bluuebunny/crossref_metadata_2025 huggingface dataset:
Diversity‐Oriented Desulfonylative Functionalization of Alkyl Allyl Sulfones
Authors: Xia Yong , Studer Armido
Published: May 2019

The diversity‐oriented desulfonylative functionalization of alkyl allyl sulfones with various sulfone‐type reagents by radical chemistry has been developed. The readily installed allylsulfonyl moiety acts as a C‐radical precursor, which is substituted by various functionalities using sulfur‐based radical trapping reagents. The generality of this approach is documented by the successful desulfonylative alkynylation, azidation, trifluoromethylthiolation, sulfenylation, trifluoromethylselenylation, halogenation, and deuteration. The method is compatible with a wide range of functional groups. Considering the deuteration, products are obtained in good yields with a high level of deuterium incorporation.
Efficient Kinetic Resolution of Sulfur‐Stereogenic Sulfoximines by Exploiting CpXRhIII‐Catalyzed C−H Functionalization
Authors: Brauns Marcus , Cramer Nicolai
Published: May 2019

Chiral sulfoximines with stereogenic sulfur atoms are promising motifs in drug discovery. We report an efficient method to access chiral sulfoximines through a C−H functionalization based kinetic resolution. A rhodium(III) complex equipped with a chiral Cpx ligand selectively participates in conjunction with phthaloyl phenylalanine in the C−H activation of just one of the two sulfoximine enantiomers. The intermediate reacts with various diazo compounds, providing access to chiral 1,2‐benzothiazines with synthetically valuable substitution patterns. Both sulfoximines and 1,2‐benzothiazines were obtained in high yields and excellent enantioselectivity, with s‐values of up to 200. The utility of the method is illustrated by the synthesis of the key intermediates of two pharmacologically relevant kinase inhibitors.
Induction of a Four‐Way Junction Structure in the DNA Palindromic Hexanucleotide 5′‐d(CGTACG)‐3′ by a Mononuclear Platinum Complex
Authors: van Rixel Vincent H. S. , Busemann Anja , Wissingh Mathijs F. , Hopkins Samantha L. , Siewert Bianka , van de Griend Corjan , Siegler Maxime A. , Marzo Tiziano , Papi Francesco , Ferraroni Marta , Gratteri Paola , Bazzicalupi Carla , Messori Luigi , Bonnet Sylvestre
Published: May 2019

Four‐way junctions (4WJs) are supramolecular DNA assemblies comprising four interacting DNA strands that in biology are involved in DNA‐damage repair. In this study, a new mononuclear platinum(II) complex 1 was prepared that is capable of driving the crystallization of the DNA oligomer 5′‐d(CGTACG)‐3′ specifically into a 4WJ‐like motif. In the crystal structure of the 1–CGTACG adduct, the distorted‐square‐planar platinum complex binds to the core of the 4WJ‐like motif through π–π stacking and hydrogen bonding, without forming any platinum–nitrogen coordination bonds. Our observations suggest that the specific molecular properties of the metal complex are crucially responsible for triggering the selective assembly of this peculiar DNA superstructure.
Atom‐by‐Atom Resolution of Structure–Function Relations over Low‐Nuclearity Metal Catalysts
Authors: Vorobyeva Evgeniya , Fako Edvin , Chen Zupeng , Collins Sean M. , Johnstone Duncan , Midgley Paul A. , Hauert Roland , Safonova Olga V. , Vilé Gianvito , López Núria , Mitchell Sharon , Pérez‐Ramírez Javier
Published: May 2019

Controlling the structure sensitivity of catalyzed reactions over metals is central to developing atom‐efficient chemical processes. Approaching the minimum ensemble size, the properties enter a non‐scalable regime in which each atom counts. Almost all trends in this ultra‐small frontier derive from surface science approaches using model systems, because of both synthetic and analytical challenges. Exploiting the unique coordination chemistry of carbon nitride, we discriminate through experiments and simulations the interplay between the geometry, electronic structure, and reactivity of palladium atoms, dimers, and trimers. Catalytic tests evidence application‐dependent requirements of the active ensemble. In the semi‐hydrogenation of alkynes, the nuclearity primarily impacts activity, whereas the selectivity and stability are affected in Suzuki coupling. This powerful approach will provide practical insights into the design of heterogeneous catalysts comprising well‐defined numbers of atoms.
A Catalase‐Like Metal‐Organic Framework Nanohybrid for O2‐Evolving Synergistic Chemoradiotherapy
Authors: He Zhimei , Huang Xiaolin , Wang Chen , Li Xiangli , Liu Yijing , Zhou Zijian , Wang Sheng , Zhang Fuwu , Wang Zhantong , Jacobson Orit , Zhu Jun‐Jie , Yu Guocan , Dai Yunlu , Chen Xiaoyuan
Published: May 2019

Tumor hypoxia, the “Achilles’ heel” of current cancer therapies, is indispensable to drug resistance and poor therapeutic outcomes especially for radiotherapy. Here we propose an in situ catalytic oxygenation strategy in tumor using porphyrinic metal‐organic framework (MOF)‐gold nanoparticles (AuNPs) nanohybrid as a therapeutic platform to achieve O2‐evolving chemoradiotherapy. The AuNPs decorated on the surface of MOF effectively stabilize the nanocomposite and serve as radiosensitizers, whereas the MOF scaffold acts as a container to encapsulate chemotherapeutic drug doxorubicin. In vitro and in vivo studies verify that the catalase‐like nanohybrid significantly enhances the radiotherapy effect, alleviating tumor hypoxia and achieving synergistic anticancer efficacy. This hybrid nanomaterial remarkably suppresses the tumor growth with minimized systemic toxicity, opening new horizons for the next generation of theranostic nanomedicines.
Subspace controllability of Boolean networks
Authors: Ji Zhengping
Published: May 2019

