bluuebunny/crossref_metadata_2025 huggingface dataset:
Quinazoline‐Based Hydroxamic Acids: Design, Synthesis, and Evaluation of Histone Deacetylase Inhibitory Effects and Cytotoxicity
Authors: Hieu Doan Thanh , Anh Duong Tien , Hai Pham‐The , Huong Le‐Thi‐Thu , Park Eun Jae , Choi Jeong Eun , Kang Jong Soon , Dung Phan Thi Phuong , Han Sang‐Bae , Nam Nguyen‐Hai
Published: April 2018

In our search for novel histone deacetylases inhibitors, we have designed and synthesized a series of novel hydroxamic acids and N‐hydroxybenzamides incorporating quinazoline heterocycles (4a – 4i, 6a – 6i). Bioevaluation showed that these quinazoline‐based hydroxamic acids and N‐hydroxybenzamides were potently cytotoxic against three human cancer cell lines (SW620, colon; PC‐3, prostate; NCI‐H23, lung). In term of cytotoxicity, several compounds, e.g., 4g, 4c, 4g – 4i, 6c, and 6h, displayed from 5‐ up to 10‐fold higher potency than SAHA (suberoylanilidehydroxamic acid, vorinostat). The compounds were also generally comparable to SAHA in inhibiting HDACs with IC50 values in sub‐micromolar range. Some compounds, e.g., 4g, 6c, 6e, and 6h, were even more potent HDAC inhibitors compared to SAHA in HeLa extract assay. Docking studies demonstrated that the compounds tightly bound to HDAC2 at the active binding site with binding affinities higher than that of SAHA. Detailed investigation on the estimation of absorption, distribution, metabolism, excretion, and toxicity (ADMET) suggested that compounds 4g, 6c, and 6g, while showing potent HDAC2 inhibitory activity and cytotoxicity, also potentially displayed ADMET characteristics desirable to be expected as promising anticancer drug candidates.
A giant adrenal cyst with an uncertain preoperative diagnosis causing a dilemma in management
Authors: Olaoye Iyiade Olatunde , Adesina Micheal Dapo , Afolayan Enoch Abiodun
Published: April 2018

Key Clinical Message

Giant Adrenal cysts are rare differentials of retroperitoneal cysts that often present dilemma in diagnosis. A man presented with a huge retroperitoneal cyst and an uncertain preoperative diagnosis. Initial working diagnosis of urinoma and an attempt at drainage had to be abandoned for complete excision before obtaining a histological diagnosis.
Methemoglobinemia should be suspected when oxygen saturation apparently decreases after prilocaine infiltration during intravenous sedation
Authors: Wakita Ryo , Fukayama Haruhisa
Published: April 2018

Key Clinical Message

During intravenous sedation, a decrease in SpO2 is usually the result of respiratory failure. However, we experienced a case with SpO2 decrease that was caused by methemoglobinemia in prilocaine infiltration anesthesia during sedation. This indicates that methemoglobinemia should be considered if low SpO2 is sustained unrelated to sedation level.
Leukemic mature B‐cell neoplasm observed during the treatment with romiplostim in patient with thrombocytopenia and liver cirrhosis
Authors: Osawa Marina , Akiyama Hideki , Mae Sunao , Fujiwara Yuko , Yamane Michio
Published: April 2018

Key Clinical Message

We report here a new adverse event of romiplostim which is a protein analog of thrombopoietin. Leukemic mature B‐cell neoplasm was observed during the treatment of thrombocytopenia in a patient with liver cirrhosis. Their relationship was suggested clinically but the mechanism of leukemic expansion of lymphoma cells was not clarified.
Unravelling Chemical Interactions with Principal Interacting Orbital Analysis
Authors: Zhang Jing‐Xuan , Sheong Fu Kit , Lin Zhenyang
Published: April 2018

Decomposing chemical interactions into bonds and other higher order interactions is a common practice to analyse chemical structures, and gave birth to many chemical concepts, despite the fact that the decomposition itself might be subjective in nature. Fragment molecular orbitals (FMOs) offer a more rigorous alternative to such intuition, but might be less interpretable due to extensive delocalisation in FMOs. Inspired by the Principal Component Analysis in statistics, we hereby present a novel framework, Principal Interacting Orbital (PIO) analysis, that can very quickly identify the “dominant interacting orbitals” that are semi‐localised and easily interpretable, while still maintaining mathematical rigor. Many chemical concepts that are often taken for granted, but could not be easily inferred from other computational techniques like FMO analysis, can now be visualised as PIOs. We have also illustrated, through various examples covering both organic and inorganic chemistry, how PIO analysis could help us pinpoint subtle features that might play determining roles in bonding and reactions.
Ion‐Pairing Assemblies of π‐Electronic Anions Formed by Intramolecular Hydrogen Bonding
Authors: Maeda Hiromitsu , Takeda Yuka , Haketa Yohei , Morimoto Yuta , Yasuda Nobuhiro
Published: April 2018

π‐Extended nitro‐substituted dipyrrolylphenol derivatives were synthesized, and upon deprotonation they provided π‐electronic anions stabilized by hydrogen bonding between the phenolate (phenoxide) moiety and the pyrrole NH group. Ion‐pairing assemblies of the deprotonated anions were formed in the solid state and as mesophases. In the solid state, the extended π plane was found to be more suitable to form charge‐by‐charge assemblies in combination with tetraalkylammonium cations with highly anisotropic orientations as a result of efficient stacking. The mesophase also included a charge‐by‐charge assembly comprising the deprotonated anion bearing aliphatic chains, as revealed by synchrotron X‐ray diffraction analysis.
Reactions of Digallanes with p‐ and d‐Block Lewis Bases: Adducts, Bis(gallyl) Complexes, and Naked Ga+ as Ligand
Authors: Schuster Julia K. , Muessig Jonas H. , Dewhurst Rian D. , Braunschweig Holger
Published: April 2018

