bluuebunny/crossref_metadata_2025 huggingface dataset:
Internationalisation strategy of iconic Malaysian high fashion brands
Authors: Kuang‐Ying Loo Benaliza , Hackley Chris
Published: August 2013

Purpose

The purpose of this paper is to explore the success factors behind four globally recognised Malaysian high fashion brands. The three main sub‐objectives are: to map the process of high fashion internationalisation onto the general retail internationalisation literature; to engage fashion within the more general marketing and branding literature; to open up a qualitative line of inquiry in internationalisation research, from an Asian business perspective.

Design/methodology/approach

The research design is qualitative, using a case study approach. The paper reports part of a wider study that entailed 32 depth interviews with leading practitioners in four countries, in addition to secondary and informal data sources.

Findings

The chosen case studies achieved their international success through a high degree of cultural assimilation obtained within locations of intense industrial concentration. Knowledge of education, location, language, networks and management systems were important to sustain world class standards of creative design, branding, quality management and marketing communication. For many Asian fashion brands, recognition in key European and American markets enhances the domestic prestige of the brand.

Research limitations/implications

The research generates contextualised insights that are not statistically generalisable.

Practical implications

The study offers first hand insights into high fashion branding and retail internationalisation from four of the most celebrated Asian designers.

Originality/value

The study responds to a need, highlighted in the literature, for more research into the internationalisation strategies of high fashion retail brands.
Why do firms cross‐list their shares on foreign exchanges? A review of cross‐listing theories and empirical evidence
Authors: Dodd Olga
Published: August 2013

Purpose

Financial markets’ integration and technological advances in equity trading may have reduced the potential benefits from listing a firm's shares on a foreign exchange. Nevertheless, a significant number of firms continue to cross‐list every year. This paper examines the recent cross‐listing trends and reviews the literature on motives to cross‐list.

Design/methodology/approach

The literature review includes a summary of theoretical studies grouped into cross‐listing theories including market segmentation, liquidity, investor recognition, information disclosure, legal bonding, proximity preference and business strategy theories, and also includes a discussion of testable implications and empirical evidence for each of the above mentioned cross‐listing theories.

Findings

An extensive cross‐listing literature offers a number of theories on the motives to cross‐list that in most cases complement each other by encompassing different aspects of the complex cross‐listing behavior. Nevertheless, continuous market developments, such as significant regulatory and technological changes in the ways capital markets operate, raise new questions on why firms cross‐list and call for further research to continue.
“Make Every Moment Count” in care for older people
Authors: A. Macintosh Edith
Published: August 2013

Purpose

– The purpose of this paper is to highlight the importance of Make Every Moment Count (MEMC) and explain the development of it.

Design/methodology/approach

– A working group of representatives from key organisations in Scotland developed the resource MEMC. It was tested out in a variety of care settings and issued to all care homes for older people and care at home services in Scotland.

Findings

– The paper highlights the importance of participating in day-to-day life on health and well-being and provides feedback from care staff on using the resource.

Practical implications

– The resource is for all those supporting someone to engage in day-to-day life. A lot of good care is given however sometimes the small, everyday interactions are taken for granted and people need reminded about the big difference this can make to someone's life.

Social implications

– MEMC has the potential to begin to change culture – to rethink “activity” which is often thought of as planned organised events to everyday activities and interactions.

Originality/value

– This paper describes an initiative which sets out to remind us all of the importance of basic human rights – dignity, respect and choice.
Exploiting extension bias in polymerase chain reaction to improve primer specificity in ensembles of nearly identical DNA templates
Authors: Wright Erik S. , Yilmaz L. Safak , Ram Sri , Gasser Jeremy M. , Harrington Gregory W. , Noguera Daniel R.
Published: August 2013

We describe a semi‐empirical framework that combines thermodynamic models of primer hybridization with experimentally determined elongation biases introduced by 3′‐end mismatches for improving polymerase chain reaction (PCR)‐based sequence discrimination. The framework enables rational and automatic design of primers for optimal targeting of one or more sequences in ensembles of nearly identical DNA templates. In situations where optimal targeting is not feasible, the framework accurately predicts non‐target sequences that are difficult to distinguish with PCR alone. Based on the synergistic effects of disparate sources of PCR bias, we used our framework to robustly distinguish between two alleles that differ by a single base pair. To demonstrate the applicability to environmental microbiology, we designed primers specific to all recognized archaeal and bacterial genera in the Ribosomal Database Project, and have made these primers available online. We applied these primers experimentally to obtain genus‐specific amplification of 16S rRNA genes representing minor constituents of an environmental DNA sample. Our results demonstrate that inherent PCR biases can be reliably employed in an automatic fashion to maximize sequence discrimination and accurately identify potential cross‐amplifications. We have made our framework accessible online as a programme for designing primers targeting one group of sequences in a set with many other sequences (http://DECIPHER.cee.wisc.edu).
Post‐chemotherapy Maturation in Supratentorial Primitive Neuroectodermal Tumors
Authors: Lafay‐Cousin Lucie , Hader Walter , Wei Xing Chang , Nordal Robert , Strother Douglas , Hawkins Cynthia , Chan Jennifer A.
Published: August 2013

