bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeted genomic analysis of Müllerian adenosarcoma
Authors: Howitt Brooke E , Sholl Lynette M , Dal Cin P , Jia Yonghui , Yuan Liping , MacConaill Laura , Lindeman Neal , Kuo Frank , Garcia Elizabeth , Nucci Marisa R , Quade Bradley J
Published: September 2014

Müllerian adenosarcoma (MA) is a rare mixed mesenchymal tumour of the female genital tract, composed of malignant stroma and benign‐appearing epithelium. Sarcomatous overgrowth (SO) is the only established histological variable associated with higher stage and shorter survival. Specific molecular or immunohistochemistry (IHC) tools for the diagnosis of MA are lacking. Our goal was to study genomic mutations and copy number variations (CNVs) in MA to understand better its pathobiology, and develop specific diagnostic and prognostic tools. DNA was extracted from 20 samples of MA from 18 subjects (12 without SO and 6 with SO), including two in which areas of both typical MA histology and SO were independently tested. Samples were analysed using a targeted next‐generation sequencing assay interrogating exonic sequences of 275 cancer genes for mutations and CNVs as well as 91 introns across 30 genes for cancer‐associated rearrangements. The mean number of mutations in MA with SO (mean 9.7; range 3–14) did not differ significantly from that in MA without SO (mean 9.6; range 5–16). MA with SO had significantly higher mean numbers of gene‐level CNVs (24.6) compared to MA without SO (5; p = 0.0002). The most frequent amplification involved MDM2 and CDK4 (5/18; 28%), accompanied by focal CDK4 and MDM2 and diffuse HMGA2 expression using immunohistochemistry. MYBL1 amplification was seen in 4/18 (22%), predominantly in SO. Alterations in PIK3CA/AKT/PTEN pathway members were seen in 13/18 (72%). Notably, TP53 mutations were uncommon, present in only two cases with SO. Three out of 18 (17%) had mutations in ATRX, all associated with SO. No chromosomal rearrangements were identified. We have identified a number of recurrent genomic alterations in MA, including some associated with SO. Although further investigation of these findings is needed, confirmation of one or more may lead to new mechanistic insights and novel markers for this often difficult‐to‐diagnose tumour. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd
CXCR4 expression enhances diffuse large B cell lymphoma dissemination and decreases patient survival
Authors: Moreno María José , Bosch Rosa , Dieguez‐Gonzalez Rebeca , Novelli Silvana , Mozos Ana , Gallardo Alberto , Pavón Miguel Ángel , Céspedes María Virtudes , Grañena Albert , Alcoceba Miguel , Blanco Oscar , Gonzalez‐Díaz Marcos , Sierra Jorge , Mangues Ramon , Casanova Isolda
Published: September 2014

The chemokine receptor CXCR4 has been implicated in the migration and trafficking of malignant B cells in several haematological malignancies. Over‐expression of CXCR4 has been identified in haematological tumours, but data concerning the role of this receptor in diffuse large B cell lymphoma (DLBCL) are lacking. CXCR4 is a marker of poor prognosis in various neoplasms, correlating with metastatic disease and decreased survival of patients. We studied CXCR4 involvement in cell migration in vitro and dissemination in vivo. We also evaluated the prognostic significance of CXCR4 in 94 biopsies of DLBCL patients. We observed that the level of expression of CXCR4 in DLBCL cell lines correlated positively with in vitro migration. Expression of the receptor was also associated with increased engraftment and dissemination, and decreased survival time in NOD/SCID mice. Furthermore, administration of a specific CXCR4 antagonist, AMD3100, decreased dissemination of DLBCL cells in a xenograft mouse model. In addition, we found that CXCR4 expression is an independent prognostic factor for shorter overall survival and progression‐free survival in DLBCL patients. These results show that CXCR4 mediates dissemination of DLBCL cells and define for the first time its value as an independent prognostic marker in DLBCL patients. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd
A new approach to blending starch with natural rubber
Authors: Trovatti Eliane , Carvalho Antonio José Felix , Gandini Alessandro
Published: September 2014

Thermoplastic starch (TPS) is the most widely used renewable and biodegradable polymer in applications such as packaging and disposable materials due to its properties, abundance and low cost. Research aimed at widening its range of applications includes the improvement of its mechanical properties by mixing it with other polymers. In this study, TPS was blended with oxidized natural rubber (ONR) in order to enhance its plasticity through higher interface compatibility. The oxidation of natural rubber was carried out to promote chemical interactions between the hydroxyl groups of ONR with those of TPS through hydrogen bonding. The blends were prepared by extrusion and characterized using dynamic mechanical analysis, tensile tests, contact angle measurements, water absorption and scanning electron microscopy. The results showed that these new materials displayed the expected improvements, as well as better water resistance and decreased brittleness. © 2014 Society of Chemical Industry
A comprehensive database of verified experimental data on protein folding kinetics
Authors: Wagaman Amy S. , Coburn Aaron , Brand‐Thomas Itai , Dash Barnali , Jaswal Sheila S.
Published: September 2014