A range of double carbene adducts of digallanes(4) are prepared from an existing double digallane adduct, and their halides are subsequently exchanged, establishing the feasibility of both base and halide‐exchange reactions from digallane adducts. Furthermore, a range of digallium species are treated with transition‐metal Lewis bases, leading alternatively to oxidative addition products, species with monocoordinate Ga+ ligands, and an unusual ditopic metal‐only Lewis pair (MOLP). These results underline the manifold and unpredictable chemistry of halogallane species with Lewis bases.
Kinetics of the Sieving Process – Determination of Sieving Time in Analysis and Multi‐Deck Sieving
Authors: Teipel Ulrich , Schlotzhauer Selina
Published: April 2018

Die Siebung ist eine der ältesten Technologien zur Klassierung und Charakterisierung partikulärer Systeme und zählt noch immer zu den am weit verbreitetsten Methoden. Die Qualität und die Effizienz eines Siebvorganges und somit des Analysenergebnisses wird sowohl durch prozesstechnische Einflussgrößen als auch von produktspezifischen Eigenschaften des Aufgabegutes beeinflusst. Beim Einsatz einer Mehrdecksiebanlage oder eines Analysensiebturms beteiligen sich Siebe mit verschiedenen Maschenweiten zeitabhängig am Siebprozess. Im Rahmen dieser Arbeit wurden verschiedene partikuläre Materialien in einem Analysensiebturm untersucht. Die Siebzeit wurde variiert und die Partikelgrößenverteilung jeder Siebfraktion für jede Siebzeit ermittelt. Die Ergebnisse werden beispielhaft für Kalkstein und zerkleinerte Walnussschalen vorgestellt.
Near‐Infrared Image Analysis as Tool for Monitoring Process Activities
Authors: Kübel‐Heising Felix , Kunkel Sven , Medina Isabel , Hien Andreas , Schmitt Lukas , Scholl Stephan , Repke Jens‐Uwe , Rädle Matthias
Published: April 2018

In der Verfahrenstechnik treten häufig Zustände auf, bei denen die lokale Verteilung von Fluiden und Feststoffen und deren zeitliche und räumliche Veränderung maßgebliche prozessrelevante Größen darstellen. Dieser Beitrag widmet sich der Überwachung solcher Vorgänge, wie der Trocknung, Benetzung und Kristallstrukturbildung, die den Einsatz ortsaufgelöster und auch molekülspezifischer Messverfahren verlangt. Ein solches berührungsloses Verfahren stellt die Nahinfrarot‐Bildanalyse mit Indium‐Gallium‐Arsenid‐Sensor dar. Die Anwendungsmöglichkeiten und das Potenzial dieser Inline‐Messmethode werden aufgezeigt und erläutert.
Fully Automated Production and Characterization of 64Cu and Proof‐of‐Principle Small‐Animal PET Imaging Using 64Cu‐Labelled CA XII Targeting 6A10 Fab
Authors: Fiedler Luise , Kellner Markus , Oos Rosel , Böning Guido , Ziegler Sibylle , Bartenstein Peter , Zeidler Reinhard , Gildehaus Franz Josef , Lindner Simon
Published: April 2018

64Cu is a cyclotron‐produced radionuclide which offers, thanks to its characteristic decay scheme, the possibility of combining positron emission tomography (PET) investigations with radiotherapy. We evaluated the Alceo system from Comecer SpA to automatically produce 64Cu for radiolabelling purposes. We established a 64Cu production routine with high yields and radionuclide purity in combination with excellent operator radiation protection. The carbonic anhydrase XII targeting 6A10 antibody Fab fragment was successfully radiolabelled with the produced 64Cu, and proof‐of‐principle small‐animal PET experiments on mice bearing glioma xenografts were performed. We obtained a high tumor‐to‐contralateral muscle ratio, which encourages further in vivo investigations of the radioconjugate regarding a possible application in diagnostic tumor imaging.
Meeting the needs of long‐term survivors: A testament to success in the care of patients with cancer
Authors: Spiegel Daphna Y. , Koontz Bridget F.
Published: April 2018

Improvements in cancer therapy have resulted in cancer survivors living longer. These individuals have expectations and needs regarding education for the early detection of disease recurrence or late toxicity and maximizing their health. Clinicians have excelled in developing treatments to cure patients with cancer; we now need to expand our efforts to excel in caring for these cancer survivors.

See also pages 2653‐60.
Cone synapses in mammalian retinal rod bipolar cells
Authors: Pang Ji‐Jie , Yang Zhuo , Jacoby Roy A. , Wu Samuel M.
Published: April 2018

Some mammalian rod bipolar cells (RBCs) can receive excitatory chemical synaptic inputs from both rods and cones (DBCR2), but anatomical evidence for mammalian cone‐RBC contacts has been sparse. We examined anatomical cone‐RBC contacts using neurobiotin (NB) to visualize individual mouse cones and standard immuno‐markers to identify RBCs, cone pedicles and synapses in mouse and baboon retinas. Peanut agglutinin (PNA) stained the basal membrane of all cone pedicles, and mouse cones were positive for red/green (R/G)‐opsin, whereas baboon cones were positive for calbindin D‐28k. All synapses in the outer plexiform layer were labeled for synaptic vesicle protein 2 (SV2) and PSD (postsynaptic density)‐95, and those that coincided with PNA resided closest to bipolar cell somas. Cone‐RBC synaptic contacts were identified by: (a) RBC dendrites deeply invaginating into the center of cone pedicles (invaginating synapses), (b) RBC dendritic spines intruding into the surface of cone pedicles (superficial synapses), and (c) PKCα immunoreactivity coinciding with synaptic marker SV2, PSD‐95, mGluR6, G protein beta 5 or PNA at cone pedicles. One RBC could form 0‐1 invaginating and 1‐3 superficial contacts with cones. 20.7% and 38.9% of mouse RBCs contacted cones in the peripheral and central retina (p < .05, n = 14 samples), respectively, while 34.4% (peripheral) and 48.5% (central) of cones contacted RBCs (p > .05). In baboon retinas (n = 4 samples), cone‐RBC contacts involved 12.2% of RBCs (n = 416 cells) and 22.5% of cones (n = 225 cells). This suggests that rod and cone signals in the ON pathway are integrated in some RBCs before reaching AII amacrine cells.
Consumers' heterogeneous preferences for corporate social responsibility in the food industry
Authors: Lerro Marco , Vecchio Riccardo , Caracciolo Francesco , Pascucci Stefano , Cembalo Luigi
Published: April 2018

