bluuebunny/crossref_metadata_2025 huggingface dataset:
Unexpected nondenitrifier nitrous oxide reductase gene diversity and abundance in soils
Authors: Sanford Robert A. , Wagner Darlene D. , Wu Qingzhong , Chee-Sanford Joanne C. , Thomas Sara H. , Cruz-García Claribel , Rodríguez Gina , Massol-Deyá Arturo , Krishnani Kishore K. , Ritalahti Kirsti M. , Nissen Silke , Konstantinidis Konstantinos T. , Löffler Frank E.
Published: November 2012

Agricultural and industrial practices more than doubled the intrinsic rate of terrestrial N fixation over the past century with drastic consequences, including increased atmospheric nitrous oxide (N
2
O) concentrations. N
2
O is a potent greenhouse gas and contributor to ozone layer destruction, and its release from fixed N is almost entirely controlled by microbial activities. Mitigation of N
2
O emissions to the atmosphere has been attributed exclusively to denitrifiers possessing NosZ, the enzyme system catalyzing N
2
O to N
2
reduction. We demonstrate that diverse microbial taxa possess divergent
nos
clusters with genes that are related yet evolutionarily distinct from the typical
nos
genes of denitirifers.
nos
clusters with atypical
nosZ
occur in Bacteria and Archaea that denitrify (44% of genomes), do not possess other denitrification genes (56%), or perform dissimilatory nitrate reduction to ammonium (DNRA; (31%). Experiments with the DNRA soil bacterium
Anaeromyxobacter dehalogenans
demonstrated that the atypical NosZ is an effective N
2
O reductase, and PCR-based surveys suggested that atypical
nosZ
are abundant in terrestrial environments. Bioinformatic analyses revealed that atypical
nos
clusters possess distinctive regulatory and functional components (e.g., Sec vs. Tat secretion pathway in typical
nos
), and that previous
nosZ
-targeted PCR primers do not capture the atypical
nosZ
diversity. Collectively, our results suggest that nondenitrifying populations with a broad range of metabolisms and habitats are potentially significant contributors to N
2
O consumption. Apparently, a large, previously unrecognized group of environmental
nosZ
has not been accounted for, and characterizing their contributions to N
2
O consumption will advance understanding of the ecological controls on N
2
O emissions and lead to refined greenhouse gas flux models.
Hydroperiod regime controls the organization of plant species in wetlands
Authors: Foti Romano , del Jesus Manuel , Rinaldo Andrea , Rodriguez-Iturbe Ignacio
Published: November 2012

With urban, agricultural, and industrial needs growing throughout the past decades, wetland ecosystems have experienced profound changes. Most critically, the biodiversity of wetlands is intimately linked to its hydrologic dynamics, which in turn are being drastically altered by ongoing climate changes. Hydroperiod regimes, e.g., percentage of time a site is inundated, exert critical control in the creation of niches for different plant species in wetlands. However, the spatial signatures of the organization of plant species in wetlands and how the different drivers interact to yield such signatures are unknown. Focusing on Everglades National Park (ENP) in Florida, we show here that cluster sizes of each species follow a power law probability distribution and that such clusters have well-defined fractal characteristics. Moreover, we individuate and model those signatures via the interplay between global forcings arising from the hydroperiod regime and local controls exerted by neighboring vegetation. With power law clustering often associated with systems near critical transitions, our findings are highly relevant for the management of wetland ecosystems. In addition, our results show that changes in climate and land management have a quantifiable predictable impact on the type of vegetation and its spatial organization in wetlands.
DLocalMotif: a discriminative approach for discovering local motifs in protein sequences
Authors: Mehdi Ahmed M. , Sehgal Muhammad Shoaib B. , Kobe Bostjan , Bailey Timothy L. , Bodén Mikael
Published: November 2012

Motivation: Local motifs are patterns of DNA or protein sequences that occur within a sequence interval relative to a biologically defined anchor or landmark. Current protein motif discovery methods do not adequately consider such constraints to identify biologically significant motifs that are only weakly over-represented but spatially confined. Using negatives, i.e. sequences known to not contain a local motif, can further increase the specificity of their discovery.

Results: This article introduces the method DLocalMotif that makes use of positional information and negative data for local motif discovery in protein sequences. DLocalMotif combines three scoring functions, measuring degrees of motif over-representation, entropy and spatial confinement, specifically designed to discriminatively exploit the availability of negative data. The method is shown to outperform current methods that use only a subset of these motif characteristics. We apply the method to several biological datasets. The analysis of peroxisomal targeting signals uncovers several novel motifs that occur immediately upstream of the dominant peroxisomal targeting signal-1 signal. The analysis of proline-tyrosine nuclear localization signals uncovers multiple novel motifs that overlap with C2H2 zinc finger domains. We also evaluate the method on classical nuclear localization signals and endoplasmic reticulum retention signals and find that DLocalMotif successfully recovers biologically relevant sequence properties.

Availability:  http://bioinf.scmb.uq.edu.au/dlocalmotif/

Contact:  m.boden@uq.edu.au

Supplementary information:  Supplementary data are available at Bioinformatics online.
Updated meta‐analysis on antithrombotic therapy in patients with heart failure and sinus rhythm
Authors: Hopper Ingrid , Skiba Marina , Krum Henry
Published: November 2012

Aim

Heart failure (HF) is a prothrombotic state, but current evidence does not support the routine use of aspirin, antiplatelet agents, or anticoagulation in these patients in sinus rhythm (SR). We conducted an updated meta‐analysis comparing these medications on outcomes in HF.

