bluuebunny/crossref_metadata_2025 huggingface dataset:
A local evaluation of the individual state‐space to scale up Bayesian spatial capture–recapture
Authors: Milleret Cyril , Dupont Pierre , Bonenfant Christophe , Brøseth Henrik , Flagstad Øystein , Sutherland Chris , Bischof Richard
Published: December 2018

Spatial capture–recapture models (SCR) are used to estimate animal density and to investigate a range of problems in spatial ecology that cannot be addressed with traditional nonspatial methods. Bayesian approaches in particular offer tremendous flexibility for SCR modeling. Increasingly, SCR data are being collected over very large spatial extents making analysis computational intensive, sometimes prohibitively so. To mitigate the computational burden of large‐scale SCR models, we developed an improved formulation of the Bayesian SCR model that uses local evaluation of the individual state‐space (LESS). Based on prior knowledge about a species’ home range size, we created square evaluation windows that restrict the spatial domain in which an individual's detection probability (detector window) and activity center location (AC window) are estimated. We used simulations and empirical data analyses to assess the performance and bias of SCR with LESS. LESS produced unbiased estimates of SCR parameters when the AC window width was ≥5σ (σ: the scale parameter of the half‐normal detection function), and when the detector window extended beyond the edge of the AC window by 2σ. Importantly, LESS considerably decreased the computation time needed for fitting SCR models. In our simulations, LESS increased the computation speed of SCR models up to 57‐fold. We demonstrate the power of this new approach by mapping the density of an elusive large carnivore—the wolverine (Gulo gulo)—with an unprecedented resolution and across the species’ entire range in Norway (> 200,000 km2). Our approach helps overcome a major computational obstacle to population and landscape‐level SCR analyses. The LESS implementation in a Bayesian framework makes the customization and fitting of SCR accessible for practitioners working at scales that are relevant for conservation and management.
Variations in age‐ and sex‐specific survival rates help explain population trend in a discrete marine mammal population
Authors: Arso Civil Mònica , Cheney Barbara , Quick Nicola J. , Islas‐Villanueva Valentina , Graves Jeff A. , Janik Vincent M. , Thompson Paul M. , Hammond Philip S.
Published: December 2018

Understanding the drivers underlying fluctuations in the size of animal populations is central to ecology, conservation biology, and wildlife management. Reliable estimates of survival probabilities are key to population viability assessments, and patterns of variation in survival can help inferring the causal factors behind detected changes in population size. We investigated whether variation in age‐ and sex‐specific survival probabilities could help explain the increasing trend in population size detected in a small, discrete population of bottlenose dolphins Tursiops truncatus off the east coast of Scotland. To estimate annual survival probabilities, we applied capture–recapture models to photoidentification data collected from 1989 to 2015. We used robust design models accounting for temporary emigration to estimate juvenile and adult survival, multistate models to estimate sex‐specific survival, and age models to estimate calf survival. We found strong support for an increase in juvenile/adult annual survival from 93.1% to 96.0% over the study period, most likely caused by a change in juvenile survival. Examination of sex‐specific variation showed weaker support for this trend being a result of increasing female survival, which was overall higher than for males and animals of unknown sex. Calf survival was lower in the first than second year; a bias in estimating third‐year survival will likely exist in similar studies. There was some support first‐born calf survival being lower than for calves born subsequently. Coastal marine mammal populations are subject to the impacts of environmental change, increasing anthropogenic disturbance and the effects of management measures. Survival estimates are essential to improve our understanding of population dynamics and help predict how future pressures may impact populations, but obtaining robust information on the life history of long‐lived species is challenging. Our study illustrates how knowledge of survival can be increased by applying a robust analytical framework to photoidentification data.
Anti‐EF‐Tu IgG titers increase with age and may contribute to protection against the respiratory pathogen Haemophilus influenzae
Authors: Thofte Oskar , Kaur Ravinder , Su Yu‐Ching , Brant Marta , Rudin Anna , Hood Derek , Riesbeck Kristian
Published: December 2018

Non‐typeable Haemophilus influenzae (NTHi) is a pathogen that commonly colonizes the nasopharynx of preschool children, causing opportunistic infections including acute otitis media (AOM). Patients suffering from chronic obstructive pulmonary disease (COPD) are persistently colonized with NTHi and occasionally suffer from exacerbations by the bacterium leading to increased morbidity. Elongation‐factor thermo unstable (EF‐Tu), a protein critical for bacterial protein synthesis, has been found to moonlight on the surface of several bacteria. Here, we show that antibodies against NTHi EF‐Tu were present in children already at 18 months of age, and that the IgG antibody titers increased with age. Children harboring NTHi in the nasopharynx also displayed significantly higher IgG concentrations. Interestingly, children suffering from AOM had significantly higher anti‐EF‐Tu IgG levels when NTHi was the causative agent. Human sera recognized mainly the central and C‐terminal part of the EF‐Tu molecule and peptide‐based epitope mapping confirmed similar binding patterns for sera from humans and immunized mice. Immunization of BALB/c and otitis‐prone Junbo (C3H/HeH) mice promoted lower infection rates in the nasopharynx and middle ear, respectively. In conclusion, our results suggest that IgG directed against NTHi EF‐Tu may play an important role in the host immune response against NTHi.
Modulation of Electronic Communication between Two Equivalent Ferrocenyl Groups Mediated Through Tricarbonylcyclobutadieneiron
Authors: Rai Dhirendra K. , Tauqeer Mohd. , Chatterjee Sobhan , Krishnan Sarathkumar , Mobin Shaikh M. , Mathur Pradeep
Published: December 2018

