bluuebunny/crossref_metadata_2025 huggingface dataset:
Rab32‐related antimicrobial pathway is involved in the progression of dextran sodium sulfate‐induced colitis
Authors: Xie Xiaodong , Ni Qingshan , Zhou Daxue , Wan Ying
Published: August 2018

Inflammatory bowel disease (IBD) is a multifactorial disease involving defective immune responses against invasive microbiota. Genes associated with innate immune responses to microbes have been highlighted in the pathogenesis of IBD. To determine the role of Rab32 in the pathogenesis of IBD, we administered dextran sodium sulfate (DSS) to CD11c+ cell‐specific Rab32 knockout (CD11c‐Cre+Rab32f/f) mice to induce colitis. Rab32 deficiency in CD11c+ cells resulted in more severe disease progression and increased mortality. Histopathological analysis showed extensive damage to the colon mucosa in DSS‐treated CD11c‐Cre+Rab32f/f mice, including more severe damage to the epithelial layer and crypts, as well as more inflammatory cell infiltration. The pro‐inflammatory cytokines IL1A, IL1B, IL6, and CSF3 and chemokines CXCL1 and CXCL2 were significantly increased, and the frequency of CD11b+Ly6G+ neutrophils was higher in CD11c‐Cre+Rab32f/f colitis mice. Furthermore, CD11c+ cells deficient for Rab32 exhibited a significant increase in bacterial translocation in inflamed colon tissue. The present data demonstrate that Rab32 knockout in CD11c+ cells aggravates the development of DSS‐induced colitis and suggest that the Rab32‐related antimicrobial pathway is involved in the pathogenesis of IBD.
Photo‐and Electroluminescence from Nitrogen‐Doped and Nitrogen–Sulfur Codoped Graphene Quantum Dots
Authors: Hasan Md Tanvir , Gonzalez‐Rodriguez Roberto , Ryan Conor , Faerber Nicolas , Coffer Jeffery L. , Naumov Anton V.
Published: August 2018

As opposed to inorganic counterparts, organic quantum dots often exhibit lower fluorescence efficiencies and are complex to synthesize. Here we develop nitrogen‐doped (N‐GQDs) and nitrogen–sulfur codoped (NS‐GQDs) graphene quantum dots exhibiting high‐yield visible and near‐IR emission that are synthesized via a single‐step microwave‐assisted hydrothermal technique with a single glucosamine‐HCl starting material (thiourea precursor used for NS‐GQDs). As‐synthesized N‐GQDs and NS‐GQDs are well‐dispersed (average sizes of 5.50 and 3.90 nm) with high crystallinity and pronounced G‐band. Formed by the bottom‐up assembly of glucosamine, they contain amine linkage and a variety of oxygen‐containing functional groups assessed by Fourier‐transform infrared spectroscopy with ≈2% sulfur for NS‐GQDs. The synthetic procedure allows varying their size and the bandgap. Unlike other graphene‐based quantum dots, these GQDs exhibit bright, stable fluorescence both in the visible and near‐IR with high quantum yields of up to 60%. Excitation‐dependent visible fluorescence is attributed to size‐dependent bandgaps, with near‐IR emission potentially arising from the emissive defect states/their arrangements. Advantageous properties of these GQDs are utilized to develop exciton recombination layer for organic light‐emitting devices exhibiting both photoluminescence and electroluminescence in the visible. Produced by ecofriendly one‐step scalable synthesis brightly‐emissive N‐GQDs and NS‐GQDs become a promising material for novel organic optoelectronics.
Low‐Voltage, Printed, All‐Polymer Integrated Circuits Employing a Low‐Leakage and High‐Yield Polymer Dielectric
Authors: Stucchi Elena , Dell'Erba Giorgio , Colpani Paolo , Kim Yun‐Hi , Caironi Mario
Published: August 2018

In the path toward the integration of organic field‐effect transistors (OFETs) and logic circuits into low‐cost and mass produced consumer products, all‐organic devices based on printed semiconductors are one of the best options to meet stringent cost requirements. Within this framework, it is still challenging to achieve low voltage operation, as required by the use of thin film batteries and energy harvesters, for which a high capacitance and reliable organic dielectric is required. Here, the development of a parylene‐C based dielectric bilayer compatible with top‐gate architectures for low‐voltage OFETs and logic circuits is presented. The polymer bilayer dielectric allows the high yield fabrication of all‐polymer, bendable, transparent p‐ and n‐type OFETs operating below 2 V, with low leakage, uniform performances, and high yield. Such a result is a key enabler for the reliable realization of complementary logic circuits that can operate already at a voltage bias of 2 V, such as well‐balanced inverters, ring‐oscillators and D‐Flip‐Flops.
Preoperative globulin‐to‐albumin ratio predicts outcome after curative resection in patients with gastric cancer
Authors: Shimizu Takayuki , Ishizuka Mitsuru , Shibuya Norisuke , Tanaka Genki , Abe Akihito , Aoki Taku , Kubota Keiichi
Published: August 2018

Aim

The globulin‐to‐albumin ratio (GAR) is useful for prognostication of patients with various cancers. However, the significance of GAR in gastric cancer (GC) remains unclear. Our purpose was to investigate the relationship between the GAR and outcome after curative resection in GC patients.

Methods

Three‐hundred and seventy‐six patients who had undergone curative resection for GC were retrospectively reviewed. Univariate and multivariate analyses using the Cox proportional hazard model were performed to detect clinical characteristics that correlated with overall survival (OS), and their cut‐off values were identified using receiver operating characteristic (ROC) curve analyses. Kaplan–Meier analysis and log‐rank test were used for comparison of OS and relapse‐free survival (RFS).

