bluuebunny/crossref_metadata_2025 huggingface dataset:
Rights of and over Animals in the Ius Naturae et Gentium (Sixteenth and Seventeenth Centuries)
Authors: Brett Annabel
Published: September 2017

De jure naturae et gentium, “The law of nature and of nations,” is the title of Samuel Pufendorf's eight-volume masterpiece of philosophical jurisprudence, first published in 1672. It provides the tag by which an entire discourse is known, one that dominated legal philosophy at European universities for over two hundred years. Pufendorf's Protestant articulation of its principles was pivotal both for transmitting it to the Eighteenth Century and for giving it a history, which in his eyes began with his fellow-Protestant Hugo Grotius. In fact, however, its roots stretch back to the early Sixteenth Century, to the lawyers whom Philip Melanchthon gathered around him at Wittenberg and (more importantly for the future structure of the discourse) to the Catholic scholastic theologians who were originally based at Salamanca in Spain but subsequently spread out over the whole of Counter-Reformation Europe. In the confessional conflict that would burn throughout the Sixteenth and Seventeenth centuries, theologians on all sides used law to define the space of the political, and used the idea of natural law to underpin that space, even while shaping it differently according to their divergent narratives of sin and redemption. While the ius naturae et gentium was an academic genre, therefore, its content was not. It was a theory and a legitimation of the state, and the arc of its reasoning from nature to the nations ran through the institution of political power. The state and its power are constructed not so much upon right (ius) per se but on the potential for the violation of right (iniuria), and the demand for such violation to be vindicated, by law or ultimately by war. At its very barest—although this is to traduce the richness and complexity of the discourse—the ius naturae et gentium is thus a theory of legitimate violence. When it comes to animals, what we find is that they are systematically excluded from the potential to suffer violation of right and therefore from political space and political justice. As we shall see, however, this did not always mean that they were totally excluded from any kind of right or that every act of violence against them was always legitimate.
The Leadership Ethics of Machiavelli’sPrince
Authors: Cosans Christopher E. , Reina Christopher S.
Published: September 2017

This article examines the place of Machiavelli’sPrincein the history of ethics and the history of leadership philosophy. Close scrutiny indicates that Machiavelli advances an ethical system for leadership that involves uprooting corruption and establishing rule of law. He draws on history and current affairs in order to obtain a realistic understanding of human behavior that forms a basis for a consequentialist ethics. While he claims a good leader might do bad things, this is in situations where necessity constrains a prince to choosing the “least bad” course of action. Furthermore, Machiavelli advocates winning the goodwill of followers through leadership as a source of power. Machiavelli’s leadership ethics has a sophistication not fully enjoyed by his reputation in management scholarship. He would not score as especially “Machiavellian” on the Mach IV. Many of his ideas contain seeds for theories that are now considered important for leadership today.
An intriguing building in the fortified Troupakis-Mourtzinos complex at Kardamyli (Messenian Mani)
Authors: Germanidou Sophia
Published: September 2017

The well-known fortified Troupakis-Mourtzinos complex includes a building that has not yet received proper attention. It is a rectangular, vaulted hall measuring 6.22 by 4.04 m., without any special features. However, one may observe a row of quadrilateral holes that pierce the outside of the walls at their mid-height, slightly below the base of the vault. On the basis of this particular detail, the building is identified as a gunpowder storeroom, while its function is examined in the context of the period when it was constructed; finally it is compared to other similar buildings within or outside the confines of Messenia.
Wave Propagation in Piezoelectric Medium with the Flexoelectric Effect Considered
Authors: Jiao F. Y. , Wei P. J. , Li Y. Q.
Published: September 2017

With the consideration of the flexoelectric effect, the dispersion feature of plane waves propagating in infinite piezoelectric medium and the reflection amplitude ratio at a mechanically traction-free and dielectrically charge-free surface of semi-infinite piezoelectric half-space are studied in this paper. The flexoelectric effect is essentially the microstructure effect of heterogeneous piezoelectric medium. Besides, the strain gradient effect and the micro-inertial effect are also introduced to reflect the influences of the microstructure. Different from the classical piezoelectric medium, there are five kinds of coupled elastic waves in the microstructured piezoelectric medium. The influences of the flexoelectric effect, the strain gradient effect and the micro-inertial effect upon the dispersion feature of the coupled elastic waves and the reflection amplitude ratio are studied numerically. The numerical results are shown graphically and are validated by the energy conservation law. It is found that these microstructure effects have obvious influences upon the dispersion feature of the coupled elastic waves and therefore also affect the reflection energy partition at the mechanically free surface. Especially, the micro-inertial effect has fundamental influences on the dispersion properties of the coupled elastic waves.
Dating Prehistoric Fortified Coastal Sites in the Balearic Islands
Authors: Anglada Montserrat , Ferrer Antoni , Ramis Damià , Salas Magdalena , Van Strydonck Mark , José León Maria , Plantalamor Lluís
Published: September 2017

A special type of coastal settlement, promontory forts defended by inland-facing walls, appeared in the Balearic Islands in an imprecise time during the Bronze Age. A research project was initiated in 2011 to study one of these sites on each of the two major islands of the archipelago. The first one, Es Coll de Cala Morell (north Menorca), is a walled promontory with a relatively large plateau, with 13 horseshoe-shaped houses (navetes). The second, Sa Ferradura (east Mallorca), is a smaller coastal cape, with a different spatial planning, with only two large built-up areas, both attached to the enclosure wall. Two of the navetes have been excavated at Es Coll de Cala Morell, showing a domestic space with a central hearth in both cases. The occupation has been dated to around 1600–1200 cal BC. At Sa Ferradura seven hearths have been recorded in a large, open-air area. Their chronology falls within the interval of approximately 1200/1100–900 cal BC. From a chronological point of view, fortified settlements in coastal promontories are not, as was expected, a unitary phenomenon in Menorca and Mallorca and have to be related to different cultural periods.
A Political Scientist Among the Anthropologists
Authors: Verghese Ajay
Published: September 2017

