bluuebunny/crossref_metadata_2025 huggingface dataset:
Systematic Theoretical Investigations for Crystal Structure Deformation in Group‐III Nitrides: A First‐Principles Study
Authors: Tsuboi Yuma , Akiyama Toru , Nakamura Kohji , Ito Tomonori
Published: October 2017

The crystal structure deformation path depending on lattice parameters and its energy barrier in group‐III nitrides are investigated by using density‐functional theory calculations. The calculations demonstrate that the energy difference in cohesive energy along the crystal structure deformation path strongly depends on the ionicity of III‐nitrides. It is also found that the lattice parameter ratio c/a of AlN and InN with Hexagonal (Hex) structure is much smaller than that of BN. Moreover, the energy barrier for structural deformation from Hex to wurtzite structures in BN is much larger than that of the other group‐III nitrides. The difference in the energy barrier originates from both the repulsive interaction among bond charges and the attractive interaction among ionic charges. These results imply that the ionicity is crucial for determining the energy change along the crystal structure deformation path as well as the structural stability of group‐III nitrides.
A comparative study on the effect of promoting the osteogenic function of osteoblasts using isoflavones from Radix Astragalus
Authors: Kong Xianghe , Wang Fang , Niu Yinbo , Wu Xianglong , Pan Yalei
Published: October 2017

Radix Astragalus has been shown to exert beneficial effects regarding the prevention postmenopausal osteoporosis. However, its mechanism of action remains to be investigated. Calycosin, formononetin, and calycosin‐7‐O‐β‐d‐glucoside are the main isoflavone constituents of Astragalus. In this study, the abilities of these 3 compounds to promote osteogenic function of osteoblasts were compared, and the structure–activity relationships of these osteotrophic isoflavones were determined. Calycosin exhibited a greater effect than formononetin and calycosin‐7‐O‐β‐d‐glucoside regarding improvements in osteogenic function of osteoblasts, as demonstrated by cell proliferation, alkaline phosphatase activity, collagen I and osteocalcin secretion, and the number and area of mineralized bone nodules. This suggests that calycosin may be better than formononetin and calycosin‐7‐O‐β‐d‐glucoside at preserving bone mass. In addition, calycosin, formononetin, and calycosin‐7‐O‐β‐d‐glucoside stimulate the expression of bone morphogenetic protein 2 and runt‐related transcription factor 2 proteins, which indicates that all 3 agents may promote the osteogenesis of osteoblasts via regulation of bone morphogenetic protein 2 expression. In conclusion, calycosin may be the best candidate, with higher osteogenic activity than formononetin and calycosin‐7‐O‐β‐d‐glucoside. The higher osteogenic activity of calycosin could be attributable to the superiority of its chemical structure (a hydroxyl group at position C3 of Ring B and no glucosyl group).
A methodology to infer and refactor an object‐oriented model from C applications
Authors: Cassol Ignacio , Arévalo Gabriela
Published: October 2017

When analyzing legacy code, generating a high‐level model of an application during the reverse engineering process helps the developers understand how the application is structured and how the dependencies relate the different software entities. Within the context of procedural programming languages (such as C), the existing approaches to get a model of the code require documentation and/or implicit knowledge that stakeholders acquire during the software building. These approaches use the code itself to build a syntactic model where we see the different software artifacts, such as variables, functions, and modules. However, there is no supporting methodology to detect and analyze if there are relationships/dependencies between those artifacts, such as which variable in a module is declared using an abstract data type described in another one, or which are the functions that are using parameters typed with an abstract data type; or any design decision taken by original developers, such as how the developer has implemented functions in different modules. On the other hand, current developers use object‐oriented (OO) paradigm to implement not only business applications but also useful methodologies/tools that allow semiautomatic analysis of any application. We must remark the legacy procedural code still has worth and is working in several industries, and as any evolving code, the developers have to be able to perform maintenance tasks minimizing the limitations offered by the language. Based on useful properties that the OO paradigm (and their supporting analysis tools) provide, such as UML models, we propose M2K as a methodology to generate a high‐level model from legacy procedural code, mainly written in Ansi C. To understand how C‐based applications were implemented is not a new problem in software reengineering. However, our contribution is based on building an OO model and suggesting different refactorings that help the developer to improve it and to eventually guide a new implementation of the target application. Specifically, the methodology builds cohesive software entities mapped from procedural code and makes the coupling between C entities explicit in the high‐level model. The result of our methodology is a set of refactored class candidates: a structure that groups a set of variables and a set of functions obtained from the C applications. Based on the class candidate model, we propose refactorings based on OO design principles to improve the design of the application. The most relevant design improvements were obtained with algorithm abstraction by applying the strategy pattern, attributes/methods relocalization, variables types generalization, and removing/renaming methods/attributes. Besides a methodology and the supporting tool, we provide 14 case studies based on real projects implemented in C, and we showed how the results validate our proposal.
ZX: A network file system for high‐latency networks
Authors: Ballesteros Francisco J. , Guardiola Gorka , Soriano Enrique
Published: October 2017