This study reveals the consumer side of corporate social responsibility (CSR) in the food industry, exploring awareness, preferences and willingness to pay for CSR of a representative sample of Italian households. The results clearly indicate that Italian consumers reveal a high level of awareness within clear, though heterogeneous, preferences for CSR initiatives. Five consumers' groups were identified: ‘environmentalists’, ‘pro‐socials’, ‘collectivists’, ‘animal friends’ and ‘selfish health centered’. Furthermore, the study reveals consumers' willingness to pay a premium price to reward food companies addressing their concerns and expectations in terms of CSR. Findings offer insights for business managers on how to promote CSR, developing communication and information strategies focusing on specific needs and personal relevance within a group of consumers.
A Rechargeable High‐Temperature Molten Salt Iron–Oxygen Battery
Authors: Peng Cheng , Guan Chengzhi , Lin Jun , Zhang Shiyu , Bao Hongliang , Wang Yu , Xiao Guoping , Chen George Zheng , Wang Jian‐Qiang
Published: April 2018

The energy and power density of conventional batteries are far lower than their theoretical expectations, primarily because of slow reaction kinetics that are often observed under ambient conditions. Here we describe a low‐cost and high‐temperature rechargeable iron–oxygen battery containing a bi‐phase electrolyte of molten carbonate and solid oxide. This new design merges the merits of a solid–oxide fuel cell and molten metal–air battery, offering significantly improved battery reaction kinetics and power capability without compromising the energy capacity. The as‐fabricated battery prototype can be charged at high current density, and exhibits excellent stability and security in the highly charged state. It typically exhibits specific energy, specific power, energy density, and power density of 129.1 Wh kg−1, 2.8 kW kg−1, 388.1 Wh L−1, and 21.0 kW L−1, respectively, based on the mass and volume of the molten salt.
Tunable Bifunctional Activity of MnxCo3−xO4 Nanocrystals Decorated on Carbon Nanotubes for Oxygen Electrocatalysis
Authors: Zhao Tingting , Gadipelli Srinivas , He Guanjie , Ward Matthew J. , Do David , Zhang Peng , Guo Zhengxiao
Published: April 2018

Invited for this month's cover is the group of Prof. Zhengxiao Guo at the University College London. The image illustrates an integrated manganese cobalt oxide/nitrogen‐doped multiwalled carbon nanotube hybrid (MnCo2O4@NCNT) catalyst for bifunctional oxygen reduction and evolution reactions (ORR/OER), out‐performing the commercial Pt/C and IrO2/C standards, with potential applications for the oxygen electrode in rechargeable metal–air batteries to power drones and electric vehicles. The Full Paper itself is available at 10.1002/cssc.201800049.
Immune regulation of the unfolded protein response at the mucosal barrier in viral infection
Authors: Wang Ran , Moniruzzaman Md. , Shuffle Eric , Lourie Rohan , Hasnain Sumaira Z
Published: April 2018

Protein folding in the endoplasmic reticulum (ER) is subject to stringent quality control. When protein secretion demand exceeds the protein folding capacity of the ER, the unfolded protein response (UPR) is triggered as a consequence of ER stress. Due to the secretory function of epithelial cells, UPR plays an important role in maintaining epithelial barrier function at mucosal sites. ER stress and activation of the UPR are natural mechanisms by which mucosal epithelial cells combat viral infections. In this review, we discuss the important role of UPR in regulating mucosal epithelium homeostasis. In addition, we review current insights into how the UPR is involved in viral infection at mucosal barriers and potential therapeutic strategies that restore epithelial cell integrity following acute viral infections via cytokine and cellular stress manipulation.
Recent novel approaches to limit oxidative stress and inflammation in diabetic complications
Authors: Pickering Raelene J , Rosado Carlos J , Sharma Arpeeta , Buksh Shareefa , Tate Mitchel , de Haan Judy B
Published: April 2018

Diabetes is considered a major burden on the healthcare system of Western and non‐Western societies with the disease reaching epidemic proportions globally. Diabetic patients are highly susceptible to developing micro‐ and macrovascular complications, which contribute significantly to morbidity and mortality rates. Over the past decade, a plethora of research has demonstrated that oxidative stress and inflammation are intricately linked and significant drivers of these diabetic complications. Thus, the focus now has been towards specific mechanism‐based strategies that can target both oxidative stress and inflammatory pathways to improve the outcome of disease burden. This review will focus on the mechanisms that drive these diabetic complications and the feasibility of emerging new therapies to combat oxidative stress and inflammation in the diabetic milieu.
Direct detection of the psychoactive substance MT‐45 in human tissue samples by probe electrospray ionization‐tandem mass spectrometry
Authors: Usui Kiyotaka , Murata Tasuku , Fujita Yuji , Kamijo Yoshito , Hanazawa Tomoki , Yoshizawa Tomohiro , Funayama Masato
Published: April 2018

