bluuebunny/crossref_metadata_2025 huggingface dataset:
Tumor mutation burden and recurrent tumors in hereditary lung cancer
Authors: Hsu Yi‐Chiung , Chang Ya‐Hsuan , Chang Gee‐Chen , Ho Bing‐Ching , Yuan Shin‐Sheng , Li Yu‐Cheng , Zeng Jhih‐Wun , Yu Sung‐Liang , Li Ker‐Chau , Yang Pan‐Chyr , Chen Hsuan‐Yu
Published: April 2019

Lung cancer is the leading cause of cancer death worldwide and cancer relapse accounts for the majority of cancer mortality. The mechanism is still unknown, especially in hereditary lung cancer without known actionable mutations. To identify genetic alternations involved in hereditary lung cancer and relapse is urgently needed. We collected genetic materials from a unique hereditary lung cancer patient's blood, first cancer tissue (T1), adjacent normal tissue (N1), relapse cancer tissue (T2), and adjacent normal tissue (N2) for whole genome sequencing. We identified specific mutations in T1 and T2, and attributed them to tumorigenesis and recurrence. These tumor specific variants were enriched in antigen presentation pathway. In addition, a lung adenocarcinoma cohort from the TCGA dataset was used to confirm our findings. Patients with high mutation burdens in tumor specific genes had decreased relapse‐free survival (P = 0.017, n = 186). Our study may provide important insight for designing immunotherapeutic treatment for hereditary lung cancer.
Phase Modulating of Cu–Ni Nanowires Enables Active and Stable Electrocatalysts for the Methanol Oxidation Reaction
Authors: Tong Wu , Shao Qi , Wang Pengtang , Huang Xiaoqing
Published: April 2019

The design and development of non‐noble metal alternatives with superior performance and promising long‐term stability that is comparable or even better than those of noble‐metal‐based catalysts is a significant challenge. Here, we report the thermal‐induced phase engineering of non‐noble‐metal‐based nanowires with superior electrochemical activity and stability for the methanol oxidation reaction (MOR) under alkaline conditions. The optimized Cu–Ni nanowires deliver an unprecedented mass activity of 425 mA mg−1, which is 4.3 times higher than that of the untreated one. Detailed catalytic investigations show that the enhanced performance is due to the large active area, the increased number of active sites (NiOOH), and fast methanol electrooxidation kinetics. In addition, the generated hollow feature in the nanowires provides a unique void space to release the volume expansion, where the activity can be maintained for 5 h without a distinct activity decay. The present work emphasizes the importance of precisely phase modulating of nanomaterials for the design of non‐noble metal electrocatalysts towards the MOR, which opens up a new pathway for the design of cost‐effective electrocatalysts with promising activity and long‐term stability.
Catalytic C−H/C−F Coupling of Azoles and Acyl Fluorides
Authors: Ogiwara Yohei , Iino Yurika , Sakai Norio
Published: April 2019

A method for the palladium/copper‐catalyzed direct acylation of azoles with acyl fluorides is described. This study reports the first examples of acyl fluorides being used as acylation reagents in transition‐metal‐catalyzed aromatic C−H bond functionalization reactions. Depending on the reaction temperature, decarbonylative coupling may also occur. Mechanistic studies suggest that the cleavage of the aromatic C−H bond, promoted by a copper‐phosphine species, is not the rate‐limiting step of this acylation.
Microbial fuel cell–based self‐powered biosensor for environment monitoring in IoT cloud framework
Authors: Saravanakumar K. , Rajeswari R.
Published: April 2019

Renewable energy sources are useful for sustainable monitoring, but still very limited today due to various implementation constraints. Microbial fuel cells (MFCs) are considered a promising renewable power source for remote monitoring applications. They are used as wireless temperature sensors and biosensors due to their ability in powering environmental sensors. MFCs can provide ultralow and dynamic power, and hence, energy improvement is crucial for self‐powered biosensors. Cloud computing–based IoT framework is proposed for environment monitoring using MFC‐based biosensors. This paper presents the electric energy harvesting from Oryza Sativa plants with bacteria as the catalyst. It adopts the technology of MFC in the plants to extract the maximum energy. An effective power management with IoT cloud framework is presented in this work to independently operate multiple MFCs to generate maximum power. Independently operated MFCs with electrically isolated electrodes have been utilized in the design of a suitable power management system. Cloud computing is utilized in this work to process the data generated in continuous monitoring of environment. Experimental results show that the proposed framework can achieve sustainable power for sensor nodes and achieves maximum performance in environment monitoring using cloud‐based IoT platform.
Formal modeling and verification of cloud‐based web service composition
Authors: Raza Kazmi Syed Asad , Qasim Awais , Khalid Adnan , Assad Ruttaba , Shahbaz Muhammad
Published: April 2019

Web service composition is a key technology to resolve cross‐organizational business process integration, and it faces many constraints and requirements as unexpected bugs can cause shutdown of the software. A high degree of reliability is expected from such systems, and formal modeling of web service composition is an active area of research. In this work, we propose a new approach for the formal modeling of diverse web service composition. Our approach verifies the terminate property on all possible runs of the system to ensure deadlock‐free workings. For a verification of the properties of interest, we use the NuSMV model checker and specify the properties in CTL*. The approach can be used to verify the soundness property of diverse web service composition to ensure live and deadlock‐free web services.
Phosphorus alleviation of salinity stress: effects of saltwater intrusion on an Everglades freshwater peat marsh
Authors: Wilson Benjamin J. , Servais Shelby , Charles Sean P. , Mazzei Viviana , Gaiser Evelyn E. , Kominoski John S. , Richards Jennifer H. , Troxler Tiffany G.
Published: April 2019