Many Boolean control networks contain independent uncontrollable subnetworks, which may affect other nodes; and the rest of the system is called subspace of sub‐controllable states. This paper investigates the problem of subspace controllability under free input sequences, while the presumption that the initial states of those independent subnetworks are designable is canceled. An algorithm based on the common asymptotic periodic properties of the states is developed to find the reachable sets. Accordingly, the existing controllability criteria for subspaces when initial states of subnetworks are designable is improved, and a necessary and sufficient condition of subspace controllability via subnetworks and free inputs is derived. A design technique involving a kind of newly defined addition is presented to construct desired controls.
Manipulability analysis of a snake robot without lateral constraint for head position control
Authors: Ariizumi Ryo , Tanaka Motoyasu
Published: May 2019

Two dynamic manipulability criteria of a snake robot with sideways slipping are proposed with the application to head trajectory tracking control in mind. The singular posture, which is crucial in head tracking control, is characterized by the manipulability and examined for families of typical robot shapes. Differences in the singular postures from those of the robot with lateral constraints, which have not been clear in previous studies, are clarified in the analysis. In addition to the examination of local properties using the concept of manipulability, we discuss the effect of isotropic friction as a global property. It is well known that, at least empirically, a snake robot needs anisotropy in friction to move by serpentine locomotion if there are no objects for it to push around. From the point of view of integrability, we show one of the necessary conditions for uncontrollability is satisfied if the friction is isotropic.
Data and Analytics Combat Water Main Failures
Authors: Grigg Neil S.
Published: May 2019

Utilities might want to consider using data analytics in a proactive approach to aging infrastructure improvement that predicts likely pipe failures and allows for selective repair or replacement.
The motivations of psychotherapists: An in‐depth survey
Authors: McBeath Alistair
Published: May 2019

Background

Examining the motivations of psychotherapists has not been a popular topic of systematic research. Knowing why people want to become therapists is clearly important because this factor will inevitably impact on therapeutic outcomes. The absence of research‐led knowledge on therapists′ motivations allows this key issue to remain a relatively unattended focus within reflective practice and personal development.

Aim

To collect data about therapists′ motivations from a large number of practitioners so that core findings could be generalised to the wider profession.

Method

A total of 540 psychotherapists completed an online survey with significant numbers offering supporting qualitative data. Quantitative data were analysed using descriptive and inferential statistics. Qualitative data were subject to thematic and textual analysis.

Results

A large majority of therapists believe that their career choice was influenced by unconscious motivations, that their motivations are likely to change over time and that their own psychic wounds can contribute to effective therapy.

Conclusion

Psychotherapists are clearly prepared to reflect, in depth, on why they have been drawn to the profession. The fact that an awareness of therapists′ motivations may be variable that they may change over time and can be linked to personal vulnerability suggests that the topic should be an integral part of practitioners′ ongoing personal development and a discrete focus in formal training programmes.
Efficient Site‐Specific Antibody–Drug Conjugation by Engineering a Nature‐Derived Recognition Tag for Microbial Transglutaminase
Authors: Ebenig Aileen , Juettner Norbert Egon , Deweid Lukas , Avrutina Olga , Fuchsbauer Hans‐Lothar , Kolmar Harald
Published: May 2019

Microbial transglutaminase (mTG) has recently emerged as a powerful tool for antibody engineering. In nature, it catalyzes the formation of amide bonds between glutamine side chains and primary amines. Being applied to numerous research fields from material sciences to medicine, mTG enables efficient site‐specific conjugation of molecular architectures that possess suitable recognition motifs. In monoclonal antibodies, the lack of native transamidation sites is bypassed by incorporating specific peptide recognition sequences. Herein, we report a rapid and efficient mTG‐catalyzed bioconjugation that relies on a novel recognition motif derived from its native substrate Streptomyces papain inhibitor (SPIP). Improved reaction kinetics compared to commonly applied sequences were demonstrated for model peptides and for biotinylation of Her2‐targeting antibody trastuzumab variants. Moreover, an antibody–drug conjugate assembled from trastuzumab that was C‐terminally tagged with the novel recognition sequence revealed a higher payload‐antibody ratio than the reference antibody.
Life‐threatening peripartum cardiomyopathy—Not expected when expecting
Authors: Magnusson Peter , Kihlström Gabriella , Wallhagen Marita , Rambaree Komalsingh
Published: May 2019

Key Clinical Message

Peripartum cardiomyopathy is challenging to diagnose as it mimics symptoms present in normal pregnancy. The clinical course and prognosis are various. In selected cases, a cardioverter implantable defibrillator with/without cardiac resynchronization therapy, mechanical ventricular assist device treatment, and transplantation is indicated.
Reversible Structural Transformations of Metal–Organic Frameworks as Artificial Switchable Catalysts for Dynamic Control of Selectively Cyanation Reaction
Authors: Huang Chao , Li Gaoxiang , Zhang Lin , Zhang Yingying , Mi Liwei , Hou Hongwei
Published: May 2019

