bluuebunny/crossref_metadata_2025 huggingface dataset:
Buchwald‐Hartwig amination reaction of aryl halides using heterogeneous catalyst based on Pd nanoparticles decorated on chitosan functionalized graphene oxide
Authors: Sarvestani Mosayeb , Azadi Roya
Published: June 2017

In this work, graphene oxide was functionalized with chitosan (GO‐Chit) followed by a simple approach for immobilization of palladium nanoparticles onto a chitosan grafted graphene oxide surface. The Pd‐nanocomposite (GO‐Chit‐Pd) was characterized using Transmission Electron Microscopy (TEM), Fourier transforms infrared spectroscopy (FT‐IR), and X‐ray diffraction (XRD) measurements. The catalytic activity of the prepared heterogeneous graphene oxide functionalized chitosan‐palladium (GO‐Chit‐Pd) was investigated in term of C‐N coupling reaction (Buchwald‐Hartwig amination reaction of aryl halides) yielding products of N‐arylamines. The easy purification, convenient operation, and environmental friendliness, combined with a high yield, render this method viable for use in both laboratory research and larger industrial scales. Studying the reusability of the catalyst in this work showed that it could be reused for five times without obvious loss in catalytic activity.
Synthesis of bromo‐cardanol novolac resins and evaluation of their effectiveness as flame retardants and adhesives for particleboard
Authors: Shishlov Oleg , Dozhdikov Sergei , Glukhikh Victor , Eltsov Oleg , Kraus Eduard , Orf Lukas , Heilig Michael , Stoyanov Oleg
Published: June 2017

The synthesis of bromo derivatives cardanolic novolac resins (BCNR) using infrared, thermogravimetric analysis, differential scanning calorimetry, gel permeation chromatography, nuclear magnetic resonance 1H and 13C methods was studied. The mechanism of thermal degradation of BCNR is proposed. It is shown, that particleboards manufactured using PU‐(BCNR) as an adhesive are materials with enhanced flame retardant properties, meeting the requirements of P7 class to EN 312 (especially durable moisture‐resistant particleboards) and the requirements of the emission class Super E0. The bromine in the structure of the cardanol‐containing polyurethane binder allows achieving both high physical and mechanical characteristics of the particleboards and resistance to flame. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45322.
Experience from an optional dissection course in a clinically‐orientated concept to complement system‐based anatomy in a reformed curriculum
Authors: Eppler Elisabeth , Serowy Steffen , Link Karl , Filgueira Luis
Published: June 2017

Profound anatomical knowledge is the basis for modern demands in medicine and surgery, but many countries worldwide including Australia and New Zealand have discontinued offering dissection courses to medical and dental students during the past decades. This educational project done in Australia aimed at enhancing basic and advanced anatomy teaching by engaging a sub‐group of second‐year undergraduate students of a compulsory prosection‐ and model‐based anatomy course (n = 54/170) in an optional multimodal course, which should easily articulate with a vertical curriculum. With topographical cadaver dissections as core, peer student‐teams prepared and peer‐assessed anatomy lectures based on clinical topics, which were rated highly by the peers and teachers. Anatomical knowledge was tested by quizzes and a multiple‐choice examination. Individual dissection skills were self‐ and teacher‐assessed. A final course grade was assigned based on these assessments. The grades in the system‐based compulsory course achieved by the attendees of the paralleling dissection course were compared with their peers attending other optional courses. After beginning of the semester, the students in the dissection course performed similar, significantly (P < 0.005) improved during the semester (78.5% vs. 69.9%, 70.1% vs. 64.1%), but in the integrated (including anatomy, biochemistry, physiology) final examination at the end of the year only tended to higher scores. As assessed through interviews and a voluntary questionnaire, all students of the optional dissection course liked these activities, which enhanced their learning experience. Thus, this concept elegantly integrates anatomical dissection with modern teaching demands and is feasible for implementation in modernized curricula. Anat Sci Educ 11: 32–43. © 2017 American Association of Anatomists.
Almost Disturbance Decoupling for a Class of Nonlinear Systems Subject to Time‐Delays Via Sampled‐Data Output Feedback Control
Authors: Meng Qinghua , Wang Pan , Sun Zong‐Yao , Chen Chih‐Chiang
Published: June 2017

This paper considers the problem of almost disturbance decoupling (ADD) via sampled‐data output feedback control for a class of uncertain nonlinear systems subject to time‐delays. Based on output feedback domination approach, a sampled‐data output feedback controller is designed to globally stabilize the system under a lower‐triangular linear growth condition. Gronwall‐Bellman‐like inequality and inductive method are introduced to estimate the state growth in the presence of time‐delays, uncertain nonlinearities and unknown disturbances. The proposed controller can attenuate the influence of disturbances on the output to an arbitrary degree in the L2 gain sense. Finally, simulation results show the effectiveness of the control method.
Empathic responding in preschool‐aged children with familial risk for autism
Authors: McDonald Nicole M. , Murphy Haley G. , Messinger Daniel S.
Published: June 2017

