bluuebunny/crossref_metadata_2025 huggingface dataset:
Template‐assisted hydrophobic porous silica membrane: A purifier sieve for organic solvents
Authors: Maitlo Inamullah , Ali Safdar , Shehzad Farooq Khurum , Nie Jun
Published: October 2017

Self‐supporting, interconnected, porous inorganic (silicon/carbon) membranes were obtained by the calcination of composite membranes at 900 °C with a porous polymer template obtained by binary‐phase solid‐state photopolymerization at −60 °C with acrylate monomers followed by chemical vapor deposition. The physicochemical properties of all of the membranes were characterized by scanning electron microscopy, energy‐dispersive spectroscopy (EDS), Fourier transform infrared (FTIR) spectroscopy, X‐ray powder diffraction (XRD), thermogravimetric analysis (TGA), and the measurement of water contact angles, water uptake, and percentage of porosity. The membranes showed contact angles ranging from 127 to 130 ± 0.5°, which were close to those of superhydrophobicity. The EDS, FTIR spectroscopy, XRD, and TGA results confirmed the formation of the Si–C composite structure after calcination and an increase in the thermal stability. The polymer and composite membranes were found to be hydrophilic, whereas Si–C was hydrophobic. The poly(ethylene glycol) diacrylate derived Si–C membrane showed a good absorption efficiency for tinted toluene from water compared to the others. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 45822.
Synthesis and stabilization of Au nanoparticles in colloidal solution using macroelectrolytes with sulfonic acid groups
Authors: Herrera‐González Ana Ana M. , García‐Serrano J. , Caldera‐Villalobos M.
Published: October 2017

Metal nanoparticles are obtained by different chemical reactions using reducing agents that are not environmentally friendly. This work report the synthesis of Au nanoparticles in colloidal solution using three monodisperse macroelectrolytes, with peripheral sulfonic acid groups bonded covalently, without toxic reducing agents. During the synthesis of Au nanoparticles were used the new macroelectrolytes as reducing and stabilizing agents in aqueous solution or ethylene glycol. The macroelectrolytes were synthesized using hexachlorocyclotriphosphazene as core, and o‐ or p‐aminobenzenesulfonic acid, obtaining acid macroelectrolytes with two and six sulfonic acid groups in ortho‐ position, and four sulfonic acid groups in para‐ position. The ultraviolet–visible (UV–vis) absorption spectroscopy and transmission electron microscopy study show that the macroelectrolytes with sulfonic acid groups in ortho‐ position are reducing agents for Au+++ ions in colloidal solution and produced Au nanoparticles with anisotropic shapes, such as decahedrons and prisms. The macroelectrolyte with sulfonic acid groups in para‐ position is reducing agent for Au+++ and produces quasispherical Au nanoparticles with sizes between 8 and 40 nm. The colloidal solutions with Au nanoparticles were stable by several months due to the protection of imine and sulfonic groups of macroelectrolytes on the Au nanoparticles. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 45888.
Magnetic Separation on a New Level: Characterization and Performance Prediction of a cGMP Compliant “Rotor‐Stator” High‐Gradient Magnetic Separator
Authors: Ebeler Moritz , Pilgram Florian , Wolz Kai , Grim Gunnar , Franzreb Matthias
Published: October 2017

The growing market of biopharmaceuticals and the constant developments in upstream fermentation have generated a strong demand for new downstream purification methods. Magnetic separation in combination with functional magnetic particles has been known for many years as a promising candidate for a direct capturing tool in protein purification but the lack of suitable GMP‐compliant purification equipment has prevented the launch of this technology in large scale bioprocessing. To tackle this bottle‐neck, the principle of a “rotor‐stator” high‐gradient magnetic separator is fully redesigned to meet the rigorous requirements of modern cGMP biotechnology purification processes. In order to fulfill regulatory requirements, the separation chamber is reengineered to allow effective cleaning and sterilization in place while maintaining excellent separation capacities and efficiencies. Two kinds of commercially available magnetic particles are used to validate key performance data and determine system related parameters in order to calculate process performance figures for process optimization of the new magnetic separation device. With separation capacities of over 400 g of magnetic particles per liter of separation chamber volume and separation efficiencies as well as recovery rates over 99%, the system is able to process more than 200 l crude feedstock per day and capture more than 1.6 kg target compounds.
Complications of the neovagina in male‐to‐female transgender surgery: A systematic review and meta‐analysis with discussion of management
Authors: Dreher Paulette Cutruzzula , Edwards Daniel , Hager Shaun , Dennis Margeaux , Belkoff Andie , Mora Jamie , Tarry Susan , Rumer Kathy L.
Published: October 2017

Gender‐affirmation surgery is often the final gender‐confirming medical intervention sought by those patients suffering from gender dysphoria. In the male‐to‐female (MtF) transgendered patient, the creation of esthetic and functional external female genitalia with a functional vaginal channel is of the utmost importance. The aim of this review and meta‐analysis is to evaluate the epidemiology, presentation, management, and outcomes of neovaginal complications in the MtF transgender reassignment surgery patients. PUBMED was searched in accordance with PRISMA guidelines for relevant articles (n = 125). Ineligible articles were excluded and articles meeting all inclusion criteria went on to review and analysis (n = 13). Ultimately, studies reported on 1,684 patients with an overall complication rate of 32.5% and a reoperation rate of 21.7% for non‐esthetic reasons. The most common complication was stenosis of the neo‐meatus (14.4%). Wound infection was associated with an increased risk of all tissue‐healing complications. Use of sacrospinous ligament fixation (SSL) was associated with a significantly decreased risk of prolapse of the neovagina. Gender‐affirmation surgery is important in the treatment of gender dysphoric patients, but there is a high complication rate in the reported literature. Variability in technique and complication reporting standards makes it difficult to assess the accurately the current state of MtF gender reassignment surgery. Further research and implementation of standards is necessary to improve patient outcomes. Clin. Anat. 31:191–199, 2018. © 2017 Wiley Periodicals, Inc.
Promote accountability, transparency to build trust, grow professionalism
Authors: Hope Joan
Published: October 2017

MILWAUKEE, Wis. — A focus on accountability and transparency can lead to improvements in your unit. A program review conducted by an outside consultant helped officials in the Northwestern University Police Department create a roadmap for improvement, said Gloria Graham, assistant vice president and deputy chief of police. She spoke at the International Association of Campus Law Enforcement Administrators annual conference.
Good community policing begins with education
Authors: Sutton Halley
Published: October 2017

Prior to working as chief of police at Bowie State University, Ernest Waiters retired as a captain of a district police station, with 23 years of experience in law enforcement in Prince George's County. While serving as a police officer, Waiters pursued his master's degree in public administration. “I started to ask questions about campus policing and I became interested in learning about the difference between campus and traditional policing,” Waiters said.
A crash course in leading through change and challenges
Authors: Skipworth Stan
Published: October 2017

When I was a young traffic enforcement officer, my responsibilities included investigating traffic collisions of all types. Over the course of a few years, I was sent to what would seem to be hundreds of the most common collisions you would expect to see: a vehicle traveling in one direction that would be struck by a vehicle coming from another direction. From those several‐hundred traffic accidents I responded to, investigated, and reported on, a small number stood out for their uniqueness.
Dehydration of Lactic Acid: The State of The Art
Authors: Bonnotte Thomas , Paul Sébastien , Araque Marcia , Wojcieszak Robert , Dumeignil Franck , Katryniok Benjamin
Published: October 2017

The dehydration of lactic acid to produce acrylic acid is a renewable alternative to the mostly used production of acrylic acid from propene. In this review, the recent developments and state of the art for the dehydration of lactic acid to acrylic acid are presented and critically commented. The most recent publications on the topic are discussed inetail with respect to the observed catalysts and process performance data. Among the different catalysts developed, three main groups can be distinguished: zeolites, sulphates, and phosphates. The latter, especially hydroxyapatites, have recently attracted the attention of academics in particular. The three families of catalysts are discussed and the recent developments and technical drawbacks in the gas phase dehydration are reported.
Characterization of Terminators in Saccharomyces cerevisiae and an Exploration of Factors Affecting Their Strength
Authors: Wei Linna , Wang Zhaoxia , Zhang Genlin , Ye Bangce
Published: October 2017

Terminators in eukaryotes play an important role in regulating the transcription process by influencing mRNA stability, translational efficiency, and localization. Herein, the strengths of 100 natural terminators in Saccharomyces cerevisiae have been characterized by inserting each terminator downstream of the TYS1p‐enhanced green fluorescent protein (eGFP) reporter gene and measuring the fluorescent intensity (FI) of eGFP. Within this library, there are 45 strong terminators, 31 moderate terminators, and 24 weak terminators. The strength of these terminators, relative to that of PGK1t standard terminator, ranges from 0.0613 to 1.8002, with a mean relative FI of 0.9945. Mutating the control elements of terminators further suggests that the efficiency element has an important effect on terminator strength. The use of strong terminators will result in an enhanced level of mRNA and protein production; this indicates that gene expression can be directly influenced by terminator selection. Pairing a terminator with an inducible promoter or a strong constitutive promoter has less effect on gene expression; however, pairing with a week promoter will significantly increase the level of gene expression. Through exchange of the reporter genes, it can be demonstrated that the terminator functions as a genetic component and is independent of the coding region. This work demonstrates that the terminator is an important regulatory element and can be considered in applications for the fine‐tuning of gene expression and metabolic pathways.
Internal Donors in Ziegler–Natta Systems: is Reduction by AlR3 a Requirement for Donor Clean‐Up?
Authors: Zaccaria Francesco , Vittoria Antonio , Correa Andrea , Ehm Christian , Budzelaar Peter H. M. , Busico Vincenzo , Cipullo Roberta
Published: October 2017

Alkyl benzoates, phthalates, and succinates are used as “internal donors” (ID) to modify the surface of MgCl2‐supported Ziegler–Natta (ZN) catalysts for polypropylene production. Phthalates, in particular, are the working horses of this catalysis, but a REACH ban of these compounds for other applications has generated a desire from the market for phthalate‐free ZN catalysts, which has in turn triggered a search for alternatives and revamped research in the area. It has been reported that under polymerization conditions certain ID classes undergo an extensive exchange with alkoxysilane “external donors” (ED), which represents an important opportunity for surface fine‐tuning. ID clean‐up has been attributed to ester group reduction by the AlR3 cocatalyst. We have now measured the activation parameters for the reactions of ethyl benzoate (EB), dibutyl phthalate (DBP), and diethyl 2,3‐diisobutylsuccinate (DiBS) with AlEt3 in toluene solution by means of variable‐temperature 1H NMR spectroscopy. Reduction is fast for EB and DBP, whereas it is slow for DiBS. Results of DFT calculations are in line with the observed reactivity. Therefore, we conclude that an irreversible reaction with AlEt3 is not the only option for ID/ED exchange. Possible alternatives are discussed.
Direct Aldehyde Csp2−H Functionalization through Visible‐Light‐Mediated Photoredox Catalysis
Authors: Vu Minh Duy , Das Mrinmoy , Liu Xue‐Wei
Published: October 2017

The development of methods for carbon–carbon bond formation under benign conditions is an ongoing challenge for synthetic chemists. In recent years there has been considerable interest in using selective C−H activation as a direct route for generating reactive intermediates. Herein, the use of visible‐light‐mediated dual photoredox organocatalysis as a mild and effective method for C
−H activation of aldehydes is reported, resulting in the generation of acyl radicals. These nucleophilic acyl radical species can undergo either addition to electrophilic alkenes or nickel‐catalyzed cross‐coupling reactions to provide a quick access to broad range of unsymmetrical ketones, which are abundantly found in many organic building blocks.
Catalytic Carbon–Chlorine Bond Activation by Selenium‐Based Chalcogen Bond Donors
Authors: Wonner Patrick , Vogel Lukas , Kniep Florian , Huber Stefan M.
Published: October 2017

Chalcogen bonding is a noncovalent interaction based on electrophilic chalcogen substituents, which shares many similarities with the more well‐known hydrogen and halogen bonding. Herein, the first application of selenium‐based chalcogen bond donors in organocatalysis is described. Cationic bifunctionalized organoselenium compounds activate the carbon–chlorine bond of 1‐chloroisochroman in a benchmark reaction. While imidazolium‐based derivatives showed no noticeable activation, benzimidazolium backbones yielded potent catalysts. In all cases, syn‐isomers were markedly more active, presumably due to bidentate coordination, which was confirmed by DFT calculations. Comparison experiments with the corresponding non‐selenated as well as the non‐cationic reference compounds clearly indicate that the catalytic activity can be ascribed to chalcogen bonding. The rate acceleration by the catalyst—compared to the non‐selenated derivative—was about 10 fold.
Pharmacokinetics of the BCL‐2 Inhibitor Venetoclax in Healthy Chinese Subjects
Authors: Cheung Tommy T. , Salem Ahmed Hamed , Menon Rajeev M. , Munasinghe Wijith P. , Bueno Orlando F. , Agarwal Suresh K.
Published: October 2017

Venetoclax has been approved in the United States, Europe, Canada, and Australia for appropriate patients with difficult‐to‐treat chronic lymphocytic leukemia (CLL). The objective of this phase 1 study was to evaluate the pharmacokinetics of venetoclax in Chinese subjects to inform the dose selection of venetoclax in a phase 2 study of patients with relapsed/refractory (R/R) CLL in China. Twelve healthy first‐generation Han Chinese subjects received a single 100‐mg dose of venetoclax following a low‐fat breakfast. Pharmacokinetic parameters were estimated using noncompartmental methods. After a single dose of venetoclax in healthy Chinese subjects, the median time to peak concentration was 6 hours (range, 4 to 6 hours), and the mean ± SD Cmax, AUCinf, and terminal half‐life were 1.0 ± 0.32 μg/mL, 12.6 ± 5.4 μg·h/mL, and 18.4 ± 2.97 hours, respectively. On average, venetoclax Cmax and AUCinf values were 94% and 66% higher, respectively, in Chinese subjects compared with those observed historically for non‐Asian subjects receiving the same dose. Based on these pharmacokinetic results and the established exposure–response relationship of venetoclax in non‐Asian CLL subjects, a 400‐mg once‐daily dosage regimen was selected for evaluating the venetoclax pharmacokinetics, efficacy, and safety in the venetoclax phase 2 open‐label study in Chinese subjects with R/R CLL.
Optimized Synthesis of ZSM‐11 Catalysts using 1,8‐Diaminooctane as a Structure‐Directing Agent
Authors: Shen Yufeng , Le Thuy T. , Li Rui , Rimer Jeffrey D.
Published: October 2017

Developing new zeolite catalysts for (petro)chemical applications is nontrivial owing to challenges that include the identification of commercially‐viable syntheses. The vast majority of syntheses require the use of an organic structure‐directing agent (OSDA), which has economic and environmental shortcomings. In the search for alternative zeolites to common industrial catalysts, such as ZSM‐5 (MFI), a promising candidate is ZSM‐11 (MEL), a close structural analogue of MFI. ZSM‐11 is comprised of 3‐dimensional straight channels that have less diffusion limitations than MFI. Side‐by‐side comparisons of ZSM‐11 and ZSM‐5 catalysts reveal the former exhibits significantly longer time‐on‐stream lifetime in many reactions; however, there are several difficulties associated with the preparation of ZSM‐11, which include the ability to identify inexpensive OSDAs that produce small crystals in high yield. Here, we examine ZSM‐11 synthesis using 1,8‐diaminooctane (DAO), which produces ZSM‐11 crystals with sizes of ca. 300 nm. We demonstrate that the use of MEL seeds allows for an order of magnitude reduction in the quantity of DAO without sacrificing crystal purity or yield (>80 %). Catalytic tests using methanol to hydrocarbons as a representative reaction show that H‐ZSM‐11 lifetime and selectivity are similar for samples prepared with and without seeds. Collectively our findings highlight an efficient method to produce ZSM‐11 as a potential alternative to ZSM‐5 for catalytic applications.
Suppression of Red Blood Cell Autofluorescence for Immunocytochemistry on Fixed Embryonic Mouse Tissue
Authors: Whittington Niteace C. , Wray Susan
Published: October 2017