Analyses of drugs and poisons in tissue samples are essential in forensic toxicology and pharmacology. However, current procedures for tissue analysis are laborious and time‐consuming. Therefore, we assessed the utility of a newly devised probe electrospray ionization (PESI) technique with tandem mass spectrometry (MS/MS) for easy, ultra‐rapid drug detection in human tissue samples. Using this system, typical pretreatment procedures, such as solid‐phase extraction, liquid–liquid extraction, deproteinization, or homogenization, can be avoided. Briefly, a tissue sample of 1–2 mm3 was supplemented with a solution of ethanol and 10 mmol/L ammonium formate, and measurements were obtained. We demonstrated the successful application of this method in a forensic case by detecting an opioid analgesic, MT‐45, in all tissue samples (liver, kidney, lung, brain, and heart). We also detected oxidized metabolites of MT‐45 in the liver. Since the analysis required only 0.5 minutes per sample, PESI–MS/MS is an ultra‐rapid detection method. Furthermore, for a quantitative approach, the total analysis time for the combination of PESI–MS/MS with the quick, easy, cheap, effective, rugged, and safe (QuEChERS) extraction method (from instrument start‐up to extraction and PESI‐analysis) was within 8 minutes. MT‐45 concentrations obtained by QuEChERS–PESI–MS/MS and liquid chromatography (LC) –MS/MS were similar for all tissue samples. PESI–MS/MS cannot be used to separate isobars/isomers (ie, compounds with the same m/z value), similar to other direct introduction techniques. Further studies are needed to validate the quantitation method. However, our results indicate that PESI–MS/MS is a potentially easy and rapid technique for the analysis of drugs and poisons in human tissue samples.
Development of –1 MV DC Filter and High‐Voltage DC Measurement Systems for ITER NBI
Authors: TAKAHASHI AKESHI , TANAKA TOSHIAKI , FUJITA HIROYUKI , HIRANUMA YUKI , ICHIMURA SATOSHI , WATANABE KAZUHIRO , KASHIWAGI MIEKO , MAEJIMA TETSUYA
Published: April 2018

This paper presents the development results of a −1 MV dc filter and dc measurement systems for an ITER (International Thermonuclear Experimental Reactor) neutral beam injector (NBI) system. High accuracy of 0.5% and fast responsivity of 3.3 μs, −3 dB are required for the dc measurement systems: both dc voltage dividers and DCCTs. Circuit design and thermal flow design were carried out to clarify and minimize their effects on the accuracy and responsivity. The validity of the established design was demonstrated by the actual‐product tests; temperature rise of each components fell below the allowable value; inner components of dc filter withstood dc −1.2 MV; each voltage divider accurately measured the voltage during the dc −1.2 MV withstand voltage test; the voltage dividers and the DCCTs were adequate to the requirements of responsivity (3.3 μs, −3 dB).
An enhanced Nonenzymatic Electrochemical Glucose Sensor Based on Copper‐Palladium Nanoparticles Modified Glassy Carbon Electrodes
Authors: Li Zhan‐Hong , Zhao Xue‐Ling , Jiang Xin‐Cheng , Wu Yi‐Hua , Chen Cheng , Zhu Zhi‐Gang , Marty Jean‐Louis , Chen Qing‐Song
Published: April 2018

Novel copper‐palladium nanoparticles modified glassy carbon electrodes (Cu−Pd/GC) with enhanced nonenzymatic sensing for glucose were facilely prepared by one‐step electrodeposition. The structure and composition of the prepared nanoparticles were characterized by XRD, SEM, TEM and EDS, respectively. The electrode modified process was characterized by electrochemical impedance spectroscopy. Cyclic voltammetry and chronoamperometric experiments were used to evaluate the electrocatalytic activities of the electrodes toward glucose. The surface morphology and the electrocatalytic activities of Cu−Pd/GC was compared to Pd and Cu nanoparticles modified glassy carbon electrodes (Pd/GC and Cu/GC), respectively. Thanks to homogeneous distribution of Cu−Pd nanoparticles and the synergistic effect of Cu and Pd atoms, Cu−Pd/GC exhibited the highest sensitivity (298 μA mM−1 cm−2) and the widest linear amperometric response (0.01 mM to 9.6 mM, R2=0.996) toward glucose compared to Pd/GC and Cu/GC. The detection limit of Cu−Pd/GC was 0.32 μM (S/N=3). In addition, the as‐prepared Cu−Pd/GC glucose sensor also exhibited exceptional capabilities of anti‐interference, reproducibility and long‐term stability. The as‐prepared sensor was also evaluated for determination of glucose concentration in human blood serum samples, which exhibited high reliability and accuracy, having great potential in clinical application.
Pretreatment of waste activated sludge by peracetic acid oxidation for enhanced anaerobic digestion
Authors: Sun Dedong , Qiao Mengyang , Xu Yanying , Ma Chun , Zhang Xinxin
Published: April 2018

This article studied the sludge reduction and supernatant changes during peracetic acid (PAA) oxidation and investigated subsequent anaerobic biodegradation. PAA oxidation treatment effectively leads to a disintegration of sewage sludge. The results suggested that the sludge solid concentration and volatile solid concentration decreased by 24.5 and 39.0% after 120 min, respectively, when the PAA dose was 30 mg PAA/g SS. The VSS to SS ratio dropped from 0.85 to 0.71. The concentration of supernatant soluble chemical oxygen demand, protein, total phosphorus, polysaccharide, and ammonia nitrogen increased by 530, 177, 166, 165, and 222%, respectively. Biogas production was enhanced when PAA was employed as a pretreatment. Compared with the control system, the cumulative biogas production increased by 20.0% after 28 days of anaerobic digestion (AD). The biogas production rate in digester with pretreated sludge reached the maximum on day 8 at 87mL/d, but the peak value was obtained on day 11 at 74mL/d in digester with the raw sludge, which indicated that PAA pretreatment could decrease the retention time of AD and increase biogas yield. © 2018 American Institute of Chemical Engineers Environ Prog, 37: 1901–1907, 2018
Alternative approach in performance analysis of organic rankine cycle (ORC)
Authors: Kılıç Bayram , Arabacı Emre
Published: April 2018

