bluuebunny/crossref_metadata_2025 huggingface dataset:
ON THE AXIOMATIZABILITY OF C*-ALGEBRAS AS OPERATOR SYSTEMS
Authors: GOLDBRING ISAAC , SINCLAIR THOMAS
Published: September 2018

We show that the class of unital C*-algebras is an elementary class in the language of operator systems and that the algebra multiplication is a definable function in this language. Moreover, we prove a general model theoretic fact which implies that the aforementioned class is ∀∃∀-axiomatizable. We conclude by showing that this class is, however, neither ∀∃-axiomatizable nor ∃∀-axiomatizable.
Monitoring of greenhouse gas emissions from farm-scale anaerobic piggery waste-water digesters
Authors: Su Jung-Jeng , Chen Yen-Jung
Published: September 2018

Pig manure management systems in Taiwan differ from the model representing the Asian region developed by the Intergovernmental Panel on Climate Change (IPCC). The current study was undertaken to update greenhouse gas (GHG) emission factors of anaerobically treated piggery waste water by operating the conventional three-step piggery waste-water treatment system from selected pig farms located in northern, central and southern Taiwan. Biogas mass flow meters were installed to the outlet of anaerobic basins prior to the biogas pressure stabilizers for direct and reliable biogas measurement. The analytic results showed that average GHG emissions were 0.088, 0.128 and 0.066 m3/head/day in the northern, central and southern pig farms, respectively. Thus, the average emission levels of methane and nitrous oxide were 14.38 and 0.055 kg/head/year, respectively, from anaerobic digestion of piggery waste water for the three pig farms. The average removal efficiency of chemical oxygen demand, biochemical oxygen demand and suspended solids by anaerobic digestion process from the three pig farms was about 77, 93 and 70%, respectively.
China, Europe, and the Great Divergence: A Study in Historical National Accounting, 980–1850
Authors: Broadberry Stephen , Guan Hanhui , Li David Daokui
Published: September 2018

As a result of recent advances in historical national accounting, estimates of GDP per capita are now available for a number of European economies back to the medieval period, including Britain, the Netherlands, Italy, and Spain. The approach has also been extended to Asian economies, including India and Japan. So far, however, China, which has been at the center of the Great Divergence debate, has been absent from this approach. This article adds China to the picture, showing that the Great Divergence began earlier than originally suggested by the California School, but later than implied by older Eurocentric writers.
Risk Aversion in a Dynamic Asset Allocation Experiment
Authors: Brocas Isabelle , Carrillo Juan D. , Giga Aleksandar , Zapatero Fernando
Published: September 2018

We conduct a controlled laboratory experiment in the spirit of Merton (1971), in which subjects dynamically choose their portfolio allocation between a risk-free and risky asset. Using the optimal allocation of an investor with hyperbolic absolute risk aversion (HARA) utility, we fit the experimental choices to characterize the risk profile of our participants. Despite substantial heterogeneity, decreasing absolute risk aversion and increasing relative risk aversion are the predominant types. We also find some evidence of increased risk taking after a gain. Finally, the session level risk attitudes show a different profile than the individual descriptions of risk attitudes.
Beyond Pessimism: A Structure of Encouragement in Augustine'sCity of God
Authors: Lamb Michael
Published: September 2018

Many critics of Augustine target his “pessimism,” arguing that his fixation on evil denies the value of this-worldly goods. This article challenges this view by exposing a methodological assumption that often underwrites it—the idea that Augustine's texts can be abstracted from their rhetorical contexts. To illustrate, I offer a close reading ofCity of God22.22–24, a passage frequently cited as evidence of Augustine's pessimism. By analyzing how Augustine uses rhetoric to “instruct” and “encourage” his readers, I argue instead that this passage should be interpreted as an exercise of hope that helps readers resist temptations toward presumption and despair. This account complicates the common binary between optimism and pessimism and supplies a novel interpretation of key passages inCity of God.
Type synthesis of legged mobile landers with one passive limb using the singularity property
Authors: Lin Rongfu , Guo Weizhong , Chen Xianbao , Li Meng
Published: September 2018

During extraterrestrial planetary exploration programs, autonomous robots are deployed using a separate immovable lander and a rover. This mode has some limitations. In this paper, a concept of a novel legged robot with one passive limb and singularity property is introduced that has inbuilt features of a lander and a rover. Currently, studies have focused primarily on a performance analysis of the lander without a walking function. However, a systematic type synthesis of the legged mobile lander has not been studied. In this study, a new approach to the type synthesis used for the robot is proposed based on the Lie group theory. The overall concept and design procedures are proposed and described. The motion requirements of the robot and its legs, which are corresponding to the multi-function, are extracted and described. The layouts of the subgroups or submanifolds of the limbs are determined. The structures of the passive and actuated limbs are synthesized. Numerous structures of the legs with a passive limb are produced and listed corresponding to the desired displacement manifolds. Numerous novel structures of legs for the legged mobile lander are presented and listed. Then, four qualitative criteria or indexes are introduced. Based on the proposed criteria, a leg's configuration is selected as the best. A typical structure of the legged mobile lander is obtained by assembling the structures of the proposed legs. Finally, the typical robot is used as an example to verify the capabilities of the novel robot using a software simulation (ADAMS).
A formation maneuvering controller for multiple non-holonomic robotic vehicles
Authors: Khaledyan Milad , de Queiroz Marcio
Published: September 2018

