bluuebunny/crossref_metadata_2025 huggingface dataset:
A Comparative Study of Video‐Assisted Thoracic Surgery with Thoracotomy for Middle Lobe Syndrome
Authors: Li Jian , Liu Chengwu , Zhao Yongsheng , Li Chuan , Liu Lunxu
Published: November 2016

Objectives

The aim of this study is to evaluate the feasibility and safety of video‐assisted thoracic surgery (VATS) for the treatment of middle lobe syndrome (MLS) through comparison with thoracotomy during the same period.

Methods

We retrospectively reviewed all consecutive patients with MLS who underwent lobectomy or lingular segmentectomy between December 2005 and November 2015 in a single institute. Thirty patients were enrolled and divided into two groups: VATS group (n = 19) and thoracotomy group (n = 11). Data regarding the patients’ demographics, medical history were collected and statistically compared.

Results

All patients received successful middle lobe resection or lingular segmentectomy. In terms of operation time, blood transfusion, chest drainage amount, duration of chest drainage and postoperative complications, no significant differences were found between the two groups (p > 0.05). The mean intraoperative blood loss of VATS group was less than thoracotomy group (79.0 ± 63.9 vs. 165 ± 94.9 ml, p = 0.04). In VATS group, the mean length of postoperative hospital stay was 6.0 ± 2.4 days, shorter than that in group thoracotomy (9.0 ± 3.5 days, p = 0.01).

Conclusions

VATS was a feasible and safe method for the surgical treatment of MLS in selected patients when no severe calcified lymph nodes surrounding hilus pulmonis was observed by preoperative chest CT scan.
Predicting aggression in late adolescent romantic relationships: A short‐term longitudinal study
Authors: Caiozzo Christina N. , Houston Jessica , Grych John
Published: November 2016

This study sought to prospectively predict aggression in the romantic relationships of 1180 college students from the United States (807 females; 373 males) over the course of two months with a set of intrapersonal risk and protective factors, including personality characteristics that rarely have been examined in this population. After accounting for prior dating aggression, perpetration of verbal aggression was predicted uniquely by aggressive attitudes, emotion regulation, and for females, narcissism. Perpetration of physical aggression was predicted by aggressive attitudes, but only at low levels of emotion regulation, and the interaction of callous‐unemotional traits, emotion regulation, and gender: males with low levels of callous‐unemotional traits perpetrated less physical aggression when they reported greater emotion regulation. These findings are among the first to show that personality traits and emotion regulation prospectively predict partner aggression in late adolescence and suggest mechanisms for continuity in interpersonal aggression from early adolescence to adulthood.
Mobilising the Diaspora
Authors: Betts Alexander , Jones Will
Published: November 2016

Over half the world lives under authoritarian regimes. For these people, the opportunity to engage in politics moves outside the state's territory. Mobilising across borders, diasporas emerge to challenge such governments. This book offers an in-depth examination of the internal politics of transnational mobilisation. Studying Rwandan and Zimbabwean exiles, it exposes the power, interests, and unexpected agendas behind mobilisation, revealing the surprising and ambivalent role played by outsiders. Far from being passive victims waiting for humanitarian assistance, refugees engage actively in political struggle. From Rwandans resisting their repatriation, to Zimbabweans preventing arms shipments, political exiles have diverse aims and tactics. Conversely, the governments they face also deploy a range of transnational strategies, and those that purport to help them often do so with hidden agendas. This shifting political landscape reveals the centrality of transnationalism within global politics, the historical and political contingency of diasporas, and the precarious agency of refugees.
Magical Hymns from Roman Egypt
Authors: Bortolani Ljuba Merlina
Published: November 2016

This interdisciplinary study investigates the divine personas in the so-called magical hymns of the Greek magical papyri which, in a corpus usually seen as a significant expression of religious syncretism with strong Egyptian influence, were long considered to be the 'most authentically Greek' contribution. Fifteen hymns receive a line-by-line commentary focusing on religious concepts, ritual practice, language and style. The overarching aim is to categorise the nature of divinity according to its Greek or Egyptian elements, examining earlier Greek and Egyptian sources and religious-magical traditions in order to find textual or conceptual parallels. Are the gods of the magical hymns Greek or Egyptian in nature? Did the magical hymns originate in a Greek or Egyptian cultural background? The book tries to answer these questions and to shed light on the religious plurality and/or fusion of the two cultures in the treatment of divinity in the Greek magical papyri.
Emerging therapies for acute intermittent porphyria
Authors: Fontanellas Antonio , Ávila Matías A. , Berraondo Pedro
Published: November 2016

Acute intermittent porphyria (AIP) is an autosomal dominant metabolic disease caused by hepatic deficiency of hydroxymethylbilane synthase (HMBS), the third enzyme of the heme synthesis pathway. The dominant clinical feature is acute neurovisceral attack associated with high production of potentially neurotoxic porphyrin precursors due to increased hepatic heme consumption. Current Standard of Care is based on a down-regulation of hepatic heme synthesis using heme therapy. Recurrent hyper-activation of the hepatic heme synthesis pathway affects about 5% of patients and can be associated with neurological and metabolic manifestations and long-term complications including chronic kidney disease and increased risk of hepatocellular carcinoma. Prophylactic heme infusion is an effective strategy in some of these patients, but it induces tolerance and its frequent application may be associated with thromboembolic disease and hepatic siderosis. Orthotopic liver transplantation is the only curative treatment in patients with recurrent acute attacks. Emerging therapies including replacement enzyme therapy or gene therapies (HMBS-gene transfer and ALAS1-gene expression inhibition) are being developed to improve quality of life, reduce the significant morbidity associated with current therapies and prevent late complications such as hepatocellular cancer or kidney failure in HMBS mutation carriers with long-standing high production of noxious heme precursors. Herein, we provide a critical digest of the recent literature on the topic and a summary of recently developed approaches to AIP treatment and their clinical implications.
A pilot study of performance among hospitalised elderly patients on a novel test of visuospatial cognition: the letter and shape drawing (LSD) test
Authors: White D. , Williams O. A. , Leonard M. , Exton C. , Adamis D. , Hannigan A. , Cullen W. , Dunne C. P. , Meagher D.
Published: November 2016