Three sets of 1,3‐ and 1,2‐ derivatives of tricarbonylcyclobutadieneiron, [Fe(CO)3‐η4‐CbFc2R2] [Cb =cyclobutadiene, Fc = ferrocenyl, R = –CHO: 1a (1,3‐isomer), 1b (1,2‐isomer); R = –CHNOH: 2a (1,3‐isomer), 2b (1,2‐isomer); R = –CN: 3a (1,3‐isomer), 3b (1,2‐isomer)] have been synthesized under facile reaction conditions starting from FcC≡C‐CHO and Fe(CO)5. Effect of changing electronic nature of tricarbonylcyclobutadieneiron, arising from substituent variation and their relative position, has been correlated with the extent of electronic communication between two ferrocenyl groups by cyclic voltammetry and differential pulse voltammetry studies and also supported by density functional calculations.
Organocatalysts Effect on the Stereoselectivity of [2,3]‐Wittig Rearrangement
Authors: Peňaška Tibor , Mojzes Melinda Meyer , Filo Juraj , Jurdáková Helena , Mečiarová Mária , Šebesta Radovan
Published: December 2018

The organocatalytic [2,3]‐Wittig rearrangement of allyloxyketones was investigated. Extensive screening of chiral amine organocatalysts showed that small pyrrolidine‐based catalysts or simple phenylethylamine with the primary amino group were the most effective ones. Interestingly, CF3‐derived pyrrolidine affords the rearrangement product with an opposite absolute configuration to the product obtained by using the corresponding non‐fluorinated proline derived catalysts. Mechanistic and computational investigations were also performed.
Post‐test Characterization of Metallic Materials and Adjacent Components in an SOFC Stack After 34,000 h Operation at 700 °C
Authors: Groß‐Barsnick S. M. , Fang Q. , Batfalsky P. , Niewolak L. , Blum L. , Quadakkers W. J.
Published: December 2018

The present paper describes the electrochemical results and the post exposure microstructural characterization by means of SEM/EDS of a four layer SOFC stack after 34,000 h operation under load at 700 °C, showing low voltage degradation rate less than 0.3% per 1,000 h. Emphasis was put on the behavior of the ferritic interconnect steel and its interaction with glass sealants as well as contacting and coating materials. The interconnect steel had formed thin protective chromia scales. Gas distributing steel foils of 200 µm showed in some locations breakaway type oxidation. It was related to local overheating caused by locally occurring combustion of a defective cell. The interaction of the steel with the glass sealant showed good adhesion. Interdiffusion at the joint between nickel contact and steel interconnect at the anode side resulted in minor oxide formation on the Ni wires and in austenite formation in the steel without formation of σ‐FeCr formation at the steel/austenite interface. The steel showed excellent compatibility with the Manganese‐Cobalt‐Ferrite (MCF) chromium retention coatings. Chromium enriched phases were found near the interface between MCF coating and perovskite contact layer. Excess glass sealing material interacted with the contact layer without showing obvious detrimental effects.
Modeling the Mechanical Integrity of Generic Solid Oxide Cell Stack Designs Exposed to Long‐term Operation
Authors: Molla T. T. , Kwok K. , Frandsen H. L.
Published: December 2018

Thermal cycling and creep in metallic interconnects during operation of solid oxide cell (SOC) stacks could cause contact losses in the interface between the interconnect and cells. The magnitude of stress and its distribution within the SOC stack depends on the overall design of the stack and the operating conditions. In this study, stresses in different types of generic SOC stack designs caused by external loading and temperature variations through long‐term operation are investigated. The investigation includes stack designs with and without contact components combined with machined (cross‐shaped) or pressed (corrugated) interconnects. Two different generic temperature profiles in the stacks are considered. Special focus is given to stresses that can cause possible delamination of the interconnect from the cell that subsequently leads to loss of electrical contact. It is found that too rigid designs cause high stresses and creep in the interconnects, and so‐called stress reversal will cause delamination between interconnect and cell during shut‐down. Furthermore, the study also presents the effect of SOC stack design and/or thermal gradient on the magnitude of in‐plane stresses in the cells. Here it is found that it advantageous to cool the stack primarily with convection, as this causes a linear thermal profile and much lower stresses than if cooling is relying on conduction in the solids, as this causes a thermal gradient in several directions.
Decoding vibrotactile choice independent of stimulus order and saccade selection during sequential comparisons
Authors: Wu Yuan‐hao , Velenosi Lisa A. , Schröder Pia , Ludwig Simon , Blankenburg Felix
Published: December 2018

Decision‐making in the somatosensory domain has been intensively studied using vibrotactile frequency discrimination tasks. Results from human and monkey electrophysiological studies from this line of research suggest that perceptual choices are encoded within a sensorimotor network. These findings, however, rely on experimental settings in which perceptual choices are inextricably linked to sensory and motor components of the task. Here, we devised a novel version of the vibrotactile frequency discrimination task with saccade responses which has the crucial advantage of decoupling perceptual choices from sensory and motor processes. We recorded human fMRI data from 32 participants while they performed the task. Using a whole‐brain searchlight multivariate classification technique, we identify the left lateral prefrontal cortex and the oculomotor system, including the bilateral frontal eye fields (FEF) and intraparietal sulci, as representing vibrotactile choices. Moreover, we show that the decoding accuracy of choice information in the right FEF correlates with behavioral performance. Not only are these findings in remarkable agreement with previous work, they also provide novel fMRI evidence for choice coding in human oculomotor regions, which is not limited to saccadic decisions, but pertains to contexts where choices are made in a more abstract form.
Attribute level overlap (and color coding) can reduce task complexity, improve choice consistency, and decrease the dropout rate in discrete choice experiments
Authors: Jonker Marcel F. , Donkers Bas , de Bekker‐Grob Esther , Stolk Elly A.
Published: December 2018

