bluuebunny/crossref_metadata_2025 huggingface dataset:
Essential role of IκBNS for in vivo CD4+ T‐cell activation, proliferation, and Th1‐cell differentiation during Listeria monocytogenes infection in mice
Authors: Frentzel Sarah , Katsoulis‐Dimitriou Konstantinos , Jeron Andreas , Schmitz Ingo , Bruder Dunja
Published: May 2019

Acquisition of effector functions in T cells is guided by transcription factors, including NF‐κB, that itself is tightly controlled by inhibitory proteins. The atypical NF‐κB inhibitor, IκBNS, is involved in the development of Th1, Th17, and regulatory T (Treg) cells. However, it remained unclear to which extend IκBNS contributed to the acquisition of effector function in T cells specifically responding to a pathogen during in vivo infection. Tracking of adoptively transferred T cells in Listeria monocytogenes infected mice antigen‐specific activation of CD4+ T cells following in vivo pathogen encounter to strongly rely on IκBNS. While IκBNS was largely dispensable for the acquisition of cytotoxic effector function in CD8+ T cells, IκBNS‐deficient Th1 effector cells exhibited significantly reduced proliferation, marked changes in the pattern of activation marker expression, and reduced production of the Th1‐cell cytokines IFN‐γ, IL‐2, and TNF‐α. Complementary in vitro analyses using cells from novel reporter and inducible knockout mice revealed that IκBNS predominantly affects the early phase of Th1‐cell differentiation while its function in terminally differentiated cells appears to be negligible. Our data suggest IκBNS as a potential target to modulate specifically CD4+ T‐cell responses.
Protein‐Templated Dynamic Combinatorial Chemistry: Brief Overview and Experimental Protocol
Authors: Hartman Alwin M. , Gierse Robin M. , Hirsch Anna K. H.
Published: May 2019

Dynamic combinatorial chemistry (DCC) is a powerful tool to identify bioactive compounds. This efficient technique allows the target to select its own binders and circumvents the need for synthesis and biochemical evaluation of all individual derivatives. An ever‐increasing number of publications report the use of DCC on biologically relevant target proteins. This minireview complements previous reviews by focusing on the experimental protocol and giving detailed examples of essential steps and factors that need to be considered, such as protein stability, buffer composition and cosolvents.
Glycoconjugates via Phosphorus Ylides
Authors: Ghonchepour Ehsan , Neochoritis Constantinos G. , Kurpiewska Katarzyna , Kalinowska‐Tłuścik Justyna , Islami Mohammad R. , Dömling Alexander
Published: May 2019

A facile, high yielding access to rare chimeric compounds combining phosphorus ylides with complex glycosyl formamides is described. We determined X‐ray structures gaining structural insight into this compounds class. In addition, data mining of similar compounds deposited within the Cambridge Structural Database was performed. These derivatives could be used either as synthetic intermediates via the ylide functionalization and glyco chemical biology synthons or improving the pharmacokinetic properties of a potential bioactive molecule, exploiting the glycosyl moiety.
Cognitive Internet of Vehicles and disaster management: A proposed architecture and future direction
Authors: Arooj Ansif , Farooq Muhammad Shoaib , Umer Tariq , Shan Rafi Us
Published: May 2019

Historically, the vehicle has just been a component of the human ambulatory system and slave to the commands of driving force. However, recent advancement in technologies such as 5G wireless systems, cloud/edge computing, machine learning, artificial intelligence, and deep learning have opened the new paradigm of the Cognitive Internet of Vehicles (CIoV). The network of heterogeneous intelligent vehicles, not only having the social interaction capabilities but also have the ability to visualize, capture, and disseminate information to dynamic cognitive engines for identifying and analyzing different patterns and prediction of optimized outcomes. From secure navigation to traffic control, transportation security for pollution control has advocated plausible applications in real‐time operations of Internet of Vehicles in humanitarian operations. Proceeding this research, this paper aimed to propose a state‐of‐the‐art architecture based on CIoV for identifying emerging capabilities of available technologies to observe, detect, and mitigate natural disasters, and to develop the CIoV ecosystem for processing the global scale data for intelligent decision making and better service provisioning in natural disaster management.
Physical activity and incident dementia in older Japanese adults: The Okayama study
Authors: Liu Yangyang , Mitsuhashi Toshiharu , Yamakawa Michiyo , Sasai Megumi , Tsuda Toshihide , Doi Hiroyuki , Hamada Jun
Published: May 2019

Objective

To evaluate the association between regular physical activity and the risk of incident dementia in older Japanese adults.

Methods

This was a retrospective cohort study performed in Okayama City, Japan. Overall, 51 477 older Japanese adults were followed from 2008 to 2014. A health checkup questionnaire was used to assess regular physical activity. The Dementia Scale of long‐term care insurance was used as a measure of incident dementia. Cox proportional hazard models were used to calculate adjusted hazard ratios, with their 95% confidence intervals, for the incidence of dementia across the categories of physical activity.

Results

During a 7‐year follow‐up, 13 816 subjects were considered as having incident dementia. Compared with participants who performed physical activity less than or equal to one time per week, the multivariate adjusted hazard ratio values (95% confidence intervals) for participants who performed physical activity greater than or equal to two times per week but not every day and those who performed physical activity every day were 0.79 (0.75‐0.84) and 0.94 (0.89‐0.98), respectively. The interaction of physical activity and sex was statistically significant (P < .01). In subgroup analysis, the multivariate‐adjusted hazard ratio values (95% confidence intervals) remained low, at 0.76 (0.70‐0.84) in males and 0.81 (0.76‐0.87) in females who performed physical activity greater than or equal to two times per week but not every day; they were 0.82 (0.76‐0.89) in males and 1.01 (0.95‐1.07) in females who performed physical activity every day.

Conclusions

Regular physical activity could reduce the risk of incident dementia in older Japanese adults, except females who performed physical activity every day.
Beyond the cost‐effectiveness acceptability curve: The appropriateness of rank probabilities for presenting the results of economic evaluation in multiple technology appraisal
Authors: Epstein David
Published: May 2019

The cost‐effectiveness acceptability curve (CEAC) shows the probability that an option ranks first for net benefit. Where more than two options are under consideration, the CEAC offers only a partial picture of the decision uncertainty. This paper discusses the appropriateness of showing the full set of rank probabilities for reporting the results of economic evaluation in multiple technology appraisal (MTA). A case study is used to illustrate the calculation of rank probabilities and associated metrics, based on Monte Carlo simulations from a decision model. Rank probabilities are often used to show uncertainty in the results of network meta‐analysis, but until now have not been used for economic evaluation. They may be useful decision‐making tools to complement the CEAC in specific MTA contexts.
OLFM4 Enhances STAT3 Activation and Promotes Tumor Progression by Inhibiting GRIM19 Expression in Human Hepatocellular Carcinoma
Authors: Ashizawa Yosuke , Kuboki Satoshi , Nojima Hiroyuki , Yoshitomi Hideyuki , Furukawa Katsunori , Takayashiki Tsukasa , Takano Shigetsugu , Miyazaki Masaru , Ohtsuka Masayuki
Published: May 2019

Olfactomedin 4 (OLFM4) induces signal transducer and activator of transcription 3 (STAT3) activation by inhibiting gene associated with retinoid‐interferon‐induced mortality 19 (GRIM19), a strong STAT3 suppressor gene; however, the mechanisms of OLFM4 for regulating GRIM19‐STAT3 cascade in hepatocellular carcinoma (HCC) remain unclear. The functions and regulations of OLFM4, GRIM19, and STAT3 activation in HCC progression were evaluated using surgical specimens collected from 111 HCC patients or 2 HCC cell lines in vitro. Moreover, the cancer stem cell–like property of OLFM4 mediated by leucine‐rich repeat‐containing G protein‐coupled receptor 5 (LGR5), known as an intestinal stem cell marker, was investigated. OLFM4 was increased in HCC compared with adjacent liver tissue. The multivariate analysis revealed that high OLFM4 expression was an independent factor for poor prognosis. OLFM4 expression was negatively correlated with GRIM19 expression and positively correlated with STAT3 activation in HCC, thereby increasing cell cycle progression. OLFM4 knockdown in HCC cells increased GRIM19 expression and inhibited STAT3 activation; however, after double knockdown of GRIM19 and OLFM4, STAT3 activation decreased by OLFM4 knockdown was increased again. OLFM4 knockdown increased cell apoptosis, inhibited cell proliferation, and suppressed cancer stem cell–like property in HCC cells. The incidence of hematogenous recurrence was higher in HCC patients with high OLFM4 expression, suggesting that anoikis resistance of HCC was enhanced by OLFM4. In clinical cases, LGR5 expression and CD133 expression was correlated with OLFM4 expression in HCC, leading to poor patient prognosis. In vitro, LGR5 enhanced cancer stem cell–like property by up‐regulating OLFM4 through the Wnt signaling pathway. Conclusion: OLFM4 is induced by the LGR5‐Wnt signaling pathway and is strongly associated with aggressive tumor progression and poor prognosis in HCC by regulating STAT3‐induced tumor cell proliferation and cancer stem cell–like property. Therefore, OLFM4 is a novel prognostic predictor and a potential therapeutic target for patients with HCC.
Microwave‐Assisted Synthesis and Transformations of Cationic CpRu(II)(naphthalene) and CpRu(II)(naphthoquinone) Complexes
Authors: Bocekova‐Gajdošíkova Eva , Epik Bugra , Chou Jingyu , Akiyama Katsuhiro , Fukui Nobuaki , Guénée Laure , Kündig E. Peter
Published: May 2019