In this paper, we present a new leader–follower type solution to the translational maneuvering problem for formations of multiple, non-holonomic wheeled mobile robots. The solution is based on the graph that models the coordination among the robots being a spanning tree. Our control law incorporates two types of position errors: individual tracking errors and coordination errors for leader–follower pairs in the spanning tree. The control ensures that the robots globally acquire a given planar formation while the formation as a whole globally tracks a desired trajectory, both with uniformly ultimately bounded errors. The control law is first designed at the kinematic level and then extended to the dynamic level. In the latter, we consider that parametric uncertainty exists in the equations of motion. These uncertainties are accounted for by employing an adaptive control scheme. The main contributions of this work are that the proposed control scheme minimizes the number of control links and global position measurements, and accounts for the uncertain vehicle dynamics. The proposed formation maneuvering controls are demonstrated experimentally and numerically.
Exploring the ‘shashification’ of teenage slang
Authors: Fajardo José Antonio Sánchez
Published: September 2018

The study of the paradigmatic traits of teenage slang has shown that a sense of togetherness is predominant (Eble, 1996; Allen, 1998; Mattiello, 2005, 2008; Smith, 2011). This cohesive linguistic device is not consciously intended to exclude unwished members from conversations or common understanding, but the idea of relying on a preserved sense of solidarity and acceptance is a human urge, especially among teenagers or young adults (cf. Mattiello, 2005: 13). These features are a necessary starting point to understand that the colloquial nature or social restriction of these words and phrases are precisely aimed to ‘establish or reinforce social identity within a group or with a trend or fashion in society at large’ (Eble, 1996: 11).
Grassroots prescriptivism
Authors: Lukač Morana
Published: September 2018

People engage in discussions on which linguistic items are ‘correct’ and ‘incorrect’, ‘acceptable’ and ‘unacceptable’ on a daily basis. They do so in private conversations, but also publicly by way of telephone calls to radio stations, letters to newspapers and, since the dawn of the participatory internet, on social media platforms, such as blogs, microblogs (i.e. Twitter), forums and Facebook. Conspicuously, however, in linguists’ theoretical models of language standardisation, speakers have traditionally been marginalised as passive followers of the norms established by language authorities. The types of discussions mentioned are viewed as having no impact on actual usage or on what it is that constitutes the standard variety, while standard language norms are, according to such accounts, enforced by language experts, codifiers and ‘model speakers [such as journalists and newsreaders] and authors’ (Ammon, 2015: 65).
The Deinstitutionalization (?) of the House of Representatives: Reflections on Nelson Polsby's “The Institutionalization of the U.S. House of Representatives” at Fifty
Authors: Jenkins Jeffery A. , Stewart Charles
Published: September 2018

This article revisits Nelson Polsby's classic article “The Institutionalization of the U.S. House of Representatives” fifty years after its publication, to examine whether the empirical trends that Polsby identified have continued. This empirical exploration allows us to place Polsby's findings in broader historical context and to assess whether the House has continued along the “institutionalization course”—using metrics that quantify the degree to which the House has erected impermeable boundaries with other institutions, created a complex institution, and adopted universalistic decision-making criteria. We empirically document that careerism plateaued right at the point Polsby wrote “Institutionalization,” and that the extension of the careerism trend has affected Democrats more than Republicans. The House remains complex, but lateral movement between the committee and party leadership systems began to reestablish itself a decade after “Institutionalization” was published. Finally, the seniority system as a mechanism for selecting committee chairs—the primary measure of universalistic decision-making criteria—has been almost thoroughly demolished. Thus, most of the trends Polsby identified have moderated, but have not been overturned. We conclude by considering the larger set of interpretive issues that our empirical investigation poses.
Reimagining the Nation-State: Indigenous Peoples and the Making of Plurinationalism in Latin America
Authors: MERINO ROGER
Published: September 2018

In the last two decades, the concept of plurinationalism has appeared in discussions about nationalism, statehood and multilevel governance, being formulated as a new state model that accommodates cultural diversity within the liberal state with the aim of solving nationalistic conflicts in countries marked by profound ethnic grievances, mainly in Europe. However, these discussions have paid less attention to the meaning of plurinationalism in ex-colonial contexts, particularly in recent experiences of state transformation in Bolivia and Ecuador, where the role of indigenous peoples in the plurinational project has been crucial. To fill this gap, this article explores the legal and political foundations, challenges and local and international dynamics in the building of the plurinational model in both countries. Under a critical engagement with Third World Approaches to International Law (TWAIL), this article argues that plurinationality from indigenous perspectives departs from multicultural liberal models associated with current European plurinational views, and addresses two challenges: a global political economy of resource extraction, and a racialized state structure working as a barrier to actual plurinational implementation. These limitations explain an intrinsic tension in the Bolivian and Ecuadorian experience: on the one hand, plurinational governments try to unify the people around the ‘national interest’ of developing extractive industries; and on the other hand, they attempt to recognize ethno-political differences that often challenge the transnational exploitation of local resources.
African International Legal Histories – International Law in Africa: Perspectives and Possibilities
Authors: ZOLLMANN JAKOB
Published: September 2018

