bluuebunny/crossref_metadata_2025 huggingface dataset:
Stereotactic body radiotherapy for patients with small hepatocellular carcinoma ineligible for resection or ablation therapies
Authors: Kimura Tomoki , Aikata Hiroshi , Takahashi Shigeo , Takahashi Ippei , Nishibuchi Ikuno , Doi Yoshiko , Kenjo Masahiro , Murakami Yuji , Honda Yohji , Kakizawa Hideaki , Awai Kazuo , Chayama Kazuaki , Nagata Yasushi
Published: May 2014

Aim

To evaluate the efficacy and safety of stereotactic body radiotherapy (SBRT) in patients with small hepatocellular carcinoma (HCC) who were ineligible for resection or ablation therapies.

Methods

Overall, 65 patients with 74 HCC (median tumor size, 16 mm) were enrolled. They were treated at the prescribed dose of 48 Gy in four fractions at the isocenter. Child–Turcotte–Pugh (CTP) scoring was used to classify 56 and nine patients into classes A and B, respectively. Local progression was defined as irradiated tumor growth on a dynamic computed tomography follow up. The median follow‐up period was 26 months. Tumor responses were assessed according to the modified Response Evaluation Criteria in Solid Tumors. Treatment‐related toxicities were evaluated according to the Common Terminology Criteria for Adverse Events version 4.0.

Results

The 2‐year overall survival, progression‐free survival and local control rates were 76.0% (95% confidence interval [CI], 65.4–86.7%), 40.0% (95% CI, 27.6–52.3%) and 100% (95% CI, 100%), respectively. At 6–12 months after SBRT, grade 3 or higher toxicities was observed in 15 (23.1%) patients. The incidence of grade 3 or higher toxicities was higher in CTP class B than in class A (P = 0.0127).

Conclusion

SBRT was effective and relatively safe for patients with small HCC who were ineligible for resection or ablation therapies.
Combined Antimicrobial Effect of Thymol and Sodium Lactate against Listeria monocytogenes and Salmonella Typhimurium in Fish Patty
Authors: Ilhak Osman Irfan , Guran Husnu Sahan
Published: May 2014

The purpose of this study was to evaluate the antimicrobial efficacy of the combinations of thymol (0.1 w/w) and sodium lactate (1 and 2% v/w) against Listeria monocytogenes and Salmonella Typhimurium in fish patty samples stored at 4C for 5 days. Treatment with the combination of 0.1% thymol + 2% sodium lactate did not show a significant inhibition on the L. monocytogenes when compared with the sample treated with 2% sodium lactate alone. However, treatment of fish patty with the combination of 0.1% thymol + 2% sodium lactate showed a synergistic effect on Salmonella Typhimurium on days 3 and 5 of storage.

Practical Applications

L. monocytogenes and Salmonella spp. are among the most important foodborne pathogens. Today, compounds with antimicrobial property have found common use in the control of these pathogens and their elimination from foods. Only small percentages of essential oils are tolerable in foods, since essential oils may negatively affects the organoleptic properties of foods. Therefore, combinations of essential oils with other preservatives may help to minimize the application concentrations required. The findings of the present study indicate that combination of 0.1% thymol + 2% sodium lactate would have a synergistic effect against Salmonella Typhimurium in fish patty.
Neuroinflammation: good, bad, or indifferent?
Authors: Kielian Tammy
Published: May 2014

This is the Preface for the Virtual Issue: “Neuroinflammation in Nervous System Disorders: Diversity in Insults and Outcomes”:
http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1471-4159/homepage/virtual_issues.htm#neuroinflammation
The challenge to health professionals when carers resist truth telling at the end of life: a qualitative secondary analysis
Authors: Noble Helen , Price Jayne E , Porter Sam
Published: May 2014

Aims and objectives

To draw out the similar complexities faced by staff around truth‐telling in a children's and adult population and to interrogate the dilemmas faced by staff when informal carers act to block truth‐telling.

Background

Policy encourages normalisation of death, but carers may act to protect or prevent the patient from being told the truth. Little is known about the impact on staff.

Design

Secondary analysis of data using a supra‐analysis design to identify commonality of experiences.

Methods

Secondary ‘supra‐analysis’ was used to transcend the focus of two primary studies in the UK, which examined staff perspectives in a palliative children's and a palliative adult setting, respectively. The analysis examined new theoretical questions relating to the commonality of issues independently derived in each primary study. Both primary studies used focus groups. Existing empirical data were analysed thematically and compared across the studies.

Results

Staff reported a hiding of the truth by carers and sustained use of activities aimed at prolonging life. Carers frequently ignored the advance of end of life, and divergence between staff and carer approaches to truth‐telling challenged professionals. Not being truthful with patients had a deleterious effect on staff, causing anger and feelings of incompetence.

Conclusions

Both children's and adult specialist palliative care staff found themselves caught in a dilemma, subject to policies that promoted openness in planning for death and informal carers who often prevented them from being truthful with patients about terminal prognosis. This dilemma had adverse psychological effects upon many staff.