The synthesis of molecular‐level artificial switchable catalysts, of which activity in different chemical processes can be switched by controlling different stimuli, has provided a new paradigm to perform mechanical tasks and measurable work. In this work, to obtain highly effective and regioselective artificial switchable catalysts, a hierarchical anion‐pillared framework {(H3O)[Cu(CPCDC)(4,4′‐bpy)]}n (1; H3CPCDC=9‐(4‐carboxyphenyl)‐9H‐carbazole‐3,6‐dicarboxylic acid, 4,4′‐bpy=4,4′‐bipyridine), including free [H3O]+ ions as guest molecules, was constructed. Upon dissolve–exchange–crystallization behavior, fascinating reversible structural transformations proceeded between anion framework 1 and neutral 2D stair‐stepping framework {[Cu(CPCDC)(4,4′‐bpe)]}n (2; 4,4′‐bpe=4,4′‐vinylenedipyridine). Moreover, frameworks 1 and 2 can act as heterogeneous artificial switchable catalysts to selectively promote the direct cyanation reaction of terminal alkynes and azobisisobutyronitrile. The results indicated that 1 and 2 exhibited excellent selectivity to generate vinyl isobutyronitrile skeletons or propiolonitrile frameworks, respectively, as unique products. Furthermore, indicating paper, GC‐MS, energy‐dispersive X‐ray spectroscopy, and X‐ray photoelectron spectroscopy analysis demonstrated that the reversible structural transformations endowed 1 and 2 with well‐defined platforms to stabilize the isobutyronitrile and CN sources through the different catalytic pathways.
Enhanced Methyl Orange Removal Using a Newly Isolated Bacterial Strain and Potassium‐Iodide‐Doped Hydroxyapatite Nanoparticles
Authors: Kilany Mona , Ibrahim Essam H. , Alshehri Ali , Ghramh Hamed A.
Published: May 2019

Due to the toxicity and mutagenicity of methyl orange (MO), it is necessary to eliminate MO from wastewater. A bacterial strain is isolated and identified that possesses a high MO decolorization ability. Furthermore, the cultural requirements and the decolorization behavior of the bacterial isolate are investigated. Potassium‐iodide‐doped hydroxyapatite (KI‐doped HAp) nanoparticles are synthesized and characterized. The enhancement of the decolorization rate using KI‐doped HAp nanoparticles is experimentally confirmed. The microbial toxicity assessment is evaluated against Bacillus subtilis, and the bacterial isolate is identified as the Enterococcus faecalis strain Kilany MO under accession number KY780590. This strain shows maximum decolorization of MO (86.4%) at 400 mg L−1, pH 6, and 30 °C for 48 h under static conditions. In addition, being extremely tolerant of concentrations of MO of up to 1000 mg L−1 or more, E. faecalis exhibited decolorizing activity through biosorption rather than adsorption. Scanning electron microscopy and energy dispersive X‐ray spectra revealed that KI‐doped HAp nanoparticles are nanorods that are 50–100 nm in size with a Ca/P molar ratio of 1.833. KI‐doped HAp nanoparticles enhanced decolorization, yielding a maximum removal of 95% within 48 h. A microbial toxicity study revealed that the bacterial metabolites are less toxic than MO. Hence, the potential of E. faecalis to withstand high concentrations of MO, especially in the presence of nanoparticles, may start a new trend in wastewater bioremediation strategy.
Convergent neuronal projections from paraventricular nucleus, parabrachial nucleus, and brainstem onto gastrocnemius muscle, white and brown adipose tissue in male rats
Authors: Doslikova Barbora , Tchir Devan , McKinty Amanda , Zhu Xinxia , Marks Daniel L. , Baracos Vickie E. , Colmers William F.
Published: May 2019

When energy balance is altered by aerobic exercise, starvation, and cold exposure, for example, there appears to be coordination of the responses of skeletal muscle, white adipose (WAT), and brown adipose (BAT) tissues. We hypothesized that WAT, BAT, and skeletal muscle may share an integrated regulation by the central nervous system (CNS); specifically, that neurons in brain regions associated with energy balance would possess neuroanatomical connections to permit coordination of multiple, complementary responses in these downstream tissues. To study this, we used trans‐neuronal viral retrograde tract tracing, using isogenic strains of pseudorabies virus (PRV) with distinct fluorescent reporters (either eGFP or mRFP), injected pairwise into male rat gastrocnemius, subcutaneous WAT and interscapular BAT, coupled with neurochemical characterization of specific cell populations for cocaine‐ and amphetamine‐related transcript (CART), oxytocin (OX), corticotrophin releasing hormone (CRH) and calcitonin gene‐related peptide (CGRP). Cells in the paraventricular (PVN) and parabrachial (PBN) nuclei and brainstem showed dual projections to muscle + WAT, muscle + BAT, and WAT + BAT. Dual PRV‐labeled cells were found in parvocellular, magnocellular and descending/pre‐autonomic regions of the PVN, and multiple structural divisions of the PBN and brainstem. In most PBN subdivisions, more than 50% of CGRP cells dually projected to muscle + WAT and muscle + BAT. Similarly, 31–68% of CGRP cells projected both to WAT + BAT. However, dual PRV‐labeled cells in PVN only occasionally expressed OX or CRH but not CART. These studies reveal for the first time both separate and shared outflow circuitries among skeletal muscle and subcutaneous WAT and BAT.
Excessive computer use as an oral health risk behaviour in 18‐year‐old youths from Poland: A cross‐sectional study
Authors: Olczak‐Kowalczyk Dorota , Tomczyk Jacek , Gozdowski Dariusz , Kaczmarek Urszula
Published: May 2019

Background

Many studies have indicated that the excessive use of computers (more than 3 hr/d) might be associated with an unhealthy life‐style.

Aim

The aim of this study was to evaluate the relationship between excessive computer use with the condition of the teeth and periodontium and the oral health behaviour of 18‐year‐olds.

