bluuebunny/crossref_metadata_2025 huggingface dataset:
Recurrent cervical cancer in a patient who was compound heterozygous for UGT1A1*6 and UGT1A1*28 presenting with serious adverse events during irinotecan hydrochloride/nedaplatin therapy
Authors: Takatori Eriko , Shoji Tadahiro , Miura Yuki , Takeuchi Satoshi , Yoshizaki Akira , Sugiyama Toru
Published: June 2013

There have been no case reports of the risk of serious adverse events associated with the administration of irinotecan hydrochloride (CPT‐11) in patients with gynecologic cancer who are compound heterozygous for UGT1A1*6 and UGT1A1*28. A 71‐year‐old patient presented with recurrent stage IIIb cervical cancer. Combined chemotherapy was initiated with CPT‐11 (60 mg/m2 on days 1 and 8) plus nedaplatin (NDP; 80 mg/m2 on day 1), with each cycle lasting for 28 days. The patient was a compound heterozygote for UGT1A1*6 and UGT1A1*28. Hematotoxic adverse events observed during the chemotherapy were grade 4 neutropenia, grade 3 anemia, and grade 4 thrombocytopenia, and the non‐hematotoxic adverse events were grade 3 diarrhea and grade 3 fatigue. The findings in this patient indicate that CPT‐11 should be administered with great care, even at a dose of 60 mg/m2, in patients receiving combined therapy with CPT‐11 and NDP who are compound heterozygous for UGT1A1*6 and UGT1A1*28.
Does postoperative pain predict the outcome of endometrial ablation?
Authors: Yuan Xi , Richmond Michael N. , Leng Yan , Li Tin‐Chiu
Published: June 2013

Aim

In this article, we hypothesized that significant pain in the immediate postoperative period is due to a deeper degree of thermal ablation, down to the myometrial layer, and consequently an increased likelihood of successful outcome.

Material and Methods

We retrospectively reviewed the medical records of 87 subjects who underwent thermal balloon endometrial ablation as the sole procedure under general anesthesia, administered by the same anesthetist using a standard protocol over a 10‐year period from 2000 to 2010 at Thornbury Hospital, Sheffield, UK. All the cases were performed by the same surgeon in one hospital.

Results

Twenty‐eight (32.2%) subjects experienced severe or intractable pain within 1 h after the thermal balloon endometrial ablation procedure, while 26 (29.9%) subjects required morphine injection in the postoperative period. Overall, more than 70% of women experienced significant reduction in their menstrual flow. There was no difference in the clinical outcome between those who did or did not experience severe pain or between those who did or did not require morphine injection in the postoperative period.

Conclusion

The amount of postoperative pain did not predict the outcome of thermal balloon endometrial ablation.
Body mass index, smoking, age and cancer mortality among women: A classification tree analysis
Authors: Kitsantas Panagiota , Wu Huichuan
Published: June 2013

Aim

Although obesity is an established risk factor for cancer mortality among women, little is known about how body mass index (BMI) is interacting with certain lifestyle behaviors and sociodemographic characteristics to increase the risk of cancer mortality. The purpose of this study was to use classification trees to examine possible interactions between BMI, smoking, age, poverty level and marital status in identifying high‐risk subgroups for all‐cause cancer mortality in women.

Material and Methods

Data from the US National Health Interview Survey linked with the National Death Index from 1990–2004 were used in this study. The data were restricted to women with complete information on all risk factors considered in the analyses. The data were analyzed using descriptive statistics and classification trees.

Results

Findings revealed that younger women (41–50 years old) who smoked had higher cancer mortality if they were underweight. Even among 51–60‐year‐old never smokers, we observed an inverse relationship between BMI and mortality. High BMI, however, was not a protective factor in 51–60‐year‐old women who were not married and did not smoke.

Conclusion

Classification tree analysis confirms and extends current knowledge about the role of BMI and smoking on cancer mortality by providing preliminary risk profiles. The findings indicate that it is imperative for cancer‐related studies to examine BMI and smoking within age‐specific groups and in the context of several sociodemographic factors that are known to independently affect cancer mortality.
Patenting Activities and Firm Performance: Does Firm Size Matter?
Authors: Andries Petra , Faems Dries
Published: June 2013

Whereas prior research has provided valuable insights into the willingness of small and medium‐sized enterprises (SMEs) and large firms to engage in patenting, a comparison of the performance implications of patenting activities across small and large firms is still lacking. This gap is important becauseSMEs and large firms, having different resources and capabilities, might benefit from patenting activities in different ways. In particular,SMEs can be expected to benefit less from patenting activities in terms of protection against imitators than large firms. On the other hand, the propensity and ability ofSMEs to license out their patents and generate additional revenue streams might be relatively higher than that of their large counterparts.

This paper studies the impact of patenting on licensing, innovation, and financial performance for bothSMEs and large firms, using multiple‐group path analyses on a sample of 358 manufacturing firms. Contrary to expectations, this study demonstrates that not only large firms, but alsoSMEs benefit from patenting in terms of commercializing product innovations. Moreover, for bothSMEs and large firms, such increased innovation performance in turn contributes to higher profit margins. Patenting activities also increase the ability ofSMEs and large firms to license out knowledge to external parties, and this positive effect is significantly stronger for large firms. However, neither inSMEs nor in large firms, these outward licensing activities generate short‐term financial benefits. Finally, the study demonstrates that patenting activities do not trigger significant cost disadvantages for eitherSMEs or large firms.

