bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetic profiling of anticancer phytocompounds using computational approach
Authors: Sharma Ashish , Sharma Shilpa , Gupta Mansi , Fatima Shehnaz , Saini Ravi , Agarwal Subhash Mohan 
Published: April 2018

AbstractIntroductionNatural products exhibit diverse scaffolds and are considered as suitable candidates for development of leads. However, poor pharmacokinetics often acts as a hindrance during the drug discovery process.ObjectiveWith a view of exploring the absorption, distribution, metabolism, excretion and toxicity (ADMET) profile of plant‐based anticancer compounds, open‐access databases (NPACT, CancerHSP and TaxKB) were analysed to identify molecules having properties favourable for drug ability.MethodologyOur workflow involved identification of molecules capable of passing each of the ADMET barriers based on physicochemical properties of molecules, and physiological barriers and factors.ResultsThe results revealed that out of 5086 phytomolecules, 63% were orally absorbable and 52% distributable. Also, an appreciable proportion of these compounds (45%) could be metabolised and excreted. Furthermore, 28% were found to be non‐toxic for cardio toxicity and central nervous system (CNS) activity. Additionally, comparison against known anticancer drugs (reference dataset) revealed that the three libraries exhibit similar trends, thus providing additional confidence to the predictions. Overall, 28% of the molecular dataset was found to have suitable pharmacokinetic properties. We have also discussed a few natural products which exhibit favourable ADMET as well as low nano‐micromolar in vitro anticancer activity.ConclusionWe have created an interactive database (ADMETCan), which provides access to predicted ADMET of these anticancer phytomolecules. The ease of availability of this dataset is expected to minimise failure rate of these compounds and thus is expected to be beneficial to the scientific community involved in anticancer identification and development.
Self‐assembly behavior of amphiphilic linear‐block‐dendritic copolymers with long subchains: Dependences on dendron generation and mixing dynamics
Authors: Li Peng‐Yun , He Chen , Xie Wei‐Xiang , Li Hui‐Juan , Haleem Abdul , Hu Chuan‐Shan , Li Xi‐Chuan , He Wei‐Dong 
Published: April 2018

ABSTRACTBlock copolymers composed of acrylic acid and methyl methacrylate with three topologies of double linear blocks, poly(acrylic acid) (PAA) linear block/poly(methyl methacrylate) (PMMA) G1‐dendron and PAA linear block/PMMA G2‐dendron have been prepared by the combination of atom transfer radical polymerization and azide–alkyne click reaction. Proton nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy, and gel permeation chromatography have been adopted thoroughly to identify the chemical structure of those block copolymers with expected topologies. The self‐assembly of those block copolymers in the selective solvent has been performed through two mixing routes of gentle and abrupt variation in solvent selectivity, and the morphology of the obtained self‐assemblies/aggregates was observed by transmission electron microscopy. Because the abrupt variation route altered sharply the solvent quality during the mixing, the intermolecular association of polymer chains resulted in the smaller self‐assemblies but the further growth of smaller self‐assemblies was not observed. On the contrary, the gentle variation route changed gradually the solvent quality during the mixing, favoring not only the intermolecular association but also the further growth of self‐assemblies to result in larger aggregates. The final morphology of those assemblies/aggregates also exhibited the dependence of PMMA dendron generation. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 1446–1456
Does stress increase risk of breast cancer? A 15‐year prospective study
Authors: Butow Phyllis , Price Melanie , Coll Joseph , Tucker Katherine , Meiser Bettina , Milne Roger , Wilson Judith , Heiniger Louise , Baylock Brandi , Bullen Tracey , Weideman Prue , Phillips Kelly‐Anne ,   on behalf of the kConFab investigators,   kConFab Clinical Follow‐Up investigators,   kConFab psychosocial investigators
Published: April 2018

AbstractObjectiveThe possible impact of stress on cancer incidence remains controversial. We prospectively evaluated associations between life event stressors, social support, personality characteristics (optimism, anger control, antiemotionality), and risk of developing primary breast cancer (BCa), in women at increased familial risk of BCa.MethodsA prospective cohort, repeated measures design was used. Recruitment was through the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, which collects genetic, epidemiological, and clinical data from Australasian families with multiple BCa cases. Acute and chronic stressors for the prior 3 years and psychosocial, clinical, and epidemiological variables were measured at cohort entry and at 3‐yearly intervals. Cox proportional hazard regression analysis controlling for BCa risk factors and familial clustering was undertaken. The primary outcome was histopathologically confirmed BCa (invasive or ductal carcinoma in situ, including occult cases diagnosed during risk‐reducing mastectomy).ResultsOf 3595 consecutive women invited to participate, 3054 (85.0%) consented. Of these, 2739 (89.7%) from 990 families (range 1‐16 per family) completed at least 1 assessment point. During the study, 103 women were diagnosed with BCa. No stressor or psychosocial variable or interaction between them was significantly associated with BCa in unadjusted or adjusted models (total acute stressors HR = 1.03 [0.99‐1.08], P = .19; total chronic stressors HR = 1.0 [0.90‐1.11], P = .98).ConclusionsThis study did not demonstrate an association between acute and chronic stressors, social support, optimism, antiemotionality or anger control, and BCa risk. Women should focus on proven methods of BCa risk reduction.
Proteomics Analysis Reveals Abnormal Electron Transport and Excessive Oxidative Stress Cause Mitochondrial Dysfunction in Placental Tissues of Early‐Onset Preeclampsia
Authors: Xu Zhongwei , Jin Xiaohan , Cai Wei , Zhou Maobin , Shao Ping , Yang Zhen , Fu Rong , Cao Jin , Liu Yan , Yu Fang , Fan Rong , Zhang Yan , Zou Shuang , Zhou Xin , Yang Ning , Chen Xu , Li Yuming 
Published: April 2018

PurposeEarly‐onset preeclampsia (EOS‐PE) refers to preeclampsia that occurred before 34 gestation weeks. This study is conducted to explore the relationship between mitochondrial dysfunction and the pathogenesis of EOS‐PE using proteomic strategy.Experimental designTo identify altering expressed mitochondrial proteins between severe EOS‐PE and healthy pregnancies, enrichment of mitochondria coupled with iTRAQ‐based quantitative proteomic method is performed. Immunohistochemistry (IHC) and western blot are performed to detect the alteration of changing expression proteins, and confirmed the accuracy of proteomic results.ResultsA total of 1372 proteins were quantified and 132 altering expressed proteins were screened, including 86 downregulated expression proteins and 46 upregulated expression proteins (p < 0.05). Bioinformatics analysis showed that differentially expressed proteins participated in numerous biological processes, including oxidation–reduction process, respiratory electron transport chain, and oxidative phosphorylation. Especially, mitochondria‐related molecules, PRDX2, PARK7, BNIP3, BCL2, PDHA1, SUCLG1, ACADM, and NDUFV1, are involved in energy‐production process in the matrix and membrane of mitochondria.Conclusions and clinical relevanceResults of the experiment show that abnormal electron transport, excessive oxidative stress, and mitochondrion disassembly might be the main cause of mitochondrial dysfunction, and is related to the pathogenesis of EOS‐PE.
Knowledge‐based intensity‐modulated radiotherapy plans for cervical cancer with overlap volume of target and organs at risk
Authors: Ma Changdong , Luo Judong , Zhang Zhongquan , Ma Changsheng 
Published: April 2018