Results

Multivariate analysis using 17 clinical characteristics selected by univariate analyses revealed that GAR (>0.80/≤0.80) was significantly associated with OS (hazard ratio [HR], 2.305; 95% CI, 1.122‐4.735; P = 0.023), as well as lymph node metastasis (presence/absence) (HR, 2.417; 95% CI, 1.077‐5.426; P = 0.032), neutrophil‐to‐lymphocyte ratio (>2.7/≤2.7) (HR, 2.368; 95% CI, 1.138‐4.930; P = 0.002), and serosal invasion (presence/absence) (HR, 3.443; 95% CI, 1.048‐11.31; P = 0.042). Kaplan–Meier analysis and log‐rank test demonstrated that the OS and RFS of patients with a high GAR (>0.80) were significantly poorer than those with low GAR (≤0.80).

Conclusions

The GAR is a useful predictor of postoperative outcome among GC patients undergoing curative resection.
Lamotrigine clearance increases by 5 weeks gestational age: Relationship to estradiol concentrations and gestational age
Authors: Karanam Ashwin , Pennell Page B. , French Jacqueline A. , Harden Cynthia L. , Allien Stephanie , Lau Connie , Barnard Sarah , Callisto Samuel P. , Birnbaum Angela K.
Published: August 2018

Objective

To determine how early lamotrigine clearance (LTG‐CL/F) increases during early pregnancy in women with epilepsy and to quantify the relationship of LTG‐CL/F to estradiol concentrations and gestational week.

Methods

This was a multicenter, observational study of pregnant women with epilepsy on lamotrigine and no interacting concomitant medications, employing frequent blood sampling prior to and early in pregnancy. A population mixed‐effects modeling approach was used to describe the relationship between LTG‐CL/F and gestational week and between LTG‐CL/F and estradiol. Akaike information criterion (AIC) compared goodness of fit between final models and a generalized estimating equation to compare differences between low and high percentage LTG‐CL/F change groups (p < 0.05).

Results

Twenty‐five pregnancies (22 participants) were available. Increases in LTG‐CL/F were present at 5 weeks gestational age. Both estradiol and gestational week were highly correlated with LTG‐CL/F changes; LTG‐CL/F increased at the rate of 0.115l/h for every gestational week and 0.844l/h for every 1ng/ml of estradiol, with women in the high LTG‐CL/F percentage change group changing at a faster rate (p < 0.001). Models using gestational week performed better than models using estradiol.

Interpretation

Gestational week was a better predictor of changes in LTG‐CL/F than estradiol concentration and may reflect additional factors, although neither was robust enough to use clinically due to substantial interpatient variability. Changes in LTG‐CL/F begin as early as the 5th gestational week, often before women know they are pregnant, emphasizing the importance of planning and early detection of pregnancy and consideration of early implementation of therapeutic drug monitoring. Ann Neurol 2018;84:556–563
Scalp electroencephalographic biomarkers in epilepsy patients with focal cortical dysplasia
Authors: Epitashvili Nino , San Antonio‐Arce Victoria , Brandt Armin , Schulze‐Bonhage Andreas
Published: August 2018

Objective

To assess scalp electroencephalographic (EEG) patterns as possible biomarkers for an underlying focal cortical dysplasia (FCD) in patients with structural epilepsy.

Methods

Scalp electroencephalograms (EEGs) of epilepsy patients with histologically confirmed diagnosis of FCD type I or II (n = 71, age = 3–66 years, 28 female) and of controls with other underlying pathologies (n = 43, age = 2–60 years, 16 female) were retrospectively evaluated regarding the presence or absence of 12 scalp EEG patterns previously reported to be associated with FCD. Furthermore, 2 subgroups of these biomarkers with common characteristics were also analyzed. Each of the 12 biomarkers was tested for association with FCD by comparing the presence of each feature in FCD patients and controls using Fisher exact test.

Results

A significant association with FCD as underlying etiology was found for 6 of 12 previously reported biomarkers. With decreasing odds ratios, these were continuous epileptiform discharges, 2 types of rhythmic epileptiform discharges, polyspikes, frequent rhythmic bursting epileptiform activity, and repetitive discharges as well as the subgroups containing repetitive activity and polyspikes, respectively. Presence of EEG biomarkers was independent of a visible underlying magnetic resonance imaging–visible lesion, and had similar prevalence with FCD I and II. Individual biomarkers had specificities of 65 to 98% and sensitivities of 17 to 61% for an underlying FCD, and combinations of EEG biomarkers achieved 100% specificity.

Interpretation

This study confirms that there are several surface EEG biomarkers significantly associated with an underlying cortical dysplasia. These biomarkers may aid in localizing suspicious brain regions and provide evidence for dysplastic brain tissue also in nonlesional patients of either histological FCD subtype. Ann Neurol 2018;84:564–575
Transition Metal Free Cycloamination of Prenyl Carbamates and Ureas Promoted by Aryldiazonium Salts
Authors: Abrams Roman , Lefebvre Quentin , Clayden Jonathan
Published: August 2018

Upon treatment with aryldiazonium salts, prenyl carbamates and ureas undergo redox‐neutral azocycloamination. In general, N‐aryl O‐prenyl carbamates cyclize in a photocatalytic reaction with visible light and an organic dye. With electron‐deficient diazonium salts, electronic matching with an electron‐rich N‐aryl substituent results in a reaction proceeding in the ground state, without either light or photocatalyst. Cyclic voltammetry suggests that this radical reaction is initiated by hydrogen‐atom abstraction mediated by an aryl radical, followed by a radical addition cascade and proton‐coupled hole propagation. The reaction proceeds at room temperature in short reaction times, and a range of functional groups is tolerated.
Ultraschnelle Photo‐RAFT‐Blockcopolymerisation von Isopren und Styrol im kontinuierlichen Flussreaktor
Authors: Lauterbach Felix , Rubens Maarten , Abetz Volker , Junkers Tanja
Published: August 2018

