bluuebunny/crossref_metadata_2025 huggingface dataset:
A key role for Rac and Pak signaling in neutrophil extracellular traps (NETs) formation defines a new potential therapeutic target
Authors: Gavillet Mathilde , Martinod Kimberly , Renella Raffaele , Wagner Denisa D. , Williams David A.
Published: November 2017

NET formation in mice (NETosis) is supported by reactive oxygen species (ROS) production by NADPH oxidase and histone hypercitrullination by peptidylarginine deiminase 4 (PAD4). Rac1 and Rac2, expressed in polymorphonuclear neutrophils (PMNs), regulate the cytoskeleton, cell shape, adhesion, and migration and are also essential components of the NADPH oxidase complex. We aimed to explore the role of the Rac signaling pathway including the upstream guanosine exchange factor (GEF) activator, Vav, and a downstream effector, the p21‐activated kinase, Pak, on NETosis in PMNs using a previously described flow‐cytometry‐based assay. Rac2‐/‐ PMNs showed reduced levels of citrullinated histone H3 (H3Cit)‐positive cells and defective NETosis. Rac1Δ/Δ; Rac2‐/‐ PMNs demonstrated a further reduction in PMA‐induced H3Cit levels and a more profound impairment of NETosis than deletion of Rac2 alone, suggesting an overlapping role of these two highly related proteins. Genetic knockouts of Vav1, or Vav2, did not impair H3Cit response to phorbol myristate ester (PMA) or NETosis. Combined, Vav1 and Vav3 deletions decreased H3Cit response and caused a modest but significant impairment of NETosis. Pharmacologic inhibition of Pak by two inhibitors with distinct mechanisms of action, led to reduced H3Cit levels after PMA stimulation, as well as significant inhibition of NETosis. We validated the importance of Pak using Pak2Δ/Δ PMNs, which demonstrated significantly impaired histone H3 citrullination and NETosis. These data confirm and more comprehensively define the key role of the Rac signaling pathway in PMN NETosis. The Rac signaling cascade may represent a valuable target for inhibition of NETosis and related pathological processes.
Self‐reported musculoskeletal disorder pain: The role of job hazards and work‐life interaction
Authors: Weale Victoria P. , Wells Yvonne , Oakman Jodi
Published: November 2017

Background

Previous research identified an association between work‐family conflict and musculoskeletal pain. This study explores how the work‐life interface might affect pain experienced by residential aged care staff.

Methods

A cross‐sectional survey of 426 employees in residential aged care was analyzed to assess the impacts of workplace hazards, work‐family conflict, and work‐life balance on self‐reported musculoskeletal pain.

Results

Work‐family conflict acts as a mediator of the relationships between workplace hazards and the total number of body regions at which musculoskeletal pain was experienced. Work‐life balance only acts as a mediator for particular hazards and only if work‐family conflict is not taken into account.

Conclusions

Addressing work‐life interaction, and in particular work‐family conflict, warrants further investigation as a legitimate means through which musculoskeletal disorder risk can be reduced. Policies and practices to improve work‐life interaction and reduce work‐family conflict should be considered as integral components of musculoskeletal disorder risk management strategies.
Integrated Transmission Electron and Single‐Molecule Fluorescence Microscopy Correlates Reactivity with Ultrastructure in a Single Catalyst Particle
Authors: Hendriks Frank C. , Mohammadian Sajjad , Ristanović Zoran , Kalirai Sam , Meirer Florian , Vogt Eelco T. C. , Bruijnincx Pieter C. A. , Gerritsen Hans C. , Weckhuysen Bert M.
Published: November 2017

Establishing structure–activity relationships in complex, hierarchically structured nanomaterials, such as fluid catalytic cracking (FCC) catalysts, requires characterization with complementary, correlated analysis techniques. An integrated setup has been developed to perform transmission electron microscopy (TEM) and single‐molecule fluorescence (SMF) microscopy on such nanostructured samples. Correlated structure–reactivity information was obtained for 100 nm thin, microtomed sections of a single FCC catalyst particle using this novel SMF‐TEM high‐resolution combination. High reactivity in a thiophene oligomerization probe reaction correlated well with TEM‐derived zeolite locations, while matrix components, such as clay and amorphous binder material, were found not to display activity. Differences in fluorescence intensity were also observed within and between distinct zeolite aggregate domains, indicating that not all zeolite domains are equally active.
Poröse Polyelektrolyte: Zusammenspiel zwischen Poren und Ladung für neue Funktionen
Authors: Zhang Weiyi , Zhao Qiang , Yuan Jiayin
Published: November 2017

Das Gebiet poröser Polyelektrolyte hat im letzten Jahrzehnt eine rasante Entwicklung genommen. Das Interesse richtet sich zurzeit auf die Synthese dieser Materialien und ihre Anwendung in der Umwelt‐, Energie‐, Biomedizin‐ und Katalysetechnik. Für poröse Polyelektrolyte stehen verschiedene funktionelle organische Gruppen und Verarbeitungstechniken zur Auswahl, attraktiv macht diese Materialien jedoch vor allem das Zusammenspiel zwischen Ladung und Porenabmessungen in verschiedenen Längenbereichen, von einzelnen Polyelektrolytgerüsten bis hin zu ihren Nano‐/Mikroüberstrukturen. Dieser Aufsatz beschäftigt sich mit neuen Entwicklungen bei porösen Polyelektrolyten und schließt Membranen, Partikel, Gerüste, Pulver sowie Harze mit großer spezifischer Oberfläche sowie deren Derivate ein. Er konzentriert sich dabei auf das Zusammenspiel zwischen Oberflächenchemie, Coulomb‐Wechselwirkungen und Porenbeschränkung, was für die Chemie und Physik dieser Materialien bei Anwendungen auf den Gebieten der Energieumwandlung, Molekültrennung, Wasseraufbereitung, Sensortechnik/Aktuation, Katalyse, Gewebezüchtung und Nanomedizin relevant ist.
GOx@ZIF‐8(NiPd) Nanoflower: An Artificial Enzyme System for Tandem Catalysis
Authors: Wang Qingqing , Zhang Xueping , Huang Liang , Zhang Zhiquan , Dong Shaojun
Published: November 2017

We report a facile approach to prepare an artificial enzyme system for tandem catalysis. NiPd hollow nanoparticles and glucose oxidase (GOx) were simultaneously immobilized on the zeolitic imidazolate framework 8 (ZIF‐8) via a co‐precipitation method. The as‐prepared GOx@ZIF‐8(NiPd) nanoflower not only exhibited the peroxidase‐like activity of NiPd hollow nanoparticles but also maintained the enzymatic activity of GOx. A colorimetric sensor for rapid detection of glucose was realized through the GOx@ZIF‐8(NiPd) based multi‐enzyme system. Moreover, the GOx@ZIF‐8(NiPd) modified electrode showed good bioactivity of GOx and high electrocatalytic activity for the oxygen reduction reaction (ORR), which could also be used for electrochemical detection of glucose.
Porous Polyelectrolytes: The Interplay of Charge and Pores for New Functionalities
Authors: Zhang Weiyi , Zhao Qiang , Yuan Jiayin
Published: November 2017

The past decade has witnessed rapid advances in porous polyelectrolytes and there is tremendous interest in their synthesis as well as their applications in environmental, energy, biomedicine, and catalysis technologies. Research on porous polyelectrolytes is motivated by the flexible choice of functional organic groups and processing technologies as well as the synergy of the charge and pores spanning length scales from individual polyelectrolyte backbones to their nano‐/micro‐superstructures. This Review surveys recent progress in porous polyelectrolytes including membranes, particles, scaffolds, and high surface area powders/resins as well as their derivatives. The focus is the interplay between surface chemistry, Columbic interaction, and pore confinement that defines new chemistry and physics in such materials for applications in energy conversion, molecular separation, water purification, sensing/actuation, catalysis, tissue engineering, and nanomedicine.
Application and developing of iron‐doped multi‐walled carbon nanotubes (Fe/MWCNTs) as an efficient and reusable heterogeneous nanocatalyst in the synthesis of heterocyclic compounds
Authors: Sharghi Hashem , Aboonajmi Jasem , Mozaffari Mozhdeh , Doroodmand Mohammad Mahdi , Aberi Mahdi
Published: November 2017

Iron‐doped multi‐walled carbon nanotubes (Fe/MWCNTs) is an efficient, ecofriendly and reusable heterogeneous nanocatalyst for the one‐pot synthesis of heterocyclic compounds including bis‐spiro piperidines, piperidines, dihydro‐2‐oxopyrroles, pyrazoles and diazepines at room temperature with good to excellent yields. The heterogeneous nanocatalyst was fully characterized by scanning electron microscopy (SEM), X‐ray diffraction (XRD), inductively coupled plasma (ICP) and FT‐IR analysis. Also, the structures of all prepared compounds were characterized by 1H NMR, 13C NMR, FT‐IR, mass spectrometry (MS) and elemental analysis. The major advantages of these protocols are mild and green reaction conditions, short reaction times, clean reaction, operational simplicity, easy purification and good to excellent yields with the reusable heterogeneous nanocatalyst. The catalyst was ten recycled without significant loss of activity.
Single and binary catalyst systems based on nickel and palladium in polymerization of ethylene
Authors: Kimiaghalam Mahsa , Isfahani Hossein Nasr , Zohuri Gholam Hossein , Keivanloo Ali
Published: November 2017

The catalyst (N,N‐bis(2,6‐dibenzhydryl‐4‐ethoxyphenyl)butane‐2,3‐diimine)nickel dibromide, a late transition metal catalyst, was prepared and used in ethylene polymerization. The effects of reaction parameters such as polymerization temperature, co‐catalyst to catalyst molar ratio and monomer pressure on the polymerization were investigated. The α‐diimine nickel‐based catalyst was demonstrated to be thermally robust at a temperature as high as 90 °C. The highest activity of the catalyst (494 kg polyethylene (mol cat)−1 h−1) was obtained at [Al]/[Ni] = 600:1, temperature of 90 °C and pressure of 5 bar. In addition, the performance of a binary catalyst using nickel‐ and palladium‐based complexes was compared with that of the corresponding individual catalytic systems in ethylene polymerization. In a study of the catalyst systems, the average molecular weight and molecular weight distribution for the binary polymerization were between those for the individual catalytic polymerizations; however, the binary catalyst activity was lower than that of the two individual ones. The obtained polyethylenes had high molecular weights in the region of 105 g mol−1. Gel permeation chromatography analysis showed a narrow molecular weight distribution of 1.44 for the nickel‐based catalyst and 1.61 for the binary catalyst system. The branching density of the polyethylenes generated using the binary catalytic system (30 branches/1000 C) was lower than that generated using the nickel‐based catalyst (51/1000 C). X‐ray diffraction study of the polymer chains showed higher crystallinity with lower branching of the polymer obtained. Also Fourier transform infrared spectra confirmed that all obtained polymers were low‐density polyethylene.
Preparation and characterization of higher degree‐deacetylated chitosan‐coated magnetic adsorbent for the removal of chromium(VI) from its aqueous mixture
Authors: Ravi T. , Anuradha Jabasingh S.
Published: November 2017

Chitosan (90% deacetylated) coated magnetic adsorbent prepared by coprecipitation method to remove Cr(VI) from its aqueous solution. The experimental studies depicts that the predominant option for removal of Chromium by adsorption from its aqueous phase using Magnetic‐Chitosan (MC). The subsequent physical, chemical, and magnetic properties of MC were characterized by X‐ray powder diffraction, scanning electron microscopy, Fourier transform infrared spectrometer, vibrating sample magnetometer. The influence of batch process parameters such as contact time, initial concentration, pH, and coexisting anions were investigated. The Box‐Behnken experimental design in response surface methodology was performed to design the experiment optimal operating conditions. The maximum percentage reduction of Cr(VI) is 96.3 that was obtained by magnetic chitosan with the optimal operating conditions of 149.53 mg/L at pH of 5.32 at the contact time of 80 min and at the temperature of 303 K. The average diameter of the magnetic chitosan was calculated from X‐ray diffractometer analysis as 24.5 nm. The equilibrium adsorption isotherm models such as Langmuir and Freundlich and the adsorption kinetics such as pseudo first order, pseudo second order and intra‐particle diffusion kinetic model were analyzed. The experimental data's suited for the best fit with the Langmuir isotherm model and pseudo first order kinetic model. It also revealed that Cr(VI) adsorption on MC is intrinsically exothermic and spontaneous. The magnetic chitosan was also used to investigate for the removal of Cr(VI) from the real water sources such as surface, underground, and tannery wastewater. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 45878.
Remendable polymers via reversible Diels–Alder cycloaddition of anthracene‐containing copolymers with fullerenes
Authors: Kötteritzsch Julia , Geitner Robert , Ahner Johannes , Abend Marcus , Zechel Stefan , Vitz Jürgen , Hoeppener Stephanie , Dietzek Benjamin , Schmitt Michael , Popp Jürgen , Schubert Ulrich S. , Hager Martin D.
Published: November 2017

Poly(lauryl methacrylate)s with anthracene moieties in the side chain were converted with C60‐fullerene and phenyl‐C61‐butyric acid methyl ester (PCBM), resulting in new remendable (self‐healing) polymeric materials. The utilization of differently substituted anthracene monomers enabled the tuning of the reactivity and the resulting mechanical properties. Copolymers with different contents of the anthracene moieties were synthesized and characterized using size exclusion chromatography, 1H nuclear magnetic resonance (NMR) spectroscopy as well as differential scanning calorimetry (DSC). 1H NMR spectroscopic studies were utilized in order to investigate the reversibility of the Diels–Alder reaction between copolymers with C60‐fullerene and PCBM, respectively, in solution. In order to investigate the conversion of the polymers with C60‐fullerene and PCBM in bulk, additionally, DSC, nanoindentation, rheology, atomic force microscopy (AFM), 3D microscopy, simultaneous thermal analysis (STA) and FT‐Raman investigations were performed. The fullerene‐containing copolymers could be healed in a temperature range of 40–80 °C. Consequently, a new generation of low temperature remendable polymers could be established. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 45916.
Individual differences in EEG correlates of recognition memory due to DAT polymorphisms
Authors: Medrano Paolo , Nyhus Erika , Smolen Andrew , Curran Tim , Ross Robert S.
Published: November 2017

Introduction

Although previous research suggests that genetic variation in dopaminergic genes may affect recognition memory, the role dopamine transporter expression may have on the behavioral and EEG correlates of recognition memory has not been well established.

Objectives

The study aims to reveal how individual differences in dopaminergic functioning due to genetic variations in the dopamine transporter gene influences behavioral and EEG correlates of recognition memory.

Methods

Fifty‐eight participants performed an item recognition task. Participants were asked to retrieve 200 previously presented words while brain activity was recorded with EEG. Regions of interest were established in scalp locations associated with recognition memory. Mean ERP amplitudes and event‐related spectral perturbations when correctly remembering old items (hits) and recognizing new items (correct rejections) were compared as a function of dopamine transporter group.

Results

Participants in the dopamine transporter group that codes for increased dopamine transporter expression (10/10 homozygotes) display slower reaction times compared to participants in the dopamine transporter group associated with the expression of fewer dopamine transporters (9R‐carriers). 10/10 homozygotes further displayed differences in ERP and oscillatory activity compared to 9R‐carriers. 10/10 homozygotes fail to display the left parietal old/new effect, an ERP signature of recognition memory associated with the amount of information retrieved. 10/10 homozygotes also displayed greater decreases of alpha and beta oscillatory activity during item memory retrieval compared to 9R‐carriers.

Conclusion

Compared to 9R‐carriers, 10/10 homozygotes display slower hit and correct rejection reaction times, an absence of the left parietal old/new effect, and greater decreases in alpha and beta oscillatory activity during recognition memory. These results suggest that dopamine transporter polymorphisms influence recognition memory.
Toenail mineral concentration and risk of esophageal squamous cell carcinoma, results from the Golestan Cohort Study
Authors: Hashemian Maryam , Murphy Gwen , Etemadi Arash , Poustchi Hossein , Brockman John D. , Kamangar Farin , Pourshams Akram , Khoshnia Masoud , Gharavi Abdolsamad , Dawsey Sanford M. , Brennan Paul. J. , Boffetta Paolo. , Hekmatdoost Azita , Malekzadeh Reza , Abnet Christian C.
Published: November 2017

Studies conducted in China linked selenium deficiency to higher risk of esophageal squamous cell carcinoma (ESCC), but this has not been widely tested outside that selenium‐deficient region. The aim of this study was to investigate the association between selenium and other mineral concentrations in toenails and risk of ESCC in a region with high incidence rates. In this nested case–control study, we identified 222 cases of ESCC from the Golestan Cohort Study, Iran, which has followed up 50,045 participants since enrollment (2004–2008). We randomly selected one control for each case matched by age and sex, using incidence density sampling. We used toenail samples collected at baseline to measure the concentration of selenium, zinc, chromium, mercury, and scandium using instrumental neutron activation analysis. Multivariate adjusted logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals. Median nail selenium, zinc, chromium, and mercury levels were 1.01, 74.59, 0.77, and 0.018 μg/g in cases and 1.02, 75.71, 0.71, and 0.023 μg/g in controls, respectively. The adjusted odds ratios comparing each fourth quartile of mineral status versus the first quartile were as follows: selenium = 0.78 (95% CI, 0.41–1.49); zinc=0.80 (95% CI, 0.42–1.53); chromium = 0.91 (95% CI, 0.46–1.80); and mercury=0.61 (95% CI, 0.27–1.38), and all trend tests were non–significant. The nail selenium concentration in our controls reflects relatively high selenium status. No evidence of association between selenium or chromium concentrations in toenails and the risk of ESCC was detected in this population.
In vivo imaging xenograft models for the evaluation of anti‐brain tumor efficacy of targeted drugs
Authors: Kita Kenji , Arai Sachiko , Nishiyama Akihiro , Taniguchi Hirokazu , Fukuda Koji , Wang Rong , Yamada Tadaaki , Takeuchi Shinji , Tange Shoichiro , Tajima Atsushi , Nakada Mitsutoshi , Yasumoto Kazuo , Motoo Yoshiharu , Murakami Takashi , Yano Seiji
Published: November 2017

Molecular‐targeted drugs are generally effective against tumors containing driver oncogenes, such as EGFR, ALK, and NTRK1. However, patients harboring these oncogenes frequently experience a progression of brain metastases during treatment. Here, we present an in vivo imaging model for brain tumors using human cancer cell lines, including the EGFR‐L858R/T790M‐positive H1975 lung adenocarcinoma cells, the NUGC4 hepatocyte growth factor (HGF)‐dependent gastric cancer cells, and the KM12SM colorectal cancer cells containing the TPM3‐NTRK1 gene fusion. We investigated the efficacy of targeted drugs by comparison with their effect in extracranial models. In vitro, H1975 cells were sensitive to the third‐generation epidermal growth factor receptor inhibitor osimertinib. Moreover, HGF stimulated the proliferation of NUGC4 cells, that was inhibited by crizotinib, which has anti‐MET activity. KM12SM cells were sensitive to the tropomyosin‐related kinase‐A inhibitors crizotinib and entrectinib. In in vivo H1975 cell models, osimertinib inhibited the progression of both brain and subcutaneous tumors. Furthermore, in in vivo NUGC4 cell models, crizotinib remarkably delayed the progression of brain tumors, and that of peritoneal carcinomatosis. Interestingly, in in vivo KM12SM cell models, treatment with crizotinib delayed the progression of liver metastases, but not that of brain tumors. Conversely, treatment with entrectinib discernibly delayed the progression of both tumor types. Thus, the effect of targeted drugs against brain tumors can differ from the one reported in extracranial tumors. Moreover, the same multikinase inhibitory drug can display different efficacies in brain tumor models containing different drivers. Therefore, our in vivo imaging model for brain tumors may prove useful for preclinical drug screening against brain metastases.
Synthesis and Immunological Evaluation of a Multicomponent Cancer Vaccine Candidate Containing a Long MUC1 Glycopeptide
Authors: Supekar Nitin T. , Lakshminarayanan Vani , Capicciotti Chantelle J. , Sirohiwal Anju , Madsen Cathy S. , Wolfert Margreet A. , Cohen Peter A. , Gendler Sandra J. , Boons Geert‐Jan
Published: November 2017

A fully synthetic MUC1‐based cancer vaccine was designed and chemically synthesized containing an endogenous helper T‐epitope (MHC class II epitope). The vaccine elicited robust IgG titers that could neutralize cancer cells by antibody‐dependent cell‐mediated cytotoxicity (ADCC). It also activated cytotoxic T‐lymphocytes. Collectively, the immunological data demonstrate engagement of helper T‐cells in immune activation. A synthetic methodology was developed for a penta‐glycosylated MUC1 glycopeptide, and antisera of mice immunized by the new vaccine recognized such a structure. Previously reported fully synthetic MUC1‐based cancer vaccines that elicited potent immune responses employed exogenous helper T‐epitopes derived from microbes. It is the expectation that the use of the newly identified endogenous helper T‐epitope will be more attractive, because it will activate cognate CD4+ T‐cells that will provide critical tumor‐specific help intratumorally during the effector stage of tumor rejection and will aid in the generation of sustained immunological memory.
A FRET Sensor to Monitor Bivalent SUMO–SIM Interactions in SUMO Chain Binding
Authors: Kost Lisa J. , Mootz Henning D.
Published: November 2017

The small ubiquitin‐like modifier (SUMO) can be assembled into polymeric chains as part of its diverse biochemical signal pattern upon conjugation to substrate proteins. SUMO chain recognition is facilitated by receptor proteins that contain at least two SUMO‐interacting motifs (SIMs). Little is known about the structure of SUMO chains, both in an unliganded form and upon complexation with multi‐SIM protein partners. A FRET sensor has been developed based on a linear dimer of human SUMO‐2 as a minimal SUMO chain analogue. The synthetic acceptor and donor dyes were conjugated by maleimide and copper‐catalyzed click chemistry to each of the two SUMO subunits. FRET changes were only observed in the presence of di‐ or multi‐SIM ligands. Alteration of the short linker sequence between SIMs 2 and 3 of RNF4 showed a great tolerance, and hence, structural flexibility, of the SUMO dimer for bivalent binding of adjacent SIMs. The di‐SUMO FRET sensor reports on the binding of SIM clusters of the proteins C5orf25 and SOBP; this suggest that these can bind to adjacent subunits of a SUMO chain. The developed FRET sensor will be a useful tool to study the importance of SIM and linker sequences, as well as biochemical and structural properties of SUMO chains and multi‐SIM proteins.
The hybrid of semisupervised manifold learning and spectrum kernel for classification
Authors: Shen Liang , Xu Qingsong , Cao Dongsheng , Liang Yizeng , Dai Hongshuai
Published: November 2017

Manifold learning classification, as an advanced semisupervised learning algorithm in recent years, has gained great popularity in a variety of fields. Moreover, kernel methods are a group of algorithms for pattern analysis, the task of which is to find and study general types of relations in datasets. Thus, under the framework of kernel methods, manifold learning classifier has been introduced and explored to directly detect the intrinsic similarity by local and global information hidden in datasets. Two validation approaches were used to evaluate the performance of our models. Experiments indicate that the proposed model can be considered as an effective and alternative modeling algorithm, and it could be further applied to the areas of biochemical science, environmental analysis, clinical, etc.
Structure‐based statistical modeling and analysis of peptide affinity and cross‐reactivity to human senile osteoporosis OSF SH3 domain
Authors: Zhang Wei , Zhong Biao , Zhan Yulin , Luo Congfeng
Published: November 2017

Human osteoclast‐stimulating factor (OSF) induces osteoclast formation and bone resorption in senile osteoporosis by recruiting multiple signaling complexes with cognate interacting partners through its N‐terminal Src homology 3 (SH3) peptide‐recognition domain. The domain can recognize and bind to the polyproline regions of its partner proteins, rendering a broad ligand specificity and cross‐reactivity. Here, the structural basis and physicochemical property of peptide affinity and cross‐reactivity to OSF SH3 domain were investigated systematically by using an integration of statistical analysis and molecular modeling. A structure‐based quantitative structure‐activity relationship method called cross‐nonbonded interaction characterization and statistical regression was used to characterize the intermolecular interactions involved in computationally modeled domain‐peptide complex structures and then to correlate the interactions with affinity for a panel of collected SH3‐binding peptide samples. Both the structural stability and generalization ability of obtained quantitative structure‐activity relationship regression models were examined rigorously via internal cross‐validation and external test, confirming that the models can properly describe even single‐residue mutations at domain‐peptide complex interface and give a reasonable extrapolation for the mutation effect on peptide affinity. Subsequently, the best model was used to investigate the promiscuity and cross‐reactivity of OSF SH3 domain binding to its various peptide ligands. It is found that few key residues in peptide ligands are primarily responsible for the domain affinity and selectivity, while most other residues only play a minor role in domain‐peptide binding affinity and stability. The peptide residues can be classified into 3 groups in terms of their contribution to ligand selectivity: key, assistant, and marginal residues. Considering that the key residues are very few so that many domain interacting partners share a similar binding profile, additional factors such as in vivo environments and biological contexts would also contribute to the specificity and cross‐reactivity of OSF SH3 domain.
Long‐term outcomes among 2‐year survivors of autologous hematopoietic cell transplantation for Hodgkin and diffuse large b‐cell lymphoma
Authors: Myers Regina M. , Hill Brian T. , Shaw Bronwen E. , Kim Soyoung , Millard Heather R. , Battiwalla Minoo , Majhail Navneet S. , Buchbinder David , Lazarus Hillard M. , Savani Bipin N. , Flowers Mary E. D. , D'Souza Anita , Ehrhardt Matthew J. , Langston Amelia , Yared Jean A. , Hayashi Robert J. , Daly Andrew , Olsson Richard F. , Inamoto Yoshihiro , Malone Adriana K. , DeFilipp Zachariah , Margossian Steven P. , Warwick Anne B. , Jaglowski Samantha , Beitinjaneh Amer , Fung Henry , Kasow Kimberly A. , Marks David I. , Reynolds Jana , Stockerl‐Goldstein Keith , Wirk Baldeep , Wood William A. , Hamadani Mehdi , Satwani Prakash
Published: November 2017

BACKGROUND

Autologous hematopoietic cell transplantation (auto‐HCT) is a standard therapy for relapsed classic Hodgkin lymphoma (cHL) and diffuse large B‐cell lymphoma (DLBCL); however, long‐term outcomes are not well described.

METHODS

This study analyzed survival, nonrelapse mortality, late effects, and subsequent malignant neoplasms (SMNs) in 1617 patients who survived progression‐free for ≥2 years after auto‐HCT for cHL or DLBCL between 1990 and 2008. The median age at auto‐HCT was 40 years; the median follow‐up was 10.6 years.

RESULTS

The 5‐year overall survival rate was 90% (95% confidence interval [CI], 87%‐92%) for patients with cHL and 89% (95% CI, 87%‐91%) for patients with DLBCL. The risk of late mortality in comparison with the general population was 9.6‐fold higher for patients with cHL (standardized mortality ratio [SMR], 9.6) and 3.4‐fold higher for patients with DLBCL (SMR, 3.4). Relapse accounted for 44% of late deaths. At least 1 late effect was reported for 9% of the patients. A total of 105 SMNs were confirmed: 44 in the cHL group and 61 in the DLBCL group. According to a multivariate analysis, older age, male sex, a Karnofsky score < 90, total body irradiation (TBI) exposure, and a higher number of lines of chemotherapy before auto‐HCT were risk factors for overall mortality in cHL. Risk factors in DLBCL were older age and TBI exposure. A subanalysis of 798 adolescent and young adult patients mirrored the outcomes of the overall study population.

CONCLUSIONS

Despite generally favorable outcomes, 2‐year survivors of auto‐HCT for cHL or DLBCL have an excess late‐mortality risk in comparison with the general population and experience an assortment of late complications. Cancer 2018;124:816‐25. © 2017 American Cancer Society.
A framework for designing patient‐specific bioprosthetic heart valves using immersogeometric fluid–structure interaction analysis
Authors: Xu Fei , Morganti Simone , Zakerzadeh Rana , Kamensky David , Auricchio Ferdinando , Reali Alessandro , Hughes Thomas J. R. , Sacks Michael S. , Hsu Ming‐Chen
Published: November 2017

Numerous studies have suggested that medical image derived computational mechanics models could be developed to reduce mortality and morbidity due to cardiovascular diseases by allowing for patient‐specific surgical planning and customized medical device design. In this work, we present a novel framework for designing prosthetic heart valves using a parametric design platform and immersogeometric fluid–structure interaction (FSI) analysis. We parameterize the leaflet geometry using several key design parameters. This allows for generating various perturbations of the leaflet design for the patient‐specific aortic root reconstructed from the medical image data. Each design is analyzed using our hybrid arbitrary Lagrangian–Eulerian/immersogeometric FSI methodology, which allows us to efficiently simulate the coupling of the deforming aortic root, the parametrically designed prosthetic valves, and the surrounding blood flow under physiological conditions. A parametric study is performed to investigate the influence of the geometry on heart valve performance, indicated by the effective orifice area and the coaptation area. Finally, the FSI simulation result of a design that balances effective orifice area and coaptation area reasonably well is compared with patient‐specific phase contrast magnetic resonance imaging data to demonstrate the qualitative similarity of the flow patterns in the ascending aorta.
Rhodium Decahedral Nanocrystals: Facile Synthesis, Mechanistic Insights, and Experimental Controls
Authors: Lee Sujin R. , Vara Madeline , Hood Zachary D. , Zhao Ming , Gilroy Kyle D. , Chi Miaofang , Xia Younan
Published: November 2017

Decahedral nanocrystals have received great attention owing to their unique symmetry and strain‐energy distribution. In contrast to other noble metals, it has been difficult to synthesize decahedral Rh nanocrystals. We report a robust, one‐pot method based on polyol reduction for the facile synthesis of Rh decahedral nanocrystals in high purity, with sub‐20 nm sizes. The success of the synthesis relied on our ability to manipulate reduction kinetics by systematically tuning experimental parameters. We found that the yield of Rh decahedral nanocrystals could be maximized by optimizing: i) the concentration of Rh(acac)3 (metal precursor); ii) the molecular weight and amount of poly(vinyl pyrrolidone) (colloidal stabilizer/capping agent); and iii) the chain length of the polyol (solvent/reducing agent), with tetraethylene glycol being the best. We believe the mechanisms elucidated herein can be extended to other syntheses to produce metal nanocrystals with multiply twinned structures.
Single‐Dose Pharmacokinetics of Oral Cannabidiol Following Administration of PTL101: A New Formulation Based on Gelatin Matrix Pellets Technology
Authors: Atsmon Jacob , Heffetz Daphna , Deutsch Lisa , Deutsch Frederic , Sacks Hagit
Published: November 2017

Cannabidiol (CBD) is the main nonpsychoactive component of the cannabis plant. It has been associated with antiseizure, antioxidant, neuroprotective, anxiolytic, anti‐inflammatory, antidepressant, and antipsychotic effects. PTL101 is an oral gelatin matrix pellets technology–based formulation containing highly purified CBD embedded in seamless gelatin matrix beadlets. Study objectives were to evaluate the safety and tolerability of PTL101 containing 10 and 100 mg CBD, following single administrations to healthy volunteers and to compare the pharmacokinetic profiles and relative bioavailability of CBD with Sativex oromucosal spray (the reference product) in a randomized, crossover study design. Administration of PTL101 containing 10 CBD, led to a 1.7‐fold higher Cmax and 1.3‐fold higher AUC compared with the oromucosal spray. Tmax following both modes of delivery was 3–3.5 hours postdosing. CBD exhibited about a 1‐hour lag in absorption when delivered via PTL101. A 10‐fold increase in the dose resulted in an ∼15‐fold increase in Cmax and AUC. Bioavailability of CBD in the 10‐mg PTL101 dose was 134% relative to the reference spray. PTL101 is a pharmaceutical‐grade, user‐friendly oral formulation that demonstrated safe and efficient delivery of CBD and therefore could be an attractive candidate for therapeutic indications.
Measuring pH of the Coxiella burnetii Parasitophorous Vacuole
Authors: Samanta Dhritiman , Gilk Stacey D.
Published: November 2017

Coxiella burnetii is the causative agent of human Q fever, a zoonotic disease that can cause a debilitating, flu‐like illness in acute cases, or a life‐threatening endocarditis in chronic patients. An obligate intracellular bacterial pathogen, Coxiella survives and multiplies in a large lysosome‐like vacuole known as the Coxiella parasitophorous vacuole (CPV). A unique characteristic of the CPV is the acidic environment (pH ∼5.0), which is required to activate Coxiella metabolism and the Coxiella type 4 secretion system (T4SS), a major virulence factor required for intracellular survival. Further, inhibiting or depleting vacuolar ATPase, a host cell protein that regulates lysosomal pH, inhibits intracellular Coxiella growth. Together, these data suggest that CPV pH is an important limiting factor for Coxiella growth and virulence. This unit describes a method to determine CPV pH using live cell microscopy of a pH–sensitive fluorophore conjugated to dextran. This technique is useful to measure changes in CPV pH during infection or in response to drug treatment. © 2017 by John Wiley & Sons, Inc.
Efficient Microwave Irradiation‐Assisted Hydrothermal Synthesis of Ammonium Vanadate Flake
Authors: Wang Jing‐peng , Zhang Yi‐min , Huang Jing , Liu Tao
Published: November 2017

The major factors and affection for hydrothermal synthesis of ammonium vanadate in microwave irradiation was investigated and optimized. The obtained material was a pure (NH4)2V6O16 phase with regular spindle and rhombic crystal shapes. Transmission electron microscope and selected‐area electron diffraction patterns confirmed that the microwave irradiation‐assisted hydrothermal treatments altered the growth pattern and expanded the [–1 0 0] interplanar spacing by approximately ∼8%–12% compared to the standard powder diffraction file data.
Metal Phosphides as Co‐Catalysts for Photocatalytic and Photoelectrocatalytic Water Splitting
Authors: Cao Shuang , Wang Chuan‐Jun , Fu Wen‐Fu , Chen Yong
Published: November 2017

Solar‐to‐hydrogen conversion based on photocatalytic and photoelectrocatalytic water splitting is considered as a promising technology for sustainable hydrogen production. Developing earth‐abundant H2‐production materials with robust activity and stability has become the mainstream in this field. Due to the unique properties and characteristics, transition metal phosphides (TMPs) have been proven to be high performance co‐catalysts to replace some of the classic precious metal materials in photocatalytic water splitting. In this Minireview, we summarize the recent significant progress of TMPs as cocatalysts for water splitting reaction with high activity and stability. Firstly, the characteristic of TMPs is briefly introduced. Then, we mainly discuss the recent research efforts toward their application as photocatalytic co‐catalysts in photocatalytic H2‐production, O2‐evolution and photoelectrochemical water splitting. Finally, the catalytic mechanism, current existing challenges and future working directions for improving the performance of TMPs are proposed.
Ruthenium Ion‐Complexed Graphitic Carbon Nitride Nanosheets Supported on Reduced Graphene Oxide as High‐Performance Catalysts for Electrochemical Hydrogen Evolution
Authors: Peng Yi , Pan Wanzhang , Wang Nan , Lu Jia‐En , Chen Shaowei
Published: November 2017

Carbon‐based materials are promising, low‐cost electrocatalysts toward hydrogen evolution reaction (HER), although the catalytic performance needs to be further improved before commercialization. In this study, ruthenium ions are incorporated into graphitic carbon nitride/reduced graphene oxide (rGO) hybrids to form Ru−C3N4/rGO composites through Ru−N coordination bonds. The incorporation of Ru ions, at a loading of 1.93 at. %, leads to electron redistribution within the materials and dramatically enhances the HER performance over those of C3N4, C3N4/rGO, and Ru−C3N4, with an overpotential of only −80 mV to reach a current density of 10 mA cm−2, a Tafel slope of 55 mV dec−1, and an exchange current density of 0.462 mA cm−2. This performance is comparable to that of Pt/C, and ascribed to the positive shift of the conduction band of the composite, where the charge carrier density increases by a factor of about 250 over that of C3N4, leading to a lower energy barrier for hydrogen evolution. The results suggest a new strategy in the design and engineering of functional nanocomposites for effective HER electrocatalysis by embedding select metal ions into carbon‐based molecular skeletons.
A 99.95% linearity readout circuit with 72 dB dynamic range for active pixel sensors
Authors: de Sá Leonardo Bruno , Dias Mauricio Henrique Costa , Dupret Antoine , de Mesquita Filho Antonio Carneiro
Published: November 2017

One of the main sources of nonlinearity and sensitivity degradation in conventional active pixel sensor (APS) architectures is the source follower buffer amplifier that isolates the photodiode node from the column bus. To extend the linear region of the output voltage, correct the sensitivity degradation, and improve the imager dynamic range, an output regulated voltage follower is proposed. All these enhancements are achieved without decreasing the pixel fill factor nor increasing the number of transistors and the addressing circuits complexity of a conventional 4T CMOS APS. The performance of the circuit is assessed using a 0.35‐μm CMOS technology. The obtained results show a 14‐dB dynamic range improvement for highly linear applications over the conventional APS readout circuit.
Normal white matter microstructure in women long‐term recovered from anorexia nervosa: A diffusion tensor imaging study
Authors: Bang Lasse , Rø Øyvind , Endestad Tor
Published: November 2017

Objectives

Studies point to white matter (WM) microstructure alterations in both adolescent and adult patients with anorexia nervosa (AN). These include reduced fractional anisotropy in several WM fiber tracts, suggesting reduced WM integrity. The extent to which these alterations are reversible with recovery from AN is unclear. There is a paucity of research investigating the presence of WM microstructure alterations in recovered AN patients, and results are inconsistent. This study aimed to investigate the presence of WM microstructure alterations in women long‐term recovered from AN.

Method

Twenty‐one adult women who were recovered from AN for at least 1 year were compared to 21 adult comparison women. Participants were recruited via user‐organizations for eating disorders, local advertisements, and online forums. Diffusion tensor imaging was used to compare WM microstructure between groups. Correlations between WM microstructure and clinical characteristics were also explored.

Results

There were no statistically significant between‐group differences in WM microstructure. These null findings remained when employing liberal alpha level thresholds. Furthermore, there were no statistically significant correlations between WM microstructure and clinical characteristics.

Discussion

Our findings showed normal WM microstructure in long‐term recovered patients, indicating the alterations observed during the acute phase are reversible. Given the paucity of research and inconsistent findings, future studies are warranted to determine the presence of WM microstructure alterations following recovery from AN.
Tumor conditions induce bone marrow expansion of granulocytic, but not monocytic, immunosuppressive leukocytes with increased CXCR2 expression in mice
Authors: Bian Zhen , Shi Lei , Venkataramani Mahathi , Abdelaal Ahmed Mansour , Culpepper Courtney , Kidder Koby , Liang Hongwei , Zen Ke , Liu Yuan
Published: November 2017

