bluuebunny/crossref_metadata_2025 huggingface dataset:
Grafting
Authors: Asselin Claire
Published: February 2018

It has been traditionally recognized by linguists that the rules of linking in French are syntactically constrained and that their application depends on the grammatical category of the constituents involved. The author of this paper agrees with the basic thesis that linking is not solely phonological. However, the traditional way of analyzing linking misses an important generalization. The purpose of this paper is thus to show that there exists a deeper explanation for the phenomenon. It will be suggested that linking is not constrained by particular grammatical categories but by the presence of a boundary. The grafting principle will be offered as an explanation for the presence of this boundary. It will also be shown that the present analysis accounts for the phenomenon of pause.
A persistent rule in Maltese
Authors: Cowan William
Published: February 2018

The Notion of persistent rule in historical phonology has been discussed by Chafe in his important asticle on the order of phonological rules (Chafe 1968). Two examples are the wellknown devoicing of final obstruants in German - a rule added to the grammar of German at a point in time in its history, and still operative so that words introduced after the adding of the rule are subject to it; and the loss of final /n/ in Livonian, so that a word like /nainen/ first becomes /naine/, then is subject to a rule that eliminates final vowels, thus becoming /nain/, which, since the n-dropping rule is still in force, becomes /nai/. Rules are said to persist when they apply either to forms resulting from rules added later than they to the grammar of the language, or to forms introduced into the language from a source other than a later rule, i.e. through borrowing.
WOMEN OF DISCORD: FEMALE POWER IN AZTEC THOUGHT
Authors: PENNOCK CAROLINE DODDS
Published: February 2018

This article addresses the perennial debate over the origins and nature of female power by examining the significance of ‘Women of Discord’ in Aztec (more properly, Mexica) culture. Influential, but often troublesome, these formidable figures embody the complex significance of female power, rooted in women's privileged access to the awesome earth forces through childbirth. This chaotic energy lent cosmological and dynastic significance to the mytho-historical Women of Discord, but also led to a persistent female association with disorder which had tangible (and often overlooked) consequences for the lives of ‘real’ women in Aztec culture. This article explores the ways in which beliefs about the female capacity for disruption both reflected and shaped reality, ensnaring all women in a cycle of myth and history which made femininity a source of both authority and apprehension. Importantly, in Tenochtitlan ideas about ‘disorderly women’ did not lead inevitably to their practical subordination or suppression; women held practical markers of influence and esteem in Aztec culture. Thus, the Women of Discord challenge our assumptions about gender by offering a distinctive perspective on the ways in which femininity and fertility may be seen as disruptive, without necessarily debasing women or depriving them of individual agency.
Precarious Finality? Reflections onRes Judicataand theQuestion of the Delimitation of the Continental ShelfCase
Authors: RIDI NICCOLÒ
Published: February 2018

This article considers the approach to theres judicataprinciple taken by the International Court of Justice (ICJ or the Court) and, specifically, its application in its 2016 judgment on preliminary objections in the latest dispute between Nicaragua and Colombia. The judgment joins the small number of ICJ decisions in which the Court was evenly split, an altogether rare situation, which, at the time of the decision, had not occurred since theNuclear WeaponsAdvisory Opinion. Intriguingly, such a fracture seems to have been prompted by differences over the operation of a procedural principle the understanding of which is comparatively uncontroversial. Upon closer analysis, however, the disagreement reveals that more significant questions were at stake, with members of the minority issuing a vocal joint dissent and several individual declarations. This study will move in three parts: first, it will provide an overview of the nature and purpose of the principle ofres judicata, its application in international adjudication, and its use by the ICJ; second, it will analyze the Court's reading of the principle in the case at issue; third, it will expose the broader implications of one such approach for the role and authority of the World Court and the international judiciary.
Self-monitoring of urinary salt excretion as a method of salt-reduction education: a parallel, randomized trial involving two groups
Authors: Yasutake Kenichiro , Miyoshi Emiko , Misumi Yukiko , Kajiyama Tomomi , Fukuda Tamami , Ishii Taeko , Moriguchi Ririko , Murata Yusuke , Ohe Kenji , Enjoji Munechika , Tsuchihashi Takuya
Published: February 2018

Objective

The present study aimed to evaluate salt-reduction education using a self-monitoring urinary salt-excretion device.

Design

Parallel, randomized trial involving two groups. The following parameters were checked at baseline and endline of the intervention: salt check sheet, eating behaviour questionnaire, 24 h home urine collection, blood pressure before and after urine collection.

Setting

The intervention group self-monitored urine salt excretion using a self-measuring device for 4 weeks. In the control group, urine salt excretion was measured, but the individuals were not informed of the result.

Subjects

Seventy-eight individuals (control group, n 36; intervention group, n 42) collected two 24 h urine samples from a target population of 123 local resident volunteers. The samples were then analysed.

Results

There were no differences in clinical background or related parameters between the two groups. The 24 h urinary Na:K ratio showed a significant decrease in the intervention group (−1·1) compared with the control group (−0·0; P=0·033). Blood pressure did not change in either group. The results of the salt check sheet did not change in the control group but were significantly lower in the intervention group. The score of the eating behaviour questionnaire did not change in the control group, but the intervention group showed a significant increase in eating behaviour stage.

