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Background: At‐risk alcohol use is a common and costly form of substance misuse that is highly prevalent among people living with HIV (PLWH). The goal of the current analysis was to test the hypothesis that PLWH with at‐risk alcohol use are more likely to meet the clinical criteria for prediabetes/diabetes than PLWH with low‐risk alcohol use. Methods: A cross‐sectional analysis was performed on measures of alcohol and glycemic control in adult PLWH (n = 105) enrolled in a prospective, interventional study (the ALIVE‐Ex Study (NCT03299205)) that investigated the effects of aerobic exercise on metabolic dysregulation in PLWH with at‐risk alcohol use. The Alcohol Use Disorders Identification Test (AUDIT), Timeline Followback, and phosphatidylethanol (PEth) level were used to measure alcohol use. Participants were stratified into low‐risk (AUDIT score < 5) and at‐risk alcohol use (AUDIT score ≥ 5). All participants underwent an oral glucose tolerance test and measures of glycemic control− the Homeostatic Model Assessment of Insulin Resistance (HOMA‐IR) and Matsuda Index − were correlated with alcohol measures and compared by AUDIT score group using mixed‐effects linear and logistic regression models, adjusting for age, sex, race, body mass index (BMI), and viral load. Results: In response to the glucose challenge, participants with at‐risk alcohol use (n = 46) had higher glucose levels and were five times more likely to meet criteria for prediabetes/diabetes (OR: 5.3 (1.8, 15.9)) than participants with an AUDIT score < 5. Two‐hour glucose values were positively associated with AUDIT score and PEth level and a higher percentage of PLWH with at‐risk alcohol use had glucose values ≥140 mg/dl than those with low‐risk alcohol use (34.8% vs. 10.2%, respectively). Conclusion: In this cohort of PLWH, at‐risk alcohol use increased the likelihood of meeting the clinical criteria for prediabetes/diabetes (2‐h glucose level ≥140 mg/dl). Established determinants of metabolic dysfunction (e.g., BMI, waist–hip ratio) were not associated with greater alcohol use and dysglycemia, suggesting that other mechanisms may contribute to the impaired glycemic control observed in this cohort. [ABSTRACT FROM AUTHOR]

Eukaryotes have evolved a variety of mRNA surveillance mechanisms to detect and degrade aberrant mRNAs with potential deleterious outcomes. Among them, nonsense-mediated mRNA decay (NMD) functions not only as a quality control mechanism targeting aberrant mRNAs containing a premature termination codon but also as a posttranscriptional gene regulation mechanism targeting numerous physiological mRNAs. Despite its well-characterized molecular basis, the regulatory scope and biological functions of NMD at an organismal level are incompletely understood. In humans, mutations in genes encoding core NMD factors cause specific developmental and neurological syndromes, suggesting a critical role of NMD in the central nervous system. Here, we review the accumulating biochemical and genetic evidence on the developmental regulation and physiological functions of NMD as well as an emerging role of NMD dysregulation in neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

There is a long-standing debate over whether new roads unavoidably lead to environmental damage, especially forest loss, but causal identification has been elusive. Using multiple causal identification strategies, we study the construction of new rural roads to over 100,000 villages and the upgrading of 10,000 kilometers of national highways in India. The new rural roads had precisely zero effect on local deforestation. In contrast, the highway upgrades caused substantial forest loss, which appears to be driven by increased timber demand along the transportation corridors. In terms of forests, last mile connectivity had a negligible environmental cost, while expansion of major corridors had important environmental impacts. [ABSTRACT FROM AUTHOR]

A new amperometric dopamine sensor has been developed on the basis of modified screen-printed electrode (SPCE) with reduced graphene oxide (RGO), polyneutral red (PNR) and gold nanoparticles (AuNP). The electrochemical behaviour of dopamine on SPCE/RGO/PNR/AuNP was investigated. The prepared sensor showed a high electrocatalytic effect on the oxidation of dopamine. In the amperometric determination of DA, optimum working conditions (optimum pH, optimum working potential, linear working range) were determined. The optimum values of these parameters in DA determination were 7.0 for pH and +0.25 V for working potential. The results of analytical characterisations, repeatability for 50 µM DA, sensitivity, the limit of detection, the limit of quantification and the linear range were found to be 2.14% (n = 10) as relative standard deviation (RSD.), 13.38 µA mM−1; 0.17 µM; 0.57 and 0.57–500 µM, respectively. Operational stability studies have shown that the initial amperometric response of the sensor to dopamine decreased by 90.05% on day 60. Storage life studies showed that the sensitivity of the biosensor decreased by 18.88% at the end of the 8th week. Amperometric electrochemical analysis of DA using SPCE/RGO/PNR/AuNP electrode was performed in the presence of interfering electroactive species AA and UA. The developed sensor was tested for DA determination in artificial blood serum samples. [ABSTRACT FROM AUTHOR]

A new amperometric NADH sensor was developed based on screen-printed electrode (SPCE) modified with reduced graphene oxide (RGO), polyneutral red (PNR) and gold nanoparticles (AuNP). Electrochemical behaviour of NADH on SPCE/RGO/PNR/AuNP was investigated. The prepared sensor showed a high electrocatalytic effect on the oxidation of NADH. The sensor response for NADH was investigated as a function of pH and working potential. Optimum values of these parameters in the NADH determination were found as 7.0 for pH and +0.15 V for working potential. Sensitivity, linear range, limit of detection and limit of quantification of the sensor were found to be 8.72 μAmM−1, 5 to 3170 μM, 0.384 μM and 1.18 μM, respectively. The relative standard deviation (RSD) was calculated to be 1.93% (for n = 10). The operational stability studies have shown that the initial amperometric response of sensor to NADH decreased by 56.15% at the 60th day. Storage life studies have shown that the sensitivity of the biosensor decreased by 48.72% at the end of 12 weeks. The developed sensor has been tested for NADH determination in the human serum sample. The developed NADH sensor is promising to be used for NADH analysis in human serum samples as simple, practical and disposable device without requiring laborious sample pre-treatment producers. [ABSTRACT FROM AUTHOR]