Insights into protein folding rely increasingly on the synergy between experimental and theoretical approaches. Developing successful computational models requires access to experimental data of sufficient quantity and high quality. We compiled folding rate constants for what initially appeared to be 184 proteins from 15 published collections/web databases. To generate the highest confidence in the dataset, we verified the reported lnkf value and exact experimental construct and conditions from the original experimental report(s). The resulting comprehensive database of 126 verified entries, ACPro, will serve as a freely accessible resource (https://www.ats.amherst.edu/protein/) for the protein folding community to enable confident testing of predictive models. In addition, we provide a streamlined submission form for researchers to add new folding kinetics results, requiring specification of all the relevant experimental information according to the standards proposed in 2005 by the protein folding consortium organized by Plaxco. As the number and diversity of proteins whose folding kinetics are studied expands, our curated database will enable efficient and confident incorporation of new experimental results into a standardized collection. This database will support a more robust symbiosis between experiment and theory, leading ultimately to more rapid and accurate insights into protein folding, stability, and dynamics.
A recommended analysis for 2 × 2 crossover trials with baseline measurements
Authors: Mehrotra Devan V.
Published: September 2014

In many two‐period, two‐treatment (2 × 2) crossover trials, for each subject, a continuous response of interest is measured before and after administration of the assigned treatment within each period. The resulting data are typically used to test a null hypothesis involving the true difference in treatment response means. We show that the power achieved by different statistical approaches is greatly influenced by (i) the ‘structure’ of the variance–covariance matrix of the vector of within‐subject responses and (ii) how the baseline (i.e., pre‐treatment) responses are accounted for in the analysis. For (ii), we compare different approaches including ignoring one or both period baselines, using a common change from baseline analysis (which we advise against), using functions of one or both baselines as period‐specific or period‐invariant covariates, and doing joint modeling of the post‐baseline and baseline responses with corresponding mean constraints for the latter. Based on theoretical arguments and simulation‐based type I error rate and power properties, we recommend an analysis of covariance approach that uses the within‐subject difference in treatment responses as the dependent variable and the corresponding difference in baseline responses as a covariate. Data from three clinical trials are used to illustrate the main points. Copyright © 2014 John Wiley & Sons, Ltd.
Expression of BDNF and TH mRNA in the Brain Following Inhaled Administration of α‐Pinene
Authors: Kasuya Hikaru , Okada Narumi , Kubohara Mika , Satou Tadaaki , Masuo Yoshinori , Koike Kazuo
Published: September 2014

Essential oils are mainly administered by inhalation. Administration by inhalation is considered to occur through two pathways, neurological transfer and pharmacological transfer. However, the relationship between the two routes is not clear. To clarify this relationship, we administered α‐pinene, which has an anxiolytic‐like effect, to mice. Emotional behavior and accumulation and expression of relevant mRNAs in the brain (brain‐derived neurotrophic factor (BDNF); tyrosine hydroxylase (TH)) were examined following inhaled administration of α‐pinene (10 μL/L air for 60 or 90 min). To evaluate the anxiolytic‐like effect, the elevated plus maze (EPM) test was used. Inhalation of α‐pinene for 60 min produced a significant increase in the total distance traveled in the EPM test compared with control (water). The concentration of α‐pinene in the brain after 60 min of inhalation was significantly increased compared with that after 90 min of inhalation. The expression of BDNF mRNA in the olfactory bulb and in the hippocampus was almost the same after 60 min of inhalation compared to that after 90 min of inhalation. The expression of TH mRNA in the midbrain after 60 min of inhalation was significantly increased compared with that of the control. Thus, an increase in α‐pinene in the brain induces an increase in TH mRNA expression and increases locomotor activity. The anxiolytic‐like effect may be related to both neurological transfer and pharmacological transfer. Copyright © 2014 John Wiley & Sons, Ltd.
Diversity and Community Structure of Fishes in the Regulated Versus Unregulated Tributaries of the Mekong River
Authors: Phomikong P. , Fukushima M. , Sricharoendham B. , Nohara S. , Jutagate T.
Published: September 2014

Diversity and community structure of fishes were studied in three neighbouring tributaries of the Mekong River in Thailand, namely the Mun, Songkhram and Gam Rivers. The rivers are located in the same ecoregion but have contrasting levels of both hydrological regulations and mitigation measures; the Mun River has a hydropower dam with a fish ladder and sluice gates that are opened during the wet season each year, the Gam River has several irrigation dams with a fish ladder at each dam site, and the Songkhram River has no dams along its river course. A total of 124 freshwater fish species were sampled in these rivers from August 2009 to June 2010. Overall species richness was highest in the Songkhram River (112), followed by the Mun (97) and Gam (54) Rivers. Average per site species richness was also significantly different among rivers but not among sampling months. Abundance–biomass comparison plots revealed considerably overlapping distributions of these two metrics from the dry to early rainy seasons in the Songkhram River and, to a lesser extent, in the Mun River. Fish assemblage data were classified into six clusters with similar community structure. Fish assemblages in the Gam River constituted a single cluster, while those in the other two rivers formed multiple clusters depending on the sampling season. The results of the cluster analysis are discussed in relation to the dominance of the three migration guilds (white, black, and grey fishes) of the Mekong River fishes. The effectiveness of the mitigation measures was determined to be limited in alleviating adverse impacts of dams in these tributaries of the Mekong River. Copyright © 2014 John Wiley & Sons, Ltd.
Using meta‐analytic structural equation modeling to advance strategic management research: Guidelines and an empirical illustration via the strategic leadership‐performance relationship
Authors: Bergh Donald D. , Aguinis Herman , Heavey Ciaran , Ketchen David J. , Boyd Brian K. , Su Peiran , Lau Cubie L. L. , Joo Harry
Published: September 2014

