Membrane Transport Generated by the Osmotic and Hydrostatic Pressure. Correlation Relation for Parameters L p, σ, and ω

Standard approach to membrane transport generated by osmotic andhydrostatic pressures, developed by Kedem and Katchalsky, is based onprinciples of thermodynamics of irreversible processes. In this paper wepropose an alternative technique. We derive transport equations from fewfairly natural assumptions and a mechanistic interpretation of the flows.In particular we postulate that a sieve-type membrane permeability isdetermined by the pore sizes and these are random within certain range.Assuming that an individual pore is either permeable or impermeable tosolute molecules, the membrane reflection coefficient depends on the ratioof permeable and impermeable pores. Considering flows through permeableand impermeable pores separately, we derive equations for the total volumeflux, solute flux and the solvent flux across the membrane. Comparing themechanistic equations to the Kedem-Katchalsky equations we find the formereasier to interpret physically. Based on the mechanistic equations we alsoderive a correlation relation for the membrane transport parameters L _p,, and . This relation eliminates the need for experimentaldetermination of all three phenomenological parameters, which in somecases met with considerable difficulties.     

Two different primate species express an identical functional MHC class I allele

 The products of the highly polymorphic and variable major histocompatibility complex (MHC) class I loci play a crucial role in host defenses against infectious disease. While similar alleles have been found in closely related species, sharing of a functional MHC class I allele between two species has never been reported. Here we show that an identical functional MHC class I molecule is present in two different primate species with an approximate divergence time of 0.7 million years. Lymphocytes from the red-crested tamarin (Saguinus geoffroyi) expressed an MHC class I allele (Sage-G ^* 01) that was identical in coding sequence to an MHC class I allele (Saoe-G ^* 08) found in the cotton-top tamarin (Saguinus oedipus). Furthermore, influenza virus-specific cytotoxic T lymphocytes (CTLs) generated in the cotton-top tamarin killed lymphocytes expressing the influenza virus nucleoprotein (NP) from the red-crested tamarin. Since the influenza virus NP epitope is bound by Saoe-G^*08 in the cotton-top tamarin, it is likely that this molecule is functional in both species. These data provide the first evidence that functional MHC class I molecules can be maintained entirely intact in two separate species. Received: 6 June 1997 / Revised: 21 July 1997     

Racial differences in genome-wide methylation profiling and gene expression in breast tissues from healthy women

Breast cancer is more common in European Americans (EAs) than in African Americans (AAs) but mortality from breast cancer is higher among AAs. While there are racial differences in DNA methylation and gene expression in breast tumors, little is known whether such racial differences exist in breast tissues of healthy women. Genome-wide DNA methylation and gene expression profiling was performed in histologically normal breast tissues of healthy women. Linear regression models were used to identify differentially-methylated CpG sites (CpGs) between EAs (n = 61) and AAs (n = 22). Correlations for methylation and expression were assessed. Biological functions of the differentially-methylated genes were assigned using the Ingenuity Pathway Analysis. Among 485 differentially-methylated CpGs by race, 203 were hypermethylated in EAs, and 282 were hypermethylated in AAs. Promoter-related differentially-methylated CpGs were more frequently hypermethylated in EAs (52%) than AAs (27%) while gene body and intergenic CpGs were more frequently hypermethylated in AAs. The differentially-methylated CpGs were enriched for cancer-associated genes with roles in cell death and survival, cellular development, and cell-to-cell signaling. In a separate analysis for correlation in EAs and AAs, different patterns of correlation were found between EAs and AAs. The correlated genes showed different biological networks between EAs and AAs; networks were connected by Ubiquitin C. To our knowledge, this is the first comprehensive genome-wide study to identify differences in methylation and gene expression between EAs and AAs in breast tissues from healthy women. These findings may provide further insights regarding the contribution of epigenetic differences to racial disparities in breast cancer.     

Facet shapes and thermo-stabilities of H<Subscript>2</Subscript>SO<Subscript>4</Subscript>•HNO<Subscript>3</Subscript> hydrates involved in polar stratospheric clouds

The nucleation, ice crystal shapes and thermodynamic stability of polar stratospheric clouds particles are interesting concerns owing to their implication in the ozone layer destruction. Some of these particles are formed by conformers of H₂O, HNO₃, and H₂SO₄. We carried out calculations using density functional theory (DFT) to obtain optimized structures. Several stable trimers are achieved —divided in two groups, one with HNO₃ moiety, second with H₂SO₄ moiety— after pre-optimization at B3LYP/6-31G and subsequently optimization at B3LYP/aug-cc-pVTZ level of theory. For both most stable conformers five H₂O molecules are added to their optimized trimers to calculate hydrated geometries. The OH stretching harmonic frequencies are provided for all aggregates. The zero-point energy correction (ZEPC), relative electronic energies (?E), relative reaction Gibbs free energies ?(?G)_k-relative, and cooling constant (K _cooling ) are reported at three temperatures: 188 K, 195 K, and 210 K. Shapes given in our calculations are compared with various experimental shapes as well as comparisons with their thermo-stabilities.

