bluuebunny/crossref_metadata_2025 huggingface dataset:
Clares Clares, Mª E. (2017). Música y noches de moda. Sociedades, cafés y salones domésticos de Murcia en el siglo XIX. Murcia: Universidad de Murcia, Servicio de Publicaciones. 474 págs.
Authors: Micó Terol Elena
Published: September 2019

El Servicio de publicaciones de la Universidad de Murcia ha editado Música y noches de moda. Sociedades, cafés y salones domésticos de Murcia en el siglo XIX, trabajo imprescindible para comprender los hábitos musicales de socialización de los murcianos durante la centuria decimonónica. El mismo título, Música y noches de moda, inspirado en el lenguaje periodístico del momento, como indica la propia autora, nos sitúa en la esencia de la obra. El objetivo principal de este trabajo es estudiar la música que se generó y consumió en los salones de asociaciones culturales, casas particulares y cafés de la Murcia del siglo XIX. Estos núcleos de producción y consumo musical, extraordinariamente dinámicos, fueron también espacios idóneos para la enseñanza de la música y de la cultura en general, como ha quedado patente en el trabajo de la Dra. Clares.
Memoria cultural en el Egipto Faraónico. Algunas reflexiones sobre su origen, función y pervivencia histórica.
Authors: Pérez Largacha Antonio
Published: September 2019

Los estudios de J. Assmann sobre las características que tiene la memoria cultural en las primeras civilizaciones han originado diferentes debates además de haber abierto nuevas líneas de investigación. En este trabajo analizaremos qué se entiende por memoria cultural para, posteriormente, buscar los orígenes de dicha memoria cultural del Egipto Faraónico cuando apareció el Estado y en tiempos predinásticos. Con posterioridad comprobaremos cómo la memoria cultural pervivió en el Egipto faraónico a lo largo de más tres mil años de historia. Una memoria cultural que se transmitió a través de los textos y, especialmente, de una forma visual con los monumentos, funerarios o no, que transmitían no solo unas creencias funerarias, también una concepción del mundo en el que los antiguos egipcios vivieron. La estrecha relación que existió entre dicha memoria cultural y lo que los antiguos egipcios veían en su entorno explica la perdurabilidad, no solo de sus creencias, también de una civilización que fue capaz de emitir unos mensajes que eran entendidos por todos los miembros de la sociedad.

J. Assmann’s studies on the characteristics observed by the phenomenon known as cultural memory in the earliest civilizations have given rise to various debates and, at the same time, it has opened new lines of research. In this paper, we shall discuss the concept of cultural memory in the Pharaonic Egypt and its origin in predynastic times and whe the State was created. Pharaonic Egypt. A cultural memory that survived through over three thousand years of history. A cultural memory which was transmitted through the texts and, especially, in a visual way with the monuments, funerary or not, that transmitted not only religious beliefs, but also a conception of the world in which the ancient Egyptians lived. The close relationship which existed between the aforementioned cultural memory and what the ancient Egyptians saw in their environment, explain the strength not only of their beliefs, but also of a civilization that was able to emit messages that were understood by all the members of the society.
La “Sala del Fresco” de Micenas. Revisión de las interpretaciones del programa iconográfico y nueva lectura en relación a los espacios.
Authors: Huerta Segovia Pelayo
Published: September 2019

En el presente estudio se aborda el programa iconográfico de la “Sala del Fresco” de Micenas con el objetivo de entender el significado de las pinturas, el propósito por el cual fueron concebidas, así como su relación con la actividad ritual del lugar. Para ello, revisando las teorías existentes, se procederá al análisis y a la interpretación de cada una de las figuras y de los motivos decorativos. Por último, se atiende al contexto arqueológico de la estancia y del resto de espacios con el fin de establecer un posible vínculo con otras salas vecinas del “Centro cultual”, cuya relación es clave para una nueva lectura de las pinturas.

The present study addresses the iconographic program of the ‘Room 31’ at Mycenae with the aim of understanding the meaning of the paintings, the purpose for which they were created as well as their relationship with the ritual activity carried out in the place. To that end, while reviewing the existing theories, we will proceed to the analysis and interpretation of each figure and the decorative motifs. To conclude, we will keep in mind the archaeological context of the room and the rest of the spaces in order to determinate a possible link with other nearby rooms of the ‘Cultual Center’, whose relationship is essential to give a new interpretation of the paintings.
Changes in the command and control potential of European cities in 2006-2016
Authors: Dorocki Sławomir , Raźniak Piotr , Winiarczyk-Raźniak Anna
Published: September 2019

The aim of the study was to analyze changes in the command and control functions of cities in 2006 and 2016 based on the method of gravity centers. The analysis was performed both for individual sectors of the economy as well as for the European economy as a whole. The shift in the center of gravity of the studied command and control functions of cities in the direction of Central Eastern Europe is examined in the paper. The fairly recent development of CEE and European integration increasing to the east and south has triggered the relocation of many companies from west to east and has also increased the importance of local companies. It may therefore be argued that the importance of the command and control functions of cities in developing countries has also increased (Poland, Russia). There is also a related decline in the importance of the so-called blue banana region and cities in Great Britain and Germany. This is especially visible in terms of the number of corporate headquarters in the western part of the continent. However, the shift in capital is not that clear – and both German and British corporations still remain the leaders in Europe.
Le contrat intelligent, nouveau vecteur de confiance dans les relations contractuelles : réalité ou rêve ?
Authors: Moradinejad Reza
Published: September 2019