This paper demonstrates how meta‐analysis can be combined with structural equation modeling (MASEM) to address new questions in strategic management research. We review this integration, describe its implementation, and compare findings from bivariate meta‐analyses, a direct‐effect structural equations model, and two mediating frameworks using data on the strategic leadership and performance relationship. Results drawn from 208 articles that collectively included data on 495,638 observations demonstrate the new insights available from MASEM while also suggesting a revision to conventional thinking on strategic leadership. Whereas some theories posit that boards of directors influence firm performance through monitoring and disciplining the top management team, MASEM provides more support for the view that boards mediate the top management teams' decisions. Implications for applying MASEM in strategic management are offered. Copyright © 2014 John Wiley & Sons, Ltd.
Board social capital and excess CEO returns
Authors: Sauerwald Steve , Lin Zhiang (John) , Peng Mike W.
Published: September 2014

ExcessCEOreturns refer toCEOfinancial returns in excess of shareholder returns. How do boards rein in excessCEOreturns? Introducing a social capital view of board monitoring, we suggest that boards face two competing normative pressures—corporate elite norms and monitoring norms. How boards conform to such normative pressures for controlling excessCEOreturns is affected by their external and internal social capital. Further, we substantiate our arguments by showing that powerfulCEOs and institutional investors may facilitate or constrain the normative pressures existing in the social network and alter the effects of board social capital on excessCEOreturns. Data from a sample ofU.S.corporations listed on theStandard andPoor's 1,500 index from 1999 to 2010 largely support our framework. Copyright © 2014 John Wiley & Sons, Ltd.
Simulation on Flow Field and Mixing Phenomenon in Single Snorkel Vacuum Degasser
Authors: Geng Dian‐Qiao , Zhang Xin , Liu Xing‐An , Wang Ping , Liu Hai‐Tao , Chen Hong‐Min , Dai Chuan‐Min , Lei Hong , He Ji‐Cheng
Published: September 2014

Numerical simulation method has been used to investigate the flow field and mixing phenomenon in single snorkel degasser with ladle bottom blowing. The numerical results showed that the flow field inside the single snorkel vacuum degasser can be optimized in order to achieve higher recirculation rates and smaller mixing times, which are important to refining. This can be done by locating the gas injection point away from the center of the ladle. Under the conditions analyzed in present work, the optimum location of the gas injection point could be located 0.3 m from the center of the ladle. The circulation flow rate twice as high as that of a similar size RH degasser can be achieved on the condition of the optimized position. However, the ladle bottom blowing gas flow rate should be kept to a maximum of 400 NL/min in order to avoid slag entrapment in present work.
Physical Simulation of the Flow Field in a Vertical Twin Roll Strip Caster – A Water Model Study
Authors: Pelss Arnis , Rückert Antje , Pfeifer Herbert
Published: September 2014

Twin‐roll strip casting is a near‐net shape method for the production of metal strips in the range of several millimeters. The benefit in comparison to other methods is the short length of the facility and the lowered energy consumption in comparison to conventional continuous slab casting. This results in a reduction of costs and large energy savings by up to 85%. In this work the flow inside the pool of a twin roll strip caster is investigated. A modular submerged entry nozzle (SEN) was designed, which allows an adjustment of the flow for the single submerged faces of the SEN in the pool. This makes it possible to control the flow in several ways, to create different flow patterns. The measurements were made for a steady state. For the measurements in the pool the particle image velocimetry method (PIV) was used to determine two‐dimensional velocity fields. The surface motion at the rolls was investigated by video analysis. It was shown that this experimental setup is suitable to create several characteristic flow patterns inside the pool by combining the three main flows (front, long, and bottom). Also, it was obtained that high volume flows through the front chambers create a very uneven meniscus with large differences in height. The best result correlated to the meniscus was achieved for a medium volume flow at the long chambers and a high volume flow through the bottom.
Meta‐Analysis of Efficacy and Safety of Fast‐Track Surgery in Gastrectomy for Gastric Cancer
Authors: Li Yuan‐jun , Huo Ting‐ting , Xing Juan , An Jia‐ze , Han Zhe‐yi , Liu Xiao‐nan , Zhao Qing‐chuan
Published: September 2014

Background

Fast‐track surgery (FTS) is a promising program for surgical patients and has been applied to several surgical diseases. FTS is much superior to conventional perioperative care. Our aim was to evaluate and compare the safety and efficacy of FTS and conventional perioperative care for patients undergoing gastrectomy using a systematic review.

Methods

We searched the literature in PubMed, SCOPUS, and EMBASE up to November 2013. No language restriction was applied. Weighted mean differences (WMDs) and odds ratios (ORs) with their 95 % confidence intervals (CIs) were used for analysis by a fixed or a random effects model according to the heterogeneity assumption.

Results

In the present meta‐analysis, we included five randomized controlled trials and one controlled clinical trial from five studies. Compared with conventional care, FTS shortened the duration of flatus (WMD −21.08; 95 % CI −27.46 to −14.71, z = 6.48, p < 0.00001 in the open surgery group; WMD −8.20; 95 % CI −12.87 to −3.53, z = 3.44, p = 0.0006 in the laparoscopic surgery group), accelerated the decrease in C‐reactive protein (WMD −15.56; 95 % CI 21.28 to 9.83, z = 5.33, p < 0.00001), shortened the postoperative stay (WMD −2.00; 95 % CI −2.69 to −1.30, z = 5.64, p < 0.00001), and reduced hospitalization costs (WMD −447.72; 95 % CI −615.92 to −279.51, z = 5.22, p < 0.00001). FTS made no significant difference in operation times (p = 0.93), intraoperative blood loss (p = 0.79), or postoperative complications (p = 0.07).