Details of the direct synthesis of cationic Ru(II)(η5‐Cp)(η6‐arene) complexes from ruthenocene using microwave heating are reported. Developed for the important catalyst precursor [Ru(II)(η5‐Cp)(η6‐1‐4,4a,8a‐naphthalene)][PF6] reaction time could be shortened from three days to 15 min. The method was extended to [Ru(II)(η6‐benzene)(η5‐Cp)][PF6], [Ru(II)(η5‐Cp)(η6‐toluene)][PF6], [Ru(II)(η5‐Cp)(η6‐mesitylene)][PF6], [Ru(II)(η5‐Cp)(η6‐hexamethylbenzene)][PF6], [Ru(II)(η5Cp)(η6‐indane)][PF6], [Ru(II)(η5‐Cp)(η6‐2,6‐dimethylnaphthalene)][PF6], and [Ru(II)(η5‐Cp)(η6‐pyrene)][PF6]. 1‐methylnaphthalene and 2,3‐dimethylnaphthalene afforded mixtures of regioisomeric complexes. [Ru(Cp)(CH3CN)3][PF6], derived from the naphthalene precursor provided access to the cationic RuCp complexes of naphthoquinone, tetralindione, 1,4‐dihydroxynaphthalene, and 1,4‐dimethoxynaphthalene. Reduction of the tetralindione complex afforded selectively the endo,endo diol derivative. X‐Ray structures of five complexes are reported.
Validation of AIST-SHANEL Model Based on Spatiotemporally Extensive Monitoring Data of Linear Alkylbenzene Sulfonate in Japan: Toward a Better Strategy on Deriving Predicted Environmental Concentrations
Authors: Nishioka Tohru , Iwasaki Yuichi , Ishikawa Yuriko , Yamane Masayuki , Morita Osamu , Honda Hiroshi
Published: May 2019

Strategies for deriving predicted environmental concentrations (PECs) using environmental exposure models have become increasingly important in the environmental risk assessment of chemical substances. However, many strategies are not fully developed owing to uncertainties in the derivation of PECs across spatially extensive areas. Here, we used 3-year environmental monitoring data (river: 11 702 points; lake: 1867 points; sea: 12 points) on linear alkylbenzene sulfonate (LAS) in Japan to evaluate the ability of the National Institute of Advanced Industrial Science and Technology (AIST)-Standardized Hydrology-Based Assessment Tool for the Chemical Exposure Load (SHANEL) model developed to predict chemical concentrations in major Japanese rivers. The results indicate that the estimation ability of the AIST-SHANEL model conforms more closely to the actual measured values in rivers than it does for lakes and seas (correlation coefficient: 0.46; proportion within the 10× factor range: 82%). In addition, the 95th percentile, 90th percentile, 50th percentile, and mean values of the distributions of the measured values (14 µg/L, 8.2 µg/L, 0.88 µg/L, and 3.4 µg/L, respectively) and estimated values (19 µg/L, 13 µg/L, 1.4 µg/L, and 4.2 µg/L, respectively) showed high concordance. The results suggest that AIST-SHANEL may be useful in estimating summary statistics (e.g., 95th and 90th percentiles) of chemical concentrations in major rivers throughout Japan. Given its practical use and high accuracy, these environmental risk assessments are suitable for a wide range of regions and can be conducted using representative estimated values, such as the 95th percentile. Integr Environ Assess Manag 2019;15:750–759. © 2019 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC).
Transcriptomic profiling reveals three molecular phenotypes of adenocarcinoma at the gastroesophageal junction
Authors: Bornschein Jan , Wernisch Lorenz , Secrier Maria , Miremadi Ahmad , Perner Juliane , MacRae Shona , O'Donovan Maria , Newton Richard , Menon Suraj , Bower Lawrence , Eldridge Matthew D. , Devonshire Ginny , Cheah Calvin , Turkington Richard , Hardwick Richard H. , Selgrad Michael , Venerito Marino , Malfertheiner Peter ,   on behalf of the OCCAMS Consortium, Fitzgerald Rebecca C.
Published: May 2019

Cancers occurring at the gastroesophageal junction (GEJ) are classified as predominantly esophageal or gastric, which is often difficult to decipher. We hypothesized that the transcriptomic profile might reveal molecular subgroups which could help to define the tumor origin and behavior beyond anatomical location. The gene expression profiles of 107 treatment‐naïve, intestinal type, gastroesophageal adenocarcinomas were assessed by the Illumina‐HTv4.0 beadchip. Differential gene expression (limma), unsupervised subgroup assignment (mclust) and pathway analysis (gage) were undertaken in R statistical computing and results were related to demographic and clinical parameters. Unsupervised assignment of the gene expression profiles revealed three distinct molecular subgroups, which were not associated with anatomical location, tumor stage or grade (p > 0.05). Group 1 was enriched for pathways involved in cell turnover, Group 2 was enriched for metabolic processes and Group 3 for immune‐response pathways. Patients in group 1 showed the worst overall survival (p = 0.019). Key genes for the three subtypes were confirmed by immunohistochemistry. The newly defined intrinsic subtypes were analyzed in four independent datasets of gastric and esophageal adenocarcinomas with transcriptomic data available (RNAseq data: OCCAMS cohort, n = 158; gene expression arrays: Belfast, n = 63; Singapore, n = 191; Asian Cancer Research Group, n = 300). The subgroups were represented in the independent cohorts and pooled analysis confirmed the prognostic effect of the new subtypes. In conclusion, adenocarcinomas at the GEJ comprise three distinct molecular phenotypes which do not reflect anatomical location but rather inform our understanding of the key pathways expressed.
Spectroelectrochemistry of Quantum Dots
Authors: Garoz‐Ruiz Jesus , Perales‐Rondon Juan V. , Heras Aranzazu , Colina Alvaro
Published: May 2019

Spectroelectrochemistry (SEC) is a set of techniques with many advantages in the study and characterization of materials. Although SEC has not yet been widely used to study quantum dots (QDs), the information extracted from SEC experiments about these nanostructures is very useful. Most of the works that use SEC to study QDs are high‐quality pieces of research. This review intends to show how to perform SEC in an easy way and what information can be obtained using these techniques. Most of the examples shown in this review are related to semiconductor and carbon QDs. After a brief introduction, some optoelectronic properties of QDs and the main SEC techniques are described. The capabilities of SEC for the study of QDs are illustrated with examples extracted from literature. Finally, the needs of SEC to become a user‐friendly technique and its evolution to become more powerful are commented in the last section of the review.
A systematic review of the cost‐effectiveness of uterotonic agents for the prevention of postpartum hemorrhage
Authors: Lawrie Theresa A. , Rogozińska Ewelina , Sobiesuo Pauline , Vogel Joshua P. , Ternent Laura , Oladapo Olufemi T.
Published: May 2019

Background

Several uterotonic options exist for prevention of postpartum hemorrhage (PPH); hence, cost‐effectiveness is an important decision‐making criterion affecting uterotonic choice.

Objective

To conduct a systematic review of cost‐effectiveness of uterotonics for PPH prevention to support a WHO guideline update.

Search strategy

We searched major databases from 1980 to June 2018 and the National Health Services Economic Evaluation (NHS EED) database from inception (1995) to March 2015 for eligible studies.

Selection criteria

We included comparative economic evaluations, cost‐utility analyses, and resource‐utilization studies.

Data collection and analysis

Two reviewers independently assessed studies and extracted data organized by birth mode and setting.

Main results

We included 15 studies across all income categories that compared misoprostol versus no uterotonic (five studies) or versus oxytocin (one study), carbetocin versus oxytocin (eight studies), and one study comparing numerous uterotonics. In specific low‐resource contexts, we found reasonably good evidence that misoprostol was cost‐effective compared with no uterotonic. In the context of cesarean delivery, carbetocin was more cost favorable than oxytocin but certainty of this evidence was low.

Conclusions

Evidence on the cost‐effectiveness of various uterotonic agents was not generalizable. As the number of competing uterotonics increases, rigorous economic evaluations including contextual factors are needed.
Precursor behavior and functional analysis: A brief review
Authors: Heath Hayden , Smith Richard G.
Published: May 2019

Researchers have developed precursor functional analyses to provide an alternative, and presumably safer, format for functional analysis of severe problem behavior. When researchers use functional analysis contingencies for precursor behaviors, it is possible to infer functional characteristics about severe problem behaviors based on patterns of less severe precursor behaviors, permitting practitioners to complete the assessment with less risk to clients, practitioners, or others. The current paper discusses recent advances in the development and validation of precursor identification, and offers suggestions and future directions for investigating and implementing precursor functional analyses. We propose a decision‐making model, in which practitioners integrate procedures to identify precursors into the functional‐analysis process, to expedite the analysis of severe problem behaviors.
Assessment of substituent effects on the parameters of 35Cl nuclear quadrupole resonance in para‐substituted benzene‐sulphenyl chloride via quantum chemical calculations
Authors: Nasrolahi Morteza , Ghiasi Reza , Shafiee Fatemeh
Published: May 2019

In this research, substituent effects on the parameters of 35Cl nuclear quadrupole resonance (NQR) in para‐substituted benzene‐sulphenyl chloride were studied at M062X/6‐311G(d,p) theory level. The 35Cl NQR parameters of the quadrupole coupling constant (QCC) and electric‐field gradient (EFG) tensor, as well as an asymmetric parameter, were shown to be correlated with Hammett constant following their calculations. The frontier orbital energy levels, HOMO‐LUMO gaps, hardness, electrophilicity, and chemical potential values of these molecules were calculated as well. natural bond orbital (NBO) analysis was applied for calculating natural populations at chlorine atoms.
Understanding variants of uncertain significance in the era of multigene panels: Through the eyes of the patient
Authors: Reuter Chloe , Chun Nicolette , Pariani Mitchel , Hanson‐Kahn Andrea
Published: May 2019

Variants of uncertain significance (VUSs) are often disclosed to patients despite ambiguous association with disease risk and lack of clinical actionability. It is important to understand how patients understand a VUS result, but few studies have assessed this. Our qualitative study explored patient recall, reaction to, and interpretation of a VUS in the context of multigene panels. We conducted 11 semi‐structured phone interviews with adults who had a VUS identified on multigene panel testing in a hereditary oncology clinic, with questions focusing on the VUS result, personal and family history, and motivations for and expectations of genetic testing. Transcripts were coded iteratively, using both deductive and inductive codes. Overall, participants usually recalled that they had a VUS, despite variation in the vocabulary used. Participants responded both emotionally and intellectually to receiving information about having a VUS, which was often a result of their expectations and motivations prior to testing. Overall, participants understood the lack of clinical significance of a VUS, yet often interpreted the etiologic significance of a VUS within the context of the personal and family history. Our study provides insight into a process by which patients translate uncertain genetic testing results into a construct that fits within their current belief framework and which may be facilitated by a genetic counselor.
Modeling and computation of double drift region transit time diode performance based on graphene‐SiC
Authors: Ghivela Girish Chandra , Sengupta Joydeep
Published: May 2019

