bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and Efficacy of Biologic Agents for the Management of Inflammatory Bowel Disease After Liver Transplantation
Authors: Shaikh Suhail A. , Fitzgerald Linda , Tischer Sarah
Published: September 2017

Primary sclerosing cholangitis (PSC) frequently progresses to end‐stage liver disease and cirrhosis, requiring liver transplantation. Approximately 70% of patients with PSC have concomitant inflammatory bowel disease (IBD) during their clinical course. After liver transplantation for PSC, corticosteroids and other high‐intensity immunosuppressants are initiated to keep IBD in remission. Patients with IBD that is refractory to these agents may need to be managed with biologic therapies. Biologic agents, however, may further increase the risks for malignancy and infection due to their immunosuppressive effects. Thus, to gain a better understanding of the risks and benefits of these agents in this high‐risk patient population, we performed a literature search of the PubMed database (2002–2017) to identify studies assessing the efficacy and safety of various biologic agents for the management of IBD in liver transplant recipients. No randomized controlled studies or retrospective comparative studies were identified; however, 15 case reports and case series were identified that met our inclusion criteria. From these case reports, we identified 67 patients who developed de novo or recurrent IBD after liver transplantation and received anti–tumor necrosis factor‐α or anti‐integrin therapy. Of the 13 published cases reporting clinical response or remission of IBD activity in liver transplant recipients (59 patients), clinical response or remission of IBD was reported in 38 (64.4%) of those patients. Adverse complications reported included cholangitis, oral candidiasis, Clostridium difficile colitis, bacterial pneumonia, cryptosporidiosis, Epstein–Barr virus–positive posttransplantation lymphoproliferative disease, and hepatotoxicity. Given the limited literature (case reports and case series) highlighted in this review, biologic agents such as tumor necrosis factor‐α inhibitors and integrin inhibitors commonly used for moderate to severe IBD may be appropriate after liver transplantation; however, consideration of risk versus benefit should always occur in a patient‐specific manner.
From chaperonins to Rubisco assembly and metabolic repair
Authors: Hayer‐Hartl Manajit
Published: September 2017

Ribulose‐1,5‐bisphosphate carboxylase/oxygenase (Rubisco) mediates the fixation of atmospheric CO2 in photosynthesis by catalyzing the carboxylation of the 5‐carbon sugar ribulose‐1,5‐bisphosphate (RuBP). Despite its pivotal role, Rubisco is an inefficient enzyme and thus has been a key target for bioengineering. However, efforts to increase crop yields by Rubisco engineering remain unsuccessful, due in part to the complex machinery of molecular chaperones required for Rubisco biogenesis and metabolic repair. While the large subunit of Rubisco generally requires the chaperonin system for folding, the evolution of the hexadecameric Rubisco from its dimeric precursor resulted in the dependence on an array of additional factors required for assembly. Moreover, Rubisco function can be inhibited by a range of sugar‐phosphate ligands. Metabolic repair of Rubisco depends on remodeling by the ATP‐dependent Rubisco activase and hydrolysis of inhibitors by specific phosphatases. This review highlights our work toward understanding the structure and mechanism of these auxiliary machineries.
Bacterial cupredoxin azurin hijacks cellular signaling networks: Protein–protein interactions and cancer therapy
Authors: Gao Meng , Zhou Jingjing , Su Zhengding , Huang Yongqi
Published: September 2017

Azurin secreted by Pseudomonas aeruginosa is an anticancer bacteriocin, which preferentially enters human cancer cells and induces apoptosis or growth inhibition. It turns out that azurin is a multi‐target anticancer agent interfering in the p53 signaling pathway and the non‐receptor tyrosine kinases signaling pathway. This suggests that azurin exerts its anticancer activity by interacting with multiple targets and interfering in multiple steps in disease progression. Therefore, azurin could overcome resistance to therapy. Besides azurin, putative bacteriocins that possess functional properties similar to those of azurin have been identified in more bacteria species. A systematic investigation on the anticancer mechanisms of azurin and the azurin‐like bacteriocins will provide more and better options in cancer therapy. In this review, we summarize how azurin and the derived peptides hijack key cellular regulators or cell surface receptors to remodel the cellular signaling networks. In particular, we highlight the necessity of determining the structure of azurin/p53 complex and investigating the influence of post‐translational modifications on interactions between azurin and p53. Therapeutic applications of azurin and derived peptides are also discussed.
Monitoring type‐2 censored reliability data in multistage processes
Authors: Asadzadeh Shervisn , Kiadaliry Fatemeh
Published: September 2017

In this paper, we propose control charts to monitor the Weibull scale parameter of type‐2 censored reliability data in multistage processes. A cumulative sum control chart and 2 exponentially weighted moving average control charts based on conditional expected values are devised to detect decreases in the mean level of reliability‐related quality characteristic. The proposed control schemes are based on standard smallest extreme value distributions derived from Weibull processes to effectively account for the cascade property, which is the main characteristic of multistage processes. Subsequently, simulation study is conducted to evaluate the performance of the control charts using average run length criterion. Extra quadratic loss, performance comparison index, and relative average run length are also used to compare the detect ability of our proposed monitoring procedures. Moreover, sensitivity analysis is done to study the impact of failure number in the sample size and to investigate the robustness of the proposed monitoring procedures against the shift in the previous stage. Finally, a real case study in a glass bottle–making company is investigated to illustrate the performance of the competing control charts. The results reveal the superiority of the cumulative sum control chart.
Reliability evaluation for wireless sensor networks with chain structures using the universal generating function
Authors: Liu Qiang , Yin Xiao , Yang Xiao , Ma Yanbo
Published: September 2017

