1,379 research outputs found

    Scaling behavior in steady-state contractile actomyosin network flow

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    Contractile actomyosin network flows are crucial for many cellular processes including cell division and motility, morphogenesis and transport. How local remodeling of actin architecture tunes stress production and dissipation and regulates large-scale network flow remains poorly understood. Here, we generate contractile actomyosin networks with rapid turnover in vitro, by encapsulating cytoplasmic Xenopus egg extracts into cell-sized 'water-in-oil' droplets. Within minutes, the networks reach a dynamic steady-state with continuous inward flow. The networks exhibit homogenous, density-independent contraction for a wide range of physiological conditions, indicating that the myosin-generated stress driving contraction is proportional to the effective network viscosity. We further find that the contraction rate approximately scales with the network turnover rate, but this relation breaks down in the presence of excessive crosslinking or branching. Our findings suggest that cells use diverse biochemical mechanisms to generate robust, yet tunable, actin flows by regulating two parameters: turnover rate and network geometry

    Education and training is a key success factor of knowledge management implementation: A case study

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    The transition from the industrial age to knowledge economy age has driven many organizations to recognize the importance of knowledge management (KM). In view of that many organizations attempt to adopt and implement KM to build up their competitive advantage. However, many empirical studies found that not all of the KM initiatives are successful implemented.The main reason is due to the lacking of education and training to the employees in an organization.The main purpose of this study is to examine the relationship between the one of the key success factors of KM implementation, namely education and training with the benefit of KM. The case study was carried out in Spice I-Gate, a Malaysian Retail Chain where the education and training (key success factor) of KM was implemented. Structured interview was conducted in order to examine the education and training (key success factor)after the KM implementation.Finding has testified that education and training is a key success factor of KM that brings the benefits to the organization

    Solubility-pH profile of desipramine hydrochloride in saline phosphate buffer: Enhanced solubility due to drug-buffer aggregates

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    Although solubility-pH data for desipramine hydrochloride (DsHCl) have been reported previously, the aim of the present study was to critically examine the aqueous solubility-pH behavior of DsHCl in buffer-free and buffered solutions, in the presence of physiologically-relevant chloride concentration, using experimental practices recommended in the recently-published “white paper” (Avdeef et al., 2016). The computer program pDISOL-X was used to design the structured experiments (pH-RSF method), to process the data, and to refine the equilibrium constants. Low-to-high and high-to-low pH assays (using HCl, H 3 PO 4 , or NaOH to adjust pH) were performed on phosphate-buffered (0.12‑0.15 M) saturated solutions of DsHCl in the pH 1.3–11.6 range. After equilibration (stirring 6 h, followed by 18 h stir-free sedimentation), filtration or centrifugation was used for phase separation. Concentration was measured using HPLC with UV/VIS detection. The 2:1 drug-phosphate solubility product (K sp 2:1 = [DsH + ] 2 [HPO 4 2− ]) was determined from data in the pH 4–9 region. The free base of desipramine was prepared and used to determine the K sp 1:1 ([DsH + ][H 2 PO 4 − ]) in chloride-free acidified suspension. In addition, phosphate-free titrations were conducted to determine the intrinsic solubility, S 0 , and the 1:1 drug-chloride solubility product, K sp DsH [rad] Cl = [DsH + ][Cl − ]. Under the assay conditions, only the phosphate-free solutions showed some supersaturation near pH max 8.0. In phosphate-containing solutions, pH max was indicated at higher pH (8.8–9.6). Oils mixed with solids were observed to form in alkaline solutions (pH > 11). Notably, soluble drug-phosphate complexes appeared to form below pH 3.9 and above pH max in saturated phosphate‑containing saline solutions. This was indicated by the systematic pH shift to higher values in the log S-pH curve in alkaline solution than expected from the Henderson-Hasselbalch equation. For pH < 3.9, saturated phosphate-containing saline solutions exhibited elevated solubility, with drug-hydrochloride as the sole precipitate. Salt solubility products, intrinsic solubility, and complexation constants, which rationalized the data, were determined. Elemental, thermogravimetric (TGA), differential scanning calorimetric (DSC), and powder X-ray diffraction (PXRD) analyses were used to characterize the precipitates isolated from suspensions at different pH.This is the peer-reviewed version of the following article: Marković, O. S.; Pešić, M. P.; Shah, A. V.; Serajuddin, A. T. M.; Verbić, T. Ž.; Avdeef, A. Solubility-PH Profile of Desipramine Hydrochloride in Saline Phosphate Buffer: Enhanced Solubility Due to Drug-Buffer Aggregates. European Journal of Pharmaceutical Sciences 2019, 133, 264–274. [https://doi.org/10.1016/j.ejps.2019.03.014]Supplementary material: [http://cherry.chem.bg.ac.rs/handle/123456789/2926