L’objectif de l’article qui suit est d’apprécier le potentiel du contrat intelligent pour devenir un nouveau vecteur de confiance dans le domaine contractuel. Pour ce faire, l’auteur présente et analyse ce phénomène récent ayant émergé à la marge de l’essor de la technologie de la chaîne de blocs (blockchain). Le contrat intelligent est le fruit de l’utilisation de deux procédés techniques : l’informatisation du contenu contractuel et le recours à la technologie de la chaîne de blocs. Ces deux initiatives ont donné naissance à un contrat infalsifiable dont l’exécution se révèle automatique et transparente. Même si le contrat intelligent, en raison notamment de limites inhérentes à l’informatisation du contenu contractuel, ne peut pas apporter une solution définitive au problème de confiance, force est de constater qu’en améliorant la transparence et en garantissant l’exécution conforme du contrat, lorsque cela est possible techniquement, il peut contribuer positivement au rétablissement du climat de confiance entre les parties.
Bacillus induced to biosynthesize VOCs & nitriles may benefit agriculture.
Authors: Perry Guenevere , Perry Diane
Published: September 2019

The scope of the project was to identify the possible agricultural applications for bacteria induced to synthesize nitriles and VOCs. The study was randomized. Cucurbit seeds and Bacillus licheniformis were selected as the plant and microbial models for two trial studies. In trial 1, 90 cucumber seeds were cultured with B.licheniformis induced to synthesize VOCs (including ethanol, 3-methyl-1-butanol, pentanol), esters (ethyl acetate), and acetonitriles. After 2 weeks the induced bacteria increased seed germination by 68% compared to control samples. Several seedlings were transferred to a small garden, infested with soil nematodes. Roots of control and induced samples appeared affected. Control samples appeared stunted in growth with decreased productivity, but cucumber plants initially planted with induced bacteria were noticeably larger in size with good productivity. Induced Bacillus increased the number of blossoms and cucumber per plant by 125% compared to control samples. Induced Bacillus did not increase solubility of nitrogen, phosphorous, or potassium in the soil, but appeared to increase plant health and defenses against pathogenic infections. Though the study findings are preliminary, soil microbes induced to synthesize VOCs and nitriles may improve plant health and productivity in cucurbit plants.
Geochemical study of Central-Eastern Lombard Prealps mineral and thermal springs
Authors: Brozzo Gianpiero
Published: September 2019

Geochemical characteristics of mineralized waters of Central Eastern Lombard Prealps (Italy) have been studied with specific attention to processes that originate waters with a complex composition. To achieve the objectives of this study, 34 samples of mineral waters were collected in the area of interest. These samples were analyzed for determination of main cations, anions and some trace elements. Elaboration of analytical data allowed to classify the waters, to identify geochemical processes that originate them and to simulate reaction paths of the different water groups. Reaction paths have been simulated with PhreeqcI geochemical software related to: (i) the evolutionary paths related to the dedolomitization process that starting from with bicarbonate-calcium waters originates sulphate-calcium waters with high magnesium contents (Boario, Angolo, Tartavalle and Salice di Prestine mineral waters), (ii) the processes that generate sulphate-calcic waters that flow from the chalky outcrops of the Brembana and Camonica valleys and (iii) the processes that give rise to the basic sulphurous waters with bicarbonatesodium composition of the Imagna, Brembilla and Cavallina valleys. Finally, by means of geothermometric techniques and mixing models, San Pellegrino and Bracca thermal waters have been studied: temperature of the thermal reservoir that feeds them has been calculated and its depth has been estimated based on local geothermal gradient.
Hydrogeochemical and hydrodynamic features affecting redox processes in groundwater
Authors: Di Curzio Diego
Published: September 2019

This research deals with some hydrogeochemical and hydrodynamic features that affect redox processes in groundwater, presenting three different case studies and methodological approaches. This information is vital when characterizing contaminated sites, planning monitoring, selecting remedial techniques, and assessing health risks. In the San Pedro Sula site case study (Honduras), new insights and an advanced method for the aquifer redox zonation were provided. The Multi-Collocated Factorial Kriging, a multivariate geostatistical technique borrowed from agriculture and soil science, identified simultaneous redox processes, acting at different scales and mainly due to eutrophicated surface-water/groundwater interaction: at short-range, Mn oxihydroxide reductive dissolution and Fe oxi-hydroxide colloidal phase precipitation; at long-range, Fe mobilization. The obtained results are supported by the Principal Component Analysis and hydrogeochemical numerical modeling. The interaction among different contamination events in the VR site allowed to get a deeper insight into the competition for organic substrate among different redox processes. To this purpose, a 1-D Advective-Reactive- Dispersive transport numerical model was implemented, and its results highlighted that the reductive dechlorination is inhibited by the inorganic Terminal Electron Accepting Processes, enriching groundwater in highly toxic by-products of the reductive dechlorination (i.e. Vinyl Chloride). As a matter of fact, the bacteria using inorganic Terminal Electron Acceptors to oxidize the organic substrate are more efficient than the halo-respiring bacteria, that favor reductive dechlorination. The contaminated site of Bussi Officine case study allowed to clarify the hydrodynamic effect on the redox processes and the anoxic condition distribution. The comparison between dissolved chlorinated solvents and the inorganic Terminal Electron Acceptors distribution in the aquifer pointed out that dispersion inhibits all the redox processes because it dilutes the organic substrate concentration in groundwater. On the other hand, the lacustrine deposits rich organic matter (i.e. peat) can be considered as “chemical reactors”, that releases by back-diffusion toxic by-product of the reductive dichlorination in groundwater.
Evaluation of Relation between Medications and Demography of Patients Committing Suicide
Authors: Ghaffarzad Amir , Naderi Zeynab , Shams Vahdati Samad , Habibollahi Paria , Asadollahi Roya
Published: September 2019