Methods and results

All randomized trials in patients with chronic HF and reduced ejection fraction (HFREF) in sinus rhythm (SR; n >100), in which the effect of aspirin, antiplatelet agents, or anticoagulants was determined, were prospectively evaluated. Four trials met the entry criteria. Intervention time was 28 months. No difference in all‐cause mortality was seen when aspirin was compared with warfarin [n = 3701, relative risk (RR) 1.00, 95% confidence interval (CI) 0.88–1.13, P = 0.94]. Compared with aspirin, significantly fewer strokes were seen with warfarin (n = 3701, RR 0.59, 95% CI 0.41–0.85, P = 0.004), and fewer fatal and non‐fatal ischaemic strokes (n = 3368, RR 0.48, 95% CI 0.32–0.73, P = 0.0006). Warfarin doubled the risk of major haemorrhage compared with aspirin (n = 3701, RR 2.02, 95% CI 1.45–2.80, P < 0.0001); however, intracranial haemorrhage was rare. There was no significant difference in HF hospitalizations with aspirin vs. warfarin (n = 3701, RR 1.16, 95% CI 0.79–1.71, P = 0.45).

Conclusion

With warfarin compared with aspirin in HFREF in SR, significant reductions in stroke risk were observed but no mortality benefit was seen. Major haemorrhage doubled but intracranial haemorrhage was rare. These findings suggest that overall the benefit of warfarin in HFREF in SR outweighs the risk. Aspirin use did not increase HF hospitalization as has been previously suggested.
Class I PI3K-mediated Akt and ERK signals play a critical role in FcεRI-induced degranulation in mast cells
Authors: Takayama Gensuke , Ohtani Masashi , Minowa Akiko , Matsuda Satoshi , Koyasu Shigeo
Published: November 2012

Class IA and IB phosphoinositide 3-kinases (PI3Ks) have been shown to regulate mast cell functions such as proliferation, development, survival and degranulation, but the functional redundancy between these two PI3K signaling pathways in mast cells remains unclear. Here, we have generated mice deficient in both class IA regulatory subunit p85α and class IB catalytic subunit p110γ, and show that p85α −/− p110γ −/− mice exhibit a more severe defect in mast cell development than single-knockout mice. In addition, the in vivo passive cutaneous anaphylaxis reaction of p85α −/− p110γ −/− mice was nearly completely abrogated, whereas single-knockout mice exhibit just marginal reduction. Pharmacological inactivation of Akt in wild-type bone marrow-derived mast cells (BMMCs) led to partial reduction of degranulation, while over-expression of a constitutively active Akt partially restored the impaired degranulation in p85α −/− p110γ −/− BMMCs. We also found that the extracellular signal-regulated kinase (ERK) signaling pathway was activated in a PI3K-dependent manner upon FcεRI stimulation and that simultaneous inhibition of Akt and ERK resulted in nearly complete blockade of FcεRI-induced degranulation. Our data provide evidence that Akt and ERK pathways play redundant roles in FcεRI-induced degranulation.
Differential localization and function of antibody-forming cells responsive to inactivated or live-attenuated influenza virus vaccines
Authors: Sealy Robert , Webby Richard J. , Crumpton Jeri C. , Hurwitz Julia L.
Published: November 2012

Currently, there are two different types of licensed influenza virus vaccines available in the USA, the live attenuated cold-adapted vaccine and the inactivated vaccine. Children greater than 2 years of age and adults younger than 50 years (apart from those suffering from immunodeficiencies or lung disease) may choose between the two vaccines. Previous studies have shown that both vaccines elicit significant serum antibody responses. However, comprehensive analyses of antibody-forming cells (AFCs) in the upper respiratory tract (URT), the critical site of pathogen entry, have been lacking. We therefore compared influenza virus-specific antibody and AFC activities in systemic and mucosal tissues following immunizations of cotton rats with inactivated or live-attenuated vaccines, including vaccines from the 2009-10 and 2010-11 seasons. Results demonstrated that inactivated and live-attenuated vaccines induced virus-specific AFCs, but patterns of residence and function were highly disparate. The inactivated vaccine elicited AFCs predominantly in the spleen and bone marrow; IgG was the main isotype. In contrast, the live attenuated vaccine elicited acute and long-sustained AFC responses in the diffuse nasal-associated lymphoid tissue (d-NALT) and lung, with IgA being the predominant isotype. The appearance of these d-NALT URT responses was confirmed by a similar study of the 2009–10 live attenuated vaccine in ferrets. Data emphasize that the inactivated and live-attenuated vaccines that are each capable of protecting humans from influenza virus disease do so by very different modes of immune surveillance.
The Interdependence between Rainfall and Temperature: Copula Analyses
Authors: Cong Rong-Gang , Brady Mark
Published: November 2012