    Centering and symmetry breaking in confined contracting actomyosin networks

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    Centering and decentering of cellular components is essential for internal organization of cells and their ability to perform basic cellular functions such as division and motility. How cells achieve proper localization of their components is still not well-understood, especially in large cells such as oocytes. Here, we study actin-based positioning mechanisms in artificial cells with persistently contracting actomyosin networks, generated by encapsulating cytoplasmic Xenopus egg extracts into cell-sized water-in-oil droplets. We observe size-dependent localization of the contraction center, with a symmetric configuration in larger cells and a polar one in smaller cells. In the symmetric state, the contraction center is actively centered, via a hydrodynamic mechanism based on Darcy friction between the contracting network and the surrounding cytoplasm. During symmetry breaking, transient attachments to the cell boundary drive the contraction center to a polar location near the droplet boundary. Our findings demonstrate a robust, yet tunable, mechanism for subcellular localization

    The role of siderite on abiotic nitrite reduction by dissolved Fe(II)

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    Iron redox reactions affect the fate and transformation of groundwater NO3-. Fe(II) present in groundwater as dissolved Fe(II) or Fe(II) sorbed onto mineral surfaces is oxidised into Fe(III) (oxyhydr)oxides using NO3- as an electron acceptor in anoxic conditions by biotic or abiotic means (Bryce et al., 2018). N2O is produced as an end product during abiotic nitrate-reducing Fe(II) oxidation (NRFO) (Wang et al., 2019). NO2-, an intermediate product during NO3- reduction by biotic or abiotic means, is chemically very reactive and readily reduced to N2O by abiotic means (Wankel et al., 2017). Studies have shown that Fe(II) minerals such as iron-rich smectites, green rust and siderite are reactive and can enhance abiotic NO2- reduction (Grabb et al., 2017). The occurrence of abiotic NO2- reduction leads to the relative segregation of the lighter and heavy isotopes of N and O (kinetic isotope fractionation, ε) (Chen & MacQuarrie, 2005) providing an effective tool to quantify abiotic NO2- reduction processes. In the light of this, batch experiments were performed to assess the potential of micro-sized siderite to enhance abiotic NO2- reduction in laboratory batch experiments

    Trends and Predictors of Syphilis Prevalence in the General Population: Global Pooled Analyses of 1103 Prevalence Measures Including 136 Million Syphilis Tests.

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    Background: This study assessed levels, trends, and associations of observed syphilis prevalence in the general adult population using global pooled analyses. Methods: A standardized database of syphilis prevalence was compiled by pooling systematically gathered data. Random-effects meta-analyses and meta-regressions were conducted using data from the period 1990-2016 to estimate pooled measures and assess predictors and trends. Countries were classified by World Health Organization region. Sensitivity analyses were conducted. Results: The database included 1103 prevalence measures from 136 million syphilis tests across 154 countries (85% from women in antenatal care). Global pooled mean prevalence (weighted by region population size) was 1.11% (95% confidence interval [CI], .99-1.22). Prevalence predictors were region, diagnostic assay, sample size, and calendar year interacting with region. Compared to the African Region, the adjusted odds ratio (AOR) was 0.42 (95% CI, .33-.54) for the Region of the Americas, 0.13 (95% CI, .09-.19) for the Eastern Mediterranean Region, 0.05 (95% CI, .03-.07) for the European Region, 0.21 (95% CI, .16-.28) for the South-East Asia Region, and 0.41 (95% CI, .32-.53) for the Western Pacific Region. Treponema pallidum hemagglutination assay (TPHA) only or rapid plasma reagin (RPR) only, compared with dual RPR/TPHA diagnosis, produced higher prevalence (AOR >1.26), as did smaller sample-size studies (2.16). Prevalence declined in all regions; the annual AORs ranged from 0.84 (95% CI, .79-.90) in the Eastern Mediterranean to 0.97 (95% CI, .97-1.01) in the Western Pacific. The pooled mean male-to-female prevalence ratio was 1.00 (95% CI, .89-1.13). Sensitivity analyses confirmed robustness of results. Conclusions: Syphilis prevalence has declined globally over the past 3 decades. Large differences in prevalence persist among regions, with the African Region consistently the most affected