Objective: Suicide is a kind of malicious violence, with the most direct and indirect victims of it being women. Since suicide is a repetitive act, it is important to identify the abundance and types of common violence and the factors leading to it. Therefore, this study examined the season and the most commonly used drug among suicide cases referred to Sina Hospital. Materials and Methods: This descriptive cross-sectional study was performed on all patients who were admitted to Sina Hospital in Tabriz by suicide detection in 1395. At the beginning of the study, a checklist was designed to collect information from the patients ‘files from the patients’ files. The patients were asked about the age, occupation, educational level, type of drug, visitation period, previous intervention and history of psychiatric illnesses. The outcome of the study was also evaluated in this study. Finally, all information was analyzed using SPSS software version 18 and statistical methods. Results: This study was conducted in one from March 2016 to March 2017, and on the data of 1176 suicides. The mean age of the patients was 30.98 ± 13.03 years and 58.9% were female. 52% were single, 4.8% had a positive history of neurological diseases and 11.4% had previous suicidal experiences, 36.66% had only one occurrence of suicidal attempts. The winter with 33.1% of the most commonly visited seasons and benzodiazepines with 34.9% were the most commonly used drug among patients. Finally, 6.5% of the patients died in the hospital. Conclusion: The results of this study showed that benzodiazepine was the most commonly used drug for suicidal patients, and winter showed the highest suicide rate.
Methods of Preventing Hospital Acquired Infection
Authors: Javadi Bashar Felor
Published: September 2019

Hospital-acquired infections can increase the rate of morbidity and mortality as well as medical costs. Nosocomial infection is spread by various ways such as surgical, intravenous catheters, surface contact (like as hands) and also through the air. Some interventions include appropriate hand and surface decontamination, sufficient staffing, improved ventilator management, usage of coated central venous and urinary catheters have all been linked with considerably lower rate of nosocomial infection. Multiple interventions simultaneously are required for comprehensive infection control and multiple actions may be given better outcome rather than a single action. Some multiple infection control protocols will possibly show more effective result instead of employing a single or few strategies. Several non-pharmacological interventions to prevent HAIs will reduce the requirement for prolonged or multiple-drug antibiotic courses for infected patients. And lower antibiotic usage will decrease risk of antibiotic-resistant organisms and may improve effectiveness of antibiotics therapy to patients with acquired infections.
Agreement between Impression of Stroke in the Emergency Department and Diagnosis at the Neurology Department
Authors: Shams-Vahdati Samad , Ala Alireza , Sadeghi-Hokmabad Eliar , Parnianfard Neda , Gheybi Maedeh , Ahmadi Sepehri Nasim
Published: September 2019

Background: Missing to detect an ischemic stroke in the emergency department leads to miss acute interventions and treatment with secondary prevention therapy. Our study examined the diagnosis of stroke in the emergency department (ED) and neurology department of an academic teaching hospital. Methods and Materials: A retrospective chart review was performed from March 2017 to March 2018. ED medical document (chart) were reviewed by a stroke neurologist to collect the clinical diagnosis and characteristics of ischemic stroke patients. For determining the cases of misdiagnosed and over diagnosed data, the administrative data codes were compared with the chart adjudicated diagnosis. The adjusted estimate of effect was estimated through testing the significant variables in a multivariable model. The comparisons were done with chi square test. Statistical significance was considered at P < 0.05. Results: Of 861 patients of the study, 54% were males and 43% were females; and the mean age of them was 66.51 ± 15.70. We find no statically significant difference between patient’s Glasgow Coma Scale (GCS) in the emergency department (12.87±3.25) and patients GCS in the neurology department (11.77±5.15). There were 18 (2.2%) overdiagnosed of ischemic stroke, 8 (0.9%) misdiagnosed of ischemic stroke and 36 (4.1%) misdiagnosed of hemorrhagic strokes in the emergency department. Conclusion: There was no significant difference between impression of stroke in the emergency department and diagnosis at the neurology department.
Computational analysis of functional SNPs in Alzheimer’s disease-associated endocytosis genes
Authors: Tey Han Jieh , Ng Chong Han
Published: September 2019

Background

From genome wide association studies on Alzheimer’s disease (AD), it has been shown that many single nucleotide polymorphisms (SNPs) of genes of different pathways affect the disease risk. One of the pathways is endocytosis, and variants in these genes may affect their functions in amyloid precursor protein (APP) trafficking, amyloid-beta (Aβ) production as well as its clearance in the brain. This study uses computational methods to predict the effect of novel SNPs, including untranslated region (UTR) variants, splice site variants, synonymous SNPs (sSNPs) and non-synonymous SNPs (nsSNPs) in three endocytosis genes associated with AD, namely PICALM, SYNJ1 and SH3KBP1.