Jointly, these findings provide unique insights in the value‐generating and cost‐increasing effects of patenting, suggesting that not only large firms, but alsoSMEs should consider patenting as a viable strategy to fully reap commercial benefits from their innovation activities. At the same time, they temper open innovation scholars’ expectations regarding the financial benefits of licensing out knowledge. Overall, these findings point to opportunities for optimizing the intellectual property management of bothSMEs and large firms.
Don't Trust Trust: A Dynamic Approach to Controlling Supplier Involvement in New Product Development
Authors: Smets Lydie P. M. , van Oorschot Kim E. , Langerak Fred
Published: June 2013

Prior literature stresses the importance for manufacturers to use formal and informal controls to coordinate collaborative new product development activities with suppliers. In doing so, the existence of trust between manufacturers and suppliers is believed to play a key role because it enables manufacturers to reduce investments in formal controls and rely more on less costly informal controls. Manufacturers and suppliers don't suddenly trust each other though: trust typically grows over time as the partners get to know each other. Trust may also decrease if manufacturers overuse formal controls or if suppliers underperform. These fluctuations in trust over the course of supplier–manufacturer relationships complicate the so‐called trust–control nexus and raise important questions about the impact of trust on the efficiency and effectiveness of formal and informal controls as coordination mechanisms. Therefore, this study examines how manufacturers should balance formal and informal controls over time to reap the full benefits of collaborative product development with suppliers. For that purpose, a conceptual and system dynamics model are developed, which incorporate the links among formal and informal controls, trust, and the supplier's development performance. In an empirical validation in the context of the shipbuilding industry, the results reject the notion that manufacturers must lessen formal controls and increase informal controls with trust. Instead, it is most efficient and effective to invest always in formal controls, particularly process control, to coordinate supplier involvement in new product development. These results have important theoretical and managerial implications: Informal controls are not as profitable as expected.
Seeking Simplicity in Complexity: The Relative Value of Ease of Use (EOU)‐Based Product Differentiation
Authors: Burke Paul F.
Published: June 2013

Models of category acceptance and diffusion, including Davis's technological acceptance model (TAM), have established that ease of use (EOU) is a significant determinant of technological product adoption. This supports user‐centered design philosophies, where aspects of cognitive attractiveness (e.g., logical to use) and emotional attractiveness (e.g., lack of frustration in use) are essential, and contrasts traditional design practices where physical attractiveness dominates concern. These studies consider the impact of EOU on category (primary) demand. It is unclear whether firms should incorporate EOU into design and positioning strategies to differentiate their products from others in the same category that perform better on functional features. A random utility theory‐based choice model is used to measure the relative value of EOU. In a new product category (DVD recorders; n = 496) and one that is more established (cell phones; n = 202), consumers were found to forgo functional features in preference for products better rated on EOU. With implications for segmentation, those seeking simplicity were older, female, educated, and with less product knowledge, while those already owning a complex phone made replacement decisions with less concern for EOU. The findings support EOU‐based differentiation strategies as a legitimate alternative to other forms of differentiation.
Legacy, Legitimacy, and Possibility
Authors: Swartz Alison
Published: June 2013

In South Africa, the response to HIV and TB epidemics is complex, varied, and contextually defined. “Task‐shifting” and a movement toward a decentralized model of care have led to an increased reliance on community health workers (CHWs) providing health care services to residents of impoverished, peri‐urban areas. Public health policy tends to present CHWs as a homogeneous group, with little attention paid to the nuances of experience, motivation, and understanding, which distinguish these care workers from one another and from other kinds of health workers. An exploration of the layered meanings of providing community health care services under financially, politically, and socially difficult conditions reveals clear distinctions of experience across the generations. Many older CHWs say that ubuntu, a notion of shared African humanity, is being “killed off” by the younger generation, whereas younger CHWs often describe older women as being “jealous” of the opportunities that this younger generation has for education, training, and employment. The structure of the South African health system, past and present responses to disease epidemics, and the legacy of apartheid's structural violence have amplified these generational differences among CHWs. Using ethnographic data collected from approximately 20 CHWS in a peri‐urban settlement in Cape Town, South Africa, I explore how CHWs experience and understand legitimacy in the moral economy of care. A call for closer attention to the experiences of CHWs is critical when designing public health policies for the delivery of health care services in impoverished communities in South Africa.
Urban behavioural adaptation
Authors: Garroway Colin J. , Sheldon Ben C.
Published: June 2013

