bluuebunny/crossref_metadata_2025 huggingface dataset:
Radical Carbofluorination of Alkenes with Arylhydrazines and Selectfluor: Additives, Mechanistic Pathways, and Polar Effects
Authors: Pirzer Anna S. , Alvarez Eva‐Maria , Friedrich Heike , Heinrich Markus R.
Published: December 2018

Radical carbofluorination reactions starting from arylhydrazines and nonactivated alkenes, in which the C−F bond is formed through the use of Selectfluor, can be improved through the addition of anisole. Because direct trapping products could be detected only in trace amounts, anisole does primarily act as a reversible scavenger for the highly reactive ammonium radical dication released from Selectfluor in the C−F bond‐forming step. As shown for three diverse substitution patterns, the main role of anisole is to prevent, or at least reduce, the undesired addition of the ammonium radical dication to the alkene, which in turn leads to an unfavorable consumption of the arylhydrazine‐derived precursors required for carbofluorination. Moreover, besides the remarkable polar effects in radical trapping, this study shows that the Selectfluor‐derived nitrogen‐centered radical dication may add directly to alkenes, which has not been described so far.
Heterogeneous catalysis in multi‐stage fluidized bed reactors: From fundamental study to industrial application
Authors: Zhang Chenxi , Qian Weizhong , Wang Yao , Luo Guohua , Wei Fei
Published: December 2018

The multi‐stage fluidized bed (MSFB) reactor with several stages connected in series prevents gas and solids back‐mixing effectively and obtains the plug‐flow reactor performance. Besides, different process steps can be accomplished in a single reactor by establishing different temperatures and/or concentrations in each stage. Therefore, multi‐stage fluidized bed reactors are acknowledged as novel and flexible multi‐phase flow reactors for heterogeneous catalytic processes, especially with the intermediates as the desired products. Typical process developments in the industry involve the methanol to aromatics (MTA), regeneration in fluid catalytic cracking (FCC), and hydrogenation of nitrobenzene to aniline. The purpose of this article is to provide a comprehensive review of the fundamental research as well as particular industrial applications on multi‐stage fluidized bed reactors in the Fluidization Laboratory of Tsinghua University (FLOTU).
Predictive Alarm Generation for Chemical Processes with Unknown Disturbance
Authors: Khan Mohammad Aminul Islam , Imtiaz Syed Ahmad , Khan Faisal
Published: December 2018

A predictive warning generation scheme for chemical processes with unknown disturbances is proposed in this paper. The proposed methodology uses predicted states of a process system evaluated from the open loop process model and disturbance estimates. Alarms are issued for two conditions, during a time delay period and at the steady state. Disturbances are estimated using unknown input estimators. The moving horizon predictor combined with bias correction is used to predict the dynamic state of a process for a time‐delay period. To generate warnings for actuator limitations, steady state gain for disturbances along with input constraints are used to check for a feasible solution for using linear programming. A warning is generated to the operator when a feasible solution does not exist. The proposed methodology is demonstrated in a simulated model for a continuous stirred tank heater system (CSTH). Results show an early detection of an abnormal situation that provides the operator a lead time to react in the case of a disturbance affecting the system.
Efficient epoxidation of vegetable oils through the employment of acidic ion exchange resins
Authors: Gómez‐de‐Miranda‐Jiménez‐de‐Aberasturi Olga , Perez‐Arce Jonatan
Published: December 2018

The epoxidation of vegetable oils is a chemical or biochemical reaction where oil triglycerides are converted into more reactive molecules. These will be further transformed into a broad variety of products with significant potential for industrial applications. The epoxidation of vegetable oils consists of a commercially established process that uses homogeneous mineral acids as catalysts. In this paper, different strong acidic ion exchange resins were evaluated as alternatives to substitute the commercial homogeneous catalysts. Amberlyst 39 was selected as the most promising one to explore the effect of the variables such as temperature, acetic acid, or hydrogen peroxide concentration in sunflower oil epoxidation. The optimal operational conditions that maximized the conversion and oxirane yield were determined. Then, these values were applied in several catalyst reuses for establishing the resin durability. Results show that by employing ion exchange resins, excellent product yields and selectivity are obtained, minimizing post‐reaction purification needs.
Identifying Lysophosphatidic Acid Acyltransferase β (LPAAT‐β) as the Target of a Nanomolar Angiogenesis Inhibitor from a Phenotypic Screen Using the Polypharmacology Browser PPB2
Authors: Poirier Marion , Awale Mahendra , Roelli Matthias A. , Giuffredi Guy T. , Ruddigkeit Lars , Evensen Lasse , Stooss Amandine , Calarco Serafina , Lorens James B. , Charles Roch‐Philippe , Reymond Jean‐Louis
Published: December 2018

By screening a focused library of kinase inhibitor analogues in a phenotypic co‐culture assay for angiogenesis inhibition, we identified an aminotriazine that acts as a cytostatic nanomolar inhibitor. However, this aminotriazine was found to be completely inactive in a whole‐kinome profiling assay. To decipher its mechanism of action, we used the online target prediction tool PPB2 (http://ppb2.gdb.tools), which suggested lysophosphatidic acid acyltransferase β (LPAAT‐β) as a possible target for this aminotriazine as well as several analogues identified by structure–activity relationship profiling. LPAAT‐β inhibition (IC50 ≈15 nm) was confirmed in a biochemical assay and by its effects on cell proliferation in comparison with a known LPAAT‐β inhibitor. These experiments illustrate the value of target‐prediction tools to guide target identification for phenotypic screening hits and significantly expand the rather limited pharmacology of LPAAT‐β inhibitors.
Discovery of Affinity‐Based Probes for Btk Occupancy Assays
Authors: Qiu Hui , Caldwell Richard , Liu‐Bujalski Lesley , Goutopoulos Andreas , Jones Reinaldo , Potnick Justin , Sherer Brian , Bender Andrew , Grenningloh Roland , Xu Daigen , Gardberg Anna , Mochalkin Igor , Johnson Theresa , Viacava Follis Ariele , Head Jared , Morandi Federica
Published: December 2018

Bruton's tyrosine kinase (Btk) is an attractive target for the treatment of a wide array of B‐cell malignancies and autoimmune diseases. Small‐molecule covalent irreversible Btk inhibitors targeting Cys481 have been developed for the treatment of such diseases. In clinical trials, probe molecules are required in occupancy studies to measure the level of engagement of the protein by these covalent irreversible inhibitors. The result of this pharmacodynamic (PD) activity provides guidance for appropriate dosage selection to optimize inhibition of the drug target and correlation of target inhibition with disease treatment efficacy. This information is crucial for successful evaluation of drug candidates in clinical trials. Based on the pyridine carboxamide scaffold of a novel solvent‐accessible pocket (SAP) series of covalent irreversible Btk inhibitors, we successfully developed a potent and selective affinity‐based biotinylated probe 12 (2‐[(4‐{4‐[5‐(1‐{5‐[(3aS,4S,6aR)‐2‐oxo‐hexahydro‐1H‐thieno[3,4‐d]imidazol‐4‐yl]pentanamido}‐3,6,9,12‐tetraoxapentadecan‐15‐amido)pentanoyl]piperazine‐1‐carbonyl}phenyl)amino]‐6‐[1‐(prop‐2‐enoyl)piperidin‐4‐yl]pyridine‐3‐carboxamide). Compound 12 has been used in Btk occupancy assays for preclinical studies to determine the therapeutic efficacy of Btk inhibition in two mouse lupus models driven by TLR7 activation and type I interferon.
Minimal residual disease–based long‐term efficacy of reduced‐intensity conditioning versus myeloablative conditioning for adult Philadelphia‐positive acute lymphoblastic leukemia
Authors: Yoon Jae‐Ho , Min Gi June , Park Sung‐Soo , Jeon Young‐Woo , Lee Sung‐Eun , Cho Byung‐Sik , Eom Ki‐Seong , Kim Yoo‐Jin , Kim Hee‐Je , Min Chang‐Ki , Cho Seok‐Goo , Kim Dong‐Wook , Lee Jong Wook , Lee Seok
Published: December 2018

Background

The sensitivity of Philadelphia chromosome (Ph)–positive acute lymphoblastic leukemia (ALL) to reduced‐intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT) versus myeloablative conditioning (MAC) allogeneic HCT by minimal residual disease (MRD) kinetics is not well established.

Methods

This study compared long‐term outcomes based on MRD kinetics for 79 patients with RIC transplants and 116 patients with MAC transplants in first complete remission (CR1) after tyrosine kinase inhibitor–based chemotherapy (median follow‐up, 67.1 months). MRD monitoring was centrally evaluated by real‐time quantitative polymerase chain reaction for all patients.

Results

RIC showed a cumulative incidence of relapse (CIR; 30.6% vs 31.7%), nonrelapse mortality (17.5% vs 14.9%), disease‐free survival (DFS; 51.9% vs 53.4%), and overall survival (61.1% vs 61.4%) comparable to those associated with MAC. In all MRD kinetics–based subgroups, no differences in CIR (early complete molecular response [CMR], 19.3% vs 4.8%; early major molecular response [MMR], 17.0% vs 26.8%; late CMR, 20.0% vs 14.3%; late MMR, 28.3% vs 31.0%; poor molecular response [PMR], 57.9% vs 62.4%) or DFS (early CMR, 71.6% vs 76.2%; early MMR, 66.9% vs 52.1%; late CMR, 50.0% vs 64.3%; late MMR, 50.7% vs 53.7%; PMR, 31.6% vs 34.1%) were observed between RIC and MAC. In a multivariate analysis, the conditioning intensity had no significant impact on transplantation outcomes.

Conclusions

RIC is a valid alternative choice for long‐term disease control and is worthy of further investigation in prospective trials for adult Ph‐positive ALL in CR1.
A multicenter study of patients with multisystem Langerhans cell histiocytosis who develop secondary hemophagocytic lymphohistiocytosis
Authors: Chellapandian Deepak , Hines Melissa R. , Zhang Rui , Jeng Michael , van den Bos Cor , Santa‐María López Vicente , Lehmberg Kai , Sieni Elena , Wang Yini , Nakano Taizo , Williams James A. , Fustino Nicholas J. , Astigarraga Itziar , Dunkel Ira J. , Abla Oussama , van Halteren Astrid G.S. , Pei Deqing , Cheng Cheng , Weitzman Sheila , Sung Lillian , Nichols Kim E.
Published: December 2018

Background

Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm characterized by the presence of abnormal CD1a‐positive (CD1a+)/CD207+ histiocytes. Hemophagocytic lymphohistiocytosis (HLH) represents a spectrum of hyperinflammatory syndromes typified by the dysregulated activation of the innate and adaptive immune systems. Patients with LCH, particularly those with multisystem (MS) involvement, can develop severe hyperinflammation mimicking that observed in HLH. Nevertheless, to the authors’ knowledge, little is known regarding the prevalence, timing, risk factors for development, and outcomes of children and young adults who develop HLH within the context of MS‐LCH (hereafter referred to LCH‐associated HLH).

Methods

To gain further insights, the authors conducted a retrospective, multicenter study and collected data regarding all patients diagnosed with MS‐LCH between 2000 and 2015.

Results

Of 384 patients with MS‐LCH, 32 were reported by their primary providers to have met the diagnostic criteria for HLH, yielding an estimated 2‐year cumulative incidence of 9.3% ± 1.6%. The majority of patients developed HLH at or after the diagnosis of MS‐LCH, and nearly one‐third (31%) had evidence of an intercurrent infection. Patient age <2 years at the time of diagnosis of LCH; female sex; LCH involvement of the liver, spleen, and hematopoietic system; and a lack of bone involvement each were found to be independently associated with an increased risk of LCH‐associated HLH. Patients with MS‐LCH who met the criteria for HLH had significantly poorer 5‐year survival compared with patients with MS‐LCH who did not meet the criteria for HLH (69% vs 97%; P < .0001).

Conclusions

Given its inferior prognosis, further efforts are warranted to enhance the recognition and optimize the treatment of patients with LCH‐associated HLH.
Colloidal FeIII, MnIII, CoIII, and CuII Hydroxides Stabilized by Starch as Catalysts of Water Oxidation Reaction with One Electron Oxidant Ru(bpy)33+
Authors: Chikunov Andrei S. , Taran Oxana P. , Pyshnaya Inna A. , Parmon Valentin N.
Published: December 2018

Colloidal catalysts for oxidation of water to dioxygen, which are stable on storage and under the reaction conditions, are synthesized based on CoIII, MnIII, FeIII and CuII hydroxides. Stabilization of the colloids with dextrated starch allows the process of hydroxide ageing to be stopped at the stage of the formation of primary nuclei (ca. 2–3 nm from transmission electron microscopy data). Molecular mechanics and dynamic light scattering studies indicate a core‐shell type structure of the catalysts, where the hydroxide core is stabilized by the molecular starch network (ca. 5–7 nm). The colloidal catalysts are highly efficient in oxidizing water with one electron oxidant Ru(bpy)33+ at pH 7 to 10. The influence of pH, catalyst concentration, and buffer nature on the oxygen yield is studied. The maximal yields are 72, 53, and 78 % over Fe‐, Mn‐ and Co‐containing catalysts, respectively, and turnover numbers are 7.8; 54 and 360, respectively. The Cu‐containing catalyst is poorly effective to the water oxidation (the maximal yield is 28 % O2). The synthesized catalysts are of interest for stopped‐flow kinetic studies of the mechanism of the water oxidation and as precursors for anchoring nanosized hydroxides onto various supports in order to develop biomimetic systems for artificial photosynthesis.
Single‐Scan Diffusion‐Ordered NMR Spectroscopy of SABRE‐Hyperpolarized Mixtures
Authors: Guduff Ludmilla , Berthault Patrick , van Heijenoort Carine , Dumez Jean‐Nicolas , Huber Gaspard
Published: December 2018

The analysis of complex mixtures of dissolved molecules is a major challenge, especially for systems that gradually evolve, e. g., in the course of a chemical reaction or in the case of chemical instability. 1D NMR is a fast and non‐invasive method suitable for detailed molecular analysis, though of low sensitivity. Moreover, the spectral resolution of proton, the most commonly used and most sensitive stable isotope in NMR, is also quite limited. Spatially encoded (SPEN) experiments aim at creating in one acquisition a 2D data set by simultaneously performing different 1D sub‐experiments on different slices of the NMR tube, at the price of an extra loss of sensitivity. Choosing translational diffusion coefficients as the additional dimension (the so‐called DOSY approach) helps to recover proton spectra of each molecule in a mixture. The sensitivity limitation of SPEN NMR can, on the other hand, be addressed with hyperpolarization methods. Within hyperpolarization methods, signal amplification by reversible exchange (SABRE), based on parahydrogen, is the cheapest and the easiest one to set up, and allows multi‐shot experiments. Here we show that the spectra of a mixture's components at millimolar concentration are resolved in few seconds by combining the SABRE, SPEN and DOSY concepts.
Operando Study Reveals the Superior Cracking Activity and Stability of Hierarchical ZSM‐5 Catalyst for the Cracking of Low‐Density Polyethylene
Authors: Tarach Karolina A. , Pyra Kamila , Siles Sandra , Melián‐Cabrera Ignacio , Góra‐Marek Kinga
Published: December 2018

A new theoretical and practical framework has been developed through operando study of the zeolite catalytic cracking of low‐density polyethylene (as a model reaction) under reaction conditions. Results show that microporous ZSM‐5 gives rise to less cracking products. Hierarchical ZSM‐5 zeolites are more active cracking catalysts, rendering more C2‐C5 hydrocarbons, with a delayed deactivation due to the secondary porosity. This tool in combination with thermogravimetric analysis provides complementary and valuable information for the study, and design of advanced catalysts.
Shear tests on thermal insulating clay unit masonry walls with thin layer mortar
Authors: Schermer Detleff , Schmalz Jonathan , Meyer Udo Joachim , Gams Matija , Lutman Marjana , Triller Petra
Published: December 2018

The paper presents the results of 20 shear tests on full scale thermal insulating clay unit masonry walls. The types of units used (units with large chambers filled with mineral wool pads and units with small corings filled with mineral wool granulate) as well as the tested wall geometries and vertical loads are representative of the most common wall constructions currently used in housing in Germany.

The aim of the investigations was the verification of the shear resistance of thermal insulating clay unit masonry under realistic conditions and comparison with the design rules in the codes and national technical approvals.

The current design rules for clay unit masonry in DIN EN 1996‐1‐1/NA are rather conservative compared to the test results for thermal insulating units.
Effect of simulation education and case management on glycemic control in type 2 diabetes
Authors: Ji Hong , Chen Ronghao , Huang Yong , Li Wenqin , Shi Chunhui , Zhou Juan
Published: December 2018

Background

The aim of the study was to investigate whether simulation education (SE) and case management had any effect on glycemic control in type 2 diabetes (T2DM) patients.

Methods

In this single center pilot trial, 100 T2DM patients who received medication and basic diabetes self‐management education (DSME) were randomly divided into a control group (n = 50) and an experimental group (n = 50), who received SE and a case management program. Evaluation of biochemical indices was conducted at baseline and after 6 months. DSME consisted of 2‐hour group trainings weekly for 2 consecutive weeks followed by 2 × 30 minute education sessions after 3 and 6 months. The SE program comprised additional 50‐minute video sessions 3 times in the first week and twice in the second week. The experimental group was supervised by a nurse case manager, who followed up participants at least once a month, and who conducted group sessions once every 3 months, focusing on realistic aspects of physical activity and nutrition, with open discussions about setting goals and strategies to overcome barriers.

Results

After 6 months, HbA1c, fasting plasma glucose, and postprandial blood glucose level improvements were superior in the experimental group compared with the control group (P < 0.05). Self‐care behavior adherence scores of healthy diet (P = 0.001), physical activity (P = 0.043), self‐monitoring of blood glucose (P < 0.001), and reducing risks (P < 0.001) were significantly increased in the experimental group compared with the control group.

Conclusions

Simulation education and case management added to routine DSME effectively improved glycemic control in T2DM patients.
Exploring the hybrid speciation continuum in birds
Authors: Ottenburghs Jente
Published: December 2018

Hybridization is increasingly recognized as a creative evolutionary force contributing to adaptation and speciation. Homoploid hybrid speciation—the process in which hybridization results in a stable, fertile, and reproductively isolated hybrid lineage where there is no change in ploidy—has been documented in several taxa. Hybridization can directly contribute to reproductive isolation or reinforce it at a later stage. Alternatively, hybridization might not be related to the evolution of reproductive isolation. To account for these different scenarios, I propose to discriminate between two types of hybrid speciation: type I where reproductive isolation is a direct consequence of hybridization and type II where it is the by‐product of other processes. I illustrate the applicability of this classification scheme with avian examples. To my knowledge, seven hybrid bird species have been proposed: Italian sparrow, Audubon's warbler, Genovesa mockingbird, Hawaiian duck, red‐breasted goose, golden‐crowned manakin, and a recent lineage of Darwin's finches on the island of Daphne Major (“Big Bird”). All studies provide convincing evidence for hybridization, but do not always confidently discriminate between scenarios of hybrid speciation and recurrent introgressive hybridization. The build‐up of reproductive isolation between the hybrid species and their parental taxa is mainly driven by premating isolation mechanisms and comparable to classical speciation events. One hybrid species can be classified as type I (“Big Bird”) while three species constitute type II hybrid species (Italian sparrow, Audubon's warbler, and golden‐crowned manakin). The diversity in hybrid bird species across a range of divergence times also provides an excellent opportunity to study the evolution of hybrid genomes in terms of genome stabilization and adaptation.
Varying dataset resolution alters predictive accuracy of spatially explicit ensemble models for avian species distribution
Authors: Curry Claire M. , Ross Jeremy D. , Contina Andrea J. , Bridge Eli S.
Published: December 2018

Species distribution models can be made more accurate by use of new “Spatiotemporal Exploratory Models” (STEMs), a type of spatially explicit ensemble model (SEEM) developed at the continental scale that averages regional models pixel by pixel. Although SEEMs can generate more accurate predictions of species distributions, they are computationally expensive. We compared the accuracies of each model for 11 grassland bird species and examined whether they improve accuracy at a statewide scale for fine and coarse predictor resolutions. We used a combination of survey data and citizen science data for 11 grassland bird species in Oklahoma to test a spatially explicit ensemble model at a smaller scale for its effects on accuracy of current models. We found that only four species performed best with either a statewide model or SEEM; the most accurate model for the remaining seven species varied with data resolution and performance measure.

Policy implications: Determination of nonheterogeneity may depend on the spatial resolution of the examined dataset. Managers should be cautious if any regional differences are expected when developing policy from range‐wide results that show a single model or timeframe. We recommend use of standard species distribution models or other types of nonspatially explicit ensemble models for local species prediction models. Further study is necessary to understand at what point SEEMs become necessary with varying dataset resolutions.
Proposal of over 100‐GHz band waveguide switch
Authors: Kawamura Takashi , Mattori Shigenori
Published: December 2018

A filter bank consisting of switches and band‐pass filters is one method for configuring a spectrum analyzer preselector. A long‐life switch with high isolation is key to this development. We propose a novel horizontal‐moving waveguide switch designed for easy addition of ports compared to commercial rotating switches. The switch has a small gap between the fixed and moving parts with the gap surrounded by chokes. This configuration offers high isolation and long life. It also reduces the size of the filter bank. This paper describes 2 proposed switch prototypes for frequency ranges from 90 to 140 GHz and from 255 to 315 GHz. The measured switch isolation is better than 50 dB and the insertion loss is less than 3 dB for both prototypes.
Copper‐Mediated Radiofluorination of Aryl Pinacolboronate Esters: A Straightforward Protocol by Using Pyridinium Sulfonates
Authors: Antuganov Dmitrii , Zykov Michail , Timofeev Vasilii , Timofeeva Ksenija , Antuganova Yulija , Orlovskaya Victoriya , Fedorova Olga , Krasikova Raisa
Published: December 2018

Radiofluorination of arylboronic acids pinacol esters (arylBPin) mediated by copper triflate pyridine complex is one of the more promising synthetic approaches for the direct introduction of nucleophilic [18F]fluoride into non‐activated arenes and heteroarenes. However, the application of this method to the production of positron emission tomography (PET) radiotracers in automated synthesizers remains a challenging task. The choice of phase‐transfer catalyst (PTC) and corresponding base used for the generation of reactive [18F]fluoride species has a profound impact on the efficiency of the 18F‐fluorination process. Herein we report the development of a simple procedure involving trapping of the aqueous [18F]fluoride on a weak anion‐exchange resin (WAX) and its release by elution with pyridinium sulfonate in dimethyl acetamide. Obtained reactive [18F]fluoride was used as‐is in a copper‐catalyzed fluorination reaction employing pyridinium salt as both PTC and base. High radiochemical conversion rates (RCCs) achieved for a series of simple arylBPin substrates and 4‐[18F]fluoro‐D,L‐phenylalanine demonstrate the efficiency of this novel 18F‐processing approach. Notably, the proposed method obviates conventional azeotropic drying steps, solvents evaporation and/or changeover and can be implemented on commercial automated synthesizers.
The role of overstrength on the seismic performance of asymmetric‐plan structures
Authors: Kaatsız Kaan , Sucuoğlu Halûk
Published: December 2018

Uneven distribution of seismic demand in asymmetric‐plan structures is a critical concern in earthquake‐resistant design. Contemporary seismic design strategies that are based on linear elastic response, single load reduction factor, and uniform ductility demand throughout an asymmetric system generally lead to unsatisfactory performance in terms of realized ductilities and nonuniform damage distribution due to strong torsional coupling associated with asymmetric‐plan systems. In many cases, actual nonlinear behavior of the structure displays significant deviation from what is estimated by a linear elastic, force‐based seismic design approach. This study investigates the prediction of seismic demand distribution among structural members of a single‐story, torsionally stiff asymmetric‐plan system. The focus is on the effect of inherent unbalanced overstrength, resulting from current force‐based design practices, on the seismic response of code‐designed single‐story asymmetric structures. The results obtained are utilized to compile unsymmetrical response spectra and uniform ductility spectra, which are proposed as assessment and preliminary design tools for estimating the seismic performance of multistory asymmetric structures. A simple design strategy is further suggested for improving the inelastic torsional performance of asymmetric systems. Providing additional strength to stiff edge members over their nominal design strength demands leads to a more balanced ductility distribution. Finally, seismic responses of several asymmetric case study structures designed with the aid of the proposed strategy are assessed for validating their improved performance.
An Investigation of the Predictive Validity of the TOEFL iBT® Test at an English‐Medium University in Turkey
Authors: O'Dwyer John , Kantarcıoğlu Elif , Thomas Carole
Published: December 2018

This study reports on an investigation of the predictive validity of the TOEFL iBT® test in an English‐medium institution (EMI) in a non‐target‐language context, namely, Turkey. The relationship between TOEFL iBT scores and academic performance was explored in a cohort of 286 undergraduate students, as was the TOEFL iBT's relationship with an institutional English proficiency exam (Certificate of Proficiency in English [COPE]) used as a benchmark for faculty entry. Performance measures included scores on TOEFL iBT and COPE, grade point averages (GPAs) for content and English for academic purposes (EAP) courses over 2 freshman semesters, and freshman language instructor evaluations of students' freshman EAP performance. Correlations between test scores confirmed a moderate to moderately high predictive validity for content course GPAs and English‐language course GPAs, respectively, and for the TOEFL iBT, particularly in technical fields. Instructor evaluations of student performance supported the findings, with fewer deficiencies in academic English skills for students with higher scores on TOEFL iBT. The study concludes that the TOEFL iBT's predictive validity is on par with the institution's own proficiency test and represents a solid performance measure for use in EMIs in a non‐target‐language context.
An analysis of the stability of the least square finite difference scheme and its shock capturing ability in inviscid flows
Authors: Mungur Maheshsingh , Dauhoo Muhammad Zaid , Elahee Mohammad Khalil
Published: December 2018

A meshless method – The Least Square Finite Difference scheme (LSFD) with diffusion is analyzed and applied to inviscid flows. The scheme is made second‐order by using a modified difference in the formulation of LSFD. Several numerical experiments, namely the Sod shock tube and the shallow water problems, are carried out and, in the limelight of the results obtained, the ability of the scheme to resolve shock wave, rarefaction wave, and contact discontinuity is discussed. The conditional stability of the LSFD scheme is established. The LSFD uses weights to diagonalize the least square matrix resulting in the spatial discretization in order to gain computational time. We prove that there exists a unique weight for the resulting optimization problem. The weighted version of LSFD is used to solve the isentropic vortex problem numerically and the results are used to discuss the dissipative nature of the scheme. Five configurations of the two‐dimensional Riemann problems are used in our numerical experiments. The capability of the scheme to capture the complex interaction of multiple planar waves is discussed in the limelight of the results on the Riemann problems. The result of the shock reflection problem shows that the scheme is minimally dissipative and leads to sharp and well‐resolved shocks.
Nuclear compartmentalization, dynamics, and function of regulatory DNA sequences
Authors: Cremer Marion , Cremer Thomas
Published: December 2018

Transcription regulatory elements (TREs) have been extensively studied on the biochemical level with respect to their interactions with transcription factors (TFs), other DNA segments, and larger protein complexes. In this review, we describe concepts and preliminary experimental evidence for positional changes of TREs within a dynamic, functional nuclear architecture. We suggest a multilayered shell‐like chromatin organization of chromatin domain clusters with increasing chromatin compaction levels from the periphery toward the interior with a decondensed transcriptionally active peripheral layer and compact repressed chromatin typically located in the interior. This model organization of nuclear architecture implies a differential accessibility of TFs to targets located in co‐aligned active and inactive nuclear compartments (ANC and INC). It is based on evidence that active, easily accessible chromatin (perichromatin region, PR) lines a network of channels (interchromatin compartment, IC) involved in nuclear import–export functions. The IC and PR constitute the ANC, whereas transcriptionally noncompetent chromatin with higher compactness is part of the likely less accessible INC. Preliminary experimental evidence shows an enrichment of active TREs in the ANC and of inactive TREs in the INC suggesting positional changes of TREs between the ANC and INC depending on changes in their functional state.
Assessing the population relevance of endocrine-disrupting effects for nontarget vertebrates exposed to plant protection products
Authors: Crane Mark , Hallmark Nina , Lagadic Laurent , Ott Katharina , Pickford Dan , Preuss Thomas , Thompson Helen , Thorbek Pernille , Weltje Lennart , Wheeler James R
Published: December 2018

The European Commission intends to protect vertebrate wildlife populations by regulating plant protection product (PPP) active substances that have endocrine-disrupting properties with a hazard-based approach. In this paper we consider how the Commission's hazard-based regulation and accompanying guidance can be operationalized to ensure that a technically robust process is used to distinguish between substances with adverse population-level effects and those for which it can be demonstrated that adverse effects observed (typically in the laboratory) do not translate into adverse effects at the population level. Our approach is to use population models within the adverse outcome pathway framework to link the nonlinear relationship between adverse effects at the individual and population levels in the following way: (1) use specific protection goals for focal wildlife populations within an ecosystem services framework; (2) model the effects of changes in population-related inputs on focal species populations with individual-based population models to determine thresholds between negligible and nonnegligible (i.e., adverse) population-level effects; (3) compare these thresholds with the relevant endpoints from laboratory toxicity tests to determine whether they are likely to be exceeded at hazard-based limits or the maximum tolerated dose/concentration from the experimental studies. If the population threshold is not exceeded, then the substance should not be classified as an endocrine disruptor with population-relevant adversity unless there are other lines of evidence within a weight-of-evidence approach to challenge this. We believe this approach is scientifically robust and still addresses the political and legal requirement for a hazard-based assessment. Integr Environ Assess Manag 2019;15:278–291. © 2018 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC)
Evaluation of magnesium alloys for use as an intraluminal tracheal for pediatric applications in a rat tracheal bypass model
Authors: Luffy Sarah A. , Wu Jingyao , Kumta Prashant N. , Gilbert Thomas W.
Published: December 2018

Tracheal stenting currently using non‐degradable stents is commonplace for treatment of trauma, prolonged intubation related adult airway obstructions, and pediatric patients‐associated tracheal stenosis conditions. Degradable tracheal stent placement will avoid complications of stent removal and restenosis. Widespread reports exist on degradable magnesium alloys success for orthopedic and cardiovascular applications but none to date for intra tracheal use. This research explores the use of pure Mg, AZ31, and Mg‐3Y alloys for degradable tracheal stent assessment. In vitro evaluation of magnesium, prototype stents in a bioreactor simulate the airway environment and corrosion. Micro‐CT imaging and biocompatibility evaluation helped assess the 24‐week degradation of intraluminal alloy stents following implantation in a rat tracheal in vivo bypass model. Histological analysis indicate tissue response of the harvested stented trachea segments after each time point. Corrosion studies for each alloy indicate significant differences between the simulated and control in vitro conditions. AZ31 exhibited the lowest volume loss of 6.8% in saline, while pure Mg displayed the lowest volume loss of 4.6% in simulated airway fluid (SAF), both at 1‐week time points. Significant differences in percentage of total volume lost after 6 months were determined between the alloys over time. MgY alloy displayed the slowest corrosion losing only 15.1% volume after 24 weeks of immersion. Additionally, in vitro magnesium alloy corrosion was not significantly different from the percentage of total volume lost in vivo at 1‐week time point. The study demonstrates promise of magnesium alloys for intraluminal tracheal stent application albeit viability of a clinically translatable model warrants further studies. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1844–1853, 2019.
Immunomodulatory response of layered small intestinal submucosa in a rat bladder regeneration model
Authors: Xia Ding , Yang Qing , Fung Kar‐Ming , Towner Rheal A. , Smith Nataliya , Saunders Debra , Greenwood‐Van Meerveld Beverley , Kropp Bradley P. , Madihally Sundararajan V. , Lin Hsueh‐Kung
Published: December 2018

Based on the hypothesis that bioscaffold permeability is a major factor in determining the outcome of histologically complete and functional bladder regeneration, we evaluated regeneration processes of four‐layer porcine small intestinal submucosa (SIS) construct; and compared results between rat bladders augmented with single‐layer SIS bioscaffolds. Sprague–Dawley female rats were subjected to hemi‐cystectomy followed by anastomosis of a patch of either single‐ or four‐layer porcine SIS. Permeability was analyzedin situusing magnetic resonance imaging (MRI) at post‐operative days 7 and 14. Bladder sections excised at days 7, 14, 28, and 56 post‐operation Samples were assessed by H&E and Masson's trichrome stains. Urothelial differentiation was analyzed using cytokeratin AE1/AE3, and uroplakin III (UPIII). In addition, quantitative and qualitative evaluations of neutrophils, mast cells, eosinophils, and macrophages were performed using anti‐myeloperoxidase, Alcian blue, Giemsa stain, and anti‐CD68 staining methods, respectively. Four‐layer SIS was consistently impermeable as evidenced by the absence of intravesical administered gadolinium with diethylenetriaminepentacetate (Gd‐DTPA) contrast signal in peripheral regions of augmented bladders compared with single‐layer SIS bioscaffold. Elevated and sustained eosinophil and neutrophil infiltrations were prominent in four‐layered SIS‐augmented bladders compared with single‐layer SIS with comparable impermeability. Delayed but consistent urothelial regeneration and differentiation were observed in four‐layer SIS‐augmented bladders; and urothelial differentiation was observed at day 56 post‐augmentation. In conclusion, four‐layer SIS enacts an elevated inflammatory response along with extended urothelial regeneration. Four‐layer SIS may activate a different but yet to be identified mechanism for inflammatory responses. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1960–1969, 2019.
Endothelial cell autophagy in chronic intermittent hypoxia is impaired by miRNA‐30a‐mediated translational control of Beclin‐1
Authors: Bi Rongrong , Dai Yancheng , Ma Zifeng , Zhang Shaoyan , Wang Lei , Lin Qichang
Published: December 2018

Chronic intermittent hypoxia (CIH) in obstructive sleep apnea causes damage of aortic endothelial cells, which predisposes the development of many cardiovascular diseases. Recently, both altered expression of microRNAs (miRNAs) and impaired autophagy were found to be associated with endothelial cell dysfunction in CIH. However, the exact molecular regulatory pathway has not been determined. Here, we address this question. In a mouse model of CIH, we detected significant upregulation of miR‐30a, a miRNA that targets 3′‐untranslated region of autophagy‐associated protein 6 (Beclin‐1) messenger RNA (mRNA) for suppressing the protein translation, which subsequently attenuated the endothelial cell autophagy against cell death. Indeed, unlike Beclin‐1 mRNA, the Beclin‐1 protein in endothelial cells did not increase after CIH. Suppression of miR‐30a by expression of antisense of miR‐30a significantly increased Beclin‐1 levels to enhance endothelial cell autophagy in vitro and in vivo, which improved endothelial cell survival against CIH. Together, these data suggest that endothelial cell autophagy in CIH may be attenuated by miR‐30a‐mediated translational control of Beclin‐1 as an important cause of endothelial cell dysfunction and damage.
Knockdown of sal‐like 4 expression by small interfering RNA induces apoptosis in breast cancer cells
Authors: Hesari Amireza , Anoshiravani Ali Arash , Talebi Samaneh , Noruzi Somayye , Mohammadi Rezvan , Salarinia Reza , Zare Reza , Ghasemi Faezeh
Published: December 2018

Breast cancer is the most prevalent cancers worldwide and causes a significant amount of deaths annually. Spalt‐like transcription factor 4 is known as a transcription factor, which has an important role in the proliferation of cancerous cells. Small interfering RNA (siRNA) is a short‐chain molecule of 20 to 25 nucleotides that protrude on two sides of the 3′, two nucleotides. In this study, using a specific sequence of siRNA against the sequence of this gene, its activity is investigated in the cell line of breast cancer. The breast cancer cells (MCF‐7) were cultured and then, using a specific anti‐sal–like 4 (SALL4) siRNA, their toxic doses were determined. Then, the gene is transfected into the cell. Proliferation and expression of the SALL4 and BCL‐2 gene were measured using the real‐time polymerase chain reaction method. The specific concentration of siRNA IC50 of the SALL4 gene was 40.35 nmole. Gene expression results indicated that the expression of the Bcl‐2 gene in the siRNA group was significantly reduced (
P < 0.05). SiRNA can increase the apoptosis of breast cancer cells by reducing the gene expression of SALL4 gene and Bcl‐2; it can be used as a novel targeted therapy. This strategy, in addition to increasing the specificity of the drug, also reduces the side effects when compared with conventional chemotherapy.
Quantitative proteomics using SILAC‐MS identifies N‐acetylcysteine‐solution‐triggered reversal response of renal cell carcinoma cell lines
Authors: Zhao Cuihong , Chen Jianhua , Ling Yong , Wang Shenghai
Published: December 2018