Objectives

Conventional bedside tests of visuospatial function such as the clock drawing (CDT) and intersecting pentagons tests (IPT) are subject to considerable inconsistency in their delivery and interpretation. We compared performance on a novel test – the letter and shape drawing (LSD) test – with these conventional tests in hospitalised elderly patients.

Methods

The LSD, IPT, CDT and the Montreal Cognitive Assessment (MoCA) were performed in 40 acute elderly medical inpatients at University Hospital Limerick The correlation between these tests was examined as well as the accuracy of the visuospatial tests to identify significant cognitive impairment on the MoCA.

Results

The patients (mean age 81.0±7.71; 21 female) had a median MoCA score of 15.5 (range=1–29). There was a strong, positive correlation between the LSD and both the CDT (r=0.56) and IPT (r=0.71). The correlation between the LSD and MoCA (r=0.91) was greater than for the CDT and IPT (both 0.67). The LSD correlated highly with all MoCA domains (ranging from 0.54 to 0.86) and especially for the domains of orientation (r=0.86), attention (0.81) and visuospatial function (r=0.73). Two or more errors on the LSD identified 90% (26/29) of those patients with MoCA scores of ⩽20, which was substantially higher than for the CDT (59%) and IPT (55%).

Conclusion

The LSD is a novel test of visuospatial function that is brief, readily administered and easily interpreted. Performance correlates strongly with other tests of visuospatial ability, with favourable ability to identify patients with significant impairment of general cognition.
The advance ratio effect on the lift augmentations of an insect-like flapping wing in forward flight
Authors: Han Jong-Seob , Chang Jo Won , Han Jae-Hung
Published: November 2016

Time-varying force/moment measurements and digital particle image velocimetry (DPIV) were conducted to reveal the influence of an advance ratio$J$on an insect-like flapping wing. A scaled-up robotic model and a servo-driven towing tank were employed to investigate nine individual$J$cases –$J=0$(hovering), 0.0625, 0.1250, 0.1875, 0.25, 0.50, 0.75, 1.0 and$\infty$(gliding motion) – at a high Reynolds number ($Re\sim 10^{4}$). At$J\leqslant 0.25$, the aerodynamic forces slightly increased from those in hover ($J=0$). The centres of pressure in these cases were concentrated in the outboard section, and the leading-edge vortices (LEVs) grew more conically than those in hover. Spanwise cross-sectional DPIV indicated that the wings generated more balanced downwashes, which effectively supported the slight lift increments in this range. At$J>0.25$, a drastic force drop appeared as$J$increased. The DPIV results in the$J=0.5$case clearly showed a strong trailing-edge vortex on the outboard trailing edges encroaching into the upper surface, which had been occupied by the LEV for lower $J$. The LEV vorticity was noticeably weakened, and coherent substructures with substantial turbulence accompanied this vorticity. In the$J=1.0$case, such encroachment was extended to 50 % of the section, and the LEV outboard became significantly irregular. The near-wake structures also showed that the$J=1.0$case had the narrowest downwash area, with unstable root and tip vortices, which reflected considerable attenuation in the lift enhancements. It was of note that all of these vortical behaviours were clearly distinguishable from aspect ratio ($AR$) effects. The$J$even played a similar role to that of the$AR$in the Navier–Stokes equation. These findings clearly indicated that the$J$could be an independent quantity governing the overall vortical system and lift enhancing mechanism on a flapping wing of a flapping-wing micro air vehicle.
Critical shear rate and torque stability condition for a particle resting on a surface in a fluid flow
Authors: Kudrolli Arshad , Scheff David , Allen Benjamin
Published: November 2016

We advance a quantitative description of the critical shear rate $\dot{\unicode[STIX]{x1D6FE}_{c}}$ needed to dislodge a spherical particle resting on a surface with a model asperity in laminar and turbulent fluid flows. We have built a cone-plane experimental apparatus which enables measurement of $\dot{\unicode[STIX]{x1D6FE}_{c}}$ over a wide range of particle Reynolds number $Re_{p}$ from $10^{-3}$ to $1.5\times 10^{3}$. The condition to dislodge the particle is found to be consistent with the torque balance condition after including the torque component due to drag about the particle centre. The data for $Re_{p}<0.5$ are in good agreement with analytical calculations of the drag and lift coefficients in the $Re_{p}\rightarrow 0$ limit. For higher $Re_{p}$, where analytical results are unavailable, the hydrodynamic coefficients are found to approach a constant for $Re_{p}>1000$. We show that a linear combination of the hydrodynamic coefficients found in the viscous and inertial limits can describe the observed $\dot{\unicode[STIX]{x1D6FE}_{c}}$ as a function of the particle and fluid properties.
Skin-friction generation by attached eddies in turbulent channel flow
Authors: de Giovanetti Matteo , Hwang Yongyun , Choi Haecheon
Published: November 2016