AbstractObjectiveTo compare the differences in the dose‐volume histograms between knowledge‐based intensity‐modulated radiotherapy (K‐IMRT) plans and conventional IMRT (C‐IMRT) plans of 20 patients with cervical cancer.MethodsA total of 70 cervical cancer patients were selected in the present study. Of these, 60 patients were selected randomly as a model group. The remaining 10 patients with overlap volume of target and organs at risk were categorized as group E1 for open‐loop verification. A total of 10 patients from the model group were selected randomly as group E2 for closed‐loop verification.ResultsThe dose parameters of the target in the K‐IMRT and C‐IMRT plans showed no significant difference. The maximum dose and homogeneity index of group E2 showed no significant difference (P > 0.05) in their K‐IMRT and C‐IMRT plans. The dose parameters in the K‐IMRT plans of organs at risk were superior to those in the C‐IMRT plans. For group E1, V20 of the rectum, and V15, V20, and V25 of the left and right femoral heads in the K‐IMRT plans decreased as compared with those in the C‐IMRT plans (P < 0.05). For group E2, V25, V30, V35, and D50 of the bladder; V25 and V30 of the rectum; and V15, V20, and V25 of the left and right femoral heads in the K‐IMRT plans decreased as compared with those in the C‐IMRT plans (P < 0.05).ConclusionIt is feasible to optimize the IMRT plans for cervical cancer patients with the overlap volume of the target and organs at risk using knowledge‐based radiation treatment automatically.
Computational assessment of folding energy landscapes in heterodimeric coiled coils
Authors: André Ingemar , Bjelic Sinisa 
Published: April 2018

AbstractThe coiled coil structural motif consists of alpha helices supercoiling around each other to form staggered knobs‐into‐holes packing. Such structures are deceptively simple, especially as they often can be described with parametric equations, but are known to exist in various conformations. Even the simplest systems, consisting of 2 monomers, can assemble into a wide range of states. They can form canonical as well as noncanonical coiled coils, be parallel or antiparallel, where helices associate with different degrees of shift, tilt, and rotation. Here, we investigate the energy landscape of heterodimeric coiled coils by carrying out de novo folding simulations starting from amino acid sequence. We folded a diverse set of 22 heterodimers and demonstrate that the approach is capable of identifying the atomic details in the experimental structure in the majority of cases. Our methodology also enables exploration of alternative states that can be accessible in solution beyond the experimentally determined structure. For many systems, we observe folding energy landscapes with multiple energy minima and several isoenergetic states. By comparing coiled coils from single domains and those extracted from larger proteins, we find that standalone coiled coils have deeper energy wells at the experimentally determined conformation. By folding the competing homodimeric states in addition to the heterodimers, we observe that the structural specificity towards the heteromeric state is often small. Taken together, our results demonstrate that de novo folding simulations can be a powerful tool to characterize structural specificity of coiled coils when coupled to assessment of energy landscapes.
Physicochemical property guidelines for modern agrochemicals
Authors: Zhang Yu , Lorsbach Beth A , Castetter Scott , Lambert William T , Kister Jeremy , Wang Nick X , Klittich Carla J R , Roth Joshua , Sparks Thomas C , Loso Mike R 
Published: April 2018

AbstractThe relentless need for the discovery and development of new agrochemicals continues as a result of driving forces such as loss of existing products through the development of resistance, the necessity for products with more favorable environmental and toxicological profiles, shifting pest spectra, and the changing agricultural needs and practices of the farming community. These new challenges underscore the demand for novel, high‐quality starting points to accelerate the discovery of new agrochemicals that address market challenges. This article discusses the efforts to identify the optimum ranges of physicochemical properties of agrochemicals through analysis of modern commercial products. Specifically, we reviewed literature studies examining physicochemical property effects and analyzed the properties typical of successful fungicides, herbicides, and insecticides (chewing and sap‐feeding pests). From the analysis, a new set of physicochemical property guidelines for each discipline, as well as building block class, are proposed. These new guidelines should significantly aid in the discovery of next‐generation agrochemicals. © 2018 Society of Chemical Industry
Using set invariance to design robust interval observers for discrete‐time linear systems
Authors: Meslem N. , Loukkas N. , Martinez J.J. 
Published: April 2018