Design

Cross‐sectional studies, using a questionnaire, were carried out on 1,611 18‐year‐olds from Poland. The questionnaire contained questions about socioeconomic status and information about health‐related behaviour. The condition of their teeth and gingivae were clinically assessed.

Results

Excessive (>3 h/d) computer use was reported by 492 (31%) of participants, who had an increased frequency of unfilled cavities (1.97 vs. 2.27, p = .047) and a higher risk of oral hygiene neglect (e.g., using dental floss 41% vs. 34%, p = .009). Excessive computer use was also seen to be associated with poor dietary habits. Individuals who declared excessive computer use also had a higher risk of gingival bleeding (35% vs. 29%, p = .009).

Conclusion

In the group studied, excessive computer use by adolescents constituted a risk factor for neglect of oral hygiene, poor dietary choices, and failure to benefit from oral health care. Therefore, these aspects should be included in the risk assessment of oral disease and incorporated into educational programs that promote a healthy lifestyle.
VoLTE cell capacity estimation using AMR‐WB codecs and considering VAF, SID, packet bundling, and TTI bundling
Authors: Senapati Rajiv , Pati Hemanta Kumar
Published: May 2019

The Voice over Long‐Term Evolution (VoLTE) cell capacity notably has an influence on Call Admission Control (CAC) in Long‐Term Evolution (LTE) network. In literature, many techniques have been studied to estimate the LTE cell capacity, but most of them are throughput‐based physical layer (PHY layer) estimate. These estimates do not consider delay requirement, transmission loss, and protocol overhead. In this paper, we have proposed novel analytical models for estimating the VoLTE cell capacity in terms of number of users by considering available physical resource blocks (PRBs) in each bandwidth, voice traffic‐based characteristics such as voice activity factor (VAF), silent insertion descriptor (SID), and radio‐specific techniques such as packet bundling and transmission time interval (TTI) bundling. Our developed analytical models are then used to investigate the effect of modulation and coding scheme (MCS) and Adaptive Multi‐RateWideband (AMR‐WB) voice codec on VoLTE cell capacity. Results show that higher order modulation scheme with lower bit voice codec accommodates maximum number of VoLTE users. Further, the impact of VAF, SID, packet bundling, and TTI bundling on VoLTE cell capacity is investigated in different radio conditions. Finally, using our proposed model, the effect of hybrid automatic repeat request (HARQ) retransmission on VoLTE cell capacity is investigated.
Quadrature space shift keying performance with dual‐hop AF relay over mixed fading
Authors: Sahu Hemanta Kumar , Sahu P. R.
Published: May 2019

Quadrature space shift keying (QSSK) modulation combined with cooperative relaying improves the reliability in communication and enhances the overall spectral efficiency. Here, QSSK scheme is analyzed for multiple‐input multiple‐output (MIMO) wireless communication system with dual‐hop amplify‐and‐forward (AF) relaying systems over asymmetric mixed Rayleigh/Rician and symmetric Nakagami‐m/Nakagami‐m fading channels. Analytical expressions for cumulative distribution function (CDF) of the end‐to‐end signal‐to‐noise ratio are derived and used to evaluate the average bit error probability (ABEP) of QSSK modulation in mixed asymmetric and symmetric fading channels. The obtained ABEP expression is in the form of Whittaker function, which can be numerically evaluated using its numerical or series representation. Numerical and simulation results are presented to illustrate the impact of fading parameters on the system performance.
Environmental DNA improves Eastern Hellbender (Cryptobranchus alleganiensis alleganiensis) detection over conventional sampling methods
Authors: Wineland Sean M. , Arrick Rachel F. , Welch Shane M. , Pauley Thomas K. , Mosher Jennifer J. , Apodaca Joseph J. , Olszack Max , Holmes Jeffrey N. , Waldron Jayme L.
Published: May 2019

Effective conservation planning relies on accurate species detection. However, conventional sampling methods used for detecting rare and cryptic aquatic species suffer from low probabilities of detection. Environmental DNA (eDNA) has emerged as an innovative and powerful sampling tool for detecting aquatic species, with previous studies suggesting a detection advantage over conventional sampling. However, comparative studies often fail to consider the appropriate sampling frameworks to adequately compare sampling methodologies and account for the influence of environmental variables on eDNA detection probabilities. In this study, we paired two detection methods (eDNA and physical sampling) at 22 sites in West Virginia, USA, to compare the probability of detecting a cryptic, elusive, and imperiled species of giant salamander, the Eastern Hellbender (Cryptobranchus alleganiensis alleganiensis). We used a multimethod occupancy modeling framework to compare method‐specific detection probabilities using a suite of predictor variables based on environmental conditions thought to influence hellbender detection. We detected hellbenders at 19/22 sites using eDNA and at 13/22 sites using physical sampling methods. The best supported model indicated that detection probability for eDNA (0.84 ± 0.06) was three times higher than conventional methods (0.28 ± 0.07). Water turbidity was the best predictor of hellbender detection and negatively impacted our ability to detect eDNA. We failed to detect an association between eDNA concentration and hellbender catch per unit effort. Our study supports previous findings that suggest eDNA sampling methods greatly increase the probability of detecting aquatic species. However, with little known about the influence of environmental variables on eDNA detection, our results highlight the negative influence turbidity and other physiochemical factors have on eDNA detection and suggest that further research on eDNA detection in turbid environments is needed.
Measurement of heat flow through cast slabs of calcium sulfate dihydrate
Authors: Engbrecht Dick C. , Hirschfeld Deidre A.
Published: May 2019