Conclusions

Based on current evidence, the FTS protocol was feasible for gastric cancer patients who underwent gastrectomy (distal subtotal gastrectomy, proximal subtotal gastrectomy, or radical total gastrectomy) via open or laparoscopic surgery. Larger studies are needed to validate our findings.
Evaluation of the Open Abdomen Classification System: A Validity and Reliability Analysis
Authors: Bjarnason Thordur , Montgomery Agneta , Acosta Stefan , Petersson Ulf
Published: September 2014

Background

Classification of the open abdomen (OA) status is essential for clinical studies on the subject and may help to improve OA therapy. This is a validity and reliability analysis of the OA classification proposed by the World Society of the Abdominal Compartment Syndrome in 2013.

Methods

Prospective data on 111 consecutive OA patients treated with vacuum‐assisted wound closure and mesh‐mediated fascial traction (VAWCM) was used. For validity analysis, OA grades were compared with fascial closure and mortality. For reliability analysis, operative reports were graded by three external raters on two different occasions and the results compared. Instructions for use of the classification were constructed and studied by the external raters beforehand.

Results

The in‐hospital mortality rate was 30 % (33/111). The delayed primary fascial closure rate was 89 % (85/95). Most complex grade (p = 0.033), deteriorating grade (p = 0.045), enteric leak (p = 0.001), and enteroatmospheric fistula (p = 0001) were associated with worse clinical outcomes, while initial grade, grade 1A only, contamination, fixation, and frozen abdomen were not. A floor effect was observed, with 20 % of patients receiving the lowest grade throughout OA period. Inter‐rater reliability, expressed as intra‐class correlation coefficient (ICC), was 0.77, 0.76, and 0.88 (95 % confidence interval 0.66–0.84, 0.65–0.84, and 0.81–0.92, respectively) and test–retest reliability 1.0, 0.99, and 0.95, respectively.

Conclusions

More complex OA grades were associated with worse clinical outcomes. However, favorable clinical results with the VAWCM technique caused many patients to receive the lowest grade, thus causing a floor effect and lower validity. Inter‐rater and test–retest reliability was ‘good’ to ‘very good’.
Thoracoscopic Aortopexy for Tracheomalacia
Authors: van der Zee David C. , Straver Marieke
Published: September 2014

Background

Tracheomalacia is a condition that may result in acute life‐threatening events. Aortopexy has become a generally accepted mode of treatment, although the impact of a thoracotomy is considerable. With the advent of minimal invasive surgery the impact of such a procedure may be greatly reduced. This study evaluates the outcome of thoracoscopic aortopexy for tracheomalacia.

Methods

Retrospective analysis of a database containing all patients with thoracoscopic aortopexy. Based on symptomatology, on indication 24 h pH study and/or rigid tracheo‐bronchoscopy were carried out to confirm the diagnosis. A three‐trocar technique was used on the left side together with intra‐operative flexible tracheoscopy through the tube. Follow‐up continued for the duration of the study.

Results

Between January 2002 and December 2012, 16 patients presented with severe tracheomalacia. Fourteen of them had a history of esophageal atresia. Age at time of aortopexy varied from 2 weeks to 12 months. All procedures were performed thoracoscopically without intra‐operative complications. In five children, there was a recurrence of symptoms within 2–4 weeks for which a re‐thoracoscopic aortopexy was carried out successfully. With a follow‐up of 6 months to 10 years all patients are thriving and are without incidents.

Conclusion

This is the largest single‐center series of thoracoscopic aortopexy for tracheomalacia so far. All procedures were completed successfully without complications. Although recurrences occur, as in open surgery, the ultimate results are satisfactory. In an era of minimal invasive surgery the thoracoscopic approach is feasible and safe, even in redo‐procedures.
A test of the effect of testosterone on a sexually selected carotenoid trait in a cardueline finch
Authors: Trigo Sandra , Mota Paulo Gama
Published: September 2014

A great number of secondary sexual traits are assumed to have evolved as honest signals of individual quality. It is known that androgens regulate many male secondary traits as well as reproductive behavior. The expression of melanin‐based coloration is modulated by androgens, particularly testosterone, and there is some evidence that carotenoid‐based coloration may also be under androgen control. In the European serin, Serinus serinus, male carotenoid‐based plumage coloration is a sexually selected trait, subjected to female choice. In this experiment, we investigated if testosterone influences the expression of this trait by manipulating testosterone levels during molt and assessing how it affected plumage color expression after molt. We found that testosterone had only a negative effect on the size of the yellow ornament. Our experiment shows that testosterone had a limited effect on carotenoid‐based coloration of a cardueline finch.
Predictive Inference Using Latent Variables with Covariates
Authors: Schofield Lynne Steuerle , Junker Brian , Taylor Lowell J. , Black Dan A.
Published: September 2014