Autofluorescence is a problem that interferes with immunofluorescent staining and complicates data analysis. Throughout the mouse embryo, red blood cells naturally fluoresce across multiple wavelengths, spanning the emission and excitation spectra of many commonly used fluorescent reporters, including antibodies, dyes, stains, probes, and transgenic proteins, making it difficult to distinguish assay fluorescence from endogenous fluorescence. Several tissue treatment methods have been developed to bypass this issue with varying degrees of success. Sudan Black B dye has been commonly used to quench autofluorescence, but can also introduce background fluorescence. Here we present a protocol for an alternative called TrueBlack Lipofuscin Autofluorescence Quencher. The protocol described in this unit demonstrates how TrueBlack efficiently quenches red blood cell autofluorescence across red and green wavelengths in fixed embryonic tissue without interfering with immunofluorescent signal intensity or introducing background staining. We also identify optimal incubation, concentration, and multiple usage conditions for routine immunofluorescence microscopy. © 2017 by John Wiley & Sons, Inc.
Genetic variation in Tertiary relics: The case of eastern‐Mediterranean Abies (Pinaceae)
Authors: Hrivnák Matúš , Paule Ladislav , Krajmerová Diana , Kulaç Şemsettin , Şevik Hakan , Turna İbrahim , Tvauri Irina , Gömöry Dušan
Published: October 2017

The eastern‐Mediterranean Abies taxa, which include both widely distributed species and taxa with minuscule ranges, represent a good model to study the impacts of range size and fragmentation on the levels of genetic diversity and differentiation. To assess the patterns of genetic diversity and phylogenetic relationships among eastern‐Mediterranean Abies taxa, genetic variation was assessed by eight nuclear microsatellite loci in 52 populations of Abies taxa with a focus on those distributed in Turkey and the Caucasus. Both at the population and the taxon level, the subspecies or regional populations of Abies nordmanniana s.l. exhibited generally higher allelic richness, private allelic richness, and expected heterozygosity compared with Abies cilicica s.l. Results of both the Structure analysis and distance‐based approaches showed a strong differentiation of the two A. cilicica subspecies from the rest as well as from each other, whereas the subspecies of A. nordmanniana were distinct but less differentiated. ABC simulations were run for a set of scenarios of phylogeny and past demographic changes. For A. ×olcayana, the simulation gave a poor support for the hypothesis of being a taxon resulting from a past hybridization, the same is true for Abies equi‐trojani: both they represent evolutionary branches of Abies bornmuelleriana.
Animal agency: wildlife management from a kincentric perspective
Authors: Bhattacharyya Jonaki , Slocombe Scott
Published: October 2017

Co‐management of wildlife and landscapes often requires managers to work with Indigenous and conventional Western worldviews. Many cultures recognize animals as non‐human persons with decision‐making agency. Such perspectives, termed “kincentric ecology,” suggest a relational approach to management that differs from convention in North America. We argue that kincentric perspectives are highly relevant to current approaches and issues in wildlife management, including the incorporation of Indigenous Knowledge. Using empirical research with the Xeni Gwet'in First Nation in British Columbia, Canada, we discuss four dimensions of kincentricity key to collaborative management, with notable parallels in emergent systems science: (1) shift in emphasis from human rights to responsibilities; (2) focus on social–ecological systems; (3) acknowledgment of uncertainty and rapid change; and (4) emphasis on locally relevant, empirical knowledge. Wildlife and land management influenced by bioculturally diverse knowledge implies a more systemic approach; adaptive processes; changed goals and values; and shifting responsibilities among stakeholders.
Phthalimide–Oxy Derivatives for 3′‐ or 5′‐Conjugation of Oligonucleotides by Oxime Ligation and Circularization of DNA by “Bis‐ or Tris‐Click” Oxime Ligation
Authors: Meyer Albert , Vasseur Jean‐Jacques , Dumy Pascal , Morvan François
Published: October 2017

A solid support and two phosphoramidites exhibiting a phthalimide–oxy group were synthesized. First, after treatment with hydrazine, the resulting 5′‐ and 3′‐oxyamine oligonucleotides were conjugated with aldehyde derivatives by oxime ligation. Second, oligonucleotides exhibiting an oxyamine at each end were circularized by means of different dialdehydes. Cyclic oligonucleotides of different lengths (9 to 31‐mer) were rapidly obtained without the need of a template. Finally, a bicyclic oligonucleotide was synthesized starting form an oligonucleotide bearing three oxyamines, which reacted with a trialdehyde to form three oxime ligations.
Perfectionism Group Treatment for Eating Disorders in an Inpatient, Partial Hospitalization, and Outpatient Setting
Authors: Levinson Cheri A. , Brosof Leigh C. , Vanzhula Irina A. , Bumberry Laura , Zerwas Stephanie , Bulik Cynthia M.
Published: October 2017

Perfectionism is elevated in individuals with eating disorders and is posited to be a risk factor, maintaining factor, and treatment barrier. However, there has been little literature testing the feasibility and effectiveness of perfectionism interventions in individuals specifically with eating disorders in an open group format. In the current study, we tested the feasibility of (a) a short cognitive behavioural therapy for perfectionism intervention delivered in an inpatient, partial hospitalization, and outpatient for eating disorders setting (combined N = 28; inpatient n = 15; partial hospital n = 9; outpatient n = 4), as well as (b) a training for disseminating the treatment in these settings (N = 9). Overall, we found that it was feasible to implement a perfectionism group in each treatment setting, with both an open and closed group format. This research adds additional support for the implementation of perfectionism group treatment for eating disorders and provides information on the feasibility of implementing such interventions across multiple settings. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.
Investigating Body Image Disturbance in Anorexia Nervosa Using Novel Biometric Figure Rating Scales: A Pilot Study
Authors: Mölbert Simone C. , Thaler Anne , Streuber Stephan , Black Michael J. , Karnath Hans‐Otto , Zipfel Stephan , Mohler Betty , Giel Katrin E.
Published: October 2017