Saltwater intrusion and salinization of coastal wetlands around the world are becoming a pressing issue due to sea level rise. Here, we assessed how a freshwater coastal wetland ecosystem responds to saltwater intrusion. In wetland mesocosms, we continuously exposed Cladium jamaicense Crantz (sawgrass) plants and their peat soil collected from a freshwater marsh to two factors associated with saltwater intrusion in karstic ecosystems: elevated loading of salinity and phosphorus (P) inputs. We took repeated measures using a 2 × 2 factorial experimental design (n = 6) with treatments composed of elevated salinity (~9 ppt), P loading (14.66 μmol P/d), or a combination of both. We measured changes in water physicochemistry, ecosystem productivity, and plant biomass change over two years to assess monthly and two‐year responses to saltwater intrusion. In the short‐term, plants exhibited positive growth responses with simulated saltwater intrusion (salinity + P), driven by increased P availability. Despite relatively high salinity levels for a freshwater marsh (~9 ppt), gross ecosystem productivity (GEP), net ecosystem productivity (NEP), and aboveground biomass were significantly higher in the elevated salinity + P treated monoliths compared to the freshwater controls. Salinity stress became evident after extended exposure. Although still higher than freshwater controls, GEP and NEP were significantly lower in the elevated salinity + P treatment than the +P treatment after two years. However, elevated salinity decreased live root biomass regardless of whether P was added. Our results suggest that saltwater intrusion into karstic freshwater wetlands may initially act as a subsidy by stimulating aboveground primary productivity of marsh plants. However, chronic exposure to elevated salinity results in plant stress, negatively impacting belowground peat soil structure and stability through a reduction in plant roots.
Prediction of Writing True Scores in Automated Scoring of Essays by Best Linear Predictors and Penalized Best Linear Predictors
Authors: Yao Lili , Haberman Shelby J. , Zhang Mo
Published: April 2019

Many assessments of writing proficiency that aid in making high‐stakes decisions consist of several essay tasks evaluated by a combination of human holistic scores and computer‐generated scores for essay features such as the rate of grammatical errors per word. Under typical conditions, a summary writing score is provided by a linear combination of the holistic scores and the feature scores. The best linear predictor (BLP) is used to approximate the true composite writing score by a linear combination of holistic scores and scores of essay features. However, because the relationship between computer‐generated feature score and human scores may depend on subgroup membership and the same scoring rules must normally be applied to all test takers, Yao, Haberman, and Zhang proposed a modified methodology of the penalized best linear predictor (PBLP) by incorporating a quadratic penalty function into the conventional BLP method. This research report contains full accounts of the BLP results as well as supplementary PBLP results to Yao et al. for three assessments of writing that aid in making high‐stakes decisions: the TOEFL iBT® Writing test, the GRE® General Analytical Writing subject test, and the Praxis® Core Academic Skills for Educators: Writing assessment. Results obtained indicate the added value in using machine features for prediction of composite true scores of essay writings and effectiveness of the penalty function in suppressing the lack of population invariance.
Evaluation of Thymus vulgaris and Thymbra spicata essential oils and plant extracts for chemical composition, antioxidant, and antimicrobial properties
Authors: Gedikoğlu Ayça , Sökmen Münevver , Çivit Ayşe
Published: April 2019

The objectives of this study were (a) to obtain the essential oils (by hydrodistillation [HD] and microwave‐assisted extraction [MAE] methods) to determine the effect of the oil extraction method on the chemical composition, oil yield (%), free radical scavenging activity (IC50), ferric reducing antioxidant power (FRAP) value, and antimicrobial properties of Thymus vulgaris (thyme) and Thymbra spicata (zahter); and (b) to determine the effect of different solvents (methanol [80%] and ethanol [80%]) on extraction by means of the phenolic acid composition, total phenolic content, total flavonoid content, IC50, and FRAP value of thyme and zahter. Gas chromatography–mass spectrometry analysis showed that the amount of thymol (55.35%; 50.53%) and p‐cymene (11.2%; 11.79%) was found to be highest in thyme, when using HD and MAE, respectively. However, the highest amounts of carvacrol (68.20%; 66.91%) and γ‐terpinene (13.25%; 13.94%) were found in zahter, when using HD and MAE, respectively. Thyme essential oil had higher antioxidant capacity for both HD and MAE in comparison with zahter essential oil. Methanol extracts of both thyme and zahter had higher phenolic composition in comparison with their ethanol extracts. Extracts of both plants did not show any antimicrobial properties. However, essential oils of both thyme and zahter showed antimicrobial activity against chosen bacteria. Highest inhibition zone (radius) was shown against Staphylococcus aureus ATCC 9144 by the essential oils.
Progress in developing decellularized bioscaffolds for enhancing skin construction
Authors: Cui Haomin , Chai Yimin , Yu Yaling
Published: April 2019