Conclusions

Self-monitoring of urinary salt excretion helps to improve 24 h urinary Na:K, salt check sheet scores and stage of eating behaviour. Thus, usage of self-monitoring tools has an educational potential in salt intake reduction.
Using a trauma-informed policy approach to create a resilient urban food system
Authors: Hecht Amelie A , Biehl Erin , Buzogany Sarah , Neff Roni A
Published: February 2018

Objective

Food insecurity is associated with toxic stress and adverse long-term physical and mental health outcomes. It can be experienced chronically and also triggered or exacerbated by natural and human-made hazards that destabilize the food system. TheBaltimore Food System Resilience Advisory Reportwas created to strengthen the resilience of the city’s food system and improve short- and long-term food security. Recognizing food insecurity as a form of trauma, the report was developed using the principles of trauma-informed social policy. In the present paper, we examine how the report applied trauma-informed principles to policy development, discuss the challenges and benefits of using a trauma-informed approach, and provide recommendations for others seeking to create trauma-informed food policy.

Design

Report recommendations were developed based on: semi-structured interviews with food system stakeholders; input from community members at outreach events; a literature review; Geographic Information System mapping; and other analyses. The present paper explores findings from the stakeholder interviews.

Setting

Baltimore, Maryland, USA.

Subjects

Baltimore food system stakeholders stratified by two informant categories: organizations focused on promoting food access (n13) and community leaders (n12).

Results

Stakeholder interviews informed the recommendations included in the report and supported the idea that chronic and acute food insecurity are experienced as trauma in the Baltimore community.

Conclusions

Applying a trauma-informed approach to the development of theBaltimore Food System Resilience Advisory Reportcontributed to policy recommendations that were community-informed and designed to lessen the traumatic impact of food insecurity.
Sinnvolle Therapie des Diabetes mellitus Typ 2: Von der Definition des therapeutischen Ziels zur Auswahl des richtigen Medikamentes
Authors: Zulewski Henryk
Published: February 2018

Zusammenfassung. Die Häufigkeit des Diabetes mellitus Typ 2 nimmt aufgrund der Alterung der Bevölkerung und der zunehmenden Adipositas weltweit zu. Für eine adäquate Behandlung ist primär die Festlegung des jeweiligen Therapieziels sinnvoll, das sich an den medizinischen Erfordernissen und individuellen Möglichkeiten des Patienten orientiert. Hiervon hängt die Intensität der Therapie und die Wahl der entsprechenden Medikamente ab, wobei das Metformin als primäres Präparat für alle, die es haben dürfen, sinnvoll ist. Die Auswahl der zur Verfügung stehenden Substanzen, die dem Metformin dazugegeben werden könnten, ist in den letzten Jahren sehr stark erweitert worden durch neuere Inkretin-basierte Therapeutika (DPP4 Inhibitoren und GLP-1 Analoga) und zuletzt auch Inhibitoren der Glukoseresorption in der Niere, den sogenannten SGLT2- Inhibitoren sowie vielfältige damit assoziierte Kombinationen. Obgleich alle neuen Präparate wesentlich teurer sind als z.B. der ältere Sulfonylharnstoff Gliclazid, ist deren Wirksamkeit in Bezug auf die HbA1c-Senkung nicht besser. Unterschiede gibt es primär im Nebenwirkungsprofil und bei einigen Präparaten kann auch eine moderate Gewichtsreduktion beobachtet werden. Grosse Aufmerksamkeit hat in den letzten Jahren die kardiovaskuläre Sicherheit der neuen Präparate bekommen. Der SGLT2-Inhibitor Empagliflozin scheint bei Hochrisikopatienten mit etablierter koronarer Herzerkrankung das Risiko für die Exazerbation einer Herzinsuffizienz sowie die Mortalität zu reduzieren und kann daher bei ausgewählten Patienten eingesetzt werden, unter Beachtung der spezifischen Nebenwirkungen. Welche Substanz zum Metformin als Medikament der ersten Wahl hinzugegeben werden soll, wenn das angestrebte HbA1c-Ziel mit Metformin alleine nicht erreicht werden konnte, ist abhängig von patientenspezifischen Faktoren, wobei für die meisten Patienten das Gliclazid wegen des sehr guten Sicherheitsprofils sicherlich eine gute Wahl darstellt.
Entwicklung einer Programmtheorie als Grundlage für die Evaluation einer Demenzstation
Authors: Adlbrecht Laura , Bartholomeyczik Sabine , Mayer Hanna
Published: February 2018

Zusammenfassung. Hintergrund: Ein bestehendes Konzept einer Demenzstation soll evaluiert werden. Damit die Evaluation gut aufgesetzt werden kann, bedarf es eines theoretischen Verständnisses für die implementierte Intervention, welches bisher nicht explizit formuliert ist. Eine Möglichkeit dafür ist die Entwicklung einer Programmtheorie. Ziel: Ziel ist es, eine Methode vorzustellen, wie eine Programmtheorie für das bestehende Wohn- und Betreuungskonzept einer Demenzstation entwickelt wird, die im Rahmen eines grösseren Projekts dazu dienen soll, dieses Konzept theoriegeleitet zu evaluieren. Methode: Die Evaluation wurde in den Strukturrahmen von van Belle et al. (2010) eingebettet und ein Action Model und ein Change Model nach Chen (2015) erstellt. Die Contribution Analysis ( Mayne, 2011 ) dient der Konkretisierung des Change Models. Es wurden Workshops mit den Entwicklern / Entwicklerinnen und den Pflegenden der Demenzstation sowie eine Literaturrecherche zu den Interventionen und Outcomes durchgeführt. Die Ergebnisse wurden in einem Konsensworkshop zusammengeführt. Ergebnisse: Das Action Model beschreibt die Interventionen der Demenzstation, die Implementierer / Implementiererinnen, die Organisation und den Kontext. Im Change Model wird dargelegt, mit welchen Mechanismen die Intervention Outcomes verändert. Schlussfolgerung: Die Ergebnisse der Programmtheorie können für die Wahl der Datenerhebungsmethoden und Instrumente der Evaluation genutzt werden. Anhand der Ergebnisse der Evaluation kann in weiterer Folge die Programmtheorie verfeinert und adaptiert werden.
Targeting oncogenic Myc as a strategy for cancer treatment
Authors: Chen Hui , Liu Hudan , Qing Guoliang
Published: February 2018