We have proposed a double drift region (DDR) Impact Avalanche Transit Time (IMPATT) diode based on graphene‐silicon carbide (SiC) substrate. Due to attractive and extensive electronics properties of graphene materials, for the first time, we have modeled and designed the diode on epitaxially grown graphene deposited on the silicon face of SiC. The direct current (DC) characteristics and small signal performance of the modeled diode are computed with the help of COMSOL Multi Physics and MATLAB software tools. Performance is evaluated at the frequency regime of Ka band. The proposed diode is validated through the boundary conditions. Profiles of electric field distribution, density of mobile space charge, conversion efficiency, power density, susceptance‐conductance, and voltage drops at different zones are obtained. The graphene‐SiC–based DDR IMPATT is giving better DC and small signal performances.
Periodontitis and tooth loss have negative impact on dietary intake: A cross‐sectional study with stable coronary artery disease patients
Authors: Mendonça Dayana D. , Furtado Mariana V. , Sarmento Roberta A. , Nicoletto Bruna B. , Souza Gabriela C. , Wagner Tassiane P. , Christofoli Barbara R. , Polanczyk Carisi A. , Haas Alex N.
Published: May 2019

Background

Despite the association between cardiovascular diseases and periodontitis, there are scarce data on the impact of oral health in the dietary intake of patients with coronary artery disease (CAD). The aim of this study was to assess the association between dietary intake with periodontitis and present teeth in individuals with stable CAD.

Methods

This cross‐sectional study included 115 patients with stable CAD (76 males, aged 61.0 ± 8.3 years) who were under cardiovascular care in an outpatient clinic for at least 3 months. Dietary intake was recorded applying a food frequency questionnaire previously validated. Periodontal examinations were performed by two calibrated examiners in six sites per tooth from all present teeth. Blood samples were collected to determine serum levels of lipids. Multivariable logistic and linear regression models were fitted to evaluate the association between dietary outcomes and oral health variables.

Results

Individuals with periodontitis had significantly higher percentage of total energy intake from fried foods, sweets, and beans, and also had lower consumption of fruits than those without periodontitis. Presence of periodontitis was associated with lower percentage of individuals who reached the nutritional recommendation of monounsaturated fatty acids and higher blood concentration of triglycerides. Having a greater number of present teeth (≥20 teeth) was associated with higher intake of fibers and total calories.

Conclusion

In patients with stable CAD, the presence of periodontitis and tooth loss were associated with a poor dietary intake of nutrients and healthy foods, which are important for cardiovascular prevention.
An insight into chiral monolithic stationary phases for enantioselective high‐performance liquid chromatography applications
Authors: Fouad Ali , Ibrahim Diana , Adly Frady G. , Ghanem Ashraf
Published: May 2019

In this review, three main classes of chiral monolithic stationary phases, namely silica‐, organic polymer‐, and hybrid‐based monolithic stationary phases, are covered. Their preparations, applications, and advantages compared with the conventional‐packed and open‐tubular capillary columns are discussed. A detailed description of the different types and techniques used for the introduction of chiral selectors into the monolithic matrices such as immobilization, functionalization, coating, encapsulation, and bonding. Special emphasis is given to the recent developments of chiral selectors in HPLC monolithic stationary phases during the past 18 years.
Identification of predictors of Boolean networks from observed attractor states
Authors: Yue Jumei , Yan Yongyi , Chen Zengqiang , Jin Xin
Published: May 2019

Predictors of Boolean networks are of significance for biologists to target their research on gene regulation and control. This paper aims to investigate how to determine predictors of Boolean networks from observed attractor states by solving logical equations. The proposed method consists of four steps. First, all possible cycles formed by known attractor states are constructed. Then, for each possible cycle, all data‐permitted predictors of each node are identified according to the known attractor states. Subsequently, the data‐permitted predictors are incorporated with some common biological constraints to generate logical equations that describe whether such possible predictors can ultimately be chosen as valid ones by the biological constraints. Finally, solve the logical equations; the solutions determine a family of predictors satisfying the known attractor states. The approach is quite different from others such as computer algorithm‐based and provides a new angle and means to understand and analyze the structures of Boolean networks.
Lithium‐Rich Mineral Water is a Highly Bioavailable Lithium Source for Human Consumption
Authors: Seidel Ulrike , Baumhof Elena , Hägele Franziska A. , Bosy‐Westphal Anja , Birringer Marc , Rimbach Gerald
Published: May 2019

Scope

Lithium is an important trace element in human nutrition and medicine. Mineral and medicinal waters may represent a significant source of dietary lithium intake.

Methods and results

The lithium concentration of 360 German mineral and 21 medicinal waters is determined. Based on a systematic screening, three different mineral waters exhibiting low (1.7 µg L−1), medium (171 µg L−1), and high lithium (1724 µg L−1) concentrations are chosen for an acute bioavailability study in male healthy volunteers. In Germany, a north‐east to south‐west gradient of analyzed lithium concentrations is observed in the 381 tested waters. The lithium concentration in the water is significantly correlated with its sodium (r = 0. 810), potassium (r = 0.716), and magnesium (r = 0.361), but not with its calcium concentration. In a randomized cross‐over trial, volunteers (n = 3×10 each) drink 1.5 L of the respective mineral waters, and lithium concentrations in serum and urine are monitored over 24 h. Consumption of the mineral waters with a medium and high lithium content results in a dose‐dependent response in serum lithium concentrations and total urinary lithium excretion.