Relevance to clinical practice

There remains a powerful death‐denying culture in many societies, and carers of dying patients may prevent staff from being truthful with their patients. The current situation is not ideal, and open discussion of this problem is the essential first step in finding a solution.
Accounting for within‐person differences in how people respond to daily incivility at work
Authors: Beattie Larissa , Griffin Barbara
Published: May 2014

This study investigated employees' behavioural responses to incivility, a form of interpersonal mistreatment, across time. Having established substantial within‐person differences in the way individuals responded to incidents, we examined how appraisals of severity and blame, the relative status of instigator, and target personality affected how a target responded on a given day. Perceived severity of the critical incident significantly predicted whether or not a target engaged in negative behaviour towards the instigator, negative behaviour towards others, support seeking, and forgiveness. Neither the hierarchical status of the instigator relative to the target, nor the target's attributions of blame for the specific incident predicted an individual's responses to that incident. Target neuroticism predicted three response categories: ignore/avoid the instigator, respond negatively to the instigator, and seek support. Neuroticism also significantly moderated the within‐person relationship between the perceived severity of an uncivil event and two daily responses: ignore/avoid the instigator and forgive the instigator. The results are discussed in terms of their practical implications for understanding how and why individuals respond to acts of incivility at work.

Practitioner points

Uncivil behaviour – rude or disrespectful interpersonal incidents – is a common occurrence in workplaces and a type of daily hassle or chronic stressor for target individuals.

Incivility has been shown to lead to an array of negative individual and organizational outcomes, including psychological distress and anxiety, greater job stress, reduced task performance and creativity, lower job satisfaction, increased job withdrawal, and higher turnover. Our findings illustrate the link between an individual's experience of an uncivil incident and their immediate behavioural responses.

Workplace interventions aimed at minimizing the harm caused by incivility could focus on educating employees about: the potential impact of incivility; how a person's perception and appraisal of an incident might change their response; how a victim might re‐frame the meaning of what happened; and appropriate actions the victim can take in response to uncivil incidents.
Diagrammatic Scale for Assessment of Bacterial Blight in Coffee Leaves
Authors: Belan Leônidas L. , Pozza Edson A. , Freitas Marcelo L. de O. , de Souza Ricardo M. , de Jesus Junior Waldir C. , Oliveira Júlia M.
Published: May 2014

Due to the lack of a standardized visual method for assessing bacterial blight (Pseudomonas syringae pv. garcae) in coffee leaves, a diagrammatic scale was developed and validated to quantify the disease. Leaves were collected in crops and nursery with different intensity of symptoms, and the true severity was determined electronically. Based on the frequency distribution of severity values and according to the Weber–Fechner's law of visual stimulus, the minimum and maximum limits and the intermediate levels in the scale were determined. Validation was performed by ten evaluators who estimated the severity of 50 leaves with different intensity of symptoms. One evaluation was performed without diagrammatic scale and two evaluations with the scale at 7‐day intervals. The accuracy, precision, repeatability and reproducibility of the estimates were evaluated. The scale had nine levels: 0 (0%), 1 (0.1–0.99%), 2 (1–2%), 3 (2.01–4%), 4 (4.01–8%), 5 (8.01–16%), 6 (16.01–25%), 7 (25.01–45%) and 8 (≥45.1%). Using the scale, the evaluators were able to improve accuracy, precision, reproducibility and repeatability of estimates, compared to evaluators without scale. The scale was appropriate to visual estimation of severity of bacterial blight in coffee leaves.
Aging and contribution of MyD88 and TRIF to expression of TLR pathway‐associated genes following stimulation with Porphyromonas gingivalis
Authors: Shaik‐Dasthagirisaheb Y. B. , Huang N. , Weinberg E. O. , Shen S. S. , Genco C. A. , Gibson F. C.
Published: May 2014

Background and Objective

Periodontal disease is a highly complex chronic inflammatory disease of the oral cavity. Multiple factors influence periodontal disease, including socio‐economic status, genetics and age; however, inflammation elicited by the presence of specific bacteria in the subgingival space is thought to drive the majority of soft‐ and hard‐tissue destruction. Porphyromonas gingivalis is closely associated with periodontal disease. Toll‐like receptors (TLRs) and their intracellular signaling pathways play roles in the host response to P. gingivalis. The focus of the current study was to use microarray analysis to define the contributions of the TLR adaptor molecules myeloid differentiation factor 88 (MyD88) and Toll/interleukin‐1 receptor domain‐containing adaptor inducing interferon‐beta (TRIF), and aging, on the expression of TLR pathway‐associated mRNAs in response to P. gingivalis.

Material and Methods

Bone marrow‐derived macrophages (BMØ) from wild‐type (Wt), MyD88 knockout (MyD88‐KO) and TrifLps2 [i.e. containing a point mutation in the lipopolysaccharide 2 (Lps2) gene rendering the Toll/interleukin (IL)‐1 receptor domain‐containing adaptor inducing interferon‐beta (TRIF) protein nonfunctional] mice, at 2‐and 12‐mo of age, were cultured with P. gingivalis. Expression of genes in BMØ cultured with P. gingivalis was determined in comparison with expression of genes in BMØ cultured in medium only.

Results

Using, as criteria, a twofold increase or decrease in mRNA expression, differential expression of 32 genes was observed when Wt BMØ from 2‐mo‐old mice were cultured with P. gingivalis compared with the medium‐only control. When compared with 2‐mo‐old Wt mice, 21 and 12 genes were differentially expressed (p < 0.05) as a result of the mutations in MyD88 or TRIF, respectively. The expression of five genes was significantly (p < 0.05) reduced in Wt BMØ from 12‐mo‐old mice compared with those from 2‐mo‐old mice following culture with P. gingivalis. Age also influenced the expression of genes in MyD88‐KO and TrifLps2 mice challenged with P. gingivalis.