The MYC family oncogene is deregulated in >50% of human cancers, and this deregulation is frequently associated with poor prognosis and unfavorable patient survival. Myc has a central role in almost every aspect of the oncogenic process, orchestrating proliferation, apoptosis, differentiation, and metabolism. Although Myc inhibition would be a powerful approach for the treatment of many types of cancers, direct targeting of Myc has been a challenge for decades owing to its “undruggable” protein structure. Hence, alternatives to Myc blockade have been widely explored to achieve desirable anti-tumor effects, including Myc/Max complex disruption, MYC transcription and/or translation inhibition, and Myc destabilization as well as the synthetic lethality associated with Myc overexpression. In this review, we summarize the latest advances in targeting oncogenic Myc, particularly for cancer therapeutic purposes.
Thrombospondin-1 protects against Aβ-induced mitochondrial fragmentation and dysfunction in hippocampal cells
Authors: Kang Seokjo , Byun Jayoung , Son Sung Min , Mook-Jung Inhee
Published: February 2018

Alzheimer’s disease (AD) is often characterized by the impairment of mitochondrial function caused by excessive mitochondrial fragmentation. Thrombospondin-1 (TSP-1), which is primarily secreted from astrocytes in the central nervous system (CNS), has been suggested to play a role in synaptogenesis, spine morphology, and synaptic density of neurons. In this study, we investigate the protective role of TSP-1 in the recovery of mitochondrial morphology and function in amyloid β (Aβ)-treated mouse hippocampal neuroblastoma cells (HT22). We observe that TSP-1 inhibits Aβ-induced mitochondrial fission by maintaining phosphorylated-Drp1 (p-Drp1) levels, which results in reduced Drp1 translocation to the mitochondria. By using gabapentin, a drug that antagonizes the interaction between TSP-1 and its neuronal receptor α2δ1, we observe that α2δ1 acts as one of the target receptors for TSP-1, and blocks the reduction of the p-Drp1 to Drp1 ratio, in the presence of Aβ. Taken together, TSP-1 appears to contribute to maintaining the balance in mitochondrial dynamics and mitochondrial functions, which is crucial for neuronal cell viability. These data suggest that TSP-1 may be a potential therapeutic target for AD.
Multiscale analysis of a regenerative therapy for treatment of volumetric muscle loss injury
Authors: Aguilar Carlos A. , Greising Sarah M. , Watts Alain , Goldman Stephen M. , Peragallo Chelsea , Zook Christina , Larouche Jacqueline , Corona Benjamin T.
Published: February 2018

Skeletal muscle possesses a remarkable capacity to regenerate when injured, but when confronted with major traumatic injury resulting in volumetric muscle loss (VML), the regenerative process consistently fails. The loss of muscle tissue and function from VML injury has prompted development of a suite of therapeutic approaches but these strategies have proceeded without a comprehensive understanding of the molecular landscape that drives the injury response. Herein, we administered a VML injury in an established rodent model and monitored the evolution of the healing phenomenology over multiple time points using muscle function testing, histology, and expression profiling by RNA sequencing. The injury response was then compared to a regenerative medicine treatment using orthotopic transplantation of autologous minced muscle grafts (~1 mm3 tissue fragments). A chronic inflammatory and fibrotic response was observed at all time points following VML. These results suggest that the pathological response to VML injury during the acute stage of the healing response overwhelms endogenous and therapeutic regenerative processes. Overall, the data presented delineate key molecular characteristics of the pathobiological response to VML injury that are critical effectors of effective regenerative treatment paradigms.
BIX-01294 sensitizes renal cancer Caki cells to TRAIL-induced apoptosis through downregulation of survivin expression and upregulation of DR5 expression
Authors: Woo Seon Min , Seo Seung Un , Min Kyoung-Jin , Kwon Taeg Kyu
Published: February 2018

BIX-01294 (BIX), a G9a histone methyltransferase inhibitor, has been reported for its anti-proliferative and anticancer activities against various cancer cell lines. In this study, we investigated whether BIX could sensitize TRAIL-mediated apoptosis in various cancer cells. Combined treatment with BIX and TRAIL markedly induced apoptosis in human renal carcinoma (Caki, ACHN, and A498), breast carcinoma (MCF-7), and lung carcinoma (A549) cells. In contrast, BIX and TRAIL co-treatment did not induce apoptosis in normal cells, specifically mouse kidney cell (TCMK-1) and human skin fibroblast (HSF). BIX downregulated protein expression levels of XIAP and survivin at the post-translational level. Overexpression of survivin markedly blocked combined BIX and TRAIL treatment-induced apoptosis, but XIAP had no effect. Furthermore, BIX induced upregulation of DR5 expression at the transcriptional levels, and knockdown of DR5 expression using small interfering RNAs (siRNAs) markedly attenuated BIX and TRAIL-induced apoptosis. Interestingly, siRNA-mediated G9a histone methyltransferase knockdown also enhanced TRAIL-induced apoptosis in Caki cells. However, knockdown of G9a did not change expression levels of XIAP, survivin, and DR5. Therefore, BIX-mediated TRAIL sensitization was independent of histone methyltransferase G9a activity. Taken together, these results suggest that BIX facilitates TRAIL-mediated apoptosis via downregulation of survivin and upregulation of DR5 expression in renal carcinoma Caki cells.