Hitherto, the ‘African part’ of the history of international law has often been limited to the (critical engagement with) ‘the acquisition of Africa’ since the 1880s and questions of ‘state succession’ and international borders following independence starting in the 1950s. In this historical narrative, the dominance of colonialism is evident. It seems that ‘Africa’ as a narrative concept in international legal history remains tied to abstract contrasts such as ‘foreign domination’ versus ‘independence’, or ‘exploitation’ versus ‘development’. However, if twenty-first century writings about ‘international law in Africa’ and its histories remain shaped by this perspective, historians may lose sight of issues, questions, or ideas formed in historical Africa that do not fit into this preconceived dichotomous matrix. After discussing methodological challenges, this article asks for other ‘contacts’, other arenas of ‘internationality’ and international law in Africa’s pre-colonial past. These contacts reach back very far in history. Three arenas are mentioned: the Red Sea area and Ethiopian-Arab relations; the Indian Ocean rim; and finally, the case of nineteenth-century Ethiopia.
Estimating the probability of freedom from bovine brucellosis in the Galapagos Islands
Authors: Gioia G. , Vinueza R. L. , Cruz M. , Jay M. , Corde Y. , Marsot M. , Zanella G.
Published: September 2018

Bovine brucellosis is a worldwide zoonotic disease that still burdens several countries in the Mediterranean, Asia, Africa and Latin America. Although the disease is present in Ecuador, the Galapagos Islands seem to be free from the disease based on a survey conducted in 1997 where all tested animals showed negative results. This study aimed at estimating the probability of freedom from brucellosis in this Ecuadorian province in 2014. A survey was implemented on the three main cattle-producing islands of the province: Santa Cruz, Isabela and San Cristóbal. Thirty-three cattle farms and 410 cattle were tested for brucellosis using the Rose Bengal test and indirect ELISA. All animals showed negative results for both tests. Probability of freedom was estimated at 98%, 91% and 88% for Santa Cruz, Isabela and San Cristóbal, respectively, considering a herd-level design seroprevalence of 20% and animal-level design seroprevalence of 15%, and assuming a perfect specificity of the survey. The negative results found in 1997 and present surveys suggest that the Galapagos Islands are free from bovine brucellosis.
Alcoholic family marital heterogeneity aggregates different child behavior problems both pre- and postseparation
Authors: Ip Ka I , Jester Jennifer M. , Puttler Leon I. , Zucker Robert A.
Published: September 2018

Children of alcoholics (COAs) are at risk for elevated internalizing and externalizing symptoms. Yet, little is known about the familial and behavioral adjustments of COAs following parental separation. Using an ecological–transactional framework, we examined how multiple risk factors contributed to the formation of different alcoholic family structures and how living in heterogeneous family structures affected COAs’ behavioral problems. The Michigan Longitudinal Study, a multiwave study on initially intact alcoholic and control families with preschool-age children (n= 503), was used to evaluate outcomes of offspring, when families either remained intact or were separated when the child was aged 12–14. Alcoholic families who later transitioned into stepfamilies were characterized with higher paternal antisociality, marital aggression, and serious family crises than alcoholic families that remained intact. COAs in stepfamilies (but not in single-parent families) exhibited higher levels of internalizing and externalizing symptoms in preadolescence compared with those in alcoholic intact families, in part because of elevated behavioral risk at age 3. Structural equation modeling indicated that the aggregated risk of stepfamily residence directly related to COAs’ internalizing and indirectly related to COAs’ externalizing problems, partially mediated by family stressors. Findings suggest targeting COAs in separated families for early intervention.
Punctuated equilibrium in democracy and autocracy: an analysis of Hungarian budgeting between 1868 and 2013
Authors: Sebők Miklós , Berki Tamás
Published: September 2018

The article investigates the dynamics of budgeting and its explanatory factors in Hungary based on a new database. Previous work for the period between 1991 and 2013 demonstrated that year-on-year changes in budgetary allocations by policy topics show a leptokurtic distribution. This distribution of policy changes is generally associated with the notion of punctuated equilibrium. We extend this analysis to cover over 155 years of Hungarian budgetary history. Our investigation of a database of 2580 spending category observations (covering the period between 1868 and 2013) lends support for the theory of punctuated equilibrium. We also analysed the impact of political regimes on budgetary dynamics. Here we provided empirical evidence for the validity of the informational advantage hypothesis which states that democracies will show lower level of kurtosis than other political regimes. This finding is also in line with the results of available comparative studies.
Endovascular stent placement for isolated superior mesenteric artery dissection with intestinal ischaemia
Authors: Liu Baochen , Chu Chengnan , Fan Xinxin , Ding Weiwei , Wu Xingjiang
Published: September 2018

Abstract. Background: Isolated superior mesenteric artery dissection (ISMAD) is rare, especially when associated with intestinal ischaemia. We report our clinical experience managing this condition. Patients and methods: Medical records from 22 patients with ISMAD and intestinal ischaemia were retrospectively analysed. Conservative treatment was given to all patients as first line therapy. Subsequently, 15 patients received endovascular stent placement and three patients received endovascular stent placement plus intestinal resection and anastomosis. Results: After conservative treatment, the symptoms of three patients were remarkably relieved; however, a repeat contrast CT showed that stenosis was aggravated. Hence, endovascular stent placement was performed in all 15 patients. Enteral nutrition was successfully restored in 12 patients. Three patients showed signs of chronic intestinal ischaemia, including peritonitis and ileus. These patients underwent intestinal resection and anastomosis. Enteral nutrition was restored at postoperative week two. No signs of intestinal ischaemia recurred during two-years of follow-up. Conclusions: We recommend endovascular stent placement as a feasible, effective, and minimally invasive procedure in patients with ISMAD and symptoms of intestinal ischaemia.
Posttraumatische Osteomyelitis: bessere Behandlungsergebnisse durch innovative Vakuumversiege‑lungstechnik mit Instillationstherapie
Authors: Jukema Gerrolt N. , Timmers Michael S. , Simmen Hans-Peter , Pape Hans-Christoph
Published: September 2018

