bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimal inventory threshold for a dynamic service make‐to‐stock system with strategic customers
Authors: Zhang Xuelu , Wang Jinting
Published: May 2019

We consider a make‐to‐stock production system with one product type, dynamic service policy, and delay‐sensitive customers. To balance the waiting cost of customers and holding cost of products, a dynamic production policy is adopted. If there is no customer waiting in the system, instead of shutting down, the system operates at a low production rate until a certain threshold of inventory is reached. If the inventory is empty and a new customer emerges, the system switches to a high production rate where the switching time is assumed to be exponentially distributed. Potential customers arrive according to the Poisson process. They are strategic in the sense that they make decisions on whether to stay for product or leave without purchase on the basis of on their utility value and the system information on whether the number of products is observable to customers or not. The strategic behavior is explored, and a Stackelberg game between production manager and customers is formulated where the former is the game leader. We find that the optimal inventory threshold minimizing the cost function can be obtained by a search algorithm. Numerical results demonstrate that the expected cost function in an observable case is not greater than that in an unobservable case. If a customer's delay sensitivity is relatively small, these two cases are entirely identical. With increasing of delay sensitivity, the optimal inventory threshold might be positive or zero, and hence, a demarcation line is depicted to determine when a make‐to‐stock policy is advantageous to the manager.
Restoring Oklahoma's Waurika Lake to a Resilient Water Supply
Authors: Keithline Dan , Umdenstock Jim , Gaddis Bob
Published: May 2019

A project in Oklahoma reversed severe drought conditions and replenished dangerously low water supply yields in Lake Waurika, a primary source of water for SIX cities.
Water Shortage Challenges and a Way Forward in India
Authors: Chakraborti Rajat K. , Kaur Jagjit , Kaur Harpreet
Published: May 2019

India should implement adaptive green and gray water management strategies as it faces an uncertain water future.
Binding interaction study on human serum albumin with bactericidal gold nanoparticles synthesized from a leaf extract of Musa balbisiana: a multispectroscopic approach
Authors: Maji Anukul , Beg Maidul , Das Somnath , Sahoo Nandan Kumar , Jha Pradeep K. , Islam Md. Maidul , Hossain Maidul
Published: May 2019

This study describes the eco‐friendly, low‐cost and room‐temperature synthesis of gold nanoparticles from Musa balbisiana leaf extract, which acts as both reducing and stabilizing agent, and characterized by ultraviolet−visible (UV–vis) light spectroscopy, fourier transform infrared (FTIR) spectroscopy, field emission scanning electron microscopy (FE‐SEM), analytical transmission electron microscopy (TEM), energy‐dispersive X‐ray spectroscopy (EDAX) and dynamic light scattering (DLS) instruments. These nanoparticles showed an average diameter of 33.83 ± 3.39 nm, which was confirmed from the size distribution histogram. The bactericidal activity of these nanoparticles was confirmed using bacteria Escherichia coli and Staphylococcus aureus at 1 and 2 nM minimum inhibitory concentrations, respectively. The interaction between nanoparticles and human serum albumin (HSA) was investigated, as this plays significant roles in biological systems. The nature of interaction, binding parameters and structural variation of HSA in the presence of these nanoparticles have been evaluated using several useful spectroscopic approaches such as UV–vis, FTIR, time‐resolved and steady‐state fluorescence, and circular dichroism in addition to the measurement of zeta potential. This interaction study revealed that static quenching occurs in this process with minimal alteration in the secondary structure, but the native structure of HSA remained unaltered. The binding constant and thermodynamic parameters of this interaction process were also evaluated.
Achieving Sustainable Development Goals in the global food sector: A systematic literature review to examine small farmers engagement in contract farming
Authors: Vabi Vamuloh Vilbert , Panwar Rajat , Hagerman Shannon M. , Gaston Christopher , Kozak Robert A.
Published: May 2019

Contract farming, a common strategy among multinational companies in the global food sector, can help achieve Sustainable Development Goals (SDGs). However, it largely depends on whether or not small farmers can participate in contract farming programs, which has been a major issue globally. Our main objective in this systematic literature review is to identify the factors that drive small farmer participation in contract farming. We analyze 97 peer‐reviewed journal articles published between 1977 and 2017. Our review finds that farmer demographic characteristics, farm structure, farmer characteristics, and farmer attitudes influence participation in contract farming although causal mechanisms remain ambiguous. We therefore suggest the need for more comprehensive methodologies to examine small farmer participation in contract farming. In the meantime, global food sector companies must consider these factors as they develop plans toward achieving SDGs.
Does doing “good” always translate into doing “well”? An eco‐efficiency perspective
Authors: Broadstock David C. , Managi Shunsuke , Matousek Roman , Tzeremes Nickolaos G.
Published: May 2019