▶ BIX facilitates TRAIL-mediated apoptosis in human renal carcinoma Caki cells.

▶ Downregulation of survivin contributes to BIX plus TRAIL-induced apoptosis.

▶ Upregulation of DR5 is involved in BIX plus TRAIL-mediated apoptosis.

▶ BIX-mediated TRAIL sensitization is independent of ROS production.
Fatty Acid Synthase induced S6Kinase facilitates USP11-eIF4B complex formation for sustained oncogenic translation in DLBCL
Authors: Kapadia Bandish , Nanaji Nahid M. , Bhalla Kavita , Bhandary Binny , Lapidus Rena , Beheshti Afshin , Evens Andrew M. , Gartenhaus Ronald B.
Published: February 2018

Altered lipid metabolism and aberrant protein translation are strongly associated with cancerous outgrowth; however, the inter-regulation of these key processes is still underexplored in diffuse large B-cell lymphoma (DLBCL). Although fatty acid synthase (FASN) activity is reported to positively correlate with PI3K-Akt-mTOR pathway that can modulate protein synthesis, the precise impact of FASN inhibition on this process is still unknown. Herein, we demonstrate that attenuating FASN expression or its activity significantly reduces eIF4B (eukaryotic initiation factor 4B) levels and consequently overall protein translation. Through biochemical studies, we identified eIF4B as a bonafide substrate of USP11, which stabilizes and enhances eIF4B activity. Employing both pharmacological and genetic approaches, we establish that FASN-induced PI3K-S6Kinase signaling phosphorylates USP11 enhancing its interaction with eIF4B and thereby promoting oncogenic translation.
EGFL7 reduces CNS inflammation in mouse
Authors: Larochelle Catherine , Uphaus Timo , Broux Bieke , Gowing Elizabeth , Paterka Magdalena , Michel Laure , Dudvarski Stankovic Nevenka , Bicker Frank , Lemaître Florent , Prat Alexandre , Schmidt Mirko H. H. , Zipp Frauke
Published: February 2018

Extracellular matrix (ECM) proteins secreted by blood-brain barrier (BBB) endothelial cells (ECs) are implicated in cell trafficking. We discovered that the expression of ECM epidermal growth factor-like protein 7 (EGFL7) is increased in the CNS vasculature of patients with multiple sclerosis (MS), and in mice with experimental autoimmune encephalomyelitis (EAE). Perivascular CD4 T lymphocytes colocalize with ECM-bound EGFL7 in MS lesions. Human and mouse activated T cells upregulate EGFL7 ligand αvβ3 integrin and can adhere to EGFL7 through integrin αvβ3. EGFL7-knockout (KO) mice show earlier onset of EAE and increased brain and spinal cord parenchymal infiltration of T lymphocytes. Importantly, EC-restricted EGFL7-KO is associated with a similar EAE worsening. Finally, treatment with recombinant EGFL7 improves EAE, reduces MCAM expression, and tightens the BBB in mouse. Our data demonstrate that EGFL7 can limit CNS immune infiltration and may represent a novel therapeutic avenue in MS.
Gene-by-environment interactions in urban populations modulate risk phenotypes
Authors: Favé Marie-Julie , Lamaze Fabien C. , Soave David , Hodgkinson Alan , Gauvin Héloïse , Bruat Vanessa , Grenier Jean-Christophe , Gbeha Elias , Skead Kimberly , Smargiassi Audrey , Johnson Markey , Idaghdour Youssef , Awadalla Philip
Published: February 2018

Uncovering the interaction between genomes and the environment is a principal challenge of modern genomics and preventive medicine. While theoretical models are well defined, little is known of the G × E interactions in humans. We used an integrative approach to comprehensively assess the interactions between 1.6 million data points, encompassing a range of environmental exposures, health, and gene expression levels, coupled with whole-genome genetic variation. From ∼1000 individuals of a founder population in Quebec, we reveal a substantial impact of the environment on the transcriptome and clinical endophenotypes, overpowering that of genetic ancestry. Air pollution impacts gene expression and pathways affecting cardio-metabolic and respiratory traits, when controlling for genetic ancestry. Finally, we capture four expression quantitative trait loci that interact with the environment (air pollution). Our findings demonstrate how the local environment directly affects disease risk phenotypes and that genetic variation, including less common variants, can modulate individual’s response to environmental challenges.
Effect of friction on oxidative graphite intercalation and high-quality graphene formation
Authors: Seiler Steffen , Halbig Christian E. , Grote Fabian , Rietsch Philipp , Börrnert Felix , Kaiser Ute , Meyer Bernd , Eigler Siegfried
Published: February 2018

Oxidative wet-chemical delamination of graphene from graphite is expected to become a scalable production method. However, the formation process of the intermediate stage-1 graphite sulfate by sulfuric acid intercalation and its subsequent oxidation are poorly understood and lattice defect formation must be avoided. Here, we demonstrate film formation of micrometer-sized graphene flakes with lattice defects down to 0.02% and visualize the carbon lattice by transmission electron microscopy at atomic resolution. Interestingly, we find that only well-ordered, highly crystalline graphite delaminates into oxo-functionalized graphene, whereas other graphite grades do not form a proper stage-1 intercalate and revert back to graphite upon hydrolysis. Ab initio molecular dynamics simulations show that ideal stacking and electronic oxidation of the graphite layers significantly reduce the friction of the moving sulfuric acid molecules, thereby facilitating intercalation. Furthermore, the evaluation of the stability of oxo-species in graphite sulfate supports an oxidation mechanism that obviates intercalation of the oxidant.
The interdependence of excitation and inhibition for the control of dynamic breathing rhythms
Authors: Baertsch Nathan Andrew , Baertsch Hans Christopher , Ramirez Jan Marino
Published: February 2018

The preBötzinger Complex (preBötC), a medullary network critical for breathing, relies on excitatory interneurons to generate the inspiratory rhythm. Yet, half of preBötC neurons are inhibitory, and the role of inhibition in rhythmogenesis remains controversial. Using optogenetics and electrophysiology in vitro and in vivo, we demonstrate that the intrinsic excitability of excitatory neurons is reduced following large depolarizing inspiratory bursts. This refractory period limits the preBötC to very slow breathing frequencies. Inhibition integrated within the network is required to prevent overexcitation of preBötC neurons, thereby regulating the refractory period and allowing rapid breathing. In vivo, sensory feedback inhibition also regulates the refractory period, and in slowly breathing mice with sensory feedback removed, activity of inhibitory, but not excitatory, neurons restores breathing to physiological frequencies. We conclude that excitation and inhibition are interdependent for the breathing rhythm, because inhibition permits physiological preBötC bursting by controlling refractory properties of excitatory neurons.
Comprehensive integrative analyses identify GLT8D1 and CSNK2B as schizophrenia risk genes
Authors: Yang Cui-Ping , Li Xiaoyan , Wu Yong , Shen Qiushuo , Zeng Yong , Xiong Qiuxia , Wei Mengping , Chen Chunhui , Liu Jiewei , Huo Yongxia , Li Kaiqin , Xue Gui , Yao Yong-Gang , Zhang Chen , Li Ming , Chen Yongbin , Luo Xiong-Jian
Published: February 2018

Recent genome-wide association studies (GWAS) have identified multiple risk loci that show strong associations with schizophrenia. However, pinpointing the potential causal genes at the reported loci remains a major challenge. Here we identify candidate causal genes for schizophrenia using an integrative genomic approach. Sherlock integrative analysis shows that ALMS1, GLT8D1, and CSNK2B are schizophrenia risk genes, which are validated using independent brain expression quantitative trait loci (eQTL) data and integrative analysis method (SMR). Consistently, gene expression analysis in schizophrenia cases and controls further supports the potential role of these three genes in the pathogenesis of schizophrenia. Finally, we show that GLT8D1 and CSNK2B knockdown promote the proliferation and inhibit the differentiation abilities of neural stem cells, and alter morphology and synaptic transmission of neurons. These convergent lines of evidence suggest that the ALMS1, CSNK2B, and GLT8D1 genes may be involved in pathophysiology of schizophrenia.
Superplastic nanoscale pore shaping by ion irradiation
Authors: Aramesh Morteza , Mayamei Yashar , Wolff Annalena , Ostrikov Kostya
Published: February 2018

Exposed to ionizing radiation, nanomaterials often undergo unusual transformations compared to their bulk form. However, atomic-level mechanisms of such transformations are largely unknown. This work visualizes and quantifies nanopore shrinkage in nanoporous alumina subjected to low-energy ion beams in a helium ion microscope. Mass transport in porous alumina is thus simultaneously induced and imaged with nanoscale precision, thereby relating nanoscale interactions to mesoscopic deformations. The interplay between chemical bonds, disorders, and ionization-induced transformations is analyzed. It is found that irradiation-induced diffusion is responsible for mass transport and that the ionization affects mobility of diffusive entities. The extraordinary room temperature superplasticity of the normally brittle alumina is discovered. These findings enable the effective manipulation of chemical bonds and structural order by nanoscale ion-matter interactions to produce mesoscopic structures with nanometer precision, such as ultra-high density arrays of sub-10-nm pores with or without the accompanying controlled plastic deformations.
Scalable on-chip quantum state tomography
Authors: Titchener James G. , Gräfe Markus , Heilmann René , Solntsev Alexander S. , Szameit Alexander , Sukhorukov Andrey A.
Published: February 2018

Quantum information systems are on a path to vastly exceed the complexity of any classical device. The number of entangled qubits in quantum devices is rapidly increasing, and the information required to fully describe these systems scales exponentially with qubit number. This scaling is the key benefit of quantum systems, however it also presents a severe challenge. To characterize such systems typically requires an exponentially long sequence of different measurements, becoming highly resource demanding for large numbers of qubits. Here we propose and demonstrate a novel and scalable method for characterizing quantum systems based on expanding a multi-photon state to larger dimensionality. We establish that the complexity of this new measurement technique only scales linearly with the number of qubits, while providing a tomographically complete set of data without a need for reconfigurability. We experimentally demonstrate an integrated photonic chip capable of measuring two- and three-photon quantum states with statistical reconstruction fidelity of 99.71%.
A personalized, multiomics approach identifies genes involved in cardiac hypertrophy and heart failure
Authors: Santolini Marc , Romay Milagros C. , Yukhtman Clara L. , Rau Christoph D. , Ren Shuxun , Saucerman Jeffrey J. , Wang Jessica J. , Weiss James N. , Wang Yibin , Lusis Aldons J. , Karma Alain
Published: February 2018