Molecular dynamics (MD) simulation of lactic acid (L‐acid) and pyruvic acid (P‐acid) in a physiological salt solution has been performed, which is used as the electrolyte in a sort of biofuel cell working on a human skin. The structure, frequency distribution of molecules, dielectric properties, rotational correlation functions, and diffusion coefficients have been calculated. The anomalous behavior of dielectric constants for the lower concentration of L‐acid and P‐acid has been obtained from MD. The anomalous dielectric constant is discussed in relation with the various physical properties of the solution including the life time of the interaction in the solution. MD results suggest that the anomalous behavior is supposed to be attributed to the difference of interactions between ions in the lower and higher concentration region. POLYM. ENG. SCI., 59:2474–2478, 2019. © 2019 Society of Plastics Engineers [ABSTRACT FROM AUTHOR]

Recently, buccal epithelium has been used to study age-dependent processes. This approach is of particular relevance due to its non-invasiveness. The purpose of this study is to establish the normal values of the buccal cytogram in different age groups, including athletes. 200 practically healthy volunteers of different ages were examined, who were divided into 5 groups in accordance with the WHO age classification. In addition, 125 professional athletes took part in the study. All patients underwent a comprehensive dental examination and a standard cytological examination of buccal smears. It has been established that the cytological characteristics of buccal epitheliocytes, indirectly reflecting disorders of the nuclear apparatus of the cell, did not change significantly with age, but there was a certain upward trend in the number of cells with such anomalies (micronucleus, protrusions).The number of binuclear cells and the apoptotic index also slightly increase with age. At the same time, a high positive correlation was found between the apoptosis index and senile age. In young athletes, an increase in the number of buccal epitheliocytes with a perinuclear vacuole (an early sign of cell damage) was foundAnalysis of the cytological examination results of the buccal epithelium in people a slight increase in the level of cytological abnormalities in old age, in particular, signs of apoptosis. In addition, in healthy young athletes (18 years old - 44 years old), an increase in the number of cells with signs of nuclear degradation, which most likely reflects increased mechanical stress on the maxillofacial apparatus during sports activities., Competing Interests: The authors declare no conflict of interest.

This review focuses on the state of research on the microbial resources of Dokdo, Korea, as a strategy for securing national microbial resources. In the Korean peninsula, studies aimed at securing microbial resources are carried out across diverse natural environments, especially in the Dokdo islands. Until 2017, a total of 61 novel microbial genera, species, or newly recorded strains have been reported. Among these, 10 new taxa have had their whole genome sequenced and published, in order to find novel useful genes. Additionally, there have been multiple reports of bacteria with novel characteristics, including promoting plant growth or inducing systemic resistance in plants, calcite-forming ability, electrical activation, and production of novel enzymes. Furthermore, fundamental studies on microbial communities help to secure and define microbial resources in the Dokdo islands. This study will propose several tactics, based on ecological principles, for securing more microbial resources to cope with the current increase in international competition for biological resources. [ABSTRACT FROM AUTHOR]

Invasive infections caused by Streptococcus pneumoniae, a commensal in the nasopharynx, pose significant risk to human health. Limited serotype coverage by the available polysaccharide-based conjugate vaccines coupled with increasing incidence of antibiotic resistance complicates therapeutic strategies. Bacterial physiology and metabolism that allows pathogens to adapt to the host are a promising avenue for the discovery of novel therapeutics. Intracellular polyamine concentrations are tightly regulated by biosynthesis, transport and degradation. We previously reported that deletion of cadA, a gene that encodes for lysine decarboxylase, an enzyme that catalyzes cadaverine synthesis results in an attenuated phenotype. Here, we report the impact of cadA deletion on pneumococcal capsule and protein expression. Our data show that genes for polyamine biosynthesis and transport are downregulated in DcadA. Immunoblot assays show reduced capsule in DcadA. Reduced capsule synthesis could be due to reduced transcription and availability of precursors for synthesis. The capsule is the predominant virulence factor in pneumococci and is critical for evading opsonophagocytosis and its loss in DcadA could explain the reported attenuation in vivo. Results from this study show that capsule synthesis in pneumococci is regulated by polyamine metabolism, which can be targeted for developing novel therapies. [ABSTRACT FROM AUTHOR]

Mudskippers are the largest group of amphibious teleost fish that are uniquely adapted to live on mudflats. During their successful transition from aqueous life to terrestrial living, these fish have evolved morphological and physiological modifications of aerial vision and olfaction, higher ammonia tolerance, aerial respiration, improved immunological defense against terrestrial pathogens, and terrestrial locomotion using protruded pectoral fins. Comparative genomic and transcriptomic data have been accumulated and analyzed for understanding molecular mechanisms of the terrestrial adaptations. Our current review provides a general introduction to mudskippers and recent research advances of their genetic adaptations to the amphibious lifestyle, which will be helpful for understanding the evolutionary transition of vertebrates from water to land. Our insights into the genomes and transcriptomes will also support molecular breeding, functional identification, and natural compound screening. [ABSTRACT FROM AUTHOR]

Two new long-chain unsaturated compounds, (2E, 6E)-10-methoxy-3,7-dimethyl-10-oxodeca-2,6-dienoic acid (1) and (2E, 6E)-3,7,11-trimethyldodeca-2,6-dienedioic acid (2), together with seven known compounds were isolated from a marine-derivedStreptomycessp. Their structures were determined by spectroscopic methods, including 2D NMR techniques. Compounds1and2were investigated for their antibacterial activities. [ABSTRACT FROM PUBLISHER]

A series of polylactic acid/hydroxyapatite/graphene oxide composite (PLA/HA/GO) were fabricated via solution blending and casting method using N,N-dimethyl-formamide (DMF) and CH2Cl2 as mutual solvents. The physicochemical properties of the resulting composites were characterized by means of FT-IR, SEM, TEM, Raman spectra, XRD and N2-physisorption. Particularly, the thermal stabilities, hydrophobic and mechanical properties of PLA/HA/GO composites were systematically investigated. The influences of GO content on thermal stabilities, hydrophobic and mechanical properties of the composites were also evaluated. The results showed that the addition of GO and HA not only improved the thermal stability of PLA, but also improved the hydrophobic property of PLA-based composites. By compared with the PLA/HA/GO composite, the tensile strength of pristine PLA is slight high. The tensile strength and hardness of PLA/HA/GO composites increased with the increase of GO content. The obtained PLA/HA/GO composite may be a promising material for load-bearing orthopedic implants. [ABSTRACT FROM AUTHOR]

Access to marine feed ingredients is considered a limiting factor for the rapidly growing aquaculture industry. With increasing inclusion of vegetable feed ingredients in aquafeeds, new challenges have arisen. Substituting marine oils and meals with vegetable ingredients has decreased the level of persistent organic pollutants ( POPs) in marine farmed fish such as Atlantic salmon. Consequently, this shift in feed ingredients has led to increased levels of polyaromatic hydrocarbons ( PAHs) in aquafeeds. Several of the PAHs listed are on EFSAs and EPAs list of priority substances. Not only are the carcinogenic and genotoxic properties of PAHs of concern, but also their ability to interact with and disrupt metabolic pathways such as vitamin metabolism and signalling. The interactions, and the potential depletion of vitamin stores that follows, are of particular interest as marine ingredients are naturally rich in micronutrients such as vitamins A and D. This study has summarized the current knowledge on the effect of PAHs commonly found in vegetable feed ingredients on vitamin metabolism/signalling and their possible implications in fish. [ABSTRACT FROM AUTHOR]

The transition from IPv4 to IPv6 is an inexorable trend in the development of Internet. However, since IPv4 has been widely deployed for many years, it is mandatory that the existing IPv4 and the newly deployed IPv6 coexist and interoperate seamlessly. With the study of various mechanisms proposed for the interoperability between IPv4 and IPv6, some mobility management protocols are also extended to work in the mixed mobile Internet. In this study, the authors carry out an in‐depth analysis of three types of standardised mobility management protocols with dual‐stack support. Owing to the difference of underlying basic protocols, their individual dual‐stack extensions have different features and thus are suited for deployment in different scenarios and stages in the evolution of the mobile Internet. [ABSTRACT FROM AUTHOR]

Aggressive and recurrent gynecological cancers are associated with worse prognosis and a lack of effective therapeutic response. Ovarian cancer (OC) patients are often diagnosed in advanced stages, when drug resistance, angiogenesis, relapse, and metastasis impact survival outcomes. Currently, surgical debulking, radiotherapy, and/or chemotherapy remain the mainstream treatment modalities; however, patients suffer unwanted side effects and drug resistance in the absence of targeted therapies. Hence, it is urgent to decipher the complex disease biology and identify potential biomarkers, which could greatly contribute to making an early diagnosis or predicting the response to specific therapies. This review aims to critically discuss the current therapeutic strategies for OC, novel drug-delivery systems, and potential biomarkers in the context of genetics and molecular research. It emphasizes how the understanding of disease biology is related to the advancement of technology, enabling the exploration of novel biomarkers that may be able to provide more accurate diagnosis and prognosis, which would effectively translate into targeted therapies, ultimately improving patients' overall survival and quality of life. [ABSTRACT FROM AUTHOR]

Mixed-ligand zinc complexes, i.e., 2-(2-hydroxyphenyl)benzothiazolato-5,7- dichloro-8-hydroxyquinolinato zinc(II) [ZnBTZ(Clq)], 2-(2-hydroxyphenyl) benzothiazolato-5,7-dimethyl-8-hydroxyquinolinato zinc(II) [ZnBTZ(Meq)], and 2-(2-hydroxyphenyl)benzothiazolato-2-carbonitril-8-hydroxyquinolinato zinc(II) [ZnBTZ(CNq)], were synthesized and characterized. The metal complexes have high thermal stability (>300°C) and high glass-transition temperature (>150°C) and are suitable for optoelectronic applications. Optical properties of the synthesized complexes were characterized by using ultraviolet-visible (UV-Vis) and photoluminescence spectroscopy. Color tuning by changing the ligand was observed in synthesized complexes. Multilayered organic electroluminescent devices were fabricated having structure indium-tin oxide (ITO)/ N, N′-diphenyl- N, N′-bis(1-naphthyl)-1,1′-biphenyl-4,4′-diamine (α-NPD)/zinc complex/2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline (BCP)/tris(quinolinolate)Al (Alq)/LiF/Al using the synthesized complexes as emissive material. The electroluminescence spectra show peak emission centered at 532 nm, 572 nm, and 541 nm, respectively, for these materials. The emitted light has chromaticity with Commission Internationale d'Éclairage coordinates x = 0.35 and y = 0.56 for ZnBTZ(Clq), x = 0.49 and y = 0.47 for ZnBTZ(Meq), and x = 0.48 and y = 0.40 for ZnBTZ(CNq) complex. [ABSTRACT FROM AUTHOR]

Organic coatings only a few nanometres thick have been prepared on surfaces of pure copper, copper alloys and stainless steel samples by self-assembly, Langmuir–Blodgett technique and dip-coating. The resulted thin films have been characterized by dynamic contact angle measurements as well as by infrared techniques. The stability of the layers in aqueous environment and their protective effect against corrosion in NaCl solution and against bacterial adhesion was investigated. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) is a mediator of a diverse array of inter- and intracellular signal transduction processes. The aim of the present study was to analyze its possible role as a second messenger in the process of neuronal differentiation of PC12 pheochromocytoma cells. Upon NGF treatment wildtype PC12 cells stop dividing and develop neurites. In contrast, a PC12 subclone (designated M-M17-26) expressing a dominant-negative mutant Ras protein keeps proliferating and fails to grow neurites after NGF treatment. Sodium nitroprusside (SNP), an NO donor, was found to induce the p53 protein and to inhibit proliferation of both PC12 and M-M17-26 cells, but failed to induce neuronal differentiation in these cell lines. Key signaling pathways (the ERK and Akt pathways) were also not affected by SNP treatment, and the phosphorylation of CREB transcription factor was only slightly stimulated. It is thus concluded from the results presented in this paper that NO is unable to activate signaling proteins acting downstream or independent of Ras that are required for neuronal differentiation. [ABSTRACT FROM AUTHOR]

Many thermal runaway incidents have been caused by organic peroxides due to the peroxy group, -O-O-, which is essentially unstable and active. Lauroyl peroxide (LPO) is also sensitive to thermal sources and is incompatible with many materials, such as acids, bases, metals, and ions. From the thermal decomposition reaction of various concentrations of nitric acid (HNO3) (from lower to higher concentrations) with LPO, experimental data were obtained as to its exothermic onset temperature (T0), heat of decomposition (ΔHd), isothermal time to maximum rate (TMRiso), and other safety parameters exclusively for loss prevention of runaway reactions and thermal explosions. As a novel finding, LPO mixed with HNO3 can produce the detonation product of 1-nitrododecane. We used differential scanning calorimetry (DSC), thermal activity monitor III (TAM III), and gas chromatography/mass spectrometer (GC/MS) analyses of the reactivity for LPO and itself mixed with HNO3 to corroborate the decomposition reactions and reaction mechanisms in these investigations. [ABSTRACT FROM AUTHOR]

Fluid and mud samples collected from Hsiaokunshui (HKS), Wushanting (WST), Yenshuikeng (YSK), Kunshuiping (KSP), Liyushan (LYS), and Sinyangnyuhu (SYNH) mud volcanoes of southwestern Taiwan were characterized for major ions, humic substances (HS) and trace elements concentrations. The relationship between the release of arsenic (As) and activities of sulfate-reducing bacteria has been assessed to understand relevant geochemical processes in the mud volcanoes. Arsenic (0.02–0.06 mg/L) and humic substances (4.13 × 10−4 to 1.64 × 10−3 mM) in the fluids of mud volcanoes showed a positive correlation (r = 0.99, p < 0.05) except in Liyushan mud volcano. Arsenic and iron in mud sediments formed two separate groups i) high As, but low Fe in HKS, WST, and SYNH; and ii) low As, but high Fe in the YSK, KSP, and LYS mud volcanoes. The EhS.H.E. values of the mud volcano liquids were characterized by mild to strongly reducing conditions. The HKS, SYNH, and WST mud volcanoes (near the Chishan Fault) belongs to strong reducing environment (−33 to −116 mV), whereas the LYS, YSK, and KSP mud volcanoes located near the coastal plain are under mild reducing environment (−11 to 172 mV). At low Eh values mud volcanoes, saturation index (SI) values of poorly crystalline phases such as amorphous ferric hydroxide indicate understaturation, whereas saturation is reached in relatively high EhS.H.E. values mud volcanoes. Arsenic contents in sediments are low, presumably due to its release to fluids (As/Fe ratio in YSK, KSP, and LYS sediment: 4.86 × 10−4−6.20 × 10−4). At low EhS.H.E. values (mild to strong reducing environment), arsenic may co-precipitate with sulfides as a consequence of sulfate reduction (As/Fe ratios in WST, HKS, and SYNH sediments: 0.42–0.69). [ABSTRACT FROM AUTHOR]

Hot springs are the important natural sources of geothermally heated groundwater from the Earth's crust. Kuan-Tzu-Ling (KTL), Chung-Lun (CL) and Bao-Lai (BL) are well-known hot springs in southern Taiwan. Fluid and mud (sediments) samples were collected from the eruption points of three hot springs for detailed biogeochemical characterization. The fluid sample displays relatively high concentrations of Na+ and Cl− compared with K+, Mg2+, Ca2+, NO2 −, and SO4 2−, suggesting a possible marine origin. The concentrations of Fe, Cr, Mn, Ni, V and Zn were significantly higher in the mud sediments compared with fluids, whereas high concentrations of As, Ba, Cu, Se, Sr and Rb were observed in the fluids. This suggests that electronegative elements were released during sediment-water interactions. High As concentration in the fluids was observed to be associated with low redox (Eh) conditions. The FTIR spectra of the humic acid fractions of the sediments showed the presence of possible functional groups of secondary amines, ureas, urethanesm (amide), and silicon. The sulfate-reducing deltaproteobacterium 99% similar to Desulfovibrio psychrotolerans (GU329907) were rich in the CL hot spring while mesophilic, proteolytic, thiosulfate- and sulfur-reducing bacterium that 99% similar to Clostridium sulfidigenes (GU329908) were rich in the BL hot spring. [ABSTRACT FROM AUTHOR]