Polymere aus Isopren und Styrol sind in verschiedensten Zusammensetzungen in alltäglichen Verbrauchsprodukten zu finden. Ihre Synthese ist dabei üblicherweise auf radikalische Emulsions‐Polymerisation oder anionische Polymerisation limitiert. In dieser Arbeit wird daher die photoinduzierte RAFT‐Polymerisation (reversible addition‐fragmentation chain transfer) von Isopren und Styrol in einem kontinuierlichen Mikroreaktor beschrieben. Die Kombination aus hoher Photoeffizienz und erhöhten Temperaturen reduziert die Reaktionszeiten im Vergleich zu konventionellen, kontrolliert radikalischen Polymerisationsmethoden drastisch und ermöglicht somit signifikanten Monomerumsatz in weniger als einer halben Stunde. Es konnten zum ersten Mal Polyisopren (PI) und Polystyrol (PS) in realisierbaren Reaktionszeiten mit hohen Funktionalisierungsgraden hergestellt werden, deren Endgruppendichte über Blockcopolymerisationen bis hin zu einem Polystyrol‐block‐Polyisopren‐block‐Polystyrol (PS‐b‐PI‐b‐PS) nachgewiesen wurde.
Geochemical Continuity and Catalyst/Cofactor Replacement in the Emergence and Evolution of Life
Authors: Fontecilla‐Camps Juan C.
Published: August 2018

The origin of life is mostly divided into “genetics first” and “metabolism first” hypotheses. The former is based on spark‐tube tests and organic species from meteorites and comets, and proposes a heterotrophic origin of life also consistent with the “RNA World” concept. The “metabolism first” hypothesis posits that life began autotrophically on minerals and/or hydrothermal vents. The lack of direct evidence means it is not possible to lend solid support to either hypothesis but the “metabolism first” option can be explored if a continuous geochemical, catalytically dynamic process is assumed. Using this approach, it is speculated that purine and pyrimidine synthesis originated on a mineral surface, which was later replaced by ATP. The same applies to redox processes where metal‐bound hydrides could have been replaced by NAD.
Correlation of the Solid‐Fat Content in Vegetable Oils with Other Parameters during Thermal Oxidation
Authors: Woo YunSik , Kim Mi‐Ja , Lee JaeHwan
Published: August 2018

Correlations of the solid‐fat content (SFC) with oxidative parameters were determined in three vegetable oils including corn, soybean, and palm oils, during thermal oxidation at 150°C. As the oxidation time increased, SFC and oxidation parameters, including conjugated dienoic acid (CDA) value, p‐anisidine value (p‐AV), acid value, and total polar materials (TPM), increased at different rates in all oils. Although corn and soybean oil underwent higher rates of lipid oxidation than palm oil, SFC changes in palm oil were observed at higher rates than those in corn and soybean oils. Palm oil showed a high correlation of SFC against p‐AV and TPM compared with corn and soybean oils. Soybean oil showed a higher correlation of SFC and oxidation parameters than corn oil except acid values. SFC could be useful to determine secondary lipid oxidation products and the level of TPM in oxidized vegetable oils.
An Initial Study of the Catalytic Reforming of Crop Oil‐Derived 1‐Alkenes with HZSM‐5 to Aromatic Hydrocarbons
Authors: Amsley‐Benzie Shelby , Fegade Swapnil , Tande Brian , Kubátová Alena , Kozliak Evguenii , Seames Wayne
Published: August 2018

This study explored the production of aromatic hydrocarbons from the longer‐chain alkenes produced by the pyrolysis/cracking of crop oils. 1‐Tetradecene, serving as a model compound for these alkenes, was reformed in a batch reactor with a HZSM‐5 catalyst to produce a liquid hydrocarbon mixture with a high‐aromatic content. These reactions resulted in a >99% conversion of the 1‐tetradecene feedstock with a yield of up to 22 wt% of aromatic hydrocarbons. Surprisingly, isomers of C3‐substituted benzenes along with xylenes and diaromatics (lower homologs of alkyl‐substituted indanes and naphthalenes) were the main aromatic products rather than their lower‐molecular‐weight (MW) homologs, benzene, toluene, ethylbenzene and xylenes, which are commonly formed with high selectivity during zeolite‐catalyzed reforming. The recovery of higher‐MW aromatics, and particularly bicyclic naphthalenes and indanes, provides mechanistic insights for zeolite‐catalyzed alkene reforming reactions suggesting that these higher‐MW aromatics are likely formed near the catalyst surface at pore openings. Furthermore, the production of acyclic diene intermediates in the size range of C7–C10 provides insight into the overall reaction pathway. The results suggest that this reaction pathway may be a commercially viable option for the production of renewable C3‐substituted aromatic chemicals/chemical intermediates as coproducts to complement the kerosene and diesel fuel blendstocks that are the primary products from crop oil cracking.
Effects of the morphology of sulfobetaine zwitterionic layers grafted onto a silicone surface on improving the hydrophilic stability, anti‐bacterial adhesion properties, and biocompatibility
Authors: Cao Qin , Wu Shuqing , Wang Liying , Shi Xuetao , Li Guangji
Published: August 2018