Conclusion

Lithium‐rich mineral and medicinal waters may be an important and highly bioavailable lithium source for human consumption.
Learning‐based automatic segmentation of arteriovenous malformations on contrast CT images in brain stereotactic radiosurgery
Authors: Wang Tonghe , Lei Yang , Tian Sibo , Jiang Xiaojun , Zhou Jun , Liu Tian , Dresser Sean , Curran Walter J. , Shu Hui‐Kuo , Yang Xiaofeng
Published: May 2019

Purpose

Stereotactic radiosurgery (SRS) is widely used to obliterate arteriovenous malformations (AVMs). Its performance relies on the accuracy of delineating the target AVM. Manual segmentation during a framed SRS procedure is time consuming and subject to inter‐ and intraobserver variation. To address these drawbacks, we proposed a deep learning‐based method to automatically segment AVMs on CT simulation image sets.

Methods

We developed a deep learning‐based method using a deeply supervised three‐dimensional (3D) V‐Net with a compound loss function. A 3D supervision mechanism was integrated into a residual network, V‐Net, to deal with the optimization difficulties when training deep networks with limited training data. The proposed compound loss function including logistic and Dice losses encouraged similarity and penalized discrepancy simultaneously between prediction and training dataset; this was utilized to supervise the 3D V‐Net at different stages. To evaluate the accuracy of segmentation, we retrospectively investigated 80 AVM patients who had CT simulation and digital subtraction angiography (DSA) acquired prior to treatment. The AVM target volume was segmented by our proposed method. They were compared with clinical contours approved by physicians with regard to Dice overlapping, difference in volume and centroid, and dose coverage changes on original plan.

Results

Contours created by the proposed method demonstrated very good visual agreement to the ground truth contours. The mean Dice similarity coefficient (DSC), sensitivity and specificity of the contours delineated by our method were >0.85 among all patients. The mean centroid distance between our results and ground truth was 0.675 ± 0.401 mm, and was not significantly different in any of the three orthogonal directions. The correlation coefficient between ground truth and AVM volume resulting from the proposed method was 0.992 with statistical significance. The mean volume difference among all patients was 0.076 ± 0.728 cc; there was no statistically significant difference. The average differences in dose metrics were all less than 0.2 Gy, with standard deviation less than 1 Gy. No statistically significant differences were observed in any of the dose metrics.

Conclusion

We developed a novel, deeply supervised, deep learning‐based approach to automatically segment the AVM volume on CT images. We demonstrated its clinical feasibility by validating the shape and positional accuracy, and dose coverage of the automatic volume. These results demonstrate the potential of a learning‐based segmentation method for delineating AVMs in the clinical setting.
Using bidirectional chemical exchange for improved hyperpolarized [13C]bicarbonate pH imaging
Authors: Korenchan David E. , Gordon Jeremy W. , Subramaniam Sukumar , Sriram Renuka , Baligand Celine , VanCriekinge Mark , Bok Robert , Vigneron Daniel B. , Wilson David M. , Larson Peder E.Z. , Kurhanewicz John , Flavell Robert R.
Published: May 2019

Purpose

Rapid chemical exchange can affect SNR and pH measurement accuracy for hyperpolarized pH imaging with [13C]bicarbonate. The purpose of this work was to investigate chemical exchange effects on hyperpolarized imaging sequences to identify optimal sequence parameters for high SNR and pH accuracy.

Methods

Simulations were performed under varying rates of bicarbonate–CO2 chemical exchange to analyze exchange effects on pH quantification accuracy and SNR under different sampling schemes. Four pulse sequences, including 1 new technique, a multiple‐excitation 2D EPI (multi‐EPI) sequence, were compared in phantoms using hyperpolarized [13C]bicarbonate, varying parameters such as tip angles, repetition time, order of metabolite excitation, and refocusing pulse design. In vivo hyperpolarized bicarbonate–CO2 exchange measurements were made in transgenic murine prostate tumors to select in vivo imaging parameters.

Results

Modeling of bicarbonate–CO2 exchange identified a multiple‐excitation scheme for increasing CO2 SNR by up to a factor of 2.7. When implemented in phantom imaging experiments, these sampling schemes were confirmed to yield high pH accuracy and SNR gains. Based on measured bicarbonate–CO2 exchange in vivo, a 47% CO2 SNR gain is predicted.

Conclusion

The novel multi‐EPI pulse sequence can boost CO2 imaging signal in hyperpolarized 13C bicarbonate imaging while introducing minimal pH bias, helping to surmount a major hurdle in hyperpolarized pH imaging.
Managing employee performance in transition economies: A study of Vietnamese public organizations
Authors: Vu Tai Anh , Plimmer Geoff , Berman Evan , Sabharwal Meghna
Published: May 2019

Employee performance management (PM) is a public sector reform that furthers development objectives by increasing employee performance, aligning employee efforts with organizational goals, and addressing poor performance. This study discusses employee PM in development contexts. Based on varied employee PM efforts in Vietnamese public organizations, it finds that (a) advanced employee PM practices significantly increase perceived organizational and employee outcomes compared with less advanced employee PM practices, and that (b) executive accountability, Human resource (HR) autonomy and entrepreneurial leadership are strongly associated with successful implementation of employee PM. This article provides detailed description of employee PM practices and suggests implications for implementing public sector reforms in transitional settings.
Characterization of CNPY5 and its family members
Authors: Schildknegt Danny , Lodder Naomi , Pandey Abhinav , Egmond Maarten , Pena Florentina , Braakman Ineke , van der Sluijs Peter
Published: May 2019