A traditional approach to investigate the genetic basis of complex diseases is to identify genes with a global change in expression between diseased and healthy individuals. However, population heterogeneity may undermine the effort to uncover genes with significant but individual contribution to the spectrum of disease phenotypes within a population. Here we investigate individual changes of gene expression when inducing hypertrophy and heart failure in 100 + strains of genetically distinct mice from the Hybrid Mouse Diversity Panel (HMDP). We find that genes whose expression fold-change correlates in a statistically significant way with the severity of the disease are either up or down-regulated across strains, and therefore missed by a traditional population-wide analysis of differential gene expression. Furthermore, those “fold-change” genes are enriched in human cardiac disease genes and form a dense co-regulated module strongly interacting with the cardiac hypertrophic signaling network in the human interactome. We validate our approach by showing that the knockdown of Hes1, predicted as a strong candidate, induces a dramatic reduction of hypertrophy by 80–90% in neonatal rat ventricular myocytes. Our results demonstrate that individualized approaches are crucial to identify genes underlying complex diseases as well as to develop personalized therapies.
Fe-oxide mineralogy of the Jiujiang red earth sediments and implications for Quaternary climate change, southern China
Authors: Yin Ke , Hong Hanlie , Algeo Thomas J. , Churchman Gordon Jock , Li Zhaohui , Zhu Zongmin , Fang Qian , Zhao Lulu , Wang Chaowen , Ji Kaipeng , Lei Weidong , Duan Zhenggang
Published: February 2018

Diffuse reflectance spectrophotometry (DRS) is a new, fast, and reliable method to characterize Fe-oxides in soils. The Fe-oxide mineralogy of the Jiujiang red earth sediments was investigated using DRS to investigate the climate evolution of southern China since the mid-Pleistocene. The DRS results show that hematite/(hematite + goethite) ratios [Hm/(Hm + Gt)] exhibit an upward decreasing trend within the Jiujiang section, suggesting a gradual climate change from warm and humid in the middle Pleistocene to cooler and drier in the late Pleistocene. Upsection trends toward higher (orthoclase + plagioclase)/quartz ratios [(Or + Pl)/Q] and magnetic susceptibility values (χlf) support this inference, which accords with global climate trends at that time. However, higher-frequency climatic subcycles observed in loess sections of northern China are not evident in the Jiujiang records, indicating a relatively lower climate sensitivity of the red earth sediments in southern China.
Improving prediction of heart transplantation outcome using deep learning techniques
Authors: Medved Dennis , Ohlsson Mattias , Höglund Peter , Andersson Bodil , Nugues Pierre , Nilsson Johan
Published: February 2018

The primary objective of this study is to compare the accuracy of two risk models, International Heart Transplantation Survival Algorithm (IHTSA), developed using deep learning technique, and Index for Mortality Prediction After Cardiac Transplantation (IMPACT), to predict survival after heart transplantation. Data from adult heart transplanted patients between January 1997 to December 2011 were collected from the UNOS registry. The study included 27,860 heart transplantations, corresponding to 27,705 patients. The study cohorts were divided into patients transplanted before 2009 (derivation cohort) and from 2009 (test cohort). The receiver operating characteristic (ROC) values, for the validation cohort, computed for one-year mortality, were 0.654 (95% CI: 0.629–0.679) for IHTSA and 0.608 (0.583–0.634) for the IMPACT model. The discrimination reached a C-index for long-term survival of 0.627 (0.608–0.646) for IHTSA, compared with 0.584 (0.564–0.605) for the IMPACT model. These figures correspond to an error reduction of 12% for ROC and 10% for C-index by using deep learning technique. The predicted one-year mortality rates for were 12% and 22% for IHTSA and IMPACT, respectively, versus an actual mortality rate of 10%. The IHTSA model showed superior discriminatory power to predict one-year mortality and survival over time after heart transplantation compared to the IMPACT model.
MicroRNA Contents in Matrix Vesicles Produced by Growth Plate Chondrocytes are Cell Maturation Dependent
Authors: Lin Zhao , McClure Michael J. , Zhao Junjun , Ramey Allison N. , Asmussen Niels , Hyzy Sharon L. , Schwartz Zvi , Boyan Barbara D.
Published: February 2018

Chondrocytes at different maturation states in the growth plate produce matrix vesicles (MVs), membrane organelles found in the extracellular matrix, with a wide range of contents, such as matrix processing enzymes and receptors for hormones. We have shown that MVs harvested from growth zone (GC) chondrocyte cultures contain abundant small RNAs, including miRNAs. Here, we determined whether RNA also exists in MVs produced by less mature resting zone (RC) chondrocytes and, if so, whether it differs from the RNA in MVs produced by GC cells. Our results showed that RNA, small RNA specifically, was present in RC-MVs, and it was well-protected from RNase by the phospholipid membrane. A group of miRNAs was enriched in RC-MVs compared RC-cells, suggesting that miRNAs are selectively packaged into MVs. High throughput array and RNA sequencing showed that ~39% miRNAs were differentially expressed between RC-MVs and GC-MVs. Individual RT-qPCR also confirmed that miR-122-5p and miR-150-5p were expressed at significantly higher levels in RC-MVs compared to GC-MVs. This study showed that growth plate chondrocytes at different differentiation stages produce different MVs with different miRNA contents, further supporting extracellular vesicle miRNAs play a role as “matrisomes” that mediate the cell–cell communication in cartilage and bone development.
High motor variability in DYT1 dystonia is associated with impaired visuomotor adaptation
Authors: Sadnicka Anna , Stevenson Anna , Bhatia Kailash P. , Rothwell John C. , Edwards Mark J. , Galea Joseph M.
Published: February 2018