Does doing “good” always translate into doing “well”? Debate over the “value” of corporate social responsibility is high on the agenda of corporate finance research. Deeper understanding is required on managers' incentives to pursue and implement corporate social responsibility related strategies, as is more thorough comprehension of the effect of these strategies to firms' performance levels as well as shareholder and wider stakeholder valuations of the firm. This paper provides a new lens by approaching the subject from a different methodological paradigm, grounded in the performance benchmarking methods more commonly applied in operational research. In so doing, we provide novel evidence of the effect of corporate choices on environmental, social, and governance (ESG) strategic investment compliance (i.e., doing good) to firms' eco‐efficiency levels (doing well). In brief, our empirical findings suggest that ESG and firm's eco‐performance are nonlinearly related. Specifically, advanced ESG policies and disclosure levels are associated with a positive affect to firms' eco‐efficiency levels, but only up to a point, after which the effect becomes “neutral,” that is, ESG demonstrates a visible pattern of diminishing marginal returns. Thus, we may humbly conclude that a firm may “do well” by doing good, but it is not clear they should ever expect to “do great” just by “doing good.” The threshold at which this “neutrality” appears varies systematically with the characteristics of the sector in which the firm is operating, as well as dimensions of board diversity. Finally, it is evident that ESG implementation choices can be a source of managerial agency problems.
Practical management in Wolcott‐Rallison syndrome with associated hypothyroidism, neutropenia, and recurrent liver failure: A case report
Authors: Lundgren Markus , De Franco Elisa , Arnell Henrik , Fischler Björn
Published: May 2019

Key Clinical Message

Wolcott‐Rallison syndrome is a rare genetic syndrome of neonatal diabetes, liver failure, and growth retardation. We present a case with a EIF2AK3 p.(Arg902Ter) mutation, additionally complicated by hypothyroidism, impaired renal function, and exocrine pancreas insufficiency, focusing on clinical management. For its optimization, thorough care of multiple organ systems is needed.
Cathode Framework of Nanostructured Titanium Nitride/Graphene for Advanced Lithium–Sulfur Batteries
Authors: Zeng Wenduo , Cheng Mark Ming‐Cheng , Ng K. Y. Simon
Published: May 2019

Nanostructured titanium nitride (TiN) and graphene composite electrodes have been fabricated through a facile method, combining ultrasonication with melt‐diffusion of elemental sulfur. Nanostructured TiN particles and tube arrays mechanically mixed with graphene substrate leads to the formation of a porous, stabilized composite structure with enhanced electrical conductivity. Such a framework may facilitate accessibility of electrolyte and fast transfer of charges. The specific capacities of the Li−S batteries with TiN nanotubes/graphene and TiN nanoparticles/graphene composites are 1229 and 1085 mAh g−1, respectively, after 180 cycles under a 0.1 C rate, which are significantly better than pure TiN nanostructures. The specific capacity and capacity retention were investigated as a function of the TiN nanotube to graphene ratio. The optimal ratio was found to be 1 : 1 TiN/graphene, with the highest capacity retention of 87.5 % after 180 cycles. This 3D hybrid structure may provide a balance of high specific capacity and electrochemical stability, allowing durable and efficient energy storage and conversion over a long cycle life.
Synthesis and Application of a Conjugated Polydianion‐Based Single‐Ion Conducting Polymer for High‐Performance Solid Lithium‐Ion Batteries
Authors: Li Dan , Zeng Zhixiang , Lu Di , Nie Feng , Wen Lele , Zhu Lijing
Published: May 2019

Fluorosulfonimide lithium salts have been widely used as conductors in solid polymer electrolytes for solid Li‐ion batteries (LIBs). However, low conductivity and poor compatibility with the polymer host (usually polyethylene oxide, PEO) remain challenges in the design of these salts. In this paper, we synthesized a highly Li+‐conductive salt containing the poly(perfluoroalkylsulfonyl)diimide (PFSDI−) dianion for the first time. LiPFSDI represents the first example of a single Li‐ion‐conducting polymer (SLICP) with a conjugated sulfonimide moiety (−SO2−N(−)−SO2−N(−)−SO2−). The PEO−LiPFSDI blend electrolyte exhibits significant enhancements in ionic conductivity (2.24×10−4 S cm−1 at 80 °C)and electrochemical stability (up to 6 V vs. Li+/Li). A prototype LiFePO4/Li battery with the PEO−LiPFSDI composite electrolyte shows excellent cycling performance with a high reversible capacity of 148 mAh g−1 at a rate of 0.1 C and 135 mAh g−1 at 0.2 C (70 °C), and maintains 100 stable cycles for over 1500 hours.
Two Types of σ‐Allenyl Complexes from Reactions of Silylenes and Germylenes with Chromium Fischer Alkynyl(alkoxy)carbenes
Authors: Cabeza Javier A. , García‐Álvarez Pablo , Gómez‐Gallego Mar , González‐Álvarez Laura , Merinero Alba D. , Sierra Miguel A.
Published: May 2019

The reactivity of amidinatotetrylenes of the type E(tBu2bzm)R1 (E=Si, Ge; tBu2bzm=N,N′‐bis(tertbutyl)benzamidinate; R1=alkyl or aryl) with the chromium Fischer alkynylcarbene complexes [Cr{C(OEt)C2R2}(CO)5] (R2=Ph; ferrocenyl, Fc) has been studied. At room temperature, two different reaction pathways have been identified: (a) attack of the amidinatotetrylene to the alkynyl C2 atom (γ‐attack), which leads to σ‐allenyl complexes in which the original Ccarbene atom maintains its attachment to the Cr(CO)5 and OEt groups (compounds 3
), and (b) attack of the amidinatotetrylene to the Ccarbene atom (α‐attack), which ends in σ‐allenyl complexes in which the original Ccarbene atom is not attached to the metal atom and has been inserted into an E−N bond of the amidinatotetrylene forming an E‐C‐N‐C‐N five‐membered ring (compounds 4
). It has been found that compounds 3
are thermodynamically less stable than their corresponding 4
isomers and that some of the former (E=Ge; R1=CH2SiMe3) can be transformed into the latter upon heating. At high temperatures (>70 °C) the reactions involving bulky amidinatotetrylenes (R1=Mes, tBu) end in the carbene‐substitution products [Cr{E(tBu2bzm)R1}(CO)5].
Enantioselective Conjugate Addition‐Protonation of 5H‐Oxazol‐4‐ones and 5‐Methylene 1,3‐Oxazolidine‐2,4‐diones: 2,2'‐Biphenol‐Induced Diastereoselectivity Switch
Authors: Lu Bohua , Xin Shuang , Zhu Bo , Chang Junbiao
Published: May 2019

