong (an urban district) and Zhangjiagang (a rural district) of Suzhou, Jiangsu Province, China. Hand-held radar speed metres were used to read travelling speeds of E-bikes and a pro forma observation checklist was used to collect data on road riding practice. Mixed-effect logistic regressions were used to calculate adjusted ORs and 95% CIs for the association between speeding, road rule violations and helmet use and their influencing factors.

Results

Among 800 E-bikes with a speed reading, 70.9% exceeded the designed speed limit of 20 km/h. Among a further 20 647 E-bikers observed, 38.3% did not comply with the road rules when entering intersections; and only 2.2% wore helmets. No regional variation was identified between urban and rural areas. Male E-bikers were associated with more speeding and road rule violations, whereas riding a pedal-equipped E-bike was associated with less road rule violations and less helmet use.

Conclusions

Unsafe riding practices such as speeding, road rule violations and lack of helmet use were commonplace among E-bikers, especially among men. The study findings indicate that measures aimed at improving E-bike safety are required in China.
Costs for collagenase injections compared with fasciectomy in the treatment of Dupuytren's contracture: a retrospective cohort study
Authors: Atroshi Isam , Strandberg Emelie , Lauritzson Anna , Ahlgren Eva , Waldén Markus
Published: January 2014

Objectives

To compare collagenase injections and surgery (fasciectomy) for Dupuytren's contracture (DC) regarding actual total direct treatment costs and short-term outcomes.

Design

Retrospective cohort study.

Setting

Orthopaedic department of a regional hospital in Sweden.

Participants

Patients aged 65 years or older with previously untreated DC of 30° or greater in the metacarpophalangeal (MCP) and/or proximal interphalangeal (PIP) joints of the small, ring or middle finger. The collagenase group comprised 16 consecutive patients treated during the first 6 months following the introduction of collagenase as treatment for DC at the study centre. The controls were 16 patients randomly selected among those operated on with fasciectomy at the same centre during the preceding 3 years.

Interventions

Treatment with collagenase was given during two standard outpatient clinic visits (injection of 0.9 mg, distributed at multiple sites in a palpable cord, and next-day finger extension under local anaesthesia) followed by night-time splinting. Fasciectomy was carried out in the operating room (day surgery) under general or regional anaesthesia using standard technique, followed by therapy and splinting.

Primary and secondary outcome measures

Actual total direct costs (salaries of all medical personnel involved in care, medications, materials and other relevant costs), and total MCP and PIP extension deficit (degrees) measured by hand therapists at 6–12 weeks after the treatment.

Results

Collagenase injection required fewer hospital outpatient visits to a therapist and nurse than fasciectomy. Total treatment cost for collagenase injection was US$1418.04 and for fasciectomy US$2102.56. The post-treatment median (IQR) total extension deficit was 10 (0–30) for the collagenase group and 10 (0–34) for the fasciectomy group.

Conclusions

Treatment of DC with one collagenase injection costs 33% less than fasciectomy with equivalent efficacy at 6 weeks regarding reduction in contracture.
Tooth trauma: pathology and the treatment options
Authors: Oxford Matthew
Published: January 2014

Tooth damage, a common injury in domestic animals, can be caused by localised traumatic injuries, such as those associated with chewing or biting, or by more widespread traumatic injuries, such as road traffic collisions. Damage may not always be externally obvious and so it is important that all suspected tooth traumas are thoroughly assessed under anaesthesia and with an accompanying radiograph. The result of untreated tooth trauma may be pain, pulpitis, pulp necrosis, root resorption, periradicular pathology and periodontitis. This article discusses the pathophysiology and diagnosis of these traumas, as well as looking at the treatment options available.
Appendices to bovine caesarean section 2. Difficult caesareans (potential pitfalls and how to overcome them)
Authors: Alexander Dominic
Published: January 2014

These appendices accompany the article printed in In Practice, January 2014, vol 36, pp 15‐26 (doi: 10.1136/inp.f7197).
Clostridial diseases of the horse
Authors: South Victoria
Published: January 2014

TheClostridiumgenus contains several species that are important equine pathogens. Clostridia are Gram‐positive spore‐forming bacteria with differing degrees of aerotolerance. ManyClostridiumspecies are intestinal commensals in healthy horses; however, some are opportunistic pathogens that cause a range of diseases. Clostridial spores are often resistant to disinfectants and can survive in extreme environmental conditions, leading to widespread exposure risk. This article describes the main clostridial diseases affecting horses, discussing differential diagnoses, prevention and treatment.
Evaluation of commercial HPV assays in the context of post-treatment follow-up: Scottish Test of Cure Study (STOCS-H)
Authors: Cubie H A , Canham M , Moore C , Pedraza J , Graham C , Cuschieri K
Published: January 2014

Aims

Human papillomavirus (HPV) testing is more sensitive than cytology for detection of residual/recurrent cervical disease after lesion treatment. Several HPV test comparison studies have been performed within triage and screening populations, but data on their comparative performance in a test of cure context is lacking. This study aims to address this gap.