Conclusions

Our results indicate that P. gingivalis induces differential expression of TLR pathway‐associated genes, and both MyD88 and TRIF play roles in the expression of these genes. Age also played a role in the expression of TLR‐associated genes following stimulation of BMØ with P. gingivalis.
Nucleotide‐binding oligomerization domain 1 regulates Porphyromonas gingivalis‐induced vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 expression in endothelial cells through NF‐κB pathway
Authors: Wan M. , Liu J. , Ouyang X.
Published: May 2014

Background and Objective

Porphyromonas gingivalis has been shown to actively invade endothelial cells and induce vascular cell adhesion molecule 1 (VCAM‐1) and intercellular adhesion molecule 1 (ICAM‐1) overexpression. Nucleotide‐binding oligomerization domain 1 (NOD1) is an intracellular pattern recognition reporter, and its involvement in this process was unknown. This study focused on endothelial cells infected with P. gingivalis, the detection of NOD1 expression and the role that NOD1 plays in the upregulation of VCAM‐1 and ICAM‐1.

Material and Methods

The human umbilical vein endothelial cell line (ECV‐304) was intruded by P. gingivalis W83, and cells without any treatment were the control group. Expression levels of NOD1, VCAM‐1, ICAM‐1, phosphorylated P65 between cells with and without treatment on both mRNA and protein levels were compared. Then we examined whether mesodiaminopimelic acid (NOD1 agonist) could increase VCAM‐1 and ICAM‐1 expression, meanwhile, NOD1 gene silence by RNA interference could reduce VCAM‐1, ICAM‐1 and phosphorylated P65 release. At last, we examined whether inhibition of NF‐κB by Bay117082 could reduce VCAM‐1 and ICAM‐ 1 expression. The mRNA levels were measured by real‐time polymerase chain reaction, and protein levels by western blot or electrophoretic mobility shift assays (for phosphorylated P65).

Results

P. gingivalis invasion showed significant upregulation of NOD1, VCAM‐1 and ICAM‐1. NOD1 activation by meso‐diaminopimelic acid increased VCAM‐1 and ICAM‐1 expression, and NOD1 gene silence reduced VCAM‐1 and ICAM‐1 release markedly. The NF‐κB signaling pathway was activated by P. gingivalis, while NOD1 gene silence decreased the activation of NF‐κB. Moreover, inhibition of NF‐κB reduced VCAM‐1 and ICAM‐1 expression induced by P. gingivalis in endothelial cells.

Conclusion

The results revealed that P. gingivalis induced NOD1 overexpression in endothelial cells and that NOD1 played an important role in the process of VCAM‐1 and ICAM‐1 expression in endothelial cells infected with P. gingivalis through the NF‐κB signaling pathway.
Role of periodontal ligament fibroblasts in osteoclastogenesis: a review
Authors: Sokos D. , Everts V. , de Vries T. J.
Published: May 2014

During the last decade it has become clear that periodontal ligament fibroblasts may contribute to the in vitro differentiation of osteoclasts. We surveyed the current findings regarding their osteoclastogenesis potential. Periodontal ligament fibroblasts have the capacity to select and attract osteoclast precursors and subsequently to retract and enable migration of osteoclast precursors to the bone surface. There, fusion of precursors takes place, giving rise to osteoclasts. The RANKL–RANK–osteoprotegerin (OPG) axis is considered crucial in this process. Periodontal ligament fibroblasts produce primarily OPG, an osteoclastogenesis‐inhibitory molecule. However, they may be influenced in vivo by direct or indirect interactions with bacteria or by mechanical loading. Incubation of periodontal ligament fibroblasts with bacteria or bacterial components causes an increased expression of RANKL and other osteoclastogenesis‐stimulating molecules, such as tumor necrosis factor‐α and macrophage‐colony stimulating factor. Similar results are observed after the application of mechanical loading to these fibroblasts. Periodontal ligament fibroblasts may be considered to play an important role in the remodelling of alveolar bone. In vitro experiments have demonstrated that periodontal ligament fibroblasts adapt to bacterial and mechanical stimuli by synthesizing higher levels of osteoclastogenesis‐stimulating molecules. Therefore, they probably contribute to the enhanced osteoclast formation observed during periodontitis and to orthodontic tooth movement.
An Evidence-Based Unified Definition of Lifelong and Acquired Premature Ejaculation: Report of the Second International Society for Sexual Medicine Ad Hoc Committee for the Definition of Premature Ejaculation
Authors: Serefoglu Ege Can , McMahon Chris G. , Waldinger Marcel D. , Althof Stanley E. , Shindel Alan , Adaikan Ganesh , Becher Edgardo F. , Dean John , Giuliano Francois , Hellstrom Wayne J.G. , Giraldi Annamaria , Glina Sidney , Incrocci Luca , Jannini Emmanuele , McCabe Marita , Parish Sharon , Rowland David , Taylor Segraves R. , Sharlip Ira , Torres Luiz Otavio
Published: May 2014

Introduction

The International Society for Sexual Medicine (ISSM) Ad Hoc Committee for the Definition of Premature Ejaculation developed the first evidence-based definition for lifelong premature ejaculation (PE) in 2007 and concluded that there were insufficient published objective data at that time to develop a definition for acquired PE.

Aim

The aim of this article is to review and critique the current literature and develop a contemporary, evidence-based definition for acquired PE and/or a unified definition for both lifelong and acquired PE.