A large and growing proportion of the world is impacted directly by human activities; among the most extreme of these is the spread of urban environments. Environmental change associated with urbanization represents a potentially potent source of selection. While urban environments generally have lowered biodiversity, some clades seem to thrive in urban settings. For example, many members of the bird family Turdidae, known as the ‘true thrushes’ and the blackbird Turdus merula (Fig. 1) in particular, are familiar urban species. Indeed, the colonization of urban environments by blackbirds has become a textbook case study for our understanding of the many ways a wild species can deal with urbanization. In this issue, Mueller et al. (Molecular Ecology, 00, 2013, 00) add to that story by beginning to address the genetic nature of behavioural adaptation of blackbirds colonizing urban areas. They do this by testing for divergence between paired urban and rural samples at a suite of candidate genes with hypothesized effects on behaviours thought to be important for the colonization of urban environments. They find evidence for consistent patterns of divergence at an exonic microsatellite associated with the SERT gene. SERT has a number of hypothesized behavioural effects, including harm avoidance, which may be associated with tolerating the hustle and bustle of urban environments. This is among the first evidence that behavioural differences between urban and rural environments have a genetic basis and this work suggests that urban environments can in some cases exert homogeneous selection pressures.
What is a genome?
Authors: Stencel A. , Crespi B.
Published: June 2013

The field of genomics is expanding rapidly, yet the meanings of the word ‘genome’ have yet to be conceptualized in explicit, coherent and useful frameworks. We develop and apply an evolutionary conceptualization of the genome, which represents a logical extension of the evolutionary definition of a gene developed by George C. Williams. An evolutionary genome thus represents a set of genetic material, in a lineage, that due to common interests tends to favour the same or similar phenotypes. This conceptualization provides novel perspectives on genome functions, boundaries and evolution, which should help to guide theoretical and empirical genomics research.
More precisely biased: increasing the number of markers is not a silver bullet in genetic bottleneck testing
Authors: Peery M. Zachariah , Reid Brendan N. , Kirby Rebecca , Stoelting Ricka , Doucet‐Bëer Elena , Robinson Stacie , Vásquez‐Carrillo Catalina , Pauli Jonathan N. , Palsbøll Per J.
Published: June 2013

In response to our review of the use of genetic bottleneck tests in the conservation literature (Peery et al. 2012, Molecular Ecology, 21, 3403–3418), Hoban et al. (2013, Molecular Ecology, in press) conducted population genetic simulations to show that the statistical power of genetic bottleneck tests can be increased substantially by sampling large numbers of microsatellite loci, as they suggest is now possible in the age of genomics. While we agree with Hoban and co‐workers in principle, sampling large numbers of microsatellite loci can dramatically increase the probability of committing type 1 errors (i.e. detecting a bottleneck in a stable population) when the mutation model is incorrectly assumed. Using conservative values for mutation model parameters can reduce the probability of committing type 1 errors, but doing so can result in significant losses in statistical power. Moreover, we believe that practical limitations associated with developing large numbers of high‐quality microsatellite loci continue to constrain sample sizes, a belief supported by a literature review of recent studies using next generation sequencing methods to develop microsatellite libraries. conclusion, we maintain that researchers employing genetic bottleneck tests should proceed with caution and carefully assess both statistical power and type 1 error rates associated with their study design.
The mobility of two kinase domains in the Escherichia coli chemoreceptor array varies with signalling state
Authors: Briegel Ariane , Ames Peter , Gumbart James C. , Oikonomou Catherine M. , Parkinson John S. , Jensen Grant J.
Published: June 2013

Motile bacteria sense their physical and chemical environment through highly cooperative, ordered arrays of chemoreceptors. These signalling complexes phosphorylate a response regulator which in turn governs flagellar motor reversals, driving cells towards favourable environments. The structural changes that translate chemoeffector binding into the appropriate kinase output are not known. Here, we apply high‐resolution electron cryotomography to visualize mutant chemoreceptor signalling arrays in well‐defined kinase activity states. The arrays were well ordered in all signalling states, with no discernible differences in receptor conformation at 2–3 nm resolution. Differences were observed, however, in a keel‐like density that we identify here as CheA kinase domains P1 and P2, the phosphorylation site domain and the binding domain for response regulator target proteins. Mutant receptor arrays with high kinase activities all exhibited small keels and high proteolysis susceptibility, indicative of mobile P1 and P2 domains. In contrast, arrays in kinase‐off signalling states exhibited a range of keel sizes. These findings confirm that chemoreceptor arrays do not undergo large structural changes during signalling, and suggest instead that kinase activity is modulated at least in part by changes in the mobility of key domains.
Effects of Geographic Search on Product Innovation in Industrial Cluster Firms in China
Authors: Wu Aiqi , Wei Jiang
Published: June 2013

The literature suggests that cluster firms may undertake both local and nonlocal geographic searches for knowledge that contributes to their product innovation, and that cluster firms must balance their local and nonlocal searches for product innovation. Yet, previous research has seen local and nonlocal searches as one-dimensional, rather than two-dimensional, activities involving search breadth and depth. In this study, we show that local search and nonlocal search are balanced by jointly considering the breadth and depth of geographic search, and that the optimal balance depends on industry dynamism. Using a sample from two industry clusters in China, we find positive relationships between relative local search depth, relative nonlocal search breadth, and the product innovation of cluster firms. Relative local search depth and relative nonlocal search breadth contribute more to product innovation in stable industries than in dynamic industries.
The Managing Emergencies in Paediatric Anaesthesia global rating scale is a reliable tool for simulation‐based assessment in pediatric anesthesia crisis management
Authors: Everett Tobias C. , Ng Elaine , Power Daniel , Marsh Christopher , Tolchard Stephen , Shadrina Anna , Bould Matthew D.
Published: June 2013

Introduction

The use of simulation‐based assessments for high‐stakes physician examinations remains controversial. The Managing Emergencies in Paediatric Anaesthesia course uses simulation to teach evidence‐based management of anesthesia crises to trainee anesthetists in the United Kingdom (UK) and Canada. In this study, we investigated the feasibility and reliability of custom‐designed scenario‐specific performance checklists and a global rating scale (GRS) assessing readiness for independent practice.