Materials and Methods

All the variants’ information was retrieved from the Ensembl genome database, and then different variation prediction analyses were performed. UTRScan was used to predict UTR variants while MaxEntScan was used to predict splice site variants. Meta-analysis by PredictSNP2 was used to predict sSNPs. Parallel prediction analyses by five different software packages including SIFT, PolyPhen-2, Mutation Assessor, I-Mutant2.0 and SNPs&GO were used to predict the effects of nsSNPs. The level of evolutionary conservation of deleterious nsSNPs was further analyzed using ConSurf server. Mutant protein structures of deleterious nsSNPs were modelled and refined using SPARKS-X and ModRefiner for structural comparison.

Results

A total of 56 deleterious variants were identified in this study, including 12 UTR variants, 18 splice site variants, eight sSNPs and 18 nsSNPs. Among these 56 deleterious variants, seven variants were also identified in the Alzheimer’s Disease Sequencing Project (ADSP), Alzheimer’s Disease Neuroimaging Initiative (ADNI) and Mount Sinai Brain Bank (MSBB) studies.

Discussion

The 56 deleterious variants were predicted to affect the regulation of gene expression, or have functional impacts on these three endocytosis genes and their gene products. The deleterious variants in these genes are expected to affect their cellular function in endocytosis and may be implicated in the pathogenesis of AD as well. The biological consequences of these deleterious variants and their potential impacts on the disease risks could be further validated experimentally and may be useful for gene-disease association study.
Physiological and anatomical investigation of the auditory brainstem in the Fat-tailed dunnart (Sminthopsis crassicaudata)
Authors: Garrett Andrew , Lannigan Virginia , Yates Nathanael J. , Rodger Jennifer , Mulders Wilhelmina
Published: September 2019

The fat-tailed dunnart (Sminthopsis crassicaudata) is a small (10–20 g) native marsupial endemic to the south west of Western Australia. Currently little is known about the auditory capabilities of the dunnart, and of marsupials in general. Consequently, this study sought to investigate several electrophysiological and anatomical properties of the dunnart auditory system. Auditory brainstem responses (ABR) were recorded to brief (5 ms) tone pips at a range of frequencies (4–47.5 kHz) and intensities to determine auditory brainstem thresholds. The dunnart ABR displayed multiple distinct peaks at all test frequencies, similar to other mammalian species. ABR showed the dunnart is most sensitive to higher frequencies increasing up to 47.5 kHz. Morphological observations (Nissl stain) revealed that the auditory structures thought to contribute to the first peaks of the ABR were all distinguishable in the dunnart. Structures identified include the dorsal and ventral subdivisions of the cochlear nucleus, including a cochlear nerve root nucleus as well as several distinct nuclei in the superior olivary complex, such as the medial nucleus of the trapezoid body, lateral superior olive and medial superior olive. This study is the first to show functional and anatomical aspects of the lower part of the auditory system in the Fat-tailed dunnart.
Copper‐Catalyzed Asymmetric Borylative Cyclization of Cyclohexadienone‐Containing 1,6‐Dienes
Authors: He Cheng‐Yu , Li Qing‐Hua , Wang Xin , Wang Feng , Tian Ping , Lin Guo‐Qiang
Published: September 2019

Due to the low reactivity of 1,6‐dienes and the challenge of selectively differentiating such two olefins, the development of metal‐catalyzed asymmetric cyclization of 1,6‐dienes remains largely underdeveloped. Herein, we describe the first copper(I)‐catalyzed asymmetric borylative cyclization of cyclohexadienone‐tethered terminal alkenes (1,6‐dienes) via a tandem process: the regioselective borocupration of the electron‐rich terminal alkene and subsequent conjugate addition of stereospecific secondary alkyl‐copper(I) to the electron‐deficient cyclohexadienone, affording enantioenriched bicyclic skeletons bearing three contiguous stereocenters in all cis‐form. Meanwhile, this mild catalytic protocol is generally compatible with a wide range of functional groups, which allows further facile conversion of the cyclization products.

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Thuricin Z: A Narrow‐Spectrum Sactibiotic that Targets the Cell Membrane
Authors: Mo Tianlu , Ji Xinjian , Yuan Wei , Mandalapu Dhanaraju , Wang Fangting , Zhong Yuting , Li Fuyou , Chen Qin , Ding Wei , Deng Zixin , Yu Shaoning , Zhang Qi
Published: September 2019

Sactionine‐containing antibiotics (sactibiotics) are a growing class of peptide antibiotics belonging to the ribosomally synthesized and post‐translationally modified peptide (RiPP) superfamily. We report the characterization of thuricin Z, a novel sactibiotic from Bacillus thuringiensis. Unusually, the biosynthesis of thuricin Z involves two radical S‐adenosylmethionine (SAM) enzymes, ThzC and ThzD. Although ThzC and ThzD are highly divergent from each other, these two enzymes produced the same sactionine ring in the precursor peptide ThzA in vitro. Thuricin Z exhibits narrow‐spectrum antibacterial activity against Bacillus cereus. A series of analyses, including confocal laser scanning microscopy, ultrathin‐sectioning transmission electron microscopy, scanning electron microscopy, and large‐unilamellar‐vesicle‐based fluorescence analysis, suggested that thuricin Z binds to the bacterial cell membrane and leads to membrane permeabilization.
I2 Promoted Synthesis of 2‐Aminothiadiazoles Employing KSCN as a Sulfur Source Under Metal‐Free Conditions
Authors: Zhu Fuyuan , Yan Zhaohua , Ai Chengmei , Wang Yanmei , Lin Sen
Published: September 2019