This study uses novel biometric figure rating scales (FRS) spanning body mass index (BMI) 13.8 to 32.2 kg/m2 and BMI 18 to 42 kg/m2. The aims of the study were (i) to compare FRS body weight dissatisfaction and perceptual distortion of women with anorexia nervosa (AN) to a community sample; (ii) how FRS parameters are associated with questionnaire body dissatisfaction, eating disorder symptoms and appearance comparison habits; and (iii) whether the weight spectrum of the FRS matters. Women with AN (n = 24) and a community sample of women (n = 104) selected their current and ideal body on the FRS and completed additional questionnaires. Women with AN accurately picked the body that aligned best with their actual weight in both FRS. Controls underestimated their BMI in the FRS 14–32 and were accurate in the FRS 18–42. In both FRS, women with AN desired a body close to their actual BMI and controls desired a thinner body. Our observations suggest that body image disturbance in AN is unlikely to be characterized by a visual perceptual disturbance, but rather by an idealization of underweight in conjunction with high body dissatisfaction. The weight spectrum of FRS can influence the accuracy of BMI estimation. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.
Detecting Eating Psychopathology in Female Athletes by Asking About Exercise: Use of the Compulsive Exercise Test
Authors: Plateau Carolyn R. , Arcelus Jon , Meyer Caroline
Published: October 2017

The present study assessed the suitability of the Compulsive Exercise Test (athlete version; CET‐A) for identifying female athletes with clinically significant features related to or comparable with eating psychopathology. Three hundred and sixty‐one female athletes (including 12 with a clinically diagnosed eating disorder) completed the Eating Disorders Examination Questionnaire and the CET‐A. Receiver operating curve analysis was employed to identify a cut‐off value on the CET‐A, which could indicate clinically significant features related to or comparable with eating psychopathology among female athletes. The analysis demonstrated that a CET‐A score of 10 successfully discriminated female athletes with a current eating disorder. The results suggest that the CET‐A may be a suitable tool for detecting eating psychopathology in female athletes. Additional longitudinal research is needed to evaluate the predictive value of the CET‐A. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.
Fast Ca2+ responses in astrocyte end‐feet and neurovascular coupling in mice
Authors: Lind Barbara Lykke , Jessen Sanne Barsballe , Lønstrup Micael , Joséphine Charlène , Bonvento Gilles , Lauritzen Martin
Published: October 2017

Cerebral blood flow (CBF) is regulated by the activity of neurons and astrocytes. Understanding how these cells control activity‐dependent increases in CBF is crucial to interpreting functional neuroimaging signals. The relative importance of neurons and astrocytes is debated, as are the functional implications of fast Ca2+ changes in astrocytes versus neurons. Here, we used two‐photon microscopy to assess Ca2+ changes in neuropil, astrocyte processes, and astrocyte end‐feet in response to whisker pad stimulation in mice. We also developed a pixel‐based analysis to improve the detection of rapid Ca2+ signals in the subcellular compartments of astrocytes. Fast Ca2+ responses were observed using both chemical and genetically encoded Ca2+ indicators in astrocyte end‐feet prior to dilation of arterioles and capillaries. A low dose of the NMDA receptor antagonist (5R,10s)‐(+)‐5‐methyl‐10,11‐dihydro‐5H‐dibenzo[a,d]cyclohepten‐5,10‐imine‐hydrogen‐maleate (MK801) attenuated fast Ca2+ responses in the neuropil and astrocyte processes, but not in astrocyte end‐feet, and the evoked CBF response was preserved. In addition, a low dose of 4,5,6,7‐tetrahydroisoxazolo[5,4‐c]pyridin‐3‐ol (THIP), an agonist for the extrasynaptic GABAA receptor (GABAAR), increased CBF responses and the fast Ca2+ response in astrocyte end‐feet but did not affect Ca2+ responses in astrocyte processes and neuropil. These results suggest that fast Ca2+ increases in the neuropil and astrocyte processes are not necessary for an evoked CBF response. In contrast, as local fast Ca2+ responses in astrocyte end‐feet are unaffected by MK801 but increase via GABAAR‐dependent mechanisms that also increased CBF responses, we hypothesize that the fast Ca2+ increases in end‐feet adjust CBF during synaptic activity.
Identifying disease foci from static and dynamic effective connectivity networks: Illustration in soldiers with trauma
Authors: Rangaprakash D. , Dretsch Michael N. , Venkataraman Archana , Katz Jeffrey S. , Denney Thomas S. , Deshpande Gopikrishna
Published: October 2017