Zusammenfassung. Die chirurgische Behandlung von posttraumatischer (fistelnder) Osteomyelitis kann sich schwierig gestalten und geht mit einem erhöhten Risiko für das Eintreten einer späteren Rezidiventzündung einher. Sehr oft wird die Osteomyelitis von einer Weichteil(defekt)-Wunde begleitet. Nach chirurgischem Debridement kann die Anwendung der Vakuumversiegelungstechnik die Wundheilung stimulieren und die lokale Durchblutung verbessern. Insbesondere mit der Einführung der innovativen Instillationstechnik der Wundschwämme kann die Effektivität der Behandlung der Infektion gesteigert werden. Durch regelmässige Spülung der Schwämme mit einer antiseptischen Polyhexanid-Lösung können die Behandlungsdauer, die Zahl der operativen Eingriffe, der stationäre Aufenthalt und die Rezidivrate bei dieser Patientengruppe statistisch signifikant gesenkt werden.
Further Evidence for Criterion Validity and Measurement Invariance of	the Luxembourg Workplace Mobbing Scale
Authors: Sischka Philipp E. , Schmidt Alexander F. , Steffgen Georges
Published: September 2018

Abstract. Workplace mobbing has various negative consequences for targeted individuals and are costly to organizations. At present it is debated whether gender, age, or occupation are potential risk factors. However, empirical data remain inconclusive as measures of workplace mobbing so far lack of measurement invariance (MI) testing – a prerequisite for meaningful manifest between-group comparisons. To close this research gap, the present study sought to further elucidate MI of the recently developed brief Luxembourg Workplace Mobbing Scale (LWMS; Steffgen, Sischka, Schmidt, Kohl, & Happ, 2016 ) across gender, age, and occupational groups and to test whether these factors represent important risk factors of workplace mobbing. Furthermore, we sought to expand data on criterion validity of the LWMS with different self-report criterion measures such as psychological health (e.g., work-related burnout, suicidal thoughts), physiological health problems, organizational behavior (i.e., subjective work performance, turnover intention, and absenteeism), and with a self-labeling mobbing index. Data were collected via computer-assisted telephone interviews (CATI) in a representative sample of 1,480 employees working in Luxembourg (aged from 16 to 66; 45.7% female). Confirmatory factor analyses revealed scalar MI across gender and occupation as well as partial scalar invariance across age groups. None of these factors impacted on the level of workplace mobbing. Correlation and receiver operating characteristic (ROC) analyses strongly support the criterion validity of the LWMS. Due to its briefness while at the same time being robust against language, age, gender, and occupational group factors and exhibiting meaningful criterion validity, the LWMS is particularly attractive for large-scale surveys as well as for single-case assessment and, thus, general percentile norms are reported in the Electronic Supplementary Materials.
Reexamining the Factorial Validity of the 16-Item Scale Measuring	Need for Cognition
Authors: Zhang Ying , Klopp Eric , Dietrich Heike , Brünken Roland , Krause Ulrike-Marie , Spinath Birgit , Stark Robin , Spinath Frank M.
Published: September 2018

Abstract. A growing body of studies has emphasized the need to consider method effects due to positively and negatively worded items for a better understanding of the factorial structure of psychological constructs. In particular, several researchers identified such method factors besides the content factor for various scales measuring Need for Cognition (NFC). However, regarding the factorial validity of the 16-item NFC scale developed by Bless, Wänke, Bohner, Fellhauer, and Schwartz (1994) , only a one-factor structure without the inclusion of possible method factors has been examined so far. Therefore, we considered such method factors in a broader reexamination of the factorial validity of this measure by investigating a range of structural models in two samples ( n = 830, n = 500). We found that a one-factor solution as proposed by Bertrams and Dickhäuser (2010) and Bless et al. (1994) did not fit the data, whereas the inclusion of method factors improved the model fit significantly. According to our results, the model including both the content factor and two uncorrelated method factors yielded the best model fit. In sum, our results provide an extended view of the factorial validity of the 16-item scale of NFC.
Using Tsunami Waves Reflected at the Coast to Improve Offshore Earthquake Source Parameters: Application to the 2016 Mw 7.1 Te Araroa Earthquake, New Zealand
Authors: Kubota Tatsuya , Saito Tatsuhiko , Ito Yoshihiro , Kaneko Yoshihiro , Wallace Laura M. , Suzuki Syuichi , Hino Ryota , Henrys Stuart
Published: September 2018