Slabs of cast calcium sulfate dihydrate have been used for decades as a heat transfer barrier in commercial and residential construction and are assessed in accordance with the parameters defined by ASTM C1396. The study described herein hypothesizes that minor impurities have significant effects on the high‐temperature performance of these casts. Five thermocouples are cast into a 20‐mm‐thick slab at approximately 4‐mm intervals are measured between ambient and approximately 1000°C in a furnace. Thermal diffusivity and inertia are estimated from this temperature profile. This study compares natural, flue gas desulfurized (FGD) and reagent grade hemihydrates that have been converted into the dihydrate form with distilled water; the common additives kaolin and borax are used to modify the cast. The thermocouple data allow an effective thermal diffusivity (α′) and an effective thermal inertia (I′) to be calculated. The hemihydrate source and kaolin content are found to affect the high‐temperature performance; the FGD source increases the thermal inertia, and kaolin inhibits the formation of other borate compounds through intercalation.
Use of poly(ε‐caprolactone)‐based films for equilibrium‐modified atmosphere packaging to extend the postharvest shelf life of garland chrysanthemum
Authors: Cheng Peifang , Yun Xueyan , Xu Chang , Yang Yang , Han Yumei , Dong Tungalag
Published: May 2019

A uniaxial‐stretched poly(ε‐caprolactone)/poly(propylene carbonate; PCL/PPC) composite film was prepared using a twin‐screw extruder, and its utility as an equilibrium‐modified atmosphere packaging (EMAP) film extending the shelf life of garland chrysanthemums stored at 2~4°C was explored. The oxygen, carbon dioxide, and water vapor penetration properties, mechanical properties, and gas permselectivity of PCL/PPC film used to package garland chrysanthemums were determined and compared to those of controlled low‐density polyethylene (LDPE) and PCL films. Physicochemical properties such as package headspace gas composition, weight loss, leaf color, total chlorophyll content, ascorbic acid content, lipid peroxidation extent, and the sensory traits of garland chrysanthemums were investigated over a storage period of 14 days to compare the preservative effects of the various packages. PPC blending decreased the PCL gas and water vapor permeability and slightly increased the CO2 permselectivity. These effects on gas and water vapor permeability, combined with the effects on gas permselectivity, enhanced preservation of packed garland chrysanthemums. Furthermore, an O2 inner atmosphere level of 2%~5%, and a CO2 concentration not greater than 8%, was established by the PCL/PPC film in the absence of condensation. The results thus suggest that biodegradable film can be used as an EMAP film to better maintain the quality of freshly harvested garland chrysanthemums and to afford a longer shelf life during cold storage compared to LDPE film. Sensory evaluation indicated that the garland chrysanthemums were market‐acceptable after 14 days of storage; LDPE‐packed chrysanthemums were acceptable only up to 8 days of storage. The film thus improved storage life compared to that afforded by LDPE.
Correlations between relatives: From Mendelian theory to complete genome sequence
Authors: Thompson Elizabeth A.
Published: May 2019

It is 100 years since R. A. Fisher proposed that a Mendelian model of genetic variant effects, additive over loci, could explain the patterns of observed phenotypic correlations between relatives. His loci were hypothetical and his model theoretical. It is only about 50 years since the first genetic markers allowed the detection of even variants with major effects on phenotype, and only 20 years since the development of single‐nucleotide polymorphism technology provided dense markers over the genome. Then both mappings in defined pedigrees and population‐based genome‐wide association studies samples allowed the detection of multiple contributing variants of smaller effect. Finally, with methods based on genotypic correlations between individuals, or on allelic associations between loci, the additive heritability contributions of the genome can be estimated from large population samples. In this review we trace, from 1918 to 2018, the analysis of observed phenotypic correlations between relatives to estimate underlying genetic components of traits in human populations. As with studies from 1918 onward, we use height as the example trait where not only data are readily available, but where Fisher's model of large numbers of variants of infinitesimal effect appears to provide a good approximation to reality. However, we also trace the use of phenotypic and genotypic correlations between relatives in mapping causal variants and resolving genetic contributions to more complex human traits. With the availability of DNA sequence data, we can hope to not only estimate the total genetic contribution to a trait, but to resolve effects of individual genetic variants on biological function.
Prognostic value of radiographically defined extranodal extension in human papillomavirus‐associated locally advanced oropharyngeal carcinoma
Authors: Tian Sibo , Ferris Matthew J. , Switchenko Jeffrey M. , Magliocca Kelly R. , Cassidy Richard J. , Jhaveri Jaymin , Aiken Ashley H. , Baugnon Kristen L. , Hudgins Patricia A. , Kendi Ayse T. K. , Patel Mihir R. , Saba Nabil F. , Curran Walter J. , Beitler Jonathan J.
Published: May 2019

Background

Pathologic extranodal extension (ENE) has traditionally guided the management of head and neck cancers. The prognostic value of radiographic ENE (rENE) in human papillomavirus (HPV)‐associated oropharyngeal squamous cell carcinoma (HPV + OPX) is uncertain.

Methods

Patients with HPV + OPX with adequate pretreatment radiographic nodal evaluation from a single institution were analyzed. rENE status was determined by neuroradiologists' at time of diagnosis. Distant metastasis‐free survival (DMFS), overall survival (OS), and locoregional recurrence‐free survival (LRFS) were estimated using Kaplan‐Meier methods. Cox proportional hazards models were fit to assess the impact of rENE on survival endpoints.

Results

Hundred sixty‐eight patients with OPX + squamous cell carcinomas diagnosed between April 2008 and December 2014 were included for analysis with median follow‐up of 3.3 years. Eighty‐eight percent of patients received concurrent chemoradiotherapy. rENE was not prognostic; its presence in patients with HPV + OPX did not significantly impact OS, LRFS, or DMFS.