One of the central questions driving my research as a political scientist is understanding why ethnic conflict in multi-ethnic states revolves around one identity rather than another. Why, for example, do some regions of a diverse polity like India experience recurrent religious conflict whereas other regions experience severe caste conflict? In my book,The Colonial Origins of Ethnic Violence in India, I argue that these patterns of conflict are shaped by the legacies of British rule, especially the enduring divide between directly ruled provinces and indirectly ruled princely states. I contend that British administrators, in the wake of the 1857 Rebellion that they interpreted as a religious (Muslim) uprising, began to emphasize caste and tribal identities in their provincial governments, creating policies of ethnic stratification that led to increased caste and tribal conflict over the long run. Princely rulers, on the other hand, did the opposite: they implemented ethnic policies on the basis of religion, thereby creating legacies of communal violence. I defend this argument using archival research and interviews carried out in four comparative case studies (comparing two sets of contiguous provinces and princely states in Rajasthan and Kerala), one additional case study, and a statistical analysis of ethnic violence across 589 Indian districts.
Making Sense of Self-Deception: Distinguishing Self-Deception from Delusion, Moral Licensing, Cognitive Dissonance and Other Self-Distortions
Authors: Khalil Elias L.
Published: September 2017

There has been no systematic study in the literature of how self-deception differs from other kinds of self-distortion. For example, the term ‘cognitive dissonance’ has been used in some cases as a rag-bag term for all kinds of self-distortion. To address this, a narrow definition is given: self-deception involves injecting a given set of facts with an erroneous fact to make anex antesuboptimal decision seem as if it wereex anteoptimal. Given this narrow definition, this paper delineates self-deception from deception as well as from other kinds of self-distortions such as delusion, moral licensing, cognitive dissonance, manipulation, and introspective illusion.
Quality of life in bipolar disorder: towards a dynamic understanding
Authors: Morton E. , Murray G. , Michalak E. E. , Lam R. W. , Beaulieu S. , Sharma V. , Cervantes P. , Parikh S. V. , Yatham L. N.
Published: September 2017

Background

Although quality of life (QoL) is receiving increasing attention in bipolar disorder (BD) research and practice, little is known about its naturalistic trajectory. The dual aims of this study were to prospectively investigate: (a) the trajectory of QoL under guideline-driven treatment and (b) the dynamic relationship between mood symptoms and QoL.

Methods

In total, 362 patients with BD receiving guideline-driven treatment were prospectively followed at 3-month intervals for up to 5 years. Mental (Mental Component Score – MCS) and physical (Physical Component Score – PCS) QoL were measured using the self-report SF-36. Clinician-rated symptom data were recorded for mania and depression. Multilevel modelling was used to analyse MCS and PCS over time, QoL trajectories predicted by time-lagged symptoms, and symptom trajectories predicted by time-lagged QoL.

Results

MCS exhibited a positive trajectory, while PCS worsened over time. Investigation of temporal relationships between QoL and symptoms suggested bidirectional effects: earlier depressive symptoms were negatively associated with mental QoL, and earlier manic symptoms were negatively associated with physical QoL. Importantly, earlier MCS and PCS were both negatively associated with downstream symptoms of mania and depression.

Conclusions

The present investigation illustrates real-world outcomes for QoL under guideline-driven BD treatment: improvements in mental QoL and decrements in physical QoL were observed. The data permitted investigation of dynamic interactions between QoL and symptoms, generating novel evidence for bidirectional effects and encouraging further research into this important interplay. Investigation of relevant time-varying covariates (e.g. medications) was beyond scope. Future research should investigate possible determinants of QoL and the interplay between symptoms and wellbeing/satisfaction-centric measures of QoL.
Autonomous Unmanned Aerial Vehicle (UAV) landing in windy conditions with MAP-Elites
Authors: Adibi Sierra A. , Forer Scott , Fries Jeremy , Yliniemi Logan
Published: September 2017

With the recent increase in the use of Unmanned Aerial Vehicles (UAVs) comes a surge of inexperienced aviators who may not have the requisite skills to react appropriately if weather conditions quickly change while their aircraft are in flight. This creates a dangerous situation, in which the pilot cannot safely land the vehicle. In this work we examine the use of the MAP-Elites algorithm to search for sets of weights for use in an artificial neural network. This neural network directly controls the thrust and pitching torque of a simulated 3-degree of freedom (2 linear, 1 rotational) fixed-wing UAV, with the goal of obtaining a smooth landing profile. We then examine the use of the same algorithm in high-wind conditions, with gusts up to 30 knots.

