bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic Combinatorial Chemistry: A New Methodology Comes of Age
Authors: Frei Priska , Hevey Rachel , Ernst Beat
Published: September 2018

Dynamic combinatorial chemistry (DCC) has repeatedly proven to be an effective approach to generate directed ligand libraries for macromolecular targets. In the absence of an external stimulus, a dynamic library forms from reversibly reacting building blocks and reaches a stable thermodynamic equilibrium. However, upon addition of a macromolecular host which can bind and stabilize certain components of the library, the equilibrium composition changes and induces an evolution‐like selection and enrichment of high‐affinity ligands. A valuable application of this so‐called target‐directed DCC (tdDCC) is the identification of potent ligands for pharmacologically relevant targets. Over time, the term tdDCC has been applied to describe a number of different experimental setups, leading to some ambiguity concerning its definition. This article systematically classifies known procedures for tdDCC and related approaches, with a special focus on the methods used for analysis and evaluation of experiments.
High Catalytic Activity of C60Pdn Encapsulated in Metal–Organic Framework UiO‐67, for Tandem Hydrogenation Reaction
Authors: Zheng Deng‐Yue , Zhou Xue‐Meng , Mutyala Suresh , Huang Xiao‐Chun
Published: September 2018

Metal nanoparticles (NPs) stabilized by MOFs are very promising for catalysis, whereas introduction of C60 into MOFs has been very rarely used, and there was no report for their cooperative catalysis in organic syntheses. In this work, C60@UiO‐67 was synthesized by a one‐pot method, so that C60 is uniformly distributed on UiO‐67 in molecular form. Pd NPs coordinating with C60 have been successfully embedded into the framework. The obtained multifunctional C60Pdn@UiO‐67 catalyst exhibits remarkable synergistic catalytic activity in cascade reactions under mild conditions, where UiO‐67 affords Lewis acidity and C60Pdn offers higher hydrogenation activity relative to solely Pd NPs.
Bis‐Naphthalene Cleft with Aggregation‐Induced Emission Properties through Lone‐Pair⋅⋅⋅π Interactions
Authors: Wang Li‐Li , Zhou Hang , Yang Ti‐Long , Ke Hua , Tu Yi‐Kuan , Yao Huan , Jiang Wei
Published: September 2018

A rigid molecular cleft shows unique aggregation‐induced emission (AIE) by restricting the motion of aldehyde through intermolecular lone pair⋅⋅⋅π interactions, which are tuned by side chains. This AIE luminogen was demonstrated to work as a fluorescent sensor for aniline and an optical chirality sensor for chiral amine.
Actinide‐Based Porphyrinic MOF as a Dehydrogenation Catalyst
Authors: Hu Kong‐Qiu , Huang Zhi‐Wei , Zhang Zhi‐Hui , Mei Lei , Qian Bing‐Bing , Yu Ji‐Pan , Chai Zhi‐Fang , Shi Wei‐Qun
Published: September 2018

Uranyl–organic frameworks (UOFs) have recently been the object of many research endeavors due to the unique coordination mode of uranyl ions and their attractive physicochemical properties. Here, a new (3,4)‐connected UOF (U‐IHEP‐4) assembled from uranyl and porphyrin ligand tetrakis(4‐carboxyphenyl)porphyrin (H4TCPP) is reported, which represents the first case of actinide porphyrinic MOFs. Adsorption experiments in DMF solution demonstrated that U‐IHEP‐4 selectively adsorbs positively charged dyes, which is in line with its negatively charged framework and large pore volume ratio (90 %). Remarkably, U‐IHEP‐4 exhibited high catalytic activity for the dehydrogenation of N‐heterocycles to synthesize the corresponding aromatic heterocycles and it can be used as an efficient heterogeneous catalyst.
Plasma Catalytical Reactors for Atmospheric Gas Conversions
Authors: Nitsche Tim , Unger Christoph , Weidner Eckhard
Published: September 2018

Plasma catalysis, the combination of non‐thermal plasma and catalyst, is a promising approach for optimizing chemical conversions as the removal of gas trace components. The various technological opportunities for the generation of atmospheric non‐thermal plasma combined with the variety of usable catalysts result in a huge amount of different experimental approaches. The aim of the presented review is to give an overview of plasma catalytic reactor designs currently discussed in literature as well as to point out technological differences and potential for up‐scaling.
Methodology for the Evaluation of CO2‐Based Syntheses by Coupling Steel Industry with Chemical Industry
Authors: Stießel Sebastian , Berger Angelina , Fernández Sanchis Elvira María , Ziegmann Markus
Published: September 2018

Carbon‐intensive sectors like steel or chemical industry need to reduce their emissions and their dependence on fossil feedstocks to help reaching climate goals. Coupling previously independent sectors by carbon capture and utilization and power‐to‐X technologies are promising concepts. Within the Carbon2Chem® project, a generic approach for the evaluation of various plant configurations with respect to future market and energy scenarios is presented. Economically and ecologically favorable concepts for the recycling of steel mill gases to valuable products, especially methanol, by integrating high amounts of renewable energies are identified for the year 2030.
Dynamic Water Electrolysis in Cross‐Sectoral Processes
Authors: Seibel Christopher , Kuhlmann Jens‐Wilhelm
Published: September 2018