In this study, artificial neural networks (ANNs) and adaptive neuro‐fuzzy (ANFIS) have been used for performance analysis of organic rankine cycle (ORC) using refrigerants R123, R125, R227, R365mfc, SES36. It is well known that the steam generator temperature, condenser temperature, subcooling temperature, and superheating temperature affect the efficiency ratio of ORC. Therefore, efficiency ratio is forecasted depending on variable system parameters values. The results of ANN are compared with ANFIS in which the same data sets are used. Furthermore, new formulations derived from ANN for five refrigerants are presented for the determination of the efficiency ratio. The R2 values obtained from the networks were 0.99917, 0.99670, 0.99870, 0.99928, and 0.99911 for the R123, R125, R227, R365mfc, SES36 respectively which is very satisfactory. © 2018 American Institute of Chemical Engineers Environ Prog, 38: 254–259, 2019
An integrative approach combining passive sampling, bioassays, and effect-directed analysis to assess the impact of wastewater effluent
Authors: Sonavane Manoj , Schollée Jennifer E. , Hidasi Anita O. , Creusot Nicolas , Brion François , Suter Marc J.-F. , Hollender Juliane , Aїt-Aїssa Selim
Published: April 2018

Wastewater treatment plant (WWTP) effluents are major sources of endocrine-disrupting chemicals (EDCs) and other chemicals of toxicological concern for the aquatic environment. In the present study, we used an integrated strategy combining passive sampling (Chemcatcher®), developmental toxicity, and mechanism-based in vitro and in vivo bioassays to monitor the impacts of a WWTP on a river. In vitro screening revealed the WWTP effluent as a source of estrogen, glucocorticoid, and aryl hydrocarbon (AhR) receptor-mediated activities impacting the downstream river site where significant activities were also measured, albeit to a lesser extent than in the effluent. Effect-directed analysis of the effluent successfully identified the presence of potent estrogens (estrone, 17α-ethinylestradiol, and 17β-estradiol) and glucocorticoids (clobetasol propionate and fluticasone propionate) as the major contributors to the observed in vitro activities, even though other unidentified active chemicals were likely present. The impact of the WWTP was also assessed using zebrafish embryo assays, highlighting its ability to induce estrogenic response through up-regulation of the aromatase promoter-dependent reporter gene in the transgenic (cyp19a1b–green fluorescent protein [GFP]) zebrafish assay and to generate teratogenic effects at nonlethal concentrations in the zebrafish embryo toxicity test. The present study argues for the use of such an integrated approach, combining passive sampling, bioassays, and effect-directed analysis, to comprehensively identify endocrine active compounds and associated hazards of WTTP effluents. Environ Toxicol Chem 2018;37:2079–2088. © 2018 SETAC
Experimental study of the influence of interior lining distributions on flashover in the enclosure with different ceiling structures
Authors: Niu Xuemin , Hasemi Yuji , Yasui Noboru , Kagiya Koji
Published: April 2018

Different distributions of interior linings in an enclosure have been studied to reveal the influence on time to flashover. Two kinds of ceiling structures, flat ceiling and flat ceiling with beams, were used for enclosure. Six full‐scale experiments were performed to investigate the occurrence of flashover in large enclosures. Heat release rate, gas temperature, and surface temperature of the enclosure were measured and analyzed. Experimental results show that time to flashover is extended for enclosure with large surface areas and large doors. Whether lining the interior linings on the ceiling or beams has a significant effect on flashover. Considering that ceiling fires have effect on the progress of the spread of flame on the wall, time to flashover is reduced for the tests that are fitted with the interior linings on the wall of the enclosure. In the enclosure with beams, the direction of spread of flame on the ceiling is changed, resulting in the change of time to flashover. Additionally, the strength of ceiling jets that is affected by the heat release rate of fire source and the area of the interior linings mounted on the fire source influenced region affects flashover. It is observed that flashover occurs when flame fronts are throughout the upper part of the back wall and the flame‐covered area on the back wall exceeds 0.2 times the area of the back wall.
The Seemingly Futile Search for the “Missing Money”
Authors: Makholm Jeff D.
Published: April 2018

Google “missing money” and you will see an endless array of resources, some managed by federal, state, and local governments, to search for “unclaimed property”—having nothing at all to do with international energy markets. But add “electricity” to the search and up come a few dozen citations pertaining to problems with “resource adequacy” in electricity markets. “Missing money” in modern power markets concerns whether the various markets for power can provide the funds to induce competitive power producers to invest in sufficient generation capacity to keep the lights on.
The cerebellum after trauma: Resting‐state functional connectivity of the cerebellum in posttraumatic stress disorder and its dissociative subtype
Authors: Rabellino Daniela , Densmore Maria , Théberge Jean , McKinnon Margaret C. , Lanius Ruth A.
Published: April 2018

The cerebellum plays a key role not only in motor function but also in affect and cognition. Although several psychopathological disorders have been associated with overall cerebellar dysfunction, it remains unclear whether different regions of the cerebellum contribute uniquely to psychopathology. Accordingly, we compared seed‐based resting‐state functional connectivity of the anterior cerebellum (lobule IV–V), of the posterior cerebellum (Crus I), and of the anterior vermis across posttraumatic stress disorder (PTSD; n = 65), its dissociative subtype (PTSD + DS; n = 37), and non‐trauma‐exposed healthy controls (HC; n = 47). Here, we observed decreased functional connectivity of the anterior cerebellum and anterior vermis with brain regions involved in somatosensory processing, multisensory integration, and bodily self‐consciousness (temporo‐parietal junction, postcentral gyrus, and superior parietal lobule) in PTSD + DS as compared to PTSD and HC. Moreover, the PTSD + DS group showed increased functional connectivity of the posterior cerebellum with cortical areas related to emotion regulation (ventromedial prefrontal and orbito‐frontal cortex, subgenual anterior cingulum) as compared to PTSD. By contrast, PTSD showed increased functional connectivity of the anterior cerebellum with cortical areas associated with visual processing (fusiform gyrus), interoceptive awareness (posterior insula), memory retrieval, and contextual processing (hippocampus) as compared to HC. Finally, we observed decreased functional connectivity between the posterior cerebellum and prefrontal regions involved in emotion regulation, in PTSD as compared to HC. These findings not only highlight the crucial role of each cerebellar region examined in the psychopathology of PTSD but also reveal unique alterations in functional connectivity distinguishing the dissociative subtype of PTSD versus PTSD.
The dynamic relationships between economic status and health measures among working‐age adults in the United States
Authors: Meraya Abdulkarim M. , Dwibedi Nilanjana , Tan Xi , Innes Kim , Mitra Sophie , Sambamoorthi Usha
Published: April 2018