Rainfall and temperature are important climatic inputs for agricultural production, especially in the context of climate change. However, accurate analysis and simulation of the joint distribution of rainfall and temperature are difficult due to possible interdependence between them. As one possible approach to this problem, five families of copula models are employed to model the interdependence between rainfall and temperature. Scania is a leading agricultural province in Sweden and is affected by a maritime climate. Historical climatic data for Scania is used to demonstrate the modeling process. Heteroscedasticity and autocorrelation of sample data are also considered to eliminate the possibility of observation error. The results indicate that for Scania there are negative correlations between rainfall and temperature for the months from April to July and September. The student copula is found to be most suitable to model the bivariate distribution of rainfall and temperature based on the Akaike information criterion (AIC) and Bayesian information criterion (BIC). Using the student copula, we simulate temperature and rainfall simultaneously. The resulting models can be integrated with research on agricultural production and planning to study the effects of changing climate on crop yields.
Long‐term (12‐month) improvement in meibomian gland function and reduced dry eye symptoms with a single thermal pulsation treatment
Authors: Greiner Jack V
Published: November 2012

Purpose

To determine the 1‐year post‐treatment dry eye status of subjects with meibomian gland dysfunction and dry eye symptoms after receiving a single LipiFlow Thermal Pulsation System treatment.

Design

Single‐centre, prospective, observational, open‐label, 1‐month‐registered clinical trial with a 1‐year follow‐up examination.

Participants

Patients with evaporative dry eye disease with meibomian gland dysfunction and dry eye symptoms who had participated in the registered 1‐month clinical trial.

Methods

Eighteen of 30 subjects initially enrolled were able to return for a 1‐year follow‐up. Both eyes of all patients were treated with a single 12‐min treatment using the LipiFlow Thermal Pulsation System. Meibomian gland function, tear break‐up time and dry eye symptoms were measured. Data are presented for pretreatment (baseline), and 1‐month and 1‐year post‐treatment.

Main Outcome Measures

Meibomian gland secretion scores, and tear break‐up time and dry eye symptoms.

Results

Significant improvement in meibomian gland secretion scores from baseline measurements (4.0 ± 3.4) to 1‐month post‐treatment (11.3 ± 4.7; P < 0.0005) was maintained at 1‐year (7.3 ± 4.6; P < 0.05). Baseline tear break‐up time (4.9 ± 3.0) was significantly increased at 1‐month (9.5 ± 6.9; P < 0.05); however, this improvement was no longer evident at 1‐year post‐treatment (6.0 ± 4.4). The significant improvement in symptom scores on Ocular Surface Disease Index and Standard Patient Evaluation of Eye Dryness questionnaires observed at 1‐month (P < 0.0005) was maintained at 1‐year (Ocular Surface Disease Index [P < 0.05]; Standard Patient Evaluation of Eye Dryness [P < 0.0005]).

Conclusion

A single 12‐min treatment with the Lipi Flow Thermal Pulsation System offers an effective treatment for evaporative dry eye and meibomian gland dysfunction resulting in significant and sustained improvement in signs and symptoms for up to 1 year.
A homozygous mutation of voltage‐gated sodium channel βI gene SCN1B in a patient with Dravet syndrome
Authors: Ogiwara Ikuo , Nakayama Tojo , Yamagata Tetsushi , Ohtani Hideyuki , Mazaki Emi , Tsuchiya Shigeru , Inoue Yushi , Yamakawa Kazuhiro
Published: November 2012

Dravet syndrome is a severe form of epileptic encephalopathy characterized by early onset epileptic seizures followed by ataxia and cognitive decline. Approximately 80% of patients with Dravet syndrome have been associated with heterozygous mutations in SCN1A gene encoding voltage‐gated sodium channel (VGSC) αI subunit, whereas a homozygous mutation (p.Arg125Cys) of SCN1B gene encoding VGSC βI subunit was recently described in a patient with Dravet syndrome. To further examine the involvement of homozygous SCN1B mutations in the etiology of Dravet syndrome, we performed mutational analyses on SCN1B in 286 patients with epileptic disorders, including 67 patients with Dravet syndrome who have been negative for SCN1A and SCN2A mutations. In the cohort, we found one additional homozygous mutation (p.Ile106Phe) in a patient with Dravet syndrome. The identified homozygous SCN1B mutations indicate that SCN1B is an etiologic candidate underlying Dravet syndrome.
Medicine use and medicine-related problems experienced by ethnic minority patients in the United Kingdom: a review
Authors: Alhomoud Faten , Dhillon Soraya , Aslanpour Zoe , Smith Felicity
Published: November 2012

Objective

The aim of this review was to establish type(s) and possible cause(s) of medicine-related problems (MRPs) experienced by ethnic minorities in the UK and to identify recommendations to support these patients in the effective use of medicines.

Methods

A systematic search of studies related to problems with medicine use experienced by ethnic minorities in the UK was performed using the following databases: PubMed, Embase, International Pharmaceutical Abstract and Scopus from 1990 to 2011. A hand search for relevant citations and key journals was also performed.

Key findings

Fifteen studies were found. The MRPs identified across studies included lack of information, problems with not taking medicines as advised, concern of dependency or side effects, lack of regular monitoring and review, risk of adverse drug reactions, adverse events and problems in accessing healthcare services. Many problems are common in other groups, however, studies examining possible explanatory factors discussed how the cultural and religious beliefs, previous experiences, different expectations, language and communication barriers, lack of knowledge of the healthcare services and underestimating patients' desire for information may contribute to the problems. Some of the recommendations were made based on the problems that were found, but these have not been evaluated.