Using a central file server is good for interactive access to files, because of the coherency implied by a centralized design. In fact, within local area networks, this is a common case. However, distributed environments in use today may exhibit round‐trip times on the order of 50 or 100 ms. This is a problem for interactive file access to a central file server because of the resulting access times. Although aggressive caching and loosely synchronized replicas may be used for distributed file access, there are cases where the better coherency provided by a central server is still desirable. In this paper, we present ZX, a distributed file system and protocol designed with latency in mind. It can use caching, but it does not require caching or batching to address latency issues. ZX relies on a novel channel‐based file system interface. It includes find requests and leverages streaming requests to work well under high‐latency conditions. Unlike other protocols designed for distributed access to a central server, ZX tolerates round‐trip times on the order of 50 or 100 ms to access a central file server for interactive usage such as compiling shared sources, running binaries, editing documents, and other similar workloads. It can be used on UNIX using a FUSE adaptor while permitting native ZX speakers to run faster.
Double CD38–/CD138– negative multiple myeloma
Authors: Mykytiv Vitaliy , Alwaheed Abrar , Hashim Nurul Asyikin Mohd
Published: October 2017

The standard diagnosis of multiple myeloma by flow cytometry is based on selection of population of CD38+/CD138+ positives cells. As the result treatment with proteasome inhibitors, CD138 may be underexpressed on atypical plasma cells. Thus, in order to improve this strategy, recently new CD138-independent method, based on CD38 positivity of plasma cells was developed. We present an unusual case of CD138– negative multiple myeloma which had become double CD138–/CD38– negative after treatment with daratumumab by which we would like to illustrate potential pitfalls of both strategies.
Successful treatment of pure red cell aplasia with high-dose dexamethasone after ABO-incompatible allogeneic hematopoietic stem cell transplantation
Authors: Gómez Rosario Varela , Vázquez Goretti Vázquez , Concepción Victor Noriega , García Andrea Galego , Saavedra Concepción Andón
Published: October 2017

The literature reports an incidence of Pure Red Cell Aplasia (PRCA) ranging from 6-30% of all cases of ABO-incompatible HSCT. Although most patients resolve spontaneously after withdrawal immunosuppression, some of them require more aggressive treatment to manage this condition.
DNMT3A (R882) mutation features and prognostic effect in acute myeloid leukemia in Coexistent with NPM1 and FLT3 mutations
Authors: Kumar Dushyant , Mehta Anurag , Kumar Panigrahi Manoj , Nath Sukanta , Kumar Saikia Kandarpa
Published: October 2017

Objective/Background:

In the absence of high-risk cytogenetic, DNMT3A (DNA Methyltrans-ferase 3a) mutation status has an impact on outcome in the presence of FLT3 (FMS-like Tyrosine Kinase3) and/or NPM1 (Nucleophosmin). In this study, we focus on the features and effect of DNMT3A (R882) mutation in acute myeloid leukemia (AML) in the presence or absence of NPM1 and FLT3 mutations.

Methods:

A total of 174 cytogenetically normal (CN)-AML cases were analyzed for NPM1, FLT3, and DNMT3A mutations. For NPM1 mutation detection, we used the pyrosequencing technique; for FLT3 mutations, polymerase chain reaction and RFLP with ECO-RV techniques were used, and for DNMT3A mutation analysis, we used Sanger sequencing and RFLP (Restriction Fragment Length Polymorphism) techniques.

Results:

NPM1 mutation was found in 40.80%, DNMT3A in 12.06%, and FLT3 mutation was found in 16.66% of 174 CN-AML patients. We also found seven cases which were (NPM1+, FLT3+), 10 cases which were (NPM1 +, DNMT3A+), and two cases were found positive for (DNMT3A+, FLT3+) mutations. Adult patients had significantly higher frequency of NPM1 mutation than children (72.22% vs. 16.66%; p = .020), whereas FLT3/ITD and DNMT3A mutation was associated with higher white blood count (p = .081). Immunophenotypically, NPM1 and DNMT3A mutations were significantly associated with the lack of CD34, whereas FLT3/ITD mutation was positively associated with the expression of CD7. We also assessed the overall survival and progression-free survival of DNMT3A mutation status among patients with CN-AML. Indeed, DNMT3A mutations within the CN-AML subset were associated with significantly shorter overall survival and progression-free survival compared to NPM1 and FLT3 mutated patients (p = .067 and p = .065, respectively).

Conclusion:

DNMT3A R882 mutation plays an important role in CN-AML patients’ prognosis and clinical outcomes in the presence and absence of NPM1 and FLT3 mutations.
Maternal undernutrition during lactation alters nicotine reward and DOPAC/dopamine ratio in cerebral cortex in adolescent mice, but does not affect nicotine‐induced nAChRs upregulation
Authors: Dutra‐Tavares Ana C. , Silva Juliana O. , Nunes‐Freitas André L. , Guimarães Vinícius M.S. , Araújo Ulisses C. , Conceição Ellen P.S. , Moura Egberto G. , Lisboa Patrícia C. , Filgueiras Cláudio C. , Manhães Alex C. , Abreu‐Villaça Yael , Ribeiro‐Carvalho Anderson
Published: October 2017