Eleven novel 1,3-bis{(6-aryl-1,2,4-triazolo[3,4-b][1,3,4]thiadiazol-3-yl)-methoxy}benzenes have been synthesised in high yields by the condensation of 5,5'-[1,3-phenylene-bis(oxymethylene)]bis(4-amino-3-mercapto-1,2,4-triazole) with substituted benzoic acids in the presence of phosphorus oxychloride under microwave irradiation. Compared with the conventional heating method, this method is facile, rapid and efficient. The structures of all new compounds were characterised by 1H NMR, IR, MS and elemental analysis. [ABSTRACT FROM AUTHOR]

Understanding basic reproductive physiology is crucial for the management of both captive and free-ranging wolf. In the present study, we determined hormonal changes during pregnancy and the estrous cycle in captive female wolf by measuring fecal steroids collected during the breeding season with high performance liquid chromatography (HPLC). These biochemical analyses were validated using chemical devivatization and mass spectrometry, and interpreted along with the behavioral data. All four females undergoing estrus cycles were copulated with their partners and delivered pups successfully. We found that estradiol concentrations were significantly higher during the estrus cycle than other stages ( p<0.01) and progesterone was also significantly increased throughout the pregnancy ( p<0.01). These hormonal fluctuations demonstrated pregnancy-specific changes in the fecal progesterone and estradiol concentrations. Patterns of fecal estradiol and progesterone concentrations during estrous cycles were similar to those reported for other canids. [ABSTRACT FROM AUTHOR]

Lithium isotope geochemistry is increasingly being used to trace deep-earth processes, reflecting the observed large variation of Li isotope ratios in mantle-derived rocks, including peridotite xenoliths associated with ancient continents. We briefly review the Li isotopic compositions of major geochemical reservoirs, the assumed mechanisms of Li isotopic fractionation, and, in particular, the origins of isotopically light Li in mantle-derived rocks based on the latest developments in Li isotope geochemistry. Comparison of Li isotope data with existing Sr-Nd isotope ratios reflects the subduction-recycling of ancient oceanic crust and the reappearance of Li in volcanic rocks. This circulation may play an important role in generating the isotopically light-Li component in the mantle - perhaps the enriched mantle end member defined by the Sr-Nd isotopic compositions of oceanic basalts. [ABSTRACT FROM AUTHOR]

Abstract  An asperity-scale wear model was developed to predict feature-scale wear in chemical–mechanical polishing (CMP), and was compared to the measured evolution of a lithographically patterned feature during full-scale CMP tests. To conduct this study, a lithographic technique was used to pattern a set of raised square features into a Cu-coated silicon wafer. Two-dimensional contact profilometry was used to measure the topography of an isolated feature on each wafer both before polishing and at various intervals throughout the polishing process. In the wear modeling formulation, a pad deflection-based contact mechanics model was developed and combined with a particle-based wear model to predict the wear evolution of the sample during CMP. The predicted wear of the sample feature was found to agree well to experimental results. [ABSTRACT FROM AUTHOR]

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Plants use seasonal cues to initiate flowering at an appropriate time of year to ensure optimal reproductive success. The circadian clock integrates these daily and seasonal cues with internal cues to initiate flowering. The molecular pathways that control the sensitivity of flowering to photoperiods (daylengths) are well described in the model plant Arabidopsis. However, much less is known for crop species, such as legumes. Here, we performed a flowering time screen of a TILLING population of Medicago truncatula and found a line with late-flowering and altered light-sensing phenotypes. Using RNA sequencing, we identified a nonsense mutation in the Phytochromobilin synthase (MtPΦBS) gene, which encodes an enzyme that carries out the final step in the biosynthesis of the chromophore required for phytochrome (phy) activity. The analysis of the circadian clock in the MtpΦbs mutant revealed a shorter circadian period, which was shared with the MtphyA mutant. The MtpΦbs and MtphyA mutants showed downregulation of the FT floral regulators MtFTa1 and MtFTb1/b2 and a change in phase for morning and night core clock genes. Our findings show that phyA is necessary to synchronize the circadian clock and integration of light signalling to precisely control the timing of flowering. [ABSTRACT FROM AUTHOR]

Bioresorbable drug-eluting films can be used in many biomedical applications. Examples for such applications include biodegradable medical support devices which combine mechanical support with drug release and antibiotic-eluting film coatings for prevention of bacterial infections associated with orthopedic implants or during gingival healing. In the current study, bioresorbable drug-loaded polymer films are prepared by solution processing. Two film structures are studied: A polymer film with large drug crystals located on its surface (A-type) and a polymer film with small drug particles and crystals distributed within the bulk (B-type). The basic mode of drug dispersion/location in the film (A or B-type) is found to be determined mainly by the process of film formation and depends mainly on the solvent evaporation rate, whereas the drug's hydrophilicity has a minor effect on this structuring process. Most release profiles from A-type films exhibit a burst effect of ≈30% and a second release stage that occurs at an approximately constant rate and is determined mainly by the polymer weight loss rate. An extremely high burst release is exhibited only by a very hydrophilic drug. The matrix (monolithic) nature of the B-type film enables release profiles that are determined mainly by the host polymer's degradation profile, with a very low burst effect in most of the studied systems. In addition to the drug location/ dispersion in the film, the host polymer and drug type also strongly affect the drug's release profile from the film. It has been demonstrated that appropriate selection of the process parameters and film components (polymer and drug) can yield film structures with desirable drug release behaviors. This can lead to the engineering of new bioresorbable drug-eluting film-based implants for various applications. [ABSTRACT FROM AUTHOR]