Plausible values (PVs) are a standard multiple imputation tool for analysis of large education survey data, which measures latent proficiency variables. When latent proficiency is the dependent variable, we reconsider the standard institutionally generated PV methodology and find it applies with greater generality than shown previously. When latent proficiency is an independent variable, we show that the standard institutional PV methodology produces biased inference because the institutional conditioning model places restrictions on the form of the secondary analysts’ model. We offer an alternative approach that avoids these biases based on the mixed effects structural equations model of Schofield (Modeling measurement error when using cognitive test scores in social science research. Doctoral dissertation. Department of Statistics and Heinz College of Public Policy. Pittsburgh, PA: Carnegie Mellon University, 2008).
Frequent use of opioids in patients with dementia and nursing home residents: A study of the entire elderly population of Denmark
Authors: Jensen-Dahm Christina , Gasse Christiane , Astrup Aske , Mortensen Preben Bo , Waldemar Gunhild
Published: September 2014

Background

Pain is believed to be undertreated in patients with dementia; however, no larger studies have been conducted. The aim was to investigate prevalent use of opioids in elderly with and without dementia in the entire elderly population of Denmark.

Method

A register‐based cross‐sectional study in the entire elderly (≥65 years) population in 2010 was conducted. Opioid use among elderly with dementia (N = 35,455) was compared with elderly without (N = 870,645), taking age, sex, comorbidity, and living status into account.

Results

Nursing home residents (NHRs) used opioids most frequently (41%), followed by home‐living patients with dementia (27.5%) and home‐living patients without dementia (16.9%). Buprenorphine and fentanyl (primarily patches) were commonly used among NHRs (18.7%) and home‐living patients with dementia (10.7%) but less often by home‐living patients without dementia (2.4%).

Conclusions

Opioid use in the elderly Danish population was frequent but particularly in patients with dementia and NHR, which may challenge patient safety and needs further investigation.
Triassic limestone, turbidites and serpentinite–the Cimmeride orogeny in the Central Pontides
Authors: OKAY ARAL I. , ALTINER DEMİR , KILIÇ ALİ MURAT
Published: September 2014

The basement of the Central Pontides, and by implication that of Crimea, consists of pre-Permian low-grade metaclastic rocks intruded by latest Permian – Early Carboniferous (305–290 Ma) granitoids. Further up in the stratigraphic sequence are Triassic limestones, which are now preserved as olistoliths in the deformed Upper Triassic turbidites. New conodont and foraminifera data indicate an Anisian to Carnian (Middle to Late Triassic) age for these hemi-pelagic Hallstatt-type limestones. The siliciclastic turbidites surrounding the Triassic limestone contain the Norian (Late Triassic) bivalveMonotis salinaria; the same species is also found in the Tauric series in Crimea. The Upper Triassic flysch in the Central Pontides is locally underlain by basaltic pillow lavas and includes kilometre-size tectonic slices of serpentinite. Both the flysch and the serpentinite are cut by an undeformed acidic intrusion with an Ar–Ar biotite age of 162 ± 4 Ma (Callovian–Oxfordian). This indicates that the serpentinite was emplaced into the turbidites before Middle Jurassic time, most probably during latest Triassic or Early Jurassic time, and that the deformation of the Triassic sequence pre-dates the Middle Jurassic. Regional geological data from the circum-Black Sea region, including widespread Upper Triassic flysch, Upper Triassic eclogites and blueschists of oceanic crustal affinity, and apparent absence of a ‘Cimmerian continent’ between the Cretaceous and Triassic accretionary complexes indicate that the latest Triassic Cimmeride orogeny was accretionary rather than collisional and is probably related to the collision and accretion of an oceanic plateau to the southern active margin of Laurasia.
FROM SPECIALITY TO A CONSTITUTIONAL SENSE OF PURPOSE: ON THE CHANGING ROLE OF THE OBJECTIVES OF THE EUROPEAN UNION
Authors: Larik Joris
Published: September 2014

After the Lisbon Treaty, the objectives of the European Union are more numerous and ambitious than ever. But what is their importance and function within the ‘thickening’ legal order of the EU? Combining insights from both the law of international organizations and comparative constitutional law, the article traces the diverging role of objectives for, on the one hand, a traditional international organization marked by the principle of ‘speciality’ and, on the other, a maturing legal order increasingly exhibiting ‘constitutional’ traits. It argues that in the case of the EU, objectives and competences have developed into two related but distinct norm categories. While objectives serve to bolster arguments to shape such powers, they no longer represent a rationale in their own right for founding competences. The EU no longer justifies its existence solely by striving for a particular set of goals. Rather, these norms represent an entrenched duty to pursue these objectives through the actors, structures and procedures available, regardless of the Union's ultimate form (finalité). Today, the EU stands for certain values and has been endowed with powers, the exercise of which is guided by promoting these various aspects of the ‘common good’.
Expression of acute phase proteins and inflammatory cytokines in mouse mammary gland followingStaphylococcus aureuschallenge and in response to milk accumulation
Authors: Nazemi Sasan , Aalbæk Bent , Kjelgaard-Hansen Mads , Safayi Sina , Klærke Dan Arne , Knight Christopher H
Published: September 2014