Though silicone rubber has been used in the biomedical field, its inherent hydrophobic nature and “hydrophobic recovery” limit its wide application. In this article, cross‐linked and comb‐like sulfobetaine zwitterionic layers were covalently grafted onto the surface of a silicone film (SF) by ultraviolet (UV) curing in the presence and absence of cross‐linking agent, respectively, after the surface was pretreated under high‐energy vacuum ultraviolet (VUV) irradiation. Comparative studies were carried out to investigate the effects of the grafting layers on the surface properties, hydrophilic stability, anti‐bacterial adhesion property, and cytocompatibility. The results showed that VUV‐UV irradiation is an efficient modification method for introducing hydrophilic groups onto SF surface. The covalently linked zwitterions endowed the silicone surface with good hydrophilicity, a better reduction in the adhesion of bacteria relative to the properties of a pristine silicone surface. The cross‐linked layer exhibited better hydrophilic stability, anti‐bacterial adhesion properties and biocompatibility due to better coverage of the surface than the comb‐like layer. The improvement in these properties provides the potential for the extensive application of modified silicone films in silastic implants and medical dressings. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci.2018,135, 46860.
Synthesis and characterization of copolyamides derived from novel aliphatic bio‐based diamine
Authors: Rwei S.‐P. , Ranganathan P. , Chiang W.‐Y. , Lee Y.‐H.
Published: August 2018

Novel aliphatic nylon 6 (PA6) copolyamides were produced by melt polymerization reaction of our newly synthesized aliphatic bio‐based diamine monomer: N1, N6‐bis (4‐aminobutyl) adipamide (BABA). The pertinent long‐chain polyamide salt (BABA/SA) monomer was isolated as white solid, utterly characterized for the first time. The chemical structure of BABA, BABA/SA salt, and copolyamides (PA6‐BABA/SA) were investigated by 1H NMR and FTIR spectroscopy. Depending on the chemical compositions, the viscosity and molecular weight of the copolyamides were in the range of 20 275–12 652 and 2.81–2.12 dL/g. With increasing BABA/SA salt weight content in the synthesized copolyamides, their melting temperatures (Tm) and glass transition temperatures (Tg) decreased from 211.0 to 164.0 °C and 66.6 to 43.5 °C. In addition XRD results were investigated revealing all the copolyamides transferred from α‐form to γ‐form. Interestingly, the as‐synthesized all copolyamides possess nearly similar thermal stability (Td = 452.2–449.5 °C) as neat PA6. Mechanical testing data revealed that with increasing BABA/SA salt content, the elongation at break of copolyamides are increased (726.19–429.34%), while the tensile strength are decreased. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46878.
Cure behavior and compatibilization of epoxide hyperbranched polyurethane on silica/benzoxazine blend
Authors: Zhang C. , Lei Z. , Zhang J. , Wang Y. , Liu Y.
Published: August 2018

The compatibility of polymer blends is pivotal for their performance enhancement due to the large surface tension and weak interaction among individual components. In this work, epoxide hyperbranched polyurethanes (EHPU) was used to realize the compatibility between silica (SiO2), generated in situ from tetraethoxysilane, and benzoxazine (BZ). The compatibilization effect and mechanism of EHPU on SiO2/BZ were investigated via the differences of cure characteristics and kinetics between BZ, SiO2/BZ, and EHPU‐SiO2/BZ blend. EHPU‐SiO2/BZ blend exhibited lower initial curing temperature and wider curing window than those of SiO2/BZ and neat BZ. In addition, the co‐curing reaction was existed between EHPU and BZ, which contributed to the reactive compatibilization. More importantly, the growth of SiO2 particles was hindered by the nonreactive compatibilization due to the hydrogen interaction between EHPU and the silanols. Thus, the compatibilization of EHPU on SiO2/BZ blend is a result of the synergetic effect of the hydrogen interaction and the co‐curing. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46879.
Efficient adsorptive extraction materials by surface protein‐imprinted polymer over silica gel for selective recognition/separation of human serum albumin from urine
Authors: Madhumanchi Sreenu , Jadda Ramana , Suedee Roongnapa
Published: August 2018

In this study, we report the development of adsorptive extraction materials by surface protein‐imprinted polymers (MIPs) over silica gel for selective recognition/separation of human serum albumin (HSA) from urine. The HSA‐imprinted polymers prepared on silica particle had at interface between the silica gel and different MIPs greatly produced enrichment for the binding of protein from the urine. The solid‐phase extraction of the optimized polymer layer was prepared by copolymerization of methacrylic acid (MAA), acrylamide (AAm), and dimethylaminoethylmethacrylate (DMAEMA) and a crosslinker methylenebisacrylamide (MBA) at the mole ratio of 1:158:88 (T:M:C) and showed moderate affinity (<104 order M−1) toward target protein HSA and selectivity. Four analogues, egg white albumin (EWA), bovine serum albumin (BSA), lysozyme (Lyz), and creatinine (Cre) were selected to study the binding efficiency of MIPs in single and binary protein solutions. We studied the influence on recognition ability for HSA and found that prepolymer mixture and matrix flexibility of the optimized thin polymer layer (35 ± 10 nm) on the submicrosilica particles. The high‐binding affinity (QMIP, 86.7 mg g−1) and fast kinetics (180 min) were observed for this synthesized HSA‐MIP when compared with other reported HSA‐MIPs in surface imprinting (5.9 and 11.3 mg g−1) and epitope surface imprinting (46.6 mg g−1) methods. We demonstrated the application in real and synthetic urine samples that the approach allowed the efficient adsorption of HSA in real urine (129.48 mg g−1) is almost double to the binding of HSA in synthetic urine (67.84 mg g−1). Apart from this, only minor interference of Cre (2.74 mg g−1) was observed, eventhough Cre is the final metabolite in urine. These adsorptive submicrosilica materials have potential in the pharmaceutical industry and clinical analysis applications. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 46894.
Examining Reservoirs in Potable Reuse, Part 2: Surface Water Augmentation and Direct Potable Reuse
Authors: Pecson Brian M. , Trussell R. Shane , Triolo Sarah C. , Trussell R. Rhodes
Published: August 2018