Summary of main observation and conclusion

A synthetic strategy for catalytic asymmetric conjugate addition‐protonation and diastereoselective switch between 5H‐oxazol‐4‐ones and 5‐methylene 1,3‐oxazolidine‐2,4‐diones was established. An array of chiral conjugate addition‐protonation products bearing 1,3‐O‐heterotertiary‐O‐heteroquarternary nonadjacent stereocenters were obtained in excellent yields, moderate to good diastereoselectivities, and excellent enantioselectivities (up to 97% yield, 11: 1 dr, and 98% ee). Induction by 2,2’‐biphenol could effectively promote the production of the corresponding diastereoisomersviacycloaddition intermedia.
Population Pharmacokinetic Modeling and Probability of Target Attainment Analyses in Asian Patients With Community‐Acquired Pneumonia Treated With Ceftaroline Fosamil
Authors: Li Jianguo , Das Shampa , Zhou Diansong , Al‐Huniti Nidal
Published: May 2019

Efficacy of ceftaroline fosamil, the prodrug of the active metabolite ceftaroline, was demonstrated in a phase 3 study of hospitalized Asian patients with Pneumonia Outcomes Research Team (PORT) risk class III–IV community‐acquired pneumonia (NCT01371838). The objectives of the current analysis were to expand an existing ceftaroline and ceftaroline fosamil population pharmacokinetic (PK) model with data from this phase 3 study and a phase 1 study (NCT01458743) assessing ceftaroline PK in healthy Chinese volunteers and to evaluate the probability of PK/pharmacodynamic (PK/PD) target attainment (PTA) in Asian patients with community‐acquired pneumonia (CAP) treated with ceftaroline fosamil. The ceftaroline plasma concentration‐time course was simulated for 5000 Asian patients with CAP for different renal function subgroups using the final model. PTA was calculated forStreptococcus pneumoniae,Staphylococcus aureus, and non‐extended‐spectrum β‐lactamase‐producingEnterobacteriaceae. PTA was also evaluated for ceftaroline MIC90values of isolates collected from Asia‐Pacific surveillance studies (2012–2014) and for EUCAST and FDA/CLSI ceftaroline susceptibility break points. The final model reasonably described the ceftaroline PK. Race was not found to be a significant covariate impacting ceftaroline PK, suggesting similar ceftaroline PK in Asian and Western populations when corrected for body weight. High PTAs (90%–100%) were predicted for Asian patients with CAP treated with ceftaroline fosamil, covering MIC90values of target CAP pathogens from the region. Similarly, >90% PTAs were predicted at EUCAST and FDA/CLSI clinical break points for these pathogens. These results support the use of the ceftaroline fosamil dosing regimens approved in Europe and the United States in Asian patients with PORT III–IV CAP.
Solvent‐Enhanced Conformational Flexibility of Cyclic Tetrapeptides
Authors: Berger Nadja , Wollny Laura J. B. , Sokkar Pandian , Mittal Sumit , Mieres‐Perez Joel , Stoll Raphael , Sander Wolfram , Sanchez‐Garcia Elsa
Published: May 2019

Solvent and temperature can affect the structural properties of cyclic peptides by controlling their flexibility. Here, we investigate two cyclic peptides, featuring beta turns. Using temperature‐dependent NMR and FT‐IR, we observed a pronounced temperature effect on the conformation of the cyclic peptide D‐1 in CHCl3 but a much smaller effect in CH3CN. Almost no effect was observed for its diastereomer L‐1 within a similar temperature range and using the same solvents. With the aid of Replica Exchange Molecular Dynamics simulations and Quantum Mechanics/Molecular Mechanics calculations, we were able to explain this behavior based on the increased flexibility of D‐1 (in CHCl3) in terms of intramolecular hydrogen bonding. The largest temperature dependence is observed for D‐1 in CHCl3, while the temperature effect is less pronounced for L‐1 in CHCl3 and for both peptides in CH3CN. This work provides new insights into the role of the environment and temperature on the conformations of cyclic peptides.
Atomic Layer Deposition of Space‐Efficient SnO2 Underlayers for BiVO4 Host–Guest Architectures for Photoassisted Water Splitting
Authors: Lamm Benjamin , Zhou Lite , Rao Pratap , Stefik Morgan
Published: May 2019

Invited for this month′s cover are the Stefik and Rao groups at the University of South Carolina and Worcester Polytechnic Institute. The image shows a fantastical submarine solar‐water‐splitting process using the host‐guest architectures described in the report. The Full Paper itself is available at 10.1002/cssc.201802566.
Categorization of species as native or nonnative using DNA sequence signatures without a complete reference library
Authors: Andersen Jeremy C. , Oboyski Peter , Davies Neil , Charlat Sylvain , Ewing Curtis , Meyer Christopher , Krehenwinkel Henrik , Lim Jun Ying , Noriyuki Suzuki , Ramage Thibault , Gillespie Rosemary G. , Roderick George K.
Published: May 2019

New genetic diagnostic approaches have greatly aided efforts to document global biodiversity and improve biosecurity. This is especially true for organismal groups in which species diversity has been underestimated historically due to difficulties associated with sampling, the lack of clear morphological characteristics, and/or limited availability of taxonomic expertise. Among these methods, DNA sequence barcoding (also known as “DNA barcoding”) and by extension, meta‐barcoding for biological communities, has emerged as one of the most frequently utilized methods for DNA‐based species identifications. Unfortunately, the use of DNA barcoding is limited by the availability of complete reference libraries (i.e., a collection of DNA sequences from morphologically identified species), and by the fact that the vast majority of species do not have sequences present in reference databases. Such conditions are critical especially in tropical locations that are simultaneously biodiversity rich and suffer from a lack of exploration and DNA characterization by trained taxonomic specialists. To facilitate efforts to document biodiversity in regions lacking complete reference libraries, we developed a novel statistical approach that categorizes unidentified species as being either likely native or likely nonnative based solely on measures of nucleotide diversity. We demonstrate the utility of this approach by categorizing a large sample of specimens of terrestrial insects and spiders (collected as part of the Moorea BioCode project) using a generalized linear mixed model (GLMM). Using a training data set of known endemic (n = 45) and known introduced species (n = 102), we then estimated the likely native/nonnative status for 4,663 specimens representing an estimated 1,288 species (412 identified species), including both those specimens that were either unidentified or whose endemic/introduced status was uncertain. Using this approach, we were able to increase the number of categorized specimens by a factor of 4.4 (from 794 to 3,497), and the number of categorized species by a factor of 4.8 from (147 to 707) at a rate much greater than chance (77.6% accuracy). The study identifies phylogenetic signatures of both native and nonnative species and suggests several practical applications for this approach including monitoring biodiversity and facilitating biosecurity.
A comprehensive evaluation of predictive performance of 33 species distribution models at species and community levels
Authors: Norberg Anna , Abrego Nerea , Blanchet F. Guillaume , Adler Frederick R. , Anderson Barbara J. , Anttila Jani , Araújo Miguel B. , Dallas Tad , Dunson David , Elith Jane , Foster Scott D. , Fox Richard , Franklin Janet , Godsoe William , Guisan Antoine , O'Hara Bob , Hill Nicole A. , Holt Robert D. , Hui Francis K. C. , Husby Magne , Kålås John Atle , Lehikoinen Aleksi , Luoto Miska , Mod Heidi K. , Newell Graeme , Renner Ian , Roslin Tomas , Soininen Janne , Thuiller Wilfried , Vanhatalo Jarno , Warton David , White Matt , Zimmermann Niklaus E. , Gravel Dominique , Ovaskainen Otso
Published: May 2019

A large array of species distribution model (SDM) approaches has been developed for explaining and predicting the occurrences of individual species or species assemblages. Given the wealth of existing models, it is unclear which models perform best for interpolation or extrapolation of existing data sets, particularly when one is concerned with species assemblages. We compared the predictive performance of 33 variants of 15 widely applied and recently emerged SDMs in the context of multispecies data, including both joint SDMs that model multiple species together, and stacked SDMs that model each species individually combining the predictions afterward. We offer a comprehensive evaluation of these SDM approaches by examining their performance in predicting withheld empirical validation data of different sizes representing five different taxonomic groups, and for prediction tasks related to both interpolation and extrapolation. We measure predictive performance by 12 measures of accuracy, discrimination power, calibration, and precision of predictions, for the biological levels of species occurrence, species richness, and community composition. Our results show large variation among the models in their predictive performance, especially for communities comprising many species that are rare. The results do not reveal any major trade‐offs among measures of model performance; the same models performed generally well in terms of accuracy, discrimination, and calibration, and for the biological levels of individual species, species richness, and community composition. In contrast, the models that gave the most precise predictions were not well calibrated, suggesting that poorly performing models can make overconfident predictions. However, none of the models performed well for all prediction tasks. As a general strategy, we therefore propose that researchers fit a small set of models showing complementary performance, and then apply a cross‐validation procedure involving separate data to establish which of these models performs best for the goal of the study.
No guts, no glory: Gut content metabarcoding unveils the diet of a flower‐associated coastal sage scrub predator
Authors: Masonick Paul , Hernandez Madison , Weirauch Christiane
Published: May 2019

Invertebrate generalist predators are ubiquitous and play a major role in food‐web dynamics. Molecular gut content analysis (MGCA) has become a popular means to assess prey ranges and specificity of cryptic arthropods in the absence of direct observation. While this approach has been widely used to study predation on economically important taxa (i.e., pests) in agroecosystems, it is less frequently used to study the broader trophic interactions involving generalist predators in natural communities such as the diverse and threatened coastal sage scrub communities of Southern California. Here, we employ DNA metabarcoding‐based MGCA and survey the taxonomically and ecologically diverse prey range of Phymata pacifica Evans, a generalist flower‐associated ambush bug (Hemiptera: Reduviidae). We detected predation on a wide array of taxa including beneficial pollinators, potential pests, and other predatory arthropods. The success of this study demonstrates the utility of MGCA in natural ecosystems and can serve as a model for future diet investigations into other cryptic and underrepresented communities.
Continuous Flow Synthesis of Highly Substituted Tetrahydrofurans
Authors: Hoffmeyer Patrick , Schneider Christoph
Published: May 2019