Methods

In April 2013, the ISSM convened a second Ad Hoc Committee for the Definition of Premature Ejaculation in Bangalore, India. The same evidence-based systematic approach to literature search, retrieval, and evaluation used by the original committee was adopted.

Results

The committee unanimously agreed that men with lifelong and acquired PE appear to share the dimensions of short ejaculatory latency, reduced or absent perceived ejaculatory control, and the presence of negative personal consequences. Men with acquired PE are older, have higher incidences of erectile dysfunction, comorbid disease, and cardiovascular risk factors, and have a longer intravaginal ejaculation latency time (IELT) as compared with men with lifelong PE. A self-estimated or stopwatch IELT of 3 minutes was identified as a valid IELT cut-off for diagnosing acquired PE. On this basis, the committee agreed on a unified definition of both acquired and lifelong PE as a male sexual dysfunction characterized by (i) ejaculation that always or nearly always occurs prior to or within about 1 minute of vaginal penetration from the first sexual experience (lifelong PE) or a clinically significant and bothersome reduction in latency time, often to about 3 minutes or less (acquired PE); (ii) the inability to delay ejaculation on all or nearly all vaginal penetrations; and (iii) negative personal consequences, such as distress, bother, frustration, and/or the avoidance of sexual intimacy.

Conclusion

The ISSM unified definition of lifelong and acquired PE represents the first evidence-based definition for these conditions. This definition will enable researchers to design methodologically rigorous studies to improve our understanding of acquired PE.
Cryptic diversity and phylogeography of the island‐associated barnacle Chthamalus moro in Asia
Authors: Wu Tsz Huen , Tsang Ling Ming , Chan Benny K. K. , Chu Ka Hou
Published: May 2014

Pleistocene glaciations were among the important historic events that shaped the population structures of marine organisms. Genetic studies of different marine fauna and flora have demonstrated the effect of Pleistocene glaciations on taxa that reside in marginal seas. However, how marine island species responded to Pleistocene glaciations remains relatively unstudied, especially in Asia. Genetic analyses based on the island‐associated barnacle Chthamalus moro collected from 14 sites in Asia reveal that C. moro comprises three distinct lineages, with COI divergence ranging from 3.9 to 8.3%. Population genetic analyses on respective lineages reveal signs of demographic expansion within the Pleistocene epoch at different times. The Ogasawara lineage, which has a more oceanic distribution, expanded the earliest, followed by the population expansion of the Ryukyu and Southern lineages that inhabit islands closer to the continent. The data suggest that the inhabitants of outer islands may have been less affected by Pleistocene glaciations than those that reside closer to the continent, as the former were able to maintain a large, stable, effective population size throughout the late Pleistocene.
Mito‐nuclear discord in six congeneric lineages of Holarctic ducks (genus Anas)
Authors: Peters Jeffrey L. , Winker Kevin , Millam Kendra C. , Lavretsky Philip , Kulikova Irina , Wilson Robert E. , Zhuravlev Yuri N. , McCracken Kevin G.
Published: May 2014

Many species have Holarctic distributions that extend across Europe, Asia and North America. Most genetics research on these species has examined only mitochondrial (mt) DNA, which has revealed wide variance in divergence between Old World (OW) and New World (NW) populations, ranging from shallow, unstructured genealogies to deeply divergent lineages. In this study, we sequenced 20 nuclear introns to test for concordant patterns of OW–NW differentiation between mtDNA and nuclear (nu) DNA for six lineages of Holarctic ducks (genus Anas). Genetic differentiation for both marker types varied widely among these lineages (idiosyncratic population histories), but mtDNA and nuDNA divergence within lineages was not significantly correlated. Moreover, compared with the association between mtDNA and nuDNA divergence observed among different species, OW–NW nuDNA differentiation was generally lower than mtDNA divergence, at least for lineages with deeply divergent mtDNA. Furthermore, coalescent estimates indicated significantly higher rates of gene flow for nuDNA than mtDNA for four of the six lineages. Thus, Holarctic ducks show prominent mito‐nuclear discord between OW and NW populations, and we reject differences in sorting rates as the sole cause of the within‐species discord. Male‐mediated intercontinental gene flow is likely a leading contributor to this discord, although selection could also cause increased mtDNA divergence relative to weak nuDNA differentiation. The population genetics of these ducks contribute to growing evidence that mtDNA can be an unreliable indicator of stage of speciation and that more holistic approaches are needed for species delimitation.
Range‐wide analysis of genetic structure in a widespread, highly mobile species (Odocoileus hemionus) reveals the importance of historical biogeography
Authors: Latch Emily K. , Reding Dawn M. , Heffelfinger James R. , Alcalá‐Galván Carlos H. , Rhodes Olin E.
Published: May 2014