A simulation‐based optimization for water electrolysis is performed to identify preferable scenarios with respect to economic as well as ecological aspects. As the electrolyzer interacts with the wholesale electricity market and with the production of bulk chemicals implying each specific dynamic characteristics, various and partly counteracting relevant impulses result in a multi‐objective optimization approach. In order to demonstrate the capability of alkaline electrolytic systems to meet these dynamic demands, a 20‐kW lab‐scale electrolyzer and a 2‐MW large‐scale electrolyzer are commissioned and tested.
Computational aeroacoustics to identify sound sources in the generation of sibilant /s/
Authors: Pont Arnau , Guasch Oriol , Baiges Joan , Codina Ramon , van Hirtum Annemie
Published: September 2018

A sibilant fricative /s/ is generated when the turbulent jet in the narrow channel between the tongue blade and the hard palate is deflected downwards through the space between the upper and lower incisors and then impinges the space between the lower incisors and the lower lip. The flow eddies in that region become a source of direct aerodynamic sound, which is also diffracted by the speech articulators and radiated outwards. The numerical simulation of these phenomena is complex. The spectrum of an /s/ typically peaks between 4 and 10 kHz, which implies that very fine computational meshes are needed to capture the eddies producing such high frequencies. In this work, a large‐scale computation of the aeroacoustics of /s/ has been performed for a realistic vocal tract geometry, resorting to two different acoustic analogies. A stabilized finite element method that acts as a large eddy simulation model has been adopted to solve the flow dynamics. Also, a numerical strategy has been implemented that allows the determination, in a single computational run, of the separate contribution of the sound diffracted by the upper incisors from the overall radiated sound. Results are presented for points located close to the lip opening showing the relative influence of the upper teeth depending on frequency.
Recreating the Munsell crayon color spectrum
Authors: Robinson Adi , Fairchild Mark D.
Published: September 2018

Munsell crayons were discontinued in 1944 but the concept of the Munsell color wheel is still a part of the Crayola Crayon Company to this day. We performed a set of measurements using an original set of Munsell crayons to see if they still hold their specification and how they compare to the entire available spectrum of the Crayola crayon family. The crayons were melted and measured using a spectrophotometer and the resulting spectra were compared using CIEDE2000. Using a conversion table, the CIELAB coordinates of each crayon were converted to Munsell specification and compared. The results of the experiment show that some Munsell crayons have a similar Crayola counterpart. It also showed that most of the Munsell crayons were not close to their original specifications.
Expression of Recombinant Genes in the Yeast Pichia pastoris
Authors: Cregg James M. , Tolstorukov Ilya , Kusari Anasua , Sunga Anthony Jay , Madden Knut , Chappell Thomas
Published: September 2018

The synthesis of specific recombinant proteins using single‐celled organisms from bacteria to mammalian tissue culture cells has become a major source of biopharmaceutical products for the industry and a source of a wide variety of proteins for academic research. A range of organisms are utilized for this purpose. One of the newest and most promising of these is the yeast Pichia pastoris. This article provides detailed basic protocols for the expression of heterologous genes and the synthesis of recombinant proteins utilizing this yeast. Specifically provided are protocols for the insertion of foreign vector DNAs into the yeast by electroporation, amplification of vector sequences by the post‐translational vector amplification (PTVA) method, and growth and expression of foreign genes in shake flask cultures. © 2018 by John Wiley & Sons, Inc.
Homo‐ and Heterodimeric Dyes for Dye‐Sensitized Solar Cells: Panchromatic Light Absorption and Modulated Open Circuit Potential
Authors: Sil Manik Chandra , Sudhakar Vediappan , Singh Ambarish Kumar , Kavungathodi Munavvar Fairoos Mele , Nithyanandhan Jayaraj
Published: September 2018

The design of dyes for panchromatic light absorption has attracted much attention in the field of dye‐sensitized solar cells (DSSCs). An approach to enhance panchromatic light absorption utilizes mixtures of complementary light‐absorbing dyes as well as dyes with specific anchoring groups that facilitate interfacial charge transfer with TiO2. Dipole‐dipole interactions between the dye molecules on the surface broaden the spectrum, which results in decreased DSSC device performance. However, controlled aggregation of dyes results in broadening the spectral profile along with enhanced photocurrent generation. To control the dye‐dye interaction, dimeric dyes with different dipole lengths D1‐Dsq, Dsq‐Dsqwere systematically designed and synthesized. The photophysical and electrochemical properties were evaluated and the EHOMO and ELUMO levels were determined; these energy levels determines the electron injection from ELUMO of the dye to ECB of TiO2 and regeneration of oxidized dye by the electrolyte, respectively. The absorption spectra of Dsq‐Dsq, D1‐Dsq were broadened in solution compared to model dye Dsq; this indicates that the dye‐dye interaction is prominent in solution. In D1‐Dsq excitation energy transfer between photoexcited D1 and Dsq was explained by using Förster resonance energy transfer (FRET). The homodimeric dye showed a device performace of 2.8 % (Voc 0.607, Jsc 6.62 mA/cm2, ff 69.3 %),whereas the heterodimeric dye D1‐Dsq showed a device performance of 3.9 % (Voc 0.652 V, Jsc 8.89 mA/cm2, ff 68.8 %). The increased photocurrent for D1‐Dsqis due to the panchromatic IPCE response compared to Dsq‐Dsq. The increased Vocis due to the effective passivation of the TiO2 surface by the spirolinker, and the effective dipole moment that shifts the conduction band on TiO2. Hence, the open circuit potential, Voc, for the devices prepared from Dsq, D1‐Dsq and Dsq‐Dsqwere systematically modulated by controlling the intermolecular π‐π and intramolecular dipole‐dipole interactions of the dimeric dyes.
Driving cognitions, rumination, and posttraumatic stress disorder in road traffic accidents survivors
Authors: Măirean Cornelia
Published: September 2018