Myeloid‐derived suppressor cells (MDSCs) promote tumor growth through, in part, inhibiting T‐cell immunity. However, mechanisms underlying MDSC expansion and guidance of MDSCs toward the tumor microenvironment remain unclear. Employing Percoll density gradients, we separate bone marrow (BM) leukocytes from tumor‐bearing mice into four density‐increasing bands with myeloid leukocytes enriched in bands III and IV. Band III comprises monocytes and low‐density granulocytes, both confirmed to be M‐MDSCs and G‐MDSCs, respectively, by displaying potent inhibition of T‐cell proliferation. However, monocytes act as M‐MDSCs not only under tumor conditions but also the healthy condition. In contrast, band IV contains non‐inhibitory, mature granulocytes. Only band III G‐MDSCs display significant expansion in mice bearing B16 melanoma, Lewis lung carcinoma, or MC38 colon carcinoma. The expanded G‐MDSCs also show increased CXCR2 expression, which guides egress out of BM, and produce arginase‐1 and ROS upon encountering antigen‐activated T cells. Adoptive transfer assays demonstrate that both G‐MDSCs and mature granulocytes infiltrate tumors, but only the former displays sustention and accumulation. Intratumoral administrations of granulocytes further demonstrate that G‐MDSCs promote tumor growth, whereas mature granulocytes exert minimal effects, or execute powerful anti‐tumor effects providing the presence of PMN activation mechanisms in the tumor microenvironment.
Synthesis, Structural Characterization and Anti‐Proliferative Activity of (κ1‐C)‐ and (κ2‐C,S)‐PtII Complexes Bearing Thioether‐Functionalized N‐Heterocyclic Carbenes
Authors: Egly Julien , Bouché Mathilde , Chen Weighang , Maisse‐François Aline , Achard Thierry , Bellemin‐Laponnaz Stéphane
Published: November 2017

A series of platinum(II) complexes bearing thioether‐functionalized N‐heterocyclic carbene ligands have been synthesized and characterized. The hemilabile and reversible character (i.e., coordination/decoordination) of the sulfur moiety in these platinum complexes has been established by ligand displacement (addition of pyridine) and ligand abstraction (on silica gel). The chemical reactivity of these complexes with glutathione has been investigated by NMR spectroscopy and mass spectrometry. Their biological activity towards various human cancer cells has been studied; these S‐functionalized NHC–platinum complexes displayed moderate cytotoxicity.
Hydroxymethylation of Quinolines with Na2S2O8 by a Radical Pathway
Authors: Zhou Luan , Okugawa Naoki , Togo Hideo
Published: November 2017

Quinolines and isoquinolines were treated with Na2S2O8 in a mixture of methanol and water at 70 °C to form hydroxymethylated quinolines and isoquinolines in good to moderate yields, under transition‐metal‐free conditions. The formed hydroxymethyl group was smoothly converted into aldehyde, ester, amide, bromomethyl, (N,N‐diethylamino)methyl, cyano, and tetrazole groups, in good yields.
Capillary‐HPLC with tandem mass spectrometry in analysis of alkaloid dyestuffs – a new approach
Authors: Dąbrowski Damian , Lech Katarzyna , Jarosz Maciej
Published: November 2017

Development of the identification method of alkaloid compounds in Amur cork tree as well as not examined so far Oregon grape and European Barberry shrubs are presented. The novel approach to separation of alkaloids was applied and the capillary‐high‐performance liquid chromatography (capillary‐HPLC) system was used, which has never previously been reported for alkaloid‐based dyestuffs analysis. Its optimization was conducted with three different stationary phases (unmodified octadecylsilane‐bonded silica, octadecylsilane modified with polar groups and silica‐bonded pentaflourophenyls) as well as with different solvent buffers. Detection of the isolated compounds was carried out using diode‐array detector (DAD) and tandem mass spectrometer with electrospray ionization (ESI MS/MS). The working parameters of ESI were optimized, whereas the multiple reactions monitoring (MRM) parameters of MS/MS detection were chosen based on the product ion spectra of the quasi‐molecular ions. Calibration curve of berberine has been estimated (y = 1712091x + 4785.03 with the correlation coefficient 0.9999). Limit of detection and limit of quantification were calculated to be 3.2 and 9.7 ng/mL, respectively. Numerous alkaloids (i.e., berberine, jatrorrhizine and magnoflorine, as well as phellodendrine, menisperine and berbamine) were identified in the extracts from alkaloid plants and silk and wool fibers dyed with these dyestuffs, among them their markers.
Prenatal diethylstilbestrol exposure and cancer risk in women
Authors: Troisi Rebecca , Hatch Elizabeth E. , Titus Linda , Strohsnitter William , Gail Mitchell H. , Huo Dezheng , Adam Ervin , Robboy Stanley J. , Hyer Marianne , Hoover Robert N. , Palmer Julie R.
Published: November 2017

In the Diethylstilbestrol [DES] Combined Cohort Follow‐up, the age‐ and calendar‐year specific standardized incidence ratio [SIR] for clear cell adenocarcinoma [CCA] was 27.6 (95% confidence interval [CI] 7.51‐70.6) for the exposed women. The SIR for breast cancer was 1.17 (95% CI 1.01‐1.36) and the hazard ratio [HR] adjusted for birth year and cohort for comparison with the unexposed was 1.05 (95% CI 0.79‐1.41). The SIR for pancreatic cancer was 2.43 (95% CI 1.21‐4.34) and the adjusted HR for comparison with unexposed women was 7.16 (95% CI 0.84‐61.5). There was little evidence of excess risk for other sites. There appeared to be a deficit in risk for endometrial cancer among the exposed (SIR 0.61; 95% CI 0.35‐0.98), and an excess in the unexposed (SIR 1.55; 95% CI 0.95‐2.40); the adjusted HR was 0.45 (95% CI 0.22‐0.93) for the internal comparison. There was no overall excess cancer risk in exposed women compared with general population rates (1.06; 95% CI 0.95‐1.17) or with unexposed participants (adjusted HR 1.03; 95% CI 0.84‐1.25). These data do not support the suggestion that there is a diathesis of cancers in DES exposed female offspring The excess risk of breast and pancreatic cancers that we observed is concerning and warrants continued follow‐up and mechanistic investigation. Environ. Mol. Mutagen. 60:395–403, 2019. Published 2017. This article is a US Government work and is in the public domain in the USA.