An evaluation of surface water augmentation offers insights that can be used in developing public health recommendations for direct potable reuse.
A Self‐Assembling Two‐Dimensional Protein Array is a Versatile Platform for the Assembly of Multicomponent Nanostructures
Authors: Thomas Alexander , Matthaei James F. , Baneyx François
Published: August 2018

Rationally designed two‐dimensional (2D) arrays that support the assembly of nanoscale components are of interest for catalysis, sensing, and biomedical applications. The computational redesign of a protein called TTM that undergoes calcium‐induced self‐assembly into nanostructured lattices capable of growing to dozens of micrometers are previously reported. The work demonstrates here that the N‐ and C‐termini of the constituent monomers are solvent‐accessible and that they can be modified with a hexahistidine extension, a gold‐binding peptide, or a biotinylation tag to decorate nickel‐nitriloacetic acid beads with self‐assembled protein islands, conjugate gold nanoparticles to planar arrays, or control the immobilization density of avidin molecules onto 2D lattices through co‐polymerization of biotinylated and wild type TTM monomers. These results showcase the potential of TTM as a versatile 2D scaffold for the fabrication of hierarchical structures comprising a broad range of nanoscale elements.
Screening anaphylactoid components of Shuang Huang Lian Injection by analyzing spectrum–effect relationships coupled with UPLC–TOF–MS
Authors: Feng Yufei , Jing Zhongxu , Li Yongji , Lv Shaowa , Li Weinan , Cai Guofeng , Yang Danqi , Wang Yanhong
Published: August 2018

Shuang Huang Lian Injection (SHLI) has been used in China for over 30 years as an effective and widely used Chinese herbal prescription to treat acute respiratory infectious. SHLI has, however, caused many severe anaphylactoid reactions. It is important to identify the potential anaphylactoid components of SHLI. Spectrum–effect relationships were used to explore potentially anaphylactoid components. Based on the original herbal formula, honeysuckle, Fructus Forsythiae and Radix Scutellariae extracts were prepared and combined in appropriate proportions. The preparations were then injected into the caudal vein of rats to obtain in vivo serum samples for pharmacological evaluation and fingerprint analysis. The release rate of β‐hexosaminidase from RBL‐2H3 cells and plasma histamine level was used as the pharmacological index. Chromatographic fingerprint analysis identified 22 common peaks. Regression analysis and correlation analysis were used to calculate the relationships between the peaks and the pharmacological effects and identified peaks 5, 6, 11, 12 and 17 as likely anaphylactoid agents. The correlated peaks were identified by comparing the fingerprints with in vitro samples and reference standard samples and the structure was identified by UPLC–TOF–MS. This study established a prospective method to clarify the anaphylactoid components in SHLI, which would provide guidances for screening anaphylactoid components in other traditional Chinese medicine injections.
Design of MSE wall with reinforcing strips using FoundationPro
Authors: Yamin Mohammad M. , Obadat Mohammad
Published: August 2018

This paper presents the development and implementation of a mechanically stabilized Earth (MSE) Wall module in FoundationPro. The software was developed to improve the teaching methodology of MSE Wall foundation design with reinforcing strips as part of the foundation engineering coursework for undergraduate level students. The user‐friendly interface software was developed using Microsoft Visual Basic. It includes several features that enables the user to perform a wide range of foundation design problems effortlessly with improved accuracy. The software, which was developed as a shareware application with no licensing restrictions, is expected to positively impact many students and educators at several engineering schools nationally and internationally.
Lewis Base Catalyzed Selective Chlorination of Monosilanes
Authors: Sturm Alexander G. , Schweizer Julia I. , Meyer Lioba , Santowski Tobias , Auner Norbert , Holthausen Max C.
Published: August 2018

A preparatively facile, highly selective synthesis of bifunctional monosilanes R2SiHCl, RSiHCl2 and RSiH2Cl is reported. By chlorination of R2SiH2 and RSiH3 with concentrated HCl/ether solutions, the stepwise introduction of Si−Cl bonds is readily controlled by temperature and reaction time for a broad range of substrates. In a combined experimental and computational study, we establish a new mode of Si−H bond activation assisted by Lewis bases such as ethers, amines, phosphines, and chloride ions. Elucidation of the underlying reaction mechanisms shows that alcohol assistance through hydrogen‐bond networks is equally efficient and selective. Remarkably, formation of alkoxysilanes or siloxanes is not observed under moderate reaction conditions.
Transition‐Metal‐Free Synthesis of Biarylmethanes from Aryl Iodides and Benzylic Ketones
Authors: Pichette Drapeau Martin , Tlili Anis , Zaid Yassir , Toummini Dounia , Ouazzani Chahdi Fouad , Sotiropoulos Jean‐Marc , Ollevier Thierry , Taillefer Marc
Published: August 2018

An original metal‐free procedure for the synthesis of biarylmethanes is disclosed herein. The reactions occur with high selectivity starting from aryl iodides and benzylic ketones in the presence of superbasic media (CsOH/DMSO). This procedure allows a straightforward access to a wide range of biarylmethane derivatives substituted with electron‐withdrawing and ‐donating substituents.
Reengineering Chemical Glycosylation: Direct, Metal‐Free Anomeric O‐Arylation of Unactivated Carbohydrates
Authors: Lucchetti Nicola , Gilmour Ryan
Published: August 2018