The skin is the largest organ in the human body, and skin defects are very common. Skin flap transplantation is the best treatment for serious wound defects, and donor site tissues are always sacrificed during this process. Decellularized biomaterials, derived mainly from various nonautologous organs and tissues, have promising applications in tissue engineering and repair of wound defects. To date, decellularized mesothelium, intestine, amniotic membrane, dermis, and skin flaps have been developed and applied for skin coverage in animal models and clinical practice. In this review, we discuss recent advances in decellularized biomaterials for skin substitutes and future perspectives. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1849–1859, 2019.
Producing hybrid nanofiber‐based on /PAN/Fe3O4/zeolite/nettle plant extract/urease and a deformed coaxial natural polymer to reduce toxicity materials in the blood of dialysis patients
Authors: Bahramimehr Faranak , Esmaeili Akbar
Published: April 2019

On incidence of kidney failure, the concentration of urea increases and there is need for patients to visit the hospital all through the week for blood purification. However, current hemodialysis has been found to reduce only 66‐75% urea in the blood of patients. The main goal of this article is to observe the effect of biocompatible and high mechanical hemodiafiltration in reducing urea and creatinine within the shortest time frame, using two methods of Nano electrospinning fiber (hybrid and coaxial). Hybrid electrospinning was made by zeolite 940‐HOA(beta), Fe3O4, polyacrylonitrile as well as the addition of nettle plant's leaf extract. Dispersing solution and enzymes were added to two different syringes and was used in making hybrid nanofibers by the electrospinning process. Nessler's Reagent adsorption method was used for measuring the concentration of ammonia after urease enzyme activation. Second coaxial filter was made by the core‐shell electrospinning system and cellulose acetate phthalate (CAP) as well as polyurethane (PU) were utilized. The data show hybrid hemodiafiltration with enzyme coating, decomposed urea and enzymes were activated for two days after electrospinning. The core‐shell filtration can also reduce creatinine. Core‐shell CAP‐PU nanofiber was previously used for intravaginal drug delivery and PU was used as an artificial renal microfluidic chip. Thus, our study focused on using CAP‐PU to reduce creatinine in dialysis patients. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1736–1743, 2019.
Foreign Direct Investment, Political Business Cycles and Welfare in Africa
Authors: Agbloyor Elikplimi Komla
Published: April 2019

We examine the relation between foreign direct investment (FDI), elections and welfare in Africa using data from 1990 to 2014. Our results show evidence that elections play a positive role in altering the relationship between FDI and welfare as they are considered by investors as risk reduction events. Interestingly, when we split the sample based on the quality of institutions, we find that the interaction between FDI and elections is mostly insignificant in countries with strong institutions. However, the interaction between FDI and elections is positive and significant in countries with weak institutions. © 2019 John Wiley & Sons, Ltd.
Bone development and remodeling in metabolic disorders
Authors: Serra‐Vinardell Jenny , Roca‐Ayats Neus , De‐Ugarte Laura , Vilageliu Lluïsa , Balcells Susanna , Grinberg Daniel
Published: April 2019

There are many metabolic disorders that present with bone phenotypes. In some cases, the pathological bone symptoms are the main features of the disease whereas in others they are a secondary characteristic. In general, the generation of the bone problems in these disorders is not well understood and the therapeutic options for them are scarce. Bone development occurs in the early stages of embryonic development where the bone formation, or osteogenesis, takes place. This osteogenesis can be produced through the direct transformation of the pre‐existing mesenchymal cells into bone tissue (intramembranous ossification) or by the replacement of the cartilage by bone (endochondral ossification). In contrast, bone remodeling takes place during the bone's growth, after the bone development, and continues throughout the whole life. The remodeling involves the removal of mineralized bone by osteoclasts followed by the formation of bone matrix by the osteoblasts, which subsequently becomes mineralized. In some metabolic diseases, bone pathological features are associated with bone development problems but in others they are associated with bone remodeling. Here, we describe three examples of impaired bone development or remodeling in metabolic diseases, including work by others and the results from our research. In particular, we will focus on hereditary multiple exostosis (or osteochondromatosis), Gaucher disease, and the susceptibility to atypical femoral fracture in patients treated with bisphosphonates for several years.
Evaluating Differences in the Working Alliance Based on Frequency of Mindfulness Practices Among Counselors‐in‐Training
Authors: JOHNSON DAVID A. , FRAZEE MELINDA , BOURN NATALYA S. , IVERS NATHANIEL N.
Published: April 2019

The authors examined whether the working alliance differed among 182 counselors‐in‐training who differed in the frequency of engaging in mindfulness practice. Participants who engaged in mindfulness practices 4 or more times per week reported higher scores on the goal and task components of the working alliance, compared with all other groups.
Greening Counseling: Examining Multivariate Relationships Between Ecowellness and Holistic Wellness
Authors: REESE RYAN F. , LEWIS TODD F.
Published: April 2019

Researchers developed the ecowellness construct to draw focus on the human–nature connection in counseling. The authors examined relationships between the EcoWellness Inventory and the Five Factor Wellness Inventory in a study with 749 participants ages 18 to 84. Results provide further support for the significance of ecowellness as a dimension of holistic wellness that merits additional attention in humanistic counseling and research.
Silencing KRT16 inhibits keratinocyte proliferation and VEGF secretion in psoriasis via inhibition of ERK signaling pathway
Authors: Chen Jin‐Guang , Fan Hua‐Yu , Wang Ting , Lin Lan‐Ying , Cai Tian‐Guo
Published: April 2019