Conclusions

Little evidence is known of what influences MRPs among ethnic minorities, despite the increased diversification of populations in countries throughout the world. To support their entire populations in the use of medicines, we have to ensure that we understand their different perspectives and needs regarding the effective use of medicines.
Role of immediate radical cystectomy in the treatment of patients with residual T1 bladder cancer on restaging transurethral resection
Authors: Sternberg Itay A. , Keren Paz Gal E. , Chen Ling Y. , Herr Harry W. , Dalbagni Guido
Published: November 2012

What's known on the subject? and What does the study add?

Bladder cancer patients with lamina propria invasion (T1 disease) and residual T1 disease on restaging transurethral resection of bladder tumour (re‐TURBT) are at a very high risk for recurrence and progression. Despite this risk, most patients are treated with a bladder preserving approach and not immediate radical cystectomy (RC).

In this study we have shown that a quarter of patients with T1 bladder cancer and residual T1 on re‐TURBT who are treated with immediate RC are found to have carcinoma invading bladder muscle at RC and 5% have lymph node metastases. We have also found that >30% of patients treated with deferred RC after initial bladder‐preserving therapy harbour carcinoma invading bladder muscle and almost 20% of these patients have lymph node metastases. Thus, immediate RC should be considered in all patients with T1 bladder cancer and residual T1 on re‐TURBT.

Objective

To report the overall survival (OS) and cancer‐specific survival (CSS) of patients with residual T1 bladder cancer on restaging transurethral resection of the bladder tumour (re‐TURBT).

Materials and Methods

We performed a retrospective review of 150 evaluable patients treated for T1 bladder cancer with residual T1 disease found on re‐TURBT between 1990 and 2007.

Patients were treated with immediate radical cystectomy (RC) or a bladder‐preserving approach (deferred or no RC).

A univariate Cox proportional hazards regression model was used to test the association between treatment approach and survival.

Results

Residual T1 bladder cancer was found in 150 evaluable patients, of whom 57 received immediate RC and 93 were treated with a bladder‐preserving approach.

Fourteen out of 57 patients receiving immediate RC and 8/26 patients receiving deferred RC had carcinoma invading bladder muscle in the RC specimen. Three out of 57 and 5/26 patients had lymph node metastases in the RC specimen.

Median follow‐up was 3.74 years.

Thirty‐nine patients died during follow‐up, 16 from bladder cancer. There was no significant association between immediate RC and CSS (hazard ratio [HR] 1.15, 95% confidence interval [CI] 0.43–3.09, P = 0.8) or OS (HR 0.79, 95% CI 0.4–1.53, P = 0.5).

Conclusions

Because of the low number of events we cannot conclude whether RC offers a survival advantage in patients with residual T1 bladder cancer on re‐TURBT.

Since a quarter of patients had carcinoma invading bladder muscle, RC should be considered in these patients.

A larger, preferably randomized, study with longer follow‐up is needed.
Does Couple and Relationship Education Work for Individuals in Stepfamilies? A Meta‐analytic Study
Authors: Lucier‐Greer Mallory , Adler‐Baeder Francesca
Published: November 2012

Recent meta‐analytic efforts have documented how couple and relationship education (CRE) programs promote healthy relationship and family functioning. The current meta‐analysis contributes to this body of literature by examining stepfamily couples, an at‐risk, subpopulation of participants, and assessing the effectiveness of CRE programs for individuals in these relationships. Findings are aggregated from 14 evaluation studies of CRE programs designed for stepcouples. Analyses examine effects by study design (i.e., comparison‐group and one‐group/pre‐post) and within specific domains (i.e., family, parental, and couple functioning). The interventions have, on average, small effects overall (comparison‐group: d = .20; one‐group/pre‐post: d = .23), and slightly larger effects in family and parental functioning when examining specific outcomes (d = .20 to .35). An examination of effectiveness over time reveals that earlier studies (i.e., 1980s and 1990s) show larger effects than more recent studies. Implications for CRE programs for stepfamilies and evaluation needs are discussed.
Examining the Early Evidence for Self‐directed Marriage and Relationship Education: A Meta‐analytic Study
Authors: McAllister Shelece , Duncan Stephen F. , Hawkins Alan J.
Published: November 2012

This meta‐analysis examines the efficacy of self‐directed marriage and relationship education (MRE) programs on relationship quality and communication skills. Programs combining traditional face‐to‐face learning with self‐directed elements are also examined, and traditional programs' effectiveness is included as a comparison point. Sixteen studies focused on self‐directed interventions; 13 studies focused on programs combining self‐directed and traditional components. For self‐directed programs, the effect size for relationship quality was small and not significant (d = .032, ns); a small, significant effect size was found for communication skills (d = .160, p < .05). For blended programs, effect sizes were significant for relationship quality (d = .429, p < .01) and communication skills (d = .715, p < .05), and blended programs produced larger effect sizes than traditional programs.
Suits you? A qualitative study exploring preferences regarding the tailoring of consumer medicines information
Authors: Dickinson Rebecca , Hamrosi Kim , Knapp Peter , Aslani Parisa , Sowter Julie , Krass Ines , Raynor David K
Published: November 2012

Objectives

To explore participants' opinions and preferences on tailored written medicines information.