This study evaluated the relationships between driving cognitions (i.e., panic‐related cognitions, accident‐related cognitions, and social‐related cognitions), rumination, and posttraumatic stress disorder (PTSD) symptoms in a sample of road traffic accidents (RTAs) survivors. We also investigated the indirect effect of driving cognitions on PTSD symptoms through rumination. The sample included 633 drivers (62% were men; Mage = 36.09; standard deviation [SD] = 11.42 years). The participants completed scales measuring driving cognitions, rumination, and PTSD symptoms, as well as providing their demographic information. The results showed that all three types of driving cognitions assessed in the present study and rumination were significantly positively associated with PTSD symptoms. Furthermore, rumination mediated the relation between social‐related cognitions and PTSD symptoms. The implications for PTSD treatment and future research are discussed.
Patient‐Focused Drug Development Methods for Benefit–Risk Assessments: A Case Study Using a Discrete Choice Experiment for Antiepileptic Drugs
Authors: Holmes Emily A.F. , Plumpton Catrin , Baker Gus A. , Jacoby Ann , Ring Adele , Williamson Paula , Marson Anthony , Hughes Dyfrig A.
Published: September 2018

Regulatory decisions may be enhanced by incorporating patient preferences for drug benefit and harms. This study demonstrates a method of weighting clinical evidence by patients’ benefit–risk preferences. Preference weights, derived from discrete choice experiments, were applied to clinical trial data to estimate the expected utility of alternative drugs. In a case study, the rank ordering of antiepileptic drugs (AEDs), as indicated from clinical studies, was compared with ordering based on weighting clinical evidence by patients’ preferences. A statistically significant change in rank ordering of AEDs was observed for women of childbearing potential who were prescribed monotherapy for generalized or unclassified epilepsy. Rank ordering inferred from trial data, valproate > topiramate > lamotrigine, was reversed. Modeling the expected utility of drugs might address the need to use more systematic, methodologically sound approaches to collect patient input that can further inform regulatory decision making.
Inference of the electron temperature in inertial confinement fusion implosions from the hard X‐ray spectral continuum
Authors: Kagan Grigory , Landen O.L. , Svyatskiy D. , Sio H. , Kabadi N.V. , Simpson R.A. , Gatu Johnson M. , Frenje J.A. , Petrasso R.D. , Shah R.C. , Joshi T.R. , Hakel P. , Weber T.E. , Rinderknecht H.G. , Thorn D. , Schneider M. , Bradley D. , Kilkenny J.
Published: September 2018

Using the free‐free continuum self‐emission spectrum at photon energies above 15 keV is one of the most promising concepts for assessing the electron temperature in inertial confinement fusion (ICF) experiments. However, these photons are due to suprathermal electrons whose mean free path is much larger than the thermal one, making their distribution deviate from Maxwellian in a finite‐size hotspot. The first study of the free‐free X‐ray emission from an ICF implosion is conducted, accounting for the kinetic modifications to the electron distribution. These modifications are found to result in qualitatively new features in the hard X‐ray spectral continuum. Inference of the electron temperature as if the emitting electrons are Maxwellian is shown to give a lower value than the actual one.
CCBE1 is required for coronary vessel development and proper coronary artery stem formation in the mouse heart
Authors: Bonet Fernando , Pereira Paulo N. G. , Bover Oriol , Marques Sara , Inácio José M. , Belo José A.
Published: September 2018

Background: Proper coronary vasculature development is essential for late‐embryonic and adult heart function. The developmental regulation of coronary embryogenesis is complex and includes the coordinated activity of multiple signaling pathways. CCBE1 plays an important role during lymphangiogenesis, enhancing VEGF‐C signaling, which is also required for coronary vasculature formation. However, whether CCBE1 plays a similar role during coronary vasculature development is still unknown. Here, we investigate the coronary vasculature development in Ccbe1 mutant embryos. Results: We show that Ccbe1 is expressed in the epicardium, like Vegf‐c, and also in the sinus venosus (SV) at the stages of its contribution to coronary vasculature formation. We also report that absence of CCBE1 in cardiac tissue inhibited coronary growth that sprouts from the SV endocardium at the dorsal cardiac wall. This disruption of coronary formation correlates with abnormal processing of VEGF‐C propeptides, suggesting VEGF‐C–dependent signaling alteration. Moreover, Ccbe1 loss‐of‐function leads to the development of defective dorsal and ventral intramyocardial vessels. We also demonstrate that Ccbe1 mutants display delayed and mispatterned coronary artery (CA) stem formation. Conclusions: CCBE1 is essential for coronary vessel formation, independent of their embryonic origin, and is also necessary for peritruncal vessel growth and proper CA stem patterning. Developmental Dynamics 247:1135‐1145, 2018. © 2018 Wiley Periodicals, Inc.
Advances in mass spectrometry‐based glycoproteomics
Authors: Yu Aiying , Zhao Jingfu , Peng Wenjing , Banazadeh Alireza , Williamson Seth D. , Goli Mona , Huang Yifan , Mechref Yehia
Published: September 2018