Psoriasis is a multisystem disease affecting about 2% of the population, while keratin16 (KRT16) has been reported to participate in psoriasis. However, the specific mechanism of KRT16 in psoriasis was inadequately investigated. The objective of the study was to elucidate the mechanism by which siRNA‐mediated silencing of KRT16 affects keratinocyte proliferation and vascular endothelial growth factor (VEGF) secretion in psoriasis through the extracellular signal‐related kinase (ERK) signaling pathway. Psoriasis‐related core gene KRT16 was screened out. Then, the expression of KRT16, VEGF, and ERK signaling pathway‐related genes was detected in psoriatic patients. To further investigate the mechanism of KRT16, keratinocytes in psoriatic patients were treated with KRT16 siRNA or/and ERK inhibitor (PD98059) to detect the changes in related gene expression and cell survival. KRT16 was involved in psoriasis development. The expression levels of KRT16, p‐ERK1/2, and VEGF in lesion tissues are significantly elevated. Keratinocytes treated with KRT16‐siRNA and KRT16‐siRNA + PD98059 exhibited reduced KRT16, p‐ERK1/2, and VEGF expression. The cell survival rate in cells treated with KRT16‐siRNA, PD98059, and KRT16‐siRNA + PD98059 reduced significantly. These findings indicate that silencing KRT16 inhibits keratinocyte proliferation and VEGF secretion in psoriasis via inhibition of ERK signaling pathway, which provides a basic theory in the treatment of psoriasis.
One‐Step Route to Ladder‐Type C–N Linked Conjugated Polymers
Authors: Ren Xiaojie , Zhang Hailei , Song Meining , Cheng Cong , Zhao Hongchi , Wu Yonggang
Published: April 2019

A one‐step synthetic method is demonstrated to construct ladder‐type conjugated polymers without the resource to post‐cyclization procedures. The ladder‐type C–N linked conjugated polymers (P1 and P2) and model compounds (1 and 2) are achieved in high yields. The obtained model compounds and polymers display desirable solubility in commonly used solvents and high thermal stability, which show a promising application in photoelectric material field.
Design and Synthesis of a Facile Solution‐Processing and Ultrastable Crosslinkable Branched Nitroxide Polymer
Authors: Qin Herong , Liu Xiu , Huang Jianbing , Liang Hui , Zhang Zishou , Lu Jiang
Published: April 2019

A general critical challenge for nitroxide polymers being used as cathode materials is keeping the good solubility during the processing and good solvent resistance during charging and discharging. To address this issue, herein, a new photo‐crosslinkable branched nitroxide polymer is designed and synthesized via reversible addition‐fragmentation chain transfer copolymerization of 2,2,6,6‐tetramethyl‐4‐piperidyl methacrylate, cinnamoyl ethyl methacrylate, and ethylene glycol dimethacrylate, followed by oxidation using 3‐chloroperoxybenzoic acid. The as‐synthesized polymer can dissolve in ethyl alcohol with environmental‐friendly processing, and then can easily change into crosslinked polymer with highly resistance to organic electrolyte after UV irradiation. The crosslinked nitroxide polymer‐based cathode achieves remarkable cycle stability with a capacity retention of 90% over 1000 charge–discharge cycles at 10 C current rate, superior to that of the un‐crosslinked one with capacity retention of 65% over 1000 cycles.
Geometric modulation of microscale surface structures for defined stimulation of osteogenic differentiation on implant materials
Authors: Gach S. , Olschok S. , Reisgen U.
Published: April 2019

Metal implants for orthopedic applications have been in use for a long time. Improvements of the osseointegration behaviour by surface‐changing processes, such as sand blasting or etching, were so far only obtained in empirical studies. It is not yet completely understood which surface chemistry and structure can support the initial cell‐implant response. Electron beam material processing in vacuum has been used successfully for many decades. The method has not been used for the targeted micro‐structuring of implant material surfaces yet. Especially the material processing in vacuum reveals advantages, due to the high affinity of titanium for oxygen. The electron beam structuring process is based on the Surfi‐Sculpt process developed by TWI ‐ The Welding Institute. A repetitive beam overflow establishes in several steps defined microstructures. This study presents the results of the investigation of the Surfi‐Sculpt process of the implant material TiAl6 V4, in particular the influence of different process parameters on the formation of structure height and geometry. Particularly the local alloy composition of the micro‐structured surface is investigated.
Solvability and semi‐cycle analysis of a class of nonlinear systems of difference equations
Authors: Stević Stevo , Tollu Durhasan T.
Published: April 2019

An analysis of semi‐cycles of positive solutions to eight systems of difference equations of the following form

urn:x-wiley:mma:media:mma5600:mma5600-math-0001
where a ∈ [0, + ∞), the sequences pn, qn, rn, sn are some of the sequences xn and yn, with positive initial values x−j,y−j, j = 1,2, is conducted in detail, and it is shown that these systems can be solved in closed‐form, which is the main result here. Two methods for showing the solvability are described.
Satellite Imaging Technology Helps Utilities Reduce Nonrevenue Water
Authors: Odle Chelsea
Published: April 2019

Water utilities have made great strides in the last few years regarding water loss control. Now, an Arkansas utility has applied a promising new tool for identifying potential leak locations.
System Specifics Drive Pressure‐Reducing Valve Selection
Authors: Brackenridge Stuart
Published: April 2019

Pressure‐reducing valves are valuable components of a water distribution network, but many details need to be considered to optimize valve selection.
Permanent antimicrobial silicone rubber based on bonding guanidine polymers
Authors: Guan Yong , Zhang Huanyao , Zheng Anna , Wei Dafu , Hu Jian , Wang Zhenzhen , Xu Xiang
Published: April 2019

Recently, silicone rubber (VMQ) was extensively used in household articles and medical devices. To develop a kind of safe and long‐term antimicrobial VMQ was of great significance. In this work, a kind of vinyl‐contained polyhexamethylene guanidine hydrochloride (VPHMG) was synthesized and used as antimicrobial additive for VMQ. With the increasing of VPHMG addition, the mechanical properties and antimicrobial properties of VMQ‐VPHMG were significantly improved. In particular, the antimicrobial rates against Escherichia coli and Staphylococcus aureus were higher than 99.99% as for 4 wt% of VPHMG addition. Moreover, the surface concentration of VPHMG as well as the antimicrobial rates revealed almost unchanged after being extracted by water and methanol. All the results indicated the vinyl‐contained VPHMG vulcanization and therefore provided the permanent antimicrobial performance for VMQ.
Preparation of highly efficient flame retardant unsaturated polyester resin by exerting the fire resistant effect in gaseous and condensed phase simultaneously
Authors: Zhou Jingshang , Xu Miaojun , Zhang Xiaohan , Leng Yang , He Yintong , Li Bin
Published: April 2019

The unsaturated polyester resins (UPR) were usually applied in electronic equipment, but the intrinsic flammability severely retrained their application. A mono‐component flame retardant poly (piperazine methylphosphonic acid neopentylglycol ester) (PPMPNG) made in our lab was selected and applied to improve their flame retardant performance. The UPR thermosets achieved UL‐94 V‐0 grade during vertical burning tests and the limiting oxygen index was as high as 32.1% when 15 wt% PPMPNG was incorporated. PPMPNG promoted the decomposition and carbonization of UPR materials in advance during heating process, and the residual mass was effectively enhanced at high temperature. The flame retardant mechanism of UPR/PPMPNG thermosets was investigated by pyrolysis‐gas chromatography/mass spectrometry tests, and the measurement of the morphologies and chemical components of the char residue. The phosphine oxygen radical was generated and then quenched the active free radicals in gas phase. Moreover, the av‐EHC of FR‐UPR was declined from 15.8 MJ kg−1 of pure UPR to 8 9 MJ kg−1 corresponding a reduction of 43.6%, which also verified the flame retardant effect in gas phase. The compact, integrated, and graphitized char layer was produced on materials surface and then exerted excellent barrier effect in condensed phase. Thus, the UPR/PPMPNG composites were conferred superior flame retardant properties.
Wet 3‐D printing of epoxy cross‐linked chitosan/carbon microtube composite
Authors: Nasri‐Nasrabadi Bijan , Kaynak Akif , Heidarian Pejman , Kouzani Abbas Z.
Published: April 2019

Over the last decays, the use of conductive biopolymer composites has been growing in areas such as biosensors, soft robotics, and wound dressing applications. They are generally soft hydrophilic materials with good elastic recovery and compatible with biological environments. However, their application and removal from the host are still challenging mainly due to poor mechanical strength. This work displays a technique for the fabrication of complex‐shaped conductive structures with improved mechanical strength by wet three‐dimensional (3‐D) printing, which uses a coagulation bath to quickly solidify an epoxy cross‐linked chitosan/carbon microtube composite ink. The fabricated conductive structure demonstrated higher elongation strength and improved elastic stability upon the introducing of polypropylene glycol diglycidyl ether (PPGDGE) as the epoxy cross‐linker, which can be due to the formation of networks between oxiran groups of PPGDGE and chitosan amino groups.
Variation in assembly stoichiometry in non‐metazoan homologs of the hub domain of Ca2+/calmodulin‐dependent protein kinase II
Authors: McSpadden Ethan D. , Xia Zijie , Chi Chris C. , Susa Anna C. , Shah Neel H. , Gee Christine L. , Williams Evan R. , Kuriyan John
Published: April 2019

The multi‐subunit Ca2+/calmodulin‐dependent protein kinase II (CaMKII) holoenzyme plays a critical role in animal learning and memory. The kinase domain of CaMKII is connected by a flexible linker to a C‐terminal hub domain that assembles into a 12‐ or 14‐subunit scaffold that displays the kinase domains around it. Studies on CaMKII suggest that the stoichiometry and dynamic assembly/disassembly of hub oligomers may be important for CaMKII regulation. Although CaMKII is a metazoan protein, genes encoding predicted CaMKII‐like hub domains, without associated kinase domains, are found in the genomes of some green plants and bacteria. We show that the hub domains encoded by three related green algae, Chlamydomonas reinhardtii, Volvox carteri f. nagarensis, and Gonium pectoral, assemble into 16‐, 18‐, and 20‐subunit oligomers, as assayed by native protein mass spectrometry. These are the largest known CaMKII hub domain assemblies. A crystal structure of the hub domain from C. reinhardtii reveals an 18‐subunit organization. We identified four intra‐subunit hydrogen bonds in the core of the fold that are present in the Chlamydomonas hub domain, but not in metazoan hubs. When six point mutations designed to recapitulate these hydrogen bonds were introduced into the human CaMKII‐α hub domain, the mutant protein formed assemblies with 14 and 16 subunits, instead of the normal 12‐ and 14‐subunit assemblies. Our results show that the stoichiometric balance of CaMKII hub assemblies can be shifted readily by small changes in sequence.
From waterfall plots to spaghetti plots in early oncology clinical development
Authors: Mercier Francois , Consalvo Nicola , Frey Nicolas , Phipps Alex , Ribba Benjamin
Published: April 2019

