bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multiobjective optimization approach to filter tuning applied to coupled hyperbolic PDEs describing gas flow dynamics
Authors: Uilhoorn Ferdinand Evert 
Published: May 2019

SummaryIn this work, we introduce a multiobjective optimization approach that seeks the optimal process noise statistics in the extended Kalman filter (EKF). The bi‐objective Mesh Adaptive Direct Search (BiMADS) algorithm was used to minimize a performance index based on state estimate errors. The EKF estimated the gas flow dynamics in a pipeline system. Simulations were conducted with outflow boundary conditions for the flow model that contain gradual changes and discontinuities. To ensure shock‐capturing properties, the model was approximated with a semidiscrete finite volume scheme using Roe's SUPERBEE limiter. The knee point in the Pareto front was based on normal boundary intersection approach and selected to compute the flow estimates. Numerical experiments demonstrated that BiMADS is suitable for tuning the EKF and, compared to the normalized weighted sum method and nondominated sorting genetic algorithm, it showed to be superior in terms of computation time and most effective in finding Pareto optimal solutions.
Engaging stakeholders in pharmacoepidemiology research: Current state and recommendations
Authors: Camelo Castillo Wendy , Heath Nicholas , Kim John , Yang Kimberly , Ritchey Mary E. , dosReis Susan , Santanello Nancy , West Suzanne L. 
Published: May 2019

AbstractPurposeGiven current efforts to enhance patient‐centered care and shared decision‐making, the International Society of Pharmacoepidemiology Workgroup on Patient Engagement assessed patient and other stakeholder engagement in pharmacoepidemiology research and provides recommendations for the field.MethodsA systematic review used MEDLINE and EMBASE to identify published literature from 2005 to 2016 addressing how stakeholders—patients, caregivers, and others—assisted researchers conducting pharmacoepidemiologic research. Three pairs of Workgroup members screened titles and abstracts to select articles for full‐text review and analysis. Two Workgroup members abstracted the following data: research focus, characterization and role of stakeholders, and type(s) of engagement strategy employed. Data were summarized descriptively.ResultsWe identified 5717 references for abstract screening. Of these, 69 met the criteria for full‐text screening, and 11 were selected for data abstraction. Of these 11 studies, seven focused on the development of a research agenda and eight had stakeholders react or advise on an aspect of the study. Although patients were the most commonly identified stakeholders, advocacy groups and health care professionals were also frequently identified. Some studies reported the engagement of other stakeholders, including local government or policy experts. Engagement strategies varied, with five studies using more than one strategy. Studies often did not indicate the involvement of stakeholders in developing the study design or with implementation.ConclusionsCurrently, few pharmacoepidemiology publications mention patient or other stakeholder engagement in the design, analysis, or reporting of research. This suggests that there are opportunities to expand stakeholder engagement and/or increase the transparency of reporting stakeholder engagement.
Lack of meaning, purpose and direction in life in personality disorder: A comparative quantitative approach using Livesley's General Assessment of Personality Disorder
Authors: Steen A. , Berghuis H. , Braam A.W. 
Published: May 2019

AbstractMeaning in life is a motivational force and an existential theme for many people. The concept of meaning comprises purpose, comprehension and mattering. According to the Section III model of personality disorder (DSM‐5), lack of meaning, purpose and direction in life is part of personality dysfunction. The present study aimed to determine the association between personality disorder (PD), personality dysfunction and ‘lack of meaning, purpose and direction’ as a distinct facet of personality dysfunction, using Livesley's self‐report questionnaire—the General Assessment of Personality Disorder. This comparative quantitative study showed significant differences in lack of meaning, purpose and direction between a group of patients with PD (n = 126, PD with depression n = 51 and PD without depression n = 75), a group of non‐PD patients (n = 76, with depression n = 27 and without depression n = 49) and a control group (n = 444). The PD groups had similar scores as the non‐PD patients with depression. Lack of meaning was significantly associated with ‘difficulty setting and attaining goals’ in all groups, with ‘lack of affiliative relationships’ in the PD groups and ‘sense of inner emptiness’ in the PD group without depression and in controls. © 2019 John Wiley & Sons, Ltd.
Identification and Quantification of Proteoforms by Mass Spectrometry
Authors: Schaffer Leah V. , Millikin Robert J. , Miller Rachel M. , Anderson Lissa C. , Fellers Ryan T. , Ge Ying , Kelleher Neil L. , LeDuc Richard D. , Liu Xiaowen , Payne Samuel H. , Sun Liangliang , Thomas Paul M. , Tucholski Trisha , Wang Zhe , Wu Si , Wu Zhijie , Yu Dahang , Shortreed Michael R. , Smith Lloyd M. 
Published: May 2019

AbstractA proteoform is a defined form of a protein derived from a given gene with a specific amino acid sequence and localized post‐translational modifications. In top‐down proteomic analyses, proteoforms are identified and quantified through mass spectrometric analysis of intact proteins. Recent technological developments have enabled comprehensive proteoform analyses in complex samples, and an increasing number of laboratories are adopting top‐down proteomic workflows. In this review, some recent advances are outlined and current challenges and future directions for the field are discussed.
Reduction and pH dual‐responsive block copolymers containing pendent p‐nitrobenzyl carbamate functionalities: Synthesis and self‐assembly behavior
Authors: Hu Cong , Dong Bingyang , Liu Li 
Published: May 2019

ABSTRACTWe report on the preparation of reduction‐responsive amphiphilic block copolymers containing pendent p‐nitrobenzyl carbamate (pNBC)‐caged primary amine moieties by reversible addition–fragmentation chain transfer (RAFT) radical polymerization using a poly(ethylene glycol)‐based macro‐RAFT agent. The block copolymers self‐assembled to form micelles or vesicles in water, depending on the length of hydrophobic block. Triggered by a chemical reductant, sodium dithionite, the pNBC moieties decomposed through a cascade 1,6‐elimination and decarboxylation reactions to liberate primary amine groups of the linkages, resulting in the disruption of the assemblies. The reduction sensitivity of assemblies was affected by the length of hydrophobic block and the structure of amino acid‐derived linkers. Using hydrophobic dye Nile red (NR) as a model drug, the polymeric assemblies were used as nanocarriers to evaluate the potential for drug delivery. The NR‐loaded nanoparticles demonstrated a reduction‐triggered release profile. Moreover, the liberation of amine groups converted the reduction‐responsive polymer into a pH‐sensitive polymer with which an accelerated release of NR was observed by simultaneous application of reduction and pH triggers. It is expected that these reduction‐responsive block copolymers can offer a new platform for intracellular drug delivery. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1333–1343
Hydrogel‐coated polyurethane/urea shape memory polymer foams
Authors: Dalton Emily , Chai Qinyuan , Shaw Molly W. , McKenzie Tucker J. , Mullins Eric S. , Ayres Neil 
Published: May 2019

ABSTRACTShape memory polymers (SMPs) are a class of responsive polymers that have attracted attention in designing biomedical devices because of their potential to improve minimally invasive surgeries. Use of porous SMPs in vascular grafts has been proposed because porosity aids in transfer of fluids through the graft and growth of vascular tissue. However, porosity also allows blood to leak through grafts so preclotting the materials is necessary. Here hydrogels have been synthesized from acrylic acid and N‐hydroxyethyl acrylamide and coated around a porous SMP produced from lactose functionalized polyurea‐urethanes. The biocompatibility of the polymers used to prepare the cross‐linked shape memory material is demonstrated using an in vitro cell assay. As expected, the hydrogel coating enhanced fluid uptake abilities without hindering the shape memory properties. These results indicate that hydrogels can be used in porous SMP materials without inhibiting the shape recovery of the material. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1389–1395
Novel 4‐pyrazole carboxamide derivatives containing flexible chain motif: design, synthesis and antifungal activity
Authors: Liu Xing‐Hai , Qiao Li , Zhai Zhi‐Wen , Cai Peng‐Peng , Cantrell Charles L , Tan Chen‐Xia , Weng Jian‐Quan , Han Liang , Wu Hong‐Ke 
Published: May 2019

AbstractBackgroundIn recent years, carboxamide fungicides, targeting succinate dehydrogenase (SDH), have shown highly efficient and broad spectrum fungicidal activity. Structure–activity relationship (SAR) results for these commercial fungicides show that the carboxamide group was a key active group. This is useful information for the discovery of new pyrazole carboxamide derivatives with fungicidal activity.ResultsTwenty‐seven novel pyrazole carboxamides were designed and synthesized. Their fungicidal activities against Gibberella zeae, Phytophthora infestans, Phytophthora capsici, Rhizoctonia solani, Alternaria solani, Botrytis cinerea, Fusarium oxysporum, Cercospora arachidicola, Sclerotinia sclerotiorum and Physalospora piricola were tested; derivatives possessed excellent inhibitory at 50 mg L−1 in particular. Furthermore, some pyrazole carboxamides exhibited remarkably high activities against Sclerotinia sclerotiorum in vitro with EC50 values of 2.04 to 15.2 μg mL−1. In addition, some compounds also exhibited high activities against Physalospora piricola, Cercospora arachidicola and Phytophthora capsici. Inhibition activities against SDH proved that the designed analogues were effective at the enzyme level. The SAR of these pyrazole carboxamides was studied by using the docking method.ConclusionIt is possible that pyrazole carboxamides, which exhibit good activity against Sclerotinia sclerotiorum, can be further optimized as a lead compounds of carboxamide fungicides. © 2019 Society of Chemical Industry
Oleandrin sensitizes human osteosarcoma cells to cisplatin by preventing degradation of the copper transporter 1
Authors: Yong Lei , Ma Yunlong , Liang Chen , He Guanping , Zhao Zhigang , Yang Chenlong , Hai Bao , Pan Xiaoyu , Liu Zhongjun , Liu Xiaoguang 
Published: May 2019

A major problem in osteosarcoma treatment is cisplatin resistance. We have reported the anti‐osteosarcoma effect of oleandrin; however, whether oleandrin sensitizes osteosarcoma to cisplatin is unknown. We investigated the chemosensitization of oleandrin and potential mechanisms in osteosarcoma cells U‐2OS, SaOS‐2, and MG‐63. The median‐effect analysis demonstrated that cisplatin + oleandrin exerted synergistic (U‐2OS and MG‐63) or additive effects (SaOS‐2), which were consistent with the changes of the intracellular accumulation of platinum (Pt) and Pt‐DNA adducts. Immunohistochemistry staining showed that the expression level of the mature form CTR1, the major influx transporter of cisplatin, was low in osteosarcoma tissue. However, oleandrin with or without cisplatin significantly increased the expression and membrane localization of the mature CTR1. Furthermore, CTR1 knockdown reversed the synergistic effect and decreased cisplatin uptake. The mRNA microarray analysis suggested that oleandrin downregulated the expression of proteasome‐related genes, which was verified by the proteasome activity assay. Besides, the proteasome inhibitor MG132 upregulated the expression of the mature CTR1 in U‐2OS and MG‐63 cells. Overall, we conclude that oleandrin sensitizes osteosarcoma cells to cisplatin in synergistic or additive manners. The synergy results from the enhanced cisplatin uptake via oleandrin‐mediated inhibition of proteasome activity and subsequent blockage of the mature CTR1 degradation
The dawn of phage therapy
Authors: Rehman Sana , Ali Zahid , Khan Momna , Bostan Nazish , Naseem Saadia 
Published: May 2019

SummaryBacteriophages or phages, being the most abundant entities on earth, represent a potential solution to a diverse range of problems. Phages are successful antibacterial agents whose use in therapeutics was hindered by the discovery of antibiotics. Eventually, because of the development and spread of antibiotic resistance among most bacterial species, interest in phage as therapeutic entities has returned, because their noninfectious nature to humans should make them safe for human nanomedicine. This review highlights the most recent advances and progress in phage therapy and bacterial hosts against which phage research is currently being conducted with respect to food, human, and marine pathogens. Bacterial immunity against phages and tactics of phage revenge to defeat bacterial defense systems are also summarized. We have also discussed approved phage‐based products (whole phage‐based products and phage proteins) and shed light on their influence on the eukaryotic host with respect to host safety and induction of immune response against phage preparations. Moreover, creation of phages with desirable qualities and their uses in cancer treatment, vaccine production, and other therapies are also reviewed to bring together evidence from the scientific literature about the potentials and possible utility of phage and phage encoded proteins in the field of therapeutics and industrial biotechnology.
Robust event‐triggered output feedback learning algorithm for voltage source inverters with unknown load and parameter variations
Authors: Vamvoudakis Kyriakos G. , Pour Safaei Farshad R. , Hespanha João P. 
Published: May 2019