Protein glycosylation, an important PTM, plays an essential role in a wide range of biological processes such as immune response, intercellular signaling, inflammation, and host–pathogen interaction. Aberrant glycosylation has been correlated with various diseases. However, studying protein glycosylation remains challenging because of low abundance, microheterogeneities of glycosylation sites, and poor ionization efficiency of glycopeptides. Therefore, the development of sensitive and accurate approaches to characterize protein glycosylation is crucial. The identification and characterization of protein glycosylation by MS is referred to as the field of glycoproteomics. Methods such as enrichment, metabolic labeling, and derivatization of glycopeptides in conjunction with different MS techniques and bioinformatics tools, have been developed to achieve an unequivocal quantitative and qualitative characterization of glycoproteins. This review summarizes the recent developments in the field of glycoproteomics over the past 6 years (2012 to 2018).
Effect of trace chloride on the char formation and flame retardancy of the LLDPE filled with NiAl‐layered double hydroxides
Authors: Wang Hongchao , Tan Shengnan , Song Rongjun
Published: September 2018

Layered double hydroxides (LDHs) have received intensive attentions for the potential as flame retardants of polyolefin. In the work, trace amounts of chloride were investigated for their synergistic effects on the char formation and flame retardancy of the linear low‐density polyethylene (LLDPE) filled with NiAl‐LDHs. Results showed that 0.5 wt% of NH4Cl incorporation enabled the char yield of 20%LDH/LLDPE (20 wt% of NiAl‐LDH) increase from 10.4% to 49.6%. Other chlorides likewise offered significant increase in the char yield of 20%LDH/LLDPE. With the flame‐retardant measurements of cone calorimeter and limiting oxygen index device, it is revealed that the flame retardancy of LLDPE filled with NiAl‐LDHs could be greatly improved when trace amounts of NH4Cl were further introduced. Thermal stability analysis illustrated that the presence of NiAl‐LDHs or NH4Cl all had positive effects on the thermal stability of LLDPE, in which the chlorides influenced the LLDPE thermal stability via direct participation in the degradation of LLDPE. The synergetic mechanism analysis reveals that the introduction of chloride enabled the LLDPE decomposed products have more tendency to grow carbon nanotubes with the presence of NiAl‐LDH catalysts. Finally, the mechanical properties of LLDPE filled with NiAl‐LDHs and NH4Cl were also investigated.
Point forecasting of intraday volume using Bayesian autoregressive conditional volume models
Authors: Huptas Roman
Published: September 2018

In this paper, we apply Bayesian inference to model and forecast intraday trading volume, using autoregressive conditional volume (ACV) models, and we evaluate the quality of volume point forecasts. In the empirical application, we focus on the analysis of both in‐ and out‐of‐sample performance of Bayesian ACV models estimated for 2‐minute trading volume data for stocks quoted on the Warsaw Stock Exchange in Poland. We calculate two types of point forecasts, using either expected values or medians of predictive distributions. We conclude that, in general, all considered models generate significantly biased forecasts. We also observe that the considered models significantly outperform such benchmarks as the naïve or rolling means forecasts. Moreover, in terms of root mean squared forecast errors, point predictions obtained within the ACV model with exponential distribution emerge superior compared to those calculated in structures with more general innovation distributions, although in many cases this characteristic turns out to be statistically insignificant. On the other hand, when comparing mean absolute forecast errors, the median forecasts obtained within the ACV models with Burr and generalized gamma distribution are found to be statistically better than other forecasts.
Mutational and cytogenetic analyses of 188 CLL patients with trisomy 12: A retrospective study from the French Innovative Leukemia Organization (FILO) working group
Authors: Roos‐Weil Damien , Nguyen‐Khac Florence , Chevret Sylvie , Touzeau Cyrille , Roux Clémence , Lejeune Julie , Cosson Adrien , Mathis Stéphanie , Feugier Pierre , Leprêtre Stéphane , Béné Marie‐Christine , Baron Marine , Raynaud Sophie , Struski Stéphanie , Eclache Virginie , Sutton Laurent , Lesty Claude , Merle‐Béral Hélène , Cymbalista Florence , Ysebaert Loïc , Davi Frédéric , Leblond Véronique ,   on behalf of the FILO working group
Published: September 2018

Trisomy 12 (tri12) is the second most frequent chromosomal aberration (15%‐20%) in chronic lymphocytic leukemia (CLL). Tri12 confers an intermediate prognosis but is a heterogeneous entity. We examined whether additional mutational or chromosomal alterations might impact tri12 patient outcomes. This retrospective study, carried out by the French Innovative Leukemia Organization, included 188 tri12 patients with comprehensive information on immunoglobulin heavy chain (IGHV) gene status, karyotypic/FISH abnormalities, and NOTCH1, TP53, SF3B1, and MYD88 mutations. The main cytogenetic abnormalities associated with tri12 were del(13q) (25%), additional trisomies (14%) (including tri19 (10%) and tri18 (4%)), 14q32 translocations (10%), del(17p) (6.5%), del(14q) (4%), and del(11q) (4%). Unmutated (UM) IGHV, NOTCH1, and TP53, mutations were identified in respectively 66%, 25%, and 8.5% of cases. Multivariate analyses showed that additional trisomies (HR = 0.43, 95% CI = 0.23‐0.78, P = .01) were associated with a significantly longer time to first treatment in Binet stage A patients and with a lower risk of relapse (HR = 0.37, 95% CI = 0.15‐0.9, P = .03) in the overall tri12 population. Binet stage B/C, TP53 disruption, and UM IGHV status were associated with a shorter time to next treatment, while Binet stage B/C (HR = 4, 95% CI = 1.6‐4.9, P = .002) and TP53 disruption (HR = 5, 95% CI = 1.94‐12.66, P = .001) conferred shorter overall survival in multivariate comparisons. These data indicate that additional cytogenetic and mutational abnormalities, and particularly additional trisomies, IGHV status, and TP53 disruption, influence tri12 patient outcomes and could improve risk stratification in this population.
Improved cytogenetic characterization and risk stratification of pediatric acute lymphoblastic leukemia using single nucleotide polymorphism array analysis: A single center experience of 296 cases
Authors: Olsson Linda , Lundin‐Ström Kristina B. , Castor Anders , Behrendtz Mikael , Biloglav Andrea , Norén‐Nyström Ulrika , Paulsson Kajsa , Johansson Bertil
Published: September 2018