Despite a growing body of recent evidence on the hierarchical organization of the self-similar energy-containing motions in the form of Townsend’s attached eddies in wall-bounded turbulent flows, their role in turbulent skin-friction generation is currently not well understood. In this paper, the contribution of each of these self-similar energy-containing motions to turbulent skin friction is explored up to $Re_{\unicode[STIX]{x1D70F}}\simeq 4000$. Three different approaches are employed to quantify the skin-friction generation by the motions, the spanwise length scale of which is smaller than a given cutoff wavelength: (i) FIK (Fukagata, Iwamoto, Kasagi) identity in combination with the spanwise wavenumber spectra of the Reynolds shear stress; (ii) confinement of the spanwise computational domain; (iii) artificial damping of the motions to be examined. The near-wall motions are found to continuously reduce their role in skin-friction generation on increasing the Reynolds number, consistent with the previous finding at low Reynolds numbers. The largest structures given in the form of very-large-scale and large-scale motions are also found to be of limited importance: due to a non-trivial scale interaction process, their complete removal yields only a 5–8 % skin-friction reduction at all of the Reynolds numbers considered, although they are found to be responsible for 20–30 % of total skin friction at $Re_{\unicode[STIX]{x1D70F}}\simeq 2000$. Application of all the three approaches consistently reveals that the largest amount of skin friction is generated by the self-similar motions populating the logarithmic region. It is further shown that the contribution of these motions to turbulent skin friction gradually increases with the Reynolds number, and that these coherent structures are eventually responsible for most of turbulent skin-friction generation at sufficiently high Reynolds numbers.
Parasites of the Brazilian flathead Percophis brasiliensis reflect West Atlantic biogeographic regions
Authors: BRAICOVICH PAOLA E. , PANTOJA CAMILA , PEREIRA ALDENICE N. , LUQUE JOSE L. , TIMI JUAN T.
Published: November 2016

With the aim of evaluating the utility of marine parasites as indicators of zoogeographical regions in the South West Atlantic, we analyzed data on assemblages of long-lived larval parasites of 488 specimens of Percophis brasiliensis distributed in 11 samples from nine localities covering the entire distribution of the species in the Argentine biogeographical Province. Near half a million long-lived parasite individuals belonging to 17 species present in the whole sample displayed clear latitudinal patterns. Data for parasite assemblages at infracommunity and component community levels were analysed in relation to the geographical distance. Significant similarity decay of parasite assemblages over distance was observed, with those based on abundances and mean abundances showing departures from predicted values of regressions. These departures were represented by higher dissimilarities between samples coming from different zoogeographical regions than between those caught within the same region, independently of the distance separating them. Consequently, zoogeographical regions were identified in a distance-decay context. Multivariate analyses corroborated a close fit of similarity between assemblages to existing zoogeographical classifications. Regressions representing distance decay of similarity, and the identification of their outliers, can therefore shed light on the existence of discontinuities or uniformities in the geographic distribution of parasite assemblages and, in turn, in the zoogeography of their fish hosts.
Multi-crossing number for knots and the Kauffman bracket polynomial
Authors: ADAMS COLIN , CAPOVILLA-SEARLE ORSOLA , FREEMAN JESSE , IRVINE DANIEL , PETTI SAMANTHA , VITEK DANIEL , WEBER ASHLEY , ZHANG SICONG
Published: November 2016

A multi-crossing (or n-crossing) is a singular point in a projection of a knot or link at which n strands cross so that each strand bisects the crossing. We generalise the classic result of Kauffman, Murasugi and Thistlethwaite relating the span of the bracket polynomial to the double-crossing number of a link, span〈K〉 ⩽ 4c2, to the n-crossing number. We find the following lower bound on the n-crossing number in terms of the span of the bracket polynomial for any n ⩾ 3:
$$\text{span} \langle K \rangle \leq \left(\left\lfloor\frac{n^2}{2}\right\rfloor + 4n - 8\right) c_n(K).$$
We also explore n-crossing additivity under composition, and find that for n ⩾ 4 there are examples of knots K1 and K2 such that cn(K1#K2) = cn(K1) + cn(K2) − 1. Further, we present the the first extensive list of calculations of n-crossing numbers of knots. Finally, we explore the monotonicity of the sequence of n-crossings of a knot, which we call the crossing spectrum.
Network analysis and modelling: Special issue ofEuropean Journal of Applied Mathematics
Authors: PORTER MASON A. , BIANCONI GINESTRA
Published: November 2016

This special issue of theEuropean Journal of Applied Mathematicsfeatures research articles onnetworks, one of the most exciting areas of applied mathematics.
Effect of guaianolides in the meiosis reinitiation of amphibian oocytes
Authors: Zapata-Martínez J. , Sánchez-Toranzo G. , Chaín F. , Catalán C.A.N. , Bühler M.I.
Published: November 2016

Sesquiterpene lactones (STLs) are a large and structurally diverse group of plant metabolites generally found in the Asteraceae family. STLs exhibit a wide spectrum of biological activities and it is generally accepted that their major mechanism of action is the alkylation of the thiol groups of biological molecules. The guaianolides is one of various groups of STLs. Anti-tumour and anti-migraine effects, an allergenic agent, an inhibitor of smooth muscle cells and of meristematic cell proliferation are only a few of the most commonly reported activities of STLs. In amphibians, fully grown ovarian oocytes are arrested at the beginning of meiosis I. Under stimulus with progesterone, this meiotic arrest is released and meiosis progresses to metaphase II, a process known as oocyte maturation. There are previous records of the inhibitory effect of dehydroleucodin (DhL), a guaianolide lactone, on the progression of meiosis. It has been also shown that DhL and its 11,13-dihydroderivative (2H-DhL; a mixture of epimers at C-11) act as blockers of the resumption of meiosis in fully grown ovarian oocytes from the amphibianRhinella arenarum(formerly classified asBufo arenarum). The aim of this study was to analyze the effect of four closely related guaianolides, i.e., DhL, achillin, desacetoxymatricarin and estafietin as possible inhibitors of meiosis in oocytes of amphibiansin vitroand discuss some structure–activity relationships. It was found that the inhibitory effect on meiosis resumption is greater when the lactone has two potentially reactive centres, either a α,β–α′,β′-diunsaturated cyclopentanone moiety or an epoxide group plus anexo-methylene-γ-lactone function.
Coatsandbrasandjeans– andclothes, too: lexical contrast between hyperonyms and hyponyms
Authors: KOSKELA ANU
Published: November 2016