Maturation in central nervous system embryonal tumors is an uncommon phenomenon that is mainly reported in the context of specific histological subgroups of medulloblastoma. In this report we describe two cases of histological maturation in patients with supratentorial primitive neuroectodermal tumor with strikingly different outcomes. We discuss the potential impact of such findings on treatment and outcome.
Development of hybrid small molecules that induce degradation of estrogen receptor‐alpha and necrotic cell death in breast cancer cells
Authors: Okuhira Keiichiro , Demizu Yosuke , Hattori Takayuki , Ohoka Nobumichi , Shibata Norihito , Nishimaki‐Mogami Tomoko , Okuda Haruhiro , Kurihara Masaaki , Naito Mikihiko
Published: August 2013

Manipulation of protein stability with small molecules has a great potential for both basic research and clinical therapy. Recently, we have developed a series of hybrid small molecules named SNIPER (Specific and Non‐genetic IAP‐dependent Protein ERaser) that induces degradation of target proteins via ubiquitin‐proteasome system. Here we report the activities of SNIPER(ER) that targets estrogen receptor alpha (ERα) for degradation. SNIPER(ER) induced degradation of ERα and inhibited estrogen‐dependent expression of pS2 gene in an estrogen‐dependent breast cancer cell line MCF‐7. A proteasome inhibitor MG132 and siRNA‐mediated downregulation of cIAP1 abrogated the SNIPER(ER)‐induced ERα degradation, suggesting that the ERα is degraded by proteasome subsequent to cIAP1‐mediated ubiquitylation. Intriguingly, after the ERα degradation, the SNIPER(ER)‐treated MCF‐7 cells undergo rapid cell death. Detailed analysis indicated that SNIPER(ER) caused necrotic cell death accompanied by a release of HMGB1, a marker of necrosis, from the cells. Following the ERα degradation, reactive oxygen species (ROS) was produced in the SNIPER(ER)‐treated MCF‐7 cells, and an anti‐oxidant N‐acetylcysteine inhibited the necrotic cell death. These results indicate that SNIPER(ER) induces ERα degradation, ROS production and necrotic cell death, implying a therapeutic potential of SNIPER(ER) as a lead for the treatment of ERα‐positive breast cancers.
Overexpression of G100S mutation in PRKAG2 causes Wolff–Parkinson–White syndrome in zebrafish
Authors: Zhang B.L. , Ye Z. , Xu R.L. , You X.H. , Qin Y.W. , Wu H. , Cao J. , Zhang J.L. , Zheng X. , Zhao X.X.
Published: August 2013

The Wolff–Parkinson–White (WPW) syndrome was believed to be associated with PRKAG2 gene mutations. In this study, we verified the pathopoiesis of G100S mutation, a novel mutation only discovered in Chinese patients with WPW, in cardiac disorder. Similar to R302Q, when overexpressed PRKAG2 G100S mutant in zebrafish, we observed a thicker heart wall, detected a decreased AMPK enzymatic activity by tissue AMPK kinase activity colorimetric technique, as well as examined an increased glycogen storage in heart wall using the method for periodic acid‐Schiff staining, in comparison with the zebrafish without exogenous PRKAG2 (mock) or with wild‐type PRKAG2 (WT). Taken together, we concluded PRKAG2 G100S mutation might contribute to impair the AMP‐activated protein kinase function, which resulted in increased cardiac glycogen storage, serving as a pathogenesis for WPW syndrome in Chinese.
Mind the (information) gap: the importance of exploration and discovery for assessing conservation priorities for freshwater fish
Authors: Alofs Karen M. , Liverpool Elford A. , Taphorn Donald C. , Bernard Calvin R. , López‐Fernández Hernán
Published: August 2013

Biodiversity conservation often is aimed at areas of high species richness and endemism. Our understanding of freshwater fish diversity in the Neotropics is biased by lack of exploration within mountainous regions that historically have been difficult to access. These regions are particularly likely to contain high species endemism. The upper Mazaruni River drainage is hydrogeographically and climatically distinct from the rest of the Essequibo Basin. Recent ichthyological expeditions to the upper Mazaruni discovered up to 32 species previously unknown to science and a fish assemblage with perhaps the highest level of endemism in the Neotropics. This unique ichthyofauna is threatened by gold mining that has severely degraded aquatic habitats and therefore requires immediate protection.
Subjective cognitive decline in patients with mild cognitive impairment and healthy older adults: Association with personality traits
Authors: Studer Joseph , Donati Alessia , Popp Julius , von Gunten Armin
Published: August 2013

Aim

In normal aging, subjective cognitive decline (SCD) might reflect personality traits or affective states rather than objective cognitive decline. However, little is known on the correlates of SCD in mild cognitive impairment (MCI). The present study investigates SCD in MCI patients and healthy older adults, and explores the association of SCD with personality traits, affective states, behavioral and psychological symptoms (BPS), and episodic memory in patients with MCI as compared with healthy older adults.

Methods

A total of 55 patients with MCI and 84 healthy older adults were recruited. Standard instruments were used to evaluate SCD, episodic memory, BPS and affective states. Premorbid and current personality traits were assessed by proxies using the NEO Personality Inventory Revised.

Results

Patients with MCI generally reported SCD more often than healthy older adults. SCD was positively associated with depressive symptoms in both groups. With regard to personality, no significant relationship was found in the healthy older group, whereas agreeableness was significantly negatively related to SCD in the MCI group. No significant association was found between SCD and episodic memory.

Conclusions

SCD is more prevalent in patients with MCI than in the healthy elderly, but it does not reflect an objective cognitive impairment. SCD rather echoes depressive symptoms in both patients with MCI and healthy subjects. The negative association of SCD with agreeableness observed in patients with MCI could indicate that MCI patients scoring high on the agreeableness trait would not report SCD in order to prevent their relatives worrying about their increasing cognitive difficulties. Geriatr Gerontol Int 2014; 14: 589–595.
The involvement of gynaecological patients in the development of a clinical guideline for resumption of (work) activities in the Netherlands
Authors: Pittens Carina A.C.M. , Vonk Noordegraaf Antonie , van Veen Saskia C. , Anema Johannes R. , Huirne Judith A.F. , Broerse Jacqueline E.W.
Published: August 2013

Context

Most initiatives for patient involvement in guideline development have been carried out for chronic diseases. The involvement of patients with incidental and non‐threatening diseases is more complicated. Little knowledge is available on how these patient groups can successfully be involved in guideline development.

Objective

To assess the effectiveness of the involvement of gynaecological patients in the guideline development for resumption of (work) activities after surgery.

Design

At three different stages patients were involved in the process: (i) three focus group discussions (FGDs) were organized, (ii) patients were involved for the instruction video, and (iii) patients tested the patient version of the clinical guideline. To assess the effectiveness, an evaluation framework was used. The guideline development process was divided into two parallel trajectories in which patients and professionals were consulted separately. Patients were primarily consulted for the development of the patient version, although their input also influenced the recommendations for resumption of (work) activities after surgery. Professionals were mainly involved in the development of the recommendations of the clinical guideline.

Discussion and conclusions

The involvement of gynaecological patients in the guideline development for resumption of (work) activities after surgery was successful in many respects. Consultation of individual patients by means of FGDs and with regular feedback moments has been rather effective for a guideline development process related to an incidental, non‐threatening disease for which there is no patient organization. Patients' input contributed to applicability of the clinical guideline in daily practice. Increased patient involvement could be achieved by integration of the two parallel trajectories with additional participatory activities, such as a dialogue meeting.
Individual mindfulness‐based psychotherapy for cannabis or cocaine dependence: A pilot feasibility trial
Authors: Dakwar Elias , Levin Frances R.
Published: August 2013

Background

Mindfulness‐based approaches may be effective treatments for substance use disorders (SUDs), but they have only been investigated for SUDs in the group setting.

Methods

A novel 10‐week individual mindfulness‐based psychotherapy was provided weekly to participants. Tolerability and therapeutic feasibility were assessed by retention rates, incidence of adverse events or clinical worsening, and abstinence rates at the end of the protocol.

Results

Twenty‐five patients were enrolled overall, and 19 completed (74% overall retention rate). Of the 14 cannabis dependent patients enrolled in the study, 11 completed (79%), and 8 achieved abstinence (57% by intent‐to‐treat analysis) at 10 weeks. Of the 11 cocaine dependent patients, 8 completed (73%), and 6 achieved abstinence (55% by ITT) at 10 weeks. Abstinence rates were substantially greater than those of historical comparison groups.

Conclusions

These findings indicate that mindfulness training can be tolerably and feasibly extended to the individual psychotherapy setting for the treatment of cocaine or cannabis dependence. (Am J Addict 2013;22:521–526)
Acupuncture and relaxation response for craving and anxiety reduction among military veterans in recovery from substance use disorder
Authors: Chang Bei‐Hung , Sommers Elizabeth
Published: August 2013

Background and Objectives

Substance use disorder (SUD) is a major health issue, especially among military veterans. We previously reported the effects of auricular acupuncture and the relaxation response (RR) on reducing craving and anxiety following 10‐week interventions among veterans who were in recovery from SUDs. Our current analysis examines effects following each intervention session and RR daily practice.

Methods

We conducted a three‐arm randomized controlled trial on residents of a homeless veteran rehabilitation program. Sixty‐Seven enroled participants were randomly assigned to acupuncture (n = 23), RR (n = 23), or usual care (n = 21). Participants in the two intervention groups rated their degree of craving for substance on a scale of 1–10 and anxiety levels on a scale of 1–4 (total score 20–80) before and after each intervention session. Mixed effects regression models were used for analysis.

Results

Craving and anxiety levels decreased significantly following one session of acupuncture (−1.04, p = .0001; −8.83, p < .0001) or RR intervention (−.43, p = .02; −4.64, p = .03). The level of craving continued to drop with additional intervention sessions (regression coefficient b = −.10, p = .01, and b = −.10, p = .02 for acupuncture and RR groups, respectively). Number of daily practice days of RR‐eliciting techniques is also associated with reduction in craving ratings (b = −.02, p = .008).

Conclusions

Findings demonstrate the value of attending regular acupuncture and RR‐eliciting intervention sessions, as well as the daily practice of RR‐eliciting techniques.

Scientific Significance

Substance addiction is a complex disease and effective treatment remains a challenge. Our study findings add to the scientific evidence of these two non‐pharmaceutical approaches for SUD. (Am J Addict 2014;23:129–136)
Does Investor Sentiment Affect Earnings Management?
Authors: Simpson Ana
Published: August 2013

I hypothesize and find that earnings management via accruals is driven partially by the prevailing market‐wide investor sentiment. Managers inflate earnings in periods of higher sentiment, but report more conservatively during periods of low sentiment. Moreover, the likelihood of income‐increasing earnings management to avoid negative earnings surprises is also positively associated with investor sentiment. These results are robust to: (i) controls for time‐varying firm characteristics such as growth, investment opportunity sets, future profitability, leverage and size; (ii) macroeconomic variables such as future inflation, GDP growth, and growth in industrial production; (iii) multiple proxies for investor sentiment; and (iv) discretionary revenues as alternative measure of earnings management. Cross‐sectional analyses reveal that firms whose stock returns co‐move more with investor sentiment are more (less) likely to manage earnings upward via abnormal accruals in quarters of higher (lower) sentiment. The findings of managers’ strategic use of abnormal accruals show the need for increased attention from boards of directors, auditors and regulators to heightened managerial incentives to overstate earnings and to report optimistic earnings numbers during periods of high investor sentiment.
Meeting the food and nutrition needs of the poor: the role of fish and the opportunities and challenges emerging from the rise of aquaculturea
Authors: Beveridge M. C. M. , Thilsted S. H. , Phillips M. J. , Metian M. , Troell M. , Hall S. J.
Published: August 2013

People who are food and nutrition insecure largely reside in Asia and Sub‐Saharan Africa and for many, fish represents a rich source of protein, micronutrients and essential fatty acids. The contribution of fish to household food and nutrition security depends upon availability, access and cultural and personal preferences. Access is largely determined by location, seasonality and price but at the individual level it also depends upon a person's physiological and health status and how fish is prepared, cooked and shared among household members. The sustained and rapid expansion of aquaculture over the past 30 years has resulted in >40% of all fish now consumed being derived from farming. While aquaculture produce increasingly features in the diets of many Asians, it is much less apparent among those living in Sub‐Saharan Africa. Here, per capita fish consumption has grown little and despite the apparently strong markets and adequate biophysical conditions, aquaculture has yet to develop. The contribution of aquaculture to food and nutrition security is not only just an issue of where aquaculture occurs but also of what is being produced and how and whether the produce is as accessible as that from capture fisheries. The range of fish species produced by an increasingly globalized aquaculture industry differs from that derived from capture fisheries. Farmed fishes are also different in terms of their nutrient content, a result of the species being grown and of rearing methods. Farmed fish price affects access by poor consumers while the size at which fish is harvested influences both access and use. This paper explores these issues with particular reference to Asia and Africa and the technical and policy innovations needed to ensure that fish farming is able to fulfil its potential to meet the global population's food and nutrition needs.
Increased phosphatidylcholine concentration in saliva reduces surface tension and improves airway patency in obstructive sleep apnoea
Authors: Kawai M. , Kirkness J. P. , Yamamura S. , Imaizumi K. , Yoshimine H. , Oi K. , Ayuse T.
Published: August 2013

Surface tension may have important role for maintaining upper airway patency in patients with obstructive sleep apnoea. It has been demonstrated that elevated surface tension increases the pharyngeal pressures required to reopen the upper airway following collapse. The aim of the study was to evaluate the associations between the concentrations of endogenous surfactants in saliva with indices of upper airway patency in obstructive sleep apnoea. We studied 20 male patients with obstructive sleep apnoea (age: 60·3 ± 10·3 years; BMI: 25·9 ± 4·6 kg m−2; AHI: 41·5 ± 18·6 events h−1). We obtained 100‐μL samples of saliva prior to overnight polysomnographic sleep study. The surface tension was determined using the pull‐off force technique. The concentration of phosphatidylcholine (PC) was evaluated by liquid chromatography‐mass spectrometry (LC‐MS/MS). Regression analysis between apnoea, hypopnoea and apnoea/hypopnoea indices and the ratio of hypopnoea time/total disordered breathing time (HT/DBT) with surface tension and PC were performed. P < 0·05 was considered significant. The mean saliva surface tension was 48·8 ± 8·0 mN m−1 and PC concentration was 15·7 ± 11·1 nM. The surface tension was negatively correlated with the PC concentration (r = −0·48, P = 0·03). There was a significant positive correlation between surface tension with hypopnoea index (r = 0·50, P = 0·03) and HT/DBT (r = 0·6, P = 0·006), but not apnoea or apnoea/hypopnoea index (P > 0·11). Similarly, PC concentration negatively correlated with hypopnoea index (r = −0·45, P = 0·04) and HT/DBT (r = −0·6, P = 0·004), but not with apnoea index or AHI (P > 0·08). An increase in salivary PC concentration may increase upper airway patency in obstructive sleep apnoea through a reduction in surface tension.
Culturally‐specific Smoking Cessation Outreach in a Rural Community
Authors: Butler Karen M. , Rayens Mary Kay , Adkins Sarah , Record Rachael , Langley Ronald , Derifield Stephanie , McGinn Carolyn , Murray Deborah , Hahn Ellen J.
Published: August 2013

Objective

Tobacco use is the leading preventable cause of death, resulting in 443,000 US deaths per year. Rural adults have higher smoking prevalence and less access to tobacco dependence treatment than their urban counterparts. This study examined exposure to a culturally specific smoking cessation outreach intervention, assessing whether exposure was associated with cessation behaviors.

Design and Sample

Post‐test only quasi‐experimental study. Targeted adult smokers (N = 251) living in a rural, economically distressed southeastern US county for at least 6 months.

Measurements

Five outreach elements (brochures/pushcards, posters, print and radio advertisements, quilt made by local artisans) based on themes from focus groups with current and former smokers and paired with brief tobacco cessation counseling, and were delivered over 6 months in 2009–2010. Exposure and cessation behavior indicators were collected via cross‐sectional random‐digit dial survey. The total intervention exposure score was 4.8 (SD = 4.3, range 0–19).

Results

Intervention exposure was associated with having talked to a health care provider about quitting smoking in the past 6 months and planning to quit smoking in the next 6 months.

Conclusions

Culturally specific outreach materials based on personal narratives are a promising population‐based intervention to motivate rural smokers to consider cessation.
Detection of a variable intracellular acid‐labile carbon pool in Thalassiosira weissflogii (Heterokontophyta) and Emiliania huxleyi (Haptophyta) in response to changes in the seawater carbon system
Authors: Isensee Kirsten , Erez Jonathan , Stoll Heather M.
Published: August 2013

Accumulation of an intracellular pool of carbon (Ci pool) is one strategy by which marine algae overcome the low abundance of dissolved CO2 (CO2(aq)) in modern seawater. To identify the environmental conditions under which algae accumulate an acid‐labile Ci pool, we applied a 14C pulse‐chase method, used originally in dinoflagellates, to two new classes of algae, coccolithophorids and diatoms. This method measures the carbon accumulation inside the cells without altering the medium carbon chemistry or culture cell density. We found that the diatom Thalassiosira weissflogii [(Grunow) G. Fryxell & Hasle] and a calcifying strain of the coccolithophorid Emiliania huxleyi [(Lohmann) W. W. Hay & H. P. Mohler] develop significant acid‐labile Ci pools. Ci pools are measureable in cells cultured in media with 2–30 µmol l−1 CO2(aq), corresponding to a medium pH of 8.6–7.9. The absolute Ci pool was greater for the larger celled diatoms. For both algal classes, the Ci pool became a negligible contributor to photosynthesis once CO2(aq) exceeded 30 µmol l−1. Combining the 14C pulse‐chase method and 14C disequilibrium method enabled us to assess whether E. huxleyi and T. weissflogii exhibited thresholds for foregoing accumulation of DIC or reduced the reliance on bicarbonate uptake with increasing CO2(aq). We showed that the Ci pool decreases with higher CO2:HCO3− uptake rates.
Music, Musicians, Medicine, and the Kidney
Authors: Raghavan Rajeev , Eknoyan Garabed
Published: August 2013

The relationship between music, medicine and nephrology is ancient; ranging from musicians afflicted with kidney disease, contributors to nephrology who were musicians, and the use of music to treat renal maladies. Musicians have long been afflicted by diseases of the kidney, particularly nephrolithiasis, for which Marin Marais in 1725 composed a unique piece for the viol detailing the harrowing experience of ‘cutting for stone.’ Beethoven and Mozart were afflicted by kidney disease, as are several current musicians. Where past musicians succumbed to their failing kidneys, the advent of renal replacement therapy has given today's musicians, such as James DePreist and Natalie Cole, the opportunity to continue performing and composing. Several notable physicians of old have excelled as musicians; one example is Jacob Henle (1809–1885), for whom the loop of Henle is named, another is Robert Christison, a contemporary of Richard Bright, who is considered a ‘founder of nephrology’. Importantly, music therapy, as used in the times of Hippocrates and King David, has evolved from an empiric to a well‐established scientific discipline. Given the recent enlarging body of scholarly studies of music therapy, its rudimentary role in nephrology deserves further exploration.
Evaluating Constant DC-Link Operation of Wave Energy Converter
Authors: Ekström Rickard , Kurupath Venugopalan , Boström Cecilia , Waters Rafael , Leijon Mats
Published: August 2013

A wave energy converter (WEC) based on a linear generator and a point-absorbing buoy has been developed at Uppsala University. Interconnecting an array of WECs in parallel requires a point of common coupling, such as a common dc-bus. The dc voltage level seen by the generator is directly linked to the electromagnetic damping of the generator. A lower dc-level results in a higher damping factor and is important for increased absorption of the wave power. The drawback is increased losses in generator windings and cable resistance. There will be an optimal dc-level for maximum power output. This is a function of not only generator and buoy characteristics, but the current sea state. Experimental results of the full-scale system have been carried out, and used as validation of a simulation model of the system. The model is then used to evaluate how the dc-level seen by the generator influence the power output. The results indicate that higher dc-levels should be used at higher sea states, and power output may vary by up to a factor five depending on which dc-level is chosen.
In vivo dosimetry with optically stimulated dosimeters and RTQA2 radiochromic film for intraoperative radiotherapy of the breast
Authors: Price Caleb , Pederson Aaron , Frazier Chanté , Duttenhaver John
Published: August 2013

Purpose:

Measurements were taken with optically stimulated luminescence dosimeters (OSLDs) and with RTQA2 radiochromic film to evaluate the use of each forin vivo dosimetry with intraoperative radiotherapy of the breast.

Methods:

Nonlinear calibration curves were established for OSLDs and RTQA2 radiochromic film using the Intrabeam 50 kVp source. Measurements were taken in a water phantom and compared to absolute dose measurements taken with an ionization chamber to investigate the characteristics of both types of dosimeters, including energy response and radiative absorption. In vivo readings were taken on the skin and in the tumor cavity using OSLDs and RTQA2 radiochromic film for 10 patients and 20 patients respectively. A prescription of 20 Gy to the surface of the applicator was used for all in vivo measurements in this study.