Single nucleotide polymorphism array (SNP‐A) analyses are increasingly being introduced in routine genetic diagnostics of acute lymphoblastic leukemia (ALL). Despite this, only few studies that have compared the diagnostic value of SNP‐A with conventional chromosome banding have been published. We here report such a comparison of 296 ALL cases, the largest series to date. Only genomic imbalances >5 Mb and microdeletions targeting the BTG1, CDKN2A/B, EBF1, ERG, ETV6, IKZF1, PAX5, and RB1 genes and the pseudoautosomal region 1 (PAR1) were ascertained, in agreement with recent guidelines. Of 36 T‐cell ALL cases, the karyotypes of 24 cases (67%) were revised by SNP‐A analyses that either revealed additional imbalances >5 Mb or better characterized the changes found by G‐banding. Of 260 B‐cell precursor (BCP) ALL cases, SNP‐A analyses identified additional copy number alterations, including the above‐mentioned microdeletions, or better characterized the imbalances found by G‐banding in 236 (91%) cases. Furthermore, the cytogenetic subtype classification of 41/260 (16%) BCP ALL cases was revised based on the SNP‐A findings. Of the subtype revisions, 12/41 (29%) had clinical implications as regards risk stratifying cytogenetic groups or genotype‐specific minimal residual disease stratification. We conclude that SNP‐A analyses dramatically improve the cytogenetic characterization of both T‐cell and BCP ALL and also provide important information pertinent to risk stratification of BCP ALL.
Telomere length, telomerase reverse transcriptase promoter mutations, and melanoma risk
Authors: Rachakonda Sivaramakrishna , Kong Haiying , Srinivas Nalini , Garcia‐Casado Zaida , Requena Celia , Fallah Mahdi , Heidenreich Barbara , Planelles Dolores , Traves Victor , Schadendorf Dirk , Nagore Eduardo , Kumar Rajiv
Published: September 2018

Telomere repeats at chromosomal ends, critical for genomic integrity, undergo age‐dependent attrition and telomere length has been associated with different disorders including cancers. In this study, based on 1469 patients and 1158 healthy controls, we show a statistically significant (P = 6 × 10−10) association between increased telomere length and melanoma risk. Mendelian randomization, using 5 telomere length‐associated polymorphisms, ruled out confounding factors or reverse causality and showed association between increased telomere length and melanoma risk with odds ratio of 2.66 (95% confidence interval: 2.07‐3.25). Age‐dependent telomere attrition was faster in melanoma cases than controls (P = .01). The carriers of a highly penetrant germline ‐57A>C TERT promoter mutation, in a previously reported melanoma family, had longer telomeres than the noncarriers. The mutation causes increased TERT and telomerase levels through creation of a binding motif for E‐twenty six (ETS) transcription factors and the carriers develop melanoma with an early age of onset and rapid progression to metastasis. In analogy, we hypothesize that increased telomere length in melanoma patients reflects stochastic increased telomerase levels due to common genetic variation. Paradoxically, we observed shorter telomeres (P = 1 × 10−5) in primary tumors from unrelated melanoma patients with (121) than without (170) somatic TERT promoter mutations that similar to the germline mutation, also create binding motifs for ETS transcription factors. However, the age‐dependent telomere attrition was faster in tumors with the TERT promoter mutations than in those without such mutations. Besides a robust association between increased telomere length and risk, our data show a perturbed telomere homeostasis in melanoma.
The influence of marital status on the survival of patients with operable gastrointestinal stromal tumor: A SEER‐based study
Authors: Chen Mo , Wang Xuan , Wei Ran , Wang Zheng
Published: September 2018

Background

Marital status has been demonstrated as a predictive factor for prognosis in diverse malignancies, but its role in the survival of gastrointestinal stromal tumor (GIST) remains unclear.

Material and methods

This study was aimed to investigate the impact of marital status on the overall survival (OS) and cancer‐specific survival (CSS) of operable GIST cases, by using data from Surveillance, Epidemiology, and End Results (SEER) database. In total, 6582 GIST patients between 1973 and 2013 were identified from SEER database.

Results

Univariate and multivariate analyses demonstrated the marital status as an independent predictive factor for survival. Married group had better 5‐year OS and CSS than unmarried group (OS: 79.2% vs 71.3%, P < .001; CSS: 88.9% vs 84.8%, P < .001). And compared to married, divorced/separated, and single group, widowed group had the lowest 5‐year OS and CSS (61.3% and 82.2%). Further subgroup analyses validated the relationship between marital status and survival among all SEER stages and different age groups. And additional sensitivity analyses according to other clinicopathological features confirmed that married cases had higher survival rate than unmarried cases.