Methods

Forty-five participants were recruited to eight focus groups, run concurrently in Australia (23 participants in four groups) and the UK (22 participants in four groups). Participants were provided with exemplar leaflets for a cardiovascular medicine based on the angiotensin-converting enzyme (ACE) inhibitor ramipril, which was tailored for a man aged 55 with hypertension. Reference to other indications of the medicine, children's doses, pregnancy and breast-feeding information were removed. A topic guide directed the discussion and explored preferences and opinions on tailored leaflets. Focus group discussions were recorded, transcribed verbatim and content analysed using adapted cross-case study analysis.

Key findings

Participants welcomed the concept of tailored information, desiring shorter and more relevant information. Information tailored to their condition or disease was most sought-after, followed by tailoring by age or gender. However, some participants voiced concerns about the potential for the wrong information being given to patients who would be unable to recognise that it was incorrect. Other concerns included how tailoring might impact upon the quality of information available and the feasibility of delivery, especially regarding the legal implications (Australia) and the cost (UK). A key finding was the participants' desire for a truly individualised approach to tailoring medicines information, as opposed to the generalised tailored information provided in the study. Participants said they would value having spoken communication with a healthcare professional at the same time as they received tailored leaflets.

Conclusions

Most participants welcomed tailored leaflets but overall valued a more personalised approach than the generalised tailored information we provided. Despite concerns about quality and delivery, many felt tailoring written medicines information could improve the relevance of the information to the individual and potentially encourage them to value it.
DNA damage induces nucleoid compaction via the Mre11‐Rad50 complex in the archaeon Haloferax volcanii
Authors: Delmas Stéphane , Duggin Iain G. , Allers Thorsten
Published: November 2012

In prokaryotes the genome is organized in a dynamic structure called the nucleoid, which is embedded in the cytoplasm. We show here that in the archaeon Haloferax volcanii, compaction and reorganization of the nucleoid is induced by stresses that damage the genome or interfere with its replication. The fraction of cells exhibiting nucleoid compaction was proportional to the dose of the DNA damaging agent, and results obtained in cells defective for nucleotide excision repair suggest that breakage of DNA strands triggers reorganization of the nucleoid. We observed that compaction depends on the Mre11‐Rad50 complex, suggesting a link to DNA double‐strand break repair. However, compaction was observed in a radA mutant, indicating that the role of Mre11‐Rad50 in nucleoid reorganisation is independent of homologous recombination. We therefore propose that nucleoid compaction is part of a DNA damage response that accelerates cell recovery by helping DNA repair proteins to locate their targets, and facilitating the search for intact DNA sequences during homologous recombination.
Immunoglobulin G4‐related lung disease: Clinicoradiological and pathological features
Authors: Matsui Shoko , Hebisawa Akira , Sakai Fumikazu , Yamamoto Horoshi , Terasaki Yasuhiro , Kurihara Yasuyuki , Waseda Yuko , Kawamura Tetsuji , Miyashita Tomoko , Inoue Hiromasa , Hata Norihiko , Masubuchi Hiroaki , Sugino Keishi , Kishi Jun , Kobayashi Hideo , Usui Yutaka , Komazaki Yoshitoshi , Kawabata Yoshinori , Ogura Takashi
Published: November 2012

Background and objective

Immunoglobulin G4 (IgG4)‐related disease is a multi‐organ disorder that can include the lungs. IgG4‐related lung disease can present in various forms; the clinical, radiological and pathological features of patients with this disease have been assessed.

Methods

Forty‐eight patients suspected of having IgG4‐related lung disease, with a high serum concentration of IgG4 and abundant IgG4‐positive plasma cell infiltration into the intrathoracic organs, were retrospectively evaluated. Their clinical features, chest imaging findings and pathological findings were examined, with final diagnoses made by an open panel conference.

Results

Of the 48 patients, 18 with extrathoracic manifestations were diagnosed as having IgG4‐related lung disease. Most of these patients were middle‐aged to elderly men. IgG4‐related lung disease was characterized by high serum concentrations of IgG and IgG4, normal white blood cell count and serum C‐reactive protein concentration and a good response to corticosteroids. Common radiological findings included mediastinal lymphadenopathy and thickening of the perilymphatic interstitium, with or without subpleural and/or peribronchovascular consolidation. Pathological examination showed massive lymphoplasmacytic infiltration with fibrosis in and around the lymphatic routes, with distribution well correlated with radiological manifestations.

Conclusions

The findings suggest that the intrathoracic manifestations of IgG4‐related lung disease develop through lymphatic routes of the lungs and show various clinical characteristics. Because some lymphoproliferative disorders show similar findings, the correlation of clinicoradiological and pathological characteristics is crucial for the diagnosis of IgG4‐related lung disease.
Social Competence in Preschool Children: Replication of Results and Clarification of a Hierarchical Measurement Model
Authors: Santos António J. , Peceguina Inês , Daniel João R. , Shin Nana , Vaughn Brian E.
Published: November 2012

This study tested assumptions and conclusions reached in an earlier confirmatory factor analysis (CFA) study of the social competence (SC) construct for preschool children. Two samples (total N = 408; a new Portuguese sample and one from US samples that had participated in the original study) contributed data. Seven SC indicators were tested for mean differences across age, sex, and sample. Significant sex differences were found for peer acceptance (favoring girls) and for initiating affectively neutral interactions (boys had higher rates), and the sex by sample interaction also was significant for initiating interactions (i.e., effect significant only in the Portuguese sample). In CFAs, the hypothesized structure of SC fits the data and was invariant across sample and age within sample in both measurement and structural tests. The model was invariant at the measurement level for sex within sample tests, but not at the structural level. The results replicate and extend understandings of SC reported in the original study.
Effects of glutamine supplementation on muscle function and stress responses in a mouse model of spinal cord injury
Authors: Chamney Carissa , Godar Michelle , Garrigan Ethan , Huey Kimberly A.
Published: November 2012

New Findings

What is the central question of this study?