Individuals with autism spectrum disorder (ASD) show deficits in social and emotional reciprocity, which often include empathic responding. The younger siblings of children with ASD (high‐risk siblings) are at elevated risk for ASD and for subclinical deficits in social‐emotional functioning. Higher levels of empathy in high‐risk siblings during the second and third years of life predict fewer ASD symptoms and likelihood of diagnosis. We conducted a multi‐method investigation of empathic responding to an examiner's accident in 30 low‐risk and 48 high‐risk siblings with (n = 12) and without ASD outcomes (n = 36) at 4–6 years of age. Empathic responding was measured through behavioral observation and parent report. Prosocial behavior did not differ by ASD outcome. Children with ASD exhibited lower levels of personal distress than high‐risk and low‐risk siblings without ASD. Per parent report, high‐risk siblings without ASD demonstrated higher levels of empathic responding than low‐risk children, while the ASD group did not differ from children without ASD on this measure. Higher levels of observed empathic concern, but not prosocial behavior, were associated with lower Social Affect scores on the Autism Diagnostic Observation Schedule in high‐risk children. Results suggest that ASD diagnosis and symptoms are associated with reduced emotional responsiveness to an adult's distress, but not associated with deficits in prosocial behavior at preschool age. Results do not support the idea that empathic responding is negatively impacted in a broader autism phenotype. Findings extend previous research by suggesting that empathy may be a protective factor in the social‐emotional development of children with familial risk for ASD. Autism Res 2017, 10: 1621–1628. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
Biosynthesis of novel 7,8‐dihydroxyflavone glycoside derivatives and in silico study of their effects on BACE1 inhibition
Authors: Pandey Ramesh Prasad , Parajuli Prakash , Pokhrel Anaya Raj , Sohng Jae Kyung
Published: June 2017

7,8‐Dihydroxyflavone (7,8‐DHF) has been conjugated with glucose moiety to produce glucoside derivatives. Three analogues of 7,8‐DHF (7‐O‐β‐d‐glucosyl‐8‐hydroxyflavone, 7‐hydroxy‐8‐O‐β‐d‐glucosyl flavone, and 7,8‐di‐O‐β‐d‐glucosylflavone) have been successfully produced from in vitro reaction using glycosyltransferase of Bacillus licheniformis. Production of these 7,8‐DHF derivatives were shifted to cheaper and easier approach in this study by using engineered Escherichia coli BL21 (DE3) ΔpgiΔzwfΔushA cells in which the flow of glucose‐6‐phospahte toward glycolysis and pentose phosphate pathway and hydrolysis of UDP‐α‐d‐glucose were blocked while directing the carbon flux toward UDP‐α‐d‐glucose by overexpressing UDP‐α‐d‐glucose pathway genes. Supplementation of 300 μM of 7,8‐DHF to the culture resulted in production of 171 μM of 7‐O‐β‐d‐glucosyl‐8‐hydroxyflavone, 68 μM of 7‐hydroxy‐8‐O‐β‐d‐glucoxyflavone, and 55 μM of 7,8‐di‐O‐β‐d‐glucoxyflavone in laboratory‐scale 3‐L fermentor, representing 98% bioconversion of initially fed substrate to respective glucoside derivatives within 48 H. These products were characterized by high‐performance liquid chromatography‐photodiode array (HPLC‐PDA), HPLC‐PDA‐quadruple time of flight‐electron spray ionization mass spectrometry, and nuclear magnetic resonance analyses. These newly synthesized derivatives were found to be able to interact with amino acids of active site of human β‐site amyloid precursor protein cleaving β‐site amyloid precursor protein cleaving enzyme 1 (BACE1) β‐secretase enzyme in in silico studies, thus displaying possible application in cure of Alzheimer's disease.
SGK1/Nedd4–2 signaling pathway regulates the activity of human organic anion transporters 3
Authors: Wang Haoxun , You Guofeng
Published: June 2017

Human organic anion transporter 3 (hOAT3) is localized at the basolateral membrane of renal proximal tubule cells and facilitates the renal secretion of numerous clinical drugs, including anti‐HIV therapeutics, anti‐tumor drugs, antibiotics, antihypertension drugs and anti‐inflammatories. The present study explored the role of serum and glucocorticoid‐inducible kinase 1 (sgk1) in the regulation of hOAT3. It was shown that over‐expression of sgk1 in hOAT3‐expressing cells stimulated hOAT3 transport activity by enhancing the transporter expression at the plasma membrane, kinetically reflected as an increased maximal transport velocity Vmax without substantial change in the substrate‐binding affinity Km. In contrast, treatment of cells with the sgk‐specific inhibitor GSK650394 resulted in a dose‐dependent inhibition of hOAT3 transport activity. Evidence was further provided that sgk1 regulation of hOAT3 activity was mediated by ubiquitin ligase Nedd4–2, an enzyme previously shown to have an inhibitory effect on hOAT3. It was shown that sgk1 phosphorylated Nedd4–2, weakened the association between Nedd4–2 and hOAT3, and decreased hOAT3 ubiquitination. Functionally, the sgk1‐stimulated hOAT3 transport activity was attenuated in the presence of a ligase‐dead mutant of Nedd4–2. In summary, the investigation established for the first time that sgk1 stimulates hOAT3 transport activity by interfering with the inhibitory effect of Nedd4–2 on the transporter.
Electrochemical Study of Ferrocene and Anthracene using Ultramicroelectrode in Chloroform over the Temperature Range of 25–50°C
Authors: Nguyen Truc Ly , Lee Eui Joo , Jeong Hyuk , Kim Byung‐Kwon
Published: June 2017

In this study, electrochemical experiments were carried out in chloroform using ferrocene (Fc) or anthracene (An). We performed cyclic voltammetry (CV) on Fc and An in chloroform containing either tetrabutylammonium perchlorate (TBAP) or tetrabutylammonium hexafluoro‐phosphate (TBAPF6
) over the temperature range of 25 to 50°C. The resulting pattern of CVs, half‐wave potential (
E
1

/2), diffusion coefficient of Fc and An, steady‐state current, solution viscosity, and long‐term stabilities were studied.
Assessing Inter and Intra‐particle Heterogeneity in Alumina‐poor H‐ZSM‐5 Zeolites
Authors: Kennes Koen , Demaret Coralie , Van Loon Jordi , Kubarev Alexey V. , Fleury Guillaume , Sliwa Michel , Delpoux Olivier , Maury Sylvie , Harbuzaru Bogdan , Roeffaers Maarten B. J.
Published: June 2017