We used a mouse model of pathogenic (Staphylococcus aureus) and non-pathogenic (teat sealing) mammary inflammation to investigate mRNA expression of several inflammatory cytokines and acute phase proteins (APP) in mammary tissue and liver, and the appearance of some of these factors in plasma and milk. The expression levels of IL1β and TNFα were markedly up-regulated inStaph. aureus-inoculated mammary tissue at 72 h, whilst IL6 was up-regulated to a lesser extent in a way which was not confined to the inoculated glands. APP expression was up-regulated at 48 and 72 h in bothStaph. aureus-inoculated and teat-sealedmammaryglands. These differences between cytokine and APP expression provide additional support for the contention that APPs are produced within the mammary tissue itself during inflammation, rather than in associated immune cells. We propose that measurement of cytokines and APP in combination might provide a tool for diagnostic discrimination between mastitis caused by pathogenic invasion and milk accumulation, and hence allow for better targeting of antibiotic therapy. In comparison with mammary expression, expression of cytokines in liver tissue was up-regulated to a similar or lesser extent, whilst expression of APP was up-regulated to a much greater extent. The first appearance of increased cytokine and APP concentrations in plasma and of milk amyloid A (MAA) in milk occurred in advance of the measurable up-regulation of expression, hence their origin cannot be stated with certainty.
Helpful Allies, Interfering Neighbours: World opinion and China in the 1950s
Authors: PANG YANG HUEI
Published: September 2014

In the aftermath of the Korean War, the People's Republic of China was effectively an international pariah. Accounts of this period in Chinese textbooks emphasize how the Chinese turned this around, either during the Geneva Conference or the Bandung Conference, through deft planning and enterprise. Yet few pay any attention to how such manipulation of world opinion became increasingly difficult for Beijing after that initial success. One outcome of China's public relations campaign meant friendly Afro-Asia leaders voiced their opinions, in alarming numbers, to their Chinese counterparts regarding issues such as Asian security, mainland China's economic development, and the Taiwan problem. Indeed, recently declassified Chinese Foreign Affairs archive documents demonstrate that China tried to marshal such non-Soviet bloc opinions to its advantage during the first Taiwan Strait crisis (1955). Chinese efforts were successful in that there was no lack of volunteers to air dissent with American foreign policy. But these new allies also wished to mediate between the United States and the Republic of China, on the one side, and mainland China on the other. Moreover, such efforts were often at variance with China's domestic and strategic outlook in the region. China thus had to embark upon an active ‘management’ of disparate world opinions, which was an entirely new endeavour. Although China tried to provide a sanitized ‘script’ for its new friends, most had their own ideas. By the time of the second Taiwan Strait crisis (1958), the volume of third party interference had grown. Overwhelmed by such international attention, China responded by openly rejecting unwelcome mediation efforts and demanded outright condemnation of the United States. Thus, ironically, with its growing prominence on the international stage, China found itself unbearably weighted down by the burden of world opinion, a position previously occupied by the United States.
Disorder-specific grey matter deficits in attention deficit hyperactivity disorder relative to autism spectrum disorder
Authors: Lim L. , Chantiluke K. , Cubillo A. I. , Smith A. B. , Simmons A. , Mehta M. A. , Rubia K.
Published: September 2014

Background.

Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are two common childhood disorders that exhibit genetic and behavioural overlap and have abnormalities in similar brain systems, in particular in frontal and cerebellar regions. This study compared the two neurodevelopmental disorders to investigate shared and disorder-specific structural brain abnormalities.

Method.

Forty-four predominantly medication-naïve male adolescents with ADHD, 19 medication-naïve male adolescents with ASD and 33 age-matched healthy male controls were scanned using high-resolution T1-weighted volumetric imaging in a 3-T magnetic resonance imaging (MRI) scanner. Voxel-based morphometry (VBM) was used to test for group-level differences in structural grey matter (GM) and white matter (WM) volumes.

Results.

There was a significant group difference in the GM of the right posterior cerebellum and left middle/superior temporal gyrus (MTG/STG).Post-hocanalyses revealed that this was due to ADHD boys having a significantly smaller right posterior cerebellar GM volume compared to healthy controls and ASD boys, who did not differ from each other. ASD boys had a larger left MTG/STG GM volume relative to healthy controls and at a more lenient threshold relative to ADHD boys.

Conclusions.

The study shows for the first time that the GM reduction in the cerebellum in ADHD is disorder specific relative to ASD whereas GM enlargement in the MTG/STG in ASD may be disorder specific relative to ADHD. This study is a first step towards elucidating disorder-specific structural biomarkers for these two related childhood disorders.
Dysfunction of emotional brain systems in individuals at high risk of mood disorder with depression and predictive features prior to illness
Authors: Whalley H. C. , Sussmann J. E. , Romaniuk L. , Stewart T. , Kielty S. , Lawrie S. M. , Hall J. , McIntosh A. M.
Published: September 2014

Background.

Abnormalities of emotion-related brain circuitry, including cortico-thalamic-limbic regions underpin core symptoms of bipolar disorder (BD) and major depressive disorder (MDD). It is unclear whether these abnormalities relate to symptoms of the disorder, are present in unaffected relatives, or whether they can predict future illness.

Method.

The Bipolar Family Study (BFS) is a prospective longitudinal study that has examined individuals at familial risk of mood disorder and healthy controls on three occasions, 2 years apart. The current study concerns imaging data from the second assessment; 51 controls and 81 high-risk (HR) individuals performing an emotional memory task. The latter group was divided into 61 HR individuals who were well, and 20 who met diagnostic criteria for MDD. At the time of the third assessment a further 11 HR individuals (from the Well group) had developed MDD. The current analyses focused on (i) differences between groups based on diagnostic status at the time of the scan, and (ii) predictors of future illness, comparing the 11 HR individuals who became unwell after the second scanning assessment to those who remained well.