Early undernutrition causes long lasting alterations that affect the response to psychoactive drugs. Particularly, undernutrition during lactation affects the acute locomotor response to nicotine during adolescence, but the reward effect of continued exposure to nicotine remains unknown. The goal of this study was to investigate the effects of undernutrition during lactation on the nicotine susceptibility indexed via conditioned place preference (CPP), on dopamine content and turnover and on nicotine‐induced nicotinic cholinergic receptor (nAChR) upregulation in the cerebral cortex, midbrain and hippocampus of adolescent mice. The impact of undernutrition and nicotine exposure on stress‐related hormones and leptin was also investigated. From postnatal day 2 (PN2) to weaning (PN21), dams were randomly assigned to one of the following groups: Control (C) – free access to standard laboratory diet (23% protein); Protein Restricted (PR) – free access to isoenergenetic diet (8% protein); Calorie Restricted (CR) – access to standard laboratory diet in restricted quantities (mean ingestion of PR). PR and CR groups showed less mass gain and less visceral fat mass. While C and CR were equally susceptible to nicotine‐induced place preference conditioning, PR failed to show a conditioning pattern. In contrast, all groups presented a nicotine‐evoked nAChR upregulation in the cerebral cortex. While dopamine and DOPAC levels did not differ between groups, the DOPAC/dopamine ratio was increased in CR animals. No differences in endocrine parameters were observed. Taken together, our results indicate that undernutrition during lactation programs for brain alterations later in life. Our data also suggest that early undernutrition does not affect the rewarding associative properties of nicotine at adolescence.
Money for Votes
Authors: Kramon Eric
Published: October 2017

Politicians distribute money to voters during campaigns in many low-income democracies. Many observers call this practice 'vote buying'. Money for Votes develops an alternative theory of electoral clientelism that emphasizes the role of monetary handouts in conveying information to voters, helping politicians enhance the credibility of their promises to deliver development resources and particularistic benefits to their constituents. Supported by interviews, experiments, and surveys in Kenya, and additional evidence from qualitative and survey data from elsewhere in Africa, the study tests the implications of this argument, and traces the consequences of electoral clientelism for voter behaviour, ethnic politics, public goods provision, and democratic accountability. Ultimately, the book suggests that the relationship of electoral clientelism to the quality of democracy is far more nuanced than our instincts might suggest.
Preparedness Training Programs for Working With Deaf and Hard of Hearing Communities and Older Adults: Lessons Learned From Key Informants and Literature Assessments
Authors: Kamau Patricia W. , Ivey Susan L. , Griese Stephanie E. , Qari Shoukat H.
Published: October 2017

Objectives

The objectives of this study were to (1) identify available training programs for emergency response personnel and public health professionals on addressing the needs of Deaf and hard of hearing individuals and older adults, (2) identify strategies to improve these training programs, and (3) identify gaps in available training programs and make recommendations for addressing these gaps.

Methods

A literature review was conducted to identify relevant training programs and identify lessons learned. Interviews were conducted by telephone or email with key informants who were subject matter experts who worked with Deaf and hard of hearing persons (n=11) and older adults (n=11).

Results

From the literature, 11 training programs targeting public health professionals and emergency response personnel serving Deaf and hard of hearing individuals (n=7) and older adults (n=4) were identified. The 4 training programs focused on older adults had corresponding evaluations published in the literature. Three (43%) of the 7 training programs focused on Deaf and hard of hearing persons included individuals from the affected communities in the development and implementation of the training. Key informant interviews identified common recommendations for improving training programs: (1) training should involve collaboration across different emergency, state, federal, and advocacy agencies; (2) training should involve members of affected communities; (3) training should be more widely accessible and affordable; and (4) training should teach response personnel varied communication techniques relevant to the Deaf and hard of hearing and older adult communities.

Conclusions

Developing effective, accessible, and affordable training programs for emergency response personnel working with Deaf and hard of hearing persons, some of whom belong to the older adult population, will require a collaborative effort among emergency response agencies, public health organizations, and members of the affected communities. (Disaster Med Public Health Preparedness. 2018;12:606–614)
KOSZUL CALCULUS
Authors: BERGER ROLAND , LAMBRE THIERRY , SOLOTAR ANDREA
Published: October 2017

We present a calculus that is well-adapted to homogeneous quadratic algebras. We define this calculus on Koszul cohomology – resp. homology – by cup products – resp. cap products. The Koszul homology and cohomology are interpreted in terms of derived categories. If the algebra is not Koszul, then Koszul (co)homology provides different information than Hochschild (co)homology. As an application of our calculus, the Koszul duality for Koszul cohomology algebras is proved foranyquadratic algebra, and this duality is extended in some sense to Koszul homology. So, the true nature of the Koszul duality theorem is independent of any assumption on the quadratic algebra. We compute explicitly this calculus on a non-Koszul example.
COERCION AND CONCILIATION AT THE EDGE OF EMPIRE: STATE-BUILDING AND ITS LIMITS IN WAZIRISTAN, 1849–1914
Authors: CONDOS MARK , RAND GAVIN
Published: October 2017

Since 2001, the geo-strategic priorities of the ‘War on Terror’ have prompted renewed attention to the historically significant region of Waziristan. Ironically, given the apparent failure of British attempts to pacify the region in the century after 1849, Waziristan’s colonial history has been picked over by policy-makers, commentators, and scholars for lessons which might be applied to current projects of state-building and counter-insurgency. Unabashedly instrumentalist, these works have reproduced the reductive stereotypes of the colonial sources and helped to entrench partial understandings of the frontier which obscure the dynamic and contingent nature of imperial state-building. This article offers an alternate frame for writing the history of the colonial frontier by re-examining how British officials attempted to constitute colonial authority through their engagements with one of the region’s most powerful groups: the Mahsud Wazirs. Challenging historiographical emphases on oscillating metropolitan strategies, this article maps crucial and largely overlooked continuities in British attempts to pacify the Mahsuds, providing new insights into state-building at the edge of empire and a more nuanced account of how imperial power was engaged, resisted, and deflected by those it sought to control.
Development of a Contextualized Version of the Multiple Errands Test for People with Substance Dependence
Authors: Valls-Serrano Carlos , Verdejo-García Antonio , Noël Xavier , Caracuel Alfonso
Published: October 2017