Our results show that MAP-Elites is an effective method for searching for control policies, and by evolving two separate controllers and switching which controller is active when the UAV is near-ground level, we can produce a wider variety of phenotypic behaviors. The best controllers achieved landing at a vertical speed of <1 m s−1 and at an angle of approach of <1° degree.
Incidence and risk factors for Dengue virus (DENV) infection in the first 2 years of life in a Brazilian prospective birth cohort
Authors: CASTANHA P. M. S. , MONTARROYOS U. R. , SILVEIRA S. M. M. , ALBUQUERQUE G. D. M. , MELLO M. J. G. , LOPES K. G. S. , CORDEIRO M. T. , MARQUES E. T. A. , MARTELLI C. M. T. , BRAGA C.
Published: September 2017

This study assessed the incidence and risk factors for dengue virus (DENV) infection among children in a prospective birth cohort conducted in the city of Recife, a hyperendemic dengue area in Northeast Brazil. Healthy pregnant women (n = 415) residing in Recife who agreed to have their children followed were enrolled. Children were followed during their first 24 months of age (May/2011–June/2014), before the 2015 Zika virus outbreak. DENV infection was detected by reverse-transcriptase polymerase chain reaction and/or serology (anti-DENV IgM/IgG). The incidence rates per 1000 person-years (py) and its association with risk factors by age bands (0–12, >12–30 months) were estimated through Poisson regression models. Forty-nine dengue infections were detected; none progressed to severe forms. The incidence rates were 107·6/1000py (95% CI 76·8–150·6) and 93·3/1000py (95% CI 56·1–154·4) in the first and second years of age, respectively. Male children (risk ratios (RR) = 2·33; 95% CI 1·09–4·98) and those born to DENV-naïve mothers (RR = 2·42; 95% CI 1·01–5·80) were at greater risk of infection in the first year of age. In the second year, children born to Caucasian/Asian descent skin colour mothers had a threefold higher risk of infection (RR = 3·34; 95% CI: 1·08–10·33). These data show the high exposure of children to DENV infection in our setting and highlight the role of biological factors in this population's susceptibility to infection.
Effects of a school readiness intervention on hypothalamus–pituitary–adrenal axis functioning and school adjustment for children in foster care
Authors: Graham Alice M. , Pears Katherine C. , Kim Hyoun K. , Bruce Jacqueline , Fisher Philip A.
Published: September 2017

Maltreated children in foster care are at high risk for dysregulated hypothalamus–pituitary–adrenal (HPA) axis functioning and educational difficulties. The present study examined the effects of a short-term school readiness intervention on HPA axis functioning in response to the start of kindergarten, a critical transition marking entry to formal schooling, and whether altered HPA axis functioning influenced children's school adjustment. Compared to a foster care comparison group, children in the intervention group showed a steeper diurnal cortisol slope on the first day of school, a pattern previously observed among nonmaltreated children. A steeper first day of school diurnal cortisol slope predicted teacher ratings of better school adjustment (i.e., academic performance, appropriate classroom behaviors, and engagement in learning) in the fall of kindergarten. Furthermore, the children's HPA axis response to the start of school mediated the effect of the intervention on school adjustment. These findings support the potential for ameliorative effects of interventions targeting critical transitional periods, such as the transition of formal schooling. This school readiness intervention appears to influence stress neurobiology, which in turn facilitates positive engagement with the school environment and better school adjustment in children who have experienced significant early adversity.
NONLINEARITIES IN THE RELATIONSHIP BETWEEN DEBT AND GROWTH: (NO) EVIDENCE FROM OVER TWO CENTURIES
Authors: Eberhardt Markus
Published: September 2017

I revisit the popular concern over a nonlinearity or threshold in the relationship between public debt and growth employing long time series data from up to 27 countries. My empirical approach recognizes that standard time series arguments for long-run equilibrium relations between integrated variables (cointegration) break down in nonlinear specifications such as those predominantly applied in the existing debt–growth literature. Adopting the novel cosummability approach, my analysis overcomes these difficulties to find no evidence for a systematic long-run relationship between debt and growth in the bivariate and economic theory-based multivariate specifications popular in this literature.
READING DIODORUS 18.9.3 AND ΜΕΤΑ ΠΟΛΛΗΣ ΗΣΥΧΙΑΣ
Authors: Walsh John
Published: September 2017

Because Diodorus’Bibliothēkēwas written as an epitome, it has been common practice to conduct a compartmentalised study of his work. One of the results of this overly simplified approach has been to segregate passages from the rest of the narrative, such as 18.9.3 where Leosthenes recruits mercenaries for the Lamian War. As a result, the intended meaning of the crucial phrase μετὰ πολλῆς ἡσυχίας has been missed and valuable insight into the event is overlooked. This paper argues that μετὰ πολλῆς ἡσυχίας in Diod. 18.9.3 means ‘without great urgency’, not, as some have interpreted it, as ‘very quietly’ or ‘secretly’.
Fossil trees, tree moulds and tree casts in the Palaeocene Mull Lava Field, NW Scotland: context, formation and implications for lava emplacement
Authors: Bell Brian R. , Williamson Ian T.
Published: September 2017

Megafossils and macrofossils of terrestrial plants (trees, leaves, fruiting bodies, etc.) are found in sedimentary and pyroclastic units interbedded with lavas in many ancient lava fields worldwide, attesting to subaerial environments of eruption and the establishment of viable plant communities during periods of volcanic quiescence. Preservation within lava is relatively rare and generally confined to the more robust woody tissues of trees, which are then revealed in the form of charcoal, mineralised tissue or as trace fossil moulds (tree moulds) and casts of igneous rock (tree casts, s.s.).

In this contribution, we document several such fossil trees (s.l.), and the lavas with which they are associated, from the Palaeocene Mull Lava Field (MLF) on the Isle of Mull, NW Scotland. We present the first detailed geological account of a unique site within the Mull Plateau Lava Formation (MPLF) at Quinish in the north of the island and provide an appraisal of the famous upright fossil tree – MacCulloch's Tree – remotely located on the Ardmeanach Peninsula on the west coast of the island, and another large upright tree (the Carsaig Tree) near Malcolm's Point in the district of Brolass, SW Mull; both occurring within the earlier Staffa Lava Formation (SLF). The taphonomy of these megafossils, along with palynological and lithofacies assessments of associated strata, allows speculation of likely taxonomic affinity and the duration of hiatuses supporting the establishment of forest/woodland communities. The Ardmeanach and Carsaig specimens, because of their size and preservation as upright (?in situ) casts enveloped by spectacularly columnar-jointed basaltic lava, appear to be unique. The aspect of these trees, the thickness of the enveloping lavas and the arrangement of cooling joints adjacent to the trees, implies rapid emplacement, ponding and slow, static cooling of voluminous and highly fluid basaltic magma. The specimens from Quinish include two prostrate casts and several prostrate moulds that collectively have a preferred orientation, aligning approximately perpendicular to that of the regional Mull Dyke Swarm, the putative fissure source of the lavas, suggesting local palaeo-flow was directed towards the WSW. The Quinish Lava is an excellent example of a classic pāhoehoe (compound-braided) type, preserving some of the best examples of surface and internal features so far noted from the Hebridean Igneous Province (HIP) lava fields.

These Mull megafossils are some of the oldest recorded examples, remarkably well preserved, and form a significant feature of the island's geotourism industry.
Nationalism and Social Sanctioning Across Ethnic Lines: Experimental Evidence from the Kenya–Tanzania Border
Authors: Jeon Sangick , Johnson Tim , Robinson Amanda Lea
Published: September 2017

Past research shows that ethnic diversity reduces the ability to sanction norm violators, ultimately undermining cooperation. We test this directly by experimentally varying the ethnic composition of groups playing a dictator game with third-party punishment among two ethnic groups along the Kenya–Tanzania border. We also implement a structurally identical game where the endowment division is randomly determined in order to isolate a punishment motivation from the motivation to rectify income inequality. While costly income adjustment in both games is driven primarily by norm violations and inequality aversion, the ethnic composition of groups also influences sharing and sanctioning behavior in Kenya but not Tanzania, consistent with documented differences in the strength of nationalism across the two countries. However, the way in which shared ethnicity affects sanctioning in Kenya—namely, increased punishment of out-group violations against in-group members—is at odds with theories that anticipate that costly sanctioning will primarily target coethnics.
Observation of topological states residing at step edges of WTe2
Authors: Peng Lang , Yuan Yuan , Li Gang , Yang Xing , Xian Jing-Jing , Yi Chang-Jiang , Shi You-Guo , Fu Ying-Shuang
Published: September 2017

Topological states emerge at the boundary of solids as a consequence of the nontrivial topology of the bulk. Recently, theory predicts a topological edge state on single layer transition metal dichalcogenides with 1T’ structure. However, its existence still lacks experimental proof. Here, we report the direct observations of the topological states at the step edge of WTe2 by spectroscopic-imaging scanning tunneling microscopy. A one-dimensional electronic state residing at the step edge of WTe2 is observed, which exhibits remarkable robustness against edge imperfections. First principles calculations rigorously verify the edge state has a topological origin, and its topological nature is unaffected by the presence of the substrate. Our study supports the existence of topological edge states in 1T’-WTe2, which may envision in-depth study of its topological physics and device applications.
Cortical Up states induce the selective weakening of subthreshold synaptic inputs
Authors: Bartram Julian , Kahn Martin C. , Tuohy Simon , Paulsen Ole , Wilson Tony , Mann Edward O.
Published: September 2017

Slow-wave sleep is thought to be important for retuning cortical synapses, but the cellular mechanisms remain unresolved. During slow-wave activity, cortical neurons display synchronized transitions between depolarized Up states and hyperpolarized Down states. Here, using recordings from LIII pyramidal neurons from acute slices of mouse medial entorhinal cortex, we find that subthreshold inputs arriving during the Up state undergo synaptic weakening. This does not reflect a process of global synaptic downscaling, as it is dependent on presynaptic spiking, with network state encoded in the synaptically evoked spine Ca2+ responses. Our data indicate that the induction of synaptic weakening is under postsynaptic control, as it can be prevented by correlated postsynaptic spiking activity, and depends on postsynaptic NMDA receptors and GSK3β activity. This provides a mechanism by which slow-wave activity might bias synapses towards weakening, while preserving the synaptic connections within active neuronal assemblies.
Microbiome profile of the amniotic fluid as a predictive biomarker of perinatal outcome
Authors: Urushiyama Daichi , Suda Wataru , Ohnishi Eriko , Araki Ryota , Kiyoshima Chihiro , Kurakazu Masamitsu , Sanui Ayako , Yotsumoto Fusanori , Murata Masaharu , Nabeshima Kazuki , Yasunaga Shin’ichiro , Saito Shigeru , Nomiyama Makoto , Hattori Masahira , Miyamoto Shingo , Hata Kenichiro
Published: September 2017

