bluuebunny/crossref_metadata_2025 huggingface dataset:
Microheterogeneity of Recombinant Antibodies: Analytics and Functional Impact
Authors: Beyer Beate , Schuster Manfred , Jungbauer Alois , Lingg Nico
Published: September 2017

Antibodies are typical examples of biopharmaceuticals which are composed of numerous, almost infinite numbers of potential molecular entities called variants or isoforms, which constitute the microheterogeneity of these molecules. These variants are generated during biosynthesis by so‐called posttranslational modification, during purification or upon storage. The variants differ in biological properties such as pharmacodynamic properties, for example, Antibody Dependent Cellular Cytotoxicity, complement activation, and pharmacokinetic properties, for example, serum half‐life and safety. Recent progress in analytical technologies such as various modes of liquid chromatography and mass spectrometry has helped to elucidate the structure of a lot of these variants and their biological properties. In this review the most important modifications (glycosylation, terminal modifications, amino acid side chain modifications, glycation, disulfide bond variants and aggregation) are reviewed and an attempt is made to give an overview on the biological properties, for which the reports are often contradictory. Even though there is a deep understanding of cellular and molecular mechanism of antibody modification and their consequences, the clinical proof of the effects observed in vitro and in vivo is still not fully rendered. For some modifications such as core‐fucosylation of the N‐glycan and aggregation the effects are clear and should be monitored, but with others such as C‐terminal lysine clipping the reports are contradictory. As a consequence it seems too early to tell if any modification can be safely ignored.
Comparison of microscopic and endoscopic view of the internal acoustic meatus: A cadaveric study
Authors: Montibeller Guilherme Ramina , Hendrix Philipp , Fries Fabian N. , Becker Kurt W. , Oertel Joachim
Published: August 2017

The endoscope is thought to provide an improved exposure of the internal acoustic meatus after retrosigmoid craniotomy for microsurgical resection of intrameatal tumors. The aim of this study is to quantify the differences in internal acoustic meatus (IAM) exposure comparing microscopic and endoscopic visualization. A retrosigmoid approach was performed on 5 cadaver heads. A millimeter gauge was introduced into the internal acoustic meatus, and examinations with a surgical microscope and 0°, 30° and 70° rigid endoscopes were performed. The extent of IAM depth visualized with the microscope and the different angled endoscopes were analyzed. The microscopic view allowed an average IAM depth visualization of 2.8 mm. The endoscope allowed an improved exposure of IAM in all cases. The 0°, 30° and 70° endoscopes permitted an exposure that was respectively 96% (5.5 mm), 139% (6.7 mm) and 200% (8.4 mm) more lateral than the microscopic view. Angled optics, however, provided an image distortion, specifically the 70° endoscope. The endoscope provides a superior visualization of the IAM compared to the microscope when using a retrosigmoid approach. The 30° endoscope represented an ideal compromise of superior visualization with marginal image distortion. Additional implementation of the endoscope into microsurgery of intrameatal tumors likely facilitates complete tumor removal and might spare facial and vestibulocochlear function. Clin. Anat. 31:398–403, 2018. © 2017 Wiley Periodicals, Inc.
Improving the Electrochemical Oxygen Reduction Activity of Manganese Oxide Nanosheets with Sulfurization‐Induced Nanopores
Authors: Zhang Tianran , Ge Xiaoming , Zhang Zhao , Tham Nguk Neng , Liu Zhaolin , Fisher Adrian , Lee Jim Yang
Published: August 2017

Low‐cost and high‐activity electrocatalysts for the oxygen reduction reaction (ORR) are necessary for the development of fuel cells and metal‐air batteries. Manganese oxide would be a good candidate because of its low cost, abundant supply, and environmental benignity if not for its relatively low activity compared with noble metals. To improve the ORR activity of manganese oxide, we developed a sulfurization process to create pores in 2 D manganese oxide nanosheets. The nanoporous MnO2 nanosheets (np‐MnO2‐ns) prepared as such contain 7 nm pores in the nanosheets and their half‐wave potential (0.73 V) is 40 mV more positive than that of pore‐free MnO2 nanosheets (0.69 V). The higher ORR activity of np‐MnO2‐ns may be attributed to the combination of a large surface area and the presence of high‐ORR‐activity Mn3+/4+ sites. The np‐MnO2‐ns also showed an enhanced oxygen evolution reaction activity and delivered a good performance in rechargeable Zn‐air batteries.
Chain‐Breaking Phenolic 2,3‐Dihydrobenzo[b]selenophene Antioxidants: Proximity Effects and Regeneration Studies
Authors: Singh Vijay P. , Yan Jiajie , Poon Jia‐Fei , Gates Paul J. , Butcher Ray J. , Engman Lars
Published: August 2017

Phenolic 2,3‐dihydrobenzo[b]selenophene antioxidants bearing an OH‐group ortho (9), meta (10, 11) and para (8) to the Se were prepared by seleno‐Claisen rearrangement/intramolecular hydroselenation. meta‐Isomer (11) was studied by X‐ray crystallography. The radical‐trapping activity and regenerability of compounds 8–11 were evaluated using a two‐phase system in which linoleic acid was undergoing peroxidation in the lipid phase while regeneration of the antioxidant by co‐antioxidants (N‐acetylcysteine, glutathione, dithiothreitol, ascorbic acid, tris(carboxyethyl)phosphine hydrochloride) was ongoing in the aqueous layer. Compound 9 quenched peroxyl radicals more efficiently than α‐tocopherol. It also provided the most long‐lasting antioxidant protection. With thiol co‐antioxidants it could inhibit peroxidation for more than five‐fold longer than the natural product. Regeneration was more efficient when the aqueous phase pH was slightly acidic. Since calculated O−H bond dissociation energies for 8–11 were substantially larger than for α‐tocopherol, an antioxidant mechanism involving O‐atom transfer from peroxyl to selenium was proposed. The resulting phenolic selenoxide/alkoxyl radical would then exchange a hydrogen atom in a solvent cage before antioxidant regeneration at the aqueous lipid interphase.
Subtle Steric Differences Impact the Structural and Conducting Properties of Radical Gold Bis(dithiolene) Complexes
Authors: Filatre‐Furcate Agathe , Roisnel Thierry , Fourmigué Marc , Jeannin Olivier , Bellec Nathalie , Auban‐Senzier Pascale , Lorcy Dominique
Published: August 2017

Among single component molecular conductors, neutral radical gold dithiolene complexes [(R‐thiazdt)2Au]. derived from the N‐alkyl‐1,3‐thiazoline‐2‐thione‐4,5‐dithiolate (R‐thiazdt) ligand provide an extensive series of conducting, non‐dimerized, half‐filled band systems. Analogues of the known R=isopropyl (iPr) derivative were investigated here with R=NMe2, cyclopropyl (cPr) and n‐propyl (nPr), aiming at rationalizing the different solid state structures adopted by these compounds despite very closely related substituents on the heterocyclic nitrogen atom. An original crisscross organization within dimerized chains is observed with R=NMe2, differing however from the analogous iPr derivative by a 180° rotation of the heterocyclic nitrogen substituent. On the other hand, the cyclopropyl and n‐propyl substituents lead to robust, uniform, non‐dimerized chains with a strongly 1 D electronic structure and a formal half‐filled electronic structure. The semiconducting behaviour of these two radical complexes is characteristic of a Mott insulator, whose sensitivity to external pressure has been evaluated up to 2.5 GPa.
Single‐Scan 13C Diffusion‐Ordered NMR Spectroscopy of DNP‐Hyperpolarised Substrates
Authors: Guduff Ludmilla , Kurzbach Dennis , van Heijenoort Carine , Abergel Daniel , Dumez Jean‐Nicolas
Published: August 2017

Diffusion‐ordered NMR spectroscopy (DOSY) is a powerful approach for the analysis of molecular mixtures, yet its application range is limited by the relatively low sensitivity of NMR. We show here that spectrally resolved 13C DOSY data can be collected, in a single scan, for substrates hyperpolarised by dissolution dynamic nuclear polarisation (D‐DNP), which provides signal enhancements of several orders of magnitude. For this we use a convection‐compensation pulse scheme, which we also analyse by numerical simulation. The proposed method further allows the acquisition of several consecutive DOSY spectra in a single D‐DNP experiment.
Ethanol:water blends separation using ultrafiltration membranes of poly(acrylamide‐co‐acrylic acid) partial sodium salt and polyacrylamide
Authors: Espinoza‐Gomez Heriberto , Saucedo‐Castillo Eduardo , Flores‐López Lucía Z. , Rogel‐Hernandez Eduardo , Martínez Manuel , Wakida Fernando T.
Published: August 2017

In this work, poly(acrylamide‐co‐acrylic acid) partial sodium salt (P(AAM‐co‐AA)Na), and polyacrylamide (PAAM) membranes were synthesized for separation of ethanol:water blends. The membrane characteristics were evaluated to determine their ability to separate mixtures of ethanol:water and get dehydrate ethanol (95 %). Synthesized membranes showed higher selectivity to ethanol compared to existing polymeric membranes. The ethanol:water blends had an ethanol concentration of 0.10 to 0.70 L/L. The results showed that a mixture of ethanol:water (75:25 L/L) can be concentrated up to 95 % ethanol. The membranes’ stability were studied in absolute ethanol and ethanol:water blend (30:70 L/L) for a period of 30 days of permanent exposure. The membrane deterioration is due to the chemical modification of the membrane active surface layer. It was found that the membranes have a high selectivity (350 times higher) compared to existing membranes, and the substantial and flow of water was 12.15 kg · m−2 · h−1.
Recent Advances and Perspectives of Transition Metal‐Catalyzed Asymmetric Fluorination Reactions
Authors: Chen Chaohuang , Fu Liang , Chen Pinhong , Liu Guosheng
Published: August 2017

The synthesis of fluorine‐containing molecules has received intensive attention in recent years due to the great value of fluorides, however, the transition metal‐catalyzed asymmetric construction of C—F bonds is much less developed. This review presents the recent advancement of transition metal‐catalyzed asymmetric fluorination reactions, in which the final C—F bond is from reductive elimination of organometallic complexes. In addition, the perspective of the field is also provided for the future studies of asymmetric fluorinations and the related transformations, such as trifluoromethylation, trifluoromethylthiolation and trifluoromethoxylation.
Semantic approach for multi‐objective optimisation of the ENTICE distributed Virtual Machine and container images repository
Authors: Gec Sandi , Kimovski Dragi , Paščinski Uroš , Prodan Radu , Stankovski Vlado
Published: August 2017

New software engineering technologies facilitate development of applications from reusable software components, such as Virtual Machine and container images (VMI/CIs). Key requirements for the storage of VMI/CIs in public or private repositories are their fast delivery and cloud deployment times. ENTICE is a federated storage facility for VMI/CIs that provides optimisation mechanisms through the use of fragmentation and replication of images and a Pareto Multi‐Objective Optimisation (MO) solver. The operation of the MO solver is, however, time‐consuming due to the size and complexity of the metadata, specifying various non‐functional requirements for the management of VMI/CIs, such as geolocation, operational cost, and delivery time. In this work, we address this problem with a new semantic approach, which uses an ontology of the federated ENTICE repository, knowledge base, and constraint‐based reasoning mechanism. Open Source technologies such as Protégé, Jena Fuseki, and Pellet were used to develop a solution. Two specific use cases, (1) repository optimisation with offline and (2) online redistribution of VMI/CIs, are presented in detail. In both use cases, data from the knowledge base are provided to the MO solver. It is shown that Pellet‐based reasoning can be used to reduce the input metadata size used in the optimisation process by taking into consideration the geographic location of the VMI/CIs and the provenance of the VMI fragments. It is shown that this process leads to reduction of the input metadata size for the MO solver by up to 60% and reduction of the total optimisation time of the MO solver by up to 68%, while fully preserving the quality of the solution, which is significant.
Boosted decision trees for behaviour mining of concurrent programmes
Authors: Avros R. , Dudka V. , Křena B. , Letko Z. , Pluháčková H. , Ur S. , Vojnar T. , Volkovich Z.
Published: August 2017

Testing of concurrent programmes is difficult since the scheduling nondeterminism requires one to test a huge number of different thread interleavings. Moreover, repeated test executions that are performed in the same environment will typically examine similar interleavings only. One possible way how to deal with this problem is to use the noise injection approach, which influences the scheduling by injecting various kinds of noise (delays, context switches, etc) into the common thread behaviour. However, for noise injection to be efficient, one has to choose suitable noise injection heuristics from among the many existing ones as well as to suitably choose values of their various parameters, which is not easy. In this paper, we propose a novel way how to deal with the problem of choosing suitable noise injection heuristics and suitable values of their parameters (as well as suitable values of parameters of the programmes being tested themselves). Here, by suitable, we mean such settings that maximize chances of meeting a given testing goal (such as, eg, maximizing coverage of rare behaviours and thus maximizing chances to find rarely occurring concurrency‐related bugs). Our approach is, in particular, based on using data mining in the context of noise‐based testing to get more insight about the importance of the different heuristics in a particular testing context as well as to improve fully automated noise‐based testing (in combination with both random as well as genetically optimized noise setting).
Communication in task‐parallel ILU‐preconditioned CG solvers using MPI + OmpSs
Authors: Aliaga José I. , Barreda María , Flegar Goran , Bollhöfer Matthias , Quintana‐Ortí Enrique S.
Published: August 2017

We target the parallel solution of sparse linear systems via iterative Krylov subspace–based methods enhanced with incomplete LU (ILU)‐type preconditioners on clusters of multicore processors. In order to tackle large‐scale problems, we develop task‐parallel implementations of the classical iteration for the CG method, accelerated via ILUPACK and ILU(0) preconditioners, using MPI + OmpSs. In addition, we integrate several communication‐avoiding strategies into the codes, including the butterfly communication scheme and Eijkhout's formulation of the CG method. For all these implementations, we analyze the communication patterns and perform a comparative analysis of their performance and scalability on a cluster consisting of 16 nodes, with 16 cores each.
X‐Ray Reciprocal Space Mapping of MBE Grown HgCdTe on Alternative Substrates
Authors: Madni Imtiaz , Umana‐Membreno Gilberto A. , Lei Wen , Gu Renjie , Antoszewski Jarek , Faraone Lorenzo
Published: August 2017

X‐ray reciprocal space mapping is used to yield quantitative information on strain, strain‐relaxation, shear, as well as dislocation density and mosaicity in MBE‐grown HgCdTe heterostructures. Triple axis x‐ray diffractometry is used to obtain the data, and analysis of the isointensity contours of scattered x‐ray intensity around reciprocal lattice points in HgCdTe epitaxial layers grown on (211)‐oriented substrates. Three different substrates, GaSb, GaAs, and CdZnTe, are used in this investigation. The in‐plane and out‐of‐plane lattice parameters, and strain of the HgCdTe epilayer and underlying CdTe buffer layer, are determined from x‐ray reciprocal space maps about the symmetric (422), and asymmetric (333 & 511) reciprocal lattice points. Analysis of X‐ray scattering about the lattice mismatched reciprocal lattice points show approximately an order of magnitude increase in shear, dislocation density, and strain for growth on alternative substrates in comparison to HgCdTe grown on lattice matched CdZnTe. HgCdTe on GaSb exhibits less shear and the layers are found to be relaxed within the buffer layer. In comparison, higher density of misfit dislocations were found in epilayers grown on GaAs. The analysis of strain distribution, and misfit dislocation density clearly indicate the potential application of GaSb as an alternative substrate for MBE growth of HgCdTe.
Insight into Aluminum Sulfate‐Catalyzed Xylan Conversion into Furfural in a γ‐Valerolactone/Water Biphasic Solvent under Microwave Conditions
Authors: Yang Tao , Zhou Yi‐Han , Zhu Sheng‐Zhen , Pan Hui , Huang Yao‐Bing
Published: August 2017