The highly diastereoselective synthesis of multiply substituted tetrahydrofurans was achieved in a sequential process under continuous flow conditions. Greatly reduced reaction times, improved selectivities and enhanced yields are the benefits of this approach in comparison to the initial batch synthesis. Moreover, gram amounts of product were produced in the flow reactor likewise due to facile upscaling. In addition, employing a novel bis(silyl)dienediolate tetrasubstituted tetrahydrofurans were made accessible as well.
α‐Methylation of Ketones with Methanol Catalyzed by Ni/SiO2‐Al2O3
Authors: Charvieux Aubin , Duguet Nicolas , Métay Estelle
Published: May 2019

α‐Methylation of ketones with methanol catalyzed by a cheap and easy to handle Ni/SiO2‐Al2O3 was explored. After optimization of the reaction between propiophenone and methanol, the desired product was obtained in 95 % isolated yield. A wide range of ketones was methylated under the optimized conditions (16 examples). This procedure was extended to a three‐component cross‐benzylation‐methylation of acetophenone.
Error in estimating area‐level air pollution exposures for epidemiology
Authors: Keller Joshua P. , Peng Roger D.
Published: May 2019

In air pollution epidemiology, measurements of relevant exposure concentrations are typically made at point locations, resulting in spatial misalignment between the exposure data and health outcomes aggregated at the area level. To obtain values that match the spatial units of the health data, observations can be averaged directly or prediction models developed. We present a framework for evaluating the error in aggregating exposure concentrations to the area unit. We present estimators of mean squared error that can be used for model selection. We find that exposure prediction models, even when misspecified, outperform monitor averages in settings with realistic numbers of monitors and that important reductions in error of the health effect estimate can be obtained when restricting to areas with a monitor. In an analysis of long‐term particulate matter concentrations across the United States, we estimated the error of the prediction model approach to be less than that of the monitor averaging approach on average across counties. We present health effect estimates about particulate matter exposure and pediatric asthma morbidity in the Medicaid population using each approach. Our findings support the use of a prediction model for estimating area‐wide averages, even when restricting to areas that contain a monitor.
Incidental detection of oropharyngeal cancer with fluciclovine PET
Authors: Jethanandani Amit , Chen Melissa M. , Gule‐Monroe Maria K. , Morrison William H. , Lai Stephen Y. , Johnson Jason M.
Published: May 2019

Background

Fluorine‐18‐labeled 1‐amino‐3‐fluorocyclobutane‐1‐carboxylic acid (fluciclovine) is a synthetic amino acid radiopharmaceutical initially developed to improve noninvasive diagnosis of gliomas and currently FDA approved for prostate cancer imaging. Although fluciclovine positron emission tomography (PET) has proven to be efficacious in detecting multiple types of cancer, its ability to detect oropharyngeal squamous cell carcinoma (OPSCC) is largely unknown.

Methods

We describe a case of incidental OPSCC detection with fluciclovine PET in a 66‐year old male patient during workup for recurrent prostate adenocarcinoma.

Results

Fluciclovine PET detected a left base of tongue (BOT) lesion, which was subsequently confirmed as invasive SCC on surgical pathology.

Conclusion

Given these findings, we discuss potential future directions for research with fluciclovine to overcome some of the known limitations of 18[F]fluorodeoxyglucose in oncological imaging.
Exploring characteristics associated with first benzodiazepine prescription in patients with affective disorders and related diagnoses
Authors: De Carlo Vera , Grancini Benedetta , Vismara Matteo , Benatti Beatrice , Arici Chiara , Cremaschi Laura , Cirnigliaro Giovanna , Degoni Luca , Oldani Lucio , Palazzo Carlotta , Glick Ira D. , Viganò Caterina , Dell'Osso Bernardo
Published: May 2019

Objective

In patients with affective disorders, benzodiazepines (BZDs) are frequently administered at the onset, sometimes inappropriately. We sought to identify clinical variables associated with first BZD prescription in a large sample of patients with affective disorders.

Methods

Four hundred sixty patients with mood or anxiety disorders attending different psychiatric services were assessed comparing those who received BZD as first treatment (BZD w/) and those who did not (BZD w/o).

Results

More than one third (35.7%) of the total sample had received BZDs as first prescription. In relation to mood disorders, BZD w/ subjects more frequently (a) had not a psychiatrist as first therapist, (b) had anxious symptoms at onset, (c) had adjustment disorder as first diagnosis, (d) were treated as outpatients. In relation to specific diagnoses, (a) personal decision of treatment for major depressive disorder, (b) outpatient status for bipolar disorder and (c) longer duration of untreated illness for adjustment disorder were more frequently associated with first BZD prescription. For anxiety disorders, the presence of stressful life events and the diagnoses of panic disorder or specific phobias were more frequently observed in BZD w/ patients.

Conclusion

Patients with affective disorders frequently received BZDs as first prescription with significant differences between and within mood and anxiety disorders.
Neddylation inhibition upregulates PD‐L1 expression and enhances the efficacy of immune checkpoint blockade in glioblastoma
Authors: Zhou Shaolong , Zhao Xinyi , Yang Zhuo , Yang Ruyi , Chen Chao , Zhao Kailiang , Wang Weiwei , Ma Yihui , Zhang Qiang , Wang Xinjun
Published: May 2019