The beneficial effects of glutamine supplementation are related to heat shock protein induction and reduced inflammation, but its effects on skeletal muscle function, heat shock protein expression and inflammatory factors after spinal cord injury (SCI) are unknown.

What is the main finding and its importance?

Using a mouse model of SCI, glutamine supplementation for 7 days following SCI was associated with significant improvements in muscle force, fatigue resistance and maintenance of contractile proteins versus placebo. Lower protein levels of heat shock proteins, interleukin‐6 and tumour necrosis factor‐α after SCI suggest that reduced stress is experienced by skeletal muscles with glutamine. The findings support glutamine as a therapeutic intervention to moderate inflammation and accelerate recovery of muscle function after SCI.

Spinal cord injury (SCI) results in loss of muscle function due to rapid breakdown of contractile proteins. Glutamine supplementation improves clinical outcomes, but its effects on muscle function after SCI are unknown. The benefits of glutamine in non‐skeletal muscle tissues involve elevated heat shock protein (Hsp)70 and Hsp25, but the muscle response may differ because it is the largest contributor to plasma glutamine. We tested the hypothesis that glutamine preserves muscle function after SCI and that this is associated with increased heat shock protein and reduced inflammatory factors, interleukin‐6 (IL‐6) and tumour necrosis factor‐α (TNFα). Changes in plantarflexor force, fatigability and total myofibrillar, Hsp70, Hsp25, IL‐6 and TNFα muscle protein levels were measured 7 days after sham or spinal cord transection surgery in mice receiving daily placebo or glutamine. Compared with placebo, after SCI glutamine significantly attenuated the reductions in maximal isometric force (0.22 ± 0.01 versus 0.31 ± 0.03 N, respectively) and fatigue resistance (34 ± 4 versus 59 ± 4% of initial force, respectively). Glutamine significantly ameliorated the loss of myofibrillar protein with spinal cord transection. Spinal cord transection was associated with decreased Hsp70 and Hsp25 with glutamine only (45 ± 3 and 44 ± 5% of placebo, respectively). Glutamine significantly reduced spinal cord transection‐associated increases in IL‐6 and TNFα compared with placebo (38 ± 6 and 37 ± 8% of placebo, respectively). Functionally, early reductions in contractile protein, force and fatigue resistance after SCI were reversed with glutamine. Spinal cord transection‐associated reductions in Hsp70, Hsp25, IL‐6 and TNFα with glutamine versus placebo suggest lower stress in the muscle, possibly related to a reduced need to produce glutamine. These findings support glutamine as a therapeutic intervention to accelerate recovery of muscle function after SCI.
Ca2+‐dependent proteolysis of junctophilin‐1 and junctophilin‐2 in skeletal and cardiac muscle
Authors: Murphy R. M. , Dutka T. L. , Horvath D. , Bell J. R. , Delbridge L. M. , Lamb G. D.
Published: November 2012

Key points

If skeletal muscle fibres are subjected to excessive activation, or stretched whilst contracting, they subsequently display long‐term reductions in their force response, apparently due in part to structural or molecular changes at the triad junction, where excitation of the surface membrane triggers Ca2+ release from the internal Ca2+ store.

The changes appear to be due to excessive or prolonged increases in intracellular Ca2+ levels, which activate Ca2+‐dependent proteases known as calpains, but their target proteins are currently unknown.

This study shows that excessive muscle stimulation, or directly raising intracellular Ca2+ levels, causes calpain activation in tandem with proteolysis of junctophilin, a key protein thought to hold the triad junction together.

Proteolysis of junctophilin is also seen in muscle of mice with muscular dystrophy and in cardiac muscle following ischaemic damage.

Proteolysis of junctophilin may be a major factor causing muscle weakness and cardiac dysfunction in a range of circumstances.

Abstract  Excessive increases in intracellular [Ca2+] in skeletal muscle fibres cause failure of excitation–contraction coupling by disrupting communication between the dihydropyridine receptors in the transverse tubular system and the Ca2+ release channels (RyRs) in the sarcoplasmic reticulum (SR), but the exact mechanism is unknown. Previous work suggested a possible role of Ca2+‐dependent proteolysis in this uncoupling process but found no proteolysis of the dihydropyridine receptors, RyRs or triadin. Junctophilin‐1 (JP1; ∼90 kDa) stabilizes close apposition of the transverse tubular system and SR membranes in adult skeletal muscle; its C‐terminal end is embedded in the SR and its N‐terminal associates with the transverse tubular system membrane. Exposure of skeletal muscle homogenates to precisely set [Ca2+] revealed that JP1 undergoes Ca2+‐dependent proteolysis over the physiological [Ca2+] range in tandem with autolytic activation of endogenous μ‐calpain. Cleavage of JP1 occurs close to the C‐terminal, yielding a ∼75 kDa diffusible fragment and a fixed ∼15 kDa fragment. Depolarization‐induced force responses in rat skinned fibres were abolished following 1 min exposure to 40 μm Ca2+, with accompanying loss of full‐length JP1. Supraphysiological stimulation of rat skeletal muscle in vitro by repeated tetanic stimulation in 30 mm caffeine also produced marked proteolysis of JP1 (and not RyR1). In dystrophic mdx mice, JP1 proteolysis is seen in limb muscles at 4 and not at 10 weeks of age. Junctophilin‐2 in cardiac and skeletal muscle also undergoes Ca2+‐dependent proteolysis, and junctophilin‐2 levels are reduced following cardiac ischaemia–reperfusion. Junctophilin proteolysis may contribute to skeletal muscle weakness and cardiac dysfunction in a range of circumstances.
Research on Hybrid Process of Laser Drilling With Jet Electrochemical Machining
Authors: Yuan Lixin , Xu Jiawen , Zhao Jianshe , Zhang Hua
Published: November 2012