A randomized controlled discrete choice experiment (DCE) with 3,320 participating respondents was used to investigate the individual and combined impact of level overlap and color coding on task complexity, choice consistency, survey satisfaction scores, and dropout rates. The systematic differences between the study arms allowed for a direct comparison of dropout rates and cognitive debriefing scores and accommodated the quantitative comparison of respondents' choice consistency using a heteroskedastic mixed logit model. Our results indicate that the introduction of level overlap made it significantly easier for respondents to identify the differences and choose between the choice options. As a stand‐alone design strategy, attribute level overlap reduced the dropout rate by 30%, increased the level of choice consistency by 30%, and avoided learning effects in the initial choice tasks of the DCE. The combination of level overlap and color coding was even more effective: It reduced the dropout rate by 40% to 50% and increased the level of choice consistency by more than 60%. Hence, we can recommend attribute level overlap, with color coding to amplify its impact, as a standard design strategy in DCEs.
Detection of circulating HPV16 DNA as a biomarker in the blood of patients with human papillomavirus‐positive oropharyngeal squamous cell carcinoma
Authors: Mazurek Agnieszka M. , Rutkowski Tomasz , Śnietura Mirosław , Pigłowski Wojciech , Suwiński Rafał , Składowski Krzysztof
Published: December 2018

Background

Development of biomarker analysis using the circulating cell‐free DNA (cfDNA) methodology is a challenge for noninvasive cancer diagnosis. In this study, a comparison between the plasma and tumor tissue HPV16 DNA viral loads (VLs) has been presented.

Methods

Real‐time polymerase chain reaction was performed for quantitating of HPV16 DNA in the plasma and tumor samples of patients with oropharyngeal cancer.

Results

Among the tissues, HPV16‐positive patients with oropharyngeal squamous cell carcinoma, nonsmoking patients, displayed significantly higher HPV16 DNA VLs in their tissue. No smoking and advanced N disease were the most important predictors for cHPV16 DNA (circulating HPV16 DNA) detection. The cHPV16‐positive women displayed significantly higher VLs in their tumor tissues compared to the men, although without notable impact on the blood detection.

Conclusions

Many factors were responsible for human papillomavirus DNA circulation in blood. As a result of the small size of the analyzed group, some observed discrepancies need to be proven on a larger cohort.
Script fading for children with autism: Generalization of social initiation skills from school to home
Authors: Wichnick‐Gillis Alison M. , Vener Susan M. , Poulson Claire L.
Published: December 2018

We used a script‐fading package to teach children with autism to initiate social interactions across various activities in the school setting, and we programmed for generalization in the untrained home setting with a sibling. The three participants, ages 8 to 10 years, demonstrated deficits in social initiations with their peers. During baseline, the participants emitted initiations to one another, although this behavior was variable and did not endure over time. With the introduction of the script‐fading package, however, social initiations systematically increased. Moreover, the effects of the script‐fading package generalized to the untrained home setting with a sibling. This study expands upon previous research by demonstrating the generalization of social initiations from school with peers to the home setting with siblings.
Maternal di‐(2‐ethylhexyl) phthalate exposure alters hepatic insulin signal transduction and glucoregulatory events in rat F1 male offspring
Authors: Rajagopal Gokulapriya , Bhaskaran Ravi Sankar , Karundevi Balasubramanian
Published: December 2018

Di‐(2‐ethylhexyl) phthalate (DEHP) is a commonly used plasticizer with endocrine disrupting properties. Its widespread use resulted in constant human exposure including fetal development and postnatal life. Epidemiological and experimental data have shown that DEHP has a negative influence on glucose homeostasis. However, the evidence regarding the effect of maternal DEHP exposure on hepatic glucose homeostasis is scarce. Hence, we investigated whether DEHP exposure during gestation and lactation disrupts glucose homeostasis in the rat F1 male offspring at adulthood. Pregnant rats were divided into three groups and administered with DEHP (10 and 100 mg/kg/day) or olive oil from gestational day 9 to postnatal day 21 (lactation period) through oral gavage. DEHP‐exposed offspring exhibited hyperglycemia, impaired glucose and insulin tolerances along with hyperinsulinemia at postnatal day 80. DEHP exposure significantly reduced the levels of insulin signaling molecules such as insulin receptors, IRS1, Akt and its phosphorylated forms. GSK3β and FoxO1 proteins increased in DEHP‐exposed groups whereas its phosphorylated forms decreased. Treated groups showed decreased glycogen synthase activity and glycogen concentration. Glucose‐6‐phosphatase and phosphoenolpyruvate carboxykinase mRNA level and enzyme activity increased in DEHP‐treated groups. The interaction between FoxO1‐glucose‐6‐phosphatase and FoxO1‐phosphoenolpyruvate carboxykinase was also increased. This study suggests that DEHP exposure impairs insulin signal transduction and alters glucoregulatory events leading to the development of type 2 diabetes in F1 male offspring.
Investigating the permeation properties of contact lenses and its influence on tear electrolyte composition
Authors: Mann Aisling , Sáez‐Martinez Virginia , Lydon Fiona , Tighe Brian
Published: December 2018