Highly mobile species that thrive in a wide range of habitats are expected to show little genetic differentiation across their range. A limited but growing number of studies have revealed that patterns of broad‐scale genetic differentiation can and do emerge in vagile, continuously distributed species. However, these patterns are complex and often shaped by both historical and ecological factors. Comprehensive surveys of genetic variation at a broad scale and at high resolution are useful for detecting cryptic spatial genetic structure and for investigating the relative roles of historical and ecological processes in structuring widespread, highly mobile species. In this study, we analysed 10 microsatellite loci from over 1900 samples collected across the full range of mule deer (Odocoileus hemionus), one of the most widely distributed and abundant of all large mammal species in North America. Through both individual‐ and population‐based analyses, we found evidence for three main genetic lineages, one corresponding to the ‘mule deer’ morphological type and two to the ‘black‐tailed deer’ type. Historical biogeographic events likely are the primary drivers of genetic divergence in this species; boundaries of the three lineages correspond well with predictions based on Pleistocene glacial cycles, and substructure within each lineage demonstrates island vicariance. However, across large geographic areas, including the entire mule deer lineage, we found that genetic variation fit an isolation‐by‐distance pattern rather than discrete clusters. A lack of genetic structure across wide geographic areas of the continental west indicates that ecological processes have not resulted in restrictions to gene flow sufficient for spatial genetic structure to emerge. Our results have important implications for our understanding of evolutionary mechanisms of divergence, as well as for taxonomy, conservation and management.
Cerebral amyloid angiopathy‐related leukoencephalopathy: Successful steroid treatment for neurological deficits and subcortical white matter lesions partly involving the cortical gray matter
Authors: Murakami Takenobu , Morimoto Julia , Hoshi Akihiko , Nakatani‐Enomoto Setsu , Ichikawa Masahiro , Tasaki Kazuhiro , Ogura Ryosuke , Toyoshima Yasuko , Kakita Akiyoshi , Saito Kiyoshi , Takahashi Hitoshi , Ugawa Yoshikazu
Published: May 2014

A 76‐year‐old woman developed subacute cognitive decline, consciousness impairment and right hemiparesis. Magnetic resonance imaging showed asymmetric white matter or cortical gray matter lesions, and multiple cerebral microbleeds. Pathological studies of biopsied brain specimen disclosed amyloid β‐protein deposits in the vessel walls. Repeated steroid‐pulse therapy improved clinical symptoms and resolved the cortico‐subcortical lesions. Steroid therapy should be considered for patients with amyloid β‐protein deposition in cerebral amyloid angiopathy‐related leukoencephalopathy.
A technique to measure the intracuff pressure continuously: an in vivo demonstration of its accuracy
Authors: Krishna Senthil G. , Ramesh Archana S. , Jatana Kris R. , Elmaraghy Charles , Merz Meredith , Ruda James , Tobias Joseph D.
Published: May 2014

Objective

A major concern with the use of cuffed endotracheal tubes (cETT) in children is hyperinflation of the cuff which may compromise tracheal mucosal perfusion. To measure the intracuff pressure (CP), we devised a method using the transducer of an invasive pressure monitoring device. The objective of the study was to test the accuracy and validity of this device for instantaneous and continuous CP monitoring.

Methods

The study was conducted in 2 phases. In Phase 1 (200 pediatric patients), after inflation of the cuff, the CP was measured using the standard manometer and the transducer simultaneously. In Phase 2 (20 pediatric patients), the transducer was left connected to the pilot balloon of the ETT to obtain a continuous CP reading and the standard manometer was used to measure the CP at 5‐min intervals. Statistical analysis included a Bland–Altman comparison and linear regression analysis.

Results

In Phase 1, linear regression analysis demonstrated an R2 value of 0.9956. The bias was 0.30 cmH2O, the precision was 0.75 cmH2O, and the 95% level of agreement (LOA) ranged from −1.16 to 1.77 cmH2O. In Phase 2, the linear regression analysis revealed an R2 value of 0.9846. The bias was 0.28 cmH2O, the precision was 0.7 cmH2O, and the 95% LOA ranged from −1.1 to 1.66 cmH2O.

Conclusion

Our study demonstrates that when cETTs are used in the pediatric population, the transducer of the invasive pressure monitoring device can be used reliably to measure the CP at the time of inflation and continuously thereafter.
Is it time to test biguanide metformin in the treatment of melanoma?
Authors: Cerezo Michael , Tomic Tijana , Ballotti Robert , Rocchi Stéphane
Published: May 2014

Metformin is the most widely used antidiabetic drug that belongs to the biguanide class. It is very well tolerated and has the major clinical advantage of not inducing hypoglycemia. Metformin decreases hepatic glucose production via a mechanism requiring liver kinase B1, which controls the metabolic checkpoint, AMP‐activated protein kinase‐mammalian target of rapamycin and neoglucogenic genes. The effects of metformin on this pathway results in reduced protein synthesis and cell proliferation. These observations have given the impetus for many investigations on the role of metformin in the regulation of tumor cell proliferation, cell‐cycle regulation, apoptosis, and autophagy. Encouraging results from these studies have shown that metformin could potentially be used as an efficient anticancer drug in various neoplasms such as prostate, breast, lung, pancreas cancers, and melanoma. These findings are strengthened by retrospective epidemiological studies that have found a decrease in cancer risk in diabetic patients treated with metformin. In this review, we have focused our discussion on recent molecular mechanisms of metformin that have been described in various solid tumors in general and in melanoma in particular.
[Ca2+]i oscillations in ASM: Relationship with persistent airflow obstruction in asthma
Authors: Sweeney David , Hollins Fay , Gomez Edith , Saunders Ruth , Challiss R.A. John , Brightling Christopher E.
Published: May 2014

The cause of airway smooth muscle (ASM) hypercontractility in asthma is not fully understood. The relationship of spontaneous intracellular calcium oscillation frequency in ASM to asthma severity was investigated. Oscillations were increased in subjects with impaired lung function abolished by extracellular calcium removal, attenuated by caffeine and unaffected by verapamil or nitrendipine. Whether modulation of increased spontaneous intracellular calcium oscillations in ASM from patients with impaired lung function represents a therapeutic target warrants further investigation.
Demography of Rumex acetosella in lowbush blueberry (Vaccinium angustifolium)
Authors: White S N , Boyd N S , Van Acker R C
Published: May 2014

The demography of Rumex acetosella ramets and seedlings was monitored within and between blueberry clones over the two‐year lowbush blueberry production cycle in Nova Scotia, Canada. Overwintering ramets constituted the majority (>70%) of the flowering ramet population. A small proportion of ramets emerging in May and June flowered, but no ramets emerging between July and November flowered in the year of emergence. Emergence of new ramets was season‐long and ramet populations were regulated by a cycle of birth and death in each production year. Ramet populations in blueberry patches had higher growth rates and lower mortality than ramet populations in bare soil patches in the non‐bearing year, resulting in large net gains to ramet populations in blueberry patches during this production year. Ramet population growth rates and mortality were similar in blueberry and bare soil patches in the bearing year and net ramet populations declined during this production year. Survival rates of overwintering and new ramets varied, but ramets from both the overwintering and monthly cohorts contributed to a distinct ramet age structure at the end of each season. Seedling survival ranged from 6 ± 6 to 51 ± 12% across sites, and no seedlings flowered in the year of emergence. Transition probabilities of ramets and seedlings were used to develop a life‐cycle model of R. acetosella for the 2‐year lowbush blueberry production cycle. This model has utility in developing new management strategies for R. acetosella in lowbush blueberry.
Muscle‐specific kinase (MuSK) autoantibodies suppress the MuSK pathway and ACh receptor retention at the mouse neuromuscular junction
Authors: Ghazanfari Nazanin , Morsch Marco , Reddel Stephen W. , Liang Simon X. , Phillips William D.
Published: May 2014

Key points

Myasthenic anti‐muscle‐specific‐kinase (MuSK) IgG was injected into mice to study its effect upon the MuSK signalling pathway and the homeostasis of postsynaptic acetylcholine receptor packing at the neuromuscular junction.

Densities of MuSK, activated Src kinase, phosphorylated ACh receptors and rapsyn were all reduced at motor endplates while β‐dystroglycan was unaffected.

Pulse‐labelling showed that the slow decline in junctional ACh receptor density could be explained largely by diminished retention of ACh receptors within the postsynaptic membrane scaffold.

The results suggest that anti‐MuSK IgG reduces the density of MuSK, associated tyrosine phosphorylation and retention of junctional ACh receptors within the postsynaptic membrane.

Muscle‐specific kinase (MuSK) autoantibodies from myasthenia gravis patients can block the activation of MuSK in vitro and/or reduce the postsynaptic localization of MuSK. Here we use a mouse model to examine the effects of MuSK autoantibodies upon some key components of the postsynaptic MuSK pathway and upon the regulation of junctional ACh receptor (AChR) numbers. Mice became weak after 14 daily injections of anti‐MuSK‐positive patient IgG. The intensity and area of AChR staining at the motor endplate was markedly reduced. Pulse‐labelling of AChRs revealed an accelerated loss of pre‐existing AChRs from postsynaptic AChR clusters without a compensatory increase in incorporation of (newly synthesized) replacement AChRs. Large, postsynaptic AChR clusters were replaced by a constellation of tiny AChR microaggregates. Puncta of AChR staining also appeared in the cytoplasm beneath the endplate. Endplate staining for MuSK, activated Src, rapsyn and AChR were all reduced in intensity. In the tibialis anterior muscle there was also evidence that phosphorylation of the AChR β‐subunit‐Y390 was reduced at endplates. In contrast, endplate staining for β‐dystroglycan (through which rapsyn couples AChR to the synaptic basement membrane) remained intense. The results suggest that anti‐MuSK IgG suppresses the endplate density of MuSK, thereby down‐regulating MuSK signalling activity and the retention of junctional AChRs locally within the postsynaptic membrane scaffold.
Noradrenergic modulation of masseter muscle activity during natural rapid eye movement sleep requires glutamatergic signalling at the trigeminal motor nucleus
Authors: Schwarz Peter B. , Mir Saba , Peever John H.
Published: May 2014

Key points

A principal role of noradrenaline is to potentiate motoneuron output in response to excitatory transmitter input.

It is unknown if α‐1 noradrenoceptor activation is sufficient to independently trigger masseter muscle activity during natural waking and sleeping behaviour in the absence of excitatory (glutamatergic) input.

Here, we use behavioural, neuropharmacological and electrophysiological techniques during rapid eye movement (REM) sleep to demonstrate that the excitatory effects of noradrenaline on motor output are lost in the absence of an endogenous glutamatergic drive.

These findings may shed light on the unremarkable therapeutic outcomes of aminergic drugs in treating certain sleep motor disorders, particularly during REM sleep.

