197 research outputs found

    Nonlinear diffusion in two-dimensional ordered porous media based on a free volume theory.

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    A continuum nonlinear diffusion model is developed to describe molecular transport in ordered porous media. An existing generic van der Waals equation of state based free volume theory of binary diffusion coefficients is modified and introduced into the two-dimensional diffusion equation. The resulting diffusion equation is solved numerically with the alternating-direction fully implicit method under Neumann boundary conditions. Two types of pore structure symmetries are considered, hexagonal and cubic. The former is modeled as parallel channels while in case of the latter equal-sized channels are placed perpendicularly thus creating an interconnected network. First, general features of transport in both systems are explored, followed by the analysis of the impact of molecular properties on diffusion inside and out of the porous matrix. The influence of pore size on the diffusion-controlled release kinetics is assessed and the findings used to comment recent experimental studies of drug release profiles from ordered mesoporous silicates

    Hydration dynamics at fluorinated protein surfaces

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    Water-protein interactions dictate many processes crucial to protein function including folding, dynamics, interactions with other biomolecules, and enzymatic catalysis. Here we examine the effect of surface fluorination on water-protein interactions. Modification of designed coiled-coil proteins by incorporation of 5,5,5-trifluoroleucine or (4S)-2-amino-4-methylhexanoic acid enables systematic examination of the effects of side-chain volume and fluorination on solvation dynamics. Using ultrafast fluorescence spectroscopy, we find that fluorinated side chains exert electrostatic drag on neighboring water molecules, slowing water motion at the protein surface

    Activation of the p53 Transcriptional Program Sensitizes Cancer Cells to Cdk7 Inhibitors

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    Cdk7, the CDK-activating kinase and transcription factor IIH component, is a target of inhibitors that kill cancer cells by exploiting tumor-specific transcriptional dependencies. However, whereas selective inhibition of analog-sensitive (AS) Cdk7 in colon cancer-derived cells arrests division and disrupts transcription, it does not by itself trigger apoptosis efficiently. Here, we show that p53 activation by 5-fluorouracil or nutlin-3 synergizes with a reversible Cdk7asinhibitor to induce cell death. Synthetic lethality was recapitulated with covalent inhibitors of wild-type Cdk7, THZ1, or the more selective YKL-1-116. The effects were allele specific; a CDK7asmutation conferred both sensitivity to bulky adenine analogs and resistance to covalent inhibitors. Non-transformed colon epithelial cells were resistant to these combinations, as were cancer-derived cells with p53-inactivating mutations. Apoptosis was dependent on death receptor DR5, a p53 transcriptional target whose expression was refractory to Cdk7 inhibition. Therefore, p53 activation induces transcriptional dependency to sensitize cancer cells to Cdk7 inhibition. Kalan et al. find that activation of the p53 tumor suppressor protein in human colon cancer-derived cells can induce transcriptional dependency on Cdk7, analogous to constitutive dependencies described in other tumors driven by oncogenic transcription factors. This work provides a proof of concept for combining p53-activating agents with Cdk7 inhibitors to elicit synthetic lethality. Keywords: Cdk7; p53; colon cancer; synthetic lethality; transcription; 5-fluorouracil; nutlin-3; apoptosis; chemical genetics; CDK inhibitorNational Institutes of Health (U.S.) (Grant HG002668

    The relation of steady evaporating drops fed by an influx and freely evaporating drops

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    We discuss a thin film evolution equation for a wetting evaporating liquid on a smooth solid substrate. The model is valid for slowly evaporating small sessile droplets when thermal effects are insignificant, while wettability and capillarity play a major role. The model is first employed to study steady evaporating drops that are fed locally through the substrate. An asymptotic analysis focuses on the precursor film and the transition region towards the bulk drop and a numerical continuation of steady drops determines their fully non-linear profiles. Following this, we study the time evolution of freely evaporating drops without influx for several initial drop shapes. As a result we find that drops initially spread if their initial contact angle is larger than the apparent contact angle of large steady evaporating drops with influx. Otherwise they recede right from the beginning

    Lubricating Bacteria Model for Branching growth of Bacterial Colonies

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    Various bacterial strains (e.g. strains belonging to the genera Bacillus, Paenibacillus, Serratia and Salmonella) exhibit colonial branching patterns during growth on poor semi-solid substrates. These patterns reflect the bacterial cooperative self-organization. Central part of the cooperation is the collective formation of lubricant on top of the agar which enables the bacteria to swim. Hence it provides the colony means to advance towards the food. One method of modeling the colonial development is via coupled reaction-diffusion equations which describe the time evolution of the bacterial density and the concentrations of the relevant chemical fields. This idea has been pursued by a number of groups. Here we present an additional model which specifically includes an evolution equation for the lubricant excreted by the bacteria. We show that when the diffusion of the fluid is governed by nonlinear diffusion coefficient branching patterns evolves. We study the effect of the rates of emission and decomposition of the lubricant fluid on the observed patterns. The results are compared with experimental observations. We also include fields of chemotactic agents and food chemotaxis and conclude that these features are needed in order to explain the observations.Comment: 1 latex file, 16 jpeg files, submitted to Phys. Rev.