We reveal the presence of significant variations in Brønsted catalytic activity within and between individual H‐ZSM‐5 zeolite crystals. Fluorescence microscopy in combination with a fluorogenic probe was used to resolve the catalytic activity at the nanoscale. The observed variations in catalytic activity could be directly linked to structural parameters and crystal morphology observed in scanning electron microscopy and by specifically staining crystal defects. The obtained results are directly compared with ensemble averaged information from techniques such as pyridine IR spectroscopy and nitrogen physisorption, typically used to characterize acid zeolites. The inter‐ and intra‐particle heterogeneities resolved by the employed fluorescence approach remain unaddressed by bulk characterization. Our experimental results relate the heterogeneous catalytic activity to variation in both the Si/Al ratio and mesoporosity induced during the zeolite synthesis.
An Investigation of the Symmetric and Asymmetric Cleavage Products in the System Aluminum Trihalide/1‐Butylimidazole
Authors: Hog Michael , Schneider Marius , Studer Gauthier , Bäuerle Monika , Föhrenbacher Steffen A. , Scherer Harald , Krossing Ingo
Published: June 2017

Mixtures of AlX3 (X=Cl, Br) with 1‐butylimidazole (BuIm) in various ratios were investigated. The mixtures were characterized by multinuclear (1H, 27Al, 13C, and 15N) NMR, IR, and Raman spectroscopy and in part by single‐crystal X‐ray diffraction. Depending on the molar fraction x(AlBr3) of the AlBr3‐based mixtures, the cationic aluminum complexes [Al(BuIm)6]3+ and [AlBr2(BuIm)4]+, the neutral adduct [AlBr3(BuIm)], as well as the anions Br−, [AlBr4]−, and [Al2Br7]− could be identified as the products of the symmetric and asymmetric cleavage of dimeric Al2Br6. Furthermore, there are hints at the formation of [AlBr2(BuIm)2]+ or related cations. Comparison of the AlBr3/BuIm system with AlCl3‐based mixtures revealed the influence of the halide: In contrast to AlBr3, the trication [Al(BuIm)6]3+ could not be detected as main product in a 1:6 mixture of AlCl3 and BuIm. Additionally, [AlCl3(BuIm)] crystallizes from a mixture with x(AlCl3)=0.60 at room temperature, whereas the corresponding AlBr3‐based mixture remains liquid even at +6 °C. Three AlBr3‐based mixtures are liquid at room temperature, whereas all other mixtures are solids with melting points between 46 and 184 °C. The three liquid mixtures exhibit medium to high viscosities (117 to >1440 mPa s), low conductivities (0.03–0.20 mS cm−1), but high densities (1.80–2.21 g cm−3). Aluminum could be successfully deposited from one of the neat Lewis acidic mixtures of the AlBr3‐based system.
Ambient Water‐Stable Dianionic Electron Donors: Intramolecular Noncovalent Conduits Assist Charge Delocalization
Authors: Keshri Sudhir Kumar , Kumar Sharvan , Mandal Kalyanashis , Mukhopadhyay Pritam
Published: June 2017

Electron‐rich π‐conjugated dianions are known to be ambient unstable and their stabilization in ambient water is yet to be realized. We report the first example of an exceptionally stable naphthalenediimide‐based dianion in ambient and hot water, forming one of the most stable redox‐active dianion. The half‐life (t1/2) of dianion (1 a2−) is more than four months in ambient water. The dianionic state was confirmed by X‐ray crystallography and by various spectroscopic methods. The noncovalent electronic conduits introduced for the first time in dianions, embrace nO→π*C≡N interactions and aid in delocalizing the dianionic charge as validated from theoretical studies. The dianions harness strong NIR absorption and electron donor ability to organic acceptors and metal ions, which make them suitable for potential green energy applications.
Interactions between Ketones and Alcohols: Rotational Spectrum and Internal Dynamics of the Acetone–Ethanol Complex
Authors: Gou Qian , Favero Laura B. , Feng Gang , Evangelisti Luca , Pérez Cristóbal , Caminati Walther
Published: June 2017

The rotational spectra of two isotopologues of the 1:1 complex formed between acetone and ethanol have been recorded and analyzed by using Fourier‐transform microwave spectroscopy. One rotamer was detected, in which ethanol adopts the gauche form. The two subunits are linked by a conventional O−H⋅⋅⋅O and a weak C−H⋅⋅⋅O hydrogen bond, forming a six‐membered ring. Each rotational transition is split into five component lines due to the internal rotations of two nonequivalent acetone methyl groups. The V3 barriers to internal rotation of the two CH3 tops of acetone were determined to be 252(4) and 220(1) cm−1, which are noticeably lower than the value for the monomer (266 cm−1).
Tuning the Porphyrin Building Block in Self‐Assembled Cages for Branched‐Selective Hydroformylation of Propene
Authors: Wang Xiaowu , Nurttila Sandra S. , Dzik Wojciech I. , Becker René , Rodgers Jody , Reek Joost N. H.
Published: June 2017

Unprecedented regioselectivity to the branched aldehyde product in the hydroformylation of propene was attained on embedding a rhodium complex in supramolecular assembly L2, formed by coordination‐driven self‐assembly of tris(meta‐pyridyl)phosphine and zinc(II) porpholactone. The design of cage L2 is based on the ligand‐template approach, in which the ligand acts as a template for cage formation. Previously, first‐generation cage L1, in which zinc(II) porphyrin units were utilized instead of porpholactones, was reported. Binding studies demonstrate that the association constant for the formation of second‐generation cage L2 is nearly an order of magnitude higher than that of L1. This strengthened binding allows cage L2 to remain intact in polar and industrially relevant solvents. As a consequence, the unprecedented regioselectivity for branched aldehyde products can be maintained in polar and coordinating solvents by using the second‐generation assembly.
Reaction of Dihalodiboranes(4) with a N‐Heterocyclic Silylene: Facile Construction of 1‐Aryl‐2‐Silyl‐1,2‐Diboraindanes
Authors: Braunschweig Holger , Brückner Tobias , Deißenberger Andrea , Dewhurst Rian D. , Gackstatter Annika , Gärtner Annalena , Hofmann Alexander , Kupfer Thomas , Prieschl Dominic , Thiess Torsten , Wang Sunewang Rixin
Published: June 2017

Dihalodiboranes(4) react with a N‐heterocyclic silylene (NHSi) to generate NHSi adducts of 1‐aryl‐2‐silyl‐1,2‐diboraindanes, as was confirmed by X‐ray crystallography, featuring the functionalization of both B−X (X=halogen) bonds and a sp3‐ or sp2‐C−H bond under mild conditions. Coordination of a third NHSi to the proposed 1,1‐diaryl‐2,2‐disilyldiborane(4) intermediates, generated by a twofold B−X insertion, may be crucial for the C−H borylation that leads to the final products. Notably, our results demonstrate the first C−H borylation with a strong B−F bond activated by silylene insertion.
New chiral stationary phases based on xanthone derivatives for liquid chromatography
Authors: Fernandes Carla , Tiritan Maria Elizabeth , Cravo Sara , Phyo Ye’ Zaw , Kijjoa Anake , Silva Artur M.S. , Cass Quezia B. , Pinto Madalena M.M.
Published: June 2017

Six chiral derivatives of xanthones (CDXs) were covalently bonded to silica, yielding the corresponding xanthonic chiral stationary phases (XCSPs). The new XCSPs were packed into stainless‐steel columns with 150 x 4.6 mm i.d. Moreover, the greening of the chromatographic analysis by reducing the internal diameter (150 x 2.1 mm i.d.) of the liquid chromatography (LC) columns was also investigated. The enantioselective capability of these phases was evaluated by LC using different chemical classes of chiral compounds, including several types of drugs. A library of CDXs was evaluated in order to explore the principle of reciprocity as well as the chiral self‐recognition phenomenon. The separation of enantiomeric mixtures of CDXs was investigated under multimodal elution conditions. The XCSPs provided high specificity for the enantiomeric mixtures of CDXs evaluated mainly under normal‐phase elution conditions. Furthermore, two XCSPs were prepared with both enantiomers of the same xanthonic selector in order to confirm the inversion order elution.
A GLOBAL WEAK FORM ELEMENT FREE METHOD FOR DIRECT CURRENT RESISTIVITY FORWARD SIMULATION
Authors: Chang‐Ying MA , Jian‐Xin LIU , Hai‐Fei LIU , Rong‐Wen GUO , Chuang‐Hua CAO
Published: June 2017

We present a global weak form element free method (EFM) for simulation of direct current resistivity. EFM is a new numerical simulation method developed on the basis of the finite element method (FEM). The key point of this method is the absence of elements and the nodes free from the elemental restraint, which makes it very flexible and simple in pre‐processing. It utilizes the nodes of local support domain to construct shape functions to achieve the accurate approximations of the local domain. Approximations of EFM are of high order and boundary conditions are enforced simply, because the radial point interpolation method (RPIM) is used to construct shape function. Therefore, EFM is more suitable to simulate complex models than FEM. First, the boundary value problem and the corresponding variational problem of direct current resistivity forward simulation are derived starting with the partial differential equation of current field. Second, the construction of RPIM shape function is introduced in details. Third, equations of the global weak form EFM for direct current resistivity are derived in details based on RPIM shape function. Then, a Fortran program is written according to the equations. By this program, a homogeneous half‐space model was used to verify our element free approach. At the same time, we compared the solutions of EFM and FEM in details which shows that the solutions of EFM are more accurate. Furthermore, the solutions indicate the correctness and effectiveness of the EFM for direct current resistivity forward simulation. Finally, we improve the simulation accuracy successfully by refining nodes arbitrarily, and the solutions of EFM forward simulation for complex geoelectric models show that EFM has a high degree of flexibility.
Assessment of programmed death‐ligand 1 expression and tumor‐associated immune cells in pediatric cancer tissues
Authors: Majzner Robbie G. , Simon Jason S. , Grosso Joseph F. , Martinez Daniel , Pawel Bruce R. , Santi Mariarita , Merchant Melinda S. , Geoerger Birgit , Hezam Imene , Marty Virginie , Vielh Phillippe , Daugaard Mads , Sorensen Poul H. , Mackall Crystal L. , Maris John M.
Published: June 2017

BACKGROUND

Programmed death 1 (PD‐1) signaling in the tumor microenvironment dampens immune responses to cancer, and blocking this axis induces antitumor effects in several malignancies. Clinical studies of PD‐1 blockade are only now being initiated in pediatric patients, and little is known regarding programmed death‐ligand 1 (PD‐L1) expression in common childhood cancers. The authors characterized PD‐L1 expression and tumor‐associated immune cells (TAICs) (lymphocytes and macrophages) in common pediatric cancers.

METHODS

Whole slide sections and tissue microarrays were evaluated by immunohistochemistry for PD‐L1 expression and for the presence of TAICs. TAICs were also screened for PD‐L1 expression.

RESULTS

Thirty‐nine of 451 evaluable tumors (9%) expressed PD‐L1 in at least 1% of tumor cells. The highest frequency histotypes comprised Burkitt lymphoma (80%; 8 of 10 tumors), glioblastoma multiforme (36%; 5 of 14 tumors), and neuroblastoma (14%; 17 of 118 tumors). PD‐L1 staining was associated with inferior survival among patients with neuroblastoma (P = .004). Seventy‐four percent of tumors contained lymphocytes and/or macrophages. Macrophages were significantly more likely to be identified in PD‐L1–positive versus PD‐L1–negative tumors (P < .001).

CONCLUSIONS

A subset of diagnostic pediatric cancers exhibit PD‐L1 expression, whereas a much larger fraction demonstrates infiltration with tumor‐associated lymphocytes. PD‐L1 expression may be a biomarker for poor outcome in neuroblastoma. Further preclinical and clinical investigation will define the predictive nature of PD‐L1 expression in childhood cancers both at diagnosis and after exposure to chemoradiotherapy. Cancer 2017;123:3807–3815. © 2017 American Cancer Society
Exploiting DNA damage without repair: The activity of platinum chemotherapy in BRCA‐mutated prostate cancers
Authors: Humeniuk Michael S. , Zhang Tian , Armstrong Andrew J.
Published: June 2017

The report in this issue by Pomerantz and colleagues demonstrates that men with metastatic prostate cancer harboring germline BRCA2 mutations are strongly associated with a prostate‐specific antigen response ≥50% during treatment with a platinum agent. However, more work will be required to classify other men who might benefit from platinum agents.

See also pages 3532‐9.
The association between germline BRCA2 variants and sensitivity to platinum‐based chemotherapy among men with metastatic prostate cancer
Authors: Pomerantz Mark M. , Spisák Sandor , Jia Li , Cronin Angel M. , Csabai Istvan , Ledet Elisa , Sartor A. Oliver , Rainville Irene , O'Connor Edward P. , Herbert Zachary T. , Szállási Zoltan , Oh William K. , Kantoff Philip W. , Garber Judy E. , Schrag Deborah , Kibel Adam S. , Freedman Matthew L.
Published: June 2017

BACKGROUND

Breast cancer 2 (BRCA2)‐associated breast and ovarian cancers are sensitive to platinum‐based chemotherapy. It is unknown whether BRCA2‐associated prostate cancer responds favorably to such treatment.

METHODS

A retrospective analysis of a single‐institution cohort of men with castration‐resistant, metastatic prostate cancer was performed to determine the association between carrier status of pathogenic BRCA2 germline variants and prostate‐specific antigen response to carboplatin‐based chemotherapy. From 2001 through 2015, 8081 adult men with prostate cancer who had a consultation and/or underwent treatment at Dana‐Farber Cancer Institute provided blood samples and consented to analyses of biologic material and clinical records. A subgroup of 141 men received at least 2 doses of carboplatin and docetaxel for castration‐resistant disease (94% were also taxane refractory). These patients were categorized according to the absence or presence of pathogenic germline mutations in BRCA2 based on DNA sequencing from whole blood. The primary outcome was the response rate to carboplatin/docetaxel chemotherapy, defined according to a decline in prostate‐specific antigen that exceeded 50% within 12 weeks of initiating this regimen. Associations between BRCA2 mutation status and response to carboplatin‐based chemotherapy were tested using the Fisher exact test, with a 2‐sided P value < .05 as the threshold for significance.

RESULTS

Pathogenic germline BRCA2 variants were observed in 8 of 141 men (5.7%; 95% confidence interval, 2.5%‐10.9%). Six of 8 BRCA2 carriers (75%) experienced prostate‐specific antigen declines >50% within 12 weeks, compared with 23 of 133 noncarriers (17%; absolute difference, 58%; 95% confidence interval, 27%‐88%; P < .001). Prostate cancer cell lines functionally corroborated these clinical findings.

CONCLUSIONS

BRCA2‐associated, castration‐resistant prostate cancer is associated with a higher likelihood of response to carboplatin‐based chemotherapy than non‐BRCA2–associated prostate cancer. Cancer 2017;123:3532‐9. © 2017 American Cancer Society.
TP53 mutation does not confer a poor outcome in adult patients with acute lymphoblastic leukemia who are treated with frontline hyper‐CVAD‐based regimens
Authors: Kanagal‐Shamanna Rashmi , Jain Preetesh , Takahashi Koichi , Short Nicholas J. , Tang Guilin , Issa Ghayas C. , Ravandi Farhad , Garcia‐Manero Guillermo , Yin Cameron C. , Luthra Rajyalakshmi , Patel Keyur P. , Khoury Joseph D. , Montalban‐Bravo Guillermo , Sasaki Koji , Kadia Tapan M. , Borthakur Gautam , Konopleva Marina , Jain Nitin , Garris Rebecca , Pierce Sherry , Wierda William , Estrov Zeev , Cortes Jorge , O'Brien Susan , Kantarjian Hagop M. , Jabbour Elias
Published: June 2017

BACKGROUND

Tumor protein 53 (TP53) mutations are uncommon in adult patients with acute lymphoblastic leukemia (ALL) and predict a poor outcome.

METHODS

TP53 mutation analysis was performed in 164 newly diagnosed adult patients with ALL using a combination of targeted amplicon‐based next‐generation sequencing and Sanger sequencing.

RESULTS

TP53 mutations were detected in 25 patients (15%), with a median allelic frequency of 42.2% (range, 5.6%‐93.8%). The majority of mutations were single‐nucleotide variants of missense type and involved the DNA‐binding domain. TP53‐mutated (TP53mut) ALL was found to be significantly associated with older age, lower median white blood cell and platelet counts, lower frequency of Philadelphia chromosome and a higher frequency of low hypodiploid karyotype compared with ALL with wild‐type TP53 (TP53wt). To evaluate the prognostic effect of TP53 mutations, the authors selected 146 patients with B‐cell immunophenotype ALL (24 with TP53mut and 122 with TP53wt) who were uniformly treated with frontline hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper‐CVAD)‐based regimens; >90% of these individuals also received a monoclonal antibody. Over a median follow‐up duration of 15 months, there was no significant difference in the median overall survival, event‐free survival, and duration of complete remission noted between patients with TP53mut ALL and those with TP53wt ALL.

CONCLUSIONS

Hyper‐CVAD‐based regimens appear to negate the poor prognostic impact of TP53 mutations in patients with adult B‐cell immunophenotype ALL. Cancer 2017;123:3717‐24. © 2017 American Cancer Society.
Preanalytic specimen triage: Smears, cell blocks, cytospin preparations, transport media, and cytobanking
Authors: da Cunha Santos Gilda , Saieg Mauro A.
Published: June 2017

With increasing requests for the evaluation of prognostic and predictive molecular biomarkers, great attention must be paid to the preanalytical issues regarding sample quality and DNA/RNA yield from all different types of cytological preparations. The objectives of this review were: 1) to provide an update regarding the importance of specimen triage as well as specimen handling and collection; 2) to discuss the different cell preparations that can be used for molecular testing, their advantages and limitations; and 3) to highlight the strategies for biobanking cytology samples. Good‐quality DNA/RNA can be harvested from fresh cells in cell suspensions, formalin‐fixed paraffin‐embedded cell blocks, archival stained smears, archival unstained cytospin preparations, liquid‐based cytology slides, FTA cards, and cryopreserved cells. In contrast to formalin‐fixed paraffin‐embedded tissue specimens (small biopsies and surgical resections), the multitude of types of sample preparations as well as the diversity in sample collection and processing procedures make cytology an ideal specimen for most genomic platforms, with less DNA and RNA degradation and a purer sample, usually with a higher concentration of tumor cells. The broad incorporation of cytological specimens into clinical practice. A should increase the number of samples potentially available for molecular tests and avoid repeat invasive procedures for tissue procurement, thereby increasing patient safety. In this context, it is of utmost importance that cytopathologists become familiar with the variables that can affect test results and embrace the goal of excellence in sample quality. Cancer Cytopathol 2017;125(6 suppl):455‐64. © 2017 American Cancer Society.
Analytic inquiry: Validation and practical considerations
Authors: Berry Anna B.
Published: June 2017

Molecular diagnostics and cytopathology ideally are complementary medical services. When used together, they provide optimal benefit to patient care with the least risk of complications. However, many cytopathology laboratories are reluctant to bring in molecular tests, in part due to inexperience with regard to molecular test validation. This article is a brief review of the basic principles of molecular test validation as it applies to cytopathology samples. Regulatory constraints, practical considerations, and issues that are particular to cytopathology samples are discussed, along with a brief review of issues that pertain specifically to next‐generation sequencing. This review should serve as a general guide to validating molecular tests in the cytopathology laboratory. Cancer Cytopathol 2017;125(6 suppl):465‐9. © 2017 American Cancer Society.
Anatomical and electrophysiological development of the hypothalamic orexin neurons from embryos to neonates
Authors: Ogawa Yukino , Kanda Takeshi , Vogt Kaspar , Yanagisawa Masashi
Published: June 2017

The amount, quality, and diurnal pattern of sleep change greatly during development. Developmental changes of sleep/wake architecture are in a close relationship to brain development. The fragmentation of wake episodes is one of the salient features in the neonatal period, which is also observed in mature animals and human individuals lacking neuropeptide orexin/hypocretin signaling. This raises the possibility that developmental changes of lateral hypothalamic orexin neurons are relevant to the development of sleep/wake architecture. However, little information is available on morphological and physiological features of developing orexin neurons. To address the cellular basis for maturation of the sleep/wake regulatory system, we investigated the functional development of orexin neurons in the lateral hypothalamus. The anatomical development as well as the changes in the electrophysiological characteristics of orexin neurons was examined from embryonic to postnatal stages in orexin‐EGFP mice. Prepro‐orexin promoter activity was detectable at embryonic day (E) 12.0, followed by expression of orexin A after E14.0. The number of orexin neurons and their membrane capacitance reached similar levels to adults by postnatal day (P) 7, while their membrane potentials, firing rates, and action potential waveforms were developed by P21. The hyperpolarizing effect of serotonin, which is a major inhibitory signal for adult orexin neurons, was detected after E18.0 and matured at P1. These results suggest that the expression of orexin peptides precedes the maturation of electrophysiological activity of orexin neurons. The function of orexin neurons gradually matures by 3 weeks after birth, coinciding with maturation of sleep/wake architecture.
Phosphorus‐Containing Polycyclic Aromatic Hydrocarbons
Authors: Szűcs Rózsa , Bouit Pierre‐Antoine , Nyulászi László , Hissler Muriel
Published: June 2017

Polycyclic aromatic hydrocarbons (PAHs) are highly appealing functional materials in the field of molecular electronics. In particular, molecular engineering of these derivatives by using organic chemistry is a powerful method to tune their properties from the point of view of the band gap and supramolecular assemblies. Another way to achieve such control is to take advantage of the specific reactivity of heteroatoms placed within the sp2‐carbon framework. This strategy has been successfully applied to nitrogen, sulfur and boron. In this review, examples of phosphorus‐containing PAHs and the effect of the phosphorus environment on the electronic properties from both experimental and theoretical points of view are discussed.
High‐throughput IDCT architecture for high‐efficiency video coding (HEVC)
Authors: Chen Yuan‐Ho , Ko Yi‐Fan
Published: June 2017