Spherical gold nanoparticles (GNPs), whose unique properties regarding biomedical applications were broadly investigated, are an object of interest as nanocarriers in drug targeted delivery systems (DTDSs). The possibility of surface functionalization, especially in enabling longer half-life in the bloodstream and enhancing cellular uptake, provides an opportunity to overcome the limitations of popular anticancer drugs (such as cisplatin) that cause severe side effects due to their nonselective transportation. Herein, we present investigations of gold nanoparticle–cisplatin systems formation (regarding reaction kinetics and equilibrium) in which it was proved that the formation efficiency and stability strongly depend on the nanoparticle surface functionalization. In this study, the capillary electrophoresis hyphenated with inductively coupled plasma tandem mass spectrometry (CE-ICP-MS/MS) was used for the first time to monitor gold–drug nanoconjugates formation. The research included optimizing CE separation conditions and determining reaction kinetics using the CE-ICP-MS/MS developed method. To characterize nanocarriers and portray changes in their physicochemical properties induced by the surface's processes, additional hydrodynamic size and ζ-potential by dynamic light scattering (DLS) measurements were carried out. The examinations of three types of functionalized GNPs (GNP-PEG-COOH, GNP-PEG-OCH3, and GNP-PEG-biotin) distinguished the essential differences in drug binding efficiency and nanoconjugate stability. [ABSTRACT FROM AUTHOR]

X-linked dystonia–parkinsonism (XDP) is a severe neurodegenerative disorder that manifests as adult-onset dystonia combined with parkinsonism. A SINE-VNTR-Alu (SVA) retrotransposon inserted in an intron of the TAF1 gene reduces its expression and alters splicing in XDP patient-derived cells. As a consequence, increased levels of the TAF1 intron retention transcript TAF1-32i can be found in XDP cells as compared to healthy controls. Here, we investigate the sequence of the deep intronic region included in this transcript and show that it is also present in cells from healthy individuals, albeit in lower amounts than in XDP cells, and that it undergoes degradation by nonsense-mediated mRNA decay. Furthermore, we investigate epigenetic marks (e.g., DNA methylation and histone modifications) present in this intronic region and the spanning sequence. Finally, we show that the SVA evinces regulatory potential, as demonstrated by its ability to repress the TAF1 promoter in vitro. Our results enable a better understanding of the disease mechanisms underlying XDP and transcriptional alterations caused by SVA retrotransposons. [ABSTRACT FROM AUTHOR]

The serotonergic system is important in Parkinson's disease (PD) pathogenesis as it can take over dopamine production after a large portion of dopaminergic neurons is lost through neurodegeneration. The aim of this study was to evaluate the effect of genetic variability of serotonergic genes on the occurrence of motor complications and psychiatric adverse events (AE) due to dopaminergic treatment. We enrolled 231 patients and their clinical data were collected. Genotyping was performed for eight genetic variants. Logistic regression was used for analysis. Carriers of the HTR1A rs6295 GC genotype (OR = 2.58; 95% CI = 1.15–5.78; p = 0.021), TPH2 rs4290270 AA genotype (OR = 2.78; 95% CI = 1.08–7.03; p = 0.034), and at least one TPH2 rs4570625 T allele (OR = 1.86; 95% CI = 1.00–3.44; p = 0.047) had increased risk for visual hallucinations (VH). Additionally, carriers of at least one SLC6A4 5-HTTPLR rs25531 S (OR = 0.52; 95% CI = 0.28–0.96; p = 0.037) or at least one LG allele (OR = 0.37; 95% CI = 0.14–0.97; p = 0.044) had a decreased chance for VH. Constructed haplotypes of the TPH2 showed increased risk for VH (OR = 1.94; 95% CI = 1.06–3.55; p = 0.032) and impulse control disorders (OR = 5.20; 95% CI = 1.86–14.50; p = 0.002). Finally, individual gene–gene interactions showed decreased odds for the development of motor AE. Our findings suggest that the serotonergic pathway may play an important role in the development of AE resulting from dopaminergic treatment. [ABSTRACT FROM AUTHOR]

Arrhythmogenic cardiomyopathy is a heritable heart disease associated with desmosomal mutations, especially premature termination codon (PTC) variants. It is known that PTC triggers the nonsense-mediated decay (NMD) mechanism. It is also accepted that PTC in the last exon escapes NMD; however, the mechanisms involving NMD escaping in 5′-PTC, such as reinitiation of translation, are less known. The main objective of the present study is to evaluate the likelihood that desmosomal genes carrying 5′-PTC will trigger reinitiation. HL1 cell lines were edited by CRISPR/Cas9 to generate isogenic clones carrying 5′-PTC for each of the five desmosomal genes. The genomic context of the ATG in-frame in the 5′ region of desmosomal genes was evaluated by in silico predictions. The expression levels of the edited genes were assessed by Western blot and real-time PCR. Our results indicate that the 5′-PTC in PKP2, DSG2 and DSC2 acts as a null allele with no expression, whereas in the DSP and JUP gene, N-truncated protein is expressed. In concordance with this, the genomic context of the 5′-region of DSP and JUP presents an ATG in-frame with an optimal context for the reinitiation of translation. Thus, 5′-PTC triggers NMD in the PKP2, DSG2* and DSC2 genes, whereas it may escape NMD through the reinitiation of the translation in DSP and JUP genes, with no major effects on ACM-related gene expression. [ABSTRACT FROM AUTHOR]

Nanostructured noble metal-semiconductor materials have been attracting increasing attention because of their broad application in the field of environmental remediation, sensing and photocatalysis. In this study, a facile approach for fabricating silver@mesoporousanataseTiO2 (Ag@mTiO2) core-shell nanoparticles employing sol-gel and hydrothermal reaction is demonstrated. The Ag@mTiO2nanoparticles display excellent surface-enhanced Raman scattering (SERS) sensitivity and they can detect the methylene blue (MB) molecules with the concentration of as low as 10−8 M. They also exhibit outstanding photocatalytic activity compared with mTiO2, due to the efficient separation and recombination restrain of electron–hole pairs under ultraviolet light. The Ag@mTiO2nanoparticles also present good stability and they can achieve recyclable photocatalytic degradation experiments for five times without loss of activity. Subsequently, the nanoparticles with dual functions were successfully used to in situ monitor the photodegradation process of MB aqueous solution. These results, demonstrating the multifunctional Ag@mTiO2 nanoparticles, hold promising applications for simultaneous SERS analysis and the removal of dye pollutants in environmental field. [ABSTRACT FROM AUTHOR]