In different protocols, wireless sensor networks (WSNs) form different topologies. The reliability evaluation of a WSN whose topology is a chain is studied in this paper. A bidirectional data transmission tree (BDTT) model is established to describe the process of data fusion and transmission on a WSN with a chain structure. From the characteristics of the measurement errors, the number of fusions, and measurement credibility, 3 definitions for the reliability of a BDTT are presented. Based on the universal generating function technique, an algorithm is suggested for evaluating the reliability of a BDTT. In the algorithm, a BDTT model is divided into 2 branches, and 2 new composition operators are defined according to data fusion and transmission. We use the first operator to obtain the u‐function of each branch and the second one to combine the u‐functions of 2 branches and obtain the u‐function of the BDTT. The process of calculating the reliability of a BDTT is illustrated with an example, and the effects of measurement errors, the number of fusions, and measurement credibility on the system reliability are analyzed.
Fibonacci sequence for modelling stop bands in random microstructure
Authors: Gitman Inna M. , Song Yilang
Published: September 2017

In this paper the mathematical concept of the Fibonacci sequence has been introduced as an accurate and reliable tool to model randomness in a heterogeneous material. It is also argued, that this randomness plays an important role and can control the response of a heterogeneous material, subjected to dynamic loading, here an elastic wave propagating through the material. A particular dynamic phenomenon, the presence of band gaps, has been analysed. It has been shown that randomness, modelled using the Fibonacci sequence, introduced into the material's structure, increases the range of stop band frequencies.
Implications of Warm Rain in Shallow Cumulus and Congestus Clouds for Large-Scale Circulations
Authors: Nuijens Louise , Emanuel Kerry , Masunaga Hirohiko , L’Ecuyer Tristan
Published: September 2017

Space-borne observations reveal that 20–40% of marine convective clouds below the freezing level produce rain. In this paper we speculate what the prevalence of warm rain might imply for convection and large-scale circulations over tropical oceans. We present results using a two-column radiative–convective model of hydrostatic, nonlinear flow on a non-rotating sphere, with parameterized convection and radiation, and review ongoing efforts in high-resolution modeling and observations of warm rain. The model experiments investigate the response of convection and circulation to sea surface temperature (SST) gradients between the columns and to changes in a parameter that controls the conversion of cloud condensate to rain. Convection over the cold ocean collapses to a shallow mode with tops near 850 hPa, but a congestus mode with tops near 600 hPa can develop at small SST differences when warm rain formation is more efficient. Here, interactive radiation and the response of the circulation are crucial: along with congestus a deeper moist layer develops, which leads to less low-level radiative cooling, a smaller buoyancy gradient between the columns, and therefore a weaker circulation and less subsidence over the cold ocean. The congestus mode is accompanied with more surface precipitation in the subsiding column and less surface precipitation in the deep convecting column. For the shallow mode over colder oceans, circulations also weaken with more efficient warm rain formation, but only marginally. Here, more warm rain reduces convective tops and the boundary layer depth—similar to Large-Eddy Simulation (LES) studies—which reduces the integrated buoyancy gradient. Elucidating the impact of warm rain can benefit from large-domain high-resolution simulations and observations. Parameterizations of warm rain may be constrained through collocated cloud and rain profiling from ground, and concurrent changes in convection and rain in subsiding and convecting branches of circulations may be revealed from a collocation of space-borne sensors, including the Global Precipitation Measurement (GPM) and upcoming Aeolus missions.
The Experience of Genetic Counselors Working with Patients Facing the Decision of Pregnancy Termination after 24 Weeks Gestation
Authors: Graziani Rachel N. A. , Nemzer Laurie , Kerns Jennifer
Published: September 2017

Prenatal genetic counselors are health care professionals who counsel women making reproductive decisions which include decisions such as terminating pregnancies due to fetal anomalies. Little is known about the experiences and practices of prenatal genetic counselors working with women who have the option of termination after 24 weeks gestation. In this national survey of 168 genetic counselors who have practiced prenatal genetic counseling, we asked about their general practice patterns, including indications for which termination is offered and types of abortion care services that are coordinated by genetic counselors. We report respondents’ self‐assessments of level of understanding of federal abortion law and abortion procedures. Seventy‐six percent of respondents have offered and counseled on termination after 24 weeks and 93% of respondents believe it is the responsibility of the counselor to discuss this option with patients. However, one‐third report that they have some or no understanding of the procedures and three‐quarters report that they have some or no understanding of federal abortion law. The results of this study provide insight into knowledge and experiences of genetic counselors working with these patients, allowing for improved genetic counselor training and continuing education to provide better guidance and develop more effective means of assisting patients.
Clinical Utility of Expanded Carrier Screening: Reproductive Behaviors of At‐Risk Couples
Authors: Ghiossi Caroline E. , Goldberg James D. , Haque Imran S. , Lazarin Gabriel A. , Wong Kenny K.
Published: September 2017