A new three‐component strategy from aldehyde, p‐toluenesulfonyl hydrazide and potassium thiocyanate for the synthesis of 2‐aminothiadiazoles promoted by I2 under metal‐free conditions has been described. Potassium thiocyanate was used as an odorless and low‐toxicity sulfur source. A wide range of aromatic aldehydes can smoothly undergo the three‐component cyclization reaction under the optimized conditions to give the corresponding products in moderate to good yields.
An analytical perturbative solution to the Merton–Garman model using symmetries
Authors: Calmet Xavier , Wiesendanger Shaw Nathaniel
Published: September 2019

In this paper, we introduce an analytical perturbative solution to the Merton–Garman model. It is obtained by doing perturbation theory around the exact analytical solution of a model which possesses a two‐dimensional Galilean symmetry. We compare our perturbative solution of the Merton–Garman model to Monte Carlo simulations and find that our solutions perform surprisingly well for a wide range of parameters. We also show how to use symmetries to build option pricing models. Our results demonstrate that the concept of symmetry is important in mathematical finance.
microRNA‐599 promotes apoptosis and represses proliferation and epithelial‐mesenchymal transition of papillary thyroid carcinoma cells via downregulation of Hey2‐depentent Notch signaling pathway
Authors: Wang Duo‐Ping , Tang Xiao‐Zhun , Liang Quan‐Kun , Zeng Xian‐Jie , Yang Jian‐Bo , Xu Jian
Published: September 2019

Although papillary thyroid carcinoma (PTC) has a favorable prognosis after surgical or medical treatment, its survival rate is still very low. Therefore, finding more reliable therapy methods to limit PTC is a necessity. Compelling evidence has implicated the role of microRNAs (miRNAs or miRs) in PTC. This study aims at investigating the possible effect of microRNA‐599 (miR‐599) on proliferation, apoptosis, and epithelial‐mesenchymal transition (EMT) of PTC cells by targeting Hey2 gene. Differentially expressed genes/miRNAs associated with PTC were screened based on microarray analysis. Then, the expression of the candidate gene, as well as, the regulatory miRNA were detected in PTC cells, the related signaling pathway was verified. Afterward, the relationship between the miR and the candidate gene was verified by dual‐luciferase reporter gene assay. Subsequently, the effects of overexpressed miR and silenced candidate gene on cell proliferation, cell apoptosis, EMT, migration, and invasion were detected. In PTC tissues and cells, miR‐599 was downregulated while Hey2 expressed highly. Hey2 is a target gene of miR‐559. In addition, the expression of Bax and E‐cadherin was elevated while that of Hey2, Notch1, Delta‐like1, Hes1, N1ICD, Jagged1, Snail, Slug, N‐cadherin and Vimentin, and Bcl‐2 was reduced in cells treated with upregulated miR‐599 or downregulated Hey2. Moreover, miR‐599 overexpression or Hey2 silencing inhibited cell proliferation, migration, invasion, along with EMT but promoted apoptosis. This study verified that miR‐599 promotes apoptosis and represses proliferation, EMT of PTC cells through inactivating the Notch signaling pathway by downregulating Hey2, which has great clinical significance for PTC treatment.
Klinische Charakteristika, Ressourcenverbrauch, Lebensqualität und Versorgungssituation beim Dravet-Syndrom in Deutschland
Authors: Kalski Malin , Schubert-Bast Susanne , Kieslich Matthias , Leyer Anne‑Christine , Polster Tilman , Herting Arne , Mayer Thomas , Trollmann Regina , Neubauer Bernd A. , Bettendorf Ulrich , Bast Thomas , Wiemer-Kruel Adelheid , von Spiczak Sarah , Kurlemann Gerhard , Wolff Markus , Kluger Gerhard , Carroll Joe , Macdonald Daniel , Pritchard Clive , Irwin John , Klein Karl Martin , Rosenow Felix , Strzelczyk Adam , Kay Lara
Published: September 2019

Fragestellung

Ziel der prospektiven, multizentrischen Studie ist die Erfassung klinischer Charakteristika, des Ressourcenverbrauches sowie der Lebensqualität bei Patienten mit der Diagnose eines Dravet-Syndroms (DS) und deren Eltern in Deutschland.

Methoden

Die Datenerhebung erfolgte mit einem validierten retrospektiven Fragebogen über 3 bzw. 12 Monate sowie mit einem prospektiven Tagebuch über 3 Monate. Es wurden Daten zur Anfallssituation, Medikamenteneinnahme, Therapieinanspruchnahme sowie zu direkten und indirekten Kosten und zur Lebensqualität erhoben. Die Fragebögen und das Tagebuch wurden den Eltern über den Dravet-Syndrom e. V. sowie beteiligte Zentren ausgehändigt.

Ergebnisse

Der Fragebogen wurde von 93 Eltern der DS-Patienten und das Tagebuch von 77 ausgefüllt. Das mittlere Alter der Patienten betrug 10 Jahre (Spannweite 15 Monate bis 33,7 Jahre). Die Zeit bis zur Syndromdiagnose eines DS war in den letzten beiden Jahrzehnten deutlich kürzer. In den letzten 12 Monaten ereignete sich bei 95 % der Patienten mindestens ein epileptischer Anfall. Als anfallsauslösende Faktoren wurden Fieber (93,4 %), Aufregung (56 %), Schlafmangel (51,6 %) und starke körperliche Anstrengung (50,5 %) berichtet. Die Lebenszeitprävalenz des Status epilepticus lag bei 77 %, und bei 28 % war mindestens 1 Episode eines Status epilepticus innerhalb des letzten Jahres aufgetreten. Die Lebensqualität (QoL) der Patienten war niedriger als die der Allgemeinbevölkerung, und von 46 % der Eltern wurden Depressionssymptome berichtet. Die direkten Kosten in 3 Monaten betrugen 6043 € pro Patient. Den größten Kostenfaktor stellten die stationären Kosten dar (1702 €), gefolgt von den Leistungen für Pflege (1130 €), den Kosten für die antikonvulsiven Medikamente (892 €) und für Therapien (559 €). Bei den Müttern betrugen die gesamten indirekten Kosten 4399 € und bei den Vätern 391 € bezogen auf 3 Monate.