Methods

After research ethics board approval, subjects were videoed managing simulated pediatric anesthesia crises in a single Canadian teaching hospital. Each subject was randomized to two of six different scenarios. All 60 scenarios were subsequently rated by four blinded raters (two in the UK, two in Canada) using the checklists and GRS. The actual and predicted reliability of the tools was calculated for different numbers of raters using the intraclass correlation coefficient (ICC) and the Spearman–Brown prophecy formula.

Results

Average measures ICCs ranged from ‘substantial’ to ‘near perfect’ (P ≤ 0.001). The reliability of the checklists and the GRS was similar. Single measures ICCs showed more variability than average measures ICC. At least two raters would be required to achieve acceptable reliability.

Conclusions

We have established the reliability of a GRS to assess the management of simulated crisis scenarios in pediatric anesthesia, and this tool is feasible within the setting of a research study. The global rating scale allows raters to make a judgement regarding a participant's readiness for independent practice. These tools may be used in the future research examining simulation‐based assessment.
Meta‐normative Realism, Evolution, and Our Reasons to Survive
Authors: Behrends Jeff
Published: June 2013

In this article, I articulate and respond to an epistemological challenge to meta‐normative realism. The challenge has it that, if realism about the normative is correct, and if evolutionary forces have significantly influenced our normative judgments, then it would be a remarkable coincidence if the content of the normative facts and our normative judgments were aligned. I criticize David Enoch's recent attempt to meet this challenge, but provide an alternative response that is structurally similar. I argue that if realism is correct, then it would be remarkable if the content of our normative judgments and the normative facts were not significantly aligned.
Reweighting South African National Household Survey Data to Create a Consistent Series Over Time: A Cross‐Entropy Estimation Approach
Authors: Branson Nicola , Wittenberg Martin
Published: June 2013

In the absence of established longitudinal panel surveys in South Africa, national cross‐sectional household survey data are frequently used to analyse change. When these data are stacked side by side, however, inconsistencies both in time trends and between household‐ and person‐level data are found. This study uses a new set of weights calibrated to the Actuarial Society of South Africa 2003 model projected totals using a cross‐entropy estimation approach. These weights are favoured because they produce consistent demographic and geographic trends. The calculated weights are similar to the initial sample weights (and hence retain the survey design benefits) but match to a series of age‐sex‐race and province marginal totals that are consistent over time. The weights are publicly available for the 14‐year period between 1994 and 2007.
Overuse and traumatic extremity injuries in schoolchildren surveyed with weekly text messages over 2.5 years
Authors: Jespersen E. , Holst R. , Franz C. , Rexen C. T. , Klakk H. , Wedderkopp N.
Published: June 2013

The objectives of this prospective cohort study were to report the incidence, prevalence, and duration of traumatic and overuse injuries during a period of 2.5 years and to estimate the odds of injury types. In all, 1259 schoolchildren, aged 6–12, were surveyed each week with an automated mobile phone text message asking questions on the presence of any musculo‐skeletal problems and participation in leisure‐time sport. Children were examined and injuries classified as overuse or traumatic. The overall injury incidence and prevalence were 1.2% and 4.6% per week, with 2.5 times more overuse than traumatic injuries in lower extremities, and mean injury duration of 5.3 and 4.8 weeks, respectively. A reverse pattern was found for upper extremities, with 3.1 times more traumatic than overuse injuries and mean durations of 3.3 and 5.2 weeks, respectively. Grade level, school type, leisure‐time sport, and seasonal variation were associated with the risk of sustaining lower extremity injuries. Only grade level was associated with upper extremity injuries. The magnitude of overuse and traumatic limb injuries emphasizes the need for health professionals, coaches, and parents to pay special attention in relation to the growing and physically active child.
Unsociability and Shyness in Chinese Children: Concurrent and Predictive Relations with Indices of Adjustment
Authors: Liu Junsheng , Coplan Robert J. , Chen Xinyin , Li Dan , Ding Xuechen , Zhou Ying
Published: June 2013

The primary goal of this study was to examine the short‐term longitudinal associations between unsociability, shyness, and indices of adjustment among Chinese children. Participants were 787 children (ages 10–14 years) in an urban area in China. Assessments of unsociability, shyness, and adjustment were obtained from multiple sources, including peer nominations, self‐reports, and school records. Results indicated that while controlling for the effects of shyness, unsociability was associated with socioemotional and school difficulties. In particular, unsociability appeared to act as a risk factor for later peer problems and internalizing difficulties across the school year. Some gender differences were also observed in the longitudinal associations between unsociability and indices of adjustment. Results are discussed in terms of the meaning and implication of unsociability in Chinese culture.
Relations Among Gender Typicality, Peer Relations, and Mental Health During Early Adolescence
Authors: Jewell Jennifer A. , Brown Christia Spears
Published: June 2013

The current study examines whether being high in gender typicality is associated with popularity, whether being low in gender typicality is associated with rejection/teasing, and whether teasing due to low gender typicality mediates the association with negative mental health. Middle school children (34 boys and 50 girls) described hypothetical popular and rejected/teased peers, and completed self‐report measures about their own gender typicality, experiences with gender‐based teasing, depressive symptoms, anxiety, self‐esteem, and body image. Participants also completed measures about their peers' gender typicality, popularity, and likeability. Results indicated that popular youth were described as more gender typical than rejected/teased youth. Further, being typical for one's gender significantly predicted being rated as popular by peers, and this relationship was moderated by gender. Finally, low gender typicality predicted more negative mental health outcomes for boys. These relationships were, at times, mediated by experiences with gender‐based teasing, suggesting that negative mental health outcomes may be a result of the social repercussions of being low in gender typicality rather than a direct result of low typicality.
What DoYouThink? The Relationship between Person Reference and Communication About the Mind in Toddlers
Authors: Markova Gabriela , Smolík Filip
Published: June 2013

The present studies examined the relationship between children's use of grammatical structures indicating self–other differentiation (i.e., personal pronouns, verb conjugation) and their ability to use language to express their own and others' mental states (MSL). In Study 1, 104 parents of two‐ to three‐year‐old children filled out online checklists assessing children's vocabulary, their use ofMSL, and first‐ and second‐person pronouns and verb forms. In Study 2, 77 mothers of 1.5‐ to 2.5‐year‐old children filled out theMacArthur–Bates communicative development inventory, and additional checklists forMSLand verb conjugation. Results of both studies showed that children's use of grammatical person reference is strongly related to their level of grammatical abilities. Importantly, pronominal and inflectional references to others were correlated with children's discourse about the mind. Thus, linguistic tools that are used to distinguish self from others are not only indicators of children's grammatical development, but also their level of sociocognitive understanding.
Rhamnogalacturonan II structure shows variation in the side chains monosaccharide composition and methylation status within and across different plant species
Authors: Pabst Martin , Fischl Richard M. , Brecker Lothar , Morelle Willy , Fauland Alexander , Köfeler Harald , Altmann Friedrich , Léonard Renaud
Published: June 2013

A paradigm regarding rhamnogalacturonans II (RGII) is their strictly conserved structure within a given plant. We developed and employed a fast structural characterization method based on chromatography and mass spectrometry, allowing analysis of RGII side chains from microgram amounts of cell wall. We found that RGII structures are much more diverse than so far described. In chain A of wild‐type plants, up to 45% of the l–fucose is substituted by l–galactose, a state that is seemingly uncorrelated with RGII dimerization capacity. This led us to completely reinvestigate RGII structures of the Arabidopsis thaliana fucose‐deficient mutant mur1, which provided insights into RGII chain A biosynthesis, and suggested that chain A truncation, rather than l–fucose to l–galactose substitution, is responsible for the mur1 dwarf phenotype. Mass spectrometry data for chain A coupled with NMR analysis revealed a high degree of methyl esterification of its glucuronic acid, providing a plausible explanation for the puzzling RGII antibody recognition. The β–galacturonic acid of chain A exhibits up to two methyl etherifications in an organ‐specific manner. Combined with variation in the length of side chain B, this gives rise to a family of RGII structures instead of the unique structure described up to now. These findings pave the way for studies on the physiological roles of modulation of RGII composition.
Multiple fates of non‐mature lumenal proteins in thylakoids
Authors: Midorikawa Takafumi , Inoue Kentaro
Published: June 2013

Most proteins found in the thylakoid lumen are synthesized in the cytosol with an N–terminal extension consisting of transient signals for chloroplast import and thylakoid transfer in tandem. The thylakoid‐transfer signal is required for protein sorting from the stroma to thylakoids, mainly via the cpSEC or cpTAT pathway, and is removed by the thylakoidal processing peptidase in the lumen. An Arabidopsis mutant lacking one of the thylakoidal processing peptidase homologs, Plsp1, contains plastids with anomalous thylakoids and is seedling‐lethal. Furthermore, the mutant plastids accumulate two cpSEC substrates (PsbO and PetE) and one cpTAT substrate (PsbP) as intermediate forms. These properties of plsp1‐null plastids suggest that complete maturation of lumenal proteins is a critical step for proper thylakoid assembly. Here we tested the effects of inhibition of thylakoid‐transfer signal removal on protein targeting and accumulation by examining the localization of non‐mature lumenal proteins in the Arabidopsis plsp1‐null mutant and performing a protein import assay using pea chloroplasts. In plsp1‐null plastids, the two cpSEC substrates were shown to be tightly associated with the membrane, while non‐mature PsbP was found in the stroma. The import assay revealed that inhibition of thylakoid‐transfer signal removal did not disrupt cpSEC‐ and cpTAT‐dependent translocation, but prevented release of proteins from the membrane. Interestingly, non‐mature PetE2 was quickly degraded under light, and unprocessed PsbO1 and PsbP1 were found in a 440‐kDa complex and as a monomer, respectively. These results indicate that the cpTAT pathway may be disrupted in the plsp1‐null mutant, and that there are multiple mechanisms to control unprocessed lumenal proteins in thylakoids.
Plasmid-Encoded Proinsulin Preserves C-Peptide While Specifically Reducing Proinsulin-Specific CD8
+
T Cells in Type 1 Diabetes
Authors: Roep Bart O. , Solvason Nanette , Gottlieb Peter A. , Abreu Joana R. F. , Harrison Leonard C. , Eisenbarth George S. , Yu Liping , Leviten Michael , Hagopian William A. , Buse John B. , von Herrath Matthias , Quan Joanne , King Robert S. , Robinson William H. , Utz Paul J. , Garren Hideki ,   The BHT-3021 Investigators, Steinman Lawrence
Published: June 2013

A plasmid encoding proinsulin reduces the frequency of CD8
+
T cells reactive to proinsulin while preserving C-peptide.
Getting to the Heart of Influenza
Authors: Yewdell Jonathan W. , Spiro David J. , Golding Hana , Quill Helen , Mittelman Abraham , Nabel Gary J.
Published: June 2013

Diverse stakeholders convened at the U.S. National Institutes of Health to devise a plan for development of universal influenza virus vaccines.
Molecular genetic testing for lung adenocarcinomas: a practical approach to clinically relevant mutations and translocations
Authors: Dacic Sanja
Published: June 2013

There is a consensus that molecular testing of the lung carcinoma should be the standard of care in the clinical management of patients with lung carcinoma. Recent practice guidelines in oncology and pathology recommend that all advanced and metastatic non-small-cell lung carcinoma with adenocarcinoma histology undergo biomarker testing for epidermal growth factor receptor gene (EGFR) mutations and anaplastic lymphoma kinase gene (ALK) rearrangements. Other types of non-small-cell carcinoma may be considered for such testing if they occur in never-smokers. The landscape of targetable biomarkers in non-small-cell carcinoma is changing rapidly, and demand for clinical testing beyondEGFRmutations andALKgene rearrangements is increasing. Many patients may test positive for other ‘drivers’. As a result, they may be treated with approved biomarker-driven therapies or may be eligible to receive investigational agents in clinical trials. This creates challenges for treating physicians and pathologists such as obtaining sufficient tissue for molecular testing and standardisation of molecular testing in clinical laboratories. This review will focus on the most important lung carcinoma biomarkers predictive of response and will discuss proposed routine molecular testing in clinical practice.
Identification of MET genomic amplification, protein expression and alternative splice isoforms in neuroblastomas
Authors: Yan Benedict , Lim Malcolm , Zhou Lihan , Kuick Chik Hong , Leong May Ying , Yong Kol Jia , Aung LeLe , Salto-Tellez Manuel , Chang Kenneth T E
Published: June 2013

Background

Crizotinib, a dual anaplastic lymphoma kinase (ALK) and mesenchymal-epithelial transition (MET) tyrosine kinase inhibitor, is currently being evaluated for the treatment of neuroblastoma. Its effects are thought to be mediated mainly via its activity against ALK. Although MET genomic/protein expression status might conceivably affect crizotinib efficacy, this issue has hitherto not received attention in neuroblastomas.

Aims/Methods

MET genomic and protein expression status was characterised by silver in situ hybridisation and immunohistochemistry (IHC) respectively, in a cohort of 54 neuroblastoma samples. MET splice isoforms were characterised in 15 of these samples by quantitative PCR.

Results

One case (1/54; prevalence 1.85%) displayedMETgenomic amplification, while another case (1/54; prevalence 1.85%) displayed strong membranous MET protein expression (IHC score 3+). Alternative exon 10-deleted and exon 14-deleted MET splice isoforms were identified.

Conclusions

MET amplification and protein expression, although low in prevalence, are present in neuroblastomas. This has implications when crizotinib is employed as a therapeutic agent in neuroblastomas. Additionally, the existence of alternatively spliced MET isoforms may have clinical and biological implications in neuroblastomas.
Discussion of “Numerical assessment of equivalent diameter equations for prefabricated vertical drains”
Authors: Wu Hui , Hu Liming
Published: June 2013

The Discussion revises the figure that compares different equivalent-diameter equations for prefabricated vertical drains, and the result of another equivalent equation that has been widely used in practice is also added into the figure. In addition, a three-dimensional (3D) numerical model is developed to compare with the two-dimensional (2D) numerical model used in the paper. The result indicates that the difference between the 3D and 2D models can be about 5%.
HAAG'S THEOREM IN THE THEORIES WITH NONPHYSICAL PARTICLES
Authors: ANTIPIN K. V. , MNATSAKANOVA M. N. , VERNOV YU. S.
Published: June 2013

Haag's theorem is extended to the case of regular representations of the canonical commutation relations in a nondegenerate indefinite inner product space.
Geomechanical impacts on flow in fractured reservoirs
Authors: Couples Gary D.
Published: June 2013

Flow responses in fractured reservoirs are difficult to predict. Apparent success in predicting flow has been achieved by developing simple rules of thumb based on (i) alterations of effective stress associated with pore pressure changes or (ii) concepts about fracture aperture alterations due to stress changes. Here it is argued that the assumptions underlying these explanations of flow are flawed, as they are based on ideas about stress that are physically wrong. It may be that these simple ideas can be fitted to some observations, but their use in this fashion is highly risky. The role of geomechanics in fractured reservoirs is more complex than suggested by the simple rules of thumb, as illustrated by numerical simulations that demonstrate the occurrence of strong non-linear interactions between the fluids, the geomechanics of blocky systems, and thermal changes. The resulting movements within fractured rock masses can cause major alterations of the upscaled flow properties. Flow performance discrepancies that are often associated with the operation of fractured reservoirs can, and often should, be seen as a consequence of motions occurring within the fractured rock mass. The explanations developed here are phenomenologically correct, and are more holistic than existing simple rules of thumb, improving the reliability of predictions.
Mass Spectrometric Studies of Non-Equilibrium Vaporizations in Knudsen Cells: A Way to the Determination of the Nature of Kinetic Processes
Authors: Chatillon C. , Nuta I.
Published: June 2013

Non-equilibrium vaporizations in Knudsen cells occur when the net rate of vaporization at the surface of the sample is slower than the rate of effusion. In such a situation, the description of the molecular flow exchanges in an effusion cell according to the Motzfeldt equation allows the determination of the evaporation coefficients from different pressure determinations of the same sample performed with different cell geometries. Further, the chemical signification of the value of the evaporation coefficients was not very often explained. Different thermodynamic analyses are presented on experimental results in order to explain the origin of retarded vaporizations of Al2O3 , SiO2 , AlN , BN and mixtures Si-SiO2 as well as amorphous SiO.
Knudsen Effusion Mass Spectrometry of Nuclear Materials: Applications and Developments
Authors: Colle J.-Y. , Freis D. , Beneš O. , Konings R. J. M.
Published: June 2013

The nuclearised Knudsen Effusion Mass Spectrometry (KEMS) facility at ITU is a unique device to measure not only the partial vapor pressure and ionization efficiency curves of actinide compounds, but also the release of fission product from irradiated fuel. Those measurements provide fundamental data for the safety assessment of nuclear fuel in normal and accidental conditions as well as for long term storage. The system is installed in a glove box and operates at very high temperatures, and thus requires a specific setup. Currently a 20 years old KEMS system equipped with a quadrupole mass spectrometer and joule heating coil is used. For a future system, a prototype of a laser-heated furnace for the Knudsen cell has been developed. It presents many advantages in comparison to standard heating techniques and fulfills key requirements for use in a nuclear environment. All these subjects are discussed.
Combination of Thermal Analysis and Knudsen Effusion Mass Spectrometry for Study of Metal Materials on Macro- and Nano-Scale
Authors: Broz Pavel , Sopousek Jiri , Vrestal Jan , Pinkas Jiri
Published: June 2013

The study of metal materials could not be possible without the use of sophisticated techniques often enabling us to do precise experiments of various types by means of multifunction equipments. One of these is an apparatus combining thermal analysis (TA) with Knudsen effusion mass spectrometry (KEMS). In the Netzsch STA 409 CD/3/403/5/G apparatus, a specially-adapted type of the commercial STA 409 CD – QMS 403/5 Skimmer Coupling Instrument, the holder for differential scanning calorimetry (DSC) or differential thermal analysis (DTA) can be replaced by another one with alumina Knudsen cell for vapour pressure measurement of activities of components. The instrument capabilities are demonstrated on several examples of TA and effusion measurements of bulk metal materials and nano-powders.
The Design, Construction, and Testing of a Knudsen Effusion Mass Spectrometric System Suitable for Studies of Nuclear Fuel Materials
Authors: Raj D. D. A. , Viswanathan R. , Manikandan P.
Published: June 2013

Benefiting hugely from many years of experience of conducting vaporization studies with a commercially bought magnetic sector instrument (VG Micromass 30 BK), we designed and constructed a KEMS system having a quadrupole mass spectrometer. It essentially consisted of two chambers, one housing the Knudsen cell furnace assembly and the other housing the QMS with an indigenously designed and fabricated vacuum-isolation valve between these two chambers. The QMS initially used was from Extrel, but later that from Hiden was installed. Systematic vaporization experiments were undertaken on iron, nickel, chromium, zirconium, a Fe-Al alloy, MnO, uranium, and a U-Zr alloy. Electron bombardment heating was employed and the temperatures were measured by sighting the optical pyrometer onto a blackbody hole drilled at the bottom of the Knudsen cell. The results on the elements and the Fe-Al alloy were satisfactory while those on MnO, U, and U-Zr alloy were disconcerting but interesting and educative.
Determination of the Dissociation Energy of Diatomic Molecules by KEMS (Knudsen Effusion Mass Spectrometry): Intragroup 14 and Group 11-Group 2 Molecules
Authors: Ciccioli A. , Gigli G.
Published: June 2013

This contribution summarize our recent work devoted to detect and thermochemically characterise by KEMS experiments (Knudsen Effusion Mass Spectrometry) a number of diatomic gaseous molecules either never observed before or whose bond energy was unknown. The results obtained over the years for the intragroup 14 and the group 11-group 2 species are here collected and compared with quantum chemical calculations at the CCSD(T) level.
Transformation of a Double Focusing B-E Mass Spectrometer for Multiple-Cell Knudsen Effusion – Part I: Scientific Concepts
Authors: Benigni P. , Berche A. , Mikaelian G. , Rogez J.
Published: June 2013

Knudsen Effusion Mass Spectrometry (KEMS) is a powerful method in the field of experimental thermodynamics at high temperatures. Since 2005, the long term project of transforming and upgrading a double-focusing VG Micromass 54-38K mass spectrometer for multiple-cell effusion has started at the IM2NP in Marseille/France. The scientific concepts underlying the transformation are presented in this first paper. The molecular beam effusing from the Knudsen cells must be sampled under restricted collimation conditions. The resulting geometric constraints are taken into account in the design of the large main vacuum chamber necessary to house a multiple-cell effusion furnace. Decrease of the molecular transmission between the cell and the ionization source needs to be counterbalanced by an increase in the sensitivity of the ionization source. Other modifications of the instrument are reviewed. The first tests and results will be the subject of a second paper to be published.
Knudsen Effusion Mass Spectrometry for Study of Vaporization Chemistry
Authors: Viswanathan R. , Lakshmi Narasimhan T. S.
Published: June 2013

The Knudsen effusion mass spectrometry (KEMS) made it possible to unravel the mystery of the vapor phases of various systems – by identification and quantification of the vapor species in equilibrium with the condense phases of interest. KEMS also enabled deduction of many thermodynamic quantities pertinent to reactions amongst the constituents of the vapor and/or the condensed phases. Since the advent of KEMS, thousands of vaporization studies have been conducted. Many studies are still being performed mostly to obtain better results or for some specific industrial applications. The basic steps of a KEMS investigation might appear routine, but the vaporization chemistry associated with each system makes every study interesting, especially those studies dealing with condensed phase transitions. We describe here a few KEMS studies which reported the effects attributed to phase transformations in congruently as well as incongruently vaporizing systems.
The Study of Cerium Tetrafluoride Vaporization by Knudsen Effusion Mass Spectrometry
Authors: Chilingarov N. S. , Shlyapnikov I. M. , Mazej Z. , Moiseev A. E. , Shlyapnikov Y. M. , Ishtubaev I. V.
Published: June 2013

The evaporation and decomposition of cerium tetrafluoride CeF4(s) at high temperatures were studied by means of Knudsen Effusion Mass Spectrometry (KEMS). The saturated vapor pressure over CeF4(s) was determined by the isothermal evaporation of the sample from Pt Knudsen cell. The enthalpy of CeF4(s) sublimation was calculated using the second and the third laws of thermodynamics.
Thermodynamic Properties of Gaseous Alkali Metal Vanadates Monomers and Dimers by High Temperature Mass Spectrometry
Authors: Shugurov S. M. , Lopatin S. I.
Published: June 2013

The stability of gaseous alkali metal vanadates and their dimers were confirmed by Knudsen effusion mass spectrometry. The molecular parameters and structures of gaseous molecules were calculated by quantum chemical computation. The standard formation enthalpies of gaseous molecules MVO3 and M2V2O6 (M = K, Rb, Cs) were determined.
Knudsen Effusion Mass Spectrometric Study of Some Congruently and Incongruently Vaporizing Systems
Authors: Lakshmi Narasimhan T. S. , Viswanathan R.
Published: June 2013

We have performed KEMS measurements on both congruently and incongruently vaporizing systems. The congruently vaporizing compounds include TeO2(s), MnTe(s), H3BO3(s), and NaBO2(s). The incongruently vaporizing systems include binary tellurides of Fe, Cr, Ni, Mo, Mn, and the ternary Mn-Te-O. The various aspects concerning the vaporization behavior of these systems will be presented in this paper.
Optimization of Cell Components on the Direct Carbon Fuel Cell
Authors: Mochidzuki Ryosuke , Sugiura Kimihiko
Published: June 2013

Although the global warming is becoming a world-wide problem, nuclear power plant, which had expected to solve this problem, has been avoided after the accident of Nuclear Power Plants at Fukushima. Therefore, it is necessary to use fossil fuels efficiently in order to solve the problem. Direct Carbon Fuel Cells (DCFC) is a type of high temperature fuel cells using a molten carbonate as electrolyte and can generate electrical energy in higher efficiency by the electrochemical oxidation of solid carbon such as a coal. However, because the study of DCFC is hardly reported, we evaluated the fundamental cell performance using the prototype-DCFC. The influence on the cell performance by kind fuel (activated carbon, brown coal) and kind of electrolyte (Li/KCO3, Li/NaCO3) is evaluated. As a result, a fuel and an electrolyte exert a big influence on the DCFC performance, and the cell structure of DCFC should be also optimized to increase the contact of the electrolyte and solid fuel on the anode side.
Recent Progress of SOFC-GT Combined System with Tubular Type Cell Stack at MHI
Authors: Kobayashi Yoshinori , Ando Yoshimasa , Kishizawa Hiroshi , Tomida Kazuo , Matake Norihisa
Published: June 2013

A solid oxide fuel cell (SOFC) is a fuel cell that can operate at high temperature. By applying its high-temperature exhaust heat to gas turbine (GT) combined-cycle power generation, an extremely high-efficiency thermal power system can be constructed, with a power generation efficiency of up to 70%. Mitsubishi Heavy Industries, Ltd. (MHI) is one of the first companies to focus on the potential of the SOFC as a component of large-scale power generation systems and has promoted both element and system development since the 1980s. New 250kW-class SOFC-MGT Hybrid System has been under trial operation since November 2012.