Brain connectivity studies report group differences in pairwise connection strengths. While informative, such results are difficult to interpret since our understanding of the brain relies on region‐based properties, rather than on connection information. Given that large disruptions in the brain are often caused by a few pivotal sources, we propose a novel framework to identify the sources of functional disruption from effective connectivity networks. Our approach integrates static and time‐varying effective connectivity modeling in a probabilistic framework, to identify aberrant foci and the corresponding aberrant connectomics network. Using resting‐state fMRI, we illustrate the utility of this novel approach in U.S. Army soldiers (N = 87) with posttraumatic stress disorder (PTSD), mild traumatic brain injury (mTBI) and combat controls. Additionally, we employed machine‐learning classification to identify those significant connectivity features that possessed high predictive ability. We identified three disrupted foci (middle frontal gyrus [MFG], insula, hippocampus), and an aberrant prefrontal‐subcortical‐parietal network of information flow. We found the MFG to be the pivotal focus of network disruption, with aberrant strength and temporal‐variability of effective connectivity to the insula, amygdala and hippocampus. These connectivities also possessed high predictive ability (giving a classification accuracy of 81%); and they exhibited significant associations with symptom severity and neurocognitive functioning. In summary, dysregulation originating in the MFG caused elevated and temporally less‐variable connectivity in subcortical regions, followed by a similar effect on parietal memory‐related regions. This mechanism likely contributes to the reduced control over traumatic memories leading to re‐experiencing, hyperarousal and flashbacks observed in soldiers with PTSD and mTBI.Hum Brain Mapp 39:264–287, 2018. ©2017 Wiley Periodicals, Inc.
Should we treat acute hepatitis C? A decision and cost‐effectiveness analysis
Authors: Bethea Emily D. , Chen Qiushi , Hur Chin , Chung Raymond T. , Chhatwal Jagpreet
Published: October 2017

It is not standard practice to treat patients with acute hepatitis C virus (HCV) infection. However, as the incidence of HCV in the United States continues to rise, it may be time to re‐evaluate acute HCV management in the era of direct‐acting antiviral (DAA) agents. In this study, a microsimulation model was developed to analyze the trade‐offs between initiating HCV therapy in the acute versus chronic phase of infection. By simulating the lifetime clinical course of patients with acute HCV infection, we were able to project long‐term outcomes such as quality‐adjusted life years (QALYs) and costs. We found that treating acute HCV versus deferring treatment until the chronic phase increased QALYs by 0.02 and increased costs by $483 in patients not at risk of transmitting HCV. The resulting incremental cost‐effectiveness ratio was $19,991 per QALY, demonstrating that treatment of acute HCV was cost‐effective using a willingness‐to‐pay threshold of $100,000 per QALY. In patients at risk of transmitting HCV, treating acute HCV became cost‐saving, increasing QALYs by 0.03 and decreasing costs by $3,655. Conclusion: Immediate treatment of acute HCV with DAAs can improve clinical outcomes and be highly cost‐effective or cost‐saving compared with deferring treatment until the chronic phase of infection. If future studies continue to demonstrate effective HCV cure with shorter 6‐week treatment duration, then it may be time to revisit current HCV guidelines to incorporate recommendations that account for the clinical and economic benefits of treating acute HCV in the era of DAAs. (Hepatology 2018;67:837–846)
Organic Synthesis: Wherefrom and Whither? (Some Very Personal Reflections)
Authors: Denmark Scott E.
Published: October 2017

This perspective represents a (highly personal) examination of the past, present and future of synthetic organic chemistry. The central thesis posits that the confluence of factors that led to the “Golden Age of Natural Product Synthesis” in the second half of the twentieth century can be traced back to the identification of the therapeutic potential of steroid hormones culminating in the introduction of oral contraceptives. The tremendous benefits of those activities to the development of organic synthesis as a vibrant discipline led to the exponential increase in strategies and methods and the ability to tackle, larger and larger molecules of greater and greater complexity. The existential challenge to the health of organic synthesis is whether a similarly dynamic future can be anticipated and if so, to what end and how. Musings on potential answers to those questions are presented.
Polypyrrole‐coated electrodes show thickness‐dependent stability in different conditions during 42‐day follow‐up in vitro
Authors: Alarautalahti V. , Hiltunen M. , Onnela N. , Nymark S. , Kellomäki M. , Hyttinen J.
Published: October 2017

Electroconductive polypyrrole/dodecylbenzenesulphonate (PPy/DBS) has been proposed as novel electrode coating for biomedical applications. However, as yet, little is known about its long‐term stability in moist conditions. This study compares the stability of PPy/DBS‐coated platinum electrodes that are either dry‐stored, incubated, or both incubated and electrically stimulated. The electrical and material properties of three different coating thicknesses were monitored for 42 days. Initially, the PPy/DBS‐coating decreased the low frequency impedance of the platinum electrodes by 52% to 79%. The dry‐stored electrodes remained stable during the follow‐up, whereas the properties of all the incubated electrodes were altered in three stages with thickness‐dependent duration: stabilization, stable, and degradation. The coated electrodes would be applicable for short‐term, low‐frequency in vitro measurements of up to 14 days without electrical stimulation, and up to 7 days with stimulation. The coating thickness is bound to other coating properties, and should therefore be selected according to the specific target application. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2202–2213, 2018.
Parathyroid Hormone Signaling in Osteocytes
Authors: Wein Marc N
Published: October 2017

Osteocytes are the most abundant cell type in bone and play a central role in orchestrating skeletal remodeling, in part by producing paracrine‐acting factors that in turn influence osteoblast and osteoclast activity. Recent evidence has indicated that osteocytes are crucial cellular targets of parathyroid hormone (PTH). Here, we will review the cellular and molecular mechanisms through which PTH influences osteocyte function. Two well‐studied PTH target genes in osteocytes are SOST and receptor activator of NF‐κB ligand (RANKL). The molecular mechanisms through which PTH regulates expression of these two crucial target genes will be discussed. Beyond SOST and RANKL, PTH/PTH‐related peptide (PTHrP) signaling in osteocytes may directly influence the way osteocytes remodel their perilacunar environment to influence bone homeostasis in a cell‐autonomous manner. Here, I will highlight novel, additional mechanisms used by PTH and PTHrP to modulate bone homeostasis through effects in osteocytes. © 2017 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.
ABIN1 inhibits HDAC1 ubiquitination and protects it from both proteasome‐ and lysozyme‐dependent degradation
Authors: Ma Yuhong , Yuan Sen , Tian Xuezhang , Lin Shanchuan , Wei Shangmou , Hu Tongtong , Chen Shiyou , Li Xueqing , Chen Shuliang , Wu Dongcheng , Wang Min , Guo Deyin
Published: October 2017

ABIN1, an important immune regulator, has been shown to be involved in various cellular functions, such as immunity, development, tissue homeostasis, and tumor progression. It inhibits TNF‐ and TLR‐induced NF‐κB signaling activation and the consequent gene expression. Despite its functional significance, the mechanism of ABIN1 in the regulation of various cellular functions remains unclear. In this study, we identified HDAC1, a key regulator of eukaryotic gene expression and many important cellular events, including cell proliferation, differentiation, cancer and immunity, as an interacting partner of ABIN1. The results showed that ABIN1 acted as a modulator to down‐regulate HDAC1 ubiquitination via three different linkages, thereby stabilizing HDAC1 by inhibiting its lysosomal and proteasomal degradation. Interestingly, the inhibitory function of ABIN1 required direct binding with HDAC1. Moreover, the level of p53, which was a tumor suppressor and a well‐studied substrate of HDAC1, was under the regulation of ABIN1 via the modulation of HDAC1 levels, suggesting that ABIN1 was physiologically significant in tumor progression. This study has revealed a new function of ABIN1 in mediating HDAC1 modification and stability.
In vitro and in vivo effect of PD‐1/PD‐L1 blockade on microglia/macrophage activation and T cell subset balance in cryptococcal meningitis
Authors: Che Yuan‐Mei , Zhang Yi , Li Ming , Li Xiao‐Peng , Zhang Lun‐Li
Published: October 2017

This study aimed to investigate the PD‐1/ PD‐L1 signaling pathway and its effects the activation of microglia/macrophage and balancing T cell subsets in cryptococcal meningitis (CM). A total of 126 CM patients and 126 healthy individuals were recruited for the study. The CM patients were treated with amphotericin B (AmB). Seventy five C57BL/6 mice were grouped into the normal control, CM model, CM + AmB, sham, and CM + PD‐1 antibodies (Ab) groups. CD4+ and CD8+ T cells as well as microglia/macrophages were analyzed by means of flow cytometry. Ionized calcium‐binding adaptor molecule 1 (Ibal) expression was detected using western blotting and immunohistochemistry techniques. And the expression of Rab5 and Rab11 were detected using an immunofluorescence assay. Both PD‐1 and PD‐L1 mRNA and protein expression among the mice in the study were evaluated by qRT‐PCR and western blotting methods. Compared to the CM model group, the CM + AmB and CM + PD‐1 Ab groups exhibited increased levels of Th1 cytokines and chemokines expression, and reduced levels of Th2 cytokines expressions. Elevated cell purity and viability of CD4+ T cell were recorded as well as increases in microglia, however, there were reductions in the number of CD8+ T cells. Depleted expressions of Ibal, Rab5, and Rab11 as well as reduced mRNA expressions of PD‐1 and PD‐L1 in CD4+, microglia, and macrophage cells. The findings suggested that suppression of the PD‐1/PD‐L1 signaling pathway restricts the proliferation of CM by down‐regulating the expressions of Th2 cells and suppressing microglia and macrophage activation.
Molecular modeling studies to explore the binding affinity of virtually screened inhibitor toward different aminoglycoside kinases from diverse MDR strains
Authors: Parulekar Rishikesh S. , Sonawane Kailas D.
Published: October 2017

Antibiotic resistance to aminoglycoside group of antibiotics mainly occurs by aminoglycoside kinases (AKs). Thus, targeting AKs from different multidrug resistant (MDR) strains could result into inhibition of AK enzymes and ultimately the resistance. Therefore, the present study aims to target one of these AKs that is APH(3')‐Ia from Acinetobacter baumannii through structure based virtual screening (SBVS) and test the binding affinity of the most stable virtually screened inhibitor with AKs from Mycobacterium tuberculosis, Acinetobacter baumannii, Enterococcus gallinarum, and Escherichia coli. SBVS investigated ZINC71575479 as a most stable inhibitor with −8.92 kcal/mol of binding energy and 0.66 µM of inhibition constant. Molecular docking results revealed that the ZINC71575479 can efficiently bind to nucleotide triphosphate (NTP) binding site of different AKs which is a known drug target site. Sequence analysis study of different AKs showed no significant similarity for active site residues; however structure superimposition study showed conserved NTP‐binding domain. Molecular dynamics (MD) simulations showed stable behavior of all docked complexes with notable conformational stability of salt bridges at NTP‐binding site of different AKs. Binding energy calculations revealed the interactions between key residues from NTP‐ binding domain of different AKs with ZINC71575479. In order to validate the MD simulations and binding energy results, crystal structure complexed with tyrphostin AG1478 a known inhibitor of AKs was kept as control. Thus, this work demonstrates the binding efficiency of ZINC71575479 toward different AKs for circumventing aminoglycoside resistance and opens avenues for the development of new antibiotics that can target diverse MDR strains with aminoglycoside resistance.
Retracted: Prognostic significance of long non‐coding RNA MALAT1 for predicting the recurrence and metastasis of gallbladder cancer and its effect on cell proliferation, migration, invasion, and apoptosis
Authors: Sun Ke‐Ke , Hu Ping‐Ping , Xu Feng
Published: October 2017