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Graphical Abstract Facet shapes and thermo-stabilities of H₂SO₄?HNO₃ hydrates involved in polar stratospheric clouds. IR spectrum of WNS-1+5W structure and its circular facet

     

Mathematical Modeling of Hepatitis C Prevalence Reduction with Antiviral Treatment Scale-Up in Persons Who Inject Drugs in Metropolitan Chicago

Background/Aim

New direct-acting antivirals (DAAs) provide an opportunity to combat hepatitis C virus (HCV) infection in persons who inject drugs (PWID). Here we use a mathematical model to predict the impact of a DAA-treatment scale-up on HCV prevalence among PWID and the estimated cost in metropolitan Chicago.

Methods

To estimate the HCV antibody and HCV-RNA (chronic infection) prevalence among the metropolitan Chicago PWID population, we used empirical data from three large epidemiological studies. Cost of DAAs is assumed $50,000 per person.

Results

Approximately 32,000 PWID reside in metropolitan Chicago with an estimated HCV-RNA prevalence of 47% or 15,040 cases. Approximately 22,000 PWID (69% of the total PWID population) attend harm reduction (HR) programs, such as syringe exchange programs, and have an estimated HCV-RNA prevalence of 30%. There are about 11,000 young PWID (<30 years old) with an estimated HCV-RNA prevalence of 10% (PWID in these two subpopulations overlap). The model suggests that the following treatment scale-up is needed to reduce the baseline HCV-RNA prevalence by one-half over 10 years of treatment [cost per year, min-max in millions]: 35 per 1,000 [$50-$77] in the overall PWID population, 19 per 1,000 [$20-$26] for persons in HR programs, and 5 per 1,000 [$3-$4] for young PWID.

Conclusions

Treatment scale-up could dramatically reduce the prevalence of chronic HCV infection among PWID in Chicago, who are the main reservoir for on-going HCV transmission. Focusing treatment on PWID attending HR programs and/or young PWID could have a significant impact on HCV prevalence in these subpopulations at an attainable cost.     

Quality Indicators for Safe Medication Preparation and Administration: A Systematic Review

Background

One-third of all medication errors causing harm to hospitalized patients occur in the medication preparation and administration phase, which is predominantly a nursing activity. To monitor, evaluate and improve the quality and safety of this process, evidence-based quality indicators can be used.

Objectives

The aim of study was to identify evidence-based quality indicators (structure, process and outcome) for safe in-hospital medication preparation and administration.

Methods

MEDLINE, EMBASE and CINAHL were searched for relevant studies published up to January 2015. Additionally, nine databases were searched to identify relevant grey literature. Two reviewers independently selected studies if (1) the method for quality indicator development combined a literature search with expert panel opinion, (2) the study contained quality indicators on medication safety, and (3) any of the quality indicators were applicable to hospital medication preparation and administration. A multidisciplinary team appraised the studies independently using the AIRE instrument, which contains four domains and 20 items. Quality indicators applicable to in-hospital medication preparation and administration were extracted using a structured form.

Results

The search identified 1683 studies, of which 64 were reviewed in detail and five met the inclusion criteria. Overall, according to the AIRE domains, all studies were clear on purpose; most of them applied stakeholder involvement and used evidence reasonably; usage of the indicator in practice was scarcely described. A total of 21 quality indicators were identified: 5 structure indicators (e.g. safety management and high alert medication), 11 process indicators (e.g. verification and protocols) and 5 outcome indicators (e.g. harm and death). These quality indicators partially cover the 7 rights.

Conclusion

Despite the relatively small number of included studies, the identified quality indicators can serve as an excellent starting point for further development of nursing specific quality indicators for medication safety. Especially on the right patient, right route, right time and right documentation there is room future development of quality indicators.     

Free Extracellular miRNA Functionally Targets Cells by Transfecting Exosomes from Their Companion Cells

Lymph node and spleen cells of mice doubly immunized by epicutaneous and intravenous hapten application produce a suppressive component that inhibits the action of the effector T cells that mediate contact sensitivity reactions. We recently re-investigated this phenomenon in an immunological system. CD8+ T lymphocyte-derived exosomes transferred suppressive miR-150 to the effector T cells antigen-specifically due to exosome surface coat of antibody light chains made by B1a lymphocytes. Extracellular RNA (exRNA) is protected from plasma RNases by carriage in exosomes or by chaperones. Exosome transfer of functional RNA to target cells is well described, whereas the mechanism of transfer of exRNA free of exosomes remains unclear. In the current study we describe extracellular miR-150, extracted from exosomes, yet still able to mediate antigen-specific suppression. We have determined that this was due to miR-150 association with antibody-coated exosomes produced by B1a cell companions of the effector T cells, which resulted in antigen-specific suppression of their function. Thus functional cell targeting by free exRNA can proceed by transfecting companion cell exosomes that then transfer RNA cargo to the acceptor cells. This contrasts with the classical view on release of RNA-containing exosomes from the multivesicular bodies for subsequent intercellular targeting. This new alternate pathway for transfer of exRNA between cells has distinct biological and immunological significance, and since most human blood exRNA is not in exosomes may be relevant to evaluation and treatment of diseases.     

Effects of seasonal and climate variations on calves’ thermal comfort and behaviour

The aim of this study was to measure the effect of season and climate variations on thermal comfