bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Small‐Molecule Inhibitors of PD‐1/PD‐L1 Protein‐Protein Interaction
Authors: Patil Sachin P. , Fink Madison A. , Enley Erika S. , Fisher James E. , Herb Marie C. , Klingos Anthony , Proulx James T. , Fedorky Megan T. 
Published: February 2018

AbstractThe protein‐protein interaction between programmed cell death protein 1 (PD‐1) and programmed cell death ligand 1 (PD−L1) proteins is one of the major checkpoint inhibition pathways responsible for the escape of tumors from immune destruction. Therefore, inhibition of the PD‐1/PD−L1 interaction presents an important therapeutic target against such tumors that express PD−L1 on their cell surface. Herein, we report structure‐based virtual screening of the National Cancer Institute Diversity Set compounds leading to the identification of several small‐molecule inhibitors of PD‐1/PD−L1 interaction. Top 4 molecules significantly inhibited PD‐1/PD−L1 interaction in a dose‐dependent manner, with the most active molecule (NSC149050) exhibiting ∼50% inhibition at 25 μM test concentration. This is remarkable considering it has a relatively low molecular weight and still is capable of inhibiting PD‐1/PD−L1 protein‐protein interaction whose binding interface spans over ∼1.970 Å2. Thus, these molecules may prove well suited for lead optimization studies leading to design of more potent analogs with improved drug‐like properties against this traditionally challenging anticancer target.
Simple Synthetic Method for the Functionalized Benzo[c]cinnolines
Authors: Lee Da Seul , Chatterjee Tanmay , Ban Jaeyoung , Rhee Hakjune , Cho Eun Jin 
Published: February 2018

AbstractFunctionalized benzo[c]cinnoline derivatives were synthesized from easily accessible 2,2‐diamino‐1,1′‐biaryls using a nitrite source. In this simple process, various functional groups were tolerated under mild reaction conditions, and the practicality of the process was demonstrated through the gram‐scale production of the benzo[c]cinnolines.
A DFT Study on CuH‐Catalyzed Reductive Relay Hydroamination for Synthesis of Remote‐Chiral Amine
Authors: Gao Yun , Wang Ping , Zhao Yang , Liu Qingyun , Liu Wei , Wang Yong 
Published: February 2018

AbstractThe reaction mechanism of copper‐hydride‐catalyzed reductive relay hydroamination for remote‐chiral amine was studied. Using density functional theory, we carefully investigated the mechanistic of the generation of R‐ and S‐amines with stereocenters. A series of steps, such as Markovnikov hydrocupration, β‐alkoxide elimination of alkylcopper, insertion of terminal alkene with copper‐hydride catalyst, the electrophile attack, and the formation of C–N bonds have been discussed in the catalytic cycle. The most favorable pathway is obtained by the Re‐attack of the catalyst with the allylic ester. In addition, noncovalent interaction (NCI) analyses show stronger noncovalent interactions in transition state Re‐TS1, frontier molecular orbital (FMO) reveal a larger lowest unoccupied molecular orbital and the highest occupied molecular orbital (LUMO‐HOMO) gap in transition state Si‐TS1, indicating the preference for the S‐configuration chiral amines, which is in good agreement with the experimental observations.
Bifunctional Al2O3 Interlayer Leads to Enhanced Open‐Circuit Voltage for Hole‐Conductor‐Free Carbon‐Based Perovskite Solar Cells
Authors: Xiong Yuli , Zhu Xiaotong , Mei Anyi , Qin Fei , Liu Shuang , Zhang Shujing , Jiang Youyu , Zhou Yinhua , Han Hongwei 
Published: February 2018

Hole‐conductor‐free carbon‐based perovskite solar cell (C‐PSC) is respected for their low cost and super stability. However, its absolut	e efficiency is hampered by the relatively low open‐circuit voltage (Voc) due to the higher recombination losses than device with hole conductors. Herein, we develop a novel architecture to improve the Voc through simple incorporation of an Al2O3 interlayer. We find that this Al2O3 interlayer not only serves as an excellent insulating layer to separate cathode and anode but also modifies the interface between the electron transport material (ETM) and perovskite, and thus effectively retards the recombination at ETM/perovskite and perovskite/counter electrode interfaces simultaneously. Significantly, the average Voc of hole‐conductor‐free C‐PSC upon the adoption of Al2O3 interlayer is increased from 836 to 942 mV. This novel architecture design combine the surface modification and spacer tuning technologies through a facile step, which makes an important step toward obtaining high efficient hole‐conductor‐free C‐PSC.
Home blood‐pressure monitoring in a hypertensive pregnant population
Authors: Perry H. , Sheehan E. , Thilaganathan B. , Khalil A. 
Published: February 2018

ABSTRACTObjectiveThe majority of patients with chronic or gestational hypertension do not develop pre‐eclampsia. Home blood‐pressure monitoring (HBPM) has the potential to offer a more accurate and acceptable means of monitoring hypertensive patients during pregnancy compared with traditional pathways of frequent outpatient monitoring. The aim of this study was to determine whether HBPM reduces visits to antenatal services and is safe in pregnancy.MethodsThis was a case–control study of 166 hypertensive pregnant women, which took place at St George's Hospital, University of London. Inclusion criteria were: chronic hypertension, gestational hypertension or high risk of developing pre‐eclampsia, no significant proteinuria (≤ 1+ proteinuria on dipstick testing) and normal biochemical and hematological markers. Exclusion criteria were maternal age < 16 years, systolic blood pressure > 155 mmHg or diastolic blood pressure > 100 mmHg, significant proteinuria (≥ 2+ proteinuria on dipstick testing or protein/creatinine ratio > 30 mg/mmol), evidence of small‐for‐gestational age (estimated fetal weight < 10th centile), signs of severe pre‐eclampsia, significant mental health concerns or insufficient understanding of the English language. Pregnant women in the HBPM group were taught how to measure and record their blood pressure using a validated machine at home and attended every 1–2 weeks for assessment depending on clinical need. The control group was managed as per the local protocol prior to the implementation of HBPM. The two groups were compared with respect to number of visits to antenatal services and outcome.ResultsThere were 108 women in the HBPM group and 58 in the control group. There was no difference in maternal age, parity, body mass index, ethnicity or smoking status between the groups, but there were more women with chronic hypertension in the HBPM group compared with the control group (49.1% vs 25.9%, P = 0.004). The HBPM group had significantly fewer outpatient attendances per patient (6.5 vs 8.0, P = 0.003) and this difference persisted when taking into account differences in duration of monitoring (0.8 vs 1.6 attendances per week, P < 0.001). There was no difference in the incidence of adverse maternal, fetal or neonatal outcome between the two groups.ConclusionHBPM in hypertensive pregnancies has the potential to reduce the number of hospital visits required by patients without compromising maternal and pregnancy outcomes. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.
A systematic review and meta-analysis of the incidence of psychotic disorders: the distribution of rates and the influence of gender, urbanicity, immigration and socio-economic level
Authors: Castillejos M. C. , Martín-Pérez C. , Moreno-Küstner B. 
Published: February 2018

BackgroundConsidering existing knowledge on the relationship between certain environmental factors and incidence rates of psychosis, we carried out a systematic review to provide a broad and updated picture of the incidences of different psychotic disorder subgroups worldwide and how some environmental factors influence these rates.MethodsStudies with original data related to the incidence of psychosis (published between 2000 and 2015) were identified via searching electronic databases (CINAHL, MEDLINE, PSYCINFO, PUBMED, and SCOPUS). Data on the following risk factors were extracted: gender, urbanicity, immigration and socio-economic level. Descriptive appraisals of variation in incidence rates (IR) and incidence rate ratios (IRR), with a 95% confidence interval were calculated. In addition, a meta-analysis was performed to calculate IR pooled by diagnosis group and IRR pooled by diagnosis and gender, urbanity, immigration and socio-economic level, using a random effects model.ResultsWe identified 33 reports to analyse. Overall IR per 100 000 persons for non-affective psychoses (IR pooled = 22.53 (16.51–28.54)) were higher than affective psychoses (IR pooled = 7.12 (5.03–9.22)). There was an increase in rates of psychosis in menv.women (IRR pooled = 1.54 (1.37–1.72)), in urbanv.rural areas (IRR pooled = 1.64 (1.38–1.95)), in immigrantsv.natives (IRR pooled = 3.09 (2.74–3.49)), and in lower socio-economic level areas (IRR pooled = 1.78 (1.43–2.22)).ConclusionsIR among different psychotic disorders was found to vary depending on gender, urbanicity, and immigration (as most of the previous literature focuses on non-affective psychosis or schizophrenia).
Genetic and hybrid algorithms for optimization of non-singular 3

P

RR planar parallel kinematics mechanism for machining application
Authors: Rosyid Abdur , El-Khasawneh Bashar , Alazzam Anas 
Published: February 2018

SUMMARYThis paper proposes a special non-symmetric topology of a 3PRR planar parallel kinematics mechanism, which naturally avoids singularity within the workspace and can be utilized for hybrid kinematics machine tools. Subsequently, single-objective and multi-objective optimizations are conducted to improve the performance. The workspace area and minimum eigenvalue, as well as the condition number of the homogenized Cartesian stiffness matrix across the workspace, have been chosen as the objectives in the optimization based on their relevance to the machining application. The single-objective optimization is conducted by using a single-objective genetic algorithm and a hybrid algorithm, whereas the multi-objective optimization is conducted by using a multi-objective genetic algorithm, a weighted sum single-objective genetic algorithm, and a weighted sum hybrid algorithm. It is shown that the single-objective optimization gives superior value in the optimized objective, while sacrificing the other objectives, whereas the multi-objective optimization compromises the improvement of all objectives by providing non-dominated values. In terms of the algorithms, it is shown that a hybrid algorithm can either verify or refine the optimal value obtained by a genetic algorithm.
EMC microwave absorber for outdoor applications
Authors: Kubacki Roman , Głuszewski Wojciech , Laskowski Dariusz , Rudyk Karol , Kuchta Marek 
Published: February 2018

AbstractIn some circumstances, electromagnetic compatibility testing must be performed not in a specialized anechoic chamber, but in an open space. However, typical absorbers used in anechoic chambers to absorb incident radiation and to reduce the amount of rays reflected from the walls and the floor, such as ferrite tiles and graphite cones, are not suitable in an open space. In this work, we present the design and a test for the absorbing material, which can successfully be used in a tent or in a similar light and portable structure. The proposed composite material is flexible, has good absorbing and mechanical properties as well as low reflectivity. As an absorber, the nanocrystalline iron alloy with graphite, mixed with an elastomer was proposed. This material was additionally exposed to the ionizing radiation in the dose of 100 kGy in the radioactive gamma source (60Co). The permittivity, permeability, and the shielding properties of the material have been analyzed as well.
Transcriptional patterns identify resource controls on the diazotrophTrichodesmiumin the Atlantic and Pacific oceans
Authors: Rouco Mónica , Frischkorn Kyle R , Haley Sheean T , Alexander Harriet , Dyhrman Sonya T 
Published: February 2018

AbstractThe N2-fixing cyanobacterium Trichodesmium is intensely studied because of the control this organism exerts over the cycling of carbon and nitrogen in the low nutrient ocean gyres. Although iron (Fe) and phosphorus (P) bioavailability are thought to be major drivers of Trichodesmium distributions and activities, identifying resource controls on Trichodesmium is challenging, as Fe and P are often organically complexed and their bioavailability to a single species in a mixed community is difficult to constrain. Further, Fe and P geochemistries are linked through the activities of metalloenzymes, such as the alkaline phosphatases (APs) PhoX and PhoA, which are used by microbes to access dissolved organic P (DOP). Here we identified significant correlations between Trichodesmium-specific transcriptional patterns in the North Atlantic (NASG) and North Pacific Subtropical Gyres (NPSG) and patterns in Fe and P biogeochemistry, with the relative enrichment of Fe stress markers in the NPSG, and P stress markers in the NASG. We also observed the differential enrichment of Fe-requiring PhoX transcripts in the NASG and Fe-insensitive PhoA transcripts in the NPSG, suggesting that metalloenzyme switching may be used to mitigate Fe limitation of DOP metabolism in Trichodesmium. This trait may underpin Trichodesmium success across disparate ecosystems.
Co-inhibition of BET proteins and NF-κB as a potential therapy for colorectal cancer through synergistic inhibiting MYC and FOXM1 expressions
Authors: Wu Tingyu , Wang Guanghui , Chen Wei , Zhu Zhehui , Liu Yun , Huang Zhenyu , Huang Yuji , Du Peng , Yang Yili , Liu Chen-Ying , Cui Long 
Published: February 2018

AbstractThe bromodomain and extra-terminal domain inhibitors (BETi) are promising epigenetic drugs for the treatment of various cancers through suppression of oncogenic transcription factors. However, only a subset of colorectal cancer (CRC) cells response to BETi. We investigate additional agents that could be combined with BETi to overcome this obstacle. JQ1-resistant CRC cells were used for screening of the effective combination therapies with JQ1. RNA-seq was performed to explore the mechanism of synergistic effect. The efficacy of combinational treatment was tested in the CRC cell line- and patient-derived xenograft (PDX) models. In BETi-sensitive CRC cells, JQ1 also impaired tumor angiogenesis through the c-myc/miR-17-92/CTGF+THBS1 axis. CTGF knockdown moderately counteracted anti-angiogenic effect of JQ1 and led to partially attenuated tumor regression. JQ1 decreased c-myc expression and NF-κB activity in BETi-sensitive CRC cells but not in resistant cells. Bortezomib synergistically sensitized BETi-resistant cells to the JQ1 treatment, and JQ1+Bortezomib induced G2/M arrest in CRC cells. Mechanistically, inhibition of NF-κB by Bortezomib or NF-κB inhibitor or IKK1/2 siRNA all rendered BETi-resistant cells more sensitive to BETi by synergistic repression of c-myc, which in turn induces GADD45s’ expression, and by synergistic repression of FOXM1 which in turn inhibit G2/M checkpoint genes’ expression. Activation of NF-κB by IκBα siRNA induced resistance to JQ1 in BETi-sensitive CRC cells. Last, JQ1+Bortezomib inhibited tumor growth and angiogenesis in CRC cell line xenograft model and four PDX models. Our results indicate that anti-angiogenic effect of JQ1 plays a vital role in therapeutic effect of JQ1 in CRC, and provide a rationale for combined inhibition of BET proteins and NF-κB as a potential therapy for CRC.
Sheep genome functional annotation reveals proximal regulatory elements contributed to the evolution of modern breeds
Authors: Naval-Sanchez Marina , Nguyen Quan , McWilliam Sean , Porto-Neto Laercio R. , Tellam Ross , Vuocolo Tony , Reverter Antonio , Perez-Enciso Miguel , Brauning Rudiger , Clarke Shannon , McCulloch Alan , Zamani Wahid , Naderi Saeid , Rezaei Hamid Reza , Pompanon Francois , Taberlet Pierre , Worley Kim C. , Gibbs Richard A. , Muzny Donna M. , Jhangiani Shalini N. , Cockett Noelle , Daetwyler Hans , Kijas James 
Published: February 2018

AbstractDomestication fundamentally reshaped animal morphology, physiology and behaviour, offering the opportunity to investigate the molecular processes driving evolutionary change. Here we assess sheep domestication and artificial selection by comparing genome sequence from 43 modern breeds (Ovis aries) and their Asian mouflon ancestor (O. orientalis) to identify selection sweeps. Next, we provide a comparative functional annotation of the sheep genome, validated using experimental ChIP-Seq of sheep tissue. Using these annotations, we evaluate the impact of selection and domestication on regulatory sequences and find that sweeps are significantly enriched for protein coding genes, proximal regulatory elements of genes and genome features associated with active transcription. Finally, we find individual sites displaying strong allele frequency divergence are enriched for the same regulatory features. Our data demonstrate that remodelling of gene expression is likely to have been one of the evolutionary forces that drove phenotypic diversification of this common livestock species.
Long-term optical brain imaging in live adult fruit flies
Authors: Huang Cheng , Maxey Jessica R. , Sinha Supriyo , Savall Joan , Gong Yiyang , Schnitzer Mark J. 
Published: February 2018

AbstractTime-lapse in vivo microscopy studies of cellular morphology and physiology are crucial toward understanding brain function but have been infeasible in the fruit fly, a key model species. Here we use laser microsurgery to create a chronic fly preparation for repeated imaging of neural architecture and dynamics for up to 50 days. In fly mushroom body neurons, we track axonal boutons for 10 days and record odor-evoked calcium transients over 7 weeks. Further, by using voltage imaging to resolve individual action potentials, we monitor spiking plasticity in dopamine neurons of flies undergoing mechanical stress. After 24 h of stress, PPL1-α’3 but not PPL1-α’2α2 dopamine neurons have elevated spike rates. Overall, our chronic preparation is compatible with a broad range of optical techniques and enables longitudinal studies of many biological questions that could not be addressed before in live flies.
Uniform two-dimensional square assemblies from conjugated block copolymers driven by π–π interactions with controllable sizes
Authors: Han Liang , Wang Meijing , Jia Xiangmeng , Chen Wei , Qian Hujun , He Feng 
Published: February 2018

AbstractTwo-dimensional (2-D) micro- and nano-architectures are attractive because of their unique properties. However, the formation of 2-D supramolecular highly symmetrical structures with considerable control is still a major challenge. Here we present a simple approach for the preparation of regular and homogeneous 2-D fluorescent square non-crystallization micelles with conjugated diblock copolymers PPV12-b-P2VP
n
through a process of dissolving–cooling–aging. The scale of the formed micelles can be controlled by the ratio of PPV/P2VP blocks and the concentration of the solution. The results reveal that the micelles of PPV12-b-P2VP
n
initially form 1-D structures and then grow into 2-D structures in solution, and the growth is driven by intermolecular π–π interactions with the PPV12 blocks. The formation of 2-D square micelles is induced by herringbone arrangement of the molecules, which is closely related to the presence of the branched alkyl chains attached to conjugated PPV12 cores.
A quantum light-emitting diode for the standard telecom window around 1,550 nm
Authors: Müller T. , Skiba-Szymanska J. , Krysa A. B. , Huwer J. , Felle M. , Anderson M. , Stevenson R. M. , Heffernan J. , Ritchie D. A. , Shields A. J. 
Published: February 2018

AbstractSingle photons and entangled photon pairs are a key resource of many quantum secure communication and quantum computation protocols, and non-Poissonian sources emitting in the low-loss wavelength region around 1,550 nm are essential for the development of fibre-based quantum network infrastructure. However, reaching this wavelength window has been challenging for semiconductor-based quantum light sources. Here we show that quantum dot devices based on indium phosphide are capable of electrically injected single photon emission in this wavelength region. Using the biexciton cascade mechanism, they also produce entangled photons with a fidelity of 87 ± 4%, sufficient for the application of one-way error correction protocols. The material system further allows for entangled photon generation up to an operating temperature of 93 K. Our quantum photon source can be directly integrated with existing long distance quantum communication and cryptography systems, and provides a promising material platform for developing future quantum network hardware.
Temperature-dependent phonon spectra of magnetic random solid solutions
Authors: Ikeda Yuji , Körmann Fritz , Dutta Biswanath , Carreras Abel , Seko Atsuto , Neugebauer Jörg , Tanaka Isao 
Published: February 2018

AbstractA first-principles-based computational tool for simulating phonons of magnetic random solid solutions including thermal magnetic fluctuations is developed. The method takes fluctuations of force constants due to magnetic excitations as well as due to chemical disorder into account. The developed approach correctly predicts the experimentally observed unusual phonon hardening of a transverse acoustic mode in Fe–Pd an Fe–Pt Invar alloys with increasing temperature. This peculiar behavior, which cannot be explained within a conventional harmonic picture, turns out to be a consequence of thermal magnetic fluctuations. The proposed methodology can be straightforwardly applied to a wide range of materials to reveal new insights into physical behaviors and to design materials through computation, which were not accessible so far.
Secondary forest regeneration benefits old-growth specialist bats in a fragmented tropical landscape
Authors: Rocha Ricardo , Ovaskainen Otso , López-Baucells Adrià , Farneda Fábio Z. , Sampaio Erica M. , Bobrowiec Paulo E. D. , Cabeza Mar , Palmeirim Jorge M. , Meyer Christoph F. J. 
Published: February 2018

AbstractTropical forest loss and fragmentation are due to increase in coming decades. Understanding how matrix dynamics, especially secondary forest regrowth, can lessen fragmentation impacts is key to understanding species persistence in modified landscapes. Here, we use a whole-ecosystem fragmentation experiment to investigate how bat assemblages are influenced by the regeneration of the secondary forest matrix. We surveyed bats in continuous forest, forest fragments and secondary forest matrix habitats, ~15 and ~30 years after forest clearance, to investigate temporal changes in the occupancy and abundance of old-growth specialist and habitat generalist species. The regeneration of the second growth matrix had overall positive effects on the occupancy and abundance of specialists across all sampled habitats. Conversely, effects on generalist species were negligible for forest fragments and negative for secondary forest. Our results show that the conservation potential of secondary forests for reverting faunal declines in fragmented tropical landscapes increases with secondary forest age and that old-growth specialists, which are often of most conservation concern, are the greatest beneficiaries of secondary forest maturation. Our findings emphasize that the transposition of patterns of biodiversity persistence in island ecosystems to fragmented terrestrial settings can be hampered by the dynamic nature of human-dominated landscapes.