This paper presents a hardware design capable of supporting high‐efficiency video coding inverse discrete cosine transform (IDCT) with a 32×32 transform unit size, using a single 1‐D IDCT core with transpose memory to reduce costs. The proposed 1‐D IDCT core employs 16 computation paths for high throughput and is implemented using distributed arithmetic to facilitate the sharing of hardware resources. The proposed 1‐D IDCT is capable of calculating 1‐D and 2‐D data simultaneously along 32 parallel paths. When implemented using Taiwan Semiconductor Manufacturing Company (TSMC) 40‐nm CMOS technology, the proposed 2‐D transform core provides throughput of 6.4 gigapixels/s with a gate count of 335 k. The results show that a superior hardware efficiency can be achieved in the proposed 32‐point IDCT core compared with the existing works. Copyright © 2017 John Wiley & Sons, Ltd.
Multiparametric Whole Blood Dissection: A one‐shot comprehensive picture of the human hematopoietic system
Authors: Basso‐Ricci Luca , Scala Serena , Milani Raffaella , Migliavacca Maddalena , Rovelli Attilio , Bernardo Maria Ester , Ciceri Fabio , Aiuti Alessandro , Biasco Luca
Published: June 2017

Human hematopoiesis is a complex and dynamic system where morphologically and functionally diverse mature cell types are generated and maintained throughout life by bone marrow (BM) Hematopoietic Stem/Progenitor Cells (HSPC). Congenital and acquired hematopoietic disorders are often diagnosed through the detection of aberrant frequency or composition of hematopoietic cell populations. We here describe a novel protocol, called “Whole Blood Dissection” (WBD), capable of analyzing in a single test‐tube, hematopoietic progenitors and all major mature cell lineages composing either BM or peripheral blood (PB) through a multiparametric flow‐cytometry analysis. WBD allows unambiguously identifying in the same tube up to 23 different blood cell types including HSPC subtypes and all the major myeloid and lymphoid lineage compartments at different stages of maturation, through a combination of 17 surface and 1 viability cell markers. We assessed the efficacy of WBD by analyzing BM and PB samples from adult (n = 8) and pediatric (n = 9) healthy donors highlighting age‐related shift in cell composition. We also tested the capability of WBD on detecting aberrant hematopoietic cell composition in clinical samples of patients with primary immunodeficiency or leukemia unveiling expected and novel hematopoietic unbalances. Overall, WBD allows unambiguously identifying >99% of the cell subpopulations composing a blood sample in a reproducible, standardized, cost‐, and time‐efficient manner. This tool has a wide range of potential pre‐clinical and clinical applications going from the characterization of hematopoietic disorders to the monitoring of hematopoietic reconstitution in patients after transplant or gene therapy. © 2017 The Authors. Cytometry Part A Published by Wiley Periodicals, Inc. on behalf of ISAC.
Metabolism of novel opioid agonists U‐47700 and U‐49900 using human liver microsomes with confirmation in authentic urine specimens from drug users
Authors: Krotulski Alex J. , Mohr Amanda L. A. , Papsun Donna M. , Logan Barry K.
Published: June 2017

Recently, the number of adverse events, including death, involving novel opioids has continued to increase, providing additional and sustained challenges for forensic and medical communities. Identification of emerging novel opioids can be challenging, compounded by detection windows and unknown metabolic profiles. In this study, human liver microsomes were used for the generation of in vitro metabolic profiles of U‐47700 and U‐49900. Generated metabolites were analyzed via a SCIEX TripleTOF® 5600+ quadrupole time‐of‐flight mass spectrometer and resulting data files were processing using MetabolitePilot™. Characterized metabolites were verified in vivo by analysis of authentic human urine specimens collected after analytically confirmed cases of overdose involving U‐47700 or U‐49900. In total, four metabolites were identified and present in urine specimens for U‐47700, and five metabolites for U‐49900. N‐Desmethyl‐U‐47700 was determined to be the primary metabolite of U‐47700. Parent U‐47700 was identified in all urine specimens. N‐Desmethyl‐U‐47700 and N,N‐didesmethyl‐U‐47700 were structurally confirmed for the first time during this study following acquisition of standard reference material. N‐Desethyl‐U‐49900 was determined to be the primary metabolite of U‐49900 following microsomal incubations, while N,N‐didesethyl‐N‐desmethyl‐U‐49900 was the most abundant in a urine specimen. Similarities in metabolic transformation were identified between U‐47700 and U‐49900, resulting in a common metabolite and isomeric species. These phenomena should be considered in cases involving U‐47700 or U‐49900. This study is the first to map the metabolic profiles of U‐47700 and U‐49900 using human liver microsomes, as well as the first to report any literature involving U‐49900 and analysis of case specimens.
Morphological and molecular evolution of the ultimobranchial gland of nonmammalian vertebrates, with special reference to the chicken C cells
Authors: Kameda Yoko
Published: June 2017

This review summarizes the current understanding of the nonmammalian ultimobranchial gland from morphological and molecular perspectives. Ultimobranchial anlage of all animal species develops from the last pharyngeal pouch. The genes involved in the development of pharyngeal pouches are well conserved across vertebrates. The ultimobranchial anlage of nonmammalian vertebrates and monotremes does not merge with the thyroid, remaining as an independent organ throughout adulthood. Although C cells of all animal species secrete calcitonin, the shape, cellular components and location of the ultimobranchial gland vary from species to species. Avian ultimobranchial gland is unique in several phylogenic aspects; the organ is located between the vagus and recurrent laryngeal nerves at the upper thorax and is densely innervated by branches emanating from them. In chick embryos, TuJ1‐, HNK‐1‐, and PGP 9.5‐immunoreactive cells that originate from the distal vagal (nodose) ganglion, colonize the ultimobranchial anlage and differentiate into C cells; neuronal cells give rise to C cells. Like C cells of mammals, the cells of fishes, amphibians, reptiles, and also a subset of C cells of birds, appear to be derived from the endodermal epithelium forming ultimobranchial anlage. Thus, the avian ultimobranchial C cells may have dual origins, neural progenitors and endodermal epithelium. Developmental Dynamics 246:719–739, 2017. © 2017 Wiley Periodicals, Inc.
Evolutionary response to global change: Climate and land use interact to shape color polymorphism in a woodland salamander
Authors: Cosentino Bradley J. , Moore Jean‐David , Karraker Nancy E. , Ouellet Martin , Gibbs James P.
Published: June 2017