The health of the cornea is paramount; the aim of this study was to assess the permeation of essential tear electrolytes through a range of commercial contact lenses. Donor/receiver conductivity measurements were recorded using a dual‐chamber diffusion system which allowed material permeability profiles and coefficients to be calculated. Water structuring properties of the contact lenses were measured by differential scanning calorimetry. Freezing water was subdivided into “ice‐like” water (free, non‐bound and has a melting point close to that of pure water) and polymer‐associated water (free but loosely bound to the polymer matrix). Each material interacts differently with each of the three salts, for example; lotrafilcon B (34% equilibrium water content [EWC]) shows a higher and larger range of receiver concentrations post KCl, NaCl, CaCl2 permeation (76, 59 and 42 mM, respectively) compared with the lower and tighter range exhibited by lotrafilcon A (22% EWC) (36, 22, and 18 mM, respectively). Additionally, in terms of the relationship between permeation and water structure, balafilcon A (34% EWC) has a high KCl permeation (P60 258 × 10−8 cm2/s) and ice‐like water (14%), but narafilcon A (44% EWC) has a low ion permeation (P60 3.9 × 10−8 cm2/s) and significantly less ice‐like water (4%). The permeation trends for the silicone hydrogel materials could not be fully explained by water content and structuring. Composition and, in particular, the microstructure and morphology of these materials must impart a greater influence on permeation capability. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1997–2005, 2019.
A shared comparison of diabetes mellitus and neurodegenerative disorders
Authors: Morsi Mahmoud , Kobeissy Firas , Magdeldin Sameh , Maher Ahmed , Aboelmagd Omnia , Johar Dina , Bernstein Larry
Published: December 2018

Diabetes mellitus (DM), one of the most prevalent metabolic diseases in the world population, is associated with a number of comorbid conditions including obesity, pancreatic endocrine changes, and renal and cardio‐cerebrovascular alterations, coupled with peripheral neuropathy and neurodegenerative disease, some of these disorders are bundled into metabolic syndrome. Type 1 DM (T1DM) is an autoimmune disease that destroys the insulin‐secreting islet cells. Type 2 DM (T2DM) is diabetes that is associated with an imbalance in the glucagon/insulin homeostasis that leads to the formation of amyloid deposits in the brain, pancreatic islet cells, and possibly in the kidney glomerulus. There are several layers of molecular pathologic alterations that contribute to the DM metabolic pathophysiology and its associated neuropathic manifestations. In this review, we describe the general signature metabolic features of DM and the cross‐talk with neurodegeneration. We will assess the underlying molecular key players associated with DM‐induced neuropathic disorders that are associated with both T1DM and T2DM. In this context, we will highlight the role of tau and amyloid protein deposits in the brain as well in the pancreatic islet cells, and possibly in the kidney glomerulus. Furthermore, we will discuss the central role of mitochondria, oxidative stress, and the unfolded protein response in mediating the DM‐associated neuropathic degeneration. This study will elucidate the relationship between DM and neurodegeneration which may account for the evolution of other neurodegenerative diseases, particularly Alzheimer's disease and Parkinson's disease as discussed later.
Galectin‐3 deficiency protects lipopolysaccharide‐induced chondrocytes injury via regulation of TLR4 and PPAR‐γ‐mediated NF‐κB signaling pathway
Authors: Wang Jian‐sheng , Xiao Wei‐wei , Zhong Yong‐sheng , Li Xue‐dong , Du Shi‐xin , Xie Peng , Zheng Gui‐zhou , Han Jing‐ming
Published: December 2018

The aim of the present study was to identify the functional role of galectin‐3 (Gal‐3) in lipopolysaccharide (LPS)‐induced injury in ATDC5 cells and to explore the probable molecular mechanisms. Here, we identified that LPS is sufficient to enhance the expression of Gal‐3 in ATDC5 cells. In addition, repression of Gal‐3 obviously impeded LPS‐stimulated inflammation damage as exemplified by a reduction in the release of inflammatory mediators interleukin (IL)‐1β, IL‐6, and tumor necrosis factor‐α, as well as the production of nitric oxide and prostaglandin E2 (PGE2) concomitant with the downregulation of matrix metalloproteinases (MMP)‐13 and MMP‐3 expression in ATDC5 cells after LPS administration. Moreover, ablation of Gal‐3 dramatically augmented cell ability and attenuated cell apoptosis accompanied by an increase in the expression of antiapoptotic protein Bcl‐2 and a decrease in the expression of proapoptotic protein Bax and caspase‐3 in ATDC5 cells subjected with LPS. Importantly, we observed that forced expression of TLR4 or blocked PPAR‐γ with the antagonist GW9662 effectively abolished Gal‐3 inhibition–mediated anti‐inflammatory and antiapoptosis effects triggered by LPS. Mechanistically, depletion of Gal‐3 prevents the NF‐κB signaling pathway. Taken together, these findings indicated that the absence of Gal‐3 exerted chondroprotective properties dependent on TLR4 and PPAR‐γ‐mediated NF‐κB signaling, indicating that Gal‐3 functions as a protector in the development and progression of osteoarthritis.
Chromogenic and fluorogenic detection of copper ions in the solution and intracellular media
Authors: Hanif Muhammad , Rafiq Muhammad , Saleem Muhammad , Mustaqeem Muhammad , Jamil Saba , Janjua Muhammad Ramzan Saeed Ashraf
Published: December 2018

The development of a fluorescent sensor for the trace detection of the metallic contamination in the ecosystem and biological media have been a demand to reduce the health risk and environmental protection. Herein, we report the synthesis of 2‐formyl‐5‐picolinyl‐substituted rhodamine B derivative through Schiff base formation for the trace detection of the copper ions in the aqueous organic media as well as inside the live cells via bioimaging experiments. The ligand was successfully employed to detect the minute copper level ratiometrically through the chromogenic and fluorogenic response. The detection limit of the sensor was found to be 0.54 × 10−9 mol/L using 3 σ/slope relations. The reversible behavior of the ligand copper complex was determined using sulfide ions that regenerate the entire native properties of the ligands by snatching copper from the complex. The bioimaging experimental results represent the efficient membrane permeability of ligands with the minimum level of toxicity in the measured range found by the MTT assay. The appearance of bright red fluorescence from the BHK‐21 (hamster kidney fibroblast) cells upon treatment of the ligand incubated cells with the copper ions represents the utility of the proposed sensor for the copper detection probe in the intracellular media.
A pH optical and fluorescent sensor based on rhodamine modified on activated cellulose paper
Authors: Taweetanavanich Thianthan , Wanno Banchob , Tuntulani Thawatchai , Pulpoka Buncha , Kaewtong Chatthai
Published: December 2018

A rhodamine‐based colorimetric and fluorescent pH chemosensor (RhA) was designed and synthesized via a coupling reaction between rhodamine ethylenediamine and succinic anhydride. RhA showed excellent pH response in aqueous solutions. In addition, common cations (Na+, K+, Ag+, Mg2+, Ca2+, Pb2+, Co2+, Ni2+, Cu2+, Zn2+, Cd2+, Hg2+, Al3+, Cr3+, Fe3+, Au3+, Pt2+, and Ru2+) did not interfere with the pH response. As it has the potential to be used as a portable pH sensor, RhA was immobilized on activated cellulose paper using N,N'‐dicyclohexylcarbodiimide (DCC) and N,N'‐dimethylpyridin‐4‐amine (DMAP) as the coupling reagent to obtain a composite pH sensor (CP‐RhA). CP‐RhA was characterized by ATR‐FTIR, UV–vis, and fluorescence spectroscopy, and by scanning electron microscopy (SEM). CP‐RhA showed a rapid response in the pH range 1–8 through color and fluorescence changes. DFT calculations showed a blue‐shifted spectrum in the protonated form compared to the neutral form. Moreover, the pH sensor paper could be reused by dipping in NaOH. Thus, our work demonstrates the potential of the rhodamine dye composite for visualizing pH changes in real systems.
Long noncoding RNA–antisense noncoding RNA in the INK4 locus accelerates wound healing in diabetes by promoting lymphangiogenesis via regulating miR‐181a/Prox1 axis
Authors: He Zhi‐You , Wei Tian‐Hong , Zhang Pi‐Hong , Zhou Jie , Huang Xiao‐Yuan
Published: December 2018

Background

Slow lymphangiogenesis is one crucial reason for the impaired wound healing process in diabetes. Accumulative evidence showed that long noncoding RNA–antisense noncoding RNA in the INK4 locus (ANRIL) could influence lymphangiogenesis. Besides, miR‐181a has been reported to regulate Prox1 that is essential for lymphangiogenesis. However, the relationship between ANRIL and miR‐181a as well as the definitive function of ANRIL in lymphangiogenesis is not clear.

Methods

The diabetic mouse model was set up to assess the wound healing rate in vivo. Quantitative real‐time polymerase chain reaction was performed to measure the expressions of ANRIL, miR‐181a, and Prox1. Western blot analysis was used to assess the expressions of vascular endothelial growth factor receptor‐3, lymphatic vessel hyaluronan receptor‐1, Prox1, and epithelial–mesenchymal transition (EMT)‐related proteins. Flow cytometry was used to assess the cell apoptosis. Wound healing assay was used to determine the effect of ANRIL on cell migration. Tube‐formation assay and immunofluorescence staining were performed to determine tube‐formation capacity of human dermal lymphatic endothelial cells (LECs).

Results

ANRIL and Prox1 were downregulated, whereas miR‐181a was upregulated in the diabetic wound healing mouse model and high glucose (HG)‐induced LECs. The wound healing rate and EMT were inhibited during the diabetic wound healing process. Dual‐luciferase assay proved that miR‐181a could bind Prox1 to repress its expression, whereas ANRIL could sponge miR‐181a to recover Prox1 expression. Overexpression of ANRIL or inhibition of miR‐181a rescued the impairments of survival, migration, EMT formation, and tube formation of LECs caused by HG.

Conclusion

ANRIL could promote lymphangiogenesis during the diabetic wound healing process via sponging miR‐181a to enhance Prox1 expression, which might help design new therapy to improve the wound healing efficacy for diabetes.
Clusterin enhances AKT2‐mediated motility of normal and cancer prostate cells through a PTEN and PHLPP1 circuit
Authors: Bertacchini Jessika , Mediani Laura , Beretti Francesca , Guida Marianna , Ghalali Aram , Brugnoli Federica , Bertagnolo Valeria , Petricoin Emanuel , Poti Francesco , Arioli Jessica , Anselmi Laura , Bari Alessia , McCubrey James , Martelli Alberto M. , Cocco Lucio , Capitani Silvano , Marmiroli Sandra
Published: December 2018

Clusterin (CLU) is a chaperone‐like protein with multiple functions. sCLU is frequently upregulated in prostate tumor cells after chemo‐ or radiotherapy and after surgical or pharmacological castration. Moreover, CLU has been documented to modulate the cellular homolog of murine thymoma virus akt8 oncogene (AKT) activity. Here, we investigated how CLU overexpression influences phosphatidylinositol 3′‐kinase (PI3K)/AKT signaling in human normal and cancer epithelial prostate cells. Human prostate cells stably transfected with CLU were broadly profiled by reverse phase protein array (RPPA), with particular emphasis on the PI3K/AKT pathway. The effect of CLU overexpression on normal and cancer cell motility was also tested. Our results clearly indicate that CLU overexpression enhances phosphorylation of AKT restricted to isoform 2. Mechanistically, this can be explained by the finding that the phosphatase PH domain leucine‐rich repeat‐containing protein phosphatase 1 (PHLPP1), known to dephosphorylate AKT2 at S474, is markedly downregulated by CLU, whereas miR‐190, a negative regulator of PHLPP1, is upregulated. Moreover, we found that phosphatase and tensin homolog (PTEN) was heavily phosphorylated at the inhibitory site S380, contributing to the hyperactivation of AKT signaling. By keeping AKT2 phosphorylation high, CLU dramatically enhances the migratory behavior of prostate epithelial cell lines with different migratory and invasive phenotypes, namely prostate normal epithelial 1A (PNT1A) and prostatic carcinoma 3 (PC3) cells. Altogether, our results unravel for the first time a circuit by which CLU can switch a low migration phenotype toward a high migration phenotype, through miR‐190‐dependent downmodulation of PHLPP1 expression and, in turn, stabilization of AKT2 phosphorylation.
MRS1754 inhibits proliferation and migration of bladder urothelial carcinoma by regulating mitogen‐activated protein kinase pathway
Authors: Zhou Yihong , Chu Xi , Yi Ye , Hao Zheng , Zheng Xiaoping , Yuxin Tang , Dai Yingbo
Published: December 2018

Bladder urothelial carcinoma (BUC) is one of the most common urological malignancies. Our previous study found that adenosine A2b receptor (A2bR) was upregulated in BUC tissues and cells. In the present study, we investigated the effect of MRS1754 (a selective A2bR antagonist) on cell proliferation and migration in two well‐studied invasive urothelial cell carcinoma lines EJ and T24. Our results showed that MRS1754 reduced BUC cell proliferation and induced a G0/G1 phase cell‐cycle arrest. Next, MRS1754 inhibited cell migration and Bay60‐6583 (a selective A2bR agonist) treatment could reverse the inhibitory effect of MRS1754 on BUC cells migration. Furthermore, our results showed MRS1754 treatment downregulated the protein levels of p‐P38, p‐JNK, and phospho‐extracellular signal‐regulated kinase (p‐ERK). These findings suggest that MRS1754 can inhibit progression of BUC via mitogen‐activated protein kinase (MAPK) pathway and indicate the therapeutic potential of A2B antagonists in BUC.
Safety Exposure‐Response Analysis for Daclatasvir, Asunaprevir, and Beclabuvir Combinations in HCV‐Infected Subjects
Authors: Osawa Mayu , Ueno Takayo , Shiozaki Tomomi , Li Hanbin , Garimella Tushar
Published: December 2018

The combination regimen of daclatasvir, asunaprevir, and beclabuvir has been developed for the treatment of hepatitis C virus infection. The objectives of this analysis were to characterize the relationship between the exposures of the daclatasvir, asunaprevir, and beclabuvir regimen and liver‐related laboratory elevations (Grade 3 or 4 alanine aminotransferase [ALT] and total bilirubin [Tbili]), and to evaluate the impact of selected covariates on the exposure‐response relationships. The exposure‐response analysis was performed with data from 1 phase 2 and 3 phase 3 studies in hepatitis C virus–infected subjects. The probability of liver‐related laboratory elevations were modeled using linear logistic regression. Selected covariates were tested using a forward‐addition and backward‐elimination approach. The final model for ALT elevation included Asian race, body weight in non‐Asian subjects, and asunaprevir exposure. The final model for Tbili elevation included Asian race, fibrosis score (F0‐F3 or F4) and asupanprevir exposure. Asian subjects had greater the Grade 3 or 4 ALT and Tbili elevation rates than non‐Asians. The Grade 3 or 4 ALT elevation rate increased with decreasing body weight in non‐Asian subjects. Subjects with F4 fibrosis score had a higher rate of Grade 3 or 4 Tbili elevation compared to subjects with F0 to F3 fibrosis score. Higher asunaprevir exposure was associated with increases in Grade 3 or 4 ALT and Tbili elevation rates; however, the impact on the ALT elevation was not clinically relevant and the effect on Tbili elevation was smaller than the other significant covariates.
Population Pharmacokinetics and Exposure‐Response Analyses for CPX‐351 in Patients With Hematologic Malignancies
Authors: Wang Qi , Banerjee Kamalika , Vasilinin Grygoriy , Marier J.F. , Gibbons Jacqueline A.
Published: December 2018