Chorioamnionitis (CAM), an inflammation of the foetal membranes due to infection, is associated with preterm birth and poor perinatal prognosis. The present study aimed to determine whether CAM can be diagnosed prior to delivery based on the bacterial composition of the amniotic fluid (AF). AF samples from 79 patients were classified according to placental inflammation: Stage III (n = 32), CAM; Stage II (n = 27), chorionitis; Stage 0-I (n = 20), sub-chorionitis or no neutrophil infiltration; and normal AF in early pregnancy (n = 18). Absolute quantification and sequencing of 16S rDNA showed that in Stage III, the 16S rDNA copy number was significantly higher and the α-diversity index lower than those in the other groups. In principal coordinate analysis, Stage III formed a separate cluster from Stage 0-I, normal AF, and blank. Forty samples were classified as positive for microbiomic CAM (miCAM) defined by the presence of 11 bacterial species that were found to be significantly associated with CAM and some parameters of perinatal prognosis. The diagnostic accuracy for CAM according to miCAM was: sensitivity, approximately 94%, and specificity, 79–87%. Our findings indicate the possibility of predicting CAM prior to delivery based on the AF microbiome profile.
Lack of NLRP3-inflammasome leads to gut-liver axis derangement, gut dysbiosis and a worsened phenotype in a mouse model of NAFLD
Authors: Pierantonelli Irene , Rychlicki Chiara , Agostinelli Laura , Giordano Debora Maria , Gaggini Melania , Fraumene Cristina , Saponaro Chiara , Manghina Valeria , Sartini Loris , Mingarelli Eleonora , Pinto Claudio , Buzzigoli Emma , Trozzi Luciano , Giordano Antonio , Marzioni Marco , Minicis Samuele De , Uzzau Sergio , Cinti Saverio , Gastaldelli Amalia , Svegliati-Baroni Gianluca
Published: September 2017

Non-Alcoholic Fatty Liver Disease (NAFLD) represents the most common form of chronic liver injury and can progress to cirrhosis and hepatocellular carcinoma. A “multi-hit” theory, involving high fat diet and signals from the gut-liver axis, has been hypothesized. The role of the NLRP3-inflammasome, which senses dangerous signals, is controversial. Nlrp3−/− and wild-type mice were fed a Western-lifestyle diet with fructose in drinking water (HFHC) or a chow diet. Nlrp3−/−-HFHC showed higher hepatic expression of PPAR γ2 (that regulates lipid uptake and storage) and triglyceride content, histological score of liver injury and greater adipose tissue inflammation. In Nlrp3−/−-HFHC, dysregulation of gut immune response with impaired antimicrobial peptides expression, increased intestinal permeability and the occurrence of a dysbiotic microbiota led to bacterial translocation, associated with higher hepatic expression of TLR4 (an LPS receptor) and TLR9 (a receptor for double-stranded bacterial DNA). After antibiotic treatment, gram-negative species and bacterial translocation were reduced, and adverse effects restored both in liver and adipose tissue. In conclusion, the combination of a Western-lifestyle diet with innate immune dysfunction leads to NAFLD progression, mediated at least in part by dysbiosis and bacterial translocation, thus identifying new specific targets for NAFLD therapy.
Growth and Fabrication of High External Quantum Efficiency AlGaN-Based Deep Ultraviolet Light-Emitting Diode Grown on Pattern Si Substrate
Authors: Tran Binh Tinh , Hirayama Hideki
Published: September 2017

Growing III-V semiconductor materials on Si substrates for opto-electronic applications is challenging because their high lattice mismatch and different thermal expansion coefficients cause the epitaxial layers to have low quality. Here we report the growth of a high-quality AlN template on a micro-circle-patterned Si substrate by using NH3 pulsed-flow multilayer AlN growth and epitaxial lateral overgrowth techniques. Then, we fabricated and characterized a deep-ultraviolet light-emitting diode (UV-LED) device using this AlN/patterned Si. By using standard lithography and inductively coupled plasma etching, the Si substrate was prepared with very high pattern density and was made deep enough to grow a thick AlN template with high crystal quality and very few threading dislocations, allowing for further re-growth of the deep UV-LED device. And by combining a transparent p-AlGaN contact layer, an electron blocking layer and using this high quality AlN template: a deep UV-LED device fabricated and showed a strong single sharp electroluminescence (EL) peak at 325 nm and achieved an external quantum efficiency (EQE) of about 0.03%, for a deep UV-LED grown on Si substrate.
Estimating the intrinsic dimension of datasets by a minimal neighborhood information
Authors: Facco Elena , d’Errico Maria , Rodriguez Alex , Laio Alessandro
Published: September 2017

Analyzing large volumes of high-dimensional data is an issue of fundamental importance in data science, molecular simulations and beyond. Several approaches work on the assumption that the important content of a dataset belongs to a manifold whose Intrinsic Dimension (ID) is much lower than the crude large number of coordinates. Such manifold is generally twisted and curved; in addition points on it will be non-uniformly distributed: two factors that make the identification of the ID and its exploitation really hard. Here we propose a new ID estimator using only the distance of the first and the second nearest neighbor of each point in the sample. This extreme minimality enables us to reduce the effects of curvature, of density variation, and the resulting computational cost. The ID estimator is theoretically exact in uniformly distributed datasets, and provides consistent measures in general. When used in combination with block analysis, it allows discriminating the relevant dimensions as a function of the block size. This allows estimating the ID even when the data lie on a manifold perturbed by a high-dimensional noise, a situation often encountered in real world data sets. We demonstrate the usefulness of the approach on molecular simulations and image analysis.
Production of immunodeficient rabbits by multiplex embryo transfer and multiplex gene targeting
Authors: Song Jun , Yang Dongshan , Ruan Jinxue , Zhang Jifeng , Chen Yuqing Eugene , Xu Jie
Published: September 2017