Methods

We compared the technical and clinical performance of Abbott RealTime High risk (HR)-HPV, Genprobe Aptima PV, Hologic Cervista HPV-HR, Qiagen Hybrid Capture 2 and Roche cobas HPV in the Early Implementation phase of a ‘test of cure’ service within the Scottish Cervical Screening Programme.

Results

Valid results with all five HPV Tests from 1020 first samples taken ∼6 months post-treatment showed HPV positivity ranging from 17.84% to 26.96%. There was perfect agreement in 74%, and greatest variation between assays was observed in cytologically negative samples. Clinical performance was judged on cumulative incidence of cervical intraepithelial neoplasia 2+ (CIN2+) during follow-up (mean: 13.2 months). There were 23 cases of CIN2+ of which 14 were CIN3+. All assays, including cytology, were 100% sensitive for detection of CIN3+. Of the nine cases of residual CIN2, three assays detected all, one assay missed one and one assay missed two cases. Specificity ranged from 75% to 84% according to assay.

Conclusions

All assays were sensitive for detection of CIN2+ at 6 months post-treatment. The range of positivity equated to a 50% increase between assays with the lowest and highest positivity rates. The relevance of HPV positivity in the absence of cytological abnormalities requires longer follow-up to determine whether additional tools for risk stratification are required.
Early detachment of the Solitaire stent during thrombectomy retrieval: an in vitro investigation
Authors: Kwon Hyon-Jo , Chueh Ju-Yu , Puri Ajit S , Koh Hyeon-Song
Published: January 2014

Objective

To elucidate the early detachment of the Solitaire stent during mechanical thrombectomy, we tested the stent in vitro under various conditions and evaluated with microscopy.

Methods

A total of five stents were tested. Using a dynamic mechanical analysis machine, we calculated the tensile force needed for separation of the four stents from the pusher wire. Stent Nos 1 and 2 were tested without any prior manipulation. During the retraction test, no sheathing around the stent–wire junction was applied to stent No 1 whereas stent No 2 was partially covered with a sheath in accordance with instructions for use (IFU) recommendations. Stent No 3 was tested after deployment and retrieval were performed three times in an in vitro vascular replica with sheathing during retrieval. Stent No 4 was tested after one deployment and retrieval using the same replica as in stent No 3 without sheathing. In addition, forward pushing force was applied intentionally during retraction to induce excessive bending of the stent. Stent No 5 was pulled apart by both hands. After separation, stent tips and pusher wires were studied for all stents under the microscope.

Results

The tensile force needed for separation was about 6 N for stent Nos 1, 2, and 3, and about 4 N for stent No 4. All of the stents showed separation at the proximal marker, not at the detachment zone.

Conclusions

Detachment of the Solitaire stent during thrombectomy can be due to separation around or inside the proximal marker. Adherence to the manufacturer's IFU of partial re-sheathing during retraction and not using the device for more than two passes might decrease the possibility of such device failure.
The clinical value of serial measurement of high-sensitivity cardiac troponin T in acute exacerbations ofchronic obstructive pulmonary disease
Authors: Høiseth Arne Didrik , Neukamm Anke , Hagve Tor-Arne , Omland Torbjørn , Brekke Pål H , Søyseth Vidar
Published: January 2014

Objective

To assess the prevalence and long-term prognostic value of a dynamic (rise/fall) pattern of cardiac troponin T (hs-cTnT) elevation during acute exacerbation of chronic obstructive pulmonary disease (AECOPD) compared with a stable hs-cTnT elevation.

Methods

Prospective cohort study of unselected patients admitted with AECOPD to the emergency room of a university hospital. Serial hs-cTnT measurements were made during admission. Survival after a median of 1.8 years was recorded.