The spatter and recast layer are main metallurgical defects in laser drilling (LD). Combining jet electrochemical process with laser can minimize such defects. The hybrid process is called electrolysis jet guided laser drilling (EJGLD). The presented experiment results show that the electrolyte jet can guide and transmit laser to the workpiece for drilling; and the electrochemical dissolution can effectively reduce spatter and recast layer. This paper introduces work on how to optimize this hybrid process, in particular, how to set a proper distance between the cathode and workpiece for best efficiency and accuracy.
Servo System Identification Using Relay Feedback: A Time-Domain Approach
Authors: Liu Jia , Wu Jianhua , Xiong Zhenhua , Zhu Xiangyang
Published: November 2012

In servo systems, the dynamic characteristics may not only differ between axes but may also vary with moving directions for a single axis. The direction dependent characteristics would result in additional tracking or positioning error and degrade the performance of the system. In this paper, relay feedback tests are successfully applied to identify the dynamic characteristics in servo systems. A time-domain method is used to analyze the relay feedback other than the conventional describing function (DF) method. The time-domain method utilizes the same oscillation parameters (oscillation amplitude and half period) as the DF method for system identification. However, the time-domain method takes several advantages: First, the direction dependent characteristics of the system can be properly revealed; second, no approximation is made in this method, so that the exact expressions of the amplitudes and the periods of the limit cycles under relay feedback can be derived. A feedforward compensator is then designed using the estimated values of the system parameters. Simulation results show that the identification results through the time-domain method are more accurate than the DF method and are more robust under different relay parameters. Real time experiments show that the feedforward compensator designed by the proposed method compensates disturbances related to the direction and hence improves the tracking and positioning performance of the servo system.
Study of Dimensional Repeatability and Fatigue Life for Deformation Machining Bending Mode
Authors: Agrawal A. , Ziegert J. , Smith S. , Woody B. , Cao J.
Published: November 2012

Deformation machining (DM) is a hybrid process which combines two emerging manufacturing processes, machining of thin structures and single-point incremental forming (SPIF). This hybrid process enables the creation of structures that have geometries that would be difficult or impossible to create using any either process alone. A comprehensive study of DM bending mode components has been carried out in this paper by studying their dimensional repeatability and fatigue life and comparing these with similar components fabricated with sheet metal. Experimental studies have been performed for part features created by the DM “bending mode” process, in which a thin vertical wall is machined on the part, and then incrementally bent with a single-point forming tool. The dimensional repeatability of DM components is compared with sheet metal components made by single-point incremental forming and conventional bending in a press brake [Agrawal et al., 2010, “Comparison of Dimensional Repeatability of Deformation Machined Components With Sheet Metal Components,” North American Manufacturing Research Conference, NAMRC 38, Transactions of NAMRI/SME, Vol. 38, pp. 571–576]. The results of this study indicate that the DM process is not capable of holding tolerances as tight as a standard milling process. This may be due to local variations in material properties that influence the yield strength and resulting springback. However, thin components created by DM are more repeatable than similar components created from sheet metal using SPIF, but less repeatable than components created by conventional bending of sheet metal. The second objective of the present work is to investigate whether components fabricated using the DM process can be considered for fatigue critical applications [Megahed et al., 1996, “Low-Cycle Fatigue in Rotating Cantilever Under Bending I: Theoretical Analysis,” Int. J. Fatigue, 18(6), pp. 401–412; Khalid et al., 2007, “Bending Fatigue Behavior of Hybrid Aluminum/Composite Drive Shafts,” Mater. Des., 28, pp. 329–334]. Studies were performed to experimentally compare the fatigue life of components fabricated by DM process with sheet metal components made by single-point incremental forming and conventional bending. Results of the study indicate that sheet metal SPIF components under the present loading conditions have significantly longer fatigue life of approximately 3900–5500 cycles, compared to DM and sheet metal conventionally bent components with approximately equal fatigue life of 2200–3900 cycles.
Finite Element Analysis of the Variation in Residual Stress Distribution in Laser Shock Peening of Steels
Authors: Voothaluru Rohit , Richard Liu C. , Cheng Gary J.
Published: November 2012