We examine the dynamic relationships between economic status and health measures using data from 8 waves of the Panel Study of Income Dynamics from 1999 to 2013. Health measures are self‐rated health (SRH) and functional limitations; economic status measures are labor income (earnings), family income, and net wealth. We use 3 different types of models: (a) ordinary least squares regression, (b) first‐difference, and (c) system‐generalized method of moment (GMM). Using ordinary least squares regression and first difference models, we find that higher levels of economic status are associated with better SRH and functional status among both men and women, although declines in income and wealth are associated with a decline in health for men only. Using system‐GMM estimators, we find evidence of a causal link from labor income to SRH and functional status for both genders. Among men only, system‐GMM results indicate that there is a causal link from net wealth to SRH and functional status. Results overall highlight the need for integrated economic and health policies, and for policies that mitigate the potential adverse health effects of short‐term changes in economic status.
Farm safety—Time to act
Authors: Lower Tony , Temperley John
Published: April 2018

Issues addressed

Agriculture is recognised as a highly dangerous sector worldwide; hence, the use of evidence‐based solutions to address injury‐related incidents is critical to prevention. The main of this article was to determine the potential for prevention by use of existing controls based on deaths data from 2001‐2016.

Methods

This study assesses data from the National Coroner's Information System for the period 2001‐2016 in regard to unintentional farm injury deaths in Australia (n = 1271). The six leading causes of death (tractors, quads [ATVs], water/dams, farm utilities [pickups], motorcycles and horses: n = 644) are reviewed against existing evidence‐based practice recommendations to ascertain the potential capacity to prevent and/or ameliorate the severity of the fatal incidents. Projections of economic costs associated with these incidents in the past five years (2012‐2016) are outlined.

Results

Of the cases involving the six leading agents (n = 644), 36% (n = 235) have the potential to be prevented with the use of designated evidence‐based controls. Meanwhile, the costs attributed to deaths involving the six leading agents in the 2012‐2016 period, exceeded $313 million.

Conclusions

Farm injury incidents and their related economic costs can be reduced by enhanced adoption of the existing evidence‐based controls.

So what

Farm safety efforts in Australia require reinvigoration and funding to focus on evidence‐based controls supported by enforcement to attain maximum impact.
Pre‐diagnostic blood immune markers, incidence and progression of B‐cell lymphoma and multiple myeloma: Univariate and functionally informed multivariate analyses
Authors: Vermeulen Roel , Saberi Hosnijeh Fatemeh , Bodinier Barbara , Portengen Lützen , Liquet Benoît , Garrido‐Manriquez Javiera , Lokhorst Henk , Bergdahl Ingvar A. , Kyrtopoulos Soterios A. , Johansson Ann‐Sofie , Georgiadis Panagiotis , Melin Beatrice , Palli Domenico , Krogh Vittorio , Panico Salvatore , Sacerdote Carlotta , Tumino Rosario , Vineis Paolo , Castagné Raphaële , Chadeau‐Hyam Marc ,   on behalf of the EnviroGenoMarkers Consortium Consortium members, Botsivali Maria , Chatziioannou Aristotelis , Valavanis Ioannis , Kleinjans Jos C.S. , de Kok Theo M.C.M. , Keun Hector C. , Athersuch Toby J. , Kelly Rachel , Lenner Per , Hallmans Goran , Stephanou Euripides G. , Myridakis Antonis , Kogevinas Manolis , Fazzo Lucia , De Santis Marco , Comba Pietro , Bendinelli Benedetta , Kiviranta Hannu , Rantakokko Panu , Airaksinen Riikka , Ruokojarvi Paivi , Gilthorpe Mark , Fleming Sarah , Fleming Thomas , Tu Yu‐Kang , Lundh Thomas , Chien Kuo‐Liong , Chen Wei J. , Lee Wen‐Chung , Kate Hsiao Chuhsing , Kuo Po‐Hsiu , Hung Hung , Liao Shu‐Fen
Published: April 2018