For the healthy motor control system, an essential regulatory role is maintaining the equilibrium between keeping unwanted motor variability in check whilst allowing informative elements of motor variability. Kinematic studies in children with generalised dystonia (due to mixed aetiologies) show that movements are characterised by increased motor variability. In this study, the mechanisms by which high motor variability may influence movement generation in dystonia were investigated. Reaching movements in the symptomatic arm of 10 patients with DYT1 dystonia and 12 age-matched controls were captured using a robotic manipulandum and features of motor variability were extracted. Given that task-relevant variability and sensorimotor adaptation are related in health, markers of variability were then examined for any co-variance with performance indicators during an error-based learning visuomotor adaptation task. First, we confirmed that motor variability on a trial-by-trial basis was selectively increased in the homogenous and prototypical dystonic disorder DYT1 dystonia. Second, high baseline variability predicted poor performance in the subsequent visuomotor adaptation task offering insight into the rules which appear to govern dystonic motor control. The potential mechanisms behind increased motor variability and its corresponding implications for the rehabilitation of patients with DYT1 dystonia are highlighted.
Cytoplasmic Transport Machinery of the SPF27 Homologue Num1 in Ustilago maydis
Authors: Zhou Lu , Obhof Theresa , Schneider Karina , Feldbrügge Michael , Nienhaus G. Ulrich , Kämper Jörg
Published: February 2018

In the phytopathogenic basidiomycete Ustilago maydis, the Num1 protein has a pivotal function in hyphal morphogenesis. Num1 functions as a core component of the spliceosome-associated Prp19/CDC5 complex (NTC). The interaction of Num1 with the kinesin motor Kin1 suggests a connection between a component of the splicing machinery and cytoplasmic trafficking processes. Previously it was shown that Num1 localizes predominantly in the nucleus; however, due to the diffraction-limited spatial resolution of conventional optical microscopy, it was not possible to attribute the localization to specific structures within the cytoplasm. We have now employed super-resolution localization microscopy to visualize Num1 in the cytoplasm by fusing it to a tandem dimeric Eos fluorescent protein (tdEosFP). The Num1 protein is localized within the cytoplasm with an enhanced density in the vicinity of microtubules. Num1 movement is found predominantly close to the nucleus. Movement is dependent on its interaction partner Kin1, but independent of Kin3. Our results provide strong evidence that, in addition to its involvement in splicing in the nucleus, Num1 has an additional functional role in the cytosol connected to the Kin1 motor protein.
Linear Micro-patterned Drug Eluting Balloon (LMDEB) for Enhanced Endovascular Drug Delivery
Authors: Lee KangJu , Lee Seul Gee , Jang Ilkwang , Park Seung Hyun , Yang Dasom , Seo Il Ho , Bong Sung-Kyung , An Duk Hwan , Lee Min Kwon , Jung In Kwon , Jang Yong Hoon , Kim Jung Sun , Ryu WonHyoung
Published: February 2018

In-stent restenosis (ISR) often occurs after applying drug eluting stents to the blood vessels suffering from atherosclerosis or thrombosis. For treatment of ISR, drug eluting balloons (DEB) have been developed to deliver anti-proliferative drugs to the lesions with ISR. However, there are still limitations of DEB such as low drug delivery efficiency and drug loss to blood flow. Although most researches have focused on alteration of drug formulation for more efficient drug delivery, there are few studies that have attempted to understand and utilize the contact modality of DEB drug delivery. Here, we developed a linear micro-patterned DEB (LMDEB) that applied higher contact pressure to enhance drug stamping to vascular tissue. Ex vivo and in vivo studies confirmed that higher contact pressure from micro-patterns increased the amount of drug delivered to the deeper regions of vessel. Finite element method simulation also showed significant increase of contact pressure between endothelium and micro-patterns. Quantitative analysis by high performance liquid chromatography indicated that LMDEBs delivered 2.3 times higher amount of drug to vascular tissue in vivo than conventional DEBs. Finally, efficacy studies using both atherosclerotic and ISR models demonstrated superior patency of diseased vessels treated with LMDEB compared to those treated with DEB.
Heterogeneous localisation of membrane proteins in Staphylococcus aureus
Authors: Weihs Felix , Wacnik Katarzyna , Turner Robert D. , Culley Siân , Henriques Ricardo , Foster Simon J.
Published: February 2018

The bacterial cytoplasmic membrane is the interface between the cell and its environment, with multiple membrane proteins serving its many functions. However, how these proteins are organised to permit optimal physiological processes is largely unknown. Based on our initial findings that 2 phospholipid biosynthetic enzymes (PlsY and CdsA) localise heterogeneously in the membrane of the bacterium Staphylococcus aureus, we have analysed the localisation of other key membrane proteins. A range of protein fusions were constructed and used in conjunction with quantitative image analysis. Enzymes involved in phospholipid biosynthesis as well as the lipid raft marker FloT exhibited a heterogeneous localisation pattern. However, the secretion associated SecY protein, was more homogeneously distributed in the membrane. A FRET-based system also identified novel colocalisation between phospholipid biosynthesis enzymes and the respiratory protein CydB revealing a likely larger network of partners. PlsY localisation was found to be dose dependent but not to be affected by membrane lipid composition. Disruption of the activity of the essential cell division organiser FtsZ, using the inhibitor PC190723 led to loss of PlsY localisation, revealing a link to cell division and a possible role for FtsZ in functions not strictly associated with septum formation.
The Cue-Approach Task as a General Mechanism for Long-Term Non-Reinforced Behavioral Change
Authors: Salomon Tom , Botvinik-Nezer Rotem , Gutentag Tony , Gera Rani , Iwanir Roni , Tamir Maya , Schonberg Tom
Published: February 2018