Schlussfolgerung

Das Dravet-Syndrom ist mit häufigen, oft therapierefraktären epileptischen Anfällen und Status epilepticus vergesellschaftet. Diese Studie zeigt die erhebliche Krankheitslast und die damit verbundenen Einschränkungen in der Lebensqualität sowie die hohen direkten und indirekten Kosten auf. Um eine Verbesserung der Lebensqualität bei Patienten mit DS und deren Eltern zu erreichen, bedarf es neuer Therapie- und Versorgungskonzepte.
Mathematical modeling of the glucagon challenge test
Authors: Masroor Saeed , van Dongen Marloes G. J. , Alvarez-Jimenez Ricardo , Burggraaf Koos , Peletier Lambertus A. , Peletier Mark A.
Published: September 2019

A model for the homeostasis of glucose through the regulating hormones glucagon and insulin is described. It contains a subsystem that models the internalization of the glucagon receptor. Internalization is a mechanism in cell signaling, through which G-protein coupled receptors are taken from the surface of the cell to the endosome. The model is used to interpret data from a glucagon challenge test in which subjects have been under treatment with a novel glucagon receptor anti-sense drug which is aimed at reducing the number of receptors in the liver. It is shown how the receptor internalization results in tolerance of the blood glucose concentration to glucagon-induced hyperglycemia. We quantify the reduction of the number of receptors using the model and the data before and after treatment.
The role of business in sustainable development and peacebuilding: Observing interaction effects
Authors: Miklian Jason
Published: September 2019

How can we better understand the complex interaction effects that are triggered when businesses and international government agencies become partners in social development? To answer, this article presents field experiences of Heineken in the Democratic Republic of Congo, ethnic cleansing in Myanmar, and the United Nations Global Compact in Dubai, to show the impact of key multi-stakeholder business-development policies as experienced by millions of people. These cases help us understand business and sustainable development interactions by exploring existing research gaps regarding issues of discourse, guidance, and legitimacy. This article has four aims: (1) to show that business-development interactions are much more complex than most case studies are able to encapsulate; (2) to explore how unintended ripple effects of even the most promising “win-win” business-development policies can carry catastrophic consequences; (3) to illustrate the potential benefits of a novel methodology for future research on business, global governance, and sustainable development; and (4) to show how business and development concerns interconnect across and through the macro- and meso-levels of analysis down to local livelihood interactions and impacts. I contextualize these experiences to emerging scholarship, opening avenues for building theory and improving policy on business, development, and peace.
Through East Asia to the sound of ‘Giovinezza’: Italian travel literature on China, Korea and Japan during the Fascistventennio
Authors: Basilone Linetto
Published: September 2019

During the Fascistventennio, prominent Italian writers and journalists, such as Mario Appelius, Raffaele Calzini, Arnaldo Cipolla, Arnaldo Fraccaroli, Roberto Suster and Cesco Tommaselli, reported from China, Japan and Korea forIl Popolo d'Italia,Corriere della SeraandLa Stampa. Their travel narratives were crucial for the creation and diffusion in Italy of the dominant representation of China and Korea as remote, decadent and exotic societies; and of Japan as a progressive society resonant with Fascist Italy. The narrativisation of these countries in Italian travelogues from the Fascistventenniowas part of a widespread discursive practice by Italian intellectuals willing to subscribe to, and actively disseminate, the guiding principles of Fascism. When emphasising China's and Korea's irreconcilable difference from, and Japan's affinity with, Fascist Italy, these intellectuals extolled the Italian race and culture, justified Italy's position in geopolitical dynamics, and propagandised the exceptionality of the Fascist ideology.
International Order in Historical East Asia: Tribute and Hierarchy Beyond Sinocentrism and Eurocentrism
Authors: Kang David C.
Published: September 2019

IR theorizing about international order has been profoundly, perhaps exclusively, shaped by the Western experiences of the Westphalian order and often assumes that the Western experience can be generalized to all orders. Recent scholarship on historical East Asian orders challenges these notions. The fundamental organizing principle in historical East Asia was hierarchy, not sovereign equality. The region was characterized by hegemony, not balance of power. This emerging research program has direct implications for enduring questions about the relative importance of cultural and material factors in both international orders and their influence on behavior—for describing and explaining patterns of war and peace across time and space, for understanding East Asia as a region made up of more than just China, and for more usefully comparing East Asia, Europe, and other regions of the world.
Comparison of nasal and olfactory functions between two surgical approaches for the treatment of concha bullosa: a randomised clinical trial
Authors: Andaloro C , La Mantia I , Castro V , Grillo C
Published: September 2019

Objective

Concha bullosa may be associated with paranasal sinus infections and nasal obstruction. Middle concha mucosa membranes have olfactory neurofibrils. This study investigated the impact of routinely used concha bullosa surgery techniques – crushing and lateral laminectomy – on nasal and olfactory functions.