Background:Substance dependence is associated with deficits in several areas of executive functioning, such as planning and multitasking. Traditional tests of executive functioning have been criticized for their low ecological validity. Shallice and Burgess (1991) developed the Multiple Errands Test (MET), where participants are required to perform multiple tasks in a real-world setting. In this study, we aimed to adapt the MET for use in populations with substance dependence.Objectives:This study aimed to: (1) examine the applicability of a contextualized version of the Multiple Errands Test, namely, the Multiple Errands Test – Contextualized Version (MET-CV); (2) study the testing context reliability and convergent validity of MET-CV scores; (3) compare the performance of people with substance dependence to a control group.Methods:Data were collected from 60 participants with substance dependence and 30 healthy controls. Both groups performed a neuropsychological assessment, which consisted of the MET-CV and traditional neuropsychological tests (Letter Number Sequencing, Zoo Map Test, Revised Strategy Application Test, Information Sampling Test, Stockings of Cambridge).Results:The MET-CV has adequate testing context reliability and moderate convergent validity relative to traditional planning measures. People with substance dependence (PWSD) showed significant deficits in executive function tests compared to healthy controls, most notably on the MET-CV rather than on traditional neuropsychological tests.Conclusions:The MET-CV can be feasibly applied in the context of therapeutic communities treatment in PWSD. The MET-CV showed adequate reliability and validity, and detected planning deficits in PWSD. (JINS, 2018,24, 347–359)
WHAT KIND OF HISTORY IS THE HISTORY OF THE SELF? NEW PERSPECTIVES FROM THE HISTORY OF MIND AND BRAIN MEDICINE
Authors: BASSIRI NIMA
Published: October 2017

In a recent forum contribution to the American Historical Review on the relationship between history and biology, Lynn Hunt proposed that the future of academic scholarship devoted to exploring the origins and development of modern selfhood would depend on the disciplinary alliance between history and neuroscience. Tabling, for the moment, the cogency of her central assertion, we can nevertheless agree that Hunt espouses a sentiment shared by many historians: “the question of the self is a huge and difficult subject on its own,” she writes, and historical analysis of some sort can help us make better sense of it. The effort to do precisely that over the past several decades, through a variety of historiographic approaches, has engendered a remarkably sizable corpus of writings on the history and conceptual development of the modern, typically Western, self.
Toward Understanding and Measuring Grandiose and Vulnerable	Narcissism Within Trait Personality Models
Authors: Derry Kate L. , Ohan Jeneva L. , Bayliss Donna M.
Published: October 2017

Abstract. Research on trait narcissism is hindered by considerable confusion over its underlying structure, especially differences between pathological and normal narcissism, and grandiose and vulnerable narcissism. To address this problem, we describe two studies that examined the factor structure of a broad range of narcissism items and the implications for current narcissism theory. In Study 1, 881 undergraduates completed a scale composed of items taken trans-theoretically from narcissism scales that targeted grandiose, vulnerable, and normal narcissism descriptions. An exploratory factor analysis (EFA) was conducted and construct validity was established. In Study 2, 298 community-based participants were surveyed. Fit indices of a reduced 20-item scale and test-retest reliability were examined. Both studies supported a hierarchical structure of distinct grandiose and vulnerable factors, each with interpersonal and intrapersonal components. Thus, trait narcissism seems best described by grandiose and vulnerable dimensions, each of which can be focused toward the self or others.
Proposed Bill Would Loosen Ocean Drilling Restrictions
Authors: Showstack Randy
Published: October 2017

The legislation would restrict the withdrawal of offshore areas from oil and gas development and overturn current planning processes.
Evolutionary history biases inferences of ecology and environment from δ13C but not δ18O values
Authors: Edgar Kirsty M. , Hull Pincelli M. , Ezard Thomas H. G.
Published: October 2017

Closely related taxa are, on average, more similar in terms of their physiology, morphology and ecology than distantly related ones. How this biological similarity affects geochemical signals, and their interpretations, has yet to be tested in an explicitly evolutionary framework. Here we compile and analyze planktonic foraminiferal size-specific stable carbon and oxygen isotope values (δ13C and δ18O, respectively) spanning the last 107 million years. After controlling for dominant drivers of size-δ13C and size-δ18O trends, such as geological preservation, presence of algal photosymbionts, and global environmental changes, we identify that shared evolutionary history has shaped the evolution of species-specific vital effects in δ13C, but not in δ18O. Our results lay the groundwork for using a phylogenetic approach to correct species δ13C vital effects through time, thereby reducing systematic biases in interpretations of long-term δ13C records—a key measure of holistic organismal biology and of the global carbon cycle.
Narrow-bandwidth sensing of high-frequency fields with continuous dynamical decoupling
Authors: Stark Alexander , Aharon Nati , Unden Thomas , Louzon Daniel , Huck Alexander , Retzker Alex , Andersen Ulrik L. , Jelezko Fedor
Published: October 2017