The Te Araroa earthquake occurred on 2 September 2016 (local time) offshore of the northeastern coast of New Zealand's North Island (Mw 7.1). When this event occurred, ocean bottom pressure gauges (OBPs), installed ~170 km south of the source area, clearly recorded direct tsunami from the source to OBPs (~ −1.5 cm), and tsunami from coastal reflections (~2 cm). We estimate the centroid location that best reproduces the OBP waveforms. When using the direct wave alone, the centroid location is poorly constrained, with a horizontal uncertainty of ~100 km. By combining both direct and reflected tsunami waveforms, we obtain a centroid location near the Global Centroid Moment Tensor centroid (~80 km northeast from the coast) with smaller uncertainty (~40 km). We also estimate the earthquake source dimension (length and width) and found that the models using coastal reflections require a source dimension larger than ~30 km long. Based on the slip distribution obtained by the finite fault inversion, we obtain an energy‐based stress drop ΔσEof 1.0 MPa, consistent with typical earthquake stress drop values. This study shows that the information added by coastal reflected tsunami provides much tighter constraints on the centroid location, source dimension, and stress drop of offshore earthquakes, which is difficult to obtain from the onshore seismic data alone. Future studies should utilize the information provided by coastal reflected waves to improve earthquake source modeling using ocean bottom pressure data.
A Polar‐Cap Patch Detection Algorithm for the Advanced Modular Incoherent Scatter Radar System
Authors: Perry G. W. , St.‐Maurice J.‐P.
Published: September 2018

We introduce an algorithm to detect polar‐cap patches in an Advanced Modular Incoherent Scatter Radar data set, using the Resolute Bay Incoherent Scatter Radar—North. Patches are detected by comparing plasma density (ne) measurements along each radar beam to a 30‐min running average of the median ne within the field‐of‐view. The algorithm is tested and shown to be an effective tool for polar‐cap patch studies. It is then used to conduct a survey of patches over Resolute Bay for two separate periods of time centered on March and December of 2010. The survey shows that polar‐cap patches are almost always present in both sunlit and nighttime conditions. However, the population is subdued during the day. The patch densities are found to vary by as much as an order of magnitude throughout the day. Their ion temperature is relatively constant, only varying by 100 K between the sunlit and nighttime conditions. By contrast, their electron temperature is very sensitive to the solar zenith angle and changes dramatically around sunrise.
Integrated Bayesian Estimation of Intensity‐Duration‐Frequency Curves: Consolidation and Extensive Testing of a Method
Authors: Boukhelifa M. , Meddi M. , Gaume E.
Published: September 2018

Intensity‐duration‐frequency (IDF) curves are one of the most common rainfall statistical models used in hydrologic design and analysis projects. The uncertainties related to the elaboration of these IDF curves have nevertheless seldom been evaluated in the past. The article will recall the existing link between the IDF formulation and some properties of the rainfall series such as simple scaling and multifractal structure. Assuming that these properties are valid, the IDF curves formulation is then the product of a dimensionless (i.e., reduced) distribution function for the annual maximum rainfall intensities/depths and a duration‐dependent scaling factor. Its parameters can be evaluated in an integrated way (i.e., based on a unique pooled sample of peak intensities over a range of durations: from 15 min to 24 hr). The use of likelihood‐based Bayesian Markov chain Monte Carlo statistical inference methods for this evaluation provides consistent uncertainties for all the parameters of the IDF relation and for the corresponding rainfall quantiles. This methodology has been tested, via a local analysis, on a large data set of 48 rain gauge records, spread over the north central part of Algeria (25,000 km2), under various climatic regimes. The integrated approach is undoubtedly consistent with estimates from annual maximum rainfall fitted to single durations. Furthermore, credibility intervals are significantly reduced. Also, this integrated approach appears to be robust: Unlike the traditional method based single durations, it generally provides rational quantile estimates, even when short observed series are available. This is a significant advantage for engineering applications.
Author Correction: Rab25 augments cancer cell invasiveness through a β1 integrin/EGFR/VEGF-A/Snail signaling axis and expression of fascin
Authors: Jeong Bo Young , Cho Kyung Hwa , Jeong Kang Jin , Park Yun-Yong , Kim Jin Man , Rha Sun Young , Park Chang Gyo , Mills Gordon B , Cheong Jae-Ho , Lee Hoi Young
Published: September 2018

After online publication of this article, the authors noticed an error in the Figure 4c and Figure 5c section.
Urinary biomarker panel for diagnosing patients with depression and anxiety disorders
Authors: Chen Jian-jun , Bai Shun-Jie , Li Wen-wen , Zhou Chan-juan , Zheng Peng , Fang Liang , Wang Hai-yang , Liu Yi-yun , Xie Peng
Published: September 2018

Available data indicate that patients with depression and anxiety disorders are likely to be at greater risk for suicide. Therefore, it is important to correctly diagnose patients with depression and anxiety disorders. However, there are still no empirical laboratory methods to objectively diagnose these patients. In this study, the multiple metabolomics platforms were used to profile the urine samples from 32 healthy controls and 32 patients with depression and anxiety disorders for identifying differential metabolites and potential biomarkers. Then, 16 healthy controls and 16 patients with depression and anxiety disorders were used to independently validate the diagnostic performance of the identified biomarkers. Finally, a panel consisting of four biomarkers—N-methylnicotinamide, aminomalonic acid, azelaic acid and hippuric acid—was identified. This panel was capable of distinguishing patients with depression and anxiety disorders from healthy controls with an area under the receiver operating characteristic curve of 0.977 in the training set and 0.934 in the testing set. Meanwhile, we found that these identified differential metabolites were mainly involved in three metabolic pathways and five molecular and cellular functions. Our results could lay the groundwork for future developing a urine-based diagnostic method for patients with depression and anxiety disorders.
LUBAC prevents lethal dermatitis by inhibiting cell death induced by TNF, TRAIL and CD95L
Authors: Taraborrelli Lucia , Peltzer Nieves , Montinaro Antonella , Kupka Sebastian , Rieser Eva , Hartwig Torsten , Sarr Aida , Darding Maurice , Draber Peter , Haas Tobias L. , Akarca Ayse , Marafioti Teresa , Pasparakis Manolis , Bertin John , Gough Peter J. , Bouillet Philippe , Strasser Andreas , Leverkus Martin , Silke John , Walczak Henning
Published: September 2018