Conclusions

In patients with HPV + OPX, rENE was not significantly associated with OS, LRFS, or DMFS.
Using Polymers to Impart Lubricity and Biopassivity to Surfaces: Are These Properties Linked?
Authors: Benetti Edmondo M. , Spencer Nicholas D.
Published: May 2019

Polymer brushes have been widely applied for the reduction of both friction and non‐specific protein adsorption. In many (but not all) applications, such as contact lenses or medical devices, this combination of properties is highly desirable. Indeed, for many polymer‐brush systems, lubricity and resistance to biofouling appear to go hand in hand, with modifications of brush architecture, for example, leading to a similar degree of enhancement (or degradation) in both properties. In the case of poly(ethylene glycol) (PEG) brushes, this has been widely demonstrated. There are, however, examples where this behavior breaks down. In systems where linear brushes are covalently crosslinked during surface‐initiated polymerization (SIP), for example, the presence and the chemical nature of links between grafted chains might or might not influence biopassivity of the films, while it always causes an increment in friction. Furthermore, when the grafted‐chain topology is shifted from linear to cyclic, chemically identical brushes show a substantial improvement in lubrication, whereas their protein resistance remains unaltered. Architectural control of polymer brush films can provide another degree of freedom in the design of lubricious and biopassive coatings, leading to new combinations of surface properties and their independent modulation.
Dietary intake of fiber, whole grains and risk of colorectal cancer: An updated analysis according to food sources, tumor location and molecular subtypes in two large US cohorts
Authors: He Xiaosheng , Wu Kana , Zhang Xuehong , Nishihara Reiko , Cao Yin , Fuchs Charlie S. , Giovannucci Edward L. , Ogino Shuji , Chan Andrew T. , Song Mingyang
Published: May 2019

Epidemiologic evidence relating fiber intake to colorectal cancer (CRC) remains inconclusive and data are limited on different food sources of fiber and heterogeneity by tumor subsite and molecular profile. We prospectively followed for CRC incidence 90,869 women from the Nurses’ Health Study (1980–2012) and 47,924 men from the Health Professionals Follow‐up Study (1986–2012), who completed a validated food frequency questionnaire every 4 years. Cox proportional hazards regression was used to examine the associations with CRC risk for total, cereal, fruit and vegetable fiber and whole grains. We also assessed the associations according to tumor subsites (proximal colon, distal colon and rectum) and molecular markers (microsatellite instability, BRAF mutation, CpG island methylator phenotype and KRAS mutation). We documented 3,178 CRC cases during 3,685,903 person‐years of follow‐up in the NHS and HPFS. Intake of total dietary fiber was not associated with CRC risk after multivariable adjustment in either women (hazard ratio [HR] comparing extreme deciles, 1.17; 95% CI, 0.92–1.48, ptrend = 0.55) or men (HR, 0.90; 95% CI, 0.67–1.21, ptrend = 0.47). Higher intake of cereal fiber and whole grains was associated with lower CRC risk in men with an HR of 0.75 (95% CI, 0.57–1.00) and 0.72 (95% CI, 0.54–0.96), respectively. No heterogeneity was detected by tumor subsite or molecular markers (pheterogeneity > 0.05). Higher intake of total dietary fiber within the range of a typical American diet is unlikely to substantially reduce CRC risk. The potential benefit of cereal fiber and whole grains in men warrants further confirmation.
Integrating gender perspectives in gynecology and obstetrics: Engaging medical colleges in Maharashtra, India
Authors: Rege Sangeeta , Bhate‐Deosthali Padma , Shingare Pravin , Gadappa Srinivas , Deshpande Sonali , Gaikwad Nandkishore , Vaidya Shailesh
Published: May 2019

Failure to acknowledge the impact of sex and gender differences affects the quality of health care provision, and is an impediment to reducing health inequities. Systematic efforts were initiated in Maharashtra, India for reducing these disparities by developing gender‐integrated curricula in undergraduate (UG) medical education between 2015 and 2018. A review of UG obstetrics and gynecology curricula indicated a lack of gender lens and focus on the reproductive rights of women. Based on these gaps, a gender‐integrated curriculum was developed, implemented, and tested with medical students. Significant positive attitudes were seen among male and female students for themes such as access to safe abortion; understanding reproductive health concerns and their complex relationship with gender roles; violence against women as a health issue; and sexuality and health. These results strengthened the resolve to advocate for such a curriculum to be integrated across all medical colleges in the state.
Robust MR image super‐resolution reconstruction with cross‐modal edge‐preserving regularization
Authors: Zhu Qingyong , Ren Yanan , Qiu Zhilang , Wang Wei
Published: May 2019

In this article, we propose a novel image super‐resolution (SR) reconstruction method in the field of magnetic resonance imaging, which is based on a cross‐modal edge‐preserving regularization integrating the internal gradient prior from the target‐modal image itself and the external gradient prior from the reference‐modal image obtained by pre‐scan in many medical imaging scenes. The reference‐modal image is a high‐resolution guidance image that has much shareable information such as gradient orientation on edge regions, which can be used to improve the image resolution of the target modal. In addition, to be robust against the misalignment between the target‐modal image and reference‐modal image, a multimodal registration is incorporated in the SR reconstruction process. In this work, the proposed SR method can be formulated as an alternating optimization problem, that is, the target‐modal and reference‐modal images are alternately updated through iterations. Experimental results on simulated and realistic images show the superior performance of the proposed approach over several state‐of‐the‐art SR techniques.
The Good Behavior Game: A brief review
Authors: Joslyn P. Raymond , Donaldson Jeanne M. , Austin Jennifer L. , Vollmer Timothy R.
Published: May 2019