The objective of this study is to explore the role of MALAT1 as a molecular indicator in predicting the recurrence, metastasis, and prognosis of gallbladder cancer (GBC) and its effect on the proliferation, invasion, migration, and apoptosis of GBC cells in vitro. GBC tissues and adjacent normal tissues were collected from 102 patients. MALAT1 short hairpin RNA (shRNA) plasmids were first constructed to transfect the GBC‐SD cells. Reverse transcription quantitative polymerase chain reaction (RT‐qPCR) was applied to detect MALAT1 expression. CCK‐8 assay, flow cytometry, and Transwell assay were applied to testify the cell proliferation, cell cycle, apoptosis, invasion, and migration. A receiver operating characteristic (ROC) curve was used to evaluate the values of MALAT1 in GBC recurrence, metastasis, and prognosis. COX regression analysis was applied to analyze the independent influencing factors of GBC patients’ survival status. ROC curve results showed that the MALAT1 expression could be a predictor of the GBC recurrence, metastasis, and prognosis. According to the COX regression analysis, MALAT1 expression, tumor size, and TNM stage were independent influencing factors of GBC patients’ survival condition. Compared with the GBC‐SD cells transfected with empty plasmids, those transfected with MALAT1 shRNA plasmids showed higher apoptosis rates, weakened proliferation, migration, and invasion. In conclusion, our findings demonstrate that lncRNA MALAT1 can be considered as an indicator for evaluating the recurrence, metastasis, and prognosis of GBC patients. We also demonstrate how the overexpression of MALAT1 confers an oncogenic function in GBC.
Protective effects of PPAR‐γ against pregnancy‐induced hypertension by differential ETR expression in rat models
Authors: Wu Ying , Ruan Yan , Shen Lin , Gong Qing
Published: October 2017

This study aims to investigate the effects of PPAR‐γ on rats with pregnancy‐induced hypertension (PIH) by regulating endothelin receptor (ETR). A total of 60 pregnant Wistar rats were selected, and 50 rats were used to establish endotoxin induced PIH rat models. Rats were equally assigned into PIH‐NS, PIH‐5 mg/kg RM, PIH‐10 mg/kg RM, PIH‐100 mg/kg ETR, and PIH‐200 mg/kg ETR groups, and the rest 10 rats were assigned to a the control group. Reverse transcription quantitative polymerase chain reaction (RT‐qPCR) and Western blotting were used for determining mRNA and protein expressions of PPAR‐γ and ETAR, respectively. Protein expression of ET‐1 was detected by immunohistochemistry. Results show that On the 22nd day of pregnancy, compared with the PIH‐NS group, SBP decreased in other groups, and platelet concentration increased most significantly in the PIH‐10 mg/kg RM and PIH‐200 mg/kg ETR groups. Compared with the control, PIH‐10 mg/kg RM and PIH‐200 mg/kg ETR groups, the increase in the expression of ET‐1 and ETAR was most significant in the PIH‐NS group. Compared with the control and PIH‐10 mg/kg RM groups, expression of PPAR‐γ was lower in the PIH‐NS, PIH‐5 mg/kg RM, PIH‐100 mg/kg ETR, and PIH‐200 mg/kg ETR groups. Compared with the PIH‐NS, PIH‐100 mg/kg ETR and PIH‐200 mg/kg ETR groups, PPAR‐γ expression was significantly higher in the PIH‐5 mg/kg RM group (all P < 0.05). Based on our findings, we conclude that PPAR‐γ activation inhibits ETR expression and reduces the effect of ET‐1 on vascular contraction thereby delaying PIH progression.
miR‐302a‐3p regulates RANKL expression in human mandibular osteoblast‐like cells
Authors: Irwandi Rizky A. , Khonsuphap Pakchisa , Limlawan Pirawish , Vacharaksa Anjalee
Published: October 2017

Receptor activator of nuclear factor kappa‐B ligand (RANKL) is important substance during osteoclastogenesis that resulted in alveolar bone loss of periodontitis. MicroRNAs (miRNAs) regulate gene expression in several biological processes including osteoclastogenesis. We investigated the function of microRNA‐302a‐3p (miR‐302a‐3p) to regulate receptor activator of nuclear factor kappa‐B ligand (RANKL) expression in human mandibular osteoblast‐like cells (HMOBs). HMOBs were incubated with prostaglandin E2 (PGE2) to mimic inflammation, or with PGE2 and interferon gamma (IFNγ) to mimic homeostasis. MicroRNA (miRNA) profiles related to RANKL expression were demonstrated by PCR array, and miR‐302a‐3p was identified. Using TargetScanHuman 7.0, a target of miR‐302a‐3p was predicted. To confirm its function, miR‐302a‐3p was overexpressed, or silenced, by transfection with miR‐302a‐3p mimic, or inhibitor, respectively. Level of miR‐302a‐3p and RANKL mRNA was assessed by qRT‐PCR. Soluble RANKL (sRANKL), and membrane‐bound RANKL (mRANKL) were measured by ELISA and by Western blot, respectively. When PGE2 stimulated RANKL in HMOBs, miR‐302a‐3p was lower than baseline level. However, upregulation of miR‐302a‐3p is observed when IFNγ suppressed RANKL expression in PGE2‐stimulated HMOBs. miR‐302a‐3p was predicted to target PRKACB mRNA encoding the catalytic subunit in cAMP/PKA pathway. Overexpression of miR‐302a‐3p could decrease RANKL expression during PGE2 stimulation. In contrast, silencing of miR‐302a‐3p by its inhibitor increased RANKL expression in PGE2‐IFNγ conditioned HMOBs. miR‐302a‐3p regulates RANKL expression in HMOBs within PGE2‐IFNγ regulatory network.