Recent prospective studies have shown that dysregulation of the immune system may precede the development of B‐cell lymphomas (BCL) in immunocompetent individuals. However, to date, the studies were restricted to a few immune markers, which were considered separately. Using a nested case–control study within two European prospective cohorts, we measured plasma levels of 28 immune markers in samples collected a median of 6 years before diagnosis (range 2.01–15.97) in 268 incident cases of BCL (including multiple myeloma [MM]) and matched controls. Linear mixed models and partial least square analyses were used to analyze the association between levels of immune marker and the incidence of BCL and its main histological subtypes and to investigate potential biomarkers predictive of the time to diagnosis. Linear mixed model analyses identified associations linking lower levels of fibroblast growth factor‐2 (FGF‐2 p = 7.2 × 10−4) and transforming growth factor alpha (TGF‐α, p = 6.5 × 10−5) and BCL incidence. Analyses stratified by histological subtypes identified inverse associations for MM subtype including FGF‐2 (p = 7.8 × 10−7), TGF‐α (p = 4.08 × 10−5), fractalkine (p = 1.12 × 10−3), monocyte chemotactic protein‐3 (p = 1.36 × 10−4), macrophage inflammatory protein 1‐alpha (p = 4.6 × 10−4) and vascular endothelial growth factor (p = 4.23 × 10−5). Our results also provided marginal support for already reported associations between chemokines and diffuse large BCL (DLBCL) and cytokines and chronic lymphocytic leukemia (CLL). Case‐only analyses showed that Granulocyte‐macrophage colony stimulating factor levels were consistently higher closer to diagnosis, which provides further evidence of its role in tumor progression. In conclusion, our study suggests a role of growth‐factors in the incidence of MM and of chemokine and cytokine regulation in DLBCL and CLL.
Characteristics of genomic alterations of lung adenocarcinoma in young never‐smokers
Authors: Luo Wenxin , Tian Panwen , Wang Yue , Xu Heng , Chen Lu , Tang Chao , Shu Yang , Zhang Shouyue , Wang Zhoufeng , Zhang Jun , Zhang Li , Jiang Lili , Liu Lunxu , Che Guowei , Guo Chenglin , Zhang Hong , Wang Jiali , Li Weimin
Published: April 2018

Non‐small‐cell lung cancer (NSCLC) has been recognized as a highly heterogeneous disease with phenotypic and genotypic diversity in each subgroup. While never‐smoker patients with NSCLC have been well studied through next generation sequencing, we have yet to recognize the potentially unique molecular features of young never‐smoker patients with NSCLC. In this study, we conducted whole genome sequencing (WGS) to characterize the genomic alterations of 36 never‐smoker Chinese patients, who were diagnosed with lung adenocarcinoma (LUAD) at 45 years or younger. Besides the well‐known gene mutations (e.g., TP53 and EGFR), our study identified several potential lung cancer‐associated gene mutations that were rarely reported (e.g., HOXA4 and MST1). The lung cancer‐related copy number variations (e.g., EGFR and CDKN2A) were enriched in our cohort (41.7%, 15/36) and the lung cancer‐related structural variations (e.g., EML4‐ALK and KIF5B‐RET) were commonly observed (22.2%, 8/36). Notably, new fusion partners of ALK (SMG6‐ALK) and RET (JMJD1C‐RET) were found. Furthermore, we observed a high prevalence (63.9%, 23/36) of potentially targetable genomic alterations in our cohort. Finally, we identified germline mutations in BPIFB1 (rs6141383, p.V284M), CHD4 (rs74790047, p.D140E), PARP1 (rs3219145, p.K940R), NUDT1 (rs4866, p.V83M), RAD52 (rs4987207, p.S346*), and MFI2 (rs17129219, p.A559T) were significantly enriched in the young never‐smoker patients with LUAD when compared with the in‐house noncancer database (p < 0.05). Our study provides a detailed mutational portrait of LUAD occurring in young never‐smokers and gives insights into the molecular pathogenesis of this distinct subgroup of NSCLC.
Second-Generation SYK Inhibitor Entospletinib Ameliorates Fully Established Inflammation and Bone Destruction in the Cherubism Mouse Model
Authors: Yoshimoto Tetsuya , Hayashi Tatsuhide , Kondo Toshio , Kittaka Mizuho , Reichenberger Ernst J , Ueki Yasuyoshi
Published: April 2018

Cherubism is a craniofacial disorder characterized by maxillary and mandibular bone destruction. Gain-of-function mutations in the SH3-domain binding protein 2 (SH3BP2) are responsible for the excessive bone resorption caused by fibrous inflammatory lesions. A homozygous knock-in (KI) mouse model for cherubism (Sh3bp2KI/KI) develops autoinflammation resulting in systemic bone destruction. Although administration of the TNF-α blocker etanercept to neonatal Sh3bp2KI/KI mice prevented the disease onset, this therapy was not effective for adult Sh3bp2KI/KI mice or human cherubism patients who already had lesions. Because genetic ablation of spleen tyrosine kinase (SYK) in myeloid cells rescues Sh3bp2KI/KI mice from inflammation, we examined whether SYK inhibitor administration can improve fully developed cherubism symptoms in adult Sh3bp2KI/KI mice. Entospletinib (GS-9973) was intraperitoneally injected into 10-week-old Sh3bp2KI/KI mice every day for 6 weeks. Treatment with GS-9973 improved facial swelling and histomorphometric analysis of lung and liver tissue showed that GS-9973 administration significantly reduced inflammatory infiltrates associated with decreased levels of serum TNF-α. Micro–computed tomography (μCT) analysis showed that GS-9973 treatment reduced bone erosion in mandibles, calvariae, and ankle and elbow joints of Sh3bp2KI/KI mice compared to Sh3bp2KI/KI mice treated with dimethyl sulfoxide (DMSO). Taken together, the results demonstrate that administration of the SYK inhibitor ameliorates an already established cherubism phenotype in mice, suggesting that pharmacological inhibition of SYK may be a treatment option for cherubism patients with active disease progression. © 2018 American Society for Bone and Mineral Research.
Beyond migration—Chemokines in lymphocyte priming, differentiation, and modulating effector functions
Authors: Laufer Julia M , Legler Daniel F
Published: April 2018

Chemokines and their receptors coordinate the positioning of leukocytes, and lymphocytes in particular, in space and time. Discrete lymphocyte subsets, depending on their activation and differentiation status, express various sets of chemokine receptors to be recruited to distinct tissues. Thus, the network of chemokines and their receptors ensures the correct localization of specialized lymphocyte subsets within the appropriate microenvironment enabling them to search for cognate antigens, to become activated, and to fulfill their effector functions. The chemokine system therefore is vital for the initiation as well as the regulation of immune responses to protect the body from pathogens while maintaining tolerance towards self. Besides the well investigated function of orchestrating directed cell migration, chemokines additionally act on lymphocytes in multiple ways to shape immune responses. In this review, we highlight and discuss the role of chemokines and chemokine receptors in controlling cell-to-cell contacts required for lymphocyte arrest on endothelial cells and immunological synapse formation, in lymphocyte priming and differentiation, survival, as well as in modulating effector functions.