A simple and efficient biphasic system with an earth‐abundant metal salt catalyst was used to produce furfural from xylan with a high yield of up to 87.8 % under microwave conditions. Strikingly, the metal salt Al2(SO4)3 exhibited excellent catalytic activity for xylan conversion, owing to a combination of Lewis and Brønsted acidity and its ability to promote good phase separation. The critical role of the SO42− anion was first analyzed, which resulted in the aforementioned characteristics when combined with the Al3+ cation. The mixed solvent system with γ‐valerolactone (GVL) as the organic phase provided the highest furfural yield, resulting from its good dielectric properties and dissolving capacity, which facilitated the absorption of microwave energy and promoted mass transfer. Mechanistic studies suggested that the xylan‐to‐furfural conversion proceeded mainly through a hydrolysis–isomerization–dehydration pathway and the hexa‐coordinated Lewis acidic [Al(OH)2(aq)]+ species were the active sites for xylose–xylulose isomerization. Detailed kinetic studies of the subreaction for the xylan conversion revealed that GVL regulates the reaction rates and pathways by promoting the rates of the key steps involved for furfural production and suppressing the side reactions for humin production. Finally, the Al2(SO4)3 catalyst was used for the production of furfural from several lignocellulosic feedstocks, revealing its great potential for other biomass conversions.
“Solid Oxide Fuel Cells, Electrolyzers and Reactors: From Development to Delivery – EFCF2016”
Authors: Brandon Nigel , Hagen Anke , Dawson Richard , Bucheli Olivier
Published: August 2017

No abstract.
Characterization of the Lower Silurian Longmaxi marine shale in Changning area in the south Sichuan Basin, China
Authors: Jiang Yuqiang , Chen Lei , Qi Lin , Luo Mingsheng , Chen Xiaoyan , Tao Yanzhong , Wang Zhanlei
Published: August 2017

On the basis of the core description, thin sections, and geochemistry data, we characterized the Lower Silurian Longmaxi marine shale in the Changning area in the south Sichuan Basin. Ten lithofacies were identified in the Lower Silurian Longmaxi marine shale: (a) massive silty shale (Lithofacies A); (b) laminated siliceous calcareous shale (Lithofacies B); (c) calcareous shale (Lithofacies C); (d) silty dolomitic shale (Lithofacies D); (e) argillaceous siltstone (Lithofacies E); (f) siltstone (Lithofacies F); (g) laminated silty shale (Lithofacies G); (h) silty calcareous shale (Lithofacies H); (i) argillaceous lime shale (marl) (Lithofacies I); and (j) bentonite (Lithofacies J). Obvious heterogeneity occurred in different lithofacies in terms of mineralogy, total organic carbon (TOC) content, porosity, permeability, pore surface area, total pore volume, and total gas content. Among these lithofacies, Lithofacies B has the highest porosity (5.4%), pore surface area (12.79 m2/g), total pore volume (0.015 cc/g), TOC content (4.37%), total gas content (3.4 m3/ton), and relatively high brittle minerals, suggesting great shale gas potential. Lithofacies A, C, and D have a relatively high brittle minerals, porosity, pore surface area, total pore volume, TOC content, and total gas content, which means that these 3 lithofacies show relatively good potential for shale gas. The rest of the lithofacies have low brittle minerals content, porosity, pore surface area, total pore volume, TOC content, and total gas content, representing poor shale gas potential.
Reactive astrocyte COX2‐PGE2 production inhibits oligodendrocyte maturation in neonatal white matter injury
Authors: Shiow Lawrence R. , Favrais Geraldine , Schirmer Lucas , Schang Anne‐Laure , Cipriani Sara , Andres Christian , Wright Jaclyn N. , Nobuta Hiroko , Fleiss Bobbi , Gressens Pierre , Rowitch David H.
Published: August 2017

Inflammation is a major risk factor for neonatal white matter injury (NWMI), which is associated with later development of cerebral palsy. Although recent studies have demonstrated maturation arrest of oligodendrocyte progenitor cells (OPCs) in NWMI, the identity of inflammatory mediators with direct effects on OPCs has been unclear. Here, we investigated downstream effects of pro‐inflammatory IL‐1β to induce cyclooxygenase‐2 (COX2) and prostaglandin E2 (PGE2) production in white matter. First, we assessed COX2 expression in human fetal brain and term neonatal brain affected by hypoxic‐ischemic encephalopathy (HIE). In the developing human brain, COX2 was expressed in radial glia, microglia, and endothelial cells. In human term neonatal HIE cases with subcortical WMI, COX2 was strongly induced in reactive astrocytes with “A2” reactivity. Next, we show that OPCs express the EP1 receptor for PGE2, and PGE2 acts directly on OPCs to block maturation in vitro. Pharmacologic blockade with EP1‐specific inhibitors (ONO‐8711, SC‐51089), or genetic deficiency of EP1 attenuated effects of PGE2. In an IL‐1β‐induced model of NWMI, astrocytes also exhibit “A2” reactivity and induce COX2. Furthermore, in vivo inhibition of COX2 with Nimesulide rescues hypomyelination and behavioral impairment. These findings suggest that neonatal white matter astrocytes can develop “A2” reactivity that contributes to OPC maturation arrest in NWMI through induction of COX2‐PGE2 signaling, a pathway that can be targeted for neonatal neuroprotection.
Psychosocial behaviour management programme for home‐dwelling people with dementia: A cluster‐randomized controlled trial
Authors: Nakanishi Miharu , Endo Kaori , Hirooka Kayo , Granvik Eva , Minthon Lennart , Nägga Katarina , Nishida Atsushi
Published: August 2017

Objective

Little is known about the effectiveness of a psychosocial behaviour management programme on home‐dwelling people with dementia. We developed a Behaviour Analytics & Support Enhancement (BASE) programme for care managers and professional caregivers of home care services in Japan. We investigated the effects of BASE on challenging behaviour of home‐dwelling people with dementia.

Methods

A cluster‐randomized controlled trial was conducted with home care providers from 3 different districts in Tokyo. Each provider recruited persons with dementia aged 65 years or older to receive home care in the BASE programme in August 2016. An online monitoring and assessment system was introduced to the intervention group for repeated measures of challenging behaviour with a total score of the Neuropsychiatric Inventory. Care professionals in both the intervention and control groups evaluated challenging behaviour of persons with dementia at baseline (September 2016) and follow‐up (February 2017).

Results

A majority of persons with dementia had Alzheimer disease (59.3%). One‐hundred and forty‐one persons with dementia were included in the intervention group and 142 in the control group. Multilevel modelling revealed a significant reduction in challenging behaviour in the intervention group after 6 months (mean score, 18.3 to 11.2) compared with that of the control group (11.6 to 10.8; P < .05).

Conclusion

The implementation of the BASE programme resulted in a reduction of challenging behaviour of home‐dwelling people with dementia. Future research should examine the long‐term effects of behaviour management programmes on behaviour, nursing home placement, and hospital admission of home‐dwelling people with dementia.
Raising quality whilst reducing cost in health care: A retrospective cohort study
Authors: Jeve Yadava B.
Published: August 2017

Objective

The objective of this study was to investigate the relationship between cost and quality within the health care sector and to establish which factors could influence this relationship. The aim was to investigate the dynamics of the relationship, in order to improve the quality whilst reducing the cost.

Design

This is a retrospective cohort study, analysing quality, safety, and financial data from a 5‐year period.

Setting

A publicly funded tertiary hospital.

Participants

The dependent variable was cost saved, and the independent variables were patient safety, patient satisfaction, and clinical efficiency.

Main outcome measures: Financial savings and quality domains.

Results

A statistically significant relationship between the variables was found. Multivariate analysis derived the equation Y = βX1 + c, where Y is the cost saved, β is the beta coefficient, X1 is the clinical efficiency, and c is a constant. R2 = 0.874 (coefficient of determination), which suggested that the cost saved by the unit varied due to clinical efficiency. Clinical efficiency accounted for 87.4% of the variation in the cost saved by the unit.

Conclusions

The results indicated that, after the trade‐off value, an improvement in the quality would result in reduced costs for the unit. Clinical efficiency of the services was found to be the key factor determining this relationship. Therefore, strategies to increase clinical efficiency, and thus overall quality, above the trade‐off level could result in significant financial savings. Patient safety and patient experience were positively correlated with clinical efficiency.
Evaluating Australia's most complex system‐of‐systems, the future submarine: A case for using new Complex Systems Governance
Authors: Bradley Joseph M. , Joiner Keith F. , Efatmaneshnik Mahmoud , Keating Charles B.
Published: August 2017

As many systems grew in complexity and connected to other existing systems, the concept of Systems of Systems (SoS) was developed to explain the behavior, operation and design of these more complex and inter‐connected systems. Early research recognized the difficulty in classic testing and evaluating (T&E) for these SoS. Much effort has been expended attempting to predict the emergent behaviors in SoSs, developing and executing T&E programs involving more sophisticated multi‐factor and multi‐response statistical techniques, and then recovering when some unpredicted emergent behaviors were discovered despite these efforts. Recently, an emerging concept of Complex System Governance (CSG) has been developed as yet another weapon in the armory for managing development of complex interdependent capability architectures. CSG is based on a firm grounding in System Theory and Management Cybernetics. The potential application of robust CSG structure to reduce or mitigate emergent T&E surprises is proposed in this paper. Using Australia's Future Submarine (FSM) program as an illustration, this paper has examined the need for such an application, examine several of the governance propositions focused on the developmental T&E regime and provided potential areas to leverage the efficacy of this approach to such major development programs.
Applying A3 reports for early validation and optimization of stakeholder communication in development projects
Authors: Frøvold Kristian , Muller Gerrit , Pennotti Michael
Published: August 2017

We observed in our company that there is too little communication between development groups and external stakeholders. Large organizational distances can explain some of these problems. Insufficient communication can lead to validation problems, if requirements are developed on the wrong basis. For development groups it can be hard to see real customer needs. Will the operator/customer be satisfied? How will the whole system function as a product?

A3 reports emerged as a problem‐solving tool from Toyota's lean development. Toyota's success with this method led to the method spreading to other domains. This study applied the method of using A3 sheets, with modeling and text, for early validation and communication purposes.

This study's goal was to create tool for early validation and communication, for system design. The study shows that by using A3 reports for early validation designers may improve communication, build a common understanding, and contribute to the early validation for a system or a system function. This research focuses on a top‐level system function, developed in a large multidisciplinary project. The function interfaced many systems and required extensive communication. By using A3 reports knowledge was collected, systemized, analyzed, shared, and incrementally improved, Participants in the study concluded that this visualization technique was supporting early validation.
Using an Agent‐Based Simulation to Evaluate the Performance of Control Algorithms for an Intelligent Traffic Light System
Authors: Panek John
Published: August 2017

This paper examines a case study for using an agent‐based model to evaluate potential solutions to the ubiquitous problem of automobile traffic. The overall objective is to use simulations to evaluate the performance of intelligent traffic light system control algorithms to improve traffic flow along an entire section of highway. The approach uses an agent‐based modeling tool to simulate the flow of traffic using several different traffic control algorithms. The methodology includes steps to define the measures of effectiveness, simulation parameters, traffic control algorithms, and identify a simulation tool, followed by simulating the algorithms, and evaluating the performance results. Several alternative algorithms were evaluated including single‐intersection control and multi‐intersection synchronized flow. The initial results show a significant performance difference between the control algorithms. However, simulated traffic conditions need to be validated, along with further model refinements, before a final assessment of the algorithm performance can be made.
A Complexity Measure for System Safety Assurance
Authors: Sheard Sarah A. , Konrad Michael D. , Weinstock Charles B. , Nichols William R.
Published: August 2017

This paper describes a two‐year research effort to define complexity measures for avionics systems in order to help the FAA identify when systems are too complex to be able to assure their safety. The research project developed a measure of complexity related to the number of ways that an avionics system error (fault) could propagate from one element to another. Since each potential propagation requires another sub‐argument in the safety case, the number of such arguments should be proportional to certification effort. Thus, the ability to show that the system is safe, through the certification process, should depend on whether a system has low enough complexity (number of ways for errors to propagate).

Our results include a formula for estimating the “error‐propagation complexity” from a system design, the results of using that formula on small and medium systems, and steps for using the formula. The test of the formula was performed by repeating that calculation on a second design for the first system and briefly on a larger design identified by the FAA, from a NASA technical report.
Model‐based design of an autonomous function for responsive satellite operations
Authors: Obata Toshihiro , Nakasuka Shinichi , Shirasaka Seiko
Published: August 2017

PROMPT (PRompt Observation Methodology with intelligent Pointing and Testing) is a concept for the responsive observation method used by a satellite with an autonomous function on board. This paper shows its concept of how to shorten the timeline to observation of days to a month that normal satellites take after their launch. It also shows a model‐based design of an autonomous function that enables a robust satellite behavior against on‐orbit uncertainties.
Environmental Asset Management: Risk Management Systems
Authors: Naudé Brian , Petzer Charl
Published: August 2017

Environmental Asset Management (EAM) includes Environmental Asset Protection (EAP). Rare, important, and valuable natural assets need protection from vandalism and criminal syndicates determined to exploit these assets, for commercial gain or other purposes until the assets are exhausted. This paper addresses elements of environmental crime and the risk management strategies as part of EAP, including risk management system functions. A unique implemented risk management system in the Kruger National Park (KNP) is presented. Aspects of implementation are discussed including; challenges, lessons learnt, and initial measurable effects obtained.
Development of a Model to Gauge Second‐order Effects of Train Component Upgrades
Authors: Scott William , Cao Vu Lam , Peculis Ricardo , Campbell Peter
Published: August 2017

When upgrading rail infrastructure ROI‐based decisions partly rely on the demonstration of immediate improvements from those upgrades to the system. The rail industry is beginning to suffer in some areas from diminishing ROI from improving parts of its infrastructure. To inform decisions and help justify large expenditures, modelling needs to be done to detect the likely improvement to dependent systems as well as the primary system. Sydney Trains (ST) has undertaken a pilot study to demonstrate how modelling can be used to propagate performance changes made in one sub‐system into its dependent neighbors. The trial examines how to model the effect of improvements to the air dryer on the reliability and lifecycle of pneumatic systems of the Tangara train which utilize the air: the doors and brakes. The very detailed level model in this case helps provide evidence of improved reliability in these dependent systems can then be used to further justify the ROI and to assist in assessing the safety of the system on an ongoing basis.
Writing Instruction and Mentor Text Habits of Mind: A Review of Writing With Mentors: How to Reach Every Writer in the Room Using Current, Engaging Mentor Texts
Authors: Kerr Kristine Rodriguez
Published: August 2017

This forum reviews a mix of resources (written texts, graphic novels, documentaries, and mixed‐media pieces) to inform pedagogy and related educational practices that foreground representations of youths and their literacy practices within and outside of school.
Comparing cross‐country estimates of Lorenz curves using a Dirichlet distribution across estimators and datasets
Authors: Chang Andrew C. , Li Phillip , Martin Shawn M.
Published: August 2017

Chotikapanich and Griffiths (Journal of Business and Economic Statistics, 2002, 20(2), 290–295) introduced the Dirichlet distribution to the estimation of Lorenz curves. This distribution naturally accommodates the proportional nature of income share data and the dependence structure between the shares. Chotikapanich and Griffiths fit a family of five Lorenz curves to one year of Swedish and Brazilian income share data using unconstrained maximum likelihood and unconstrained nonlinear least squares. We attempt to replicate the authors' results and extend their analyses using both constrained estimation techniques and five additional years of data. We successfully replicate a majority of the authors' results and find that some of their main qualitative conclusions also hold using our constrained estimators and additional data.
Vertebral Fracture Risk in Diabetic Elderly Men: The MrOS Study
Authors: Napoli Nicola , Schwartz Ann V , Schafer Anne L , Vittinghoff Eric , Cawthon Peggy M , Parimi Neeta , Orwoll Eric , Strotmeyer Elsa S , Hoffman Andrew R , Barrett-Connor Elizabeth , Black Dennis M ,   for the Osteoporotic Fractures in Men (MrOS) Study Research Group
Published: September 2017

Type 2 diabetes (T2DM) is associated with a significant increase in risk of nonvertebral fractures, but information on risk of vertebral fractures (VFs) in subjects with T2DM, particularly among men, is lacking. Furthermore, it is not known whether spine bone mineral density (BMD) can predict the risk of VF in T2DM. We sought to examine the effect of diabetes status on prevalent and incident vertebral fracture, and to estimate the effect of lumbar spine BMD (areal and volumetric) as a risk factor for prevalent and incident morphometric vertebral fracture in T2DM (n = 875) and nondiabetic men (n = 4679). We used data from the Osteoporotic Fractures in Men (MrOS) Study, which enrolled men aged ≥65 years. Lumbar spine areal BMD (aBMD) was measured with dual-energy X-ray absorptiometry (DXA), and volumetric BMD (vBMD) by quantitative computed tomography (QCT). Prevalence (7.0% versus 7.7%) and incidence (4.4% versus 4.5%) of VFs were not higher in T2DM versus nondiabetic men. The risk of prevalent (OR, 1.05; 95% CI, 0.78 to 1.40) or incident vertebral-fracture (OR, 1.28; 95% CI, 0.81 to 2.00) was not higher in T2DM versus nondiabetic men in models adjusted for age, clinic site, race, BMI, and aBMD. Higher spine aBMD was associated with lower risk of prevalent VF in T2DM (OR, 0.55; 95% CI, 0.48 to 0.63) and nondiabetic men (OR, 0.66; 95% CI, 0.5 to 0.88) (p for interaction = 0.24) and of incident VF in T2DM (OR, 0.50; 95% CI, 0.41 to 0.60) and nondiabetic men (OR, 0.54; 95% CI, 0.33 to 0.88) (p for interaction = 0.77). Results were similar for vBMD. In conclusion, T2DM was not associated with higher prevalent or incident VF in older men, even after adjustment for BMI and BMD. Higher spine aBMD and vBMD are associated with lower prevalence and incidence of VF in T2DM as well as nondiabetic men. © 2017 American Society for Bone and Mineral Research.
Model‐Based Approach to Predict Adherence to Protocol During Antiobesity Trials
Authors: Sharma Vishnu D. , Combes François P. , Vakilynejad Majid , Lahu Gezim , Lesko Lawrence J. , Trame Mirjam N.
Published: August 2017

Development of antiobesity drugs is continuously challenged by high dropout rates during clinical trials. The objective was to develop a population pharmacodynamic model that describes the temporal changes in body weight, considering disease progression, lifestyle intervention, and drug effects. Markov modeling (MM) was applied for quantification and characterization of responder and nonresponder as key drivers of dropout rates, to ultimately support the clinical trial simulations and the outcome in terms of trial adherence. Subjects (n = 4591) from 6 Contrave® trials were included in this analysis. An indirect‐response model developed by van Wart et al was used as a starting point. Inclusion of drug effect was dose driven using a population dose‐ and time‐dependent pharmacodynamic (DTPD) model. Additionally, a population‐pharmacokinetic parameter‐ and data (PPPD)‐driven model was developed using the final DTPD model structure and final parameter estimates from a previously developed population pharmacokinetic model based on available Contrave® pharmacokinetic concentrations. Last, MM was developed to predict transition rate probabilities among responder, nonresponder, and dropout states driven by the pharmacodynamic effect resulting from the DTPD or PPPD model. Covariates included in the models and parameters were diabetes mellitus and race. The linked DTPD‐MM and PPPD‐MM was able to predict transition rates among responder, nonresponder, and dropout states well. The analysis concluded that body‐weight change is an important factor influencing dropout rates, and the MM depicted that overall a DTPD model‐driven approach provides a reasonable prediction of clinical trial outcome probabilities similar to a pharmacokinetic‐driven approach.
Personal characteristics associated with individual degree of family function in residents of Rumoi City, Hokkaido
Authors: Takeda Shinichi , Sasagawa Yutaka , Mori Mitsuru
Published: August 2017

Background

We assessed the association of personal factors with Family APGAR not only among the subjects in nonsingle households, but also in single households.

Methods

We randomly chose 1 000 persons aged from 50 to 89 years in Rumoi City of the west area of Hokkaido as study candidates, and 493 subjects responded to the survey. We compared the group of high Family APGAR (FA) score of more than or equal to seven with the group of low FA score of less than or equal to 6 with regard to health‐related QOL (HRQOL), measured with SF‐8, Index of Social interaction (ISI), and other personal characteristics. Being in the low FA group indicates living with a status of poor family function.

Results

As a result of the multivariate logistic regression model, living in single households, currently smoking, a low score of mental component summary (MCS) in HRQOL, and a low score of lSI were all significantly associated with being in the low FA group. A low score of MCS was significantly associated with being in the low FA group both in the stratum of nonsingle households, and in the stratum of single households.