To sustain innovation in glycobiology, effective routes to well‐defined carbohydrate probes must be developed. For over a century, glycosylation has been dominated by the formation of the anomeric Csp3−O acetal junction in glycostructures. A dissociative mechanistic spectrum spanning SN1 and SN2 is frequently operational thereby reducing the efficiency. By reengineering this fundamental process, an orthogonal disconnection allows the acetal to be formed directly from the reducing sugar without the need for substrate pre‐functionalisation. The use of stable aryliodonium salts facilitates a formal O−H functionalisation reaction. This allows lactols to undergo mild, metal‐free O‐arylation at ambient temperature. The efficiency of the transformation has been validated using a variety of pyranoside and furanoside monosaccharides in addition to biologically relevant di‐ and trisaccharides (up to 85 %). Fluorinated mechanistic probes that augment the anomeric effect were employed. It is envisaged that this strategy will prove expansive for the construction of complex acetals under substrate‐based stereocontrol.
Characterizing the Sources of Pharmacokinetic Variability for TAK‐117 (Serabelisib), an Investigational Phosphoinositide 3‐Kinase Alpha Inhibitor: A Clinical Biopharmaceutics Study to Inform Development Strategy
Authors: Patel Chirag G. , Rangachari Lakshmi , Patti Mark , Griffin Celina , Shou Yaping , Venkatakrishnan Karthik
Published: August 2018

TAK‐117 (also known as MLN1117 or serabelisib) is an orally available inhibitor of phosphoinositide 3‐kinase alpha being developed for treatment of solid tumors. This clinical study in healthy subjects assessed the relative bioavailability of a TAK‐117 tablet compared with a capsule formulation (part 1) and the effect of food (part 2) and intragastric pH modulation (part 3) on TAK‐117 pharmacokinetics. In part 1, subjects received single doses of 900 mg TAK‐117 under fasting conditions as capsules and tablets on 2 different occasions in random order. In part 2, subjects received a single dose of 600 mg TAK‐117 under fed (high‐fat meal) or fasted conditions on 2 different occasions in random order. In part 3, subjects received a single dose of 900 mg TAK‐117 alone and in combination with lansoprazole in a fixed sequence. Blood samples were collected up to 72 hours after each TAK‐117 dose. The geometric mean ratios (90% confidence intervals) for the area under the TAK‐117 plasma concentration‐time curves were 1.53 (0.93‐2.51) for tablets versus capsules, 1.50 (1.00‐2.25) for fed versus fasted, and 0.02 (0.01‐0.04) for TAK‐117 plus lansoprazole compared with TAK‐117 alone. The most common adverse event was nausea, the incidence of which was reduced when TAK‐117 was administered with food despite the increased systemic exposure. The incidence of all adverse events was reduced when TAK‐117 was administered with lansoprazole, which was consistent with the substantial reduction in bioavailability. Intersubject variability of TAK‐117 was high. Careful management of intragastric pH‐modulatory concomitant medications and food intake may be required.
Accelerating the computation of FLAPW methods on heterogeneous architectures
Authors: Davidović Davor , Fabregat‐Traver Diego , Höhnerbach Markus , Di Napoli Edoardo
Published: August 2018

Legacy codes in computational science and engineering have been very successful in providing essential functionality to researchers. However, they are not capable of exploiting the massive parallelism provided by emerging heterogeneous architectures. The lack of portable performance and scalability puts them at high risk, ie, either they evolve or they are destined to be executed on older platforms and small clusters. One example of a legacy code which would heavily benefit from a modern redesign is FLEUR, a software for electronic structure calculations. In previous work, the computational bottleneck of FLEUR was partially reengineered to have a modular design that relies on standard building blocks, namely, BLAS and LAPACK libraries. In this paper, we demonstrate how the initial redesign enables the portability to heterogeneous architectures. More specifically, we study different approaches to port the code to architectures consisting of multi‐core CPUs equipped with one or more coprocessors such as Nvidia GPUs and Intel Xeon Phis. Our final code attains over 70% of the architectures' peak performance, and outperforms Nvidia's and Intel's libraries. On JURECA, the large tier‐0 cluster where FLEUR is often executed, the code takes advantage of the full power of the computing nodes, attaining 5× speedup over the sole use of the CPUs.
Virtual machine migration algorithm for energy efficiency optimization in cloud computing
Authors: Zhou Zhou , Yu Junyang , Li Fangmin , Yang Fei
Published: August 2018

Cloud computing has gained more and more attention from industrial and academic circle since it offers pay‐as‐you‐go model, and business applications based on the cloud are also increasing. These applications meet the requirement of users while at the same time triggering the problem of high energy consumption in data centers. To deal with the problem, we propose a new algorithm named EEOM (Energy Efficiency Optimization of VM Migrations). Under considering CPU and memory factors, the key three steps for EEOM algorithm, including trigger time, VM selection, and host location, are optimized. EEOM algorithm takes use of the virtualization technology and migrates some VMs on the lightly loaded host and heavily loaded host to other hosts. The idle hosts are switched to low‐power mode or shut down so as to save energy consumption. The experimental results show that, as compared with Double Threshold (DT) algorithm, the EEOM algorithm saves 7% energy consumption and reduces 13% SLA violations.
Screening Strategies for the Discovery of Ion Channel Monoclonal Antibodies
Authors: Colley Caroline S. , England Elizabeth , Linley John E. , Wilkinson Trevor C. I.
Published: August 2018