Review on functions of chemokines and their receptors in lymphocyte biology that go beyond guiding directional cell migration.
MAIT cell-mediated cytotoxicity: Roles in host defense and therapeutic potentials in infectious diseases and cancer
Authors: Rudak Patrick T , Choi Joshua , Haeryfar S M Mansour
Published: April 2018

Mucosa-associated invariant T (MAIT) cells are unconventional, innate-like T lymphocytes that sense the presence of MHC-related protein 1 (MR1)-restricted ligands and select inflammatory cues. Consequently, they release potent immunomodulatory mediators, including IFN-γ, TNF-α, and/or IL-17. MAIT cells can also be viewed as killer cells. They display several NK cell-associated receptors, carry granules containing cytotoxic effector molecules, and swiftly upregulate perforin and granzymes upon activation. Accordingly, MAIT cells are capable of lysing MR1-expressing cells infected with a variety of pathogenic bacteria in in vitro settings and may also mount cytotoxic responses during microbial infections in vivo. Of note, MAIT cell hyperactivation during certain infections may impede their ability to elicit inflammatory and/or cytotoxic responses to secondary stimuli. In addition, MAIT cells isolated from within and from the margin of tumor masses exhibit diminished functions. We propose that MAIT cell-mediated cytotoxicity can be induced, bolstered, or restored to assist in clearing infections and potentially in reducing tumor loads. In this review, we discuss our current understanding of MAIT cells’ lytic functions and highlight the pressing questions that need to be addressed in future investigations. We also offer a picture, however hypothetical at this point, of how harnessing the full cytotoxic potentials of MAIT cells may be a valuable approach in the immunotherapy of infectious and malignant diseases.

Review on MAIT cells as effector cells that can destroy infected cells and may also have the capacity to eliminate neoplastic cells.
The Influence of Posttraumatic Stress Disorder on Health Functioning in Active‐Duty Military Service Members
Authors: Asnaani Anu , Kaczkurkin Antonia N. , Benhamou Kathy , Yarvis Jeffrey S. , Peterson Alan L. , Young‐McCaughan Stacey , Borah Elisa V. , Dondanville Katherine A. , Hembree Elizabeth A. , Litz Brett T. , Mintz Jim , Foa Edna B. ,   for the STRONG STAR Consortium
Published: April 2018

Researchers have suggested that posttraumatic stress disorder (PTSD) is associated with significant healthcare burden and utilization of medical services. The purpose of this study was to examine the impact of PTSD symptoms on health functioning among active‐duty military personnel. Participants in the study were 366 treatment‐seeking service members who had returned from deployment and were participating in a larger PTSD treatment study. Assessments included measures of PTSD symptom severity, combat experiences, life stress, health functioning, alcohol use, and depression. We hypothesized that at baseline, PTSD severity and its symptom clusters would be significantly associated with poorer physical and mental health functioning. We conducted separate hierarchical multiple regressions to examine the predictive contribution the hypothesized factors would have on the variance in physical and mental health scores. Consistent with previous literature, we found that PTSD severity was significantly associated with poorer mental health functioning, B = −0.25, SE = 0.08, β = −0.15, t(342) = −3.07, R2 = .37, p = .002; however, contrary to our hypotheses, PTSD severity was not associated with poorer physical health functioning. Further, the hyperarousal symptom cluster was significantly associated with poorer physical health functioning, B = −0.83, SE = 0.26, β = −0.18, t(340) = −3.16, R2 = .11, p = .002, but not mental health functioning. Limitations of our study included the use of self‐report measures only and lack of objective measures. Future directions for study include examination of how health functioning perceptions change over a longer duration of PTSD symptoms and after treatment.
Secondary Traumatic Stress and Burnout Among Refugee Resettlement Workers: The Role of Coping and Emotional Intelligence
Authors: Akinsulure‐Smith Adeyinka M. , Espinosa Adriana , Chu Tracy , Hallock Ryan
Published: April 2018

To promote a better understanding of the impact of refugee resettlement work on refugee resettlement workers, this study examined the prevalence rates of deleterious mental health and occupational outcomes, such as secondary traumatic stress and burnout, among a sample of 210 refugee resettlement workers at six refugee resettlement agencies in the United States. The study also explored coping mechanisms used by service providers to manage work‐related stress and the influence of such strategies and emotional intelligence on secondary traumatic stress and burnout. Our findings show that certain coping strategies, including self‐distraction, humor, venting, substance use, behavioral disengagement, and self‐blame, were strongly related to deleterious outcomes, βs = .18 to .38, ps = .023 to < .001. Emotional intelligence was a negative correlate for all outcomes, βs = −.25 to −.30, ps < .001, above and beyond the effects of trauma, coping styles, job, and demographic characteristics. These findings have potential implications for clinical training and organizational policy regarding refugee mental health.
Choosing the Right Laser for Microelectronic Packaging Tasks
Authors: Müller Dirk
Published: April 2018

The size of semiconductor dies and packaged devices continues to shrink in order to support more sophisticated and compact tablets, phones, watches and other wearables. This trend creates greater opportunities for lasers because of their unique ability to perform diverse materials processing tasks with high precision and minimal heat‐affected zone (HAZ). As a result, lasers are finding increased use in wafer dicing, package singulation, optical debonding, micro‐via drilling, RDL (re‐distribution layer) structuring, dicing tape cutting (EMI shield), soldering, annealing and laser‐assisted bonding, to name just a few. In this article, we review several laser‐based processes used in advanced packaging and examine some of the key benefits and trade‐offs in order to help guide engineers to choosing the optimum source for their particular task.