Immunodeficient mice have been used predominantly in biomedical research. Realizing that large animal species may have an enhanced ability to predict clinical outcome relative to mice, we worked to develop immunodeficient rabbits by CRISPR/Cas9. We first demonstrated that multiplex embryo transfer efficiently produced multiple lines of single-gene mutant (SGM) founders. Embryos microinjected with single sgRNA targeting FOXN1, RAG2, IL2RG or PRKDC were pooled for embryo transfer. As few as three recipients were used to produce twenty SGM founders for four genes. We then demonstrated the powerful multiplex targeting capacity of CRISPR/Cas9. First, two genes on the same chromosome were targeted simultaneously, resulting in three RAG1/RAG2 double-gene mutant (DGM) founders. Next we microinjected forty-five embryos each with five sgRNAs targeting FOXN1, RAG1, RAG2, IL2RG and PRKDC, and transferred them to two recipients. Five founders were produced: one SGM, two DGM, one triple-gene mutant and one quadruple-gene mutant. The present work demonstrates that multiplex embryo transfer and multiplex gene targeting can be used to quickly and efficiently generate mutant rabbit founders. Four lines of SGM (e.g. FOXN1, RAG2, IL2RG, and PRKDC) immunodeficient rabbits, as well as multigenic mutant immunodeficient rabbits have been produced. These animals may prove useful for biomedical research.
Visualisation of a flexible modular structure of the ER folding-sensor enzyme UGGT
Authors: Satoh Tadashi , Song Chihong , Zhu Tong , Toshimori Takayasu , Murata Kazuyoshi , Hayashi Yugo , Kamikubo Hironari , Uchihashi Takayuki , Kato Koichi
Published: September 2017

In the endoplasmic reticulum (ER), a protein quality control system facilitates the efficient folding of newly synthesised proteins. In this system, a series of N-linked glycan intermediates displayed on the protein surface serve as quality tags. The ER folding-sensor enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) acts as a gatekeeper in the ER quality control system by specifically catalysing monoglucosylation onto incompletely folded glycoproteins, thereby enabling them to interact with lectin–chaperone complexes. Here we characterise the dynamic structure of this enzyme. Our crystallographic data demonstrate that the sensor region is composed of four thioredoxin-like domains followed by a β-rich domain, which are arranged into a C-shaped structure with a large central cavity, while the C-terminal catalytic domain undergoes a ligand-dependent conformational alteration. Furthermore, small-angle X-ray scattering, cryo-electron microscopy and high-speed atomic force microscopy have demonstrated that UGGT has a flexible modular structure in which the smaller catalytic domain is tethered to the larger folding-sensor region with variable spatial arrangements. These findings provide structural insights into the working mechanism whereby UGGT operates as a folding-sensor against a variety of glycoprotein substrates through its flexible modular structure possessing extended hydrophobic surfaces for the recognition of unfolded substrates.
Simultaneous increase in strength and ductility by decreasing interface energy between Zn and Al phases in cast Al-Zn-Cu alloy
Authors: Han Seung Zeon , Choi Eun-Ae , Park Hyun Woong , Lim Sung Hwan , Lee Jehyun , Ahn Jee Hyuk , Hwang Nong-Moon , Kim Kwangho
Published: September 2017

Cast-Al alloys that include a high amount of the second element in their matrix have comparatively high strength but low ductility because of the high volume fraction of strengthening phases or undesirable inclusions. Al–Zn alloys that have more than 30 wt% Zn have a tensile strength below 300 MPa, with elongation under 5% in the as-cast state. However, we found that after substitution of 2% Zn by Cu, the tensile strength of as-cast Al–Zn–Cu alloys was 25% higher and ductility was four times higher than for the corresponding Al–35% Zn alloy. Additionally, for the Al–43% Zn alloy with 2% Cu after 1 h solution treatment at 400 °C and water quenching, the tensile strength unexpectedly reached values close to 600 MPa. For the Al–33% Zn alloy with 2% Cu, the tensile strength was 500 MPa with 8% ductility. The unusual trends of the mechanical properties of Al–Zn alloys with Cu addition observed during processing from casting to the subsequent solution treatment were attributed to the precipitation of Zn in the Al matrix. The interface energy between the Zn particles and the Al matrix decreased when using a solution of Cu in Zn.
Infection with Burkholderia pseudomallei – immune correlates of survival in acute melioidosis
Authors: Dunachie Susanna J. , Jenjaroen Kemajittra , Reynolds Catherine J. , Quigley Kathryn J. , Sergeant Ruhena , Sumonwiriya Manutsanun , Chaichana Panjaporn , Chumseng Suchintana , Ariyaprasert Pitchayanant , Lassaux Patricia , Gourlay Louise , Promwong Charuporn , Teparrukkul Prapit , Limmathurotsakul Direk , Day Nicholas P. J. , Altmann Daniel M. , Boyton Rosemary J.
Published: September 2017

Melioidosis, caused byBurkholderia pseudomallei, is a potentially lethal infection with no licensed vaccine. There is little understanding of why some exposed individuals have no symptoms, while others rapidly progress to sepsis and death, or why diabetes confers increased susceptibility. We prospectively recruited a cohort of 183 acute melioidosis patients and 21 control subjects from Northeast Thailand and studied immune parameters in the context of survival status and the presence or absence of diabetes. HLA-B*46 (one of the commonest HLA class I alleles in SE Asia) and HLA-C*01 were associated with an increased risk of death (odds ratio 2.8 and 3.1 respectively). Transcriptomic analysis during acute infection in diabetics indicated the importance of interplay between immune pathways including those involved in antigen presentation, chemotaxis, innate and adaptive immunity and their regulation. Survival was associated with enhanced T cell immunity to nine of fifteen immunodominant antigens analysed including AhpC (BPSL2096), BopE (BPSS1525), PilO (BPSS1599), ATP binding protein (BPSS1385) and an uncharacterised protein (BPSL2520). T cell immunity to GroEL (BPSL2697) was specifically impaired in diabetic individuals. This characterization of immunity associated with survival during acute infection offers insights into correlates of protection and a foundation for design of an effective multivalent vaccine.
A combination of NMDA and AMPA receptor antagonists retards granule cell dispersion and epileptogenesis in a model of acquired epilepsy
Authors: Schidlitzki Alina , Twele Friederike , Klee Rebecca , Waltl Inken , Römermann Kerstin , Bröer Sonja , Meller Sebastian , Gerhauser Ingo , Rankovic Vladan , Li Dandan , Brandt Claudia , Bankstahl Marion , Töllner Kathrin , Löscher Wolfgang
Published: September 2017