The Good Behavior Game (GBG) is a group contingency that reduces disruption and increases engagement in various contexts. In recent years, researchers have extended the GBG in at least 3 ways: (a) demonstrating its efficacy with novel populations, settings, and behaviors, (b) examining procedural variations that improve contextual fit, and (c) using more comprehensive data collection methods to explore the behavior of individual students and indirect effects. The purpose of the current review is to summarize recent advances, discuss implications of recent studies and potential mechanisms for the general efficacy of the GBG, and suggest future directions.
Mechanochemical enzymatic synthesis of 1,4‐dihydropyridine calcium antagonists and derivatives
Authors: Jiang Ling , Ye Li‐dan , Gu Jia‐li , Su Wei‐ke , Ye Wen‐ting
Published: May 2019

BACKGROUND

Enzyme promiscuity has attracted significant attention from chemists and biochemists in recent years. However, long reaction time and use of toxic organic solvents limit its applications for industrial processes. 1,4‐Dihydropyridine (1,4‐DHP) calcium antagonists are recommended for the first line treatment of hypertension. Although some chemical protocols for the preparation of 1,4‐DHP calcium antagonists have been developed, enzymatic synthesis of these compounds still remains uncovered.

RESULTS

Solvent‐free quick synthesis of 1,4‐DHP calcium antagonists felodipine, nitrendipine, nifedipine and nemadipine B and their derivatives was achieved by Lipozyme® RM IM (triacylglycerol acylhydrolase, EC3.1.1.3)‐catalyzed multicomponent reactions of aromatic aldehyde, alkyl acetoacetate and alkyl 3‐aminocrotonate under ball‐milling conditions. The products were obtained in moderate yields (up to 86.8%) and the influence of reaction conditions including catalyst loading, grinding auxiliary and grinding frequency was investigated.

CONCLUSION

The protocol successfully overcame some longstanding problems in the field of enzymatic promiscuity research, such as long reaction time and use of harmful organic solvents, and demonstrated the potential application value of promiscuous enzyme‐catalyzed reactions under ball‐milling conditions for pharmaceutical synthesis. © 2019 Society of Chemical Industry
Synthesis of Novel 3‐Aryl‐5‐dichloromethyl‐Δ2‐1,2,4‐oxadiazolines
Authors: Guirado Antonio , Sandoval José A. , Alarcón Enrique , Vera María , Bautista Delia , Gálvez Jesús
Published: May 2019

The first synthetic approach to hitherto unknown 3‐aryl‐5‐dichloromethyl‐Δ2‐1,2,4‐oxadiazolines, of synthetic and biological interest, has been developed involving high‐yield reactions between N‐(2,2‐dichlorovinyl)benzimidoyl chlorides and hydroxylamine. The molecular structure of one member of this new family of compounds—5‐dichloromethyl‐3‐(4‐fluorophenyl)‐1,2,4‐oxadiazoline—has been determined by X‐ray crystallography. Density functional theory calculations supporting the proposed reaction pathway for the formation of these products have been carried out.
Simultaneous phase‐contrast MRI and PET for noninvasive quantification of cerebral blood flow and reactivity in healthy subjects and patients with cerebrovascular disease
Authors: Ishii Yosuke , Thamm Thoralf , Guo Jia , Khalighi Mohammad Mehdi , Wardak Mirwais , Holley Dawn , Gandhi Harsh , Park Jun Hyung , Shen Bin , Steinberg Gary K. , Chin Frederick T. , Zaharchuk Greg , Fan Audrey Peiwen
Published: May 2019

Background

H215O‐positron emission tomography (PET) is considered the reference standard for absolute cerebral blood flow (CBF). However, this technique requires an arterial input function measured through continuous sampling of arterial blood, which is invasive and has limitations with tracer delay and dispersion.

Purpose

To demonstrate a new noninvasive method to quantify absolute CBF with a PET/MRI hybrid scanner. This blood‐free approach, called PC‐PET, takes the spatial CBF distribution from a static H215O‐PET scan, and scales it to the whole‐brain average CBF value measured by simultaneous phase‐contrast MRI.

Study Type

Observational.

Subjects

Twelve healthy controls (HC) and 13 patients with Moyamoya disease (MM) as a model of chronic ischemic disease.

Field Strength/Sequences

3T/2D cardiac‐gated phase‐contrast MRI and H215O‐PET.

Assessment

PC‐PET CBF values from whole brain (WB), gray matter (GM), and white matter (WM) in HCs were compared with literature values since 2000. CBF and cerebrovascular reactivity (CVR), which is defined as the percent CBF change between baseline and post‐acetazolamide (vasodilator) scans, were measured by PC‐PET in MM patients and HCs within cortical regions corresponding to major vascular territories.

Statistical Tests: Linear, mixed effects models were created to compare CBF and CVR, respectively, between patients and controls, and between different degrees of stenosis.

Results

The mean CBF values in WB, GM, and WM in HC were 42 ± 7 ml/100 g/min, 50 ± 7 ml/100 g/min, and 23 ± 3 ml/100 g/min, respectively, which agree well with literature values. Compared with normal regions (57 ± 23%), patients showed significantly decreased CVR in areas with mild/moderate stenosis (47 ± 17%, P = 0.011) and in severe/occluded areas (40 ± 16%, P = 0.016).

Data Conclusion: PC‐PET identifies differences in cerebrovascular reactivity between healthy controls and cerebrovascular patients. PC‐PET is suitable for CBF measurement when arterial blood sampling is not accessible, and warrants comparison to fully quantitative H215O‐PET in future studies.

Level of Evidence: 3

Technical Efficacy Stage: 2

J. Magn. Reson. Imaging 2019. J. Magn. Reson. Imaging 2020;51:183–194.
Glycogen metabolism is impaired in the brain of male type 2 diabetic Goto‐Kakizaki rats
Authors: Soares Ana Francisca , Nissen Jakob D. , Garcia‐Serrano Alba M. , Nussbaum Sakura S. , Waagepetersen Helle S. , Duarte João M. N.
Published: May 2019

Diabetes impacts the central nervous system predisposing to cognitive decline. While glucose is the main source of energy fueling the adult brain, brain glycogen is necessary for adequate neuronal function, synaptic plasticity and memory. In this study, we tested the hypothesis that brain glycogen metabolism is impaired in type 2 diabetes (T2D). 13C magnetic resonance spectroscopy (MRS) during [1‐13C]glucose i.v. infusion was employed to detect 13C incorporation into whole‐brain glycogen in male Goto‐Kakizaki (GK) rats, a lean model of T2D, and control Wistar rats. Labeling from [1‐13C]glucose into brain glycogen occurred at a rate of 0.25 ± 0.12 and 0.48 ± 0.22 µmol/g/h in GK and Wistar rats, respectively (p = 0.028), despite similar brain glycogen concentrations. In addition, the appearance of [1‐13C]glucose in the brain was used to evaluate glucose transport and consumption. T2D caused a 31% reduction (p = 0.031) of the apparent maximum transport rate (Tmax) and a tendency for reduced cerebral metabolic rate of glucose (CMRglc; −29%, p = 0.062), indicating impaired glucose utilization in T2D. After MRS in vivo, gas chromatography‐mass spectrometry was employed to measure regional 13C fractional enrichment of glucose and glycogen in the cortex, hippocampus, striatum, and hypothalamus. The diabetes‐induced reduction in glycogen labeling was most prominent in the hippocampus and hypothalamus, which are crucial for memory and energy homeostasis, respectively. These findings were further supported by changes in the phosphorylation rate of glycogen synthase, as analyzed by Western blotting. Altogether, the present results indicate that T2D is associated with impaired brain glycogen metabolism.
Effects of nitrogen feeding for extraradical mycelium of Rhizophagus irregularis maize symbiosis incorporated with phosphorus availability
Authors: Li Zhifang , Ngwene Benard , Hong Ting , George Eckhard
Published: May 2019

In terrestrial ecosystems, plants are frequently in symbiosis with arbuscular mycorrhizal fungi (AMF) with mineral nutrients and photosynthesis carbon exchanges in between. This research sought to identify the effects of phosphorus (P) levels on the nitrogen (N) uptake via extraradical mycelium (ERM) and the mycorrhizal growth response (MGR) of maize plants within the AMF symbiosis. Pots were separated into root compartments and hyphae compartments (HCs) with two layers of a 30‐μm mesh membrane and an air gap in between, where only hyphae could pass through, to avoid both N diffusion and root growth effects. Maize plants were inoculated with Rhizophagus irregularis with different N fertilization in HCs under two different P fertilization levels. Our results indicated that a strong increase in MGR with low‐P fertilization. The same tendency was not observed with high‐P fertilization, although both had a large increase in P concentration as a potential source of growth in shoot tissue of mycorrhizal plants. Substantial effects (10.5% more N) were observed in the case of high‐P availability for the host plants from ERM fed with N, whereas under low‐P conditions ERM may prioritize P uptake rather than N uptake. The AM fungi increase the uptake of N and P, which are most limiting in the soil with fewer forces from soil resources. In addition, there was still more P accumulated than N due to the high N for ERM with high‐P supply. Low N in HCs corresponded with a lower colonization rate in roots but with high hyphae density in HCs; this result suggest that N and P availability might change the ratio of extraradical to intraradical hyphae length.
Glutathione foliar fertilisation prevents lime‐induced iron chlorosis in soil grownMedicago scutellata
Authors: Gheshlaghi Zahra , Khorassani Reza , Abadía Javier , Kafi Mohammad , Fotovat Amir
Published: May 2019

It has been proposed that glutathione can relieve the effects of Fe deficiency. This study tested the effects of glutathione foliar treatments to prevent Fe chlorosis, using as positive controls soil and foliar Fe fertilisation.Medicago scutellataplants were grown in soil (5.7% CaCO3) supplemented or not with 4 and 8% CaCO3. Two Fe(III)‐EDDHA soil treatments (5 and 10 mg Fe kg−1), and three foliar treatments (three applications each of 2.14 mM Fe(III)‐EDDHA, 1 mM glutathione, and the previous two combined) were applied. Measurements include leaf chlorophyll and Fe concentrations, biomass, leaf enzymatic and non‐enzymatic antioxidant systems and carboxylates. The addition of CaCO3caused typical Fe deficiency symptoms, including changes in chlorophyll, Fe, antioxidant systems and carboxylates, which were prevented by soil and foliar Fe fertilisation. The foliar treatment with glutathione also led to higher chlorophyll, leaf extractable Fe and root Fe, as well as decreases in some antioxidant systems, whereas leaf Fe concentrations decreased. The combined foliar application of glutathione and Fe was even more efficient in preventing chlorosis. Including glutathione in foliar fertilisation programs should be considered as an option for Fe chlorosis prevention, especially when relatively large leaf total Fe concentrations occur in the so called chlorosis paradox.