Results:

OSLDs were found to have an approximate uncertainty of ±7% for readings near the surface of the applicator and ±17% for readings at distances typical to the skin. The radiative absorption by OSLD was negative, indicating that this type of dosimeter absorbs less radiation than water in the targeted intraoperative radiotherapy energy range. RTQA2 film exhibited no energy dependence and all film readings were within ±8% of the delivered dose. The maximum radiative absorption in film was 8.5%. Radiochromic film measurements were found to be on average 18.2 ± 3.3 Gy for the tumor cavity and 2.1 ± 0.8 Gy for positions on the skin superior and inferior to the Intrabeam applicator. Average cavity measurements taken with OSLDs were 15.9 ± 3.9 Gy and average skin doses were 1.4 ± 0.8 Gy.

Conclusions:

OSLDs produce results with an uncertainty comparable to other dosimeters near the surface of the applicator but the uncertainty increases to an unacceptably high level with distance from the applicator. RTQA2 radiochromic film is shown to be accurate both at the surface of the applicator and at distances of 1–2 cm.
Opposite Feedbacks in the Hippo Pathway for Growth Control and Neural Fate
Authors: Jukam David , Xie Baotong , Rister Jens , Terrell David , Charlton-Perkins Mark , Pistillo Daniela , Gebelein Brian , Desplan Claude , Cook Tiffany
Published: August 2013

Complexity and Diversity

Complex organisms must produce and maintain an extraordinary diversity of cell and tissue types with a limited number of genes and molecular pathways. Cells accomplish this by reusing the same signaling networks at different times, in different tissues, and for different purposes, yet how this context-specificity is achieved is poorly understood.

Jukam
et al.

(
1238016
, published online 29 August) show how a set of genes that function in cell and tissue growth can be used again in nondividing fly photoreceptor neurons to ensure that flies develop appropriate sensitivity to both blue and green light. The Hippo pathway undergoes a regulatory change—from negative to positive feedback—that requires a tissue-specific transcription factor network. This network uses evolutionarily conserved regulatory factors whose mutations in humans result in degenerative retinal diseases. The context-appropriate positive feedback in flies ensures an all-or-nothing fate decision necessary to establish a functional visual system.
Villification: How the Gut Gets Its Villi
Authors: Shyer Amy E. , Tallinen Tuomas , Nerurkar Nandan L. , Wei Zhiyan , Gil Eun Seok , Kaplan David L. , Tabin Clifford J. , Mahadevan L.
Published: August 2013

Intestinal Villus Formation

The intestinal villi are essential elaborations of the lining of the gut that increase the epithelial surface area for nutrient absorption.

Shyer
et al.

(p.
212
, published online 29 August; see the Perspective by

Simons

) show that in both the developing human and chick gut, the villi are formed in a step-wise progression, involving the sequential folding of the endoderm into longitudinal ridges, via a zigzag pattern, to finally form individual villi. These changes are established through the differentiation of the smooth muscle layers of the gut, restricting the expansion of the adjacent proliferating and growing endoderm and mesenchyme, generating compressive stresses that lead to the buckling and folding of the tissue.
Draft Genome Sequences of Paenibacillus alvei A6-6i and TS-15
Authors: Luo Yan , Wang Charles , Allard Sarah , Strain Errol , Allard Marc W. , Brown Eric W. , Zheng Jie
Published: August 2013

Here, we report draft genomes of
Paenibacillus alvei
strains A6-6i and TS-15, which were isolated, respectively, from plant material and soil in the Virginia Eastern Shore (VES) tomato growing area. An array of genes related to antimicrobial biosynthetic pathways have been identified with whole-genome analyses of these strains.
Autoimmune limbic encephalitis presenting as relapsing psychosis
Authors: Hopkins Sarah A , Moodley Kuven K , Chan Dennis
Published: August 2013

A 34-year-old woman with a history of relapsing psychosis presented with a 15-month history of impassivity and social withdrawal associated with cognitive impairment. The subsequent recurrence of psychomotor agitation, auditory hallucinations and delusional thinking resulted in an emergency admission under psychiatric services. Initial investigations, including MRI of the brain and cerebrospinal fluid studies were unremarkable and she was treated for a primary psychiatric disorder. The diagnosis of autoimmune limbic encephalitis was established after further investigations revealed the presence of antibodies to the NR1 subunit of theN-Methyl-d-aspartate receptor (NMDAR). Immunotherapy resulted in rapid resolution of psychosis and marked improvement in cognitive and social function. This case underlines the importance of considering anti-NMDAR encephalitis within the differential diagnosis of psychosis associated with cognitive impairment even in those with an apparent previous psychiatric history and response to antipsychotics.
From glanders to Hendra virus: 125 years of equine infectious diseases
Authors: Slater Josh
Published: August 2013

Josh Slater looks back at the past 125 years of developments in equine infectious disease, including landmark discoveries in microbiology and genomics, and considers what the future may hold
Gravity before Einstein and Schwinger before gravity
Authors: Trimble Virginia
Published: August 2013