State-of-the-art methods for sensing weak AC fields are only efficient in the low frequency domain (<10 MHz). The inefficiency of sensing high-frequency signals is due to the lack of ability to use dynamical decoupling. In this paper we show that dynamical decoupling can be incorporated into high-frequency sensing schemes and by this we demonstrate that the high sensitivity achieved for low frequency can be extended to the whole spectrum. While our scheme is general and suitable to a variety of atomic and solid-state systems, we experimentally demonstrate it with the nitrogen-vacancy center in diamond. For a diamond with natural abundance of 13C, we achieve coherence times up to 1.43 ms resulting in a smallest detectable magnetic field strength of 4 nT at 1.6 GHz. Attributed to the inherent nature of our scheme, we observe an additional increase in coherence time due to the signal itself.
Altered surface mGluR5 dynamics provoke synaptic NMDAR dysfunction and cognitive defects in Fmr1 knockout mice
Authors: Aloisi Elisabetta , Le Corf Katy , Dupuis Julien , Zhang Pei , Ginger Melanie , Labrousse Virginie , Spatuzza Michela , Georg Haberl Matthias , Costa Lara , Shigemoto Ryuichi , Tappe-Theodor Anke , Drago Filippo , Vincenzo Piazza Pier , Mulle Christophe , Groc Laurent , Ciranna Lucia , Catania Maria Vincenza , Frick Andreas
Published: October 2017

Metabotropic glutamate receptor subtype 5 (mGluR5) is crucially implicated in the pathophysiology of Fragile X Syndrome (FXS); however, its dysfunction at the sub-cellular level, and related synaptic and cognitive phenotypes are unexplored. Here, we probed the consequences of mGluR5/Homer scaffold disruption for mGluR5 cell-surface mobility, synaptic N-methyl-D-aspartate receptor (NMDAR) function, and behavioral phenotypes in the second-generationFmr1knockout (KO) mouse. Using single-molecule tracking, we found that mGluR5 was significantly more mobile at synapses in hippocampalFmr1KO neurons, causing an increased synaptic surface co-clustering of mGluR5 and NMDAR. This correlated with a reduced amplitude of synaptic NMDAR currents, a lack of their mGluR5-activated long-term depression, and NMDAR/hippocampus dependent cognitive deficits. These synaptic and behavioral phenomena were reversed by knocking down Homer1a inFmr1KO mice. Our study provides a mechanistic link between changes of mGluR5 dynamics and pathological phenotypes of FXS, unveiling novel targets for mGluR5-based therapeutics.
Screening and identification of critical transcription factors involved in the protection of cardiomyocytes against hydrogen peroxide-induced damage by Yixin-shu
Authors: Zhang Jingjing , Geng Ya , Guo Feifei , Zhang Fangbo , Liu Mingwei , Song Lei , Ma Yuexiang , Li Defeng , Zhang Yi , Xu Haiyu , Yang Hongjun
Published: October 2017

Oxidative stress initiates harmful cellular responses, such as DNA damage and protein denaturation, triggering a series of cardiovascular disorders. Systematic investigations of the transcription factors (TFs) involved in oxidative stress can help reveal the underlying molecular mechanisms and facilitate the discovery of effective therapeutic targets in related diseases. In this study, an integrated strategy which integrated RNA-seq-based transcriptomics techniques and a newly developed concatenated tandem array of consensus TF response elements (catTFREs)-based proteomics approach and then combined with a network pharmacology analysis, was developed and this integrated strategy was used to investigate critical TFs in the protection of Yixin-shu (YXS), a standardized medical product used for ischaemic heart disease, against hydrogen peroxide (H2O2)-induced damage in cardiomyocytes. Importantly, YXS initiated biological process such as anti-apoptosis and DNA repair to protect cardiomyocytes from H2O2-induced damage. By using the integrated strategy, DNA-(apurinic or apyrimidinic site) lyase (Apex1), pre B-cell leukemia transcription factor 3 (Pbx3), and five other TFs with their functions involved in anti-oxidation, anti-apoptosis and DNA repair were identified. This study offers a new understanding of the mechanism underlying YXS-mediated protection against H2O2-induced oxidative stress in cardiomyocytes and reveals novel targets for oxidative stress-related diseases.
Immunotherapy with subcutaneous immunogenic autologous tumor lysate increases murine glioblastoma survival
Authors: Belmans Jochen , Van Woensel Matthias , Creyns Brecht , Dejaegher Joost , Bullens Dominique M. , Van Gool Stefaan W.
Published: October 2017

Immunotherapeutic strategies for glioblastoma, the most frequent malignant primary brain tumor, aim to improve its disastrous consequences. On top of the standard treatment, one strategy uses T cell activation by autologous dendritic cells (DC) ex vivo loaded with tumor lysate to attack remaining cancer cells. Wondering whether ‘targeting’ in vivo DCs could replace these ex vivo ones, immunogenic autologous tumor lysate was used to treat glioma-inoculated mice in the absence of ex vivo loaded DCs. Potential immune mechanisms were studied in two orthotopic, immunocompetent murine glioma models. Pre-tumoral subcutaneous lysate treatment resulted in a survival benefit comparable to subcutaneous DC therapy. Focussing on the immune response, glioma T cell infiltration was observed in parallel with decreased amounts of regulatory T cells. Moreover, these results were accompanied by the presence of strong tumor-specific immunological memory, shown by complete survival of a second glioblastoma tumor, inoculated 100 days after the first one. Finally, in combination with temozolomide, survival of established glioma in mice could be increased. Our results show the potential of immunogenic autologous tumor lysate used to treat murine glioblastoma, which will be worthwhile to study in clinical trials as it has potential as a cost-efficient adjuvant treatment strategy for gliomas.
A deterministic detector for vector vortex states
Authors: Ndagano Bienvenu , Nape Isaac , Perez-Garcia Benjamin , Scholes Stirling , Hernandez-Aranda Raul I. , Konrad Thomas , Lavery Martin P. J. , Forbes Andrew
Published: October 2017