SummaryBased on interval and invariant set computation, an interval version of the Luenberger state observer for uncertain discrete‐time linear systems is proposed in this work. This new interval observer provides a punctual estimation of the state vector and guaranteed bounds on the estimation error. An off‐line and an on‐line approach to characterize, in a guaranteed way, the estimation error are introduced. Compared with the existing approaches, the proposed interval observer design method is not restrictive in terms of required assumptions, complexity, and on‐line computation time. Furthermore, the convergence issue of the estimation error is well established and to reduce the conservatism of the estimated state enclosure induced by the bounded additive state disturbance and noise measurement, an H∞ method to compute the optimal observer gain is proposed. The performance of the proposed state estimation approach are highlighted on different illustrative examples.
Stabilization of a class of cascade nonlinear switched systems with application to chaotic systems
Authors: Aghababa Mohammad Pourmahmood 
Published: April 2018

SummaryIn this study, the problem of finite‐time practical control of a class of nonlinear switched systems in the presence of input nonlinearities is investigated. The subsystems of the switched system are considered as complex nonlinear systems with a cascade structure. Each subsystem is fluctuated by lumped uncertainties. Moreover, some parts of the system's dynamics are considered to be unknown in advance. This paper sets no restrictive assumption on the switching logic of the system. Therefore, the aim is to propose a controller to work under any arbitrary switching signals. After providing a smooth sliding manifold, a simple adaptive control input is developed such that the system trajectories approach the prescribed sliding mode dynamics in finite‐time sense. The adopted control signal does not use the upper bounds of the lumped uncertainties, and it is robust against unknown nonlinear parts of the subsystems. It is proved that the origin is the (practical) finite‐time stable equilibrium point of the overall closed‐loop system. Subsequently, the proposed control rule is modified to handle the same switched system with no input nonlinearities. Computer simulations via 2 chaotic electric direct current machines demonstrate the robust performance of the derived variable structure control algorithm against system fluctuations and nonlinear inputs.
Nitrogen cycling in large temperate floodplain rivers of contrasting nutrient regimes and management
Authors: Richardson W.B. , Bartsch L.A. , Bartsch M.R. , Kiesling R. , Lafrancois B.M. 
Published: April 2018

AbstractHydraulic connection between channels and floodplains (“connectivity”) is a fundamental determinant of ecosystem function in large floodplain rivers. Factors controlling material processing in these rivers depend not only on the degree of connectivity but also on the sediment conditions, nutrient loads, and source. Nutrient cycling in the nutrient‐rich upper Mississippi River (MISS) is relatively well studied, whereas that of less eutrophic tributaries is not (e.g., St Croix River; SACN). We examined components of nitrogen cycling in 2 floodplain rivers of contrasting nutrient enrichment and catchment land use to test the hypothesis that N‐cycling rates will be greater in the MISS with elevated nutrient loads and productivity in contrast to the relatively nutrient‐poor SACN. Nitrate (NO3−‐N) concentrations were greatest in flowing habitats in the MISS and often undetectable in isolated backwaters except where groundwater inputs occurred. In the SACN, NO3−‐N concentrations were greatest in the flowing backwater where groundwater inputs were high. Ambient nitrification in the MISS was twice that in the SACN and tended to be lowest in the main channel. Denitrification was 3× greater in the MISS than that in the SACN, N‐limited in both rivers. Community production/respiration was >1 in the MISS and likely provisioned labile C to fuel microbial metabolism and dissimilatory NO3−‐N reduction, whereas the heterotrophic (production/respiration < 1) nature of the SACN likely limited microbial metabolism and NO3−‐N dissimilation. It appears that N‐cycling in the SACN was driven by groundwater, whereas that in the MISS was supported mainly by water column N‐sources.
Rollover Cyclopalladation via Remote C‐H Bond Activation of Br‐Pyridinbenzothiazole: An Experimental Study
Authors: Tovar‐Ramírez Martin E. , Ramírez‐Zúńiga Rosario , Nicasio‐Collazo Juan , Wrobel Katarzyna , Alvarado‐Rodríguez José G. , Wrobel Kazimierz , Serrano Oracio 
Published: April 2018