Julian Schwinger was a child prodigy, and Albert Einstein distinctly not; Schwinger had something like 73 graduate students, and Einstein very few. But both thought that gravity was important. They were not, of course, the first, nor is the disagreement on how one should think about gravity, which was highlighted at the June 2012 meeting of the American Astronomical Society, the first such dispute. Explored here are several views of what gravity is supposed to do: action at a distance versus luminiferous ether, universal gravitation versus action only on solids, finite versus infinite propagation speed, and whether the exponent in the 1/r2 law is precisely two, or two plus a smidgeon (a suggestion by Simon Newcomb among others). Second, an attempt is made to describe Julian Schwinger’s early work and how it might have prefigured his “source theory,” beginning with his unpublished 1934 paper “on the interaction of several electrons,” through his days at Berkeley with Oppenheimer, Gerjuoy, and others, to the application of nuclear physics ideas to radar, and of radar engineering techniques to nuclear physics. Those who believe that good jobs are difficult to come by now might want to contemplate the couple of years Schwinger spent teaching introductory physics at Purdue before moving on to the Radiation Laboratory in 1942.
THE IMPORTANCE OF LOCAL CLUSTERS FOR THE DIFFUSION OF OPINIONS AND BELIEFS IN INTERPERSONAL COMMUNICATION NETWORKS
Authors: PFEFFER JÜRGEN , CARLEY KATHLEEN M.
Published: August 2013

Opinions and beliefs are essential ingredients in the diffusion of innovation. We present a framework to model and simulate diffusion processes of opinions and beliefs in interpersonal communication networks. We introduce an algorithm to create stylized networks with attributes of real-world interpersonal communication networks. We also introduce a simple, but expandable model for simulating the dynamics of the diffusion processes of opinions and beliefs. We apply network multi-agent simulations to show the importance of local clusters of connected agents for keeping opinions and beliefs endemic in a social system. We also argue that due to the structure of interpersonal networks, these local clusters have the capability to propagate opinions and ideas into the entire system.
The kinetic studies of the solvent-promoted aggregation of a steroid-porphyrin derivative
Authors: Naitana Mario L. , Dukh Mykhaylo , Zelenka Karel , Trnka Tomáš , Venanzi Mariano , Lettieri Raffaella , Drašar Pavel , Monti Donato
Published: August 2013

The study of the aggregation of a steroid-functionalised porphyrin derivative shows the formation of chiral suprastuctures. Kinetic studies indicate that the mechanism of the aggregation strongly depends on both the nature of the media and on the concentration of the tetrapyrrolic macrocycle.
Influence of obestatin on the gastric longitudinal smooth muscle from mice: mechanical and electrophysiological studies
Authors: Squecco Roberta , Garella Rachele , Francini Fabio , Baccari Maria Caterina
Published: August 2013

Obestatin is a hormone released from the stomach deriving from the same peptide precursor as ghrelin. It is known to act as an anorectic hormone decreasing food intake, but contrasting results have been reported about the effects of obestatin on gastrointestinal motility. The aim of the present study was to investigate whether this peptide may act on the gastric longitudinal smooth muscle by using a combined mechanical and electrophysiological approach. When fundal strips from mice were mounted in organ baths for isometric recording of the mechanical activity, obestatin caused a tetrodotoxin-insensitive decrease of the basal tension and a reduction in amplitude of the neurally induced cholinergic contractile responses, even in the presence of the nitric oxide synthesis inhibitor NG-nitro-l-arginine. Obestatin reduced the amplitude of the response to the ganglionic stimulating agent dimethylphenyl piperazinium iodide but did not influence that to methacholine. In nonadrenergic, noncholinergic conditions, obestatin still decreased the basal tension of the preparations without influencing the neurally induced relaxant responses. For comparison, in circular fundal strips, obestatin had no effects. Notably, in the longitudinal antral ones, obestatin only caused a decrease of the basal tension. Electrophysiological experiments, performed by a single microelectrode inserted in a gastric longitudinal smooth muscle cell, showed that obestatin had similar effects in fundal and antral preparations: it decreased the resting specific membrane conductance, inhibited Ca2+ currents, and positively shifted their voltage threshold of activation. In conclusion, the present results indicate that obestatin influences gastric smooth muscle exerting site-specific effects.
Alpha 7 integrin preserves the function of the extensor digitorum longus muscle in dystrophin-null mice
Authors: Hakim Chady H. , Burkin Dean J. , Duan Dongsheng
Published: August 2013

The dystrophin-associated glycoprotein complex (DGC) and the α7β1-integrin complex are two independent protein complexes that link the extracellular matrix with the cytoskeleton in muscle cells. These associations stabilize the sarcolemma during force transmission. Loss of either one of these complexes leads to muscular dystrophy. Dystrophin is a major component of the DGC. Its absence results in Duchenne muscular dystrophy (DMD). Because α7-integrin overexpression has been shown to ameliorate muscle histopathology in mouse models of DMD, we hypothesize that the α7β1-integrin complex can help preserve muscle function. To test this hypothesis, we evaluated muscle force, elasticity, and the viscous property of the extensor digitorum longus muscle in 19-day-old normal BL6, dystrophin-null mdx4cv, α7-integrin-null, and dystrophin/α7-integrin double knockout mice. While nominal changes were found in single knockout mice, contractility and passive properties were significantly compromised in α7-integrin double knockout mice. Our results suggest that DGC and α7β1-integrin complexes may compensate each other to maintain normal skeletal muscle function. α7β1-Integrin upregulation may hold promise to treat not only histological, but also physiological, defects in DMD.
In Vitro and In Vivo Therapeutic Efficacy of Carfilzomib in Mantle Cell Lymphoma: Targeting the Immunoproteasome
Authors: Zhang Liang , Pham Lan V. , Newberry Kate J. , Ou Zhishuo , Liang Rong , Qian Jianfei , Sun Luhong , Blonska Marzenna , You Yun , Yang Jing , Lin Xin , Rollo Alex , Tamayo Archito T. , Lee John , Ford Richard J. , Zhao Xiurong , Kwak Larry W. , Yi Qing , Wang Michael
Published: August 2013