Results

83 patients with a mean age of 72 years and a mean forced expiratory volume in 1 s (FEV1) of 0.9 L. The mortality rate was 62%. The median hs-cTnT at admission was 27 ng/L (IQR 13.4–51)). 65 patients (78%) had at least one hs-cTnT measurement ≥14 ng/L, and among these the median change in hs-cTnT was 50.7% (IQR 25.2–89.4). Of the patients with serial hs-cTnT measurements, 53 (82%) had a dynamic pattern (ie, ΔTnT ≥20%). In multivariate analysis, stable hs-cTnT elevation was associated with increasing age (OR per 5 years with 95% CI 1.9 (1.01 to 3.7), p=0.045) and low Hb (OR 7.3 (1.1 to 49), p=0.039). Stable hs-cTnT elevation was associated with increased mortality with an HR of 2.4 (95%CI 1.1 to 5.3, p=0.027) in the multivariate Cox regression analysis.

Conclusions

Among the patients with at least one hs-cTnT above the 99th centile, 82% had a rise/fall pattern, as requested to make a diagnosis of myocardial infarction. Compared to a dynamic rise/fall pattern of hs-cTnT, a stable and moderately elevated hs-cTnT during AECOPD is associated with poor long-term prognosis.
Applying games technology to veterinary teaching
Authors: Balogh Márton
Published: January 2014

Veterinarian Márton Balogh has been interested in computers, gaming and programming since he was eight years old. Here, he explains how he is using software that is more often associated with the creation of 3D computer games to develop an immersive, virtual consultation room, complete with patient, to help train veterinary students in clinical examination techniques
Plume–plate interaction
Authors: Burke Kevin , Cannon J. Matthew
Published: January 2014

Having discerned competition among vigorous plumes on the 108 year timescale, Tuzo Wilson suggested that plumes control plate behavior and are “the mainsprings of geological history”. Here we revisit that idea by discussing selected examples of plume–plate interaction and find that modern observational, instrumental, computational, and modeling capabilities are revealing a wonderful variety and complexity in plume–plate interaction. The degree to which plumes control plate behavior is poorly constrained. However, the examples we consider suggest complex interactions between plumes and plates that, during the past 70 million years, have led to separate episodes of extreme plate acceleration and near complete cessation of plate motion in the deep mantle reference frame. The recognition of contrasting convective behavior within two newly distinguished “Active Plume Heads”, both reaching to depths of ∼1200 km, one beneath Hawaii and the other between Iceland and Norway, represent new opportunities in studying plume–plate interaction. Wilson’s suggestion continues to inspire stimulating questions for future research.
Tree growth response to fuel reduction treatments along a topographic moisture gradient in mixed-oak forests of Ohio, U.S.A.
Authors: Anning Alexander K. , Dyer James M. , McCarthy Brian C.
Published: January 2014

This study examined the effect of the soil moisture gradient on tree growth response to prescribed fire and thinning in oak-dominated forests of Ohio. Six hundred and ninety-six increment cores (348 trees, five species) were collected from eighty 0.1 ha plots distributed across four treatments (control, thin, burn, thin + burn) in two sites. Ring widths were converted to basal area increments (BAIs). A water balance approach based on geographic information systems (GIS) was used to assess the potential evapotranspiration (PET) and moisture deficit for each tree, along with a long-term integrated moisture index, also based on GIS. The moisture gradients varied considerably across the landscape, with the highest PET and moisture deficit on ridges and south-facing slopes. This variation influenced the BAI of the studied species, but more strongly in the control stands than in the managed stands, where treatment effects became the main drivers of growth. Oaks exhibited greater BAI on sites with intermediate moisture demand or stress, whereas the non-oaks had greater BAI on more mesic sites. Moisture deficit and PET also interacted to influence BAI of yellow-poplar (Liriodendron tulipifera L.) and white oak (Quercus alba L.), particularly in the control. These results demonstrate the strong regulatory effect of the topographically controlled soil moisture gradient on tree growth in mixed-oak (Quercus spp.) forests, which can be explored to better understand community response to prescribed fire and thinning treatments.
INTERACTING MODIFIED HOLOGRAPHIC RICCI DARK ENERGY MODEL AND STATEFINDER DIAGNOSIS IN FLAT UNIVERSE
Authors: PANKUNNI PRASEETHA , MATHEW TITUS K.
Published: January 2014

In this paper, we have considered the modified holographic Ricci dark energy interacting with dark matter through a nongravitational coupling. We took three phenomenological forms for the interaction term Q in the model, where, in general, it is proportional to the Hubble parameter and densities of the dark sectors, that Q = ρde+ρm, ρmand ρde, respectively. We have obtained analytical solutions for the three interacting models, and studied the evolutions of equations of state parameter and deceleration parameter. The results are compared with the observationally constrained values for the best parameters of the model. In general, we have shown that the equation of state of models are showing a de Sitter type behavior, in the far future evolution of the universe. We have also done the statefinder analysis of the model to discriminate it from other standard models of dark energy and have shown that the present r–s values of the models were in the range of the r–s value of the Chaplygin gas model of dark energy.
IN–IN FORMALISM, PSEUDO-INSTANTONS AND RETHINKING QUANTUM COSMOLOGY
Authors: KAYA ALI
Published: January 2014

Unlike flat space quantum field theories that focus on scattering amplitudes, the main observables in quantum cosmology are correlation functions. The systematic way of calculating correlators is called in–in formalism, which requires only a single asymptotic region, i.e. past infinity. The rules in perturbation theory and the path integral measure are very different for in–in and in–out formalisms, and thus the results which are standard in one approach may not necessarily hold in the other one. We show that stationary phase approximation works completely different for a scalar in–in path integral. Hence, in a cosmological background there are solutions, pseudo-instantons, that allow tunneling between locally stable vacua even in infinite volume, which is counterintuitive from an in–out perspective. We argue that various familiar notions of in–out formalism must be re-examined in the in–in formalism, which might have important consequences for quantum cosmology.
A SIMPLE TIME-CONSISTENT MODEL FOR THE FORWARD DENSITY PROCESS
Authors: HULT HENRIK , LINDSKOG FILIP , NYKVIST JOHAN
Published: January 2014

In this paper, a simple model for the evolution of the forward density of the future value of an asset is proposed. The model allows for a straightforward initial calibration to option prices and has dynamics that are consistent with empirical findings from option price data. The model is constructed with the aim of being both simple and realistic, and avoid the need for frequent re-calibration. The model prices of n options and a forward contract are expressed as time-varying functions of an (n + 1)-dimensional Brownian motion and it is investigated how the Brownian trajectory can be determined from the trajectories of the price processes. An approach based on particle filtering is presented for determining the location of the driving Brownian motion from option prices observed in discrete time. A simulation study and an empirical study of call options on the S&P 500 index illustrate that the model provides a good fit to option price data.
CODING THEORY ON FIBONACCI n-STEP NUMBERS
Authors: BASU MANJUSRI , DAS MONOJIT
Published: January 2014

We consider the series of Fibonacci n-step numbers and a class of square matrix of order n based on Fibonacci n-step numbers with determinant +1 or -1. Thereby, we introduce a new coding theory called Fibonacci n-step coding theory and establish generalized relation among the code elements for all values of n. For n = 2, the correct ability of the method is 93.33%; for n = 3, the correct ability of the method is 99.80% and for n = 4, the correct ability of the method is 99.998%. In general, the correct ability of the method increases as n increases.
Journeys in Science: Glycobiology and Other Paths
Authors: Dwek Raymond A.
Published: January 2014

My scientific journeys began at Oxford nearly 50 years ago. My paths have taken me from magnetic resonance through enzyme systems to antibodies, which led directly to glycobiology. Oxford University's first industrial grant helped the development of the technology for isolating and sequencing oligosaccharides from glycoproteins. This technology was disseminated through a spin-off company, Oxford GlycoSystems, and by the establishment of the Glycobiology Institute. The technology gave rise to the concept of glycoforms, which allow diversification of a protein's properties. Iminosugars, which are glucosidase inhibitors, can interfere with the initial steps of glycan processing on proteins and inhibit three-dimensional folding of glycoproteins. Glucosidase targets for therapy include viral envelope glycoproteins. Clinical trials of an iminosugar as an antiviral for dengue virus are under way. Another iminosugar activity, inhibition of glycolipid synthesis, resulted in a drug for Gaucher disease, which was approved worldwide in 2002. The success of the company and the institute allowed me to undertake several initiatives, in the United Kingdom and abroad, that might help the paths of future generations of scientists.
Broadband Ocean-Bottom Seismology
Authors: Suetsugu Daisuke , Shiobara Hajime
Published: January 2014

Broadband ocean-bottom seismographs (BBOBSs) were first developed in the 1980s and have since been used to explore the structure of Earth's interior beneath oceanic regions—for example, mid-oceanic ridges, subduction zones, hot spots, and the oceanic lithosphere-asthenosphere boundary. The best approach for broadband seismic observations in oceanic regions is that of a borehole seismic observatory attached to the ocean-floor cable, which is realized in several near-coast networks. Considering the high cost of such networks, there is still a need to develop autonomous BBOBSs with a better signal-to-noise ratio for temporary observations of focused scientific targets far from the coast.
Falling in Love with Waves
Authors: Kanamori Hiroo
Published: January 2014

Desire to understand the physics of natural grandeur and the beauty of wave theories brought me to geophysics and seismology. Advancements in theory, practice, and instrumentation have allowed seismologists to unravel the mysteries carried by seismic waves and to use the acquired knowledge for the benefit of society.
β-Adrenergic blockade enhances coronary vasoconstrictor response to forehead cooling
Authors: Muller Matthew D. , Gao Zhaohui , Patel Hardikkumar M. , Heffernan Matthew J. , Leuenberger Urs A. , Sinoway Lawrence I.
Published: January 2014

Forehead cooling activates the sympathetic nervous system and can trigger angina pectoris in susceptible individuals. However, the effect of forehead cooling on coronary blood flow velocity (CBV) is not well understood. In this human experiment, we tested the hypotheses that forehead cooling reduces CBV (i.e., coronary vasoconstriction) and that this vasoconstrictor effect would be enhanced under systemic β-adrenergic blockade. A total of 30 healthy subjects (age range, 23–79 years) underwent Doppler echocardiography evaluation of CBV in response to 60 s of forehead cooling (1°C ice bag on forehead). A subset of subjects (n = 10) also underwent the procedures after an intravenous infusion of propranolol. Rate pressure product (RPP) was used as an index of myocardial oxygen demand. Consistent with our first hypothesis, forehead cooling reduced CBV from 19.5 ± 0.7 to 17.5 ± 0.8 cm/s ( P < 0.001), whereas mean arterial pressure increased by 11 ± 2 mmHg (P < 0.001). Consistent with our second hypothesis, forehead cooling reduced CBV under propranolol despite a significant rise in RPP. The current studies indicate that forehead cooling elicits a sympathetically mediated pressor response and a reduction in CBV, and this effect is augmented under β-blockade. The results are consistent with sympathetic activation of β-receptor coronary vasodilation in humans, as has been demonstrated in animals.
Mechanisms in cardiac fibroblast growth: an obligate role for Skp2 and FOXO3a in ERK1/2 MAPK-dependent regulation of p27kip1
Authors: Pramod S. , Shivakumar K.
Published: January 2014

Cardiac fibroblast hyperplasia associated with enhanced matrix deposition is a major determinant of tissue remodeling in several disease states of the heart. However, mechanisms controlling cell cycle progression in cardiac fibroblasts remain unexplored. Identification of cell cycle regulatory elements in these cells is important to develop strategies to check adverse cardiac remodeling under pathological conditions. This study sought to probe the mechanisms underlying ERK1/2-mediated p27Kip1 regulation in mitogenically stimulated cardiac fibroblasts. Addition of 10% fetal calf serum to quiescent cultures of adult rat cardiac fibroblasts promoted ERK1/2 activation, as evidenced by its phosphorylation status. Reduction in [3H]thymidine incorporation into DNA increased population doubling time, flow cytometry, and Western blot analysis showing reduced levels of cyclins D and A, p27Kip1 induction, and retinoblastoma protein (Rb) hypophosphorylation in ERK1/2-inhibited cells indicated ERK1/2 dependence of G1-S transition in cardiac fibroblasts. Lack of p27Kip1 protein in serum-stimulated, ERK1/2-active cells was associated with increased levels of Skp2, an E3 ubiquitin ligase for p27Kip1, whose knockdown by RNA interference induced p27Kip1 expression. Further, forced expression of Skp2 in ERK1/2-inhibited cells downregulated p27Kip1. Transcriptional upregulation of p27Kip1 mRNA in ERK1/2-inhibited cells, demonstrated by real-time PCR, correlated with forkhead box O 3a (FOXO3a) transcription factor activation, shown by gel shift assay. FOXO3a knockdown attenuated p27Kip1 mRNA and protein expression in ERK1/2-inhibited cells. We provide evidence for the first time that, in cardiac fibroblasts, activated ERK1/2 regulates p27Kip1 expression transcriptionally and posttranslationally via FOXO3a- and Skp2-dependent mechanisms. Additionally, this study uncovers interesting interactions between critical cell cycle regulatory elements that are only beginning to be understood.
Eccentric exercise: acute and chronic effects on healthy and diseased tendons
Authors: Kjaer Michael , Heinemeier Katja M.
Published: January 2014

Eccentric exercise can influence tendon mechanical properties and matrix protein synthesis. mRNA for collagen and regulatory factors thereof are upregulated in animal tendons, independent of muscular contraction type, supporting the view that tendon, compared with skeletal muscle, is less sensitive to differences in type and/or amount of mechanical stimulus with regard to expression of collagen, regulatory factors for collagen, and cross-link regulators. In overused (tendinopathic) human tendon, eccentric exercise training has a beneficial effect, but the mechanism by which this is elicited is unknown, and slow concentric loading appears to have similar beneficial effects. It may be that tendinopathic regions, as long as they are subjected to a certain magnitude of load at a slow speed, independent of whether this is eccentric or concentric in nature, can reestablish their normal tendon fibril alignment and cell morphology.
Premenopausal Plasma Ferritin Levels, HFE Polymorphisms, and Risk of Breast Cancer in the Nurses' Health Study II
Authors: Graff Rebecca E. , Cho Eunyoung , Lindström Sara , Kraft Peter , Willett Walter C. , Eliassen A. Heather
Published: January 2014

Background: Evidence from the Nurses' Health Study II (NHSII) suggests that red meat consumption is associated with increased breast cancer risk in premenopausal women. Iron may be responsible by contributing to oxidative stress or effects on immune function.

Methods: We conducted a case–control study nested within the NHSII, examining prediagnostic plasma ferritin (n = 795 cases, 795 controls), 15 hemochromatosis gene (HFE) single-nucleotide polymorphisms (SNP; n = 765 cases, 1,368 controls), and breast cancer risk. Cases were diagnosed after providing blood samples between 1996 and 1999. ORs and 95% confidence intervals (CI) were calculated for ferritin levels by conditional logistic regression and for HFE SNPs by unconditional logistic regression.

Results: We did not observe a significant association between ferritin levels and breast cancer (top vs. bottom quartile multivariate OR: 1.05; 95% CI, 0.77–1.45; PTrend = 0.77). Results did not change when restricted to women who were premenopausal at blood draw, and were similar when cases were examined by hormone receptor status, and menopausal status at diagnosis. No HFE SNPs were significantly associated with breast cancer in a log-additive manner. Among controls, ferritin levels were nominally associated with SNPs rs9366637 (PTrend = 0.04), rs6918586 (PTrend = 0.06), and rs13161 (PTrend = 0.07), but results did not remain significant after adjusting for multiple testing.

Conclusions: Ferritin levels and HFE SNPs were not associated with breast cancer risk in this population.

Impact: Components of red meat other than iron are likely responsible for its positive association with breast cancer in premenopausal women. Cancer Epidemiol Biomarkers Prev; 23(3); 516–24. ©2014 AACR.
Ontario's ColonCancerCheck: Results from Canada's First Province-Wide Colorectal Cancer Screening Program
Authors: Rabeneck Linda , Tinmouth Jill M. , Paszat Lawrence F. , Baxter Nancy N. , Marrett Loraine D. , Ruco Arlinda , Lewis Nancy , Gao Julia
Published: January 2014

Background: ColonCancerCheck (CCC), Canada's first province-wide colorectal cancer screening program, was publicly launched in Ontario in April 2008. The objective of this article is to report on key indicators of CCC Program performance since its inception.

Methods: The CCC Program recommends biennial guaiac-based fecal occult blood test (gFOBT) for persons 50 to 74 years of age at average risk for colorectal cancer and colonoscopy for those at increased risk (having one or more first-degree relatives with a diagnosis of colorectal cancer). Opportunistic screening with colonoscopy is available in Ontario. Five data sources were used to compute indicators of program performance during 2008 to 2011. The indicators computed were FOBT participation, overdue for screening, FOBT positivity, positive predictive value (PPV) of FOBT for colorectal cancer, diagnostic follow-up, and colorectal cancer detection rate.

Results: In 2011, FOBT participation was 29.8% and 46.8% of the target population was overdue for screening. FOBT positivity was higher among men (5.1%) than women (3.5%), and the PPV of FOBT for cancer was 4.3% in 2011. Follow-up colonoscopy within 6 months of a positive FOBT was completed by 74.6% of Program participants in 2011. The cancer detection rates for FOBT and for colonoscopy in those with a family history were 1.3 per 1,000 and 4.0 per 1,000, respectively, in 2011.

Conclusion: These results provide an early indication of Program performance and provide findings relevant to other organized colorectal cancer screening programs.

Impact: The greater cancer detection rate in those at increased risk due to family history who undergo colonoscopy screening suggests that a strategy of risk stratification will enhance the impact of FOBT-based screening programs. Cancer Epidemiol Biomarkers Prev; 23(3); 508–15. ©2014 AACR.
Molecular Classification of Malignant Pleural Mesothelioma: Identification of a Poor Prognosis Subgroup Linked to the Epithelial-to-Mesenchymal Transition
Authors: de Reyniès Aurélien , Jaurand Marie-Claude , Renier Annie , Couchy Gabrielle , Hysi Ilir , Elarouci Nabila , Galateau-Sallé Françoise , Copin Marie-Christine , Hofman Paul , Cazes Aurélie , Andujar Pascal , Imbeaud Sandrine , Petel Fabien , Pairon Jean-Claude , Le Pimpec-Barthes Francoise , Zucman-Rossi Jessica , Jean Didier
Published: January 2014

Purpose: Despite research efforts to develop more effective diagnostic and therapeutic approaches, malignant pleural mesothelioma (MPM) prognosis remains poor. The assessment of tumor response to therapy can be improved by a deeper phenotypical classification of the tumor, with emphasis on its clinico-biological heterogeneity. The identification of molecular profiles is a powerful approach to better define MPM subclasses and targeted therapies.

Experimental Design: Molecular subclasses were defined by transcriptomic microarray on 38 primary MPM cultures. A three-gene predictor, identified by quantitative reverse transcription PCR, was used to classify an independent series of 108 frozen tumor samples. Gene mutations were determined in BAP1, CDKN2A, CDKN2B, NF2, and TP53. Epithelial-to-mesenchymal transition (EMT) markers were studied at the mRNA and protein levels.

Results: Unsupervised hierarchical clustering on transcriptomic data defined two robust MPM subgroups (C1 and C2), closely related to prognosis and partly to histologic subtypes. All sarcomatoid/desmoplastic MPM were included in the C2 subgroup. Epithelioid MPM were found in both subgroups, with a worse survival prognosis in the C2 subgroup. This classification and its association with histologic subtypes and survival were validated in our independent series using the three-gene predictor. Similar subgroups were found after classification of other MPM series from transcriptomic public datasets. C1 subgroup exhibited more frequent BAP1 alterations. Pathway analysis revealed that EMT was differentially regulated between MPM subgroups. C2 subgroup is characterized by a mesenchymal phenotype.

Conclusions: A robust classification of MPM that defines two subgroups of epithelioid MPM, characterized by different molecular profiles, gene alterations, and survival outcomes, was established. Clin Cancer Res; 20(5); 1323–34. ©2014 AACR.
Smoking, p53 Mutation, and Lung Cancer
Authors: Gibbons Don L. , Byers Lauren A. , Kurie Jonathan M.
Published: January 2014

This issue marks the 50th anniversary of the release of the U.S. Surgeon General's Report on Smoking and Health. Perhaps no other singular event has done more to highlight the effects of smoking on the development of cancer. Tobacco exposure is the leading cause of cancers involving the oral cavity, conductive airways, and the lung. Owing to the many carcinogens in tobacco smoke, smoking-related malignancies have a high genome-wide burden of mutations, including in the gene encoding for p53. The p53 protein is the most frequently mutated tumor suppressor in cancer, responsible for a range of critical cellular functions that are compromised by the presence of a mutation. Herein, we review the epidemiologic connection between tobacco exposure and cancer, the molecular basis of p53 mutation in lung cancer, and the normal molecular and cellular roles of p53 that are abrogated during lung tumor development and progression as defined by in vitro and in vivo studies. We also consider the therapeutic potential of targeting mutant p53 in a clinical setting based upon the cellular role of mutant p53 and data from genetic murine models. Mol Cancer Res; 12(1); 3–13. ©2014 AACR.