The Canopy (CNPY) family consists of four members predicted to be soluble proteins localized to the endoplasmic reticulum (ER). They are involved in a wide array of processes, including angiogenesis, cell adhesion, and host defense. CNPYs are thought to do so via regulation of secretory transport of a diverse group of proteins, such as immunoglobulin M, growth factor receptors, toll‐like receptors, and the low‐density lipoprotein receptor. Thus far, a comparative analysis of the mammalian CNPY family is missing. Bioinformatic analysis shows that mammalian CNPYs, except the CNPY1 homolog, have N‐terminal signal sequences and C‐terminal ER‐retention signals and that mammals have an additional member CNPY5, also known as plasma cell‐induced ER protein 1/marginal zone B cell‐specific protein 1. Canopy proteins are particularly homologous in four hydrophobic alpha‐helical regions and contain three conserved disulfide bonds. This sequence signature is characteristic for the saposin‐like superfamily and strongly argues that CNPYs share this common saposin fold. We showed that CNPY2, 3, 4, and 5 (termed CNPYs) localize to the ER. In radioactive pulse‐chase experiments, we found that CNPYs rapidly form disulfide bonds and fold within minutes into their native forms. Disulfide bonds in native CNPYs remain sensitive to low concentrations of dithiothreitol (DTT) suggesting that the cysteine residues forming them are relatively accessible to solutes. Possible roles of CNPYs in the folding of secretory proteins in the ER are discussed.
Depressive disorders: Treatment failures and poor prognosis over the last 50 years
Authors: Blackburn Thomas P.
Published: May 2019

Depression like many diseases is pleiotropic but unlike cancer and Alzheimer's disease for example, is still largely stigmatized and falls into the dark shadows of human illness. The failure of depression to be in the spotlight for successful treatment options is inherent in the complexity of the disease(s), flawed clinical diagnosis, overgeneralization of the illness, inadequate and biased clinical trial design, restrictive and biased inclusion/exclusion criteria, lack of approved/robust biomarkers, expensive imaging technology along with few advances in neurobiological hypotheses in decades. Clinical trial studies summitted to the regulatory agencies (FDA/EMA) for approval, have continually failed to show significant differences between active and placebo. For decades, we have acknowledged this failure, despite vigorous debated by all stakeholders to provide adequate answers to this escalating problem, with only a few new antidepressants approved in the last 20 years with equivocal efficacy, little improvement in side effects or onset of efficacy. It is also clear that funding and initiatives for mental illness lags far behind other life‐treating diseases. Thus, it is no surprise we have not achieved much success in the last 50 years in treating depression, but we are accountable for the many failures and suboptimal treatment. This review will therefore critically address where we have failed and how future advances in medical science offers a glimmer of light for the patient and aid our future understanding of the neurobiology and pathophysiology of the disease, enabling transformative therapies for the treatment of depressive disorders.
Innovative approaches to exploit host plant metabolites in malaria control
Authors: Torto Baldwyn
Published: May 2019

Malaria is the most important vector‐borne disease in sub‐Saharan Africa (SSA). Recent reports indicate that the levels of malaria‐associated mortality and morbidity in SSA have remained the same. Malaria vectors have modified their feeding behavior in response to the selective pressure from indoor‐based interventions, and there is emerging malaria parasite resistance to artemisinin‐based combination therapies. These challenges have created an altered malaria landscape, especially within local scales in some malaria‐endemic countries in SSA. To address these challenges, complementary new strategies are urgently required for malaria control. This paper argues that to develop the next generation of vector and chemotherapeutic tools for malaria control, especially based on natural products with novel modes of action, a better understanding of mosquito bioecology and, more importantly, plant sugar feeding is needed. © 2019 Society of Chemical Industry
Promising sensitizers for dye sensitized solar cells: A comparison of Ru(II) with other earth's scarce and abundant metal polypyridine complexes
Authors: Sen Anik , Groß Axel
Published: May 2019

There has recently been a growing interest in dye sensitized solar cells (DSSCs) based on ruthenium metal, but due to the scarcity and high price of ruthenium, design of better and cheaper light adsorbent dyes based on more abundant metal ions is one of the key issues for future development of the DSSCs. Using density functional theory (DFT) and time‐dependent DFT we have studied the properties of new and abundant metal ion‐based polypyridyl dyes for p‐type DSSCs and compared with ruthenium and other scarce metal ions. Molecular geometries, electronic structures, and optical absorption spectra have been calculated using an implicit solvent corresponding to acetonitrile. The calculated fair light harvesting efficiency, high hole injection efficiency and Gibbs free energy for the hole injection and longer excited state lifetime (important for reflecting the efficiency of solar cells) for the new abundant metal ions (V3+ and Cr2+) based dyes could provide promising sensitizers for efficient next generation DSSC's for p‐SC.
Robust precision attitude tracking of an uncertain rigid spacecraft based on regulation theory
Authors: He Jiafan , Sheng Andong , Xu Dabo , Chen Zhiyong , Wang Dan
Published: May 2019