Methods

Forty-three adult patients who had undergone surgery for a symptomatic concha bullosa completed the odour test, nasal obstruction visual analogue scale, 22-item Sino-Nasal Outcome Test, and peak nasal inspiratory flow test, pre-operatively and three months post-operatively. The pre- and post-operative results within and between the two treatment groups were compared.

Results

Intragroup comparison of mean pre- versus post-treatment changes revealed statistically significant findings for the nasal obstruction visual analogue scale, Sino-Nasal Outcome Test, peak nasal inspiratory flow and olfaction tests (allp< 0.05). However, there were no statistically significant changes when comparing the scores between the groups (intergroup comparison).

Conclusion

Lateral laminectomy and crushing in concha bullosa surgery have no negative effects on olfactory function. Concha bullosa surgery provides positive outcomes regarding nasal complaints in symptomatic patients.
Recent Trends in the Chinese Economy
Authors: Rawski Thomas G.
Published: September 2019

The past 15 years have been eventful ones for the Chinese economy. They
have seen an ambitious attempt at economic acceleration decline into
agricultural crisis, a major reversal of the direction of economic policy,
agricultural recovery and resurgent economic momentum. These years have
brought major changes to the Chinese economy: whole new industries have
appeared; official policy towards such diverse areas as education, income
distribution, regional dispersion of industry and economic specialization
has shifted repeatedly; the organization of agricultural production has also
changed.
The association between intimate partner violence against women and newborn telomere length
Authors: Chan Ko Ling , Lo Camilla K. M. , Ho Frederick K. , Leung Wing Cheong , Yee Benjamin K. , Ip Patrick
Published: September 2019

Intimate partner violence (IPV) against women negatively impacts infant health. However, its impact on infant’s biology, in particular on telomere length (TL) is unknown. The aim of this study was to examine the association between IPV against women before childbirth and cord blood TL in their newborn. A total of 774 pregnant women in the 20th–24th week of gestation were recruited at a public hospital in Hong Kong. The mothers’ exposure to IPV before childbirth, demographic characteristics, obstetric outcomes, health and mental health were measured at the time of recruitment and 4 weeks after childbirth. Umbilical cord blood was collected by midwives at the time of delivery. The newborn TL was quantified using quantitative PCR method and expressed in T/S ratio (the ratio of telomere repeat copy numbers to single-copy gene numbers). After adjusting for a number of confounding variables, the mothers’ exposure to any IPV before childbirth (β = −0.08, 95% CI = −0.14, −0.01) was associated with shorter TL. Specifically, psychological abuse against women before childbirth (β = −0.08, 95% CI = −0.15, −0.02) and sexual abuse against women before childbirth (β = −0.22, 95% CI = −0.43 to −0.01) were significantly associated with reduced newborn TL. This study is the first to provide evidence of an association between IPV against women before childbirth and TL shortening in their newborns. Through TL- dependent transcription and epigenetic mechanisms, our finding suggests maternal exposure to IPV may exert a life-long impact on the offspring’s health.
Trends in the risk of second primary malignancies among survivors of chronic lymphocytic leukemia
Authors: Kumar Vivek , Ailawadhi Sikander , Bojanini Leyla , Mehta Aditya , Biswas Suman , Sher Taimur , Roy Vivek , Vishnu Prakash , Marin-Acevedo Julian , Alegria Victoria R. , Paulus Aneel , Aulakh Sonikpreet , Iqbal Madiha , Manochakian Rami , Tan Winston , Chanan-Khan Asher , Ailawadhi Meghna
Published: September 2019

With improving survivorship in chronic lymphocytic leukemia (CLL), the risk of second primary malignancies (SPMs) has not been systematically addressed. Differences in risk for SPMs among CLL survivors from the Surveillance, Epidemiology, and End Results (SEER) database (1973–2015) were compared to risk of individual malignancies expected in the general population. In ~270,000 person-year follow-up, 6487 new SPMs were diagnosed with a standardized incidence ratio (SIR) of 1.2 (95% CI:1.17–1.23). The higher risk was for both solid (SIR 1.15; 95% CI:1.12–1.18) and hematological malignancies (SIR 1.61; 95% CI:1.5–1.73). The highest risk for SPMs was noted between 2 and 5 months after CLL diagnosis (SIR 1.57; 95% CI:1.41–1.74) and for CLL patients between 50- and 79-years-old. There was a significant increase in SPMs in years 2003–2015 (SIR 1.36; 95% CI:1.3–1.42) as compared to 1973–1982 (SIR 1.19; 95% CI:1.12–1.26). The risk of SPMs was higher in CLL patients who had received prior chemotherapy (SIR 1.38 95% CI:1.31–1.44) as compared to those untreated/treatment status unknown (SIR 1.16, 95% CI:1.13–1.19, p < 0.001). In a multivariate analysis, the hazard of developing SPMs was higher among men, post-chemotherapy, recent years of diagnosis, advanced age, and non-Whites. Active survivorship plans and long-term surveillance for SPMs is crucial for improved outcomes of patients with a history of CLL.
Stromal cells downregulate miR-23a-5p to activate protective autophagy in acute myeloid leukemia
Authors: Ganesan Saravanan , Palani Hamenth Kumar , Lakshmanan Vairavan , Balasundaram Nithya , Alex Ansu Abu , David Sachin , Venkatraman Arvind , Korula Anu , George Biju , Balasubramanian Poonkuzhali , Palakodeti Dasaradhi , Vyas Neha , Mathews Vikram
Published: September 2019