The linear ubiquitin chain assembly complex (LUBAC), composed of HOIP, HOIL-1 and SHARPIN, is required for optimal TNF-mediated gene activation and to prevent cell death induced by TNF. Here, we demonstrate that keratinocyte-specific deletion of HOIP or HOIL-1 (E-KO) results in severe dermatitis causing postnatal lethality. We provide genetic and pharmacological evidence that the postnatal lethal dermatitis inHoipE-KOandHoil-1E-KOmice is caused by TNFR1-induced, caspase-8-mediated apoptosis that occurs independently of the kinase activity of RIPK1. In the absence of TNFR1, however, dermatitis develops in adulthood, triggered by RIPK1-kinase-activity-dependent apoptosis and necroptosis. Strikingly, TRAIL or CD95L can redundantly induce this disease-causing cell death, as combined loss of their respective receptors is required to prevent TNFR1-independent dermatitis. These findings may have implications for the treatment of patients with mutations that perturb linear ubiquitination and potentially also for patients with inflammation-associated disorders that are refractory to inhibition of TNF alone.
Lineage dynamics of murine pancreatic development at single-cell resolution
Authors: Byrnes Lauren E. , Wong Daniel M. , Subramaniam Meena , Meyer Nathaniel P. , Gilchrist Caroline L. , Knox Sarah M. , Tward Aaron D. , Ye Chun J. , Sneddon Julie B.
Published: September 2018

Organogenesis requires the complex interactions of multiple cell lineages that coordinate their expansion, differentiation, and maturation over time. Here, we profile the cell types within the epithelial and mesenchymal compartments of the murine pancreas across developmental time using a combination of single-cell RNA sequencing, immunofluorescence, in situ hybridization, and genetic lineage tracing. We identify previously underappreciated cellular heterogeneity of the developing mesenchyme and reconstruct potential lineage relationships among the pancreatic mesothelium and mesenchymal cell types. Within the epithelium, we find a previously undescribed endocrine progenitor population, as well as an analogous population in both human fetal tissue and human embryonic stem cells differentiating toward a pancreatic beta cell fate. Further, we identify candidate transcriptional regulators along the differentiation trajectory of this population toward the alpha or beta cell lineages. This work establishes a roadmap of pancreatic development and demonstrates the broad utility of this approach for understanding lineage dynamics in developing organs.
Single cell molecular alterations reveal target cells and pathways of concussive brain injury
Authors: Arneson Douglas , Zhang Guanglin , Ying Zhe , Zhuang Yumei , Byun Hyae Ran , Ahn In Sook , Gomez-Pinilla Fernando , Yang Xia
Published: September 2018

The complex neuropathology of traumatic brain injury (TBI) is difficult to dissect, given the convoluted cytoarchitecture of affected brain regions such as the hippocampus. Hippocampal dysfunction during TBI results in cognitive decline that may escalate to other neurological disorders, the molecular basis of which is hidden in the genomic programs of individual cells. Using the unbiased single cell sequencing method Drop-seq, we report that concussive TBI affects previously undefined cell populations, in addition to classical hippocampal cell types. TBI also impacts cell type-specific genes and pathways and alters gene co-expression across cell types, suggesting hidden pathogenic mechanisms and therapeutic target pathways. Modulating the thyroid hormone pathway as informed by the T4 transporter transthyretin Ttr mitigates TBI-associated genomic and behavioral abnormalities. Thus, single cell genomics provides unique information about how TBI impacts diverse hippocampal cell types, adding new insights into the pathogenic pathways amenable to therapeutics in TBI and related disorders.
The evolution of multiple active site configurations in a designed enzyme
Authors: Hong Nan-Sook , Petrović Dušan , Lee Richmond , Gryn’ova Ganna , Purg Miha , Saunders Jake , Bauer Paul , Carr Paul D. , Lin Ching-Yeh , Mabbitt Peter D. , Zhang William , Altamore Timothy , Easton Chris , Coote Michelle L. , Kamerlin Shina C. L. , Jackson Colin J.
Published: September 2018

Developments in computational chemistry, bioinformatics, and laboratory evolution have facilitated the de novo design and catalytic optimization of enzymes. Besides creating useful catalysts, the generation and iterative improvement of designed enzymes can provide valuable insight into the interplay between the many phenomena that have been suggested to contribute to catalysis. In this work, we follow changes in conformational sampling, electrostatic preorganization, and quantum tunneling along the evolutionary trajectory of a designed Kemp eliminase. We observe that in the Kemp Eliminase KE07, instability of the designed active site leads to the emergence of two additional active site configurations. Evolutionary conformational selection then gradually stabilizes the most efficient configuration, leading to an improved enzyme. This work exemplifies the link between conformational plasticity and evolvability and demonstrates that residues remote from the active sites of enzymes play crucial roles in controlling and shaping the active site for efficient catalysis.
Sex and species specific hearing mechanisms in mosquito flagellar ears
Authors: Su Matthew P. , Andrés Marta , Boyd-Gibbins Nicholas , Somers Jason , Albert Joerg T.
Published: September 2018