Results.

All groups demonstrated typical emotional modulation of memory and associated brain activations. For analysis (i) the HR MDD group demonstrated increased thalamic activation v. HR Well. (ii) HR Well individuals who subsequently became ill showed increased activation of thalamus, insula and anterior cingulate compared to those who remained well.

Conclusions.

These findings suggest evidence for specific changes related to the presence of illness and evidence that changes in brain function in cortico-thalamic-limbic regions precede clinical illness.
A Swedish population-based study of the mechanisms of parent–offspring transmission of criminal behavior
Authors: Kendler K. S. , Ohlsson H. , Morris N. A. , Sundquist J. , Sundquist K.
Published: September 2014

Background.

While children of parents with criminal behavior (CB) are at increased risk for CB, we have limited knowledge about the causes of this cross-generational transmission.

Method.

We examined intergenerational continuity in CB in the Swedish population ascertained from the national conviction registers in three family types: intact (n= 21 11 074), ‘not-lived-with’ (n= 16 53 15 where biological parents never lived with their offspring) and ‘step’ (n= 1 24 800 offspring) which reflected, respectively, the effects of genes + rearing, genes only and rearing only. We also examined three criminal conviction subtypes: violent CB (VCB), property CB (PCB) and white-collar CB (WCCB).

Results.

Combined across mothers and fathers, the hazard ratio (HR) for CB in offspring given parental CB was 1.95 in intact, 1.56 in ‘not-lived-with’ and 1.28 in stepfamilies. In all three family types, all forms of CB in parents (VCB, PCB and WCCB) significantly predicted risk for all forms of CB in offspring. However, VCB in offspring was most strongly predicted by VCB in parents in intact, not-lived-with and stepfamilies. In intact families only, some specific parent–offspring transmission was also seen for WCCB.

Conclusions.

Both genetic and environmental factors contribute substantially to parent–offspring resemblance for CB. With respect to criminal subtypes, much of parent–offspring transmission appears to be non-specific. However, specific genetic and environmental risk factors for VCB are transmitted across generations. A limitation of these analyses is that CB was assessed only via official criminal convictions.
Behandlung der Hepatitis C – eine Revolution steht bevor
Authors: Schärer Verena , Bruggmann Philip , Müllhaupt Beat , Fehr Jan
Published: September 2014

Die Behandlung der Hepatitis C steht kurz vor einer Revolution. In den letzten Jahren wurden verschiedene Medikamente entwickelt, die direkt in den viralen Replikationszyklus eingreifen. Die künftige Hepatitis-C-Therapie wird ohne Interferon auskommen. Die neuen Therapien werden kürzer, effizienter und haben weniger Nebenwirkungen. Die Belastung der Patienten durch die Therapie wird spürbar sinken. Die Heilungschancen steigen deutlich auch in bisher schwierig zu therapierenden Gruppen, wie z.B. Patienten mit Leberzirrhose, HIV/Hepatitis-C-Koinfizierte und Lebertransplantierte. Damit mehr Patienten von den neuen Therapien profitieren können, muss die Identifikation und Abklärung von Infizierten verbessert werden.
Der Einfluss von Sport auf kognitive Funktionen bei Kindern mit ADHS
Authors: Lehnert Katrin
Published: September 2014

Der positive Einfluss sportlicher Aktivitäten auf kognitive und exekutive Funktionen (EF) wurde mittlerweile vielfach aufgezeigt. EF stellen zugleich ein zentrales Defizit bei ADHS dar, weshalb betroffene Kinder und Jugendliche im Besonderen von sportlichen Aktivitäten profitieren könnten. Dieser Überblicksbeitrag verfolgt das Ziel, den aktuellen Forschungsstand zum Einfluss von sportlichen Aktivitäten auf Kognitionen allgemein und im Besonderen auf EF für Kinder und Jugendliche mit ADHS aufzuzeigen sowie auf einer theoretisch-konzeptionellen Ebene Erklärungsansätze zu liefern. Es wird deutlich, dass eine heterogene Befundlage vorliegt, die unter anderem mit einer zu geringen Differenzierung der sportlichen Aktivitäten begründet wird. Interessante sportspezifische Erklärungen stammen aus der aktuellen Kognitionsforschung an gesunden Kindern und Jugendlichen, wo eine physiologische und/oder kognitive Aktivierung durch sportliche Aktivitäten diskutiert wird. Die gewonnenen Erkenntnisse fließen in ein Rahmenmodell von Tomporowski, Lambourne und Okumura (2011) ein, welches für den Anwendungsbereich von ADHS adaptiert wurde, und wo bereits identifizierte Mediatoren und Moderatoren im Sport-Kognitions-Zusammenhang beinhaltet sind.
Interlocked DNA nanostructures controlled by a reversible logic circuit
Authors: Li Tao , Lohmann Finn , Famulok Michael
Published: September 2014