Expanded carrier screening (ECS) analyzes dozens or hundreds of recessive genes to determine reproductive risk. Data on the clinical utility of screening conditions beyond professional guidelines are scarce. Individuals underwent ECS for up to 110 genes. Five‐hundred thirty‐seven at‐risk couples (ARC), those in which both partners carry the same recessive disease, were invited to participate in a retrospective IRB‐approved survey of their reproductive decision making after receiving ECS results. Sixty‐four eligible ARC completed the survey. Of 45 respondents screened preconceptionally, 62% (n = 28) planned IVF with PGD or prenatal diagnosis (PNDx) in future pregnancies. Twenty‐nine percent (n = 13) were not planning to alter reproductive decisions. The remaining 9% (n = 4) of responses were unclear. Of 19 pregnant respondents, 42% (n = 8) elected PNDx, 11% (n = 2) planned amniocentesis but miscarried, and 47% (n = 9) considered the condition insufficiently severe to warrant invasive testing. Of the 8 pregnancies that underwent PNDx, 5 were unaffected and 3 were affected. Two of 3 affected pregnancies were terminated. Disease severity was found to have significant association (p = 0.000145) with changes in decision making, whereas guideline status of diseases, controlled for severity, was not (p = 0.284). Most ARC altered reproductive planning, demonstrating the clinical utility of ECS. Severity of conditions factored into decision making.
Progressive sampling-based Bayesian optimization for efficient and automatic machine learning model selection
Authors: Zeng Xueqiang , Luo Gang
Published: September 2017

Purpose

Machine learning is broadly used for clinical data analysis. Before training a model, a machine learning algorithm must be selected. Also, the values of one or more model parameters termed hyper-parameters must be set. Selecting algorithms and hyper-parameter values requires advanced machine learning knowledge and many labor-intensive manual iterations. To lower the bar to machine learning, miscellaneous automatic selection methods for algorithms and/or hyper-parameter values have been proposed. Existing automatic selection methods are inefficient on large data sets. This poses a challenge for using machine learning in the clinical big data era.

Methods

To address the challenge, this paper presents progressive sampling-based Bayesian optimization, an efficient and automatic selection method for both algorithms and hyper-parameter values.

Results

We report an implementation of the method. We show that compared to a state of the art automatic selection method, our method can significantly reduce search time, classification error rate, and standard deviation of error rate due to randomization.

Conclusions

This is major progress towards enabling fast turnaround in identifying high-quality solutions required by many machine learning-based clinical data analysis tasks.
The Politics of Heresy in Ambrose of Milan
Authors: Williams Michael Stuart
Published: September 2017

Ambrose of Milan is famous above all for his struggle with, and triumph over, 'Arian' heresy. Yet, almost all of the evidence comes from Ambrose's own writings, and from pious historians of the next generation who represented him as a champion of orthodoxy. This detailed study argues instead that an 'Arian' opposition in Milan was largely conjured up by Ambrose himself, lumping together critics and outsiders in order to secure and justify his own authority. Along with new interpretations of Ambrose's election as bishop, his controversies over the faith, and his clashes with the imperial court, this book provides a new understanding of the nature and significance of heretical communities in Late Antiquity. In place of rival congregations inflexibly committed to doctrinal beliefs, it envisages a world of more fluid allegiances in which heresy - but also consensus - could be a matter of deploying the right rhetorical frame.
Rome and the Third Macedonian War
Authors: Burton Paul J.
Published: September 2017

This is the first full-length study of the final war between Rome and the ancient Macedonian monarchy and its last king, Perseus. The Roman victory at the Battle of Pydna in June 168 BC was followed by the abolition of the kingdom of Macedon - the cradle of Philip II, Alexander the Great, and the Antigonid monarchs who followed. The first historian of Rome's rise to world power, and a contemporary of the war, Polybius of Megalopolis, recognized the significance of these events in making Rome an almost global power beyond compare - a sole superpower, in other words. Yet Roman authority did not lack challenges from lesser states and insurgents in the decades that followed. The book's meticulous documentation, close analysis, and engagement in scholarly controversy will appeal to academics and students, while general readers will appreciate its brisk narrative style and pacing.
Gerard Manley Hopkins and the Poetry of Religious Experience
Authors: Dubois Martin
Published: September 2017

This nuanced yet accessible study is the first to examine the range of religious experience imagined in Hopkins's writing. By exploring the shifting way in which Hopkins imagines religious belief in individual history, Martin Dubois contests established views of his poetry as a unified project. Combining detailed close readings with extensive historical research, Dubois argues that the spiritual awareness manifest in Hopkins's poetry is varied and fluctuating, and that this is less a failure of his intellectual system than a sign of the experiential character of much of his poetry's thought. Individual chapters focus on biblical language and prayer, as well as on the spiritual ideal seen in the figures of the soldier and the martyr, and on Hopkins's ideas of death, judgement, heaven and hell. Offering fresh interpretations of the major poems, this volume reveals a more diverse and exploratory poet than has been recognised.
Protection in Life and Death: Pendant Crosses from the Cemetery of Apollo Klarios at Sagalassos, Turkey
Authors: Cleymans Sam , Talloen Peter
Published: September 2017