A special case of lexical contrast involves contrasting a hyperonym and a hyponym (as inclothes and socks), leading to the narrowing of the hyperonym's sense. However, not all hyperonym/hyponym pairs are amenable to contrast (e.g.?animals and cats). While category prototype structure forms a strong motivating and constraining factor for hyperonym/hyponym contrast (e.g. Lehrer 1990), what is lacking in previous work is a systematic consideration of the co-hyponyms in real language use. To that end, data from the GloWbE corpus (Davies 2013) were used to investigate which terms for items of clothing (e.g.coat,bra,jeans) can be contrasted with their hyperonym (eitherclothesorclothing). While marginal members of theitem of clothingcategory (e.g.belt,hat) have a stronger potential for contrasting with the hyperonym, even prototypical hyponyms (e.g.shirt,jeans) contrasted withclothes/clothingin at least some contexts. Language users can therefore manipulate category boundaries to meet their discourse needs, exploiting a range of dimensions of difference to create contrast. Many clothing terms were also found to contrast more readily withclothesthan withclothing, suggesting that the meaning ofclothesis generally narrower than that of its near-synonymclothing.
Archaeology after interpretation. Returning humanity to archaeological theory
Authors: Barrett John C.
Published: November 2016

Do archaeologists recover the material record of past processes or the residues of the material conditions that made the presence of a kind of humanness possible? This paper attempts to emphasize the importance of distinguishing between these two options and argues the case for, and briefly contemplates the practical implications of, an archaeology of the human presence.
Against object agency. A counterreaction to Sørensen's ‘Hammers and nails’
Authors: Ribeiro Artur
Published: November 2016

This paper commends some ideas that Torill Christine Lindstrøm presented in this journal on the subject of ‘object agency’ (2015) and contends, against Tim Flohr Sørensen's reaction paper (2016), that object agency subsists on philosophically questionable premises. I argue that Sørensen relies on a definition of ‘agency’ which is too labile and virtually indistinguishable from ‘cause’. Moreover, certain premises that Sørensen supports lead to some contradictions with regard to social responsibility. Finally, I argue that object agency is part of a larger intellectual trend which perceives agency as a dynamic global force – and that a return to a more constrained understanding of agency would be of more benefit to archaeology.
CONFORMALLY FLAT CONTACT THREE-MANIFOLDS
Authors: CHO JONG TAEK , YANG DONG-HEE
Published: November 2016

In this paper, we consider contact metric three-manifolds $(M;\unicode[STIX]{x1D702},g,\unicode[STIX]{x1D711},\unicode[STIX]{x1D709})$ which satisfy the condition $\unicode[STIX]{x1D6FB}_{\unicode[STIX]{x1D709}}h=\unicode[STIX]{x1D707}h\unicode[STIX]{x1D711}+\unicode[STIX]{x1D708}h$ for some smooth functions $\unicode[STIX]{x1D707}$ and $\unicode[STIX]{x1D708}$, where $2h=\unicode[STIX]{x00A3}_{\unicode[STIX]{x1D709}}\unicode[STIX]{x1D711}$. We prove that if $M$ is conformally flat and if $\unicode[STIX]{x1D707}$ is constant, then $M$ is either a flat manifold or a Sasakian manifold of constant curvature $+1$. We cannot extend this result for a smooth function $\unicode[STIX]{x1D707}$. Indeed, we give such an example of a conformally flat contact three-manifold which is not of constant curvature.
The Relations between Prosocial Behaviors and Self-Regulation: Evidences from the Validation of the PTM-R for Portuguese Early Adolescents
Authors: Simões Francisco , Calheiros Maria Manuela
Published: November 2016

The main goal of this study is to understand the relationship between different types of prosocial behaviors and different forms of self-regulation, as part of the adaptation and validation of the Portuguese version of the Prosocial Tendencies Measure-Revised (PTM-R). A total of 403 early adolescents (M= 11.81;SD= .92; 52.91% girls) completed self-reported measures. The evaluation of psychometric properties of the PTM-R involved a confirmatory factorial analysis, followed by the examination of factorial internal consistency and factorial invariance analyses across gender groups and school retention groups (retentionvs.no-retention). The results support the premise that a 6-factor model similar to the original measure is the most appropriate factorial solution for the PTM-R Portuguese version (χ2(174) = 1.725,p< .001, CFI = .95, RMSEA = .030, SRMR = .08). The levels of internal consistency for the different subscales ranged from .67 to .78. Further convergent and divergent validity tests reveal that different forms of prosocial behavior are more often related to girls’ cognitive, affective and behavioral regulation and that students who failed at least one school year and thus had to repeat it denote poorer relations between prosocial behaviors and self-regulation dimensions, as opposed to more successful students. In conclusion, the Portuguese version of the PTM-R has adequate psychometric properties and its use for research purposes in the field of social development may be appropriate. The discussion focuses on the implications of these findings for future research on prosociality.
Demography and Demographers in Modern Germany: Social Science and Ideology across Political Regimes
Authors: Hochstadt Steve
Published: November 2016