Ion channels play crucial roles in physiology by modulation of cellular functions that include electrical excitability, secretion, cell migration, and gene transcription. They are an important target class for drug discovery and have historically been targeted using small molecule approaches. A significant opportunity exists to target these channels with antibodies and alternative forms of biologics. Antibodies display high specificity, selectivity, and affinity for their target antigen, thus having the potential to target ion channels very precisely. Nonetheless, isolating antibodies to ion channels is challenging due to the difficulties in expression and purification of ion channels in a format suitable for antibody drug discovery and due to the complexities of screening for function. In this overview, we focus on an array of screening methods, ranging from direct antibody binding screens to complex electrophysiological assays, and describe how these assays can be used to identify functional monoclonal antibodies. We also provide some insights into specific considerations which are required to enable these screens to be used for antibody drug discovery. © 2018 by John Wiley & Sons, Inc.
Overview of Transporters in Pharmacokinetics and Drug Discovery
Authors: Zhang Yan
Published: August 2018

Transporters play important roles in absorption, distribution, metabolism, and elimination (ADME) processes, as well as drug pharmacokinetics (PK) and pharmacodynamics (PD). They are also important in maintaining the homeostasis of endogenous compounds and nutrients in the body. Increasing evidences also suggest that they are important in mediating drug‐drug interactions (DDIs). While the significance of transporters in drug pharmacodynamics and DDIs are beyond the scope of this overview, the basic concepts of transporters, their contributions in membrane permeation processes, and their roles in influencing drug ADME pathway and PK will be discussed. © 2018 by John Wiley & Sons, Inc.
Trajectory tracking and recovery attacks in VANET systems
Authors: Wang Kun , Wang Lei , Cui Minhao
Published: August 2018

Investigating the mechanisms of various attacks in vehicular ad hoc networks (VANETs) provides fundamental basis to develop safeguard techniques for network security issues. As they develops, attacking strategies are also needed to be established for people to learn how to defend. Previous works failed to consider multiple victims recovery and minimum road side units (RSUs) deployment issues. In this paper, we approach the attacking strategy from an adversarial point of view and develop a trajectory tracking and recovering attack based on matrix completion (TTRA). By randomly sampling locations of vehicles, TTRA is capable of recovering locations of any user with tolerable deviation. After that, the problem of how to minimize the number of RSUs while tracking all vehicles in the whole region is also considered by converting this problem into set covering problem. A heuristic algorithm based on hierarchical clustering is proposed accordingly. To the best of our knowledge, this is the first attempt of recovering mobile users' trajectories by applying these novel techniques. Finally, simulation analysis is used to show the performance of the proposed scheme. Simulation results demonstrate the merits of the scheme in terms of tracking results, location error, and influences of sampling ratio, among others.
Nanostructured high insulating autoclaved aerated concrete
Authors: Stumm Andreas , Schweike Uwe , Stemmermann Peter
Published: August 2018

Efficient insulation for residential buildings is one of the keys for implementing an energy transition. The technology used for exterior walls is usually made by combining load‐bearing and difficult to recycle insulating components. For this reason, Celitement GmbH, Karlsruhe Institute of Technology and Xella Technology and Research have joined their forces to develop a high insulating AAC, which is also resource efficient using the main components quick lime, sand, and water. The thermal conductivity of the AAC was reduced. Macropores formed in the conventional production process by hydrogen gas, diameter of approximately 1 mm, could be partially replaced by lightweight aggregates, with an average pore diameter of 50 nm. A process for producing lightweight aggregate, which is based on optimized, hydraulically active calcium hydro silicate binders (Celitement), was developed. The aggregate quantity in AAC could be raised to 40% by weight through optimizing formulation and mixing. This project, sponsored by the German Federal Ministry of Education and Research, ended in 2017. Based on the results so far, it is worth pursuing this approach in the future, whereby the material properties of the CSH granules could be further improved to obtain the sought final AAC product.
FKBP51 modulates steroid sensitivity and NFκB signalling: A novel anti‐inflammatory drug target
Authors: Kästle Marc , Kistler Barbara , Lamla Thorsten , Bretschneider Tom , Lamb David , Nicklin Paul , Wyatt David
Published: August 2018

Steroid refractory inflammation is an unmet medical need in the management of inflammatory diseases. Thus, mechanisms, improving steroid sensitivity and simultaneously decreasing inflammation have potential therapeutic utility. The FK506‐binding protein 51 (FKBP51) is reported to influence steroid sensitivity in mental disorders. Moreover, biochemical data highlight a connection between FKBP51 and the IKK complex. The aim of this study was to elucidate whether FKBP51 inhibition had utility in modulating steroid resistant inflammation by increasing the sensitivity of the glucocorticoid receptor (GR) signalling and simultaneously inhibiting NFκB‐driven inflammation. We have demonstrated that FKBP51 silencing in a bronchial epithelial cell line resulted in a 10‐fold increased potency for dexamethasone towards IL1beta‐induced IL6 and IL8, whilst FKBP51 over‐expression of FKBP51 reduced significantly the prednisolone sensitivity in a murine HDM‐driven pulmonary inflammation model. Immunoprecipitation experiments with anti‐FKBP51 antibodies, confirmed the presence of FKBP51 in a complex comprising Hsp90, GR and members of the IKK family. FKBP51 silencing reduced NFκB (p50/p65) nucleus translocation, resulting in reduced ICAM expression, cytokine and chemokine secretion. In conclusion, we demonstrate that FKBP51 has the potential to control inflammation in steroid insensitive patients in a steroid‐dependent and independent manner and thus may be worthy of further study as a drug target.
Impact of aerosols on reservoir inflow: A case study for Big Creek Hydroelectric System in California
Authors: Kabir Farzana , Yu Nanpeng , Yao Weixin , Wu Longtao , Jiang Jonathan H. , Gu Yu , Su Hui
Published: August 2018