This article presents the different types of pendant crosses found in the burials of a Middle Byzantine graveyard at the Pisidian settlement of Sagalassos in south-western Turkey. The aim is to study both the chronology and function of these pectoral crosses. A variety of sources are used, ranging from stratigraphy and radiocarbon dates to contextual information and skeletal data. The crosses could be broadly dated to between the eleventh and thirteenth centuryAD, thus providing an indication of the lifespan of the cemetery. Moreover, the typological evolution, which was corroborated by parallels from other sites in the Byzantine Empire, allowed us to establish a horizontal stratigraphy for the graveyard. The pectoral crosses discussed here shed light on the funerary practices in this part of the Byzantine world. These generally proved to belong to very young children. They constitute a category of material culture that not only provides insights into the lives of the Byzantine population, especially in early childhood, but are also the material manifestation of the intersection between popular religion, magic, and funerary rites.
Structuring Particularist Publics: Logistics, Language, and Early Modern Wales
Authors: Bowen Lloyd
Published: September 2017

This article examines how early modern publics were shaped partly by dynamics of linguistic difference and physical distance. Taking Wales as its focus, it argues that barriers to communication have yet to be considered sufficiently in a literature which presents English language metropolitan discourses as normative. Particularist publics that drew upon different cultural heritages and employed different communicative practices to those prevailing in and around London deserve greater attention. This is illustrated principally by the vernacularizing impulses of Protestant reform in sixteenth-century Wales and the responses these elicited from Catholic interests, and also the attempts to construct political publics in Wales during the 1640s and 1650s. Early modern Welsh public culture was characterized by a degree of isolation from the genres and sites of critical opinion (such as newsbooks and coffeehouses); print production was underdeveloped; and there were logistical barriers to the spread of news. Conceptualizing early modern Wales as a “particularist public” can help enrich our understanding of center-locality relationships in other parts of the English (and subsequently British) realm.
Print Culture, State Formation, and an Anglo-Scottish Public, 1640–1648
Authors: Peacey Jason
Published: September 2017

Based upon the idea that debates regarding the “public sphere” have paid insufficient attention to the notion of multiple publics and the movement of texts across state borders, this article explores how print culture provided ways of promoting transterritorial publics. It does so by revisiting the vexed notion of the “British problem” in the seventeenth century and relations between Scottish Covenanters and English parliamentarians, and by emphasizing the need to consider print culture in tandem with state formation. It demonstrates that a significant volume of printed material––produced both in England and Scotland, and sometimes collaboratively––reflected and promoted cross-border cooperation, thereby fostering a nascent Anglo-Scottish public. It also emphasizes that the practices involved were intimately linked to attempts to establish federal political institutions that both responded to the existence of a “British” public and necessitated its further development. Ultimately, however, the need to address and maintain such a public led to printed texts being used to navigate tensions between Covenanters and parliamentarians, to the point where Anglo-Scottish interests gave way to national interests, where resistance grew to the legitimacy of using print as a cross-border device, and where print helped to undermine cross-border cooperation.
NEWLY DISCOVERED FRIEZES AT THE PERUVIAN SITE OF TAUKACHI-KONKÁN: A POSSIBLE GLIMPSE INTO INITIAL PERIOD COSMOLOGY
Authors: Pozorski Shelia , Pozorski Thomas , Marín Jave Rosa
Published: September 2017

Excavations conducted in 2015 and 2016 discovered a unique set of friezes at the Initial period (2100–1000 cal BC) site of Taukachi-Konkán in the coastal Peruvian valley of Casma. At this time, the Casma Valley was dominated by the Sechín Alto polity, a cultural development of unprecedented complexity characterized by large planned cities, monumental constructions, and strong interconnections among component settlements. Friezes are known from all major Sechín Alto polity sites where they typically adorn structure facades; however, the Taukachi-Konkán friezes are unusual because they cover all four interior walls of a sunken court with restricted access. Based on analysis of the context and content of these friezes, we suggest that the collective imagery depicts aspects of Sechín Alto polity cosmology, including possible iconography relating to their creation myth. Furthermore, motifs from the Taukachi-Konkán sunken court can be found at contemporary sites both within and outside the Casma Valley. This suggests that the worldview we reconstructed may have been widespread during the Initial period.
The Lepcitanian territory: cultural heritage in danger in war and peace
Authors: Munzi Massimiliano , Zocchi Andrea
Published: September 2017

Since 1995 the Archaeological Mission to Libya of Roma Tre University has carried out several surveys in the territory and suburbs of Lepcis Magna. Besides the survey of the archaeological and historical sites, the Roma Tre team has also had the opportunity to observe and record the development of the landscape through periods of war and peace.