CPX‐351, a dual‐drug liposomal encapsulation of cytarabine and daunorubicin at a synergistic ratio, is approved in the United States for adults with newly diagnosed therapy‐related acute myeloid leukemia or acute myeloid leukemia with myelodysplasia‐related changes. Population pharmacokinetics analyses were performed using nonlinear mixed‐effect modeling on pooled data from 3 clinical studies, and the impact of CPX‐351 exposures on efficacy and safety was assessed. The pharmacokinetics of cytarabine and daunorubicin were described using 2‐compartment models with linear elimination. None of the evaluated covariates had a clinically significant impact on plasma exposure to total cytarabine or daunorubicin, while bilirubin and formulation showed statistically significant effects on pharmacokinetic parameters of cytarabine and daunorubicin, respectively. In patients with mild/moderate renal impairment or serum bilirubin ≤3 mg/dL, plasma exposures to cytarabine and daunorubicin following CPX‐351 were within the variability range for patients with normal kidney function or serum bilirubin levels. Exposure‐response analysis demonstrated that better efficacy outcomes were associated with higher CPX‐351 exposure quartiles. Early mortality rates in all CPX‐351 exposure quartiles were lower vs the 7 + 3 control group, and lower mortality rates were associated with higher exposure quartiles. A trend toward greater frequency of grade 3 treatment‐emergent adverse events (but not grade 4/5 events) was observed at higher CPX‐351 exposure quartiles. Overall, the population pharmacokinetic analyses indicate no adjustments to the recommended dose and schedule of CPX‐351 are warranted for patients with mild/moderate renal impairment or serum bilirubin ≤3 mg/dL. Results from the exposure‐response analyses suggest the current CPX‐351 regimen provides a favorable risk‐benefit profile.
Vitamin D supplements for trunk muscle morphology in older adults: secondary analysis of a randomized controlled trial
Authors: Cuellar William A. , Blizzard Leigh , Hides Julie A. , Callisaya Michele L. , Jones Graeme , Cicuttini Flavia , Wluka Anita E. , Ding Changhai , Winzenberg Tania M.
Published: December 2018

Background

The effect of vitamin D supplementation on postural muscles of the trunk is of particular interest because low 25‐hydroxyvitamin D [25(OH) D] levels are associated with decreased postural balance and increased risk of falls. Understanding the role of vitamin D supplementation plays in trunk muscle function of older adults is necessary, as this is a potentially modifiable factor to improve postural muscle function and decrease the risk of falling of older adults. The objective of this randomized controlled trial was to evaluate the effect of 12 months of vitamin D supplementation compared with placebo, on morphology and function of the trunk muscles of adults aged 50 to 79 years with low serum 25(OH) D levels.

Methods

This was a secondary analysis of a randomized, placebo‐controlled, and double‐blind clinical trial conducted between June 2010 and December 2013 in Tasmania, Australia. The clinical trial was registered with the Australian New Zealand clinical trial registration agency, ClinicalTrials.gov identifier: NCT01176344; Australian New Zealand Clinical Trials Registry: ACTRN 12610000495022. Participants were aged 50–79 years with ongoing symptoms of knee osteoarthritis and with low serum [25(OH) D] (12.5 to 60 nmol/L, 5.2 to 24 ng/mL). Participants were randomly assigned to either monthly 50 000 IU oral vitamin D3 (n = 104) or an identical placebo (n = 113) for 24 months as per clinical trial protocol. The primary outcomes in this pre‐specified secondary analysis were between‐group differences in change in size of rectus abdominis, transversus abdominis, internal oblique, external oblique, and lumbar multifidus muscles and function (assessed by change in thickness on contraction) of these muscles (excepting rectus abdominis) from baseline to 12 months. Muscle size was assessed using ultrasound imaging.

Results

Of 217 participants (mean age 63 years, 48% women), 186 (85.7%) completed the study. There were no significant between‐group differences in change in size or function of the abdominal or multifidus muscles after 12 months of vitamin D supplementation.

Conclusions

A monthly dose of 50 000 IU of vitamin D3 alone for 12 months does not affect the size or ability to contract trunk muscles of independent community‐dwelling older adults with symptomatic knee osteoarthritis and low serum 25(OH) D levels regardless of body mass index status or degree of vitamin D deficiency. An effect of vitamin D supplementation on other aspects of trunk muscle function such as strength, power, or physical function cannot be ruled out.
Revalorization of grape marc waste from liqueur wine: biomethanization
Authors: Javier Hungría , Ángel Siles J , Aida Gil , del Carmen Gutiérrez M , de los Ángeles Martín M
Published: December 2018

BACKGROUND

Grapes are one of the largest crops produced worldwide and are used mainly to produce wine, which generates a large volume of waste. Certain designations of origin, such as the Montilla‐Moriles PDO of Cordoba (Spain) produce liqueur wines at low yield. The possibility of generating by‐products from the waste during the winemaking process might provide an additional economic input.

RESULTS

Anaerobic digestion of grape marc waste derived from the Pedro Ximénez variety (ecological crop) was evaluated under mesophilic conditions at laboratory scale. The loads added to the reactors varied from 0.50 to 1.25 gVS (volatile solids) L−1, with an average methane production coefficient of 252 ± 31 mLSTP CH4 g−1 VSadded (STP: 0 °C, 1 atm). The highest methane rate production was found to be 47.97 ± 4.29 mLSTP CH4 L−1 h for 1.25 gVS L−1 of grape marc waste. The volatile fatty acids concentration increased, and the pH and alkalinity slightly decreased over the experimental time. Moreover, the digestate contained lower metal concentration in comparison with waste derived from nonecological crops.