Epilepsy may arise following acute brain insults, but no treatments exist that prevent epilepsy in patients at risk. Here we examined whether a combination of two glutamate receptor antagonists, NBQX and ifenprodil, acting at different receptor subtypes, exerts antiepileptogenic effects in the intrahippocampal kainate mouse model of epilepsy. These drugs were administered over 5 days following kainate. Spontaneous seizures were recorded by video/EEG at different intervals up to 3 months. Initial trials showed that drug treatment during the latent period led to higher mortality than treatment after onset of epilepsy, and further, that combined therapy with both drugs caused higher mortality at doses that appear safe when used singly. We therefore refined the combined-drug protocol, using lower doses. Two weeks after kainate, significantly less mice of the NBQX/ifenprodil group exhibited electroclinical seizures compared to vehicle controls, but this effect was lost at subsequent weeks. The disease modifying effect of the treatment was associated with a transient prevention of granule cell dispersion and less neuronal degeneration in the dentate hilus. These data substantiate the involvement of altered glutamatergic transmission in the early phase of epileptogenesis. Longer treatment with NBQX and ifenprodil may shed further light on the apparent temporal relationship between dentate gyrus reorganization and development of spontaneous seizures.
Fluoxetine and thioridazine inhibit efflux and attenuate crystalline biofilm formation by Proteus mirabilis
Authors: Nzakizwanayo Jonathan , Scavone Paola , Jamshidi Shirin , Hawthorne Joseph A. , Pelling Harriet , Dedi Cinzia , Salvage Jonathan P. , Hind Charlotte K. , Guppy Fergus M. , Barnes Lara M. , Patel Bhavik A. , Rahman Khondaker M. , Sutton Mark J. , Jones Brian V.
Published: September 2017

Proteus mirabilis forms extensive crystalline biofilms on indwelling urethral catheters that block urine flow and lead to serious clinical complications. The Bcr/CflA efflux system has previously been identified as important for development of P. mirabilis crystalline biofilms, highlighting the potential for efflux pump inhibitors (EPIs) to control catheter blockage. Here we evaluate the potential for drugs already used in human medicine (fluoxetine and thioridazine) to act as EPIs in P. mirabilis, and control crystalline biofilm formation. Both fluoxetine and thioridazine inhibited efflux in P. mirabilis, and molecular modelling predicted both drugs interact strongly with the biofilm-associated Bcr/CflA efflux system. Both EPIs were also found to significantly reduce the rate of P. mirabilis crystalline biofilm formation on catheters, and increase the time taken for catheters to block. Swimming and swarming motilies in P. mirabilis were also significantly reduced by both EPIs. The impact of these drugs on catheter biofilm formation by other uropathogens (Escherichia coli, Pseudomonas aeruginosa) was also explored, and thioridazine was shown to also inhibit biofilm formation in these species. Therefore, repurposing of existing drugs with EPI activity could be a promising approach to control catheter blockage, or biofilm formation on other medical devices.
Separate neural representations of depression, anxiety and apathy in Parkinson’s disease
Authors: Dan Rotem , Růžička Filip , Bezdicek Ondrej , Růžička Evžen , Roth Jan , Vymazal Josef , Goelman Gadi , Jech Robert
Published: September 2017

Depression, anxiety and apathy are distinct neuropsychiatric symptoms that highly overlap in Parkinson’s disease (PD). It remains unknown whether each symptom is uniquely associated with a functional network dysfunction. Here, we examined whether individual differences in each neuropsychiatric symptom predict functional connectivity patterns in PD patients while controlling for all other symptoms and motor function. Resting-state functional connectivity MRI were acquired from 27 PD patients and 29 healthy controls. Widespread reduced functional connectivity was identified in PD patients and explained by either the neuropsychiatric or motor symptoms. Depression in PD predicted increased functional connectivity between the orbitofrontal, hippocampal complex, cingulate, caudate and thalamus. Apathy in PD predicted decreased caudate-thalamus and orbitofrontal-parahippocampal connectivity. Anxiety in PD predicted three distinct types of functional connectivity not described before: (i) increased limbic-orbitofrontal cortex; (ii) decreased limbic-dorsolateral prefrontal cortex and orbitofrontal-dorsolateral prefrontal cortices and (iii) decreased sensorimotor-orbitofrontal cortices. The first two types of functional connectivity suggest less voluntary and more automatic emotion regulation. The last type is argued to be specific to PD and reflect an impaired ability of the orbitofrontal cortex to guide goal-directed motor actions in anxious PD patients.
Up-regulation of claudin-2 expression by aldosterone in colonic epithelial cells of mice fed with NaCl-depleted diets
Authors: Furukawa Chisa , Ishizuka Noriko , Hayashi Hisayoshi , Fujii Naoko , Manabe Aya , Tabuchi Yoshiaki , Matsunaga Toshiyuki , Endo Satoshi , Ikari Akira
Published: September 2017