In this article, the issues related to the cultural heritage in the area of the modern city of Khoms and in the Lepcis hinterland are analysed and particular consideration is given to the damage and destruction that has occurred since the Italian occupation (1911) until the present day. The Lepcitanian/Khoms territory is an interesting case study in which the cultural heritage has been, and still is, at risk due to ‘civilian’ and ‘conflict’ causes. Besides the damage that occurred during the Italo-Turkish War and – to a minor extent – during WWII, the main damage seems to have occurred in the last sixty years due to the expansion of Khoms and to the ongoing unstable political situation in which the lack of central government control is playing an important role. In particular, since 2011, Islamic fundamentalists have demolished in these areas several ancient marabouts, destroying one of the most characteristic aspects of the Tripolitanian/Libyan cultural landscape.
Quand observations et interprétations diffèrent : le cas de l'arc de triomphe de Tripoli dans les sources arabes
Authors: Mkacher Anis
Published: September 2017

The only building which has been preserved from the ancient urban fabric of Tripoli, Oea in antiquity, is the Triumphal Arch. By considering Arab sources, we may shed new light on its evolution, the place it had been in the past and the way it was considered during those times. If we compare two excerpts from Arab-Muslim historiography, written by local travellers, with Western testimonies, we see that the monument was reinterpreted in the light of the new culture which was established in the region and of the local history of the city.
Biased Elites, Unfit Policies: Reflections on the Lacunae of Roma Integration Strategies
Authors: Matache Margareta
Published: September 2017

In this article, I argue that policymakers employed unconscious biases and racist beliefs in the formulation and the implementation of the current EU Framework for National Roma Integration Strategies (ʻEU Roma Frameworkʼ) and its corresponding national strategies. Using Critical Race Theory, I explore how these policies have reinforced the commonly held belief in the need to civilize and otherwise change the habits of the Roma, and consequently have further reinforced the power imbalance between the Roma and the dominant majority groups (hereinafter used interchangeably with ʻnon-Romaʼ). I analyse examples of Roma versus universal policies comparatively, emphasizing biases in formulation, implementation, and discourse. I show that the objectives of the EU Roma Framework and national Roma strategies toward Roma education involve ethnic presuppositions and are far less ambitious than the avowed Europe 2020 strategy; this policy mismatch will likely lead to further educational discrepancies post-2020. Finally, I conclude that policies focused on the Roma are doomed to fail if no prior and concurrent actions are taken to change prejudiced attitudes and the behaviours of non-Roma, in particular those biases influencing policy formulation and implementation.
Abraham Kuyper among the Nations
Authors: Joustra Robert J.
Published: September 2017

Abraham Kuyper, Dutch Prime Minister (1901–1905) and modern Calvinist, was a controversial figure, not least in his foreign affairs. Yet while Kuyper's legacy has been felt in the world of religious, especially Christian, political, and social theory, very little has been made of Kuyper's actual record as a foreign policy maker and a Prime Minister. So, what was Kuyper's “Christian” perspective and policy on foreign affairs? Using newly available English translations, this article outlines Kuyper's “overseas manifesto” made most plain in Our Program, and compares it against Kuyper's commentary and policy in three major foreign crises: the Boer Cause, in South Africa; the “pacification” of Aceh, in modern-day Indonesia; and finally, the calamity of the Great War in Europe. From these I will paint an introductory, if general, picture of a serious, religious foreign policy maker, and a commentator on world affairs; a complex picture of religiously inflected policy in the early 20th century, with lessons and warnings for scholars of religion and foreign policy today.
Potential Benefit and Risk of Fluridone as a Fall Germination Stimulant in Western Canada
Authors: Tidemann Breanne D. , Hall Linda M. , Harker K. Neil , Beckie Hugh J.
Published: September 2017

Herbicide resistance has increased the need for novel weed control strategies. Fluridone has herbicidal as well as potential germination stimulant activity. The objectives of this study were to evaluate fluridone as a fall-applied germination stimulant for weed control and to assess rotational crop tolerance. Fall-applied fluridone was compared with a nontreated control in areas established with false cleavers, volunteer canola, and wild oat at Lacombe, AB, in 2014–2015 and 2015–2016, and at St Albert, AB, in 2015–2016. In the fall, there was a trend for weed densities to be higher in fluridone treatments than in untreated controls across site-years. The stimulatory effect of fluridone on weed germination was not statistically significant in fall assessments, while the weed control effect was significant in 33% of spring assessments. While fluridone reduced weed biomass for some site-years, it also reduced canola crop emergence and biomass at St Albert in 2015–2016, and caused injury symptoms on wheat and field pea. Risk of carryover to subsequent crops outweighed the benefits of using fluridone in the fall to stimulate weed germination in this study.
Prostatakarzinom – von der konventionellen zur molekularen Diagnostik
Authors: Grobholz Rainer
Published: September 2017

Zusammenfassung. Das Prostatakarzinom ist der häufigste Tumor des Mannes und aufgrund von Vorsorgeprogrammen und verbesserter Aufklärung ist die Inzidenz derzeit weiter steigend. Neben der verbesserten klinischen Diagnostik hat die Bildgebung mittels multiparametrischer Magnetresonanztomographie (mpMRT) grosse Fortschritte erzielt. In Verbindung mit dem transrektalen Ultraschall (TRUS) und den MRT Daten ist eine gezieltere Diagnostik von auffälligen Herden in Form von sogenannten Fusionsbiopsien möglich. Die Einbindung der mpMRT in das Biopsieverfahren hat, im Vergleich zur konventionellen TRUS gesteuerten Biopsie, zu einer erhöhten Sensitivität für die Detektion klinisch signifikanter Tumoren geführt. Da das biologische Verhalten der Prostatakarzinome eine starke Heterogenität aufweist, ist es wichtig, behandlungsbedürftige Tumoren früh zu erkennen. Neben den klinischen Parametern spielt die bioptische Diagnostik dabei eine zentrale Rolle. Für die Einschätzung der Aggressivität ist der Gleason-Score nach wie vor einer der zentralen Parameter. Derzeit liegt die dritte Überarbeitung seit der Originalpublikation im Jahre 1966 vor. Um die Probleme des Gleason-Gradings zu umgehen, wurden neue Grad-Gruppen entwickelt, welche auf dem Gleason-Grading aufbauen. Hierbei werden einzelne oder mehrere Gleason-Scores in fünf verschiedene Gruppen mit gleichem biologischen Outcome zusammengefasst. Diese Gruppen erlauben eine sehr gute Unterteilung in Tumoren mit exzellenter Prognose und nur sehr geringem Progressionsrisiko sowie in Tumoren mit schlechter Prognose und hohem Progressionsrisiko. Diese Einteilung erleichtert das Gespräch mit dem Patienten und hilft bei der Auswahl der passenden Therapie. Gleichwohl gibt es noch Fälle, bei denen mehrere Optionen möglich sind und bei denen die Entscheidung für die eine oder andere Therapiestrategie schwierig sein kann. Um der Lösung dieses Problems näher zu kommen, sind derzeit Multigentests verfügbar, welche das Tumorgewebe auf eine bestimmte Anzahl von Genveränderungen untersuchen und daraus einen Scorewert berechnen, anhand welchem eine Risikoabstufung für ein aggressives biologisches Verhalten abgeleitet werden kann. Die Verfügbarkeit dieser Multigentests konnte die klinische Entscheidungsfindung hinsichtlich des weiteren therapeutischen Procedere verbessern, wie die ersten prospektiven Studien zu diesem Thema zeigen konnten. Grössere multizentrische prospektive klinische Studien mit entsprechenden klinischen Verlaufsdaten stehen jedoch noch aus, weshalb derzeit seitens der Fachgesellschaften noch keine Empfehlungen für den Einsatz von Multigentests abgegeben wurden.
Rumination Moderates the Association Between Resting High-Frequency	Heart Rate Variability and Perceived Ethnic Discrimination
Authors: Williams DeWayne P. , Pandya Kinjal D. , Hill LaBarron K. , Kemp Andrew H. , Way Baldwin M. , Thayer Julian F. , Koenig Julian
Published: September 2017

Abstract. Ethnic discrimination (ED) is both an unfortunate and uncontrollable phenomenon that uniquely impacts African Americans (AAs) and other individuals of ethnic minority status. Perceived ethnic discrimination (PED), defined as the degree to which an individual consciously perceives a negative event as discriminatory and threatening, largely determines the impact that ED can have on target individuals. However, research has not yet considered how individual differences in both emotion regulation abilities, as indexed by resting high-frequency heart rate variability (HF-HRV), and rumination, a maladaptive emotion regulation strategy, may predict PED in AAs. The following investigation examined this relationship in a sample of 101 college-aged students (45 AAs and 56 Caucasian Americans). Resting HF-HRV was assessed via electrocardiogram during a 5-minute-resting period. Rumination was assessed using the ruminative responses scale and everyday PED was assessed using the perceived ethnic discrimination questionnaire. Results showed a significant negative relationship between resting HF-HRV and PED in AAs only. Rumination significantly moderated this relationship, such that lower HF-HRV was related to higher PED only in AAs who reported moderate to higher, β = 0.417 (0.125), p < .01, levels of trait rumination. These results suggest that greater HF-HRV and lesser ruminative tendencies are key factors in reducing PED and therefore possibly, negative consequences associated with ED.
Erratum: High performance platinum single atom electrocatalyst for oxygen reduction reaction
Authors: Liu Jing , Jiao Menggai , Lu Lanlu , Barkholtz Heather M. , Li Yuping , Wang Ying , Jiang Luhua , Wu Zhijian , Liu Di-jia , Zhuang Lin , Ma Chao , Zeng Jie , Zhang Bingsen , Su Dangsheng , Song Ping , Xing Wei , Xu Weilin , Wang Ying , Jiang Zheng , Sun Gongquan
Published: September 2017

Nature Communications 8: Article number: 15938 (2017); Published: 24 July 2017; Updated: 27 September 2017. The affiliation details for one of the corresponding authors, Ying Wang, are incorrect in this Article. This author is incorrectly affiliated with ‘University of Chinese Academy of Sciences, Beijing 100049, China.
Correction: Corrigendum: Alternative splicing promotes tumour aggressiveness and drug resistance in African American prostate cancer
Authors: Wang Bi-Dar , Ceniccola Kristin , Hwang SuJin , Andrawis Ramez , Horvath Anelia , Freedman Jennifer A. , Olender Jacqueline , Knapp Stefan , Ching Travers , Garmire Lana , Patel Vyomesh , Garcia-Blanco Mariano A. , Patierno Steven R. , Lee Norman H.
Published: September 2017