The history of German research and writing about migration has been heavily influenced by politics. The assumptions and methods of successive generations of migration researchers demonstrate the interplay of social science and politics across very different political regimes. Soon after serious research began in the late nineteenth century, migration researchers divided into two camps. Urban statisticians with liberal political ideas used city migration registration data to analyze the circulatory movement of migrants within Germany. Conservative writers used census data to argue that migration was essentially movement from countryside to city, and was politically and morally injurious to the German people. These two sides hardened after World War I, as the conservative side increasingly incorporated racist ideas into their critique of migration. This debate continued even after the Nazis took power in 1933 with the competing publications of Rudolf Heberle and Wilhelm Brepohl. Heberle was forced to leave Germany and Brepohl became the Nazis’ favorite analyst of migration. After 1945, Brepohl retained his standing as a leading migration researcher in the German Federal Republic. The dominance of this conservative interpretation of migration continued into the 1970s. In recent decades, the writings of the liberal statisticians from the late nineteenth and early twentieth centuries have been rediscovered, and German migration research has shifted again toward a more empirically based understanding of migration.
The “Problem” of Interdisciplinarity in Theory, Practice, and History
Authors: Graff Harvey J.
Published: November 2016

Interdisciplinarity is among the most talked about but most misunderstood topics in education on all levels today. Seen as the savior of research and teaching, especially in universities, and of society, or the seeds of destruction, interdisciplinarity's proponents and critics talk past each other. Seldom do they seek common terms; typically, they mean very different approaches when they refer to interdisciplinarity. They erroneously dichotomize disciplines and interdisciplines, confuse specialization and synthesis, and misconstrue “integration.” They also date the historical turn to interdisciplinarity too late. This article critically reviews the history, historiography, and sociology of knowledge of interdisciplinarity with a focus on etiology, epistemology, definitions, relationships among and between disciplines, intellectual and institutional locations, and the organization of knowledge. A new, more historical approach to the “problem” of interdisciplinarity is proposed.
Strahlentherapie beim Pankreaskarzinom
Authors: Roeder Falk
Published: November 2016

Zusammenfassung. Dieser Review fasst die aktuelle Datenlage zu strahlentherapeutischen Ansätzen beim Pankreaskarzinom zusammen. Obwohl eine alleinige adjuvante Chemotherapie als durch randomisierte Studien gut abgesicherter Standard gelten muss, kann auf Basis hervorragender single-center Ergebnisse eine (additive) adjuvante Radiochemotherapie bei selektionierten Patienten durchaus erwogen werden. Im neoadjuvanten Setting beim resektablen Pankreaskarzinom stellt die Radiochemotherapie aktuell keinen Therapiestandard dar und sollten deshalb nur im Rahmen von Studien angeboten werden. Beim lokal-fortgeschrittenen, primär nicht- oder borderline-resektablen Pankreaskarzinom stellt sich die Situation unterschiedlich dar. In Abwesenheit eindeutiger Ergebnisse aus randomisierten Studien legen die publizierten Arbeiten nahe, dass eine neoadjuvante Radiochemotherapie in einem substantiellen Anteil der Patienten (30 – 40 %) zu sekundärer Resektabilität und damit zu einer deutlichen Verbesserung der Prognose führt. Hierbei werden Überlebensraten erreicht (median ~24 Monate), welche denjenigen bei primärer Resektabilität einschließlich adjuvanter Therapie entsprechen können. Selbst bei Nicht-Erreichen sekundärer Resektabilität kann zumindest eine Verbesserung der Lebensqualität durch dauerhafte Verhinderung einer lokalen Problematik resultieren. Eine Kombination mit einer Induktionschemotherapie scheint dabei insbesondere bei Verwendung moderner potenter Systemtherapieansätze (Folfirinox, Gem/nab-Paclitaxel) sinnvoll und wird derzeit in größeren Studien untersucht. Moderne perkutane Radiotherapietechniken (IMRT, IGRT, SBRT), neue Strahlqualitäten (Protonen, Schwerionen) oder die Kombination mit alternativen Boostverfahren (IORT) können die therapeutische Breite erhöhen und zur Steigerung der Effektivität und/oder zur Reduktion der Toxizität beitragen. Sie eröffnen innovative Therapiemöglichkeiten, welche in kontrollierten Studien untersucht werden sollten.
CME: Konservative und invasive Behandlungsmethoden in der Therapie des Lungenemphysems
Authors: Gautschi Fiorenza , Franzen Daniel
Published: November 2016

Zusammenfassung. Die COPD (chronic obstructive pulmonary disease) kennzeichnet sich durch eine persistierende und progrediente Einschränkung des Atemflusses aus, die durch eine chronische Entzündung der Atemwege bedingt ist. Das Lungenemphysem wird weitgehend als eine Spätfolge verstanden, wobei es dabei zur irreversiblen Zerstörung der Alveolen mit konsekutiver Überblähung kommt. Als Hauptursache in den Industrienationen gilt der Zigarettenkonsum, weshalb das primäre Therapieziel der Rauchstopp darstellt. Die Behandlung ist abhängig vom Schweregrad der Erkrankung, sowie den vorhandenen Komorbiditäten. Nach Ausschöpfung aller konservativer Massnahmen stellen bei sistiertem Zigarettenkonsum die chirurgische oder endoskopische Lungenvolumenreduktion oder in Abhängigkeit von Alter und Komorbiditäten eine Lungentransplantation eine mögliche Therapieoptionen dar.
Canil and Elliott Receive 2016 N. L. Bowen Award
Authors:   AGU
Published: November 2016