Conclusions

There were three risk factors of low FA. The first is a single household, second is currently smoking in a nonsingle household, and the third is low ISI. Worse mental status is found to be associated with low FA among the subjects not only in nonsingle households, but also in single households.
Synthesis of Novel Chromene, Pyridine, Pyrazole, Pyrimidine, and Imidazole Derivatives via One‐pot Multicomponent Reaction
Authors: Khodairy Ahmed , Ali Ali M. , El‐Wassimy Mohamed T.
Published: August 2017

New series of chromenes 2–4, pyridines 5–8, and pyranopyrazoles 9a,b were synthesized via one‐pot multicomponent reaction of 4‐tosyloxybenzaldehyde (1) and malononitrile with phenols, amines or hydrazines, and ethyl acetoacetate, respectively. Compound 9a was reacted with acetic anhydride, formic acid, or formamide to afford N‐acetyl derivative 10 and pyrazolopyranopyrimidines 11–13, respectively. Imidazole derivatives 14 and 15a–d were obtained by multicomponent reaction between compound 1 with ammonium acetate and benzil or aromatic amines in (1:2:1) or (1:1:1:1) ratio, respectively. The structures of new compounds were elucidated by elemental and spectral analyses.
An Efficient Synthesis of Pyrrolo[1,2‐a] or Pyrido[1,2‐a]benzo[4,5]imidazo[1,2‐c]quinazoline Derivatives in Ionic Liquids Catalyzed by Iodine
Authors: Wang Yue , Liu Jian‐Quan , Wang Xiang‐Shan
Published: August 2017

2‐(1H‐benzo[d]imidazol‐2‐yl)anilines reacted with haloketones including 5‐chloropentan‐2‐one and 6‐chlorohexan‐2‐one catalyzed by iodine, giving benzo[4,5]imidazo[1,2‐c]pyrrolo[1,2‐a]quinazoline and 6H‐benzo[4,5]imidazo[1,2‐c]pyrido[1,2‐a]quinazoline derivatives, respectively. This domino‐type reaction formed two new heterocycles and three new covalent bonds in one‐pot procedure and provided a green method for the synthesis of fused pentacyclic heterocycles bearing both quinazoline and benzimidazole moieties in ionic liquids.
Facile and Stereospecific Synthesis of Various Dienones Using Task‐specific Ionic Liquid/Borohydride as Stable and Promoted Hydrogen Release Reagent
Authors: Mouradzadegun Arash , Ganjali Mohammad Reza , Sabbagh Elham , Abadast Fatemeh
Published: August 2017

In this work, for the first time, task‐specific ionic liquid, 1‐n‐butyl‐3‐methylimidazolium borohydride ([bmim]BH4), was used as the medium as well as reagent for the regiospecific reduction of triarylpyrylium perchlorates to provide aromatic dienones as only product. The [bmim]BH4 having a reactive anion also could promote the desired reaction thereby reducing the reaction times and improving the yields substantially. The products could be easily isolated from the reaction mixture by simple extraction.
Myelin content changes in probable Alzheimer's disease and mild cognitive impairment: Associations with age and severity of neuropsychiatric impairment
Authors: Kavroulakis Eleftherios , Simos Panagiotis G. , Kalaitzakis Georgios , Maris Thomas G. , Karageorgou Dimitra , Zaganas Ioannis , Panagiotakis Simeon , Basta Maria , Vgontzas Alexandros , Papadaki Efrosini
Published: September 2017

Background

Existing indices of white matter integrity such as fractional anisotropy and magnetization transfer ratio may not provide optimal specificity to myelin content. In contrast, myelin water fraction (MWF) derived from the multiecho T2 relaxation time technique may serve as a more direct measure of myelin content.

Purpose/Hypothesis

The goal of the present study was to identify markers of regional demyelination in patients with probable Alzheimer's disease (AD) and mild cognitive impairment (MCI) in relation to age and severity of neuropsychiatric impairment.

Population

The sample included patients diagnosed with probable AD (n = 25) or MCI (n = 43), and cognitively intact elderly controls (n = 33).

Field Strength/Sequence Assessment

Long T2, short T2, and MWF values were measured with a 1.5T scanner in periventricular and deep normal‐appearing white matter (NAWM), serving as indices of intra/extracellular water content and myelin content. A comprehensive neuropsychological and neuropsychiatric assessment was administered to all participants.

Statistical Tests, Results

AD patients displayed higher age‐adjusted long and short T2 values and reduced MWF values in left temporal/parietal and bilateral periventricular NAWM than controls and MCI patients (P < 0.004; one‐way analysis of covariance [ANCOVA] tests). Short T2/MWF values in temporal, frontal, and periventricular NAWM of controls and/or MCI patients were significantly associated with episodic and semantic memory performance and depressive symptomatology (P < 0.004; partial correlation indices). The impact of age on memory performance was significantly (P < 0.01; mediated linear regression analyses) mediated by age‐related changes in short T2 and MWF values in these regions.

Data Conclusion

Age‐related demyelination is associated with memory impairment (especially in prodromal dementia states) and symptoms of depression in an anatomically specific manner.

Level of Evidence: 1

Technical Efficacy: Stage 3

J. Magn. Reson. Imaging 2018;47:1359–1372.