Nature Communications 8: Article number: 15921 (2017); Published: 30 June 2017; Updated: 27 September 2017 Contributions of the author Steven R. Patierno are not fully acknowledged in this Article. The Author Contributions section should have included the following: ‘S.R.P. was involved in the co-conception of the study, and was co-principal investigator of the initial portion of this study by obtaining NCI Center to Reduce Cancer Health Disparities grant supplement U01CA11637-05S2 (to S.
Enhanced thermal stability of organic solar cells comprising ternary D-D-A bulk-heterojunctions
Authors: Landerer Dominik , Mertens Adrian , Freis Dieter , Droll Robert , Leonhard Tobias , Schulz Alexander Deniz , Bahro Daniel , Colsmann Alexander
Published: September 2017

Ternary absorber blends have recently been identified as promising concepts to spectrally broaden the absorption of organic bulk-heterojunction solar cells and hence to improve their power conversion efficiencies. In this work, we demonstrate that D-D-A ternary blends comprising two donor polymers and the acceptor PC61BM can also significantly enhance the thermal stability of the solar cell. Upon harsh thermal stress at 120 °C for 2 h, the ternary solar cells show only a minor relative deterioration of 10%. Whereas the polymer/fullerene blend PTB7-Th:PC61BM is rather unstable under these conditions, its degradation was efficiently suppressed by incorporating the near infrared-absorbing polymer PDTP–DFBT. Spectroscopic ellipsometry investigations and an effective medium analysis of the ternary absorber blend revealed that the domain conformation in presence of PDTP–DFBT remains stable whereas the domain conformation changes in its absence. The ternary PTB7-Th:PDTP–DFBT:PC61BM solar cells yield thermally stable power conversion efficiencies of up to 6%.
Solution-based polycrystalline silicon transistors produced on a paper substrate
Authors: Trifunovic Miki , Sberna Paolo Maria , Shimoda Tatsuya , Ishihara Ryoichi
Published: September 2017

Printing of electronics is pursued as a low-cost alternative to conventional manufacturing processes. In addition, owing to relatively low process temperatures, flexible substrates can be used enabling novel applications. Among flexible substrates, paper was found to be a particularly interesting candidate, since it has an order of magnitude lower price than low-cost polymer alternatives, and is biodegradable. As ink materials, organic and metal-oxide semiconductors are thoroughly being investigated; however, they lack in electric performance compared to silicon in terms of device mobility, reliability, and energy efficiency. In recent years, liquid precursors for silicon were found and used to create polycrystalline silicon (poly-Si). However, fabrication of transistors on top of low-cost flexible substrates such as paper has remained an outstanding challenge. Here we demonstrate both p-channel and n-channel poly-Si thin-film transistors (TFTs) fabricated directly on top of paper with field-effect mobilities of 6.2 and 2.0 cm2/V s, respectively. Many fabrication challenges have been overcome by limiting the maximum process temperature to approximately 100 °C, and avoiding liquid chemicals commonly used for etching and cleaning. Patterning of poly-Si has been achieved by additive selective crystallization of the precursor film using an excimer laser. This work serves as a proof of concept, and has the potential to further improve device performance. Owing to the low-cost, biodegradable nature of paper, and the high performance, reliability, and energy efficiency of poly-Si TFTs, this work opens a pathway toward truly low-cost, low-power, recyclable applications including smart packages, biodegradable health monitoring units, flexible displays, and disposable sensor nodes.
Systems biology reveals uncoupling beyond UCP1 in human white fat-derived beige adipocytes
Authors: Nyman Elin , Bartesaghi Stefano , Melin Rydfalk Rebecka , Eng Sandra , Pollard Charlotte , Gennemark Peter , Peng Xiao-Rong , Cedersund Gunnar
Published: September 2017

Pharmaceutical induction of metabolically active beige adipocytes in the normally energy storing white adipose tissue has potential to reduce obesity. Mitochondrial uncoupling in beige adipocytes, as in brown adipocytes, has been reported to occur via the uncoupling protein 1 (UCP1). However, several previous in vitro characterizations of human beige adipocytes have only measured UCP1 mRNA fold increase, and assumed a direct correlation with metabolic activity. Here, we provide an example of pharmaceutical induction of beige adipocytes, where increased mRNA levels of UCP1 are not translated into increased protein levels, and perform a thorough analysis of this example. We incorporate mRNA and protein levels of UCP1, time-resolved mitochondrial characterizations, and numerous perturbations, and analyze all data with a new fit-for-purpose mathematical model. The systematic analysis challenges the seemingly obvious experimental conclusion, i.e., that UCP1 is not active in the induced cells, and shows that hypothesis testing with iterative modeling and experimental work is needed to sort out the role of UCP1. The analyses demonstrate, for the first time, that the uncoupling capability of human beige adipocytes can be obtained without UCP1 activity. This finding thus opens the door to a new direction in drug discovery that targets obesity and its associated comorbidities. Furthermore, the analysis advances our understanding of how to evaluate UCP1-independent thermogenesis in human beige adipocytes.
Chondroitin Sulfate Is Required for Onset and Offset of Critical Period Plasticity in Visual Cortex
Authors: Hou Xubin , Yoshioka Nozomu , Tsukano Hiroaki , Sakai Akiko , Miyata Shinji , Watanabe Yumi , Yanagawa Yuchio , Sakimura Kenji , Takeuchi Kosei , Kitagawa Hiroshi , Hensch Takao K. , Shibuki Katsuei , Igarashi Michihiro , Sugiyama Sayaka
Published: September 2017

