bluuebunny/crossref_metadata_2025 huggingface dataset:
Building Information Modelling – A new tool for the successful implementation of major projects of German railways / Building Information Modelling – Ein neues Werkzeug zur erfolgreichen Realisierung von Großprojekten der Deutschen Bahn
Authors: Ehrbar Heinz
Published: December 2016

If correctly applied, digitalisation can also create great added value for railways, which explains why German Railways (DB) is taking it seriously. As with many other construction client organisations, the DB with their portfolio of major projects was and is confronted with the situation that cost targets and deadlines can often not be maintained. The causes for such deviations are various and in addition to the many external reasons, are also due to the current methods of controlling construction projects. The DB has recognised that the use of digital methods of project implementation such as Building Information Modelling (BIM) can achieve a great contribution to the improvement of project stability. While DB has already consistently furthered the use of BIM for station buildings in recent years, BIM has only been in use on DB infrastructure projects since 2015. By the end of 2020, however, the running up process of BIM at DB should have reached the stage that all complex major projects and all projects suitable for standardisation are designed and controlled with BIM. The DB hopes to gain from the use of BIM more transparency on projects, considerable economic benefits and the strengthening of the collaboration of all sides as partners.

Richtig eingesetzt kann die Digitalisierung auch bei der Eisenbahn einen hohen Mehrwert schaffen, weshalb die Deutsche Bahn (DB) der Digitalisierung einen sehr hohen Stellenwert gibt. Wie viele andere Bauherrenorganisationen auch, war und ist die DB mit ihrem Portfolio an Großprojekten mit der Tatsache konfrontiert, dass Kosten‐ und Terminziele in einem nicht unerheblichen Ausmaß nicht eingehalten werden können. Die Ursachen für solche Abweichungen sind vielfältig und liegen neben vielen externen Gründen auch in der Art und Weise der aktuellen Steuerung von Bauprojekten. Die DB hat erkannt, dass mit dem Einsatz digitaler Methoden zur Projektabwicklung wie Building Information Modelling (BIM) ein großer Beitrag zur Verbesserung der Projektstabilität geleistet werden kann. Während im Bereich der Bahnhofsbauten der DB die Anwendung von BIM bereits in den letzten Jahren konsequent vorangetrieben wurde, kommt BIM für die Infrastrukturprojekte der DB Netz AG erst seit 2015 zum Einsatz. Bis Ende 2020 soll der BIM‐Hochlauf bei der DB aber so geschaffen sein, dass alle komplexen Großprojekte und alle standardisierbaren Projekte mit BIM geplant und gesteuert werden. Die DB verspricht sich von dem Einsatz von BIM mehr Transparenz in den Projekten, erhebliche wirtschaftliche Vorteile und eine Stärkung der partnerschaftlichen Zusammenarbeit nach allen Seiten.
Implementation of BIM in the tunnel design – Engineering consultant's aspect
Authors: Daller Josef , Žibert Marko , Exinger Christoph , Lah Martin
Published: December 2016

The importance of information management was recognised in surface construction industry decades ago, and is increasingly being recognised through formal processes and laws. Around the world, these laws and codes of practice are currently being drafted and enacted, to reflect the development of software tools and corresponding increasing adoption by industry. This paper deals with general overview of BIM and its benefits as well as specifics of implementing information modelling in the tunnelling business utilizing BIM (Building Information Modelling) technology developed for buildings as well as similar technology developed for the mining industry. Although BIM was initially recognised as a 3D digital representation of physical and functional characteristics of a facility, the benefits of using it are much wider than anticipated by its definition. This paper focuses on aspect of consultants and the role of other parties in developing projects.
Research@ZaB – Start of construction of the “ZaB – Zentrum am Berg” research and development, training and education centre / Research@ZaB – Baubeginn für das Forschungs‐ und Entwicklungs‐ sowie Trainings‐ und Schulungszentrum Zentrum am Berg
Authors: Galler Robert
Published: December 2016

The creation of sustainable infrastructure is increasingly being provided in underground facilities. In terms of construction and maintenance, this leads to greater challenges for construction, transport and energy‐provider companies. This also applies for emergency services organisations as well as to ensure the safety for the users of the infrastructure. The project “Research@ZaB – Zentrum am Berg” will establish an underground facility for research and development, education and training purposes. On the one hand, the centre should meet the requirements of public institutions; on the other hand it represents a “development factory” for private companies as well as concerned universities.

Untertägige Anlagen sind substanzielle Elemente der innerstädtischen sowie überregionalen Infrastruktur und des Energiewesens. Die Schaffung zukunftsfähiger Infrastrukturen erfolgt zunehmend in unterirdischen Anlagen, was gleichzeitig zu größeren Herausforderungen für die Bau‐, Verkehrs‐ und Energieunternehmen, aber auch die Einsatzorganisationen hinsichtlich der Herstellung, der Erhaltung und Wartung sowie der Gewährleistung der Sicherheit für die Nutzer der Infrastrukturen führt. Mit dem Projekt “Research@ZaB – Zentrum am Berg” wird eine für den Hohlraumbau fehlende Untertage‐Einrichtung zu Forschungs‐, Entwicklungs‐, Schulungs‐ und Trainingszwecken errichtet, die einerseits die Anforderungen der öffentlichen Institutionen erfüllen soll, aber gleichzeitig eine “Weiterentwicklungsfabrik” für private Unternehmen und für die zuständigen Universitäten darstellt.
A comparison study of multivariate fixed models and Gene Association with Multiple Traits (GAMuT) for next‐generation sequencing
Authors: Chiu Chi‐Yang , Jung Jeesun , Wang Yifan , Weeks Daniel E. , Wilson Alexander F. , Bailey‐Wilson Joan E. , Amos Christopher I. , Mills James L. , Boehnke Michael , Xiong Momiao , Fan Ruzong
Published: December 2016

In this paper, extensive simulations are performed to compare two statistical methods to analyze multiple correlated quantitative phenotypes: (1) approximate F‐distributed tests of multivariate functional linear models (MFLM) and additive models of multivariate analysis of variance (MANOVA), and (2) Gene Association with Multiple Traits (GAMuT) for association testing of high‐dimensional genotype data. It is shown that approximate F‐distributed tests of MFLM and MANOVA have higher power and are more appropriate for major gene association analysis (i.e., scenarios in which some genetic variants have relatively large effects on the phenotypes); GAMuT has higher power and is more appropriate for analyzing polygenic effects (i.e., effects from a large number of genetic variants each of which contributes a small amount to the phenotypes). MFLM and MANOVA are very flexible and can be used to perform association analysis for (i) rare variants, (ii) common variants, and (iii) a combination of rare and common variants. Although GAMuT was designed to analyze rare variants, it can be applied to analyze a combination of rare and common variants and it performs well when (1) the number of genetic variants is large and (2) each variant contributes a small amount to the phenotypes (i.e., polygenes). MFLM and MANOVA are fixed effect models that perform well for major gene association analysis. GAMuT can be viewed as an extension of sequence kernel association tests (SKAT). Both GAMuT and SKAT are more appropriate for analyzing polygenic effects and they perform well not only in the rare variant case, but also in the case of a combination of rare and common variants. Data analyses of European cohorts and the Trinity Students Study are presented to compare the performance of the two methods.
Leveraging population information in family‐based rare variant association analyses of quantitative traits
Authors: Jiang Yu , Ji Yunqi , Sibley Alexander B. , Li Yi‐Ju , Allen Andrew S.
Published: December 2016

Confounding due to population substructure is always a concern in genetic association studies. Although methods have been proposed to adjust for population stratification in the context of common variation, it is unclear how well these approaches will work when interrogating rare variation. Family‐based association tests can be constructed that are robust to population stratification. For example, when considering a quantitative trait, a linear model can be used that decomposes genetic effects into between‐ and within‐family components and a test of the within‐family component is robust to population stratification. However, this within‐family test ignores between‐family information potentially leading to a loss of power. Here, we propose a family‐based two‐stage rare‐variant test for quantitative traits. We first construct a weight for each variant within a gene, or other genetic unit, based on score tests of between‐family effect parameters. These weights are then used to combine variants using score tests of within‐family effect parameters. Because the between‐family and within‐family tests are orthogonal under the null hypothesis, this two‐stage approach can increase power while still maintaining validity. Using simulation, we show that this two‐stage test can significantly improve power while correctly maintaining type I error. We further show that the two‐stage approach maintains the robustness to population stratification of the within‐family test and we illustrate this using simulations reflecting samples composed of continental and closely related subpopulations.
Measurements of CO2‐brine relative permeability in Berea sandstone using pressure taps and a long core
Authors: Chen Xiongyu , Kianinejad Amir , A. DiCarlo David
Published: December 2016

We measured CO2‐brine relative permeability by performing five steady‐state primary drainage experiments in a 116 mD Berea sandstone core at 20°C and 10.34 MPa. We used a long (60.8 cm) core and four pressure taps to study and minimize end effects that can plague CO2‐brine relative permeability measurements, and we obtained in situ saturation profiles using a medical X‐ray Computed Tomography (CT) scanner. We found that entrance and exit effects propagated ∼5 cm into the core, but the center sections of the core had uniform saturation. From the saturations and pressure drops, we obtained both CO2 and brine relative permeability in the center sections. We also obtained CO2 relative permeability at the entrance section where the brine saturation was lower and not uniform. The 15‐cm long exit section of the core had non‐uniform saturation and a measured pressure drop that was on the order of the capillary pressure and hence was unreliable for calculating relative permeability. We found that the CO2 and brine relative permeabilities determined in five experiments were consistent with each other and followed two simple Corey‐type models that are similar to those seen in oil‐brine relative permeability measurements. We discuss why end effects are much greater in the CO2‐brine system than in oil‐brine systems, and how this is a possible explanation of the low CO2 relative permeabilities recently reported for the CO2‐brine systems. © 2016 Society of Chemical Industry and John Wiley & Sons, Ltd.
Is Best–Worst Scaling Suitable for Health State Valuation? A Comparison with Discrete Choice Experiments
Authors: Krucien Nicolas , Watson Verity , Ryan Mandy
Published: December 2016

Health utility indices (HUIs) are widely used in economic evaluation. The best–worst scaling (BWS) method is being used to value dimensions of HUIs. However, little is known about the properties of this method. This paper investigates the validity of the BWS method to develop HUI, comparing it to another ordinal valuation method, the discrete choice experiment (DCE). Using a parametric approach, we find a low level of concordance between the two methods, with evidence of preference reversals. BWS responses are subject to decision biases, with significant effects on individuals' preferences. Non parametric tests indicate that BWS data has lower stability, monotonicity and continuity compared to DCE data, suggesting that the BWS provides lower quality data. As a consequence, for both theoretical and technical reasons, practitioners should be cautious both about using the BWS method to measure health‐related preferences, and using HUI based on BWS data. Given existing evidence, it seems that the DCE method is a better method, at least because its limitations (and measurement properties) have been extensively researched. Copyright © 2016 John Wiley & Sons, Ltd.
Activation of interleukin‐6 and ‐8 expressions by methylmercury in human U937 macrophages involves RelA and p50
Authors: Yamamoto Megumi , Khan Noureen , Muniroh Muflihatul , Motomura Eriko , Yanagisawa Rie , Matsuyama Takami , Vogel Christoph F. A.
Published: December 2016

The accumulation of macrophages has been observed around lesions of the brain in patients with Minamata disease. In this condition, mercury has been detected histochemically in macrophages throughout the brain. However, the role of macrophages in the neurotoxicity of methylmercury (MeHg) and the molecular mechanisms of their response to MeHg exposure remain to be elucidated. Here, we investigated how MeHg affects the expression of proinflammatory cytokines such as interleukin (IL)‐6 and IL‐8 in cultured human U937 macrophages. Compared with controls, IL‐6 and IL‐8 mRNA expression was maximally induced in U937 macrophages after treatment with 10 μM MeHg for 6 h. The protein secretion of IL‐6 and IL‐8 was significantly stimulated by MeHg in U937 macrophages. Results from luciferase reporter assay indicated functional activation of nuclear factor kappa B and the involvement of subunit RelA and p50 in MeHg‐induced IL‐6 and IL‐8 activation, which was confirmed by siRNA knockdown experiments. MeHg exposure at 4 μM also significantly induced IL‐8 expression in U‐87 MG cells at mRNA and protein level, indicating that IL‐8 induction might be a general mode of action of MeHg treatment among different cell types. These results indicate a possible involvement of an early inflammatory response, including IL‐6 and IL‐8 expression in the pathogenesis of MeHg. N‐acetyl‐l‐cysteine suppressed MeHg‐induced activation of IL‐6 and IL‐8 mRNA expression in U937 macrophages, indicating the effectiveness of N‐acetyl‐l‐cysteine as a therapeutic drug in MeHg‐induced inflammation. Copyright © 2016 John Wiley & Sons, Ltd.
Mulberroside A suppresses PXR‐mediated transactivation and gene expression of P‐gp in LS174T cells
Authors: Li Yuhua , Huang Ling , Sun Jiahong , Wei Xiaohua , Wen Jinhua , Zhong Guoping , Huang Min , Bi Huichang
Published: December 2016

Mulberroside A (Mul A) is the main bioactive constituents of Sangbaipi, which is officially listed in the Chinese Pharmacopoeia. The pregnane X receptor (PXR) has been recognized as the critical mediator of human P‐glycoprotein (P‐gp) gene transactivation. In this study, the effect of Mul A on PXR‐mediated transactivation and gene expression of P‐gp was investigated. It was found that Mul A significantly suppressed PXR‐mediated P‐gp luciferase activity induced by rifampicin (Rif). Furthermore, Rif induced an elevation of P‐gp expression and transport activity, which was apparently suppressed by Mul A. However, Mul A did not suppress the P‐gp luciferase activity, P‐gp expression, and function in the absence of Rif. These findings suggest that Mul A suppresses PXR‐mediated transactivation and P‐gp expression induced by Rif. This should be taken into consideration to predict any potential herb–drug interactions when Mul A or Sangbaipi are co‐administered with Rif or other PXR agonist drugs.
Projective‐Planar Graphs with no K3, 4‐Minor. II
Authors: Maharry John , Slilaty Daniel
Published: December 2016

The authors previously published an iterative process to generate a class of projective‐planar K3, 4‐free graphs called “patch graphs.” They also showed that any simple, almost 4‐connected, nonplanar, and projective‐planar graph that is K3, 4‐free is a subgraph of a patch graph. In this article, we describe a simpler and more natural class of cubic K3, 4‐free projective‐planar graphs that we call Möbius hyperladders. Furthermore, every simple, almost 4‐connected, nonplanar, and projective‐planar graph that is K3, 4‐free is a minor of a Möbius hyperladder. As applications of these structures we determine the page number of patch graphs and of Möbius hyperladders.
Hemoglobin during ribavirin‐based HCV therapy is closely related to circulating levels of DHEA
Authors: Bodeau Sandra , Lemouel Jean‐Philippe , Diouf Momar , Duverlie Gilles , Nguyen‐Khac Eric , Brochot Etienne
Published: December 2016

Ribavirin‐induced anemia is the major side effect observed
during HCV therapy. In an in vitro study, we recently discovered that DHEA can strongly inhibit this adverse event. We also evaluated a possible link between pre‐treatment serum DHEA and hemoglobin during HCV therapy. Among the 108 patients of our cohort serum baseline DHEA levels were associated with hemoglobin levels at week 12 of treatment (r = 0.35; P = 0.0021). Patients with low baseline serum DHEA developed severe anemia. A serum level of DHEA less than 1,500 ng/ml had a sensitivity of 94.3% and a positive predictive value of 93.1% for the detection of hemoglobin less than 11 g/dl during the first 12 week of treatment. With pre‐treatment DHEA levels below the cutoff, anemia was observed in 24.4% and 60.5% of patients treated with dual therapy and triple therapy, respectively, versus 0% and 15% of patients with higher DHEA levels. At week 12, the mean difference between patients with serum DHEA below and above the cutoff, in terms of absolute hemoglobin for dual and triple therapy groups were 1.2 and 1.7 g/dl, respectively (P = 0.005 and <0.001). Pretreatment DHEA levels are associated with hemoglobin levels during treatment. Based on these data, pretreatment assay of DHEA could be considered systematically in order to propose DHEA supplementation to potentiate the efficacy of the current and future use of ribavirin for HCV and HEV therapy. J. Med. Virol. 89:1033–1039, 2017. © 2016 Wiley Periodicals, Inc.
Influence of neodymium on microstructure and corrosion behavior of Mg‐8Li‐3Al‐2Zn alloy
Authors: Gu M. Y. , Wei G. L. , Liu W. C. , Wu G. H.
Published: December 2016

The influence of Nd addition on microstructure and corrosion behavior of LAZ832 alloy was investigated by immersion test, electrochemical experiments, scanning electron microscopy (SEM), and X‐ray photoelectron spectroscopy (XPS). The results indicate that Nd addition leads to the coarsening of grains and the improvement of corrosion resistance. Meanwhile, results of XPS demonstrate that the corrosion film of LAZ832 consists of Mg(OH)2, while the corrosion film of the LAZ832‐0.5Nd alloy is composed of Mg(OH)2 and Nd2O3. The improvement of corrosion resistance is attributed to the purifying effects of Nd addition and the appearance of Nd2O3, which changes the structure of the corrosion film and inhibits the penetration of the detrimental anions. Finally, Nd addition improves the corrosion resistance of the alloy, but it doesn't change the corrosion mechanism of the alloy.
Geometric properties of the Cassinian metric
Authors: Klén Riku , Mohapatra Manas Ranjan , Sahoo Swadesh Kumar
Published: December 2016

In this paper we prove a sharp distortion property of the Cassinian metric under Möbius transformations of a punctured ball onto another punctured ball. The paper also deals with discussion on local convexity properties of the Cassinian metric balls in proper subdomains of . Inclusion properties of the Cassinian metric balls with other hyperbolic‐type metric balls are also investigated. In particular, several conjectures are also stated in response to sharpness of the inclusion relations.
Rational Design of High‐Performance Wide‐Bandgap (≈2 eV) Polymer Semiconductors as Electron Donors in Organic Photovoltaics Exhibiting High Open Circuit Voltages (≈1 V)
Authors: Chochos Christos L. , Katsouras Athanasios , Gasparini Nicola , Koulogiannis Chrysanthos , Ameri Tayebeh , Brabec Christoph J. , Avgeropoulos Apostolos
Published: December 2016

Systematic optimization of the chemical structure of wide‐bandgap (≈2.0 eV) “donor–acceptor” copolymers consisting of indacenodithiophene or indacenodithieno[3,2‐b]thiophene as the electron‐rich unit and thieno[3,4‐c]pyrrole‐4,6‐dione as the electron‐deficient moiety in terms of alkyl side chain engineering and distance of the electron‐rich and electron‐deficient monomers within the repeat unit of the polymer chain results in high‐performance electron donor materials for organic photovoltaics. Specifically, preliminary results demonstrate extremely high open circuit voltages (V
ocs) of ≈1.0 V, reasonable short circuit current density (J
sc) of around 11 mA cm−2, and moderate fill factors resulting in efficiencies close to 6%. All the devices are fabricated in an inverted architecture with the photoactive layer processed by doctor blade equipment, showing the compatibility with roll‐to‐roll large‐scale manufacturing processes. From the correlation of the chemical structure—optoelectronic properties—photovoltaic performance, a rational guide toward further optimization of the chemical structure in this family of copolymers, has been achieved.

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Sensitive enhancement of vessel wall imaging with an endoesophageal Wireless Amplified NMR Detector (WAND)
Authors: Zeng Xianchun , Barbic Mladen , Chen Liangliang , Qian Chunqi
Published: December 2016

Purpose

To improve the imaging quality of vessel walls with an endoesophageal Wireless Amplified NMR Detector (WAND).

Methods

A cylindrically shaped double‐frequency resonator has been constructed with a single metal wire that is self‐connected by a pair of nonlinear capacitors. The double‐frequency resonator can convert wirelessly provided pumping power into amplified MR signals. This compact design makes the detector easily insertable into a rodent esophagus.

Results

The detector has good longitudinal and axial symmetry. Compared to an external surface coil, the WAND can enhance detection sensitivity by at least 5 times, even when the distance separation between the region of interest and the detector's cylindrical surface is twice the detector's own radius. Such detection capability enables us to observe vessel walls near the aortic arch and carotid bifurcation with elevated sensitivity.

Conclusion

A cylindrical MRI detector integrated with a wireless‐powered amplifier has been developed as an endoesophageal detector to enhance detection sensitivity of vessel walls. This detector can greatly improve the imaging quality for vessel regions that are susceptible to atherosclerotic lesions. Magn Reson Med 78:2048–2054, 2017. © 2016 International Society for Magnetic Resonance in Medicine.
Aus DNA wird Solarzelle
Authors: Hofsäß Robert , Fritz Yannic , Wagenknecht Hans‐Achim
Published: December 2016

Jenseits ihrer biologischen Funktion dient DNA als Gerüst, um supramolekulare Chromophoraggregate herzustellen. Über die entstehende helikale Anordnung lassen sich die optoelektronischen Eigenschaften der Chromophore kontrollieren. Konjugiert mit Fullerenen eignen sich diese Architekturen für Solarzellen.
Das Wechselspiel von Theorie und Kristallographie
Authors: Grabowsky Simon
Published: December 2016

Quantenkristallographie ist mehr als die Summe von Quantenchemie und Kristallographie. Mit ihr lassen sich aus Röntgenbeugungsexperimenten präzise und akkurate molekulare Strukturen sowie eine Wellenfunktion gewinnen, deren Informationsgehalt über den des quantenchemischen Ansatzes hinaus geht.
Insekten als Indikatoren
Authors: Groß Michael
Published: December 2016

Schmetterlinge werden seit Jahrhunderten beobachtet, gesammelt und wissenschaftlich untersucht bis hin zur molekularen Ebene. Selbst genetische Untersuchungen an historischen Exemplaren sind möglich und aufschlussreich. Die Daten dokumentieren den Schwund der Artenvielfalt und Verlust der Lebensräume.
Spurensuche im Fluss
Authors: Meier Florian , Kohl Yvonne
Published: December 2016

Die steigenden Produktionsmengen von Nanomaterialien führen dazu, dass Mensch und Umwelt diesen vermehrt ausgesetzt sind. Bisher fehlten die Messmethoden, um geringe Dosen von Nanopartikeln nachzuweisen und das Risiko zu bewerten, das von ihnen ausgeht. Eine Methode, Nanopartikel in Umweltmatrizes zu detektieren, ist die Feldflussfraktionierung.
Doktorandenseminar Nucleinsäurechemie in Bad Herrenalb
Authors: Richert Clemens
Published: December 2016

Ende September trafen sich vierzig Teilnehmer zum dritten Doktorandenseminar der Deutschen Nucleinsäurechemiegemeinschaft (DNG) in Bad Herrenalb. Die zweitägige Veranstaltung bestand aus zehn Doktorandenvorträgen, vier Methodenvorträgen von etablierten Wissenschaftlern und Flash Talks zur Vorstellung der zwölf angemeldeten Poster.
Berliner Blau: Elektrochromie in der Schule
Authors: Oetken Marco , Wagner Corina
Published: December 2016

Elektrochrome Fensterscheiben, smart windows, wechseln auf Knopfdruck ihre Farbe und lassen mal mehr, mal weniger Licht durch. In Gebäude eingebaut, sollen sie zur Energieeffizienz beitragen. Im Chemieunterricht zeigen selbstbeschichtete leitfähige Gläser, wie solche Fenster funktionieren.
25. Nachwuchsgruppentreffen Bioorganische Chemie
Authors: Beemelmanns Christine , Stallforth Pierre
Published: December 2016

Ende September trafen sich etwa 40 Gruppenleiter, Juniorprofessoren und Postdoktoranden mit Leitungsfunktion am Leibniz‐Institut für Naturstoff‐Forschung und Infektionsbiologie (Hans‐Knöll‐Institut, HKI) in Jena zum Nachwuchsgruppentreffen Bioorganische Chemie. An drei Tagen referierten und diskutierten die Teilnehmer über Themen, die von Strukturbiologie und biomolekularer Chemie über Naturstoffchemie bis zur Katalyse reichten.
4. Niedersächsisches Katalyse‐Symposium
Authors: Kreft Alexander
Published: December 2016

Mitte September 2016 trafen sich etwa 120 Teilnehmer in Braunschweig, um zum vierten Mal auf dem zweitägigen niedersächsischen Katalyse‐Symposium über Entwicklungen der Katalyseforschung zu diskutieren. Die Veranstaltung organisierten Matthias Tamm und Thomas Bannenberg mit Doktoranden der TU Braunschweig im Rahmen des Programms Catalysis for Sustainable Synthesis, das die TU Braunschweig in Kooperation mit der Universität Göttingen durchführt.
A novel two‐nucleotide deletion in HPS6 affects mepacrine uptake and platelet dense granule secretion in a family with Hermansky–Pudlak syndrome
Authors: Andres Oliver , Wiegering Verena , König Eva‐Maria , Schneider Anna Lena , Semeniak Daniela , Stritt Simon , Klopocki Eva , Schulze Harald
Published: December 2016

Background

Hermansky–Pudlak syndrome (HPS) is a rare autosomal recessive disease characterized by oculocutaneous albinism and platelet dysfunction. We report on a novel HPS6 homozygous frameshift variant (c.1919_1920delTC; p.Val640Glyfs*29) in a nonconsanguineous Caucasian family with two affected siblings (index patients) who presented with oculocutaneous albinism at birth and a mild bleeding phenotype during childhood and adolescence.

Procedure

Genetic analysis was conducted by panel‐based next‐generation sequencing (NGS) and Sanger sequencing. Platelets of the index patients, their parents, and the unaffected sister were then comprehensively evaluated by luminoaggregometry, whole blood flow cytometry, immunoblotting, immunofluorescence, and transmission electron microscopy.

Results

The homozygous frameshift variant in HPS6 gene detected by panel‐based NGS and its segregation in the family was confirmed by Sanger sequencing. Flow cytometric analysis of the patients’ platelets revealed a substantially decreased mepacrine uptake and release upon activation with a thrombin receptor agonist. Electron microscopy of resting platelets confirmed diminished dense granule content and enhanced vacuolization. Reduced release of adenosine triphosphate and CD63 neoexposition upon activation indicated not only a lack of dense granule content, but even an impairment of dense granule release.

Conclusions

Our results demonstrate that the novel loss‐of‐function variant in the HPS6 subunit of biogenesis of lysosome‐related organelles complex 2 is pathologic and leads to a reduced platelet dense granules and their release. The findings are compatible with an impaired platelet function and hence an enhanced bleeding risk. In future, a valid genotype–phenotype correlation may translate into best supportive care, especially regarding elective surgery or trauma management.
Operational and Clinical Strategies to Address Drug Cost Containment in the Acute Care Setting
Authors: McConnell Karen J. , Guzman Oscar E. , Pherwani Nisha , Spencer Dustin D. , Van Cura Jennifer D. , Shea Katherine M.
Published: December 2016

Objective

To provide clinical and operational strategies to generate drug cost savings in the hospital setting.

Methods

A search of the PubMed database was performed with no time limit through July 2016. All original prospective and retrospective studies, peer‐reviewed guidelines, consensus statements, review articles, and accompanying references were evaluated for inclusion. Only articles published in the English language were included.

Main results

Investigators reviewed 937 abstracts. The review of the literature showed that acute care hospitals are under increasing financial pressures, and the pharmacy is often responsible for opportunities to manage drug costs. The literature also indicated that cost‐containment strategies in the acute care setting range from pharmacy‐directed activities to initiatives requiring interdisciplinary collaboration and strategic planning. Hospital pharmacies should consider establishing an interdisciplinary team that is responsible for systematically reviewing drug cost implications and leading any initiatives that are deemed necessary. Acute care settings can use various operational and clinical strategies to lower their expenditures on high‐cost drugs. Operational strategies include various activities that pharmacy staff implement related to contracting, purchasing, and inventory management. Clinical strategies utilize clinical pharmacists working with interdisciplinary teams to develop and maintain a formulary, implement established‐use criteria for select drugs, use dose optimization, and implement other clinical tactics aimed at cost containment. After initiatives are implemented, assessing the outcomes of the initiatives is important to determine how successful they were at lowering costs safely and effectively.

Conclusion

Acute care hospitals can use various operational and clinical strategies to lower overall drug costs. A systematic stepwise approach is recommended to ensure relevant drugs are regularly reviewed and addressed as needed.
Approaches to polymeric mechanochromic materials
Authors: Calvino Céline , Neumann Laura , Weder Christoph , Schrettl Stephen
Published: December 2016

Mechanochromic materials respond to mechanical stimuli with a change of their optical properties. Such materials are of interest for many technological applications and support fundamental research as they help improving the understanding of stress transfer in polymeric objects and aid in the identification of the processes that lead to mechanical failure. In this highlight, different approaches are discussed that permit the design of polymeric materials, which signal mechanical stresses through a chromic response. This highlight emphasizes materials that exhibit mechanically induced changes of their intrinsic absorption or emission properties. These responses almost exclusively originate from changes of molecular structure, conformational rearrangements, or disruption of intermolecular interactions. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 640–652
Physical microscopic free‐choice model in the framework of a Darwinian approach to quantum mechanics
Authors: Baladrón Carlos
Published: December 2016

A compatibilistic model of free choice for a fundamental particle is built within a general framework that explores the possibility that quantum mechanics be the emergent result of generalised Darwinian evolution acting on the abstract landscape of possible physical theories. The central element in this approach is a probabilistic classical Turing machine –basically an information processor plus a randomiser– methodologically associated with every fundamental particle. In this scheme every system acts not under a general law, but as a consequence of the command of a particular, evolved algorithm. This evolved programme enables the particle to algorithmically anticipate possible future world configurations in information space, and as a consequence, without altering the natural forward causal order in physical space, to incorporate elements to the decision making procedure that are neither purely random nor strictly in the past, but in a possible future.
Analysis of universality in transient dynamics of coherent electronic transport
Authors: Seoane Souto R. , Martín‐Rodero A. , Levy Yeyati A.
Published: December 2016

We analyze the time‐dependent full‐counting statistics of charges transmitted through a quantum dot in the coherent regime. The generating function for the time‐dependent charge transfer statistics is evaluated numerically by discretizing the Keldysh time contour, which allows us to compute the higher order charge and current cumulants. We also develop an analytic expression for all order cumulants at any time given as a function of the zeros of the generating function, finding that the short time universality is due to the presence of a dominant single zero. The robustness of the universal features at short times is studied in both the sequential and coherent regimes.
Heat and charge transport measurements to access single‐electron quantum characteristics
Authors: Moskalets Michael , Haack Géraldine
Published: December 2016

In the framework of the Floquet scattering‐matrix theory, we discuss how electrical and heat currents accessible in mesoscopics are related to the state of excitations injected by a single‐electron source into an electron waveguide. We put forward an interpretation of a single‐particle heat current, which differs essentially from that of an electrical current. We show that the knowledge of both a time‐dependent electrical current and a time‐dependent heat current allows the full reconstruction of a single‐electron wave function. In addition, we compare electrical and heat shot noise caused by splitting of a regular stream of single‐electron excitations. If only one stream impinges on a wave splitter, the heat shot noise is proportional to the well‐known expression of the charge shot noise, reflecting the partitioning of the incoming single particles. The situation differs when two electronic streams collide at the wave splitter. The shot noise suppression, due to the Pauli exclusion principle, is governed by different overlap integrals in the case of charge and of heat.
Α Markov model for longitudinal studies with incomplete dichotomous outcomes
Authors: Efthimiou Orestis , Welton Nicky , Samara Myrto , Leucht Stefan , Salanti Georgia ,   on behalf of GetReal Work Package 4
Published: December 2016

Missing outcome data constitute a serious threat to the validity and precision of inferences from randomized controlled trials. In this paper, we propose the use of a multistate Markov model for the analysis of incomplete individual patient data for a dichotomous outcome reported over a period of time. The model accounts for patients dropping out of the study and also for patients relapsing. The time of each observation is accounted for, and the model allows the estimation of time‐dependent relative treatment effects. We apply our methods to data from a study comparing the effectiveness of 2 pharmacological treatments for schizophrenia. The model jointly estimates the relative efficacy and the dropout rate and also allows for a wide range of clinically interesting inferences to be made. Assumptions about the missingness mechanism and the unobserved outcomes of patients dropping out can be incorporated into the analysis. The presented method constitutes a viable candidate for analyzing longitudinal, incomplete binary data.
Rovibrational spectra of bounded diatomic molecules
Authors: Lumb Sonia , Lumb Shalini , Prasad Vinod
Published: December 2016

Spectra of a bounded diatomic molecule is studied numerically. Shifted Deng–Fan oscillator potential has been used to model the molecule. The accurate five‐point finite difference method has been used to solve the Schrödinger equation for rovibrational motion of the molecule. The energies of the bound states as well as free states of the molecule have been calculated. In addition, radial matrix elements like
, n = 1, 2, and 3 have been calculated. These have been used to calculate the
‐pole static polarizabilities. The variation of bound state energies, matrix elements and
‐pole static polarizabilities with the boundary radius has also been studied. The Stark effect in case of this bounded system has also been investigated.
Examination of the Effect of N‐terminal Diproline and Charged Side Chains on the Stabilization of Helical Conformation in Alanine–based Short Peptides: A Molecular Dynamics Study
Authors: Goyal Bhupesh , Srivastava Kinshuk Raj , Durani Susheel
Published: December 2016

The effect of N‐terminal diproline segment and charged side chains on the stabilization of helical conformation in alanine‐based short peptides are examined using molecular dynamics (MD) simulations. The cationic peptides, Ac–Pro1–Pro2–Ala3–Lys4–Ala5–Lys6–Ala7–Lys8–Ala9–NH2 (Ia) and Ac–DPro1–Pro2–Ala3–Lys4–Ala5–Lys6–Ala7–Lys8–Ala9–NH2 (IIa) are examined for the role of lysine side chains on the inducement of helical conformation in alanine‐based short peptides. To examine the influence of lysine and glutamic acid in the i, i + 4 arrangement on the stabilization of helical conformation, cationic peptides, Ia and IIa, are modified as ion‐pair peptides, Ac–Pro1–Pro2–Glu3–Glu4–Ala5–Ala6–Lys7–Lys8–Ala9–NH2 (Ib) and Ac–DPro1–Pro2–Glu3–Glu4–Ala5–Ala6–Lys7–Lys8–Ala9–NH2 (IIb), respectively. MD simulations manifest enhanced occupancies in the α basin of ϕ, ψ space for ion‐pair peptides as compare to cationic peptides. The radial distribution function (RDF) analysis highlight that large side chain substituents of lysine and glutamic acid assist in helix formation by blocking water molecules from solvating backbone CO and NH groups.
Two 3D POM‐Based Inorganic–organic Hybrid Compounds Constructed from Different {VO3}4n Subunits and N‐donor ligands: Syntheses, Structures, Electrocatalytic and Magnetic Properties
Authors: Xiong Yao , Zhou Shuai , Hou WenTao , Xu Yan
Published: December 2016

Two new 3D organic‐inorganic hybrid materials Cu(bim)V2O6 (1) (bim=bis(1‐imidazolyl)methane) and Co(2‐mbim)V2O6 (2) (2‐mbim=bis(2‐methylimidazol‐1‐yl)methane) based on polyoxovanadates (POVs) and organic ligands decorated transition metal units have been synthesized by solvothermal methods. Single crystal XRD, soild UV‐vis and IR spectra, powder XRD, magnetic measurement and thermogravimetric (TG) measurements were performed to analyze the structures and properties of 1 and 2. The topological structures of both compounds are interesting, and not reported previously. Structural analysis indicates that compound 1 features a 3D zeolite‐like framework, constructed by wave‐like {V4O12}n4n− chains and [Cu(bim)2]n2n+ chains. These parallel chains constitute the fundamental motif via ‐(Cu‐O−V)‐ helical bridges. In the structure of 2, {V4O12}4− cycle is linked with four {V4O12}4− cycles giving rise to 2D {Co2V4O12}n layers which were further pillared by the organic 2‐mbim ligand via N–Co–O linkages to form the 3D framework. Electrochemical studies exhibit that compound 1 possesses excellent electrocatalytic activity toward the reduction of hydrogen peroxide. The magnetic susceptibility measurement indicates antiferromagnetic interactions in both 1 and 2.
Label‐Free Virus Capture and Release by a Microfluidic Device Integrated with Porous Silicon Nanowire Forest
Authors: Xia Yiqiu , Tang Yi , Yu Xu , Wan Yuan , Chen Yizhu , Lu Huaguang , Zheng Si‐Yang
Published: December 2016

Viral diseases are perpetual threats to human and animal health. Detection and characterization of viral pathogens require accurate, sensitive, and rapid diagnostic assays. For field and clinical samples, the sample preparation procedures limit the ultimate performance and utility of the overall virus diagnostic protocols. This study presents the development of a microfluidic device embedded with porous silicon nanowire (pSiNW) forest for label‐free size‐based point‐of‐care virus capture in a continuous curved flow design. The pSiNW forests with specific interwire spacing are synthesized in situ on both bottom and sidewalls of the microchannels in a batch process. With the enhancement effect of Dean flow, this study demonstrates that about 50% H5N2 avian influenza viruses are physically trapped without device clogging. A unique feature of the device is that captured viruses can be released by inducing self‐degradation of the pSiNWs in physiological aqueous environment. About 60% of captured viruses can be released within 24 h for virus culture, subsequent molecular diagnosis, and other virus characterization and analyses. This device performs viable, unbiased, and label‐free virus isolation and release. It has great potentials for virus discovery, virus isolation and culture, functional studies of virus pathogenicity, transmission, drug screening, and vaccine development.
Geklebte Kreishohlprofilanschlüsse in Stahlkonstruktionen
Authors: Albiez Matthias , Ummenhofer Thomas , Bucak Ömer , Ehard Heinrich , Fricke Holger , Vallée Till
Published: December 2016

Herrn Univ.‐Prof. Dr.‐Ing. Gerhard Hanswille zur Vollendung seines 65. Lebensjahres gewidmet

Derzeit werden Kreishohlprofilanschlüsse im Stahlbau in der Regel durch das Fügeverfahren Schweißen realisiert. Bei nicht ruhender Beanspruchung stellen die Schweißnähte jedoch stets den Ausgangsort von Ermüdungsrissen dar. Dieser Beitrag gibt einen Überblick über die Ergebnisse des abgeschlossenen FOSTA‐Forschungsprojektes P 884. Gegenstand dieses Projektes war die Entwicklung einer geklebten Verbindung zum Anschluss von Kreishohlprofilen an Stahlgussknoten unter Berücksichtigung der Anforderungen und Randbedingungen des Bauwesens. Die Verbindung wird dabei als Überlappungsstoß ausgeführt. Aufgrund der Maßtoleranzen der Fügeteile sind Dickschichtklebungen in der Größenordnung von mehreren Millimetern erforderlich. Die außerordentliche Leistungsfähigkeit der entwickelten Klebverbindung wird durch umfangreiche experimentelle Untersuchungen aufgezeigt.

Adhesively bonded structural hollow sections in steel constructions. Up to now, structural hollow sections, in particular tubulars, are connected by welding. However, welded joints are critical with regard to fatigue loads, and represent starting points of cracks that are difficult to monitor. This paper summarizes the findings of the FOSTA research project P 884, which focused on the development of adhesively bonded connections of tubular hollow sections to cast‐steel nodes. Particular attention was devoted to consider the particular conditions prevalent in civil engineering. Joints were designed as tubular lap joints. To compensate the hollow structural sections' manufacturing tolerances, adhesive layers of several millimeters in thickness were considered. The outstanding performance of the resulting adhesively bonded joints was proven in a large experimental campaign.
Overall Optimization for Offshore Wind Farm Electrical System
Authors: Hou Peng , Hu Weihao , Chen Cong , Chen Zhe
Published: December 2016

Based on particle swarm optimization (PSO), an optimization platform for offshore wind farm electrical system (OWFES) is proposed in this paper, where the main components of an offshore wind farm and key technical constraints are considered as input parameters. The offshore wind farm electrical system is optimized in accordance with initial investment by considering three aspects: the number and siting of offshore substations (OS), the cable connection layout of both collection system (CS) and transmission system (TS) as well as the selection of electrical components in terms of voltage level and capacity. Because hundreds of optimization variables, continuous or discrete, are involved in the problem, a mix integer PSO (MIPSO) is required to obtain the solution. The fuzzy C‐means clustering (FCM) algorithm is used to partition the wind farm into several sub regions. The collection system layout in each sub region as well as the connection scheme between offshore substations are optimized by an adaptive PSO‐minimum spanning tree algorithm (APSO‐MST) which has been proposed in a previous work. The simulation results show that the proposed optimization platform can find an optimized layout that save 3.01% total cost compared with the industrial layout, and can be a useful tool for OWFES design and evaluation. Copyright © 2016 John Wiley & Sons, Ltd.
Counselees’ Perspectives of Genomic Counseling Following Online Receipt of Multiple Actionable Complex Disease and Pharmacogenomic Results: a Qualitative Research Study
Authors: Sweet Kevin , Hovick Shelly , Sturm Amy C. , Schmidlen Tara , Gordon Erynn , Bernhardt Barbara , Wawak Lisa , Wernke Karen , McElroy Joseph , Scheinfeldt Laura , Toland Amanda E. , Roberts J. S. , Christman Michael
Published: December 2016

Genomic applications raise multiple challenges including the optimization of genomic counseling (GC) services as part of the results delivery process. More information on patients’ motivations, preferences, and informational needs are essential to guide the development of new, more efficient practice delivery models that capitalize on the existing strengths of a limited genetic counseling workforce. Semi‐structured telephone interviews were conducted with a subset of counselees from the Coriell Personalized Medicine Collaborative following online receipt of multiple personalized genomic test reports. Participants previously had either in‐person GC (chronic disease cohort, n = 20; mean age 60 years) or telephone GC (community cohort, n = 31; mean age 46.8 years). Transcripts were analyzed using a Grounded Theory framework. Major themes that emerged from the interviews include 1) primary reasons for seeking GC were to clarify results, put results into perspective relative to other health‐related concerns, and to receive personalized recommendations; 2) there is need for a more participant driven approach in terms of mode of GC communication (in‐person, phone, video), and refining the counseling agenda pre‐session; and 3) there was strong interest in the option of follow up GC. By clarifying counselees’ expectations, views and desired outcomes, we have uncovered a need for a more participant‐driven GC model when potentially actionable genomic results are received online.