    The core of secondary level quantum education: a multi-stakeholder perspective

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    Quantum physics (QP) education at the secondary school level is still in its infancy. Not only is there ongoing discussion about how to teach this subject, but there is also a lack of coherence in the selection of concepts to be taught, both across countries and over time. To contribute to this discussion, we investigated the perspectives of high school teachers, university-level physics educators, and physics education researchers regarding the essential concepts in QP and the corresponding illustrations that should be introduced at the secondary school level. We examined the prominence of different key concepts and illustrations, as well as the level of consensus among the various professional groups. Our analysis revealed that certain key concepts are universally valued across all professional groups, while others are specific to particular groups. Additionally, we explored the relationships between these key concepts and their corresponding illustrations. Overall, our study offers valuable insights into the perspectives of different stakeholders, emphasizing the essential concepts and visualizations that should be considered when designing and implementing the teaching of QP at the secondary school level

    Nutritional status of children living within institution-based care: a retrospective analysis with funnel plots and control charts for programme monitoring

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    ObjectivesThe aim of this study is to fill a key information gap on the nutrition-related epidemiology of orphaned and vulnerable children living within institution-based care (IBC) across six countries.DesignA retrospective analysis with Shewhart control charts and funnel plots to explore intersite and over time variations in nutritional status.SettingWe conducted a retrospective analysis of records from Holt International’s Child Nutrition Programme from 35 sites in six countries; Mongolia, India, Ethiopia, Vietnam, China and the Philippines.ParticipantsDeidentified health records from Holt International’s online nutrition screening database included records from 2926 children, 0–18 years old. Data were collected from 2013 to 2020 and included demographic and health information.ResultsAt initial screening, 717 (28.7%) children were anaemic, 788 (34.1%) underweight, 1048 (37.3%) stunted, 212 (12.6%) wasted, 135 (12%) overweight or obese and 339 (31%) had small head circumference. Many had underlying conditions: low birth weight, 514 (57.5%); prematurity, 294 (42.2%) and disabilities, 739 (25.3%). Children with disabilities had higher prevalence of malnutrition compared with counterparts without disabilities at baseline and 1-year screenings. There was marked intersite variation. Funnel plots highlight sites with malnutrition prevalence outside expected limits for this specific population taking into consideration natural variation at baseline and at 1 year. Control charts show changes in site mean z-scores over time in relation to site control limits.ConclusionsMalnutrition is prevalent among children living within IBC, notably different forms of undernutrition (stunting, underweight, wasting). Underlying risk factors are also common: prematurity, low birth weight and disability. Nutrition interventions should take into account the needs of this vulnerable population, especially for infants and those with disabilities. Using control charts to present data could be especially useful to programme managers as sites outside control limits could represent: problems to be investigated; good practices to be shared.</jats:sec

    Nutritional status of children living within institution-based care: a retrospective analysis with funnel plots and control charts for programme monitoring

    Get PDF
    Objectives The aim of this study is to fill a key information gap on the nutrition-related epidemiology of orphaned and vulnerable children living within institution-based care (IBC) across six countries. Design A retrospective analysis with Shewhart control charts and funnel plots to explore intersite and over time variations in nutritional status. Setting We conducted a retrospective analysis of records from Holt International’s Child Nutrition Programme from 35 sites in six countries; Mongolia, India, Ethiopia, Vietnam, China and the Philippines. Participants Deidentified health records from Holt International’s online nutrition screening database included records from 2926 children, 0–18 years old. Data were collected from 2013 to 2020 and included demographic and health information. Results At initial screening, 717 (28.7%) children were anaemic, 788 (34.1%) underweight, 1048 (37.3%) stunted, 212 (12.6%) wasted, 135 (12%) overweight or obese and 339 (31%) had small head circumference. Many had underlying conditions: low birth weight, 514 (57.5%); prematurity, 294 (42.2%) and disabilities, 739 (25.3%). Children with disabilities had higher prevalence of malnutrition compared with counterparts without disabilities at baseline and 1-year screenings. There was marked intersite variation. Funnel plots highlight sites with malnutrition prevalence outside expected limits for this specific population taking into consideration natural variation at baseline and at 1 year. Control charts show changes in site mean z-scores over time in relation to site control limits. Conclusions Malnutrition is prevalent among children living within IBC, notably different forms of undernutrition (stunting, underweight, wasting). Underlying risk factors are also common: prematurity, low birth weight and disability. Nutrition interventions should take into account the needs of this vulnerable population, especially for infants and those with disabilities. Using control charts to present data could be especially useful to programme managers as sites outside control limits could represent: problems to be investigated; good practices to be shared
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