Pevonedistat (MLN4924), a specific NEDD8‐activating enzyme inhibitor, has been considered as a promising treatment for glioblastoma, which is currently in Phase I/II clinical trials. On the other hand, inhibition of neddylation pathway substantially upregulates the expression of T cell negative regulator programmed death‐ligand 1 (PD‐L1), which might account for the potential resistance via evasion of immune surveillance checkpoints. Whether administration of anti‐PD‐L1 enhances the efficacy of pevonedistat through a cytotoxic T cell‐dependent mechanism in glioblastoma needs to be investigated. Here, we report that depletion of neddylation pathway key enzymes markedly elevates PD‐L1 expression in glioblastoma cancer cells. Consistently, neddylation inhibitor pevonedistat significantly enhances PD‐L1 expression in both glioblastoma cancer cell lines and animal models. Mechanistically, pevonedistat increases PD‐L1 mRNA levels mainly through inhibiting Cullin1‐F‐box and WD repeat domain‐containing 7 E3 ligase activity and accumulating c‐MYC proteins, a direct transcriptional activator of PD‐L1 gene expression. In addition, inhibition of Cullin3 activity by pevonedistat also blocks PD‐L1 protein degradation. Importantly, pevonedistat attenuates T cell killing through PD‐L1 induction, and blockade of PD‐L1 restores the sensitivity of pevonedistat‐treated glioblastoma cancer cells to T cell killing. The combination of pevonedistat and anti‐PD‐L1 therapy compared to each agent alone significantly increased the therapeutic efficacy in vivo. Our study demonstrates inhibition of neddylation pathway suppresses cancer‐associated immunity and provides solid evidence to support the combination of pevonedistat and PD‐L1/programmed cell death protein 1 immune checkpoint blockade as a potential therapeutic strategy to treat glioblastoma.
Self‐Sorting in Supramolecular Assembly of π‐Systems
Authors: Kar Haridas , Ghosh Suhrit
Published: May 2019

Self‐sorting is a term, which broadly identifies sorting out the individual components within a mixture, which is ubiquitous in Nature. In the recent past such self‐sorting phenomenon has been studied with great interest in supramolecular assembly of wide‐ranging building blocks. In this article, we particularly highlight the examples related to self‐sorting in co‐assembly of donor and acceptor type chromophoric systems. Supramolecular design principles based on immiscibility of chromophore appended chains, π‐surface mismatch, H‐bonding, chirality and others have been discussed in length. Examples correlating molecular assembly features with macroscopic picture have also been discussed particularly in context of implications in organic electronic applications of self‐sorted donor acceptor assemblies.
“Weathering the storm:” Mothers’ and fathers’ experiences of parenting a preterm infant
Authors: O'Donovan Aisling , Nixon Elizabeth
Published: May 2019

Parenting preterm infants is a unique experience distinct from parenting full‐term infants, characterized by a delayed transition to parenthood and limited caregiving opportunities. This study explored mothers’ and fathers’ lived experiences of parenting during infancy in the context of preterm birth. Semistructured qualitative interviews were conducted with 13 parents (6 fathers, 7 mothers) of preterm infants. Data were analyzed using interpretative phenomenological analysis. Four superordinate themes emerged: (a) An unnatural disaster: The traumatic nature of preterm birth, (b) The immediate aftermath: Disconnected and displaced, (c) Breaking the ice: Moving from frozen to melted, and (d) Aftershocks: Transitioning home. Both parents experienced preterm birth as traumatic. Similarities and differences in mothers’ and fathers’ experiences were identified. Preterm birth posed challenges for nurturant and social caregiving and resulted in anxiety, hypervigilance, and overprotective parenting behavior. The results highlight the need for trauma‐informed care and further research developing and testing empirically based interventions.
Ultrahigh figure‐of‐merit of Cu2Se incorporated with carbon coated boron nanoparticles
Authors: Li Meng , Islam Sheik Md. Kazi Nazrul , Yahyaoglu Mujde , Pan Deng , Shi Xun , Chen Lidong , Aydemir Umut , Wang Xiaolin
Published: May 2019

Cu2Se based thermoelectric materials are of great potential for high‐temperature energy harvesting due to their high‐temperature figure‐of‐merit (zT). For further development of Cu2Se, both engineering and mid‐temperature figure‐of‐merit need to be improved. In this work, we report that carbon‐coated boron (C/B) nanoparticles incorporation can significantly improve both mid‐ and high‐temperature zT in Cu2Se. The nanoparticle inclusions can result in a homogeneous distribution of Cu:C:B interfaces responsible for both improvement of the Seebeck coefficient and significantly reduction in thermal conductivity. Ultrahigh mid‐ and high temperature thermoelectric performance with zT = 1.7 at 700 K and 2.23 at 1000 K as well as significantly improved engineering zT are achieved in the C/B incorporated Cu2Se with desirable mechanical properties and cycling stability. Our findings will stimulate further study and exploration for the Cu2Se based thermoelectric materials for broad applications in converting waste heat to electricity with competitive energy conversion efficiency.
More than the sum of the parts: Toward full‐length receptor tyrosine kinase structures
Authors: Diwanji Devan , Thaker Tarjani , Jura Natalia
Published: May 2019