Hearing is essential for the courtship of one of the major carriers of human disease, the mosquito. Males locate females through flight-tone recognition and both sexes engage in mid-air acoustic communications, which can take place within swarms containing thousands of individuals. Despite the importance of hearing for mosquitoes, its mechanisms are still largely unclear. We here report a multilevel analysis of auditory function across three disease-transmitting mosquitoes (Aedes aegypti, Anopheles gambiae and Culex quinquefasciatus). All ears tested display transduction-dependent power gain. Quantitative analyses of mechanotransducer function reveal sex-specific and species-specific variations, including male-specific, highly sensitive transducer populations. Systemic blocks of neurotransmission result in large-amplitude oscillations only in male flagellar receivers, indicating sexually dimorphic auditory gain control mechanisms. Our findings identify modifications of auditory function as a key feature in mosquito evolution. We propose that intra-swarm communication has been a driving force behind the observed sex-specific and species-specific diversity.
Author Correction: MYC-driven epigenetic reprogramming favors the onset of tumorigenesis by inducing a stem cell-like state
Authors: Poli Vittoria , Fagnocchi Luca , Fasciani Alessandra , Cherubini Alessandro , Mazzoleni Stefania , Ferrillo Sara , Miluzio Annarita , Gaudioso Gabriella , Vaira Valentina , Turdo Alice , Gaggianesi Miriam , Chinnici Aurora , Lipari Elisa , Bicciato Silvio , Bosari Silvano , Todaro Matilde , Zippo Alessio
Published: September 2018

The original version of this Article contained an error in the spelling of the author Miriam Gaggianesi, which was incorrectly given as Miriam Giaggianesi. Furthermore, the affiliation details for Gabriella Gaudioso, Valentina Vaira, and Silvano Bosari incorrectly omitted ‘Division of Pathology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, 20122, Italy’. Finally, the affiliation details for Alice Turdo, Miriam Gaggianesi, Aurora Chinnici and Elisa Lipari were incorrectly given as ‘Dipartimento di Biotecnologie Mediche e Medicina Legale Sezione di Biochimica Medica, Facoltà di Medicina e Chirurgia, Policlinico “P.Giaccone”, Università di Palermo, Palermo, 90127, Italy’. The correct affiliation is ‘Department of Surgical, Oncological and Stomatological Sciences, University of Palermo, Palermo, 90127, Italy’. These errors have now been corrected in both the PDF and HTML versions of the Article.
Unraveling connectivity changes due to dopaminergic therapy in chronically treated Parkinson’s disease patients
Authors: Ballarini Tommaso , Růžička Filip , Bezdicek Ondrej , Růžička Evžen , Roth Jan , Villringer Arno , Vymazal Josef , Mueller Karsten , Schroeter Matthias L. , Jech Robert
Published: September 2018

The effects of dopaminergic therapy for Parkinson’s disease (PD) on the brain functional architecture are still unclear. We investigated this topic in 31 PD patients (disease duration: 11.2 ± (SD) 3.6 years) who underwent clinical and MRI assessments under chronic dopaminergic treatment (duration: 8.3 ± (SD) 4.4 years) and after its withdrawal. Thirty healthy controls were also included. Functional and morphological changes were studied, respectively, with eigenvector centrality mapping and seed-based connectivity, and voxel-based morphometry. Patients off medication, compared to controls, showed increased connectivity in cortical sensorimotor areas extending to the cerebello-thalamo-cortical pathway and parietal and frontal brain structures. Dopaminergic therapy normalized this increased connectivity. Notably, patients showed decreased interconnectedness in the medicated compared to the unmedicated condition, encompassing putamen, precuneus, supplementary motor and sensorimotor areas bilaterally. Similarly, lower connectivity was found comparing medicated patients to controls, overlapping with the within-group comparison in the putamen. Seed-based analyses revealed that dopaminergic therapy reduced connectivity in motor and default mode networks. Lower connectivity in the putamen correlated with longer disease duration, medication dose, and motor symptom improvement. Notably, atrophy and connectivity changes were topographically dissociated. After chronic treatment, dopaminergic therapy decreases connectivity of key motor and default mode network structures that are abnormally elevated in PD off condition.
Brain Connectivity Exposed by Anisotropic X-ray Dark-field Tomography
Authors: Wieczorek Matthias , Schaff Florian , Jud Christoph , Pfeiffer Daniela , Pfeiffer Franz , Lasser Tobias
Published: September 2018