Dante Canil and Tim Elliott will receive the 2016 N. L. Bowen Award at the 2016 American Geophysical Union Fall Meeting, to be held 12–16 December in San Francisco, Calif. The award recognizes "outstanding contributions to volcanology, geochemistry, or petrology."
Cracking Comet: A Window to the Past
Authors: Wendel JoAnna
Published: November 2016

An unusual feature on comet 67P/Churyumov-Gerasimenko offers insights into cometary origins.
Inhibition of autophagy increased AGE/ROS-mediated apoptosis in mesangial cells
Authors: Xu Li , Fan Qiuling , Wang Xu , Zhao Xue , Wang Lining
Published: November 2016

The aim of our study was to investigate the role of autophagy, a homeostatic process involved in the lysosomal degradation of damaged cell organelles and proteins, in regulating the survival of mesangial cells treated with advanced glycation end products (AGEs). In the present study, AGEs induced mitochondrial depolarization and led to mitochondrial-dependent apoptosis in mesangial cells, as shown by the loss of the mitochondrial membrane potential; increased Bax processing; increased Caspase-9, Caspase-3 and PARP cleavage; and decreased Bcl-2 expression. Meanwhile, AGEs also triggered autophagy flux in mesangial cells, as confirmed by the presence of autophagic vesicles, the conversion of LC3II/LC3I and the increase/decrease in Beclin-1/p62 expression. Interestingly, this study reported apparent apoptosis and autophagy that were dependent on reactive oxygen species (ROS) production. Scavenging ROS with N-acetyl-l-cysteine could prevent the appearance of the autophagic features and reverse AGE-induced apoptosis. Moreover, AGE-triggered mitophagy, which was confirmed by the colocalization of autophagosomes and mitochondria and Parkin translocation to mitochondria, played a potential role in reducing ROS production in mesangial cells. Additionally, inhibition of autophagy significantly enhanced AGE-induced cell apoptosis. Taken together, our data suggest that ROS were the mediators of AGE-induced mesangial cell apoptosis and that autophagy was likely to be the mechanism that was triggered to repair the ROS-induced damage in the AGE-treated cells and thereby promote cell survival. This study provides new insights into the molecular mechanism of autophagy involved in AGE-induced apoptosis in mesangial cells.
Extrasynaptic NMDA receptor-induced tau overexpression mediates neuronal death through suppressing survival signaling ERK phosphorylation
Authors: Sun Xu-Ying , Tuo Qing-Zhang , Liuyang Zhen-Yu , Xie Ao-Ji , Feng Xiao-Long , Yan Xiong , Qiu Mei , Li Shen , Wang Xiu-Lian , Cao Fu-Yuan , Wang Xiao-Chuan , Wang Jian-Zhi , Liu Rong
Published: November 2016

Intracellular accumulation of the hyperphosphorylated tau is a pathological hallmark in the brain of Alzheimer disease. Activation of extrasynaptic NMDA receptors (E-NMDARs) induces excitatory toxicity that is involved in Alzheimer’s neurodegeneration. However, the intrinsic link between E-NMDARs and the tau-induced neuronal damage remains elusive. In the present study, we showed in cultured primary cortical neurons that activation of E-NMDA receptors but not synaptic NMDA receptors dramatically increased tau mRNA and protein levels, with a simultaneous neuronal degeneration and decreased neuronal survival. Memantine, a selective antagonist of E-NMDARs, reversed E-NMDARs-induced tau overexpression. Activation of E-NMDARs in wild-type mouse brains resulted in neuron loss in hippocampus, whereas tau deletion in neuronal cultures and in the mouse brains rescued the E-NMDARs-induced neuronal death and degeneration. The E-NMDARs-induced tau overexpression was correlated with a reduced ERK phosphorylation, whereas the increased MEK activity, decreased binding and activity of ERK phosphatase to ERK, and increased ERK phosphorylation were observed in tau knockout mice. On the contrary, addition of tau proteins promoted ERK dephosphorylation in vitro. Taking together, these results indicate that tau overexpression mediates the excitatory toxicity induced by E-NMDAR activation through inhibiting ERK phosphorylation.
Doxorubicin attenuates CHIP-guarded HSF1 nuclear translocation and protein stability to trigger IGF-IIR-dependent cardiomyocyte death
Authors: Huang Chih-Yang , Kuo Wei-Wen , Lo Jeng-Fan , Ho Tsung-Jung , Pai Pei-ying , Chiang Shu-Fen , Chen Pei-Yu , Tsai Fu-Jen , Tsai Chang-Hai , Huang Chih-Yang
Published: November 2016

Doxorubicin (DOX) is one of the most effective antitumor drugs, but its cardiotoxicity has been a major concern for its use in cancer therapy for decades. Although DOX-induced cardiotoxicity has been investigated, the underlying mechanisms responsible for this cardiotoxicity have not been completely elucidated. Here, we found that the insulin-like growth factor receptor II (IGF-IIR) apoptotic signaling pathway was responsible for DOX-induced cardiotoxicity via proteasome-mediated heat shock transcription factor 1 (HSF1) degradation. The carboxyl-terminus of Hsp70 interacting protein (CHIP) mediated HSF1 stability and nuclear translocation through direct interactions via its tetratricopeptide repeat domain to suppress IGF-IIR expression and membrane translocation under physiological conditions. However, DOX attenuated the HSF1 inhibition of IGF-IIR expression by diminishing the CHIP–HSF1 interaction, removing active nuclear HSF1 and triggering HSF1 proteasomal degradation. Overexpression of CHIP redistributed HSF1 into the nucleus, inhibiting IGF-IIR expression and preventing DOX-induced cardiomyocyte apoptosis. Moreover, HSF1A, a small molecular drug that enhances HSF1 activity, stabilized HSF1 expression and minimized DOX-induced cardiac damage in vitro and in vivo. Our results suggest that the cardiotoxic effects of DOX result from the prevention of CHIP-mediated HSF1 nuclear translocation and activation, which leads to an upregulation of the IGF-IIR apoptotic signaling pathway. We believe that the administration of an HSF1 activator or agonist may further protect against the DOX-induced cell death of cardiomyocytes.
A novel crosstalk between CCAR2 and AKT pathway in the regulation of cancer cell proliferation
Authors: Restelli Michela , Magni Martina , Ruscica Vincenzo , Pinciroli Patrizia , De Cecco Loris , Buscemi Giacomo , Delia Domenico , Zannini Laura
Published: November 2016