N‐acetylcysteine (NAC), a precursor for glutathione (GSH), causes permeable antioxidation protecting normal cells and disrupting cancer cells. In the present study, we found that a NAC‐based medium can trigger a reversal response of human clear cell renal cell carcinoma (ccRCC). To further investigate the action of a NAC‐based solution in ccRCC cell lines, 786‐O and SN12C were incubated in a serum‐free acid medium (low pH) in the presence of 2 mM NAC for 24 hours or in a serum‐free medium (normal pH) as the control, and then a phenotypic and proteomic analyses were performed. To determine the reversal occurrence, we tested the phenotypic features associated with cancer cells. Under this premise, a systematic and in‐depth analysis of NAC‐solution‐triggered protein alterations was carried out by quantitative proteomics in both cell lines. Among the paramount protein signature, we identified a large number of proteins associated with cancer features were downregulated, but other proteins in the KEGG pathways associated with recovery of the missing tumorigenicity, such as the p53 pathway and repair pathway, were significantly upregulated. Quantification of notable proteins was validated by messenger RNA (mRNA) and protein levels in the ccRCC cell line. Collectively, our data indicate that the NAC‐based solution inhibits human ccRCC cell growth by decreasing cell proliferation and inducing apoptosis, limiting their migration by limiting cell motility and completely changing their metabolic mode. Thus, NAC‐based solutions could be used for the prevention or treatment of ccRCC.
Extracts of Coleus forskohlii relieves cough and asthma symptoms via modulating inflammation and the extracellular matrix
Authors: Ma Chaozhi , Zou Liyuan , Xia Yu , Tu Yijun , Xue Daquan , Yang Yanfang , Liu Dan , Liu Yanwen , Wu Hezhen , Dan Hanxiong , You Pengtao
Published: December 2018

Asthma is characterized by airway inflammatory infiltration, which leads to airway remodeling and airway hyperreactivity. Coleus forskohlii (CFK) has been used to treat asthma, however, the mechanism involved is not clear. To explore the antiasthma mechanism of extracts of Coleus forskohlii (ECFK), guinea pigs were administered with a spray of phosphoric acid histamine, and rats were sensitized with ovalbumin (OVA). Hematoxylin and eosin staining (H&E) were used to evaluate pathological changes in lung tissue. Enzyme‐linked immunosorbent assay (ELISA) was used to determine cytokine levels in serum and bronchoalveolar lavage fluid (BALF). Immunohistochemistry and Western blot analysis were used to assess the expression of intercellular cell adhesion molecule‐1 (ICAM‐1), phosphorylation of p65 (p‐p65), matrix metallopeptidase 9 (MMP‐9), and tissue inhibitor of metalloproteinase 1 (TIMP‐1). After ECFK treatment, the asthma incubation period of guinea pigs was significantly prolonged. The H&E results showed that the number of eosinophils in the 12.8 g/kg ECFK group was significantly lower when compared with the control group. Moreover, ELISA results demonstrated that interleukin (IL)‐4, IL‐5, and IL‐17 in serum and BALF were significantly decreased, and interferon‐γ (IFN‐γ) and IL‐10 were increased after ECFK treatment. In addition, ECFK treatment resulted in downregulation of ICAM‐1, p‐p65, MMP‐9, and TIMP‐1 in lung tissue after being sensitized by OVA. In conclusion, our findings indicated that ECFK significantly alleviated OVA‐induced inflammatory infiltration and airway remodeling in asthma. This study laid a theoretical foundation for the clinical use of ECFK.
Casticin inhibits growth and enhances ionizing radiation–induced apoptosis through the suppression of STAT3 signaling cascade
Authors: Lee Jong Hyun , Kim Chulwon , Ko Jeong‐Hyeon , Jung Young Yun , Jung Sang Hoon , Kim Eunok , Kong Moonkyoo , Chinnathambi Arunachalam , Alahmadi Tahani Awad , Alharbi Sulaiman Ali , Sethi Gautam , Ahn Kwang Seok
Published: December 2018

Casticin (CTC), one of the major components of Vitex rotundifolia L., has been reported to exert significant beneficial pharmacological activities and can function as an antiprolactin, anticancer, anti‐inflammatory, neuroprotective, analgesic, and immunomodulatory agent. This study aimed at investigating whether the proapoptotic effects of CTC may be mediated through the abrogation of signal transducers and activators of transcription‐3 (STAT3) signaling pathway in a variety of human tumor cells. We found that CTC significantly decreased cell viability in a concentration‐dependent manner and suppressed cell proliferation in 786‐O, YD‐8, and HN‐9 cells. CTC also induced programmed cell death that was found to be mediated via caspase‐3 activation and induction of poly(ADP‐ribose) polymerase cleavage. Interestingly, CTC repressed both constitutive and interleukin‐6‐induced STAT3 activation in 786‐O and YD‐8 cells but only affected constitutive STAT3 phosphorylation in HN‐9 cells. Moreover, CTC could potentiate ionizing radiation–induced apoptotic effects leading to the downregulation of STAT3 activation and thus may be used in combination with radiation against diverse malignancies.
Synthesis of 4‐((2‐hydroxynaphthalen‐1‐yl)(aryl)methyl)‐5‐methyl‐2‐phenyl‐1H‐pyrazol‐3(2H)‐ones using nano‐Zn‐[2‐boromophenyl‐salicylaldimine‐methylpyranopyrazole]Cl2 nanoparticles
Authors: Goudarziafshar Hamid , Moosavi‐Zare Ahmad Reza , Jalilian Zahra , Abdolmaleki Mehdi
Published: December 2018

Nano‐Zn‐[2‐boromophenyl‐salicylaldimine‐methylpyranopyrazole]Cl2 (nano‐[Zn‐2BSMP]Cl2) as a nanoparticle Schiff base complex and a catalyst was introduced for the solvent‐free synthesis of 4‐((2‐hydroxynaphthalen‐1‐yl)(aryl)methyl)‐5‐methyl‐2‐phenyl‐1H‐pyrazol‐3(2H)‐ones by the multicomponent condensation reaction of various aromatic aldehydes, β‐naphthol, ethyl acetoacetate, and phenyl hydrazine at room temperature.