Noradrenergic neurotransmission in the brainstem is closely coupled to changes in muscle activity across the sleep–wake cycle, and noradrenaline is considered to be a key excitatory neuromodulator that reinforces the arousal‐related stimulus on motoneurons to drive movement. However, it is unknown if α‐1 noradrenoceptor activation increases motoneuron responsiveness to excitatory glutamate (AMPA) receptor‐mediated inputs during natural behaviour. We studied the effects of noradrenaline on AMPA receptor‐mediated motor activity at the motoneuron level in freely behaving rats, particularly during rapid eye movement (REM) sleep, a period during which both AMPA receptor‐triggered muscle twitches and periods of muscle quiescence in which AMPA drive is silent are exhibited. Male rats were subjected to electromyography and electroencephalography recording to monitor sleep and waking behaviour. The implantation of a cannula into the trigeminal motor nucleus of the brainstem allowed us to perfuse noradrenergic and glutamatergic drugs by reverse microdialysis, and thus to use masseter muscle activity as an index of motoneuronal output. We found that endogenous excitation of both α‐1 noradrenoceptor and AMPA receptors during waking are coupled to motor activity; however, REM sleep exhibits an absence of endogenous α‐1 noradrenoceptor activity. Importantly, exogenous α‐1 noradrenoceptor stimulation cannot reverse the muscle twitch suppression induced by AMPA receptor blockade and nor can it elevate muscle activity during quiet REM, a phase when endogenous AMPA receptor activity is subthreshold. We conclude that the presence of an endogenous glutamatergic drive is necessary for noradrenaline to trigger muscle activity at the level of the motoneuron in an animal behaving naturally.
Performance of the Merced Demonstration XCPC Collector and Double Effect Chiller
Authors: Widyolar Bennett , Winston Roland , Jiang Lun , Poiry Heather
Published: May 2014

A solar thermal cooling system using novel nontracking external compound parabolic concentrators (XCPC) has been built at the University of California, Merced and operated for two cooling seasons. Its performance in providing power for space cooling has been analyzed. This solar cooling system is comprised of 53.3 m2 of XCPC trough collectors which are used to power a 23 kW double effect (LiBr) absorption chiller. This is the first system that combines both XCPC and absorption chilling technologies. Performance of the system was measured in both sunny and cloudy conditions, with both clean and dirty collectors. It took, on average, about 2 h for the collector system to reach operating temperatures between 160 and 180 °C. When operated in this temperature range, the XCPC collector array collected solar energy with an average daily efficiency of 36.7% and reached instantaneous efficiencies up to 40%. The thermal coefficient of performance (COP) of the system (including thermal losses and COP of absorption chiller) averaged at 0.99 and the daily solar COP of the entire system averaged at 0.363. It was found that these collectors are well suited at providing thermal power to drive absorption cooling systems and that both the coinciding of available thermal power with cooling demand and the simplicity of the XCPC collectors compared to other solar thermal collectors makes them a highly attractive candidate for cooling projects. Consequently, the XCPC technology is currently being commercialized in the U.S. and India. The XCPC's numerous potential applications include solar heating, cooling, desalination, oil extraction, electricity generation, and food processing.
Flow Fields Inside Stocked Fish Cages and the Near Environment
Authors: Gansel Lars C. , Rackebrandt Siri , Oppedal Frode , McClimans Thomas A.
Published: May 2014

This study explores the average flow field inside and around stocked Atlantic salmon (Salmo salar L.) fish cages. Laboratory tests and field measurements were conducted to study flow patterns around and through fish cages and the effect of fish on the water flow. Currents were measured around an empty and a stocked fish cage in a fjord to verify the results obtained from laboratory tests without fish and to study the effects of fish swimming in the cage. Fluorescein, a nontoxic, fluorescent dye, was released inside a stocked fish cage for visualization of three-dimensional flow patterns inside the cage. Atlantic salmon tend to form a torus shaped school and swim in a circular path, following the net during the daytime. Current measurements around an empty and a stocked fish cage show a strong influence of fish swimming in this circular pattern: while most of the oncoming water mass passes through the empty cage, significantly more water is pushed around the stocked fish cage. Dye experiments show that surface water inside stocked fish cages converges toward the center, where it sinks and spreads out of the cage at the depth of maximum biomass. In order to achieve a circular motion, fish must accelerate toward the center of the cage. This inward-directed force must be balanced by an outward force that pushes the water out of the cage, resulting in a low pressure area in the center of the rotational motion of the fish. Thus, water is pulled from above and below the fish swimming depth. Laboratory tests with empty cages agree well with field measurements around empty fish cages, and give a good starting point for further laboratory tests including the effect of fish-induced currents inside the cage to document the details of the flow patterns inside and adjacent to stocked fish cages. The results of such experiments can be used as benchmarks for numerical models to simulate the water flow in and around net pens, and model the oxygen supply and the spreading of wastes in the near wake of stocked fish farms.
Surface chemistry of a Cu(I) beta-diketonate precursor and the atomic layer deposition of Cu2O on SiO2 studied by x-ray photoelectron spectroscopy
Authors: Dhakal Dileep , Waechtler Thomas , Schulz Stefan E. , Gessner Thomas , Lang Heinrich , Mothes Robert , Tuchscherer André
Published: May 2014