DNA nanostructures constitute attractive devices for logic computing and nanomechanics. An emerging interest is to integrate these two fields and devise intelligent DNA nanorobots. Here we report a reversible logic circuit built on the programmable assembly of a double-stranded (ds) DNA [3]pseudocatenane that serves as a rigid scaffold to position two separate branched-out head-motifs, a bimolecular i-motif and a G-quadruplex. The G-quadruplex only forms when preceded by the assembly of the i-motif. The formation of the latter, in turn, requires acidic pH and unhindered mobility of the head-motif containing dsDNA nanorings with respect to the central ring to which they are interlocked, triggered by release oligodeoxynucleotides. We employ these features to convert the structural changes into Boolean operations with fluorescence labelling. The nanostructure behaves as a reversible logic circuit consisting of tandem YES and AND gates. Such reversible logic circuits integrated into functional nanodevices may guide future intelligent DNA nanorobots to manipulate cascade reactions in biological systems.
Cavity-free plasmonic nanolasing enabled by dispersionless stopped light
Authors: Pickering Tim , Hamm Joachim M. , Page A. Freddie , Wuestner Sebastian , Hess Ortwin
Published: September 2014

When light is brought to a standstill, its interaction with gain media increases dramatically due to a singularity in the density of optical states. Concurrently, stopped light engenders an inherent and cavity-free feedback mechanism, similar in effect to the feedback that has been demonstrated and exploited in large-scale disordered media and random lasers. Here we study the spatial, temporal and spectral signatures of lasing in planar gain-enhanced nanoplasmonic structures at near-infrared frequencies and show that the stopped-light feedback mechanism allows for nanolasing without a cavity. We reveal that in the absence of cavity-induced feedback, the subwavelength lasing mode forms dynamically as a phase-locked superposition of quasi dispersion-free waveguide modes. This mechanism proves remarkably robust against interface roughness and offers a new route towards nanolasing, the experimental realization of ultra-thin surface emitting lasers, and cavity-free active quantum plasmonics.
Histone deacetylases inhibition by SAHA/Vorinostat normalizes the glioma microenvironment via xCT equilibration
Authors: Wolf Ines M. L. , Fan Zheng , Rauh Manfred , Seufert Sebastian , Hore Nirjhar , Buchfelder Michael , Savaskan Nic E. , Eyüpoglu Ilker Y.
Published: September 2014

Malignant gliomas are characterized by neurodegenerative actions leading to the destruction of surrounding brain parenchyma. The disturbance in glutamate homeostasis caused by increased expression of the glutamate transporter xCT plays a key role in glioma progression. We demonstrate that the HDAC-inhibitor SAHA specifically inhibits the xCT-transporter expression. Thereby, tumor cell stress is engendered, marked by increase in ROS. Moreover, SAHA dependent xCT-reduction correlates with the inhibition of ATF4-expression, a factor known to foster xCT expression. Since xCT/system Xc- is pivotal for the brain tumor microenvironment, normalization of this system is a key in the management of malignant gliomas. To date, the problem lay in the inability to specifically target xCT due to the ubiquitous expression of the xCT-transporter—i.e. in non-cancerously transformed cells too—as well as its essential role in physiological CNS processes. Here, we show xCT-transporter equilibration through SAHA is specific for malignant brain tumors whereas SAHA does not affect the physiological xCT levels in healthy brain parenchyma. Our data indicate that SAHA operates on gliomas specifically via normalizing xCT expression which in consequence leads to reduced extracellular glutamate levels. This in turn causes a marked reduction in neuronal cell death and normalized tumor microenvironment.
Flat Focusing Mirror
Authors: Cheng Y. C. , Kicas S. , Trull J. , Peckus M. , Cojocaru C. , Vilaseca R. , Drazdys R. , Staliunas K.
Published: September 2014

The control of spatial propagation properties of narrow light beams such as divergence, focusing or imaging are main objectives in optics and photonics. In this letter, we propose and demonstrate experimentally a flat focusing mirror, based on an especially designed dielectric structure without any optical axis. More generally, it also enables imaging any light pattern in reflection. The flat focusing mirror with a transversal invariance can largely increase the applicability of structured photonic materials for light beam propagation control in small-dimension photonic circuits.
Cerium; Crystal Structure and Position in The Periodic Table
Authors: Johansson Börje , Luo Wei , Li Sa , Ahuja Rajeev
Published: September 2014

The properties of the cerium metal have intrigued physicists and chemists for many decades. In particular a lot of attention has been directed towards its high pressure behavior, where an isostructural volume collapse (γ phase → α phase) has been observed. Two main models of the electronic aspect of this transformation have been proposed; one where the 4f electron undergoes a change from being localized into an itinerant metallic state and one where the focus is on the interaction between the 4f electron and the conduction electrons, often referred to as the Kondo volume collapse model. However, over the years it has been repeatedly questioned whether the cerium collapse really is isostructural. Most recently, detailed experiments have been able to remove this worrisome uncertainty. Therefore the isostructural aspect of the α-γ transition has now to be seriously addressed in the theoretical modeling, something which has been very much neglected. A study of this fundamental characteristic of the cerium volume collapse is made in present paper and we show that the localized ⇌ delocalized 4f electron picture provides an adequate description of this unique behavior. This agreement makes it possible to suggest that an appropriate crossroad position for cerium in The Periodic Table.
Ruthenium-catalyzed double-fold C–H tertiary alkoxycarbonylation of arenes using di-tert-butyl dicarbonate
Authors: Hong Xiaohu , Wang Hao , Liu Bingxin , Xu Bin
Published: September 2014

An efficient ruthenium-catalyzed double-fold C–H bond alkoxycarbonylation of arenes was developed using commercially available Boc2O as the tertiary esterification reagent.