    Diagnostic challenges in critical care management of fluid and electrolyte disturbances in a poor-resource setting: a survey of critical care doctors

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    Background: To determine the challenges in diagnostic support for adequate fluid and electrolyte (F/E) management in a poor-resource critical care setting.Methods: This cross-sectional survey was conducted between March and May 2017 in one hundred and four (104) doctors practicing in four tertiary hospitals in North-central Nigeria. These doctors were currently working in Accidents and Emergency Units (A/E), Intensive care Units (ICU) and Children Emergency Units and have worked for at least two months prior to the study. They were given a structured questionnaire to fill and return. The questionnaire among other things, addressed laboratory-related factors that affect management of F/E disturbances.Results: Unavailability of some laboratory tests, inaccuracy of laboratory results, incomplete test results and delay in obtaining results, hampered F/E management in critical care according to more than 75% of the surveyed doctors. About sixty percent of the doctors reported a turnaround time (TAT) of ≥3 hours for electrolytes and most emergency biochemical tests (except urine dipstick and Blood gases). Also ≤25% of doctors responded that electrolytes and most emergency biochemical tests (except urine dipstick and Blood gases) were offered in the ICU/Emergency unit laboratories. Ten percent or less of doctors reported that electrolytes and the emergency biochemical test were available by Point of care testing (POCT).Conclusions: There is an urgent need for the managers of healthcare in LMICs to establish functional laboratories in ICUs, explore the use of POCT and build capacity for diagnostic critical care

    Interrogating the Venom of the Viperid Snake Sistrurus catenatus edwardsii by a Combined Approach of Electrospray and MALDI Mass Spectrometry

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    The complete sequence characterization of snake venom proteins by mass spectrometry is rather challenging due to the presence of multiple isoforms from different protein families. In the present study, we investigated the tryptic digest of the venom of the viperid snake Sistrurus catenatus edwardsii by a combined approach of liquid chromatography coupled to either electrospray (online) or MALDI (offline) mass spectrometry. These different ionization techniques proved to be complementary allowing the identification a great variety of isoforms of diverse snake venom protein families, as evidenced by the detection of the corresponding unique peptides. For example, ten out of eleven predicted isoforms of serine proteinases of the venom of S. c. edwardsii were distinguished using this approach. Moreover, snake venom protein families not encountered in a previous transcriptome study of the venom gland of this snake were identified. In essence, our results support the notion that complementary ionization techniques of mass spectrometry allow for the detection of even subtle sequence differences of snake venom proteins, which is fundamental for future structure-function relationship and possible drug design studies

    Pathways and efficiency of nitrogen attenuation in wastewater effluent through soil aquifer treatment

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    Soil Aquifer Treatment (SAT) is used to increase groundwater resources and enhance the water quality of wastewater treatment plant (WWTP) effluents. The resulting water quality needs to be assessed. In this study, we investigate attenuation pathways of nitrogen (N) compounds (predominantly NH4+) from a secondary treatment effluent in pilot SAT systems: both a conventional one (SAT-Control system) and one operating with a permeable reactive barrier (PRB) to provide extra dissolved organic carbon to the recharged water. The goal is to evaluate the effectiveness of the two systems regarding N compounds by means of chemical and isotopic tools. Water chemistry (NO3-, NH4+, Non-Purgeable Dissolved Organic Carbon (NPDOC), and O2) and isotopic composition of NO3- (ẟ15N-NO3- and ẟ18O-NO3-) and NH4+ (ẟ15N-NH4+) were monitored in the inflow and at three different sections and depths along the aquifer flow path. Chemical and isotopic results suggest that coupled nitrification-denitrification were the principal mechanisms responsible for the migration and distribution of inorganic N in the systems and that nitrification rate decreased with depth. At the end of the study period, 66% of the total N in the solution was removed in the SAT-PRB system and 69% in the SAT-Control system, measured at the outlet of the systems. The residual N in solution in the SAT-PRB system had an approximately equal proportion of N-NH4+ and N-NO3- while in the SAT-Control system, the residual N in solution was primarily N-NO3-. Isotopic data also confirmed complete NO3- degradation in the systems from July to September with the possibility of mixing newly generated NO3- with the residual NO3- in the substrate pool
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