Ocular dominance plasticity is easily observed during the critical period in early postnatal life. Chondroitin sulfate (CS) is the most abundant component in extracellular structures called perineuronal nets (PNNs), which surround parvalbumin-expressing interneurons (PV-cells). CS accumulates in PNNs at the critical period, but its function in earlier life is unclear. Here, we show that initiation of ocular dominance plasticity was impaired with reduced CS, using mice lacking a key CS-synthesizing enzyme, CSGalNAcT1. Two-photon in vivo imaging showed a weaker visual response of PV-cells with reduced CS compared to wild-type mice. Plasticity onset was restored by a homeoprotein Otx2, which binds the major CS-proteoglycan aggrecan and promotes its further expression. Continuous CS accumulation together with Otx2 contributed bidirectionally to both onset and offset of plasticity, and was substituted by diazepam, which enhances GABA function. Therefore, CS and Otx2 may act as common inducers of both onset and offset of the critical period by promoting PV-cell function throughout the lifetime.
Fine population structure analysis method for genomes of many
Authors: Pan Xuedong , Wang Yi , Wong Emily H. M. , Telenti Amalio , Venter J. Craig , Jin Li
Published: September 2017

Fine population structure can be examined through the clustering of individuals into subpopulations. The clustering of individuals in large sequence datasets into subpopulations makes the calculation of subpopulation specific allele frequency possible, which may shed light on selection of candidate variants for rare diseases. However, as the magnitude of the data increases, computational burden becomes a challenge in fine population structure analysis. To address this issue, we propose fine population structure analysis (FIPSA), which is an individual-based non-parametric method for dissecting fine population structure. FIPSA maximizes the likelihood ratio of the contingency table of the allele counts multiplied by the group. We demonstrated that its speed and accuracy were superior to existing non-parametric methods when the simulated sample size was up to 5,000 individuals. When applied to real data, the method showed high resolution on the Human Genome Diversity Project (HGDP) East Asian dataset. FIPSA was independently validated on 11,257 human genomes. The group assignment given by FIPSA was 99.1% similar to those assigned based on supervised learning. Thus, FIPSA provides high resolution and is compatible with a real dataset of more than ten thousand individuals.
The regulatory effect of choice in Situation Selection reduces experiential, exocrine and respiratory arousal for negative emotional stimulations
Authors: Thuillard Simon , Dan-Glauser Elise S.
Published: September 2017

Situation selectionis a seldom studied emotion regulation strategy that entails choosing an upcoming emotional situation. Two mechanisms may drive its regulatory effect on emotional responses. One relates to the evaluation of the chosen option, people generally selecting the most positive. The other one implies thathaving the choiceregarding the upcoming emotional situation is already regulatory, independently of what we choose. This research aimed at investigating this latter hypothesis. In a within-subject design, we compared emotional responses of 65 participants when they viewed negative and positive images they could select (use ofSituation selection) vs. when they were imposed theexact same images(Situation selectionnot used). Results show that having the choice in negative contexts decreased negative experience, skin conductance, and respiration reactivity, while enhancing expressivity and cardiovascular reactivity. In positive contexts, choosing generally reinforced the image calming effect. Thus, contrary to other strategies that are efficient for negative but usually impair positive reactions (e.g., distraction),Situation selectionmay be used widely to reduce negative experience, while avoiding depletion of positive responses. This is particularly notable in emotion experience. Remarkably, these effects are not driven by the content of the situations, but by the act of choosing itself.
Targeting the alternative sigma factor RpoN to combat virulence in Pseudomonas aeruginosa
Authors: Lloyd Megan G. , Lundgren Benjamin R. , Hall Clayton W. , Gagnon Luke B.-P. , Mah Thien-Fah , Moffat Jennifer F. , Nomura Christopher T.
Published: September 2017

Pseudomonas aeruginosa is a Gram-negative, opportunistic pathogen that infects immunocompromised and cystic fibrosis patients. Treatment is difficult due to antibiotic resistance, and new antimicrobials are needed to treat infections. The alternative sigma factor 54 (σ54, RpoN), regulates many virulence-associated genes. Thus, we evaluated inhibition of virulence in P. aeruginosa by a designed peptide (RpoN molecular roadblock, RpoN*) which binds specifically to RpoN consensus promoters. We expected that RpoN* binding to its consensus promoter sites would repress gene expression and thus virulence by blocking RpoN and/or other transcription factors. RpoN* reduced transcription of approximately 700 genes as determined by microarray analysis, including genes related to virulence. RpoN* expression significantly reduced motility, protease secretion, pyocyanin and pyoverdine production, rhamnolipid production, and biofilm formation. Given the effectiveness of RpoN* in vitro, we explored its effects in a Caenorhabditis elegans–P. aeruginosa infection model. Expression of RpoN* protected C. elegans in a paralytic killing assay, whereas worms succumbed to paralysis and death in its absence. In a slow killing assay, which mimics establishment and proliferation of an infection, C. elegans survival was prolonged when RpoN* was expressed. Thus, blocking RpoN consensus promoter sites is an effective strategy for abrogation of P. aeruginosa virulence.