Dietary NaCl depletion increases Na+ absorption and K+ secretion in the colon, but the mechanisms are not fully understood. In mice fed with NaCl-depleted diets, the expression of claudin-2 and -7 increased compared to those in control mice. Aldosterone (ALD) concentration was also increased. We examined the regulatory mechanism of claudin expression by ALD using the murine colonic epithelial MCE301 cells. ALD dose-dependently increased claudin-2 expression without affecting the expression of claudin-4, -7, -8, and -15. ALD increased nuclear distribution of mineralocorticoid receptor (MR), which was inhibited by spironolactone, an MR antagonist. The ALD-induced elevation of claudin-2 mRNA and protein expression was inhibited by spironolactone, but not by RU-486, a glucocorticoid receptor antagonist. Luciferase reporter assay showed that ALD interacts with the promoter region between -2,021 and -2,008 of human claudin-2. The binding of MR on the promoter region of claudin-2 was increased by ALD, which was inhibited by spironolactone in chromatin immunoprecipitation assay. Our data suggest that ALD acts on MR and increases paracellular permeability to ions mediated by the elevation of claudin-2 expression in the colon. NaCl depletion may increase ALD secretion from adrenal cortex, resulting in the elevation of paracellular permeability to cations in the colon.
Green light activated hydrogen sensing of nanocrystalline composite ZnO-In2O3 films at room temperature
Authors: Ilin A. S. , Ikim M. I. , Forsh P. A. , Belysheva T. V. , Martyshov M. N. , Kashkarov P. K. , Trakhtenberg L. I.
Published: September 2017

The possibility of reducing the operating temperature of H2 gas sensor based on ZnO-In2O3 down to room temperature under green illumination is shown. It is found that sensitivity of ZnO-In2O3 composite to H2 nonmonotonically depends on the oxides’ content. The optimal ratio between the components is chosen. The new mechanism of nanocrystalline ZnO-In2O3 sensor sensitivity to H2 under illumination by green light is proposed. The mechanism considers the illumination turns the composite into nonequilibrium state and the photoconductivity change in the H2 atmosphere is linked with alteration of nonequilibrium charge carriers recombination rate.
Glutaminase 2 expression is associated with regional heterogeneity of 5-aminolevulinic acid fluorescence in glioblastoma
Authors: Kim Sojin , Kim Ja Eun , Kim Yong Hwy , Hwang Taeyoung , Kim Sung Kwon , Xu Wen Jun , Shin Jong-Yeon , Kim Jong-Il , Choi Hyoungseon , Kim Hee Chan , Cho Hye Rim , Choi Anna , Chowdhury Tamrin , Seo Youngbeom , Dho Yun-Sik , Kim Jin Wook , Kim Dong Gyu , Park Sung-Hye , Kim Hyeonjin , Choi Seung Hong , Park Sunghyouk , Lee Se-Hoon , Park Chul-Kee
Published: September 2017

Fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) is now a widely-used modality for glioblastoma (GBM) treatment. However, intratumoral heterogeneity of fluorescence intensity may reflect different onco-metabolic programs. Here, we investigated the metabolic mechanism underlying the heterogeneity of 5-ALA fluorescence in GBM. Using an in-house developed fluorescence quantification system for tumor tissues, we collected 3 types of GBM tissues on the basis of their fluorescence intensity, which was characterized as strong, weak, and none. Expression profiling by RNA-sequencing revealed 77 genes with a proportional relationship and 509 genes with an inverse relationship between gene expression and fluorescence intensity. Functional analysis and in vitro experiments confirmed glutaminase 2 (GLS2) as a key gene associated with the fluorescence heterogeneity. Subsequent metabolite profiling discovered that insufficient NADPH due to GLS2 underexpression was responsible for the delayed metabolism of 5-ALA and accumulation of protoporphyrin IX (PpIX) in the high fluorescence area. The expression level of GLS2 and related NADPH production capacity is associated with the regional heterogeneity of 5-ALA fluorescence in GBM.
Overexpression of ovine AANAT and HIOMT genes in switchgrass leads to improved growth performance and salt-tolerance
Authors: Huang Yan-Hua , Liu Si-Jia , Yuan Shan , Guan Cong , Tian Dan-Yang , Cui Xin , Zhang Yun-Wei , Yang Fu-Yu
Published: September 2017

Melatonin is a well-known bioactive molecule with an array of health-promoting properties. Here, we detected the physiological function of melatonin in transgenic switchgrass overexpressing the homologous sheep arylalkylamine N-acetyltransferase and hydroxyindole O-methyltransferase genes, which catalyze the last two steps of melatonin synthesis. Compared to the wild-type (WT) and transgenic control (EV, expressing the empty vector only) plants, the transgenic switchgrass showed higher melatonin levels. Melatonin was detected in almost all switchgrass tissues, and relatively higher levels were detected in the roots and stems. Besides, melatonin showed diurnal or circadian rhythms in switchgrass similar to that in other species. Furthermore, we also found that melatonin positively affected switchgrass growth, flowering and salt tolerance. The genes related to flowering (APL3, SL1, FT1, FLP3, MADS6 and MADS15) and salt stress resistance (PvNHX1) in transgenic switchgrass exhibited a different expression profiles when compared to the control plants. Our study provided valuable findings that melatonin functions as a promoter in the regulation of switchgrass growth, flowering and salt tolerance.