The surface chemistry of the bis(tri-n-butylphosphane) copper(I) acetylacetonate, [(nBu3P)2Cu(acac)] and the thermal atomic layer deposition (ALD) of Cu2O using this Cu precursor as reactant and wet oxygen as coreactant on SiO2 substrates are studied by in-situ x-ray photoelectron spectroscopy (XPS). The Cu precursor was evaporated and exposed to the substrates kept at temperatures between 22 °C and 300 °C. The measured phosphorus and carbon concentration on the substrates indicated that most of the [nBu3P] ligands were released either in the gas phase or during adsorption. No disproportionation was observed for the Cu precursor in the temperature range between 22 °C and 145 °C. However, disproportionation of the Cu precursor was observed at 200 °C, since C/Cu concentration ratio decreased and substantial amounts of metallic Cu were present on the substrate. The amount of metallic Cu increased, when the substrate was kept at 300 °C, indicating stronger disproportionation of the Cu precursor. Hence, the upper limit for the ALD of Cu2O from this precursor lies in the temperature range between 145 °C and 200 °C, as the precursor must not alter its chemical and physical state after chemisorption on the substrate. Five hundred ALD cycles with the probed Cu precursor and wet O2 as coreactant were carried out on SiO2 at 145 °C. After ALD, in-situ XPS analysis confirmed the presence of Cu2O on the substrate. Ex-situ spectroscopic ellipsometry indicated an average film thickness of 2.5 nm of Cu2O deposited with a growth per cycle of 0.05 Å/cycle. Scanning electron microscopy and atomic force microscopy (AFM) investigations depicted a homogeneous, fine, and granular morphology of the Cu2O ALD film on SiO2. AFM investigations suggest that the deposited Cu2O film is continuous on the SiO2 substrate.
Electron scattering analysis based on electron ray-tracing in extreme ultraviolet photomask
Authors: Choi Jin , Sup Ahn Byung , Jeon Chan Uk
Published: May 2014

The electron distribution in extreme ultraviolet (EUV) photomask and its impact on patterning quality are investigated by Monte Carlo simulation and experiments. The simulation of electron ray tracing was accomplished using geant4 software to investigate the electron scattering properties within ArF and EUV photomask. The authors showed that EUV photomask has an additional electron distribution in the range of 2 μm, and that it is generated by the transverse propagation of electrons at the boundary of the Mo and Si layers. Furthermore, the specific electron distribution of EUV photomask results in a size error of the measured pattern, with respect to the design size, according to pattern density and electron dose. To correct this size error, the authors propose the use of an electron beam (100 keV), or H+ ion beam (50 keV), or a mask-process-correction based on data biasing.
rpoD
Gene Pyrosequencing for the Assessment of Pseudomonas Diversity in a Water Sample from the Woluwe River
Authors: Sánchez David , Matthijs Sandra , Gomila Margarita , Tricot Catherine , Mulet Magdalena , García-Valdés Elena , Lalucat Jorge
Published: May 2014

A water sample from a noncontaminated site at the source of the Woluwe River (Belgium) was analyzed by culture-dependent and -independent methods.
Pseudomonas
isolates were identified by sequencing and analysis of the
rpoD
gene. Culture-independent methods consisted of cloning and pyrosequencing of a
Pseudomonas
rpoD
amplicon from total DNA extracted from the same sample and amplified with selective
rpoD
gene primers. Among a total of 14,540 reads, 6,228 corresponded to
Pseudomonas
rpoD
gene sequences by a BLAST analysis in the NCBI database. The selection criteria for the reads were sequences longer than 400 bp, an average
Q
40
value greater than 25, and >85% identity with a
Pseudomonas
species. Of the 6,228
Pseudomonas
rpoD
sequences, 5,345 sequences met the established criteria for selection. Sequences were clustered by phylogenetic analysis and by use of the QIIME software package. Representative sequences of each cluster were assigned by BLAST analysis to a known
Pseudomonas
species when the identity with the type strain was greater than or equal to 96%. Twenty-six species distributed among 12 phylogenetic groups or subgroups within the genus were detected by pyrosequencing.
Pseudomonas stutzeri
,
P. moraviensis
, and
P. simiae
were the only cultured species not detected by pyrosequencing. The predominant phylogenetic group within the
Pseudomonas
genus was the
P. fluorescens
group, as determined by culture-dependent and -independent analyses. In all analyses, a high number of putative novel phylospecies was found: 10 were identified in the cultured strains and 246 were detected by pyrosequencing, indicating that the diversity of
Pseudomonas
species has not been fully described.
Metabolic Shift of Escherichia coli under Salt Stress in the Presence of Glycine Betaine
Authors: Metris A. , George S. M. , Mulholland F. , Carter A. T. , Baranyi J.
Published: May 2014

An important area of food safety focuses on bacterial survival and growth in unfavorable environments. In order to understand how bacteria adapt to stresses other than nutrient limitation in batch cultures, we need to develop mechanistic models of intracellular regulation and metabolism under stress. We studied the growth of
Escherichia coli
in minimal medium with added salt and different osmoprotectants. To characterize the metabolic efficiency with a robust parameter, we identified the optical density (OD) values at the inflection points of measured “OD versus time” growth curves and described them as a function of glucose concentration. We found that the metabolic efficiency parameter did not necessarily follow the trend of decreasing specific growth rate as the salt concentration increased. In the absence of osmoprotectant, or in the presence of proline, the metabolic efficiency decreased with increasing NaCl concentration. However, in the presence of choline or glycine betaine, it increased between 2 and 4.5% NaCl before declining at 5% NaCl and above. Microarray analysis of the transcriptional network and proteomics analysis with glycine betaine in the medium indicated that between 4.5 and 5% NaCl, the metabolism switched from aerobic to fermentative pathways and that the response to osmotic stress is similar to that for oxidative stress. We conclude that, although the growth rate appeared to decrease smoothly with increasing NaCl, the metabolic strategy of cells changed abruptly at a threshold concentration of NaCl.