Complex molecular cross talk between stromal cells and the leukemic cells in bone marrow is known to contribute significantly towards drug-resistance. Here, we have identified the molecular events that lead to stromal cells mediated therapy-resistance in acute myeloid leukemia (AML). Our work demonstrates that stromal cells downregulate miR-23a-5p levels in leukemic cells to protect them from the chemotherapy induced apoptosis. Downregulation of miR-23a-5p in leukemic cells leads to upregulation of protective autophagy by targeting TLR2 expression. Further, autophagy inhibitors when used as adjuvants along with conventional drugs can improve drug sensitivity in vitro as well in vivo in a mouse model of leukemia. Our work also demonstrates that this mechanism of bone marrow stromal cell mediated regulation of miR-23a-5p levels and subsequent molecular events are relevant predominantly in myeloid leukemia. Our results illustrate the critical and dynamic role of the bone marrow microenvironment in modulating miRNA expression in leukemic cells which could contribute significantly to drug resistance and subsequent relapse, possibly through persistence of minimal residual disease in this environment.
The structural basis for RNA selectivity by the IMP family of RNA-binding proteins
Authors: Biswas Jeetayu , Patel Vivek L. , Bhaskar Varun , Chao Jeffrey A. , Singer Robert H. , Eliscovich Carolina
Published: September 2019

The IGF2 mRNA-binding proteins (ZBP1/IMP1, IMP2, IMP3) are highly conserved post-transcriptional regulators of RNA stability, localization and translation. They play important roles in cell migration, neural development, metabolism and cancer cell survival. The knockout phenotypes of individual IMP proteins suggest that each family member regulates a unique pool of RNAs, yet evidence and an underlying mechanism for this is lacking. Here, we combine systematic evolution of ligands by exponential enrichment (SELEX) and NMR spectroscopy to demonstrate that the major RNA-binding domains of the two most distantly related IMPs (ZBP1 and IMP2) bind to different consensus sequences and regulate targets consistent with their knockout phenotypes and roles in disease. We find that the targeting specificity of each IMP is determined by few amino acids in their variable loops. As variable loops often differ amongst KH domain paralogs, we hypothesize that this is a general mechanism for evolving specificity and regulation of the transcriptome.
Stable memory with unstable synapses
Authors: Susman Lee , Brenner Naama , Barak Omri
Published: September 2019

What is the physiological basis of long-term memory? The prevailing view in Neuroscience attributes changes in synaptic efficacy to memory acquisition, implying that stable memories correspond to stable connectivity patterns. However, an increasing body of experimental evidence points to significant, activity-independent fluctuations in synaptic strengths. How memories can survive these fluctuations and the accompanying stabilizing homeostatic mechanisms is a fundamental open question. Here we explore the possibility of memory storage within a global component of network connectivity, while individual connections fluctuate. We find that homeostatic stabilization of fluctuations differentially affects different aspects of network connectivity. Specifically, memories stored as time-varying attractors of neural dynamics are more resilient to erosion than fixed-points. Such dynamic attractors can be learned by biologically plausible learning-rules and support associative retrieval. Our results suggest a link between the properties of learning-rules and those of network-level memory representations, and point at experimentally measurable signatures.
CENP-A nucleosome clusters form rosette-like structures around HJURP during G1
Authors: Andronov Leonid , Ouararhni Khalid , Stoll Isabelle , Klaholz Bruno P. , Hamiche Ali
Published: September 2019

CENP-A is an essential histone H3 variant that epigenetically marks the centromeric region of chromosomes. Here we show that CENP-A nucleosomes form characteristic clusters during the G1 phase of the cell cycle. 2D and 3D super-resolution microscopy and segmentation analysis reveal that these clusters encompass a globular rosette-like structure, which evolves into a more compact structure in late G1. The rosette-like clusters contain numerous CENP-A molecules and form a large cellular structure of ∼250–300 nm diameter with remarkably similar shapes for each centromere. Co-localization analysis shows that HJURP, the CENP-A chaperone, is located in the center of the rosette and serves as a nucleation point. The discovery of an HJURP-mediated CENP-A nucleation in human cells and its structural description provide important insights into the mechanism of CENP-A deposition and the organization of CENP-A chromatin in the centromeric region.
Integration of single photon emitters in 2D layered materials with a silicon nitride photonic chip
Authors: Peyskens Frédéric , Chakraborty Chitraleema , Muneeb Muhammad , Van Thourhout Dries , Englund Dirk
Published: September 2019

Photonic integrated circuits (PICs) enable the miniaturization of optical quantum circuits because several optic and electronic functionalities can be added on the same chip. Integrated single photon emitters (SPEs) are central building blocks for such quantum photonic circuits. SPEs embedded in 2D transition metal dichalcogenides have some unique properties that make them particularly appealing for large-scale integration. Here we report on the integration of a WSe2 monolayer onto a Silicon Nitride (SiN) chip. We demonstrate the coupling of SPEs with the guided mode of a SiN waveguide and study how the on-chip single photon extraction can be maximized by interfacing the 2D-SPE with an integrated dielectric cavity. Our approach allows the use of optimized PIC platforms without the need for additional processing in the SPE host material. In combination with improved wafer-scale CVD growth of 2D materials, this approach provides a promising route towards scalable quantum photonic chips.