Human CCAR2 has recently emerged as having a pivotal role in the DNA damage response, promoting apoptosis and repair of heterochromatic DNA breaks. However, less is known about the function of CCAR2 in tumor formation and cancer progression. Here, we demonstrate, for the first time, that CCAR2 loss inhibits the proliferation of cancer cells, but preserves the growth of normal cells. Investigating the mechanisms responsible for this differential effect, we found that CCAR2 depletion specifically impairs the activation of AKT pathway in cancer cells, but not in normal cells, by reducing AKT phosphorylation on Ser473. This effect is achieved through the transcriptional upregulation ofTRB3gene and accumulation of TRB3 protein, which then binds to and inhibits the phosphorylation and activation of AKT. The defective activation of AKT finally results in reduced GSK3βphosphorylation, prevention of G1/S transition and inhibition of cancer cell growth. These results establish an important role for CCAR2 in cancer cells proliferation and could shed new light on novel therapeutic strategies against cancer, devoid of detrimental side effects.
What causes mating system shifts in plants? Arabidopsis lyrata as a case study
Authors: Mable B K , Hagmann J , Kim S-T , Adam A , Kilbride E , Weigel D , Stift M
Published: November 2016

The genetic breakdown of self-incompatibility (SI) and subsequent mating system shifts to inbreeding has intrigued evolutionary geneticists for decades. Most of our knowledge is derived from interspecific comparisons between inbreeding species and their outcrossing relatives, where inferences may be confounded by secondary mutations that arose after the initial loss of SI. Here, we study an intraspecific breakdown of SI and its consequences in North American Arabidopsis lyrata to test whether: (1) particular S-locus haplotypes are associated with the loss of SI and/or the shift to inbreeding; (2) a population bottleneck may have played a role in driving the transition to inbreeding; and (3) the mutation(s) underlying the loss of SI are likely to have occurred at the S-locus. Combining multiple approaches for genotyping, we found that outcrossing populations on average harbour 5 to 9 S-locus receptor kinase (SRK) alleles, but only two, S1 and S19, are shared by most inbreeding populations. Self-compatibility (SC) behaved genetically as a recessive trait, as expected from a loss-of-function mutation. Bulked segregant analysis in SC × SI F2 individuals using deep sequencing confirmed that all SC plants were S1 homozygotes but not all S1 homozygotes were SC. This was also revealed in population surveys, where only a few S1 homozygotes were SC. Together with crossing data, this suggests that there is a recessive factor that causes SC that is physically unlinked to the S-locus. Overall, our results emphasise the value of combining classical genetics with advanced sequencing approaches to resolve long outstanding questions in evolutionary biology.
Splenic differentiation and emergence of CCR5+CXCL9+CXCL10+ monocyte-derived dendritic cells in the brain during cerebral malaria
Authors: Hirako Isabella C. , Ataide Marco A. , Faustino Lucas , Assis Patricia A. , Sorensen Elizabeth W. , Ueta Hisashi , Araújo Natalia M. , Menezes Gustavo B. , Luster Andrew D. , Gazzinelli Ricardo T.
Published: November 2016

Dendritic cells have an important role in immune surveillance. After being exposed to microbial components, they migrate to secondary lymphoid organs and activate T lymphocytes. Here we show that during mouse malaria, splenic inflammatory monocytes differentiate into monocyte-derived dendritic cells (MO-DCs), which are CD11b+F4/80+CD11c+MHCIIhighDC-SIGNhighLy6c+ and express high levels of CCR5, CXCL9 and CXCL10 (CCR5+CXCL9/10+ MO-DCs). We propose that malaria-induced splenic MO-DCs take a reverse migratory route. After differentiation in the spleen, CCR5+CXCL9/10+ MO-DCs traffic to the brain in a CCR2-independent, CCR5-dependent manner, where they amplify the influx of CD8+ T lymphocytes, leading to a lethal neuropathological syndrome.
Erratum: High-Resolution Imaging by Adaptive Optics Scanning Laser Ophthalmoscopy Reveals Two Morphologically Distinct Types of Retinal Hard Exudates
Authors: Yamaguchi Muneo , Nakao Shintaro , Kaizu Yoshihiro , Kobayashi Yoshiyuki , Nakama Takahito , Arima Mitsuru , Yoshida Shigeo , Oshima Yuji , Takeda Atsunobu , Ikeda Yasuhiro , Mukai Shizuo , Ishibashi Tatsuro , Sonoda Koh-hei
Published: November 2016

Scientific Reports 6: Article number: 33574; published online: 19 September 2016; updated: 03 November 2016
An anti-infective synthetic peptide with dual antimicrobial and immunomodulatory activities
Authors: Silva O. N. , de la Fuente-Núñez C. , Haney E. F. , Fensterseifer I. C. M. , Ribeiro S. M. , Porto W. F. , Brown P. , Faria-Junior C. , Rezende T. M. B. , Moreno S. E. , Lu T. K. , Hancock R. E. W. , Franco O. L.
Published: November 2016