SummaryWe consider the output feedback event‐triggered control of an off‐grid voltage source inverter (VSI) with unknown inductance‐capacitance (L − C) filter dynamics and connected load in the presence of an input disturbance acting at the inverter. Due to uncertain dynamics and unmodeled parameters in the L − C filter connected to the VSI, we use an adaptive observer to reconstruct the system's states by measuring only the voltage at the output. The control mechanism is constructed based on an impulsive actor/critic framework that approximates the cost, the event‐triggered controller, and the worst case disturbance and generates the desired AC output with the least energy dissipation. We provide rigorous stability proofs and illustrate the applicability of our results through a simulation example.
Hierarchical Architecture of Electrospun Hybrid PAN/Ag‐rGO/Fe3O4 Composite Nanofibrous Mat for Antibacterial Applications
Authors: Sadasivam Rajkumar , Sankarakuttalam Chockalingam , Gopinath Packirisamy 
Published: May 2019

AbstractFabrication procedures are crucial for the design and development of composite nanofibrous materials in order to obtain effective antibacterial properties. In this work, solvent homogenization and blend electrospinning are the methodology followed for the synthesis of filler nanomaterials. Earlier the hydrothermally synthesized filler rGO/Fe nanocomposites (NCs) was incorporated through the hierarchical combination onto the PAN/Ag blend to obtain PAN/Ag‐rGO/Fe3O4 composite polymeric melt. Further the homogenous solution was fed into the electrospinning setup which utilizes the electrostatic forces to form one‐ dimensional (1D) nanofibers and on further deposition leads to the formation of nanofibrous mat. The obtained nanofibrous mat was characterized by various analytical techniques in order to study its innate material properties and behaviour. The quality and composition of the nanofibrous mat along with its nanocomposite counterparts were investigated by XPS and Raman spectroscopic analysis for comparison. Apart from the conventional antibacterial assays that are followed in several studies, the present work also demonstrated the antibacterial efficacy of the nanomaterial through estimation of live/dead bacteria by the flow cytometry method. These quantitative assessments gives information associated with the antibacterial effect of the nanomaterials which will establish the practicality and feasibility for the development of such nano‐fillers functionalized nanofibrous filter for water purification.
Alternative polyadenylation and the stress response
Authors: Sadek Jason , Omer Amr , Hall Derek , Ashour Kholoud , Gallouzi Imed Eddine 
Published: May 2019

AbstractThe cellular stress response is a universal mechanism necessary for the survival of all organisms. This multifaceted process is primarily driven by regulation of gene expression to produce an intracellular environment suitable for promoting cell survival and recovery. Posttranscriptional regulatory events are considered as critical mechanisms that modulate core characteristics of mRNA transcripts to promote cell adaptation to various assaults. While the impact of processes such as mRNA splicing, turnover, localization, and translation on the cellular stress response has been extensively studied, recent observations highlight the role of alternative polyadenylation (APA) in response to challenges such as oxidative stress, heat shock, and starvation. The role of APA is comprehensive with far reaching effects on mRNA stability, mRNA localization, and protein coding sequences. Nonetheless, APA remains a relatively unappreciated mode of gene regulation despite its role in regulating key mediators of the stress response. The goal of this review is to provide an overview of the recent advances in our understanding of the various ways by which APA affects cell adaptation to its environment and discuss how a defect in APA could have deleterious consequences on cell survival.This article is categorized under:
RNA in Disease and Development > RNA in Disease
RNA Structure and Dynamics > Influence of RNA Structure in Biological Systems
RNA Processing > 3′ End Processing
Population pharmacokinetics of PF-05280014 (a trastuzumab biosimilar) and reference trastuzumab (Herceptin®) in patients with HER2-positive metastatic breast cancer
Authors: Chen Xiaoying , Li Cheryl , Ewesuedo Reginald , Yin Donghua 
Published: May 2019

Abstract
Purpose
PF-05280014 is a biosimilar to trastuzumab (Herceptin®). Following demonstration of pharmacokinetic (PK) similarity in healthy volunteers, a comparative clinical study in patients with HER2-positive metastatic breast cancer (mBC) compared the efficacy, safety and immunogenicity of PF-05280014 and trastuzumab sourced from the EU (trastuzumab-EU), both with paclitaxel.

Methods
Population PK of PF-05280014 and trastuzumab-EU was evaluated.

Results
Overall, 702 patients were treated: PF-05280014 (n = 349) and trastuzumab-EU (n = 353). Peak-and-trough serum drug concentration samples were collected (selected doses) following repeated intravenous administration of PF-05280014 or trastuzumab-EU. Population PK analysis was performed with drug concentration–time data to cycle 17 for each compound, using nonlinear mixed effect modeling. Potential baseline covariates (circulating HER2 concentrations, body weight, Japanese race, Eastern Cooperative Oncology Group status, number of metastatic sites and antidrug antibody status) were evaluated. Concentration–time data of PF-05280014 and trastuzumab-EU were adequately described by a two-compartment model with first-order elimination, with inter-individual variability (IIV) on clearance (CL), volumes of distribution in central compartment (V1) and peripheral compartments, and intercompartment clearance. Similar estimated PK parameters and IIV were obtained for both treatments. For PF-05280014 and trastuzumab-EU, baseline body weight was an influential covariate on CL and V1; the magnitude was comparable between treatments. PK was consistent between the limited number of Japanese and non-Japanese patients for both compounds.

Conclusions
PF-05280014 and trastuzumab-EU had similar PK parameters and influential PK covariates in patients with HER2-positive mBC. These results provided further evidence in patients for PK similarity between PF-05280014 and trastuzumab-EU.

Clinical trial registration
ClinicalTrials.gov, NCT01989676.
Musashi‐2 and related stem cell proteins in the mouse suprachiasmatic nucleus and their potential role in circadian rhythms
Authors: Beligala Dilshan H. , De Arpan , Malik Astha , Silver Rae , Rimu Kania , LeSauter Joseph , McQuillen Hugh J. , Geusz Michael E. 
Published: May 2019

AbstractBackgroundThe suprachiasmatic nucleus (SCN) of the mammalian hypothalamus contains the master circadian clock of the body and an unusually large number of cells expressing stem cell‐related proteins. These seemingly undifferentiated cells may serve in entrainment of the SCN circadian clock to light cycles or allow it to undergo neural plasticity important for modifying its rhythmic output signals. These cells may also proliferate and differentiate into neurons or glia in response to episodic stimuli or developmental events requiring alterations in the SCN's control of physiology and behavior.ProblemTo characterize expression of stem cell related proteins in the SCN and the effects of stem‐like cells on circadian rhythms.MethodsExplant cultures of mouse SCN were maintained in medium designed to promote survival and growth of stem cells but not neuronal cells. Several stem cell marker proteins including SRY‐box containing gene 2 (SOX2), nestin, vimentin, octamer‐binding protein 4 (OCT4), and Musashi RNA‐binding protein 2 (MSI2) were identified by immunocytochemistry in histological sections from adult mouse SCN and in cultures of microdissected SCN. A bioinformatics analysis located potential SCN targets of MSI2 and related RNA‐binding proteins.ResultsCells expressing stem cell markers proliferated in culture. Immunostained brain sections and bioinformatics supported the view that MSI2 regulates immature properties of SCN neurons, potentially providing flexibility in SCN neural circuits. Explant cultures had ongoing mitotic activity, indicated by proliferating‐cell nuclear antigen, and extensive cell loss shown by propidium iodide staining. Cells positive for vasoactive intestinal polypeptide (VIP) that are highly enriched in the SCN were diminished in explant cultures. Despite neuronal cell loss, tissue remained viable for over 7 weeks in culture, as shown by bioluminescence imaging of explants prepared from SCN of Per1::luc transgenic mice. The circadian rhythm in SCN gene expression persisted in brain slice cultures in stem cell medium. Prominent, widespread expression of RNA‐binding protein MSI2 supported the importance of posttranscriptional regulation in SCN functions and provided further evidence of stem‐like cells.ConclusionThe results show that the SCN retains properties of immature neurons and these properties persist in culture conditions suitable for stem cells, where the SCN stem‐like cells also proliferate. These properties may allow adaptive circadian rhythm adjustments. Further exploration should examine stem‐like cells of the SCN in vivo, how they may affect circadian rhythms, and whether MSI2 serves as a master regulator of SCN stem‐like properties.