Encoding information in high-dimensional degrees of freedom of photons has led to new avenues in various quantum protocols such as communication and information processing. Yet to fully benefit from the increase in dimension requires a deterministic detection system, e.g., to reduce dimension dependent photon loss in quantum key distribution. Recently, there has been a growing interest in using vector vortex modes, spatial modes of light with entangled degrees of freedom, as a basis for encoding information. However, there is at present no method to detect these non-separable states in a deterministic manner, negating the benefit of the larger state space. Here we present a method to deterministically detect single photon states in a four dimensional space spanned by vector vortex modes with entangled polarisation and orbital angular momentum degrees of freedom. We demonstrate our detection system with vector vortex modes from the |$${\boldsymbol{\ell }}$$
ℓ
| = 1 and |$${\boldsymbol{\ell }}$$
ℓ
| = 10 subspaces using classical and weak coherent states and find excellent detection fidelities for both pure and superposition vector states. This work opens the possibility to increase the dimensionality of the state-space used for encoding information while maintaining deterministic detection and will be invaluable for long distance classical and quantum communication.
Role of the luxS gene in bacteriocin biosynthesis by Lactobacillus plantarum KLDS1.0391: A proteomic analysis
Authors: Jia Fang-Fang , Pang Xue-Hui , Zhu De-Quan , Zhu Zong-Tao , Sun Si-Rui , Meng Xiang-Chen
Published: October 2017

Certain probiotic species of lactic acid bacteria, especially Lactobacillus plantarum, regulate bacteriocin synthesis through quorum sensing (QS) systems. In this study, we aimed to investigate the luxS-mediated molecular mechanisms of QS during bacteriocin synthesis by L. plantarum KLDS1.0391. In the absence of luxS, the ‘spot-on-the-lawn’ method showed that the bacteriocin production by L. plantarum KLDS1.0391 significantly decreased upon co-cultivation with L. helveticus KLDS1.9207 (P < 0.01) but did not change significantly when mono-cultivated. Furthermore, liquid chromatography-electrospray ionization tandem mass spectrometry analysis showed that, as a response to luxS deletion, L. plantarum KLDS1.0391 altered the expression level of proteins involved in carbohydrate metabolism, amino acid metabolism, fatty acid synthesis and metabolism, and the two-component regulatory system. In particular, the sensor histidine kinase AgrC (from the two-component system, LytTR family) was expressed differently between the luxS mutant and the wild-type strain during co-cultivation, whereas no significant differences in proteins related to bacteriocin biosynthesis were found upon mono-cultivation. In summary, we found that the production of bacteriocin was regulated by carbohydrate metabolism, amino acid metabolism, fatty acid synthesis and metabolism, and the two-component regulatory system. Furthermore, our results demonstrate the role of luxS-mediated molecular mechanisms in bacteriocin production.
Seawater transfer alters the intestinal microbiota profiles of Atlantic salmon (Salmo salar L.)
Authors: Dehler Carola E. , Secombes Christopher J. , Martin Samuel A. M.
Published: October 2017

Atlantic salmon undergo dramatic physiological changes as they migrate from freshwater to the marine environment. Osmoregulatory adaptation is the most crucial change, necessitating functional adaptations of the gills, kidney and intestine. Additionally, novel pathogens, microbes and dietary items are encountered in the saltwater environment, which suggests major changes in the intestinal microbiota following movement to saltwater. Here we compared the intestinal microbiota harboured in the distal digesta of Atlantic salmon freshwater fish (FW) kept in a commercial Scottish freshwater hatchery with that of their full-siblings after seawater acclimatisation (SW) by a 16S rRNA (V3-V4) high-throughput sequencing approach. Alpha- and beta-diversity were found significantly higher in FW compared to SW, both in terms of richness and diversity. Metastats analysis identified a higher number of Operational Taxonomic Units (OTUs) unique to FW compared to SW, with an additional 238 OTUs found at significantly different abundance. A core microbiota of 19 OTUs was identified in 100% of all fish, which indicates that certain microbes are maintained to fulfil minimal functions within the gut. Furthermore we show that the uniqueness of the respective microbial profiles can be correlated with significant differences in KEGG pathways including lipid and amino acid metabolism.
Computational reconstruction reveals a candidate magnetic biocompass to be likely irrelevant for magnetoreception
Authors: Friis Ida , Sjulstok Emil , Solov’yov Ilia A.
Published: October 2017