Conclusion

In conclusion, marriage could be a protective prognostic factor for survival, and widowed patients had a higher risk of death.
Ligand‐activated interaction of PPARδ with c‐Myc governs the tumorigenicity of breast cancer
Authors: Ham Sun Ah , Kim Eunsu , Yoo Taesik , Lee Won Jin , Youn Ju Ho , Choi Mi‐Jung , Han Sung Gu , Lee Chi‐Ho , Paek Kyung Shin , Hwang Jung Seok , Seo Han Geuk
Published: September 2018

Peroxisome proliferator‐activated receptor (PPAR) δ is a promising therapeutic target in metabolic and inflammatory disorders. However, its role in oncogenesis is controversial, and its therapeutic potential remains to be determined. In our study, we show that ligand‐activated PPARδ forms a complex with the proto‐oncogene product c‐Myc. The interaction of PPARδ with c‐Myc affected the transcriptional activity of c‐Myc and the expression of its target genes. The PPARδ‐dependent regulation of c‐Myc activity was associated with decreased tumorigenicity in breast cancer cells. Administration of the PPARδ ligand GW501516 inhibited tumor growth in xenograft model mice bearing MDA‐MB‐231 cells stably expressing wild‐type PPARδ, but not those expressing dominant‐negative PPARδ, by interfering with c‐Myc function through protein–protein interaction. Our results indicating that PPARδ forms an antitumorigenic complex with c‐Myc in the presence of ligand suggest a potential role of PPARδ in breast cancer development.
An Ecological View of School Counselor Ratios and Student Academic Outcomes: A National Investigation
Authors: Goodman‐Scott Emily , Sink Christopher A. , Cholewa Blaire E. , Burgess Melanie
Published: September 2018

The effect of student‐to‐school‐counselor ratios on academic outcomes has been widely studied, yet few researchers have taken a multilevel approach. Using the nationally representative High School Longitudinal Study: 2009 dataset, the authors found ratios were significantly associated with student grade point average (GPA) and graduation. Attending a Title I school also was associated with students’ GPA, advanced placement/international baccalaureate credits earned, and postsecondary course taking. The authors discuss implications for advocacy and practice, contextualizing their findings within an ecological framework.
Exploration of Prelicensed Counselors’ Experiences Prioritizing Information for Clinical Supervision
Authors: Cook Ryan M. , Sackett Corrine R.
Published: September 2018

This qualitative study explored prelicensed counselors’ experiences prioritizing information for clinical supervision. Through phenomenological interviews, 7 counselors seeking licensure discussed how they self‐report salient information to their supervisors. Using interpretative phenomenological analysis, the authors identified 3 themes: (a) learned to maximize supervision based on structure of supervision, (b) influences on decision to present, and (c) rationale for presenting client case. Implications for counselors and supervisors are discussed.
Remote ischemic conditioning as a cytoprotective strategy in vasculopathies during hyperhomocysteinemia: An emerging research perspective
Authors: Majumder Avisek , Singh Mahavir , George Akash K. , Homme Rubens Petit , Laha Anwesha , Tyagi Suresh C.
Published: September 2018

Higher levels of nonprotein amino acid homocysteine (Hcy), that is, hyperhomocysteinemia (HHcy) (~5% of general population) has been associated with severe vasculopathies in different organs; however, precise molecular mechanism(s) as to how HHcy plays havoc with body’s vascular networks are largely unknown. Interventional modalities have not proven beneficial to counter multifactorial HHcy’s effects on the vascular system. An ancient Indian form of exercise called ‘yoga’ causes transient ischemia as a result of various body postures however the cellular mechanisms are not clear. We discuss a novel perspective wherein we argue that application of remote ischemic conditioning (RIC) could, in fact, deliver anticipated results to patients who are suffering from chronic vascular dysfunction due to HHcy. RIC is the mechanistic phenomenon whereby brief episodes of ischemia‐reperfusion events are applied to distant tissues/organs; that could potentially offer a powerful tool in mitigating chronic lethal ischemia in target organs during HHcy condition via simultaneous reduction of inflammation, oxidative and endoplasmic reticulum stress, extracellular matrix remodeling, fibrosis, and angiogenesis. We opine that during ischemic conditioning our organs cross talk by releasing cellular messengers in the form of exosomes containing messenger RNAs, circular RNAs, anti‐pyroptotic factors, protective cytokines like musclin, transcription factors, small molecules, anti‐inflammatory, antiapoptotic factors, antioxidants, and vasoactive gases. All these could help mobilize the bone marrow–derived stem cells (having tissue healing properties) to target organs. In that context, we argue that RIC could certainly play a savior’s role in an unfortunate ischemic or adverse event in people who have higher levels of the circulating Hcy in their systems.
Identification of novel biomarkers for hepatocellular carcinoma using transcriptome analysis
Authors: Xia Qianlin , Li Zehuan , Zheng Jianghua , Zhang Xu , Di Yang , Ding Jin , Yu Die , Yan Li , Shen Longqiang , Yan Dong , Jia Ning , Chen Weiping , Feng Yanling , Wang Jin
Published: September 2018

Hepatocellular carcinoma (HCC) is the third leading cause of death from cancer in the world. To comprehensively investigate the utility of microRNAs (miRNAs) and protein‐encoding transcripts (messenger RNAs [mRNAs]) in HCC as potential biomarkers for early detection and diagnosis, we exhaustively mined genomic data from three available omics datasets (GEO, Oncomine, and TCGA), analyzed the overlaps among gene expression studies from 920 hepatocellular carcinoma samples and 508 healthy (or adjacent normal) liver tissue samples available from six laboratories, and identified 178 differentially expressed genes (DEGs) associated with HCC. Paired with miRNA and lncRNA data, we identified 23 core genes that were targeted by nine differentially expressed miRNAs and 21 HCC‐specific lncRNAs. We further demonstrated that alterations in these 23 genes were quite frequent, with five genes altered in over 5% of the population. Patients with high levels of YWHAZ, ENAH, and HMGN4 tended to have high‐grade tumors and shorter overall survival, suggesting that these genes could be promising candidate biomarkers for disease and poor prognosis in patients with HCC. Our comprehensive mRNA, miRNA, and lncRNA omics analyses from multiple independent datasets identified robust molecules that may be used as biomarkers for early HCC detection and diagnosis.
NEAT1 induces osteosarcoma development by modulating the miR‐339‐5p/TGF‐β1 pathway
Authors: Zhang Lin , Lu Xiao‐Qing , Zhou Xiao‐Qing , Liu Qin‐Bai , Chen Liang , Cai Feng
Published: September 2018