Evolutionary change has been demonstrated to occur rapidly in human‐modified systems, yet understanding how multiple components of global change interact to affect adaptive evolution remains a critical knowledge gap. Climate change is predicted to impose directional selection on traits to reduce thermal stress, but the strength of directional selection may be mediated by changes in the thermal environment driven by land use. We examined how regional climatic conditions and land use interact to affect genetically based color polymorphism in the eastern red‐backed salamander (Plethodon cinereus). P. cinereus is a woodland salamander with two primary discrete color morphs (striped, unstriped) that have been associated with macroclimatic conditions. Striped individuals are most common in colder regions, but morph frequencies can be variable within climate zones. We used path analysis to analyze morph frequencies among 238,591 individual salamanders across 1,170 sites in North America. Frequency of striped individuals was positively related to forest cover in populations occurring in warmer regions (>7°C annually), a relationship that was weak to nonexistent in populations located in colder regions (≤7°C annually). Our results suggest that directional selection imposed by climate warming at a regional scale may be amplified by forest loss and suppressed by forest persistence, with a mediating effect of land use that varies geographically. Our work highlights how the complex interaction of selection pressures imposed by different components of global change may lead to divergent evolutionary trajectories among populations.
Perspective of garlic processing wastes as low‐cost substrates for production of high‐added value products: A review
Authors: Kallel Fatma , Ellouz Chaabouni Semia
Published: June 2017

The large amounts of solid biological wastes produced in industrial activities increases production costs. As a consequence, it is common to develop strategies to reuse these wastes by transforming them for usage in other processes/industries. This paper is the first paper examining the use of garlic by‐products as bioresource. This study delineates firstly the physicochemical and biological characterization of garlic by‐products such as straw and peels, secondly provides the various applications of garlic by‐products in different domains and unveils their potential for industrial applications such as feed alimentation, soil amendment and bioenergy. They presented potential exploitation as bioadsorbents for wastewater treatment. Finally, these by‐products could be exploited for further industrial purposes such as extraction of bioactive components and extraction of functional ingredients and production of phenolic compounds and biofuel such as biogas and bio‐oil. © 2017 American Institute of Chemical Engineers Environ Prog, 36: 1765–1777, 2017
Performance‐based grouping methods of bridge classes for regional seismic risk assessment: Application of ANOVA, ANCOVA, and non‐parametric approaches
Authors: Mangalathu Sujith , Jeon Jong‐Su , Padgett Jamie E. , DesRoches Reginald
Published: June 2017

One of the key tasks to enable a regional risk assessment is to group structures with similar seismic performances and generate fragility curves representative of the grouped structures. The grouping has been traditionally performed based primarily on engineering judgment and prior experience. This paper (i) presents an overview of various statistical techniques such as analysis of variance, analysis of covariance, and Kruskal–Wallis test for grouping the bridges of similar performance; (ii) compares the groupings that emerge from the various grouping techniques; and (iii) identifies the method that has more statistical power in creating bridge sub‐classes of distinct structural performance. The grouping is achieved by comparing the structural responses of bridge classes obtained from the non‐linear time history analysis of bridges. The relative merits of these grouping techniques are discussed with the case study of box‐girder bridges in California. Copyright © 2017 John Wiley & Sons, Ltd.
Risk assessment of imidacloprid use in forest settings on the aquatic macroinvertebrate community
Authors: Benton Elizabeth P. , Grant Jerome F. , Nichols Rebecca J. , Webster R. Jesse , Schwartz John S. , Bailey Joseph K.
Published: June 2017

The isolated effects of a single insecticide can be difficult to assess in natural settings because of the presence of numerous pollutants in many watersheds. Imidacloprid use for suppressing hemlock woolly adelgid, Adelges tsugae (Annand) (Hemiptera: Adelgidae), in forests offers a rare opportunity to assess potential impacts on aquatic macroinvertebrates in relatively pristine landscapes. Aquatic macroinvertebrate communities were assessed in 9 streams in Great Smoky Mountains National Park (southern Appalachian Mountains, USA). The streams flow through hemlock conservation areas where imidacloprid soil drench treatments were applied for hemlock woolly adelgid suppression. Sites were located upstream and downstream of the imidacloprid treatments. Baseline species presence data (pre-imidacloprid treatment) were available from previous sample collections at downstream sites. Downstream and upstream sites did not vary in numerous community measures. Although comparisons of paired upstream and downstream sites showed differences in diversity in 7 streams, higher diversity was found more often in downstream sites. Macroinvertebrate functional feeding groups and life habits were similar between downstream and upstream sites. Downstream and baseline stream samples were similar. While some functional feeding group and life habit species richness categories varied, variations did not indicate poorer quality downstream communities. Imidacloprid treatments applied according to US Environmental Protection Agency federal restrictions did not result in negative effects to aquatic macroinvertebrate communities, which indicates that risks of imidacloprid use in forest settings are low. Environ Toxicol Chem 2017;36:3108–3119. © 2017 SETAC