Intercellular communication governs complex physiological processes ranging from growth and development to the maintenance of cellular and organ homeostasis. In nearly all metazoans, receptor tyrosine kinases (RTKs) are central players in these diverse and fundamental signaling processes. Aberrant RTK signaling is at the root of many developmental diseases and cancers and it remains a key focus of targeted therapies, several of which have achieved considerable success in patients. These therapeutic advances in targeting RTKs have been propelled by numerous genetic, biochemical, and structural studies detailing the functions and molecular mechanisms of regulation and activation of RTKs. The latter in particular have proven to be instrumental for the development of new drugs, selective targeting of mutant forms of RTKs found in disease, and counteracting ensuing drug resistance. However, to this day, such studies have not yet yielded high‐resolution structures of intact RTKs that encompass the extracellular and intracellular domains and the connecting membrane‐spanning transmembrane domain. Technically challenging to obtain, these structures are instrumental to complete our understanding of the mechanisms by which RTKs are activated by extracellular ligands and of the effect of pathological mutations that do not directly reside in the catalytic sites of tyrosine kinase domains. In this review, we focus on the recent progress toward obtaining such structures and the insights already gained by structural studies of the subdomains of the receptors that belong to the epidermal growth factor receptor, insulin receptor, and platelet‐derived growth factor receptor RTK families. © 2019 IUBMB Life, 71(6):706–720, 2019
Expression of troponin subunits in the rat renal afferent arteriole
Authors: Takeya Kosuke , Kathol Iris , Sutherland Cindy , Wang Xuemei , Loutzenhiser Rodger , Walsh Michael P.
Published: May 2019

Vascular smooth muscle cells of the renal afferent arteriole are unusual in that they must be able to contract very rapidly in response to a sudden increase in systemic blood pressure in order to protect the downstream glomerular capillaries from catastrophic damage. We showed that this could be accounted for, in part, by exclusive expression, at the protein level, of the “fast” (B) isoforms of smooth muscle myosin II heavy chains in the afferent arteriole, in contrast to other vascular smooth muscle cells such as the rat aorta and efferent arteriole which express exclusively the “slow” (A) isoforms (Shiraishi et al. (2003) FASEB. J. 17, 2284–2286). As contraction of the more rapidly contracting striated (skeletal and cardiac) muscles is regulated by the thin filament‐associated troponin (Tn) system, we hypothesized that Tn or a Tn‐like system may exist in afferent arteriolar cells and contribute to the unusually rapid contraction of this tissue in response to increased intraluminal pressure. We examined the expression of TnC (Ca2+‐binding subunit), TnI (inhibitory subunit), and TnT (tropomyosin‐binding subunit) in vascular smooth muscle cells of the rat renal afferent arteriole at the mRNA level. Fast‐twitch skeletal muscle and slow‐twitch skeletal muscle/cardiac TnC isoforms and slow‐twitch skeletal muscle and cardiac TnI isoforms were detected by reverse transcription‐polymerase chain reaction (RT‐PCR) and confirmed by cDNA sequencing. Furthermore, cardiac and slow‐twitch skeletal muscle TnI isoforms, but not fast‐twitch skeletal muscle TnI, were detected in isolated afferent arterioles at the protein level by proximity ligation assay. Finally, striated muscle myosin II heavy chain expression was identified in isolated rat afferent arterioles by RT‐PCR. We conclude that, in addition to Ca2+‐mediated phosphorylation of myosin II regulatory light chains, contraction of the afferent arteriole may be regulated by a mechanism normally associated with the much more rapidly contracting cardiac and skeletal muscles, which involves Ca2+ binding to TnC, leading to alleviation of inhibition of the actomyosin MgATPase by TnI and tropomyosin and rapid contraction of the vessel.
To tweet or not to tweet? A primer on social media for pharmacists
Authors: Dixon Dave L. , Reed Brent N.
Published: May 2019

Social media has evolved considerably since its humble beginnings in the late 1990s. Today, three billion individuals worldwide use social media. While its traditional use has been to connect with family and friends, social media has also been integrated into many other areas of society, including health care. Today, many health care professionals, including pharmacists, use social media for developing their own personal brand, professional networking, professional development, scholarly activity, pharmacy education, and even patient care. Despite the benefits of actively engaging with social media, the available evidence would suggest that pharmacists' engagement with social media for professional use has been limited. This is likely due to several well‐publicized criticisms of social media, including the potential for users to segregate themselves into echo chambers of only like‐minded individuals, inability to confirm the accuracy of shared information, its potential as a distractor from other tasks and responsibilities, and personal and patient privacy concerns. Fortunately, most of these concerns can be minimized if pharmacists develop a strategy for social media engagement that is intentional and consistent with their personal goals. Pharmacists should consider becoming not only passive “lurkers” on social media but also creating original content that shares knowledge and encourages conversations with others. We propose that pharmacists use a design‐based approach to ensure their use of social media is effective and sustainable. The “ABCDE” approach includes analyzing one's goals and audience, brainstorming ideas for how best to use social media, creating content that is relevant, practical, and useful, disseminating content efficiently and effectively, and periodically evaluating how well one's goals are being met and identifying opportunities for improvement.
Structural changes in heterogeneous panels with endogenous regressors
Authors: Baltagi Badi H. , Feng Qu , Kao Chihwa
Published: May 2019

This paper extends Pesaran's (Econometrica, 2006, 74, 967–1012) common correlated effects (CCE) by allowing for endogenous regressors in large heterogeneous panels with unknown common structural changes in slopes and error factor structure. Since endogenous regressors and structural breaks are often encountered in empirical studies with large panels, this extension makes Pesaran's CCE approach empirically more appealing. In addition to allowing for slope heterogeneity and cross‐sectional dependence, we find that Pesaran's CCE approach is also valid when dealing with unobservable factors in the presence of endogenous regressors and structural changes in slopes and error factor loadings. This is supported by Monte Carlo experiments.
Retracted: Upregulation of microRNA‐140‐3p inhibits epithelial‐mesenchymal transition, invasion, and metastasis of hepatocellular carcinoma through inactivation of the MAPK signaling pathway by targeting GRN
Authors: Zhang Qiu‐Yin , Men Chang‐Jun , Ding Xue‐Wei
Published: May 2019