AbstractRollover palladacycles complexes containing pyridinebenzothiazole fragments were synthetized via remote C−H bond activation by PdCl2 in DMF. The structures of these compounds were proposed based on NMR analysis and high‐resolution mass spectrometry; in selected case of compound 1, its molecular structure was corroborated by single crystal X‐ray diffraction experiment. Upon solubilization in acetonitrile and using ESI‐QTOFMS, this complex was found as unusual tricoordinate cationic complex 1‐NCCH3 with acetonitrile attachment via Pd−Cl bond activation. Of note, synthesis success when PdCl2 was used as the starting material and mild heating (60 °C) of the reaction mixture was necessary to obtain the desired compound in a reasonable time (7 days). Evidence is provided that DMF solvent plays a key mechanistic role enabling the formation of organometallic rollover compounds; whereas using another solvent like DMSO, NCCH3 or acetone, a classic coordination complex is obtained.
Design, Synthesis, DNA Binding, and Docking Studies of Thiazoles and Thiazole‐Containing Triazoles as Antibacterials
Authors: Santosh Rangappa , Selvam Mukunthan K. , Kanekar Saptami U. , Nagaraja Gundibasappa K. , Kumar Madan 
Published: April 2018

AbstractA series of thiazoles 4 a‐g and thiazole clubbed triazoles 5 a‐f were synthesized and showed good antibacterial activity against, Pseudomonas aeruginosa, Escherchia coli, Staphylococcus aureus and Bacillus subtilis. Particularly, 4 a (methyl), 5 b (nitro) and 5 d (fluoro) derivatives demonstrated a broad range of activity over other derivatized compounds. In addition, Computational interaction, ADMET (absorption, distribution, metabolism, and excretion ‐ toxicity in pharmacokinetics), Lipinski's rule and DNA binding studies of all the results stacked together indicated that 5 b can be further developed as lead molecule against bacterial pathogens.
Effects of Surgically Implanted Acoustic Tags on Body Condition, Growth, and Survival in a Small, Laterally Compressed Forage Fish
Authors: Klinard Natalie V. , Halfyard Edmund A. , Fisk Aaron T. , Stewart Thomas J. , Johnson Timothy B. 
Published: April 2018

AbstractTelemetry studies often assume a lack of adverse effects caused by tag attachment and presence in various species and size‐classes, which may lead to inaccurate conclusions about fish behavior in field studies. Studies that examine the effects of tagging are typically performed on salmonids and adult fishes rather than on the small fishes that are increasingly becoming the focus of telemetry studies. The objectives of this study were to assess the effects of intracoelomic acoustic tagging on growth, condition, survival, and tag retention in subadult hatchery Bloaters Coregonus hoyi (a focal species for restoration efforts in the Laurentian Great Lakes) and to determine the maximum tag burden below which tag effects are reduced. Fish were either tagged with one of three dummy acoustic transmitters (Vemco V6: n = 50; V7: n = 50; V9: n = 50) or were followed as controls (n = 50; anesthesia, PIT‐tagging, and handling only) or sham individuals (n = 49; anesthesia, surgery, suturing, and PIT‐tagging but no acoustic tag implanted). Tags represented 1.3–9.0% of body mass. All fish received a PIT tag for individual identification throughout the 6‐month monitoring period (November 2014–May 2015). Survival exceeded 90% in all treatment groups, and the tag retention rate was 100%. All surviving fish appeared healthy and in excellent condition at the conclusion of the experiment. The results of this study suggest that acoustic transmitters with a tag mass : body mass ratio of 9% or less can be successfully implanted intracoelomically into subadult Bloaters—small, laterally compressed pelagic fish—with no adverse effects.
On the tails of the wind ramp distributions
Authors: DeMarco Adam , Basu Sukanta 
Published: April 2018

AbstractWe analyzed several multiyear wind speed datasets from 4 different geographical locations. The probability density functions of wind ramps from all these sites revealed remarkably similar shapes. The tails of the probability density functions are much heavier than a Gaussian distribution, and they also systematically depend on time increments. Quite interestingly, from a purely statistical standpoint, the characteristics of the extreme ramp‐up and ramp‐down events are found to be almost identical. With the aid of extreme value theory, we describe several other inherent features of extreme wind ramps in this paper.