Birds use the magnetic field of the Earth to navigate during their annual migratory travel. The possible mechanism to explain the biophysics of this compass sense involves electron transfers within the photoreceptive protein cryptochrome. The magnetoreceptive functioning of cryptochromes is supposedly facilitated through an iron rich polymer complex which couples to multiple cryptochromes. The present investigation aims to independently reconstruct this complex and describe its interaction with Drosophila melanogaster cryptochromes. The polymer complex consists of ISCA1 protein monomers with internally bound iron sulphur clusters and simultaneously binds ten cryptochromes. Through molecular dynamics we have analysed the stability of the ISCA1-cryptochrome complex and characterized the interaction at the binding sites between individual cryptochrome and ISCA1. It is found that the cryptochrome binding to the ISCA1 polymer is not uniform and that the binding affinity depends on its placement along the ISCA1 polymer. This finding supports the claim that the individual ISCA1 monomer acts as possible intracellular interaction partner of cryptochrome, but the proposed existence of an elongated ISCA1 polymer with multiple attached cryptochromes appears to be questionable.
Structural, physicochemical and dynamic features conserved within the aerolysin pore-forming toxin family
Authors: Cirauqui Nuria , Abriata Luciano A. , van der Goot F. Gisou , Dal Peraro Matteo
Published: October 2017

Aerolysin is the founding member of a major class of β-pore-forming toxins (β-PFTs) found throughout all kingdoms of life. PFTs are cytotoxic proteins produced as soluble monomers, which oligomerize at the membrane of target host cells forming pores that may lead to osmotic lysis and cell death. Besides their role in microbial infection, they have become interesting for their potential as biotechnological sensors and delivery systems. Using an approach that integrates bioinformatics with molecular modeling and simulation, we looked for conserved features across this large toxin family. The cell surface-binding domains present high variability within the family to provide membrane receptor specificity. On the contrary, the novel concentric double β-barrel structure found in aerolysin is highly conserved in terms of sequence, structure and conformational dynamics, which likely contribute to preserve a common transition mechanism from the prepore to the mature pore within the family.Our results point to the key role of several amino acids in the conformational changes needed for oligomerization and further pore formation, such as Y221, W227, P248, Q263 and L277, which we propose are involved in the release of the stem loop and the two adjacent β-strands to form the transmembrane β-barrel.
Quantum coherence of the Heisenberg spin models with Dzyaloshinsky-Moriya interactions
Authors: Radhakrishnan Chandrashekar , Parthasarathy Manikandan , Jambulingam Segar , Byrnes Tim
Published: October 2017

We study quantum coherence in a spin chain with both symmetric exchange and antisymmetric Dzyaloshinsky-Moriya couplings. Quantum coherence is quantified using the recently introduced quantum Jensen-Shannon divergence, which has the property that it is easily calculable and has several desirable mathematical properties. We calculate exactly the coherence for arbitrary number of spins at zero temperature in various limiting cases. The σ
z
σ
z
interaction tunes the amount of coherence in the system, and the antisymmetric coupling changes the nature of the coherence. We also investigate the effect of non-zero temperature by looking at a two-spin system and find similar behavior, with temperature dampening the coherence. The characteristic behavior of coherence resembles that of entanglement and is opposite to that of discord. The distribution of the coherence on the spins is investigated and found that it arises entirely due to the correlations between the spins.
Simulating Moral Actions: An Investigation of Personal Force in Virtual Moral Dilemmas
Authors: Francis K. B. , Terbeck S. , Briazu R. A. , Haines A. , Gummerum M. , Ganis G. , Howard I. S.
Published: October 2017

Advances in Virtual Reality (VR) technologies allow the investigation of simulated moral actions in visually immersive environments. Using a robotic manipulandum and an interactive sculpture, we now also incorporate realistic haptic feedback into virtual moral simulations. In two experiments, we found that participants responded with greater utilitarian actions in virtual and haptic environments when compared to traditional questionnaire assessments of moral judgments. In experiment one, when incorporating a robotic manipulandum, we found that the physical power of simulated utilitarian responses (calculated as the product of force and speed) was predicted by individual levels of psychopathy. In experiment two, which integrated an interactive and life-like sculpture of a human into a VR simulation, greater utilitarian actions continued to be observed. Together, these results support a disparity between simulated moral action and moral judgment. Overall this research combines state-of-the-art virtual reality, robotic movement simulations, and realistic human sculptures, to enhance moral paradigms that are often contextually impoverished. As such, this combination provides a better assessment of simulated moral action, and illustrates the embodied nature of morally-relevant actions.
Calcineurin/P-ERK/Egr-1 Pathway is Involved in Fear Memory Impairment after Isoflurane Exposure in Mice
Authors: Yang Xiaoxuan , Li Guohui , Xue Qingsheng , Luo Yan , Wang Sensen , Xia Yimeng , Zhuang Lei , Yu Buwei
Published: October 2017