Mantle cell lymphoma (MCL) remains incurable due to its inevitable pattern of relapse after treatment with current existing therapies. However, the promise of a cure for MCL lies in the burgeoning area of novel agents. In this study, we elucidated the therapeutic effect and mechanism of carfilzomib, a novel long-acting second-generation proteasome inhibitor, in MCL cells. We found that carfilzomib induced growth inhibition and apoptosis in both established MCL cell lines and freshly isolated primary MCL cells in a dose-dependent manner. In contrast, carfilzomib was less toxic to normal peripheral blood mononuclear cells from healthy individuals. The carfilzomib-induced apoptosis of MCL cells was mediated by the activation of JNK, Bcl-2, and mitochondria-related pathways. In addition, carfilzomib inhibited the growth and survival signaling pathways NF-κB and STAT3. Interestingly, we discovered that expression of immunoproteasome (i-proteasome) subunits is required for the anti-MCL activity of carfilzomib in MCL cells. In MCL-bearing SCID mice/primary MCL-bearing SCID-hu mice, intravenous administration of 5 mg/kg carfilzomib on days 1 and 2 for 5 weeks slowed/abrogated tumor growth and significantly prolonged survival. Our preclinical data show that carfilzomib is a promising, potentially less toxic treatment for MCL. Furthermore, an intact i-proteasome, especially LMP2, appears to be necessary for its anti-MCL activity, suggesting that i-proteasome could serve as a biomarker for identifying patients who will benefit from carfilzomib. Mol Cancer Ther; 12(11); 2494–504. ©2013 AACR.
Everolimus in Postmenopausal, Hormone Receptor-Positive Advanced Breast Cancer: Summary and Results of an Austrian Expert Panel Discussion
Authors: Gnant Michael , Greil Richard , Hubalek Michael , Steger Günther
Published: August 2013

In patients with hormone receptor-positive advanced breast cancer, response to endocrine therapy is frequently limited by endocrine resistance. One important mechanism of resistance is related to mammalian target of rapamycin (mTOR), a molecule involved in the activation of alternative signaling pathways. Preclinically, resensitization of endocrine resistance can be achieved by the addition of the mTOR inhibitor everolimus to endocrine therapy. Recent results of clinical trials confirmed the clinical activity of combining everolimus and endocrine therapy in neoadjuvant and advanced breast cancer. The BOLERO-2 trial demonstrated significant progression-free survival benefits for the addition of everolimus to exemestane. These data were the basis for the recent approval of everolimus in combination with exemestane for the treatment of advanced hormone receptor-positive breast cancer. In clinical practice, the following 3 patient groups are particularly suitable for this treatment: those with progression on aromatase inhibitor therapy, those who respond well to chemotherapy and might benefit from subsequent endocrine therapy, and those with non-aggressive tumor biology. Everolimus treatment requires careful clinical monitoring due to the potentially serious side effects, e.g. stomatitis and pneumonitis. It is also important to educate patients and physicians in order to increase their awareness of side effects. At present, everolimus is investigated in clinical trials.
Vasospasm of Atherosclerotic Coronary Arteries Precipitates Acute Ischemic Myocardial Damage in Myocardial Infarction–Prone Strain of the Watanabe Heritable Hyperlipidemic Rabbits
Authors: Shiomi Masashi , Ishida Tatsuro , Kobayashi Tsutomu , Nitta Norihisa , Sonoda Akinaga , Yamada Satoshi , Koike Tomonari , Kuniyoshi Nobue , Murata Kiyoshi , Hirata Ken-ichi , Ito Takashi , Libby Peter
Published: August 2013

Objective—

This study tested the hypothesis that vasospasm can trigger coronary plaque injury and acute ischemic myocardial damage.

Approach and Results—

Myocardial infarction–prone strain of the Watanabe heritable hyperlipidemic rabbits received an intravenous bolus of ergonovine maleate (0.45 µmol/kg) during intravenous infusion of norepinephrine (12 nmol/kg per minute) to provoke coronary spasm in vivo. After this treatment, coronary angiography demonstrated vasospasm, and the ECG showed ischemic abnormalities (ST depression/elevation and T-wave inversion) in 77% of animals (23/30). These changes normalized after nitroglycerin injection. In rabbits that demonstrated these ECG findings for >20 minutes, echocardiograms showed left ventricular wall motion abnormality. Serum levels of heart-type fatty acid–binding protein, cardiac troponin-I, and myoglobin increased markedly 4 hours after spasm provocation. In coronary lesions of myocardial infarction–prone strain of the Watanabe heritable hyperlipidemic rabbits with provoked coronary spasm, we observed intimal injury in 60.9% in the form of endothelial cell protrusions (39.1%), denudation (30.4%), and macrophage extravasation (56.5%). Plaque disruption with luminal thrombus, however, was only seen in 2 of 23 animals (8.7%), and mural microthrombus was rarely observed (4.3%).

Conclusions—

These observations show that provocation of vasospasm in myocardial infarction–prone strain of the Watanabe heritable hyperlipidemic rabbits associates with subsequent ischemic myocardial damage. Although treatment with spasmogens altered aspects of plaque morphology, for example, endothelial protrusion and macrophage emigration, thrombosis was rare in these animals with chronic atherosclerotic disease.