The application of coherent detection to indoor optical free-space communications is considered here. Analytical expressions are derived for a wide line-of-sight (W-LOS) optical link which determine the coverage area and the required photo-detection area given different binary digital transmission schemes and a given bit rate. The coverage area is maximised for systems using both metal–semiconductor–metal (MSM) and PIN photo-detectors. Results show that MSM photo-detectors, due to their inherently lower capacitance per unit photo-detection area, result in a greater coverage area than their PIN counterparts. To demonstrate the viability of implementing coherent detection indoors, a 200 Mb/s LOS optical link which uses coherent detection is also reported. [ABSTRACT FROM AUTHOR]

An overview of the developments in optical wireless systems viewed from the traditional communications viewpoint of transmitter, channel and receiver is presented. The trends in modulation formats that match information to the optical wireless channel are considered. This is followed by the discussion of recent transmitter and receiver innovations, particularly the utilisation of diversity transceivers. As a preliminary to the following treatment, the nature and modelling of the optical wireless channel are introduced, with particular emphasis on its unique features in terms of transmitted power constraints and non-negativity. From the examination of modulation formats, on-off-keying remains the format of choice for basic binary transmission, whereas pulse-position modulation and its derivatives are preferred for more sophisticated requirements. The recent introduction of techniques from radio systems employing subcarriers is seen to be the most promising development in modulation techniques at present. In receiver technology, quasi-diffuse systems employing multispot diffusion and angular diversity are significant developments. They offer lower path loss and less multipath dispersion, at a lower transmission power compared to ‘conventional’ wide-angle diffuse systems, while providing a high level of user mobility compared to line-of-sight transmission. These developments are helping optical wireless systems to fulfil their promise by adopting a philosophy inspired by the radio domain to accommodate operation within a hostile channel. [ABSTRACT FROM AUTHOR]

1. A broiler experiment was conducted to assess the effectiveness of L-lysine·H2SO4 relative to L-lysine·HCl. Four concentrations of L-lysine·H2SO4 and L-lysine·HCl (0·9, 1·8, 2·7 and 3·6 g/kg diet) were each added to a basal diet that met the nutrient requirements of broilers except for lysine. 2. Birds responded significantly to the supplements in daily gain, feed intake, feed conversion efficiency, nitrogen retention and plasma urea nitrogen during each period (d 4 to 21, d 22 to 42 and d 4 to 42). 3. Regression analysis showed that the bioefficacy of L-lysine·H2SO4 relative to L-lysine·HCl was 0·93, 0·86 and 0·95 for daily gain, feed conversion efficiency and nitrogen retention, respectively, during the starter period (d 4 to 21), and was 1·01, 1·36 and 1·06, respectively, during the grower period (d 22 to 42). It was 0·99, 1·07 and 1·03, respectively, for the overall period (d 4 to 42), when the bioefficacy of L-lysine·HCl was set at 1·0. 4. The bioefficacy of L-lysine·H2SO4 differed with different response criteria. The average bioavailability of L-lysine·H2SO4 relative to L-lysine·HCl was 1·03 on an equimolar basis in the present study. In conclusion, L-lysine·H2SO4 and L-lysine·HCl are equally efficacious to broiler chickens. [ABSTRACT FROM AUTHOR]

The aim of this study was to identify the clinical factors associated with the need for peri-operative blood transfusion in non-anaemic patients undergoing hip or knee arthroplasty. We prospectively evaluated 162 consecutive patients who underwent total hip or knee arthroplasty. Analysis was performed to establish the relationship between all independent variables and the need for postoperative transfusion. Univariate analysis revealed a significant relationship between the need for postoperative blood transfusion and the pre-operative haemoglobin levels ( P= 0·001), weight ( P= 0·019) and age ( P= 0·018). Multivariate analysis identified a significant relationship only between the need for transfusion and the pre-operative haemoglobin level ( P= 0·0001). The pre-operative haemoglobin level of the patient was the only variable to independently predict the need for blood transfusion after primary hip or knee arthroplasty. [ABSTRACT FROM AUTHOR]

Diffuse Indoor Optical wireless systems (DIOWS) have potential applications in indoor WLAN. The major problems faced by these systems are their reduced bandwidth and restricted mobility caused by multi-path reflections from the indoor surfaces. These systems also suffer from non-uniform power distribution. Over the last decade several techniques have been suggested to circumvent these problems, most of them requiring complex trans-receiver design. One simple technique that can solve the non-uniformity problem is the use of multiple sources in place of a single source. In this paper we compare the received power levels on the floor computed using the extended ceiling bounce and the modified recursive models. The effect of multiple sources and their positions on the channel bandwidth is also analyzed. We show that the channel bandwidth for a given trans-receiver configuration depends on both the horizontal separation (between the transmitter and the receiver) and their actual positions. [ABSTRACT FROM AUTHOR]

In this study we report an atomic force microscopy (AFM) investigation of the actin cortical cytoskeleton of Xenopus laevis oocytes. Samples consisted of inside-out orientated plasma membrane patches of X. laevis oocytes with overhanging cytoplasmic material. They were spread on a freshly cleaved mica surface, subsequently treated with Triton X-100 detergent and chemically fixed. The presence of actin fibres in oocyte patches was proved by fluorescence microscopy imaging. Contact mode AFM imaging was performed in air in constant force conditions. Reproducible high-resolution AFM images of a filamentous structure were obtained. The filamentous structure was identified as an actin cortical cytoskeleton, investigating its disaggregation induced by cytochalasin D treatment. The thinnest fibres showed a height of 7 nm in accordance with the diameter of a single actin microfilament. The results suggest that AFM imaging can be used for the high-resolution study of the actin cortical cytoskeleton of the X. laevis oocyte and its modifications mediated by the action of drugs and toxins. [ABSTRACT FROM AUTHOR]