CONCLUSION

Anaerobic digestion of Pedro Ximénez grape marc waste is feasible and might be implemented for waste management, thus reducing the large volume of waste generated. © 2018 Society of Chemical Industry
Suppressed oxygen evolution during chlorate formation from hypochlorite in the presence of chromium(VI)
Authors: Endrődi Balázs , Sandin Staffan , Wildlock Mats , Simic Nina , Cornell Ann
Published: December 2018

Background

Chromium(VI) is a crucial electrolyte component in industrial chlorate production. Due to its toxicity, it urgently needs to be abandoned and its functions fulfilled by new solutions. In the industrial production of sodium chlorate, homogeneous decomposition of the hypochlorite intermediate to chlorate is a key step. As a competing loss reaction, hypochlorite can decompose to oxygen. How chromium(VI) affects these reactions is not well understood.

Results

This work shows, for the first time, that chromium(VI) selectively accelerates the chlorate formation from hypochlorite both in dilute and concentrated, industrially relevant solutions. The effect of the ionic strength and the specific contribution of different electrolyte components were systematically studied. By simultaneously measuring the concentration decay of hypochlorite (UV–vis spectroscopy) and the oxygen formation (mass spectrometry), both the rate and the selectivity of the reactions were evaluated.

Conclusion

In the presence of chromium(VI) the hypochlorite decomposition is described by the sum of an uncatalyzed and a parallel catalyzed reaction, where oxygen only forms in the uncatalyzed reaction. When removing chromium(VI), the homogeneous oxygen formation increases, causing economic and safety concerns. The need for a catalyst selective for chlorate formation is emphasized. © 2018 The Authors. Journal of Chemical Technology & Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Cross‐linked enzyme aggregates of recombinant cyclodextrin glycosyltransferase for high‐purity β‐cyclodextrin production
Authors: Zhang Jianguo , Li Mengla , Mao Hongli
Published: December 2018

BACKGROUND

High‐purity α‐, β‐, or γ‐cyclodextrin (CD) production using cyclodextrin glycosyltransferase (CGTase) as biocatalyst to cyclize starch is advantageous owing to its low cost of purification and product specificity. Several approaches have been investigated to enhance product specificity of CGTase, such as new CGTase isolation, CGTase gene (cgt) mutation, and chemical addition.

RESULTS

Recombinant CGTase was cross‐linked by glutaraldehyde to obtain cross‐linked enzyme aggregates of recombinant CGTase (CLEA‐CGTase) at 85 °C because free CGTase showed high product specificity at 85 °C. The CLEA‐CGTase was prepared under the conditions 75 U mL−1 CGTase with 0.1% (v/v) glutaraldehyde for 10 min at 85 °C after optimization first, and produced a high proportion of β‐CD from soluble starch at 50 °C in the conversion system. The conversion process was carried out with 10 to 200 U mL−1 CLEA‐CGTase, resulting in 100% β‐CD from soluble starch after 420 min conversion of the potato starch solution at 50 °C. And the proportion of β‐CD was still higher than 90% when 8000 U mL−1 CLEA‐CGTase was added.

CONCLUSIONS

CLEA technology maintained CGTase conformation of 85 °C, and produced a high proportion of β‐CD at 50 °C. This research showed the CLEA technology kept the conformation of enzyme for specific product production. © 2018 Society of Chemical Industry
On the Kőnig‐Egerváry theorem for ‐paths
Authors: Bessy Stéphane , Ochem Pascal , Rautenbach Dieter
Published: December 2018

The famous Kőnig‐Egerváry theorem is equivalent to the statement that the matching number equals the vertex cover number for every induced subgraph of some graph if and only if that graph is bipartite. Inspired by this result, we consider the set of all graphs such that, for every induced subgraph, the maximum number of disjoint paths of order equals the minimum order of a set of vertices intersecting all paths of order . For , we give complete structural descriptions of the graphs in . Furthermore, for odd , we give a complete structural description of the graphs in that contain no cycle of order less than . For these graph classes, our results yield efficient recognition algorithms as well as efficient algorithms that determine maximum sets of disjoint paths of order and minimum sets of vertices intersecting all paths of order .
Synthesis and Anti‐proliferative Activity of Novel Polysubstitued Indazole Derivatives
Authors: Bassou Oulemda , Chicha Hakima , Allam Afaf , Monticone Massimiliano , Gangemi Rosaria , Maric Irena , Viale Maurizio , Rakib El Mostapha
Published: December 2018

A simple and efficient process is developed for the synthesis of new N‐(1‐alkyl‐3‐chloro‐4‐ethoxy‐1H‐indazol‐5‐yl)‐arylsulfonamides 4a–d and N‐(1‐alkyl‐3‐chloro‐1H‐indazol‐5‐yl)‐arylsulfonamides 5a–d through the reduction of 1‐alkyl‐3‐chloro‐5‐nitroindazoles 2a,b with SnCl2 in ethanol followed by coupling the corresponding amine with arylsulfonyl chlorides in pyridine. All the newly synthesized compounds have been characterized by elemental analysis and spectroscopic data. Some compounds were tested for their in vitro antiproliferative activities against two selected human cancer cell lines A2780 and A549. Among all of these derivatives, compound 5d showed the most potent antiproliferative activity against A2780 (IC50 = 5.47 ± 1.45 μM) and A549 (IC50 = 7.73 ± 1.66 μM) cell lines.