This paper explores regulation theory for the design of robust precision attitude tracking of an uncertain rigid spacecraft with external disturbances. Focusing on the attitude system in terms of unit quaternions with an unknown inertia matrix and unmodeled input disturbances, we first introduce specific nonlinear logic such that the resultant error‐quaternion system has an input‐to‐state stability property. Then, we establish an attitude deviation system with an output feedback normal form that has a strict vector relative degree of unity. This enables us to achieve robust output regulation based on an internal model. In particular, we can construct a high‐gain stabilizer for the relevant augmented system. As a major consequence, our study achieves not only precision attitude tracking with exponential convergence but also the input‐to‐state stability disturbance attenuation for the closed‐loop system. Finally, we show extensive simulation and experimental results to illustrate the approach.
Generalized extended state observer–based repetitive control for systems with mismatched disturbances
Authors: Zhou Lan , Cheng Lei , She Jinhua , Zhang Zhu
Published: May 2019

A generalized extended state observer (GESO) is devised to improve the disturbances rejection performance in a repetitive‐control system (RCS) for a class of single‐input, single‐output nonlinear plants with nonintegral chain form and mismatched disturbances. By appropriately choosing a disturbance compensation gain and incorporating the disturbance estimate into a repetitive control law, a GESO‐based RCS is established. In this system, the repetitive controller ensures tracking of a periodic reference input, and the incorporation of the disturbance compensation into the control input enables attenuating the lumped disturbance from the system output. Stability criteria and design algorithms have been developed for the system. A case study on the speed control of a rotational control system exhibits that the GESO‐based RCS delivers not only a promising disturbance rejection performance but also a superior property of tracking performance.
Seismic behavior of reinforced engineered cementitious composite members and reinforced concrete/engineered cementitious composite members: A review
Authors: Hou Lijun , Xu Ran , Chen Da , Xu Shilang , Aslani Farhad
Published: May 2019

Seismic performance is of paramount importance for structures in regions with high seismic risk. Engineered cementitious composite (ECC) exhibits tensile strain hardening behavior and excellent crack dispersion capacity, as well as good workability. The application of ECC material may be a feasible way to improve the seismic behavior of engineering structures. This paper presents a comprehensive review of experimental and simulation studies concerning seismic behavior of reinforced ECC members and reinforced concrete/ECC composite members. The review is mainly focused on design programs for structural members and their seismic response behavior. The effectiveness of the application of ECC for seismic improvement is discussed. Several design recommendations are provided, based on comparison of the related studies.
Bond behavior of micro steel fibers embedded in ultra‐high performance concrete subjected to monotonic and cyclic loading
Authors: Lanwer Jan‐Paul , Oettel Vincent , Empelmann Martin , Höper Svenja , Kowalsky Ursula , Dinkler Dieter
Published: May 2019

Ultra‐high performance fiber‐reinforced concrete (UHPFRC) is usually applied for thin‐walled and lean constructions because of its excellent mechanical properties. However, these lightweight constructions such as bridge girders, masts, towers, and railway tracks, for example, are susceptible to oscillations due to cyclic loading. A model describing the fatigue behavior of UHPFRC is required. Therefore, the material behavior of all mixture components and the composite itself, each subjected to cyclic tensile loading, is studied experimentally and numerically on the mesoscale at iBMB, Division of Concrete Construction and Institute of Structural Analysis both at TU Braunschweig. In this paper, first findings concerning bond processes of single and multiple micro steel fibers embedded in ultra‐high performance concrete as well as a new geometrically and physically nonlinear bond model are presented.
Applying standard independent verification and validation techniques within an agile framework: Identifying and reconciling incompatibilities
Authors: Dabney James B. , Arthur James D.
Published: May 2019

Agile methods have gained wide acceptance over the past several years. They are now a standard management and execution approach for small‐scale system development projects. While Agile methods are not generally applicable to large multiyear and mission‐critical systems, hybrid Agile approaches are being developed to exploit the productivity improvements of Agile while retaining the necessary process rigor and coordination needs of these types of projects. From the perspective of Independent Verification and Validation (IV&V), however, adoption of these hybrid‐Agile frameworks is becoming problematic. Hence, we find it prudent to question the compatibility of conventional IV&V techniques with hybrid‐Agile practices.

This paper documents investigation of relevant literature, the modification and adoption of Agile frameworks to accommodate the development of large scale, mission‐critical systems, and the compatibility of standard IV&V techniques within hybrid‐Agile development frameworks. Specific to the latter, we find that the IV&V techniques employed within a hybrid‐Agile process can be divided into three groups: early lifecycle techniques that are fully compatible with the hybrid frameworks, techniques that focus on tracing requirements, test objectives, etc, which are somewhat problematic, but can be tailored with modest effort, and techniques involving an assessment requiring artifact completeness, and consequently, are not compatible with hybrid‐Agile processes. We identify seven prominent techniques in this third category and propose alternative approaches that achieve similar goals and which can be applied within an Agile development process.
Communication on “architecting portfolios of systems”
Authors: Maier Mark W.
Published: May 2019

During the review process for the paper “Architecting Portfolios of Systems” in this issue one of the reviewers suggested that part of the reviewer‐author dialog be published because it clarified some issues beyond the paper itself and illustrated some different perspectives. This paper elaborates three major topics: The categorization of different types of collections of systems, the concept of requisite modeling in how we choose to model systems under development across a spectrum of rigor, and how to judge the success of research in systems engineering processes and methods.