Recent findings show that preferences for food items can be modified without external reinforcements using the cue-approach task. In the task, the mere association of food item images with a neutral auditory cue and a speeded button press, resulted in enhanced preferences for the associated stimuli. In a series of 10 independent samples with a total of 255 participants, we show for the first time that using this non-reinforced method we can enhance preferences for faces, fractals and affective images, as well as snack foods, using auditory, visual and even aversive cues. This change was highly durable in follow-up sessions performed one to six months after training. Preferences were successfully enhanced for all conditions, except for negative valence items. These findings promote our understanding of non-reinforced change, suggest a boundary condition for the effect and lay the foundation for development of novel applications.
Dynamic control of particle separation in deterministic lateral displacement separator with viscoelastic fluids
Authors: Li Yuke , Zhang Hongna , Li Yongyao , Li Xiaobin , Wu Jian , Qian Shizhi , Li Fengchen
Published: February 2018

We proposed an innovative method to achieve dynamic control of particle separation by employing viscoelastic fluids in deterministic lateral displacement (DLD) arrays. The effects of shear-thinning and elasticity of working fluids on the critical separation size in DLD arrays are investigated. It is observed that each effect can lead to the variation of the critical separation size by approximately 40%. Since the elasticity strength of the fluid is related to the shear rate, the dynamic control can for the first time be easily realized through tuning the flow rate in microchannels.
Selective state spectroscopy and multifractality in disordered Bose-Einstein condensates: a numerical study
Authors: Werner Miklós Antal , Demler Eugene , Aspect Alain , Zaránd Gergely
Published: February 2018

We propose to apply a modified version of the excitation scheme introduced by Volchkov et al. on bosons experiencing hyperfine state dependent disorder to address the critical state at the mobility edge of the Anderson localization transition, and to observe its intriguing multifractal structure. An optimally designed, spatially focused external radio frequency pulse can be applied to generate transitions to eigenstates in a narrow energy window close to the mobility edge, where critical scaling and multifractality emerge. Alternatively, two-photon laser scanning microscopy is proposed to address individual localized states even close to the transition. The projected image of the cloud is shown to inherit multifractality and to display universal density correlations. Interactions – unavoidably present – are taken into account by solving the Gross-Pitaevskii equations, and their destructive effect on the spectral resolution and the multifractal spectrum is analyzed. Time of flight images of the excited states are predicted to show interference fringes in the localized phase, while they allow one to map equal energy surfaces deep in the metallic phase.
Factors influencing intention to obtain the HPV vaccine in South East Asian and Western Pacific regions: A systematic review and meta-analysis
Authors: Santhanes Diviya , Yong Che Pui , Yap Yan Ye , Saw Pui San , Chaiyakunapruk Nathorn , Khan Tahir Mehmood
Published: February 2018

Since licensing in 2006, there has been poor uptake of the HPV vaccine among the targeted population in the South East Asia Region (SEAR) and Western Pacific Region (WPR). A systematic review was conducted to identify the studies exploring the relationship between factors and intention for HPV vaccination among women in SEAR and WPR countries. Nineteen studies were identified as suitable for qualitative synthesis, and three as suitable for meta-analysis. Most women had a positive intention to have an HPV vaccine (range 57%–85%). Having a positive intention to vaccinate was significantly higher among women not aware of HPV infection (OR: 1.34, 95% CI: 1.02–1.76) and HPV vaccine (OR: 1.57, 95% CI: 1.26–1.96). Lower knowledge level and less confidence in safety and efficacy of the vaccine, negatively affected intention to vaccinate. Perceiving the vaccine to be expensive, low perception of contracting HPV infection and cervical cancer, and lack of concrete recommendations from healthcare providers also negatively affected intention to vaccinate. This review suggests the decision-making processes of women in SEAR and WPR is influenced by the cost of vaccination, perceived efficacy and safety of vaccine, provision of information on vaccination, and the awareness about HPV infection and the HPV vaccine.
Clinical Utility of FDG PET/CT in Patients with Autoimmune Pancreatitis: a Case-Control Study
Authors: Cheng Mei-Fang , Guo Yue Leon , Yen Ruoh-Fang , Chen Yi-Chieh , Ko Chi-Lun , Tien Yu-Wen , Liao Wei-Chih , Liu Chia-Ju , Wu Yen-Wen , Wang Hsiu-Po
Published: February 2018

Autoimmune pancreatitis (AIP) shares overlapping clinical features with pancreatic cancer (PC). Importantly, treatment of the two conditions is different. We investigated the clinical usefulness of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in patients with suspected AIP before treatment. From September 2008 to July 2016, 53 patients with suspected AIP at National Taiwan University Hospital had PET/CT prior to therapy to exclude malignancy and evaluate the extent of inflammation. Their scans were compared with those from 61 PC patients. PET imaging features were analyzed using logistic regression. Significant differences in pancreatic tumor uptake morphology, maximum standardized uptake value, high-order primary tumor texture feature (i.e. high-gray level zone emphasis value), and numbers and location of extrapancreatic foci were found between AIP and PC. Using the prediction model, the area under curve of receiver-operator curve was 0.95 (P < 0.0001) with sensitivity, specificity, positive predictive, and negative predictive values of 90.6%, 84.0%, 87.9%, and 87.5% respectively, in differentiating AIP from PC. FDG PET/CT offers high sensitivity, albeit slightly lower specificity in differentiating AIP from PC. Nonetheless, additional systemic inflammatory foci detected by the whole body PET/CT help confirm diagnosis of AIP in these patients before initiating steroid therapy, especially when biopsy is inconclusive.