Invasion and metastasis in hepatocellular carcinoma (HCC) results in poor prognosis. Human intervention in these pathological processes may benefit the treatment of HCC. The aim of the present study is to elucidate the mechanism of miR‐140‐3p affecting epithelial‐mesenchymal transition (EMT), invasion, and metastasis in HCC. Microarray analysis was performed for differentially expressed genes screening. The target relationship between miR‐140‐3p and GRN was analyzed. Small interfering RNA (siRNA) against granulin (GRN) was synthesized. EMT markers were detected, and invasion and migration were evaluated in HCC cells introduced with a miR‐140‐3p inhibitor or mimic, or siRNA against GRN. A mechanistic investigation was conducted for the determination of mitogen‐activated protein kinase (MAPK) signaling pathway‐related genes and EMT markers (E‐cadherin, N‐cadherin, and Vimentin). GRN was highlighted as an upregulated gene in HCC. GRN was a target gene of miR‐140‐3p. Elevation of miR‐140‐3p or inhibition of GRN restrained the EMT process and suppressed the HCC cell migration and invasion. HCC cells treated with the miR‐140‐3p mimic or siRNA‐GRN exhibited decreased GRN expression and downregulated the expressions of the MAPK signaling pathway‐related genes, N‐cadherin, and Vimentin but upregulated the expression of E‐cadherin. GRN silencing can reverse the activation of the MAPK signaling pathway and induction of EMT mediated by miR‐140‐3p inhibition. Taken together, the results show that miR‐140‐3p confers suppression of the MAPK signaling pathway by targeting GRN, thus inhibiting EMT, invasion, and metastasis in HCC.
Eco‐friendly, ultrasound‐assisted, and facile synthesis of one‐pot multicomponent reaction of acridine‐1,8(2H,5H)‐diones in an aqueous solvent
Authors: Chavan Pravin N. , Pansare Dattatraya N. , Shelke Rohini N.
Published: May 2019

A one‐pot, multistep synthesis of acridine‐1,8(2H,5H)‐diones (4a–m) was achieved by three‐component reaction of dimedone (1) with an aromatic aldehyde (2a–m) and an ammonium acetate (3) using water as a green solvent without any catalyst and a simple, easily handled, and ultrasonic technique as well as conventional method.
Enzyme immobilized on the surface geometry pattern of groove‐typed microchannel reactor enhances continuous flow catalysis
Authors: Zhu Chang‐Tong , Gong An , Zhang Fan , Xu Yan , Sheng Sheng , Wu Fu‐An , Wang Jun
Published: May 2019

BACKGROUND

Enzymatic catalysis in a microchannel under continuous flow has attracted increasing scientific interest. It allows for surfaces with higher specificities for heat and mass transfer and makes it easier to control reaction parameters. However, its applications are limited by a lesser amount of loading and cycle of use of the immobilized enzyme. A series of groove‐typed channel microreactors with surface geometry patterns were first established for effective immobilization of naringinase, which was used to produce isoquercitrin from rutin via hydrolysis.

RESULTS

Of the tested groove‐typed channel microreactors with surface geometry patterns, the enzyme adsorbing capacities of all were increased compared to that with smooth surface. The enzyme adsorbing capacity increased 1.32‐fold in the grooved microreactor with triangular pattern. Excellent yields of isoquercitrin production were produced in grooved channel immobilized enzyme microreactors with triangular surfaces. A yield of 91.72 ± 0.65% was obtained in 10 min, the microreactor could be reused 12 times with a residual activity over 56%. Efficient transfer of heat and mass were attained in the grooved microreactors with surface geometry patterns. The Poiseuille number and Nusselt number were increased by 20.61% and 29.63%, respectively, using fluid mechanics analysis in the grooved microreactor with triangular pattern.

CONCLUSION

The grooved microreactor with geometry pattern surface provided an efficient method for the high production of isoquercitrin, which is promising for enzyme immobilization and catalysis. © 2019 Society of Chemical Industry
Dissecting protein‐protein interactions in proteasome assembly: Implication to its self‐assembly
Authors: Pilla Smita P. , R Babu , Bahadur Ranjit P.
Published: May 2019

The 26S proteasome is a multi‐catalytic ATP‐dependent protease complex that recognizes and cleaves damaged or misfolded proteins to maintain cellular homeostasis. The 26S subunit consists of 20S core and 19S regulatory particles. 20S core particle consists of a stack of heptameric alpha and beta subunits. To elucidate the structure‐function relationship, we have dissected protein‐protein interfaces of 20S core particle and analyzed structural and physiochemical properties of intra‐alpha, intra‐beta, inter‐beta, and alpha‐beta interfaces. Furthermore, we have studied the evolutionary conservation of 20S core particle. We find the size of intra‐alpha interfaces is significantly larger and is more hydrophobic compared with other interfaces. Inter‐beta interfaces are well packed, more polar, and have higher salt‐bridge density than other interfaces. In proteasome assembly, residues in beta subunits are better conserved than alpha subunits, while multi‐interface residues are the most conserved. Among all the residues at the interfaces of both alpha and beta subunits, Gly is highly conserved. The largest size of intra‐alpha interfaces complies with the hypothesis that large interfaces form first during the 20S assembly. The tight packing of inter‐beta interfaces makes the core particle impenetrable from outer wall of the cylinder. Comparing the three domains, eukaryotes have large and well‐packed interfaces followed by archaea and bacteria. Our findings provide a structural basis of assembly of 20S core particle in all the three domains of life.