A new approach for solving permutation scheduling problems with ant colony optimization (ACO) is proposed in this paper. The approach assumes that no precedence constraints between the jobs have to be fulfilled. It is tested with an ACO algorithm for the single-machine total weighted deviation problem. In the new approach the ants allocate the places in the schedule not sequentially, as in the standard approach, but in random order. This leads to a better utilization of the pheromone information. It is shown by experiments that adequate combinations between the standard approach which can profit from list scheduling heuristics and the new approach perform particularly well. [ABSTRACT FROM AUTHOR]

SMG6 is an endonuclease, which cleaves mRNAs during nonsense-mediated mRNA decay (NMD), thereby regulating gene expression and controling mRNA quality. SMG6 has been shown as a differentiation license factor of totipotent embryonic stem cells. To investigate whether it controls the differentiation of lineage-specific pluripotent progenitor cells, we inactivated Smg6 in murine embryonic neural stem cells. Nestin-Cre-mediated deletion of Smg6 in mouse neuroprogenitor cells (NPCs) caused perinatal lethality. Mutant mice brains showed normal structure at E14.5 but great reduction of the cortical NPCs and late-born cortical neurons during later stages of neurogenesis (i.e., E18.5). Smg6 inactivation led to dramatic cell death in ganglionic eminence (GE) and a reduction of interneurons at E14.5. Interestingly, neurosphere assays showed self-renewal defects specifically in interneuron progenitors but not in cortical NPCs. RT-qPCR analysis revealed that the interneuron differentiation regulators Dlx1 and Dlx2 were reduced after Smg6 deletion. Intriguingly, when Smg6 was deleted specifically in cortical and hippocampal progenitors, the mutant mice were viable and showed normal size and architecture of the cortex at E18.5. Thus, SMG6 regulates cell fate in a cell type-specific manner and is more important for neuroprogenitors originating from the GE than for progenitors from the cortex. [ABSTRACT FROM AUTHOR]

Racial, ethnic, and socioeconomic disparities in childhood obesity in the United States (U.S.) originate in early life. Maternal sugar-sweetened beverage (SSB) consumption is an early life risk factor for later offspring obesity. The goal of this study was to test the effects of policy-relevant messages delivered by text messages mobile devices (mHealth) on maternal SSB consumption. In this three-arm 1-month randomized controlled trial (RCT), pregnant women or mothers of infants in predominantly Hispanic/Latino New York City neighborhoods were randomized to receive one of three text message sets: graphic beverage health warning labels, beverage sugar content information, or attention control. The main outcome was change in maternal self-reporting of average daily SSB consumption from baseline to one month. Among 262 participants, maternal SSB consumption declined over the 1-month period in all three arms. No intervention effect was detected in primary analyses. In sensitivity analyses accounting for outliers, graphic health warning labels reduced maternal SSB consumption by 28 kcal daily (95% CI: −56, −1). In this mHealth RCT among pregnant women and mothers of infants, graphic health warning labels and beverage sugar content information did not reduce maternal SSB consumption. [ABSTRACT FROM AUTHOR]

Phospholipase A2 (PLA2) enzymes were first recognized as an enzyme activity class in 1961. The secreted (sPLA2) enzymes were the first of the five major classes of human PLA2s to be identified and now number nine catalytically-active structurally homologous proteins. The best-studied of these, group IIA sPLA2, has a clear role in the physiological response to infection and minor injury and acts as an amplifier of pathological inflammation. The enzyme has been a target for anti-inflammatory drug development in multiple disorders where chronic inflammation is a driver of pathology since its cloning in 1989. Despite intensive effort, no clinically approved medicines targeting the enzyme activity have yet been developed. This review catalogues the major discoveries in the human group IIA sPLA2 field, focusing on features of enzyme function that may explain this lack of success and discusses future research that may assist in realizing the potential benefit of targeting this enzyme. Functionally-selective inhibitors together with isoform-selective inhibitors are necessary to limit the apparent toxicity of previous drugs. There is also a need to define the relevance of the catalytic function of hGIIA to human inflammatory pathology relative to its recently-discovered catalysis-independent function. [ABSTRACT FROM AUTHOR]

In this work, we report a complete analysis by theoretical and spectroscopic methods of the short-time behaviour of 4-(dimethylamino)benzonitrile (DMABN) in the gas phase as well as in cyclohexane, tetrahydrofuran, acetonitrile, and water solution, after excitation to the L a state. The spectroscopic properties of DMABN were investigated experimentally using UV absorption and fluorescence emission spectroscopy. The computational study was developed at different electronic structure levels and using the Polarisable Continuum Model (PCM) and explicit solvent molecules to reproduce the solvent environment. Additionally, excited state quantum dynamics simulations in the diabatic picture using the direct dynamics variational multiconfigurational Gaussian (DD-vMCG) method were performed, the largest quantum dynamics "on-the-fly" simulations performed with this method until now. The comparison with fully converged multilayer multiconfigurational time-dependent Hartree (ML-MCTDH) dynamics on parametrised linear vibronic coupling (LVC) potentials show very similar population decays and evolution of the nuclear wavepacket. The ring C=C stretching and three methyl tilting modes are identified as the responsible motions for the internal conversion from the L a to the L b states. No major differences are observed in the ultrafast initial decay in different solvents, but we show that this effect depends strongly on the level of electronic structure used. [ABSTRACT FROM AUTHOR]