To understand the interaction of different parts of the human brain it is essential to know how they are connected. Such connections are predominantly related to the brain’s white matter, which forms the neuronal pathways, the axons. These axons, also referred to as nerve fibers, have a size on the micrometer scale and are therefore too small to be imaged by standard X-ray systems. In this paper, we use a grating interferometer and a method based on Anisotropic X-ray Dark-field Tomography (AXDT) with the goal to generate a three-dimensional tomographic reconstruction of these functional structures. A first preclinical survey shows that we successfully reconstruct the orientations of the brain fibers connectivity with our approach.
Prediagnostic detection of mesothelioma by circulating calretinin and mesothelin – a case-control comparison nested into a prospective cohort of asbestos-exposed workers
Authors: Johnen Georg , Burek Katarzyna , Raiko Irina , Wichert Katharina , Pesch Beate , Weber Daniel G. , Lehnert Martin , Casjens Swaantje , Hagemeyer Olaf , Taeger Dirk , Brüning Thomas ,   MoMar Study Group, Brik Alexander , Delbanco Judith , Dumont Bettina , Gleichenhagen Jan , Gross Ulrike , Heimann Heike , Heinze Evelyn , Kobek Monika , Lechtenfeld Claudia , Meier Swetlana , Meinig Carmen , Naumann Simone , Putzke Simone , Rihs Hans-Peter , Rozynek Peter , Schonefeld Sandra , Schreiber Jens , Szafranski Katja , Wiethege Thorsten , Zilch-Schöneweis Sandra
Published: September 2018

Malignant mesothelioma (MM) is strongly associated with a previous asbestos exposure. To improve timely detection of MM in asbestos workers, better screening tools – like minimally-invasive biomarkers – are desirable. Between 2008 and 2018 2,769 patients with benign asbestos-related diseases were recruited to participate in annual screens. Using a nested case-control design the protein markers calretinin and mesothelin were determined by enzyme-linked immunosorbent assays in prediagnostic plasma samples of 34 MM cases as well as 136 matched controls from the cohort. Conditional on a pre-defined specificity of 98% for calretinin and 99% for mesothelin the markers reached individual sensitivities of 31% and 23%, respectively, when including the incident cases with samples taken between one and 15 months before diagnosis. The combination of both markers increased the sensitivity to 46% at 98% specificity. Marker complementation increased with earlier sampling. The marker combination improves the sensitivity of the individual markers, indicating a useful complementation and suggesting that additional markers may further improve the performance. This is the first prospective cohort study to evaluate a detection of MM by calretinin and its combination with mesothelin up to about a year before clinical diagnosis. Whether an earlier diagnosis will result in reduced mortality has yet to be demonstrated.
Differential effect of parity on rat mammary carcinogenesis after pre- or post-pubertal exposure to radiation
Authors: Takabatake Masaru , Daino Kazuhiro , Imaoka Tatsuhiko , Blyth Benjamin J. , Kokubo Toshiaki , Nishimura Yukiko , Showler Kaye , Hosoki Ayaka , Moriyama Hitomi , Nishimura Mayumi , Kakinuma Shizuko , Fukushi Masahiro , Shimada Yoshiya
Published: September 2018

Radiation exposure during the peri-pubertal period is a proven risk factor for breast cancer, whereas parity is an established protective factor. The present study investigated whether parity imposes differential protective effects against radiation-induced rat mammary carcinoma depending on the age at exposure. Pre- and post-pubertal female rats, irradiated or left unirradiated, were mated and allowed to nurse until weaning or left unmated. Appearance of mammary tumors was monitored, and serum concentrations of estradiol and progesterone were measured following weaning. Carcinomas were evaluated by immunohistochemistry for estrogen receptor, progesterone receptor, and the cell proliferation marker Ki-67. Parity reduced the risk of carcinoma in unirradiated and pre-pubertally irradiated rats but not post-pubertally irradiated rats. Although radiation exposure increased serum progesterone level, parity after pre-pubertal exposure significantly decreased the elevated progesterone to a normal level, reflecting a protective effect. Moreover, parity significantly decreased the proportion of hormone receptor–positive carcinomas after pre-pubertal exposure. Parity was also related to the observed positive association between progesterone receptor and Ki-67 indices in cancer tissue, implying progesterone receptor–dependent cell proliferation. Thus, parity protects against radiation-induced rat mammary carcinogenesis depending on the age at exposure; the mechanisms may involve changes in hormone levels and cancer tissue.
Quantifying paraspinal muscle tone and stiffness in young adults with chronic low back pain: a reliability study
Authors: Hu Xiaoqian , Lei Di , Li Le , Leng Yan , Yu Qiuhua , Wei Xiaoyu , Lo Wai Leung Ambrose
Published: September 2018

The reliability of a handheld myotonometer when used in a clinical setting to assess paraspinal muscle mechanical properties is unclear. This study aimed to investigate the between-session intra-rater reliability of a handheld myotonometer in young adults with low back pain (LBP) in a clinical environment. One assessor recorded lumbar paraspinal muscle tone and stiffness in an outpatient department on two occasions. The intraclass correlation coefficient (ICC), standard error of measurement (SEM), smallest real difference (SRD) and Bland-Altman analysis were conducted to assess reliability. The results indicated acceptable between-days intra-rater reliability (ICC > 0.75) for all measurements. The SEM of the muscle tone and stiffness measurements ranged between 0.20–0.66 Hz and 7.91–16.51 N/m, respectively. The SRD was 0.44–1.83 Hz for muscle tone and 21.93–52.87 N/m for muscle stiffness. SEM and SRD at L1-L2 were higher than those at other levels. The magnitude of agreement appeared to decrease as muscle tone and stiffness increased. The myotonometer demonstrated acceptable reliability when used in a clinical setting in young adults with chronic LBP. Measurements of the upper lumbar levels were not as reliable as those of the lower lumbar levels. The crural attachment of the diaphragm at L1 and L2 may affect paraspinal muscle tone and stiffness during respiratory cycles.