The long noncoding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) has been recognized as a tumor oncogene involved in the development of multiple cancers. However, the function of NEAT1 and its molecular mechanism in osteosarcoma (OS) remain unclear. First, we detected the NEAT1 expression in OS cell lines by performing quantitative reverse‐transcription polymerase chain reaction. Next, the effects of NEAT1 on OS cell growth, apoptosis, migration, and invasion were tested by lentivirus‐mediated downregulation. We observed that inhibition of NEAT1 restrained OS cell progression greatly. Interestingly, in the last few years, increasing studies have shown that some lncRNAs can act as miRNA sponges and reduce the amount of the same. Here, we found that NEAT1 can modulate OS development via sponging miR‐339‐5p. MiR‐339‐5p was significantly decreased in OS cells, and its overexpression can remarkably repress the OS proliferation. These results indicated that NEAT1 could function as a tumor oncogene in OS by inhibiting miR‐339‐5p in vitro. Then, the following assays validated that transforming growth factor β1 (TGF‐β1) can act as a functional target of miR‐339‐5p in OS cells. Finally, we indicated that NEAT1 could mediate TGF‐β1 expression by competitively sponging miR‐339‐5p. NEAT1 induced OS cell proliferation and cell mobility by binding to miR‐339‐5p and increasing TGF‐β1 in OS. It was demonstrated in our study that lncRNA NEAT1 could impede miR‐339‐5p expression to maintain the expression of TGF‐β1, which led to the development of OS. Our findings implied that the novel identified NEAT1/miR‐339‐5p/TGF‐β1 axis might be a new molecular pathway or therapeutic target for OS diagnosis and treatment.
Tyrosine phosphorylation signaling regulates Ca2+ entry by affecting intracellular pH during human sperm capacitation
Authors: Brukman Nicolás Gastón , Nuñez Sol Yanel , Puga Molina Lis del Carmen , Buffone Mariano Gabriel , Darszon Alberto , Cuasnicu Patricia Sara , Da Ros Vanina Gabriela
Published: September 2018

Capacitation is a mandatory process for the acquisition of mammalian sperm fertilization competence and involves the activation of a complex and still not fully understood system of signaling pathways. Under in vitro conditions, there is an increase in both protein tyrosine phosphorylation (pTyr) and intracellular Ca2+ levels in several species. In human sperm, results from our group revealed that pTyr signaling can be blocked by inhibiting proline‐rich tyrosine kinase 2 (PYK2). Based on the role of PYK2 in other cell types, we investigated whether the PYK2‐dependent pTyr cascade serves as a sensor for Ca
2+ signaling during human sperm capacitation. Flow cytometry studies showed that exposure of sperm to the PYK2 inhibitor
N‐[2‐[[[2‐[(2,3‐dihydro‐2‐oxo‐1
H‐indol‐5‐yl)amino]‐5‐(trifluoromethyl)‐4‐pyrimidinyl]amino]methyl]phenyl]‐
N‐methyl‐methanesulfonamide hydrate (PF431396) produced a significant and concentration‐dependent reduction in intracellular Ca
2+ levels during capacitation. Further studies revealed that PF431396‐treated sperm exhibited a decrease in the activity of CatSper, a key sperm Ca
2+ channel. In addition, time course studies during capacitation in the presence of PF431396 showed a significant and sustained decrease in both intracellular Ca
2+ and pH levels after 2 hr of incubation, temporarily coincident with the activation of PYK2 during capacitation. Interestingly, decreases in Ca
2+ levels and progressive motility caused by PF431396 were reverted by inducing intracellular alkalinization with NH
4Cl, without affecting the pTyr blockage. Altogether, these observations support pTyr as an intracellular sensor for Ca
2+ entry in human sperm through regulation of cytoplasmic pH. These results contribute to a better understanding of the modulation of the polymodal CatSper and signaling pathways involved in human sperm capacitation.
Preparation and evaluation of a polymer–metal–enzyme hybrid nanowire for the immobilization of multiple oxidoreductases
Authors: Zhang Yong‐Hui , Chen Kai‐Nan , Zhang Jun‐Nan , Ren Hong , Zhang Xin‐Yu , Huang Jing‐Han , Wang Shi‐Zhen , Fang Bai‐Shan
Published: September 2018

BACKGROUND

The immobilization of multiple oxidoreductases has attracted a lot of research interest for its industrial application in eco‐friendly production. Here, a novel immobilization strategy was developed using manganese ion chelated linear polyethyleneimine as artificial hybrid scaffold that allowed self‐assembly of bifunctional oxidoreductase (glycerol dehydrogenase‐NADH oxidase) via multipoint coordination interaction.