Isoflurane exposure adversely influences subsequent fear memory formation in mice. Calcineurin (CaN), a phosphatase, prevents the establishment of emotional memory by dephosphorylating substrates and inhibiting the expression of learning and memory related genes. We investigated whether isoflurane impairment of fear memory formation was associated with altered CaN activity and downstream phosphorylated-extracellular signal-regulated kinases (p-ERK) and early growth response gene-1 (Egr-1) expression in hippocampus and amygdala. We also tested whether memory performance can be rescued by the CaN inhibitor FK506. Adult C57BL/6 mice were injected FK506 or vehicle after being exposed to 1.3% isoflurane or air for 1 h. After a 1 h- recovery, mice underwent classical fear conditioning (FC) training. Fear memory were tested 30 min, 48 h and 7 days after training. The activity of CaN, and expression of p-ERK and Egr-1 in hippocampus and amygdala were analyzed. Isoflurane exposure reduced mice freezing time in contextual and tone FC tests 30 min and 48 h after training. Hippocampus and amygdala from isoflurane-exposed mice had enhanced CaN activity, reduced p-ERK/ERK and Egr-1 expression. All these changes in isoflurane-exposed mice were attenuated by FK506 treatment. These results indicate calcineurin/p-ERK/Egr-1 Pathway is involved in fear memory impairment after isoflurane exposure in mice.
Peripheral CD19hi B cells exhibit activated phenotype and functionality in promoting IgG and IgM production in human autoimmune diseases
Authors: Liu Zhicui , Zeng Weihong , Huang Xiangyang , Wang Shujun , Zheng Jie , Pan Meng , Wang Ying
Published: October 2017

Systemic Lupus Erythematosus (SLE) and pemphigus are two representative autoimmune diseases driven by pathogenic autoantibody systemically and organ-specifically, respectively. Given the involvement of antibody in the pathogenesis, B cells are inclined to differentiate and function in an abnormal activation model. Here we defined a unique CD19hi B cell population existing in the periphery of SLE and pemphigus patients as well as in human tonsils. CD19hi B cells could be induced in vitro after co-culturing fully activated CD4+ T cells with autologous B cells. They expressed high levels of HLA-DR, IgG, IgM and multiple ligands of costimulatory molecules with the capacity to produce extra IgG and IgM. Transcirptome assay revealed that genes involved in B-cell activation and differentiation were up-regulated in CD19hi B cells. Antibody blockade experiments showed that the interactions between costimulatory molecules contributed to CD19hi B-cell generation and IgG/IgM production. What is more, frequencies of peripheral CD19hi B cells from SLE and pemphigus patients were correlated with serum total IgG and IgM, but not with autoantigen-specific antibodies and disease severity. Therefore, our investigation demonstrates that CD19hi B cells might contain B cell precursors for terminal differentiation and contribute to total IgG/IgM production in human autoimmune diseases.
Uptake of glucose-conjugated MGMT inhibitors in cancer cells: role of flippases and type IV P-type ATPases
Authors: Tomaszowski Karl-Heinz , Hellmann Nadja , Ponath Viviane , Takatsu Hiroyuki , Shin Hye-Won , Kaina Bernd
Published: October 2017

The DNA repair proteinO6-methylguanine-DNA-methyltransferase (MGMT) is a key determinant of cancer resistance. The MGMT inhibitorsO6-benzylguanine (O6BG) andO6-(4-bromothenyl)guanine (O6BTG) failed to enhance the therapeutic response due to toxic side effects when applied in combination with alkylating chemotherapeutics, indicating a need of inhibitor targeting. We assessed MGMT targeting that relies on conjugating the inhibitors O6BG and O6BTG to ß-D-glucose, resulting in O6BG-Glu and O6BTG-Glu, respectively. This targeting strategy was selected by taking advantage of high demand of glucose in cancers. Contrary to our expectation, the uptake of O6BG-Glu and O6BTG-Glu was not dependent on glucose transporters. Instead, it seems that after membrane binding the conjugates are taken up via flippases, which normally transport phospholipids. This membrane binding is the consequence of the amphiphilic character of the conjugates, which at higher concentrations lead to the formation of micelle-like particles in aqueous solution. The unusual uptake mechanism of the conjugates highlights the importance of proper linker selection for a successful ligand-based drug delivery strategy. We also demonstrate that proteins of the P4-Type ATPase family are involved in the transport of the glucose conjugates. The findings are not only important for MGMT inhibitor targeting, but also for other amphiphilic drugs.
Association of muscle lipidomic profile with high-fat diet-induced insulin resistance across five mouse strains
Authors: Montgomery Magdalene K. , Brown Simon H. J. , Mitchell Todd W. , Coster Adelle C. F. , Cooney Gregory J. , Turner Nigel
Published: October 2017

Different mouse strains exhibit variation in their inherent propensities to develop metabolic disease. We recently showed that C57BL6, 129X1, DBA/2 and FVB/N mice are all susceptible to high-fat diet-induced glucose intolerance, while BALB/c mice are relatively protected, despite changes in many factors linked with insulin resistance. One parameter strongly linked with insulin resistance is ectopic lipid accumulation, especially metabolically active ceramides and diacylglycerols (DAG). This study examined diet-induced changes in the skeletal muscle lipidome across these five mouse strains. High-fat feeding increased total muscle triacylglycerol (TAG) content, with elevations in similar triacylglycerol species observed for all strains. There were also generally consistent changes across strains in the abundance of different phospholipid (PL) classes and the fatty acid profile of phospholipid molecular species, with the exception being a strain-specific difference in phospholipid species containing two polyunsaturated fatty acyl chains in BALB/c mice (i.e. a diet-induced decrease in the other four strains, but no change in BALB/c mice). In contrast to TAG and PL, the high-fat diet had a minor influence on DAG and ceramide species across all strains. These results suggest that widespread alterations in muscle lipids are unlikely a major contributors to the favourable metabolic profile of BALB/c mice and rather there is a relatively conserved high-fat diet response in muscle of most mouse strains.