Accurate and reliable reservoir inflow forecast is instrumental to the efficient operation of the hydroelectric power systems. It has been discovered that natural and anthropogenic aerosols have a great influence on meteorological variables such as temperature, snow water equivalent, and precipitation, which in turn impact the reservoir inflow. Therefore, it is imperative for us to quantify the impact of aerosols on reservoir inflow and to incorporate the aerosol models into future reservoir inflow forecasting models. In this paper, a comprehensive framework was developed to quantify the impact of aerosols on reservoir inflow by integrating the Weather Research and Forecasting model with Chemistry (WRF‐Chem) and a dynamic regression model. The statistical dynamic regression model produces forecasts for reservoir inflow based on the meteorological output variables from the WRF‐Chem model. The case study was performed on the Florence Lake and Lake Thomas Alva Edison of the Big Creek Hydroelectric Project in the San Joaquin Region. The simulation results show that the presence of aerosols results in a significant reduction of annual reservoir inflow by 4–14%. In the summer, aerosols reduce precipitation, snow water equivalent, and snowmelt that leads to a reduction in inflow by 11–26%. In the spring, aerosols increase temperature and snowmelt which leads to an increase in inflow by 0.6–2%. Aerosols significantly reduce the amount of inflow in the summer when the marginal value of water is extremely high and slightly increase the inflow in the spring when the run‐off risk is high. In summary, the presence of aerosols is detrimental to the optimal utilization of hydroelectric power systems.
Histamine H1 receptor gene polymorphism acts as a biological indicator of the prediction of therapeutic efficacy in patients with allergic rhinitis in the Chinese Han population
Authors: Chu Jin‐Tao
Published: August 2018

H1‐antihistamine has been shown to be effective in treating patients with allergic rhinitis (AR), but its mechanism is still uncertain. We investigated effects of histamine H1 receptor (HRH1) gene polymorphisms on the efficacy of oral H1‐antihistamine in perennial patients with AR caused by mites in the Chinese Han population for the first time. A total of 224 Han Chinese patients with AR and 165 Han Chinese healthy volunteers were selected. Genotype and allele frequency distribution of −17C/T in HRH1 gene in patients with AR, serum levels of eosinophil cationic protein (ECP), total immunoglobulin E (IgE), and specific IgE were detected. The clinical symptoms of patients with AR were evaluated with visual analogue scale (VAS). Direct counting method was applied to calculate genotype and allele frequencies. Higher levels of serum ECP and total IgE were shown in the AR group. Moreover, patients with CT, TT, or CT+TT genotype increased the risk of AR incidence in the in the −17C/T site of HRH1, and CC genotype and CT+TT genotype were associated with gender, asthma, VAS score, total IgE level, and specific IgE level in patients with AR. In addition, oral administration of H1‐antihistamines improves clinical symptoms of patients with AR. At last, patients with the CC genotype showed the increased efficacy of H1‐antihistamines in patients with AR. Our study provides evidence that HRH1 gene polymorphisms may correlate with oral H1‐antihistamine efficacy for the treatment of patients with AR, which can be used as a biological indicator of the prediction of therapeutic efficacy of patients with AR.
Identification of diagnostic biomarker in patients with gestational diabetes mellitus based on transcriptome‐wide gene expression and pattern recognition
Authors: Wang Yeping , Wang Zuo , Zhang Hongping
Published: August 2018

Gestational diabetes mellitus (GDM) is becoming a growing threat for all pregnancies. In this study, we set up an automatic screening method combining both transcriptomic databases and support vector machine (SVM)‐based pattern recognition to select biomarkers that can be used in predicting and preventing GDM for gravidas. We screened 63 samples (32 GDM samples and 31 normal controls) in GEO database for the GDM‐specific biomarkers. Differentially expressed genes between patients with GDM and normal controls were picked out using edgeR package. Enrichment analysis was performed using database for annotation, visualization, and integrated discovery. The regulatory gene network was constructed based on the KEGG pathway database. Genes in the hub of the network were selected as specific biomarkers of GDM and further validated through document investigation. Finally, the GDM prediction model was verified using the SVMs. In total, 189 probes corresponding to 69 genes that differentially expressed between GDM and controls were screened out by edgeR package. Nineteen pathways were clustered by KEGG enrichment analysis and were integrated into a regulatory network containing 572 nodes and 1874 edges. The intersection of 50 hub genes extracted from the network and 69 differential genes picked out by edgeR was a collection of six genes, including members of HLA superfamily. In the SVM model, the six genes had a good capacity of predicting GDM in both the training data set (area under curve [AUC] is 0.781) and the testing data set (AUC is 0.710) and had been reported to be associated with GDM. We found that the collection of six genes can be potentially applied as a biomarker for GDM diagnosis.
Synthesis and Utility of α,β‐Unsaturated Ketone Bearing Naphthalene and Benzofuran Rings in the Synthesis of Some N‐heterocycles with Their Antiviral and Antitumor Activity Evaluation
Authors: Gouhar Rasha S. , Ewies Ewies F. , El‐Shehry Mohamed F. , Shaheen Mohamed N. F. , Ibrahim El‐Mahdy M. E.
Published: August 2018

A chalcone bearing naphthalene–benzofuran rings was synthesized. The behavior of this chalcone towards some nitrogen and carbon nucleophiles with formation of pyrazole, isooxazole, thiazole, pyrimidine, pyran, and pyridine rings was studied. Also, pyridine acetohydrazide was synthesized and utilized as a key starting material in the synthesis of 2,4‐dioxothiazolidine and 2,4‐dioxoquinazolin derivatives. The structures of all the products obtained were illustrated from their analytical and spectral data. Some new compounds were selected and evaluated as antiviral agents against hepatitis A virus. In addition, the antitumor activities of certain selected new compounds were screened, in vitro, against HepG2 and MCF‐7 cell lines.