Antibiotic-resistant infections are predicted to kill 10 million people per year by 2050, costing the global economy $100 trillion. Therefore, there is an urgent need to develop alternative technologies. We have engineered a synthetic peptide called clavanin-MO, derived from a marine tunicate antimicrobial peptide, which exhibits potent antimicrobial and immunomodulatory properties both in vitro and in vivo. The peptide effectively killed a panel of representative bacterial strains, including multidrug-resistant hospital isolates. Antimicrobial activity of the peptide was demonstrated in animal models, reducing bacterial counts by six orders of magnitude, and contributing to infection clearance. In addition, clavanin-MO was capable of modulating innate immunity by stimulating leukocyte recruitment to the site of infection, and production of immune mediators GM-CSF, IFN-γ and MCP-1, while suppressing an excessive and potentially harmful inflammatory response by increasing synthesis of anti-inflammatory cytokines such as IL-10 and repressing the levels of pro-inflammatory cytokines IL-12 and TNF-α. Finally, treatment with the peptide protected mice against otherwise lethal infections caused by both Gram-negative and -positive drug-resistant strains. The peptide presented here directly kills bacteria and further helps resolve infections through its immune modulatory properties. Peptide anti-infective therapeutics with combined antimicrobial and immunomodulatory properties represent a new approach to treat antibiotic-resistant infections.
Fluselenamyl: A Novel Benzoselenazole Derivative for PET Detection of Amyloid Plaques (Aβ) in Alzheimer’s Disease
Authors: Sundaram G. S. M. , Dhavale Dhruva D. , Prior Julie L. , Yan Ping , Cirrito John , Rath Nigam P. , Laforest Richard , Cairns Nigel J. , Lee Jin-Moo , Kotzbauer Paul T. , Sharma Vijay
Published: November 2016

Fluselenamyl (5), a novel planar benzoselenazole shows traits desirable of enabling noninvasive imaging of Aβ pathophysiology in vivo; labeling of both diffuse (an earlier manifestation of neuritic plaques) and fibrillar plaques in Alzheimer’s disease (AD) brain sections, and remarkable specificity for mapping Aβ compared with biomarker proteins of other neurodegenerative diseases. Employing AD homogenates, [18F]-9, a PET tracer demonstrates superior (2–10 fold higher) binding affinity than approved FDA tracers, while also indicating binding to high affinity site on Aβ plaques. Pharmacokinetic studies indicate high initial influx of [18F]-9 in normal mice brains accompanied by rapid clearance in the absence of targeted plaques. Following incubation in human serum, [18F]-9 indicates presence of parental compound up to 3h thus indicating its stability. Furthermore, in vitro autoradiography studies of [18F]-9 with AD brain tissue sections and ex vivo autoradiography studies in transgenic mouse brain sections show cortical Aβ binding, and a fair correlation with Aβ immunostaining. Finally, multiphoton- and microPET/CT imaging indicate its ability to penetrate brain and label parenchymal plaques in transgenic mice. Following further validation of its performance in other AD rodent models and nonhuman primates, Fluselenamyl could offer a platform technology for monitoring earliest stages of Aβ pathophysiology in vivo.
LPA receptor activity is basal specific and coincident with early pregnancy and involution during mammary gland postnatal development
Authors: Acosta Deanna , Bagchi Susmita , Broin Pilib Ó , Hollern Daniel , Racedo Silvia E. , Morrow Bernice , Sellers Rani S. , Greally John M. , Golden Aaron , Andrechek Eran , Wood Teresa , Montagna Cristina
Published: November 2016

During pregnancy, luminal and basal epithelial cells of the adult mammary gland proliferate and differentiate resulting in remodeling of the adult gland. While pathways that control this process have been characterized in the gland as a whole, the contribution of specific cell subtypes, in particular the basal compartment, remains largely unknown. Basal cells provide structural and contractile support, however they also orchestrate the communication between the stroma and the luminal compartment at all developmental stages. Using RNA-seq, we show that basal cells are extraordinarily transcriptionally dynamic throughout pregnancy when compared to luminal cells. We identified gene expression changes that define specific basal functions acquired during development that led to the identification of novel markers. Enrichment analysis of gene sets from 24 mouse models for breast cancer pinpoint to a potential new function for insulin-like growth factor 1 (Igf1r) in the basal epithelium during lactogenesis. We establish that β-catenin signaling is activated in basal cells during early pregnancy, and demonstrate that this activity is mediated by lysophosphatidic acid receptor 3 (Lpar3). These findings identify novel pathways active during functional maturation of the adult mammary gland.
Non-invasive, transient determination of the core temperature of a heat-generating solid body
Authors: Anthony Dean , Sarkar Daipayan , Jain Ankur
Published: November 2016

While temperature on the surface of a heat-generating solid body can be easily measured using a variety of methods, very few techniques exist for non-invasively measuring the temperature inside the solid body as a function of time. Measurement of internal temperature is very desirable since measurement of just the surface temperature gives no indication of temperature inside the body, and system performance and safety is governed primarily by the highest temperature, encountered usually at the core of the body. This paper presents a technique to non-invasively determine the internal temperature based on the theoretical relationship between the core temperature and surface temperature distribution on the outside of a heat-generating solid body as functions of time. Experiments using infrared thermography of the outside surface of a thermal test cell in a variety of heating and cooling conditions demonstrate good agreement of the predicted core temperature as a function of time with actual core temperature measurement using an embedded thermocouple. This paper demonstrates a capability to thermally probe inside solid bodies in a non-invasive fashion. This directly benefits the accurate performance prediction and control of a variety of engineering systems where the time-varying core temperature plays a key role.