RESULT

The immobilization formed a highly ordered polymer–metal–enzyme complex structure shaped like a leaf vein with 200‐nm‐wide nanowires. Preliminary results showed that the immobilization could not only retain but substantially increased the biological activity of the immobilized enzyme by 8.2‐fold. The equilibrium concentration of the reaction product DHA also was increased by 4.5‐fold compared with that of the free enzyme, exhibiting higher elimination efficiency of product inhibition compared with other enzyme immobilization strategy using nanoparticles or activated agarose beads. At the same time, linear polyethyleneimine (LPEI)–manganese scaffolds could prevent enzyme subunit disassociation and stabilize the active multimeric form, which improved catalytic condition adaption and thermal stability of target enzyme.

CONCLUSION

These results indicated a great potential of polymer–metal–enzyme hybrid in the enzyme immobilization and have provided a simple and efficient strategy for the immobilization of multiple oxidoreductases. © 2018 Society of Chemical Industry
3D ultrashort echo time MRI of the lung using stack‐of‐spirals and spherical k‐Space coverages: Evaluation in healthy volunteers and parenchymal diseases
Authors: Dournes Gaël , Yazbek Joseph , Benhassen Wadie , Benlala Ilyes , Blanchard Elodie , Truchetet Marie‐Elise , Macey Julie , Berger Patrick , Laurent François
Published: September 2018

Background

Ultrashort echo time (UTE) has been shown to improve lung MRI quality in three dimensions. The evaluation of 3D‐UTE stack‐of‐spirals VIBE (3D‐USV) sequence for parenchymal diseases and a comparison of performance with that of a spherical mode of acquisition is needed.

Purpose

To assess MRI quality using a prototypical 3D‐USV sequence and to compare performance with that of a spherical acquisition using Pointwise Encoding Time Reduction with Radial Acquisition (PETRA).

Study Type

Monocenter, prospective.

Population

Twelve healthy volunteers and 32 adult patients with either cystic fibrosis (CF; n = 16) or interstitial lung disease (ILD; n = 16).

Field Strength/Sequence

Both free‐breathing 3D‐USV and PETRA were completed at 1.5T.

Assessment

In healthy volunteers, visual analysis of imaging quality was scored using a Likert scale. Quantitative evaluation of apparent signal ratio (Sr) and contrast ratio (Cr) was measured. Patients with CF and ILD completed both computed tomography (CT) and MRI. Depiction of structural alterations was assessed using dedicated clinical scores. All evaluations were done in consensus by two readers.

Statistical Tests

Comparison of means was assessed using the Wilcoxon signed rank test. Concordance and agreement between CT and MRI were assessed using the intraclass correlation coefficient (ICC) and kappa test.

Results

In controls, 3D‐USV yielded lower artifacts owing to better automatic respiratory synchronization than PETRA (P < 0.001). However, Sr and Cr of 3D‐USV were found significantly lower by 2.25‐ and 2.36‐fold, respectively (P < 0.001). In patients, 3D‐USV and PETRA showed comparable performances to assess airway severity in CF (Bhalla score, ICC = 0.89 and ICC = 0.92, respectively) and presence of structural alterations in ILD such as honeycombing (kappa = 0.68 and kappa = 0.69, respectively).

Data Conclusion

3D‐USV enables high‐resolution morphological imaging of the lung without need of an external device to compensate respiratory motions. Automation and robustness of the method may facilitate clinical application for both airway and interstitial lung investigations.

Level of Evidence: 2

Technical Efficacy: Stage 1

J. Magn. Reson. Imaging 2018;48:1489–1497
Potential surface hydrologic responses to increases in greenhouse gas concentrations and land use and land cover changes
Authors: Hu Zuheng , Xu Zhongfeng , Ma Zhuguo , Mahmood Rezaul , Yang Zongliang
Published: September 2018

To investigate the impacts of increased greenhouse gas (GHG) concentrations and land use and land cover change (LULCC) on various components of hydrologic cycle, three sets of numerical experiments were performed using the fully coupled Community Earth System Model (CESM). In the first set of experiments, GHG concentrations were set to preindustrial (1850) levels, but the land was set with potential and current vegetation cover. In the second set of experiments, GHG concentrations levels were set to present day (2000) and land covers were, again set to potential and current vegetation. The third set of experiments was same as the second one, except using a different version of CESM, to examine the reliability of LULCC‐induced climate effects. In the model, the increased GHG concentrations led to statistically significant increases in precipitation and evapotranspiration at mid‐ and high latitudes during both warm (May–September) and cold (November–March) seasons. LULCC caused the weakening hydrological cycle in eastern Asia, southern Asia, Europe, and the semi‐arid region of North America. During both seasons, LULCC plays relatively a more important role than increased GHG concentrations in changing evapotranspiration in southern Asia and Europe. In contrast, increased GHG concentrations play a dominant role in determining changes in evapotranspiration in the semi‐arid region of eastern Asia during the cold season, as well as changes in precipitation, evapotranspiration, and runoff at high latitudes during both seasons. In some regions, LULCC‐induced changes can compensate or equal to GHG‐induced changes in hydrological cycle, especially in evapotranspiration.
Resale price maintenance: A managerial perspective
Authors: Blair Roger D. , Whitman Joseph
Published: September 2018

Managers can improve firm profits by selecting the appropriate pricing strategy. In this article, we show how managers can use one particular controversial pricing strategy—resale price maintenance (RPM)—to enhance firm profits. We first discuss the antitrust treatment of RPM, both in the United States and internationally. Then we examine the economic effects of implementing RPM in several key contexts: product promotion, quality certification, prestige goods, and online retail. We also discuss the effects of RPM on entry of new firms.