Waterfall plots are used to describe changes in tumor size observed in clinical studies. They are frequently used to illustrate the overall drug response in oncology clinical trials because of its simple representation of results. Unfortunately, this visual display suffers a number of limitations including (1) potential misguidance by masking the time dynamics of tumor size, (2) ambiguous labelling of the y‐axis, and (3) low data‐to‐ink ratio. We offer some alternatives to address these shortcomings and recommend moving away from waterfall plots to the benefit of plots showing the individual time profiles of sum of lesion diameters (according to RECIST). The spider plot presents the individual changes in tumor measurements over time relative to baseline tumor burden. Baseline tumor size is a well‐known confounding factor of drug effect which has to be accounted for when analyzing data in early clinical trials. While spider plots are conveniently correct for baseline tumor size, they cannot be presented in isolation. Indeed, percentage change from baseline has suboptimal statistical properties (including skewed distribution) and can be overly optimistic in favor of drug efficacy. We argued that plots of raw data (referred to as spaghetti plots) should always accompany spider plots to provide an equipoised illustration of the drug effect on lesion diameters.
Marine glycan–based antiviral agents in clinical or preclinical trials
Authors: Hao Cui , Yu Guangli , He Yanli , Xu Cuijing , Zhang Lijuan , Wang Wei
Published: April 2019

The constant outbreak of diseases caused by viral infections has caused serious harm to human health all over the world. Although many antiviral drugs have been approved for clinical use during the past decade, important issues, such as unsatisfactory efficacy, toxicity, and high cost of drugs, remain unresolved. Glycans are major components of the surfaces of both host cells and most viruses and play critical roles in the steps of viral infection. Marine glycans have more structural diversities than those found in humans. Most importantly, low toxicity and low‐cost marine glycans have demonstrated potent antiviral activities through multiple molecular mechanisms. As a result, a series of marine glycan–derived agents are undergoing preclinical and clinical trials. This review discusses the recent progress in research on the marine glycan–based antiviral agents in clinical trials, relating to their structural features and clinical applications. In addition, molecular mechanisms of marine glycans involved in viral infection and novel strategies used in glycan‐based drug development are critically reviewed and discussed.
Modeling lottery incentives for daily adherence
Authors: Humphrey Colman H. , Small Dylan S. , Jensen Shane T. , Volpp Kevin G. , Asch David A. , Zhu Jingsan , Troxel Andrea B.
Published: April 2019

Many health issues require adherence to recommended daily activities, such as taking medication to manage a chronic condition, walking a certain distance to promote weight loss, or measuring weights to assess fluid balance in heart failure. The cost of nonadherence can be high, with respect to both individual health outcomes and the healthcare system. Incentivizing adherence to daily activities can promote better health in patients and populations and potentially provide long‐term cost savings.

Multiple incentive structures are possible. We focus here on a daily lottery incentive in which payment occurs when both the participant's lottery number matches the number drawn and the participant adheres to the targeted daily behavior.

Our objective is to model the lottery's effect on participants' probability to complete the targeted task, particularly over the short term. We combine two procedures for analyzing such binary time series: a parameter‐driven regression model with an autocorrelated latent process and a comparative interrupted time series. We use the output of the regression model as the control generator for the comparative time series in order to create a quasi‐experimental design.
The limitations of access to continuing professional development amongst Australia's rural sonographers and its effect on job satisfaction: A pilot study
Authors: Van Binst Anouck , Kennedy Narelle , Harland Sonya , Aziz Aamer , Quinton Ann
Published: April 2019

Introduction

Sonographers in Australia form an important component of health care within rural and remote communities. Being remotely located brings its own set of difficulties in accessing continuing professional development (CPD). There is little research investigating the rural sonographers' experience with access to CPD and how this affects job satisfaction.

Method

The purpose of this research was to investigate if limited access to CPD is experienced in the rural setting, what barriers to participation exist, and if reduced access has a negative effect on job satisfaction. Data were collected via the Australasian Sonographers Association (ASA) members' forum, inviting rural and remote sonographers to participate in an anonymous online questionnaire.

Results

This study showed that various barriers to CPD participation exist, with in‐person CPD participation seen as highly valuable.

Conclusion

This study opens an opportunity for further conversations on how to improve CPD access amongst rural sonographers with the possible underlying solution being increased employer support.
Quantitative analysis of cembranoids in tobacco leaf by using heart‐cutting two‐dimensional liquid chromatography
Authors: Chen Min , Dong Huizhong , Shen Shihao , Wang Jiale , Wu Da , Liu Baizhan
Published: April 2019

A novel heart‐cutting two dimensional liquid chromatography method had been developed to analyze two cembranoids tobacco leaf. The reversed phase liquid chromatography column was employed for separation. Then target elution was cut to the trap column by on‐line dilution from the compensate pump. After switching the six‐port valve, the analytes were eluted to the second dimension. The two cembranoids were determined qualitatively and quantitatively by UV detection. The new method was fairly simplified sample pretreatment. When the approach was engaged to real samples, it showed high sensitivity without matrix interference. Limits of detection for two cembranoids were 0.0083 and 0.0060 mg/g, and limits of quantification were 0.027 and 0.020 mg/g, respectively. The intra‐day and inter‐day relative standard deviation of the cembranoids were within 1.8%. Spiked recoveries were ranged from 98.4 to 109.5%. Therefore, the two dimensional liquid chromatography method was successfully utilized to cembranoids detection in a wide range of the tobacco samples.
The rise of ingredient disclosure: The California and New York experience
Authors: Bergeson Lynn L.
Published: April 2019

In the recent past, two important states—California and New York—have launched extensive and precedent‐setting ingredient disclosure laws regarding cleaning products with the clear goal of prompting the deselection of certain chemical substances and forcing product reformulation. Industry prefers to refer to this trend as “ingredient communication,” a goal we can all agree is desirable. By whatever name, these state measures will have a significant impact on ingredient disclosure trends across product lines, likely well beyond their stated application to cleaning products. These state laws are summarized below, followed by a discussion of their similarities, key differences, and their implications.
Nonparametric density estimation for high‐dimensional data—Algorithms and applications
Authors: Wang Zhipeng , Scott David W.
Published: April 2019

Density estimation is one of the central areas of statistics whose purpose is to estimate the probability density function underlying the observed data. It serves as a building block for many tasks in statistical inference, visualization, and machine learning. Density estimation is widely adopted in the domain of unsupervised learning especially for the application of clustering. As big data become pervasive in almost every area of data sciences, analyzing high‐dimensional data that have many features and variables appears to be a major focus in both academia and industry. High‐dimensional data pose challenges not only from the theoretical aspects of statistical inference, but also from the algorithmic/computational considerations of machine learning and data analytics. This paper reviews a collection of selected nonparametric density estimation algorithms for high‐dimensional data, some of them are recently published and provide interesting mathematical insights. The important application domain of nonparametric density estimation, such as modal clustering, is also included in this paper. Several research directions related to density estimation and high‐dimensional data analysis are suggested by the authors.

This article is categorized under:

Statistical and Graphical Methods of Data Analysis > Multivariate Analysis

Statistical and Graphical Methods of Data Analysis > Density Estimation

Statistical Learning and Exploratory Methods of the Data Sciences > Clustering and Classification
Questioning Late Antique prosperity: the case of Lycia (southwest Turkey)
Authors: Terpoy Kristina
Published: April 2019

The concept of a prosperous late antique eastern Mediterranean has become well-established in scholarship. Lycia (Turkey) is considered to be one such prosperous region in particular. This article questions the notion of ‘prosperity’ and its application to the Lycian region and argues that only certain coastal areas experienced what might be considered ‘prosperity’ in this period. Moreover, it is argued that some settlements, specifically those of the interior, did not experience ‘prosperity’, but may have even declined. Thus, a generalized application of ‘prosperity’ should be approached with caution as it masks nuances in the settlement development and economy of micro-regions.
Manuel I Komnenos and the Stone of Unction
Authors: Drpić Ivan
Published: April 2019

For John Duffy

This article explores the fate of the Stone of Unction — the marble slab upon which, according to tradition, the dead body of Christ had been anointed for burial — in twelfth-century Byzantium. Focusing upon the Stone's association with Manuel I Komnenos, the article examines the imperial handling of this Passion relic in relation to broader trends in the devotional culture of the contemporary Byzantine élite. The special bond between the emperor and the relic, it is argued, should be seen as a manifestation of the pervasive desire, much in evidence during the Komnenian era, to personalise and even privatise the sacred.
Investigation of healthcare infection risks from water-related organisms: Summary of CDC consultations, 2014—2017
Authors: Perkins Kiran M. , Reddy Sujan C. , Fagan Ryan , Arduino Matthew J. , Perz Joseph F.
Published: April 2019

Objective:

Water exposures in healthcare settings and during healthcare delivery can place patients at risk for infection with water-related organisms and can potentially lead to outbreaks. We aimed to describe Centers for Disease Control and Prevention (CDC) consultations involving water-related organisms leading to healthcare-associated infections (HAIs).

Design:

Retrospective observational study.

Methods:

We reviewed internal CDC records from January 1, 2014, through December 31, 2017, using water-related terms and organisms, excludingLegionella, to identify consultations that involved potential or confirmed transmission of water-related organisms in healthcare. We determined plausible exposure pathways and routes of transmission when possible.

Results:

Of 620 consultations during the study period, we identified 134 consultations (21.6%), with 1,380 patients, that involved the investigation of potential water-related HAIs or infection control lapses with the potential for water-related HAIs. Nontuberculous mycobacteria were involved in the greatest number of investigations (n = 40, 29.9%). Most frequently, investigations involved medical products (n = 48, 35.8%), and most of these products were medical devices (n = 40, 83.3%). We identified a variety of plausible water-exposure pathways, including medication preparation near water splash zones and water contamination at the manufacturing sites of medications and medical devices.