Laser shock peening (LSP) is a surface treatment technique similar to conventional shot peening. The laser induced plasma causes plastic deformations and compressive residual stresses that are useful for developing improved properties in the fields of resistance to fatigue, wear or stress corrosion cracking. The actual distribution of residual stresses is extremely important while designing for improved fatigue life using laser shock peening, as fatigue cracks would initiate from the weakest point in the structure. In this paper, the variations in distribution of residual stresses due to laser shock peening are studied with a focus on two materials, annealed 1053 and hardened 52100 AISI steels. A 3D finite element model was developed to study the actual distributions of the residual stresses due to laser shock peening. The effect of hardness on the distribution of the residual stresses and the presence of tensile residual stresses in the surrounding regions of the impact is analyzed. Much larger variations in the residual stress distributions were observed in case of the 1053 steel as compared to hardened 52100 steel. A comprehensive analysis of the simulation results was performed in order to address and explain this behavior. It was observed that the extent of overlap would also affect the variations in the residual stress distributions. The tensile residual stresses present in the areas surrounding the shocked region were also analyzed based upon the extent of overlap and the hardness of the material. It was observed that the ratio of peak tensile to compressive residual stresses developed in 1053 steel was much higher as compared to that in the hardened 52100 steel.
A Simple High-Performance Liquid Chromatography Method for Simultaneous Determination of Three Triazole Antifungals in Human Plasma
Authors: Zhang Mei , Moore Grant A. , Barclay Murray L. , Begg Evan J.
Published: November 2012

A rapid and simple high-performance liquid chromatography (HPLC) assay was developed for the simultaneous determination of three triazole antifungals (voriconazole, posaconazole, and itraconazole and the metabolite of itraconazole, hydroxyitraconazole) in human plasma. Sample preparation involved a simple one-step protein precipitation with 1.0 M perchloric acid and methanol. After centrifugation, the supernatant was injected directly into the HPLC system. Voriconazole, posaconazole, itraconazole, its metabolite hydroxyitraconazole, and the internal standard naproxen were resolved on a C
6
-phenyl column using gradient elution of 0.01 M phosphate buffer, pH 3.5, and acetonitrile and detected with UV detection at 262 nm. Standard curves were linear over the concentration range of 0.05 to 10 mg/liter (
r
2
> 0.99). Bias was <8.0% from 0.05 to 10 mg/liter, intra- and interday coefficients of variation (imprecision) were <10%, and the limit of quantification was 0.05 mg/liter.
Colistin Methanesulfonate and Colistin Pharmacokinetics in Critically Ill Patients Receiving Continuous Venovenous Hemodiafiltration
Authors: Karvanen Matti , Plachouras Diamantis , Friberg Lena E. , Paramythiotou Elisabeth , Papadomichelakis Evangelos , Karaiskos Ilias , Tsangaris Iraklis , Armaganidis Apostolos , Cars Otto , Giamarellou Helen
Published: November 2012

This report describes the pharmacokinetics of colistin methanesulfonate (CMS) and colistin in five intensive care unit patients receiving continuous venovenous hemodiafiltration. For CMS, the mean maximum concentration of drug in plasma (
C
max
) after the fourth dose was 6.92 mg/liter and total clearance (CL) 8.23 liters/h. For colistin, the mean concentration was 0.92 mg/liter and CL/metabolized fraction (f
m
) 18.91 liters/h. Colistin concentrations were below the current MIC breakpoints, and the area under the concentration-time curve for the free, unbound fraction of the drug over 24 h in the steady state divided by the MIC (
f
AUC/MIC) was lower than recommended, suggesting that a dosage regimen of 160 mg CMS every 8 h (q8h) is inadequate.
Mechanism-Based Model of Parasite Growth and Dihydroartemisinin Pharmacodynamics in Murine Malaria
Authors: Patel Kashyap , Batty Kevin T. , Moore Brioni R. , Gibbons Peter L. , Bulitta Jürgen B. , Kirkpatrick Carl M.
Published: November 2012

Murine models are used to study erythrocytic stages of malaria infection, because parasite morphology and development are comparable to those in human malaria infections. Mechanism-based pharmacokinetic-pharmacodynamic (PK-PD) models for antimalarials are scarce, despite their potential to optimize antimalarial combination therapy. The aim of this study was to develop a mechanism-based growth model (MBGM) for
Plasmodium berghei
and then characterize the parasiticidal effect of dihydroartemisinin (DHA) in murine malaria (MBGM-PK-PD). Stage-specific (ring, early trophozoite, late trophozoite, and schizont) parasite density data from Swiss mice inoculated with
Plasmodium berghei
were used for model development in S-ADAPT. A single dose of intraperitoneal DHA (10 to 100 mg/kg) or vehicle was administered 56 h postinoculation. The MBGM explicitly reflected all four erythrocytic stages of the 24-hour
P. berghei
life cycle. Merozoite invasion of erythrocytes was described by a first-order process that declined with increasing parasitemia. An efflux pathway with subsequent return was additionally required to describe the schizont data, thus representing parasite sequestration or trapping in the microvasculature, with a return to circulation. A 1-compartment model with zero-order absorption described the PK of DHA, with an estimated clearance and distribution volume of 1.95 liters h
−1
and 0.851 liter, respectively. Parasite killing was described by a turnover model, with DHA inhibiting the production of physiological intermediates (IC
50
, 1.46 ng/ml). Overall, the MBGM-PK-PD described the rise in parasitemia, the nadir following DHA dosing, and subsequent parasite resurgence. This novel model is a promising tool for studying malaria infections, identifying the stage specificity of antimalarials, and providing insight into antimalarial treatment strategies.