Conclusions:

Water-related investigations represent a substantial proportion of CDC HAI consultations and likely represent only a fraction of all water-related HAI investigations and outbreaks occurring in US healthcare facilities. Water-related HAI investigations should consider all potential pathways of water exposure. Finally, healthcare facilities should develop and implement water management programs to limit the growth and spread of water-related organisms.
Global well-posedness of advective Lotka–Volterra competition systems with nonlinear diffusion
Authors: Wang Qi , Yang Jingyue , Yu Feng
Published: April 2019

This paper investigates the global well-posedness of a class of reaction–advection–diffusion models with nonlinear diffusion and Lotka–Volterra dynamics. We prove the existence and uniform boundedness of the global-in-time solutions to the fully parabolic systems under certain growth conditions on the diffusion and sensitivity functions. Global existence and uniform boundedness of the corresponding parabolic–elliptic system are also obtained. Our results suggest that attraction (positive taxis) inhibits blowups in Lotka–Volterra competition systems.
Aminochronology and time averaging of Quaternary land snail assemblages from colluvial deposits in the Madeira Archipelago, Portugal
Authors: New Evan , Yanes Yurena , Cameron Robert A.D. , Miller Joshua H. , Teixeira Dinarte , Kaufman Darrell S.
Published: April 2019

Understanding the properties of time averaging (age mixing) in a stratigraphic layer is essential for properly interpreting the paleofauna preserved in the geologic record. This work assesses the age and quantifies the scale and structure of time averaging of land snail-rich colluvial sediments from the Madeira Archipelago (Portugal) by dating individual shells using amino acid racemization calibrated with graphite-target and carbonate-target accelerator mass spectrometry radiocarbon methods. Gastropod shells of Actinella nitidiuscula were collected from seven sites on the volcanic islands of Bugio and Deserta Grande (Desertas Islands), where snail shells are abundant and well preserved in Quaternary colluvial deposits. Results show that the shells ranged in age from modern to ~48 cal ka BP (calibrated radiocarbon age), covering the last glacial and present interglacial periods. Snail shells retrieved from two of the colluvial sites exhibit multimillennial age mixing (>6 ka), which significantly exceeds the analytical error from dating methods and calibration. The observed multimillennial mixing of these assemblages should be taking into consideration in upcoming paleoenvironmental and paleoecological studies in the region. The extent of age mixing may also inform about the time span of colluvial deposition, which can be useful in future geomorphological studies. In addition, this study presents the first carbonate-target radiocarbon results for land snail shells and suggests that this novel, rapid, and more affordable dating method offers reliable age estimates for small land snail shells younger than ~20 cal ka BP.
Fish oil supplementation during adolescence attenuates metabolic programming of perinatal maternal high-fat diet in adult offspring
Authors: Souza Aline F. P. , Souza Luana L. , Oliveira Lorraine S. , Cordeiro Aline , Souza Eliete , Kluck George E. G. , Atella Georgia C. , Trevenzoli Isis H. , Pazos-Moura Carmen C.
Published: April 2019

Perinatal maternal high-fat diet (HFD) increases susceptibility to obesity and fatty liver diseases in adult offspring, which can be attenuated by the potent hypolipidaemic action of fish oil (FO), ann-3 PUFA source, during adult life. Previously, we described that adolescent HFD offspring showed resistance to FO hypolipidaemic effects, although FO promoted hepatic molecular changes suggestive of reduced lipid accumulation. Here, we investigated whether this FO intervention only during the adolescence period could affect offspring metabolism in adulthood. Then, female Wistar rats received isoenergetic, standard (STD: 9 % fat) or high-fat (HFD: 28·6 % fat) diet before mating, and throughout pregnancy and lactation. After weaning, male offspring received the standard diet; and from 25 to 45 d old they received oral administration of soyabean oil or FO. At 150 d old, serum and hepatic metabolic parameters were evaluated. Maternal HFD adult offspring showed increased body weight, visceral adiposity, hyperleptinaemia and decreased hepatic pSTAT3/STAT3 ratio, suggestive of hepatic leptin resistance. FO intake only during the adolescence period reduced visceral adiposity and serum leptin, regardless of maternal diet. Maternal HFD promoted dyslipidaemia and hepatic TAG accumulation, which was correlated with reduced hepatic carnitine palmitoyl transferase-1a content, suggesting lipid oxidation impairment. FO intake did not change serum lipids; however, it restored hepatic TAG content and hepatic markers of lipid oxidation to STD offspring levels. Therefore, we concluded that FO intake exclusively during adolescence programmed STD offspring and reprogrammed HFD offspring male rats to a healthier metabolic phenotype in adult life, reducing visceral adiposity, serum leptin and hepatic TAG content in offspring adulthood.
Theory and Testing of Governments' Credible Apologies: A Reply to Lowry' ‘Comment on Yap's “Non-Electoral Responsiveness Mechanisms”’
Authors: YAP O. FIONA
Published: April 2019

I appreciate the work that Professor Lowry has put into the evaluation of the credible apologies argument presented in my article, ‘Non-Electoral Responsiveness Mechanisms’. Lowry states that I assume ‘a causal arrow running from poor economic performance to credible apologies’. I am obliged to point out that this is inaccurate – I make no such assumption. What does cause the government's credible apologies? It is the need for the economic resources of labour quiescence and production investment from the respective resource-owners. Theory and empirical studies suggest that the withdrawal of such resources follows less-than-optimal economic performance; it follows, then, that governments in the less-democratic countries who need these resources are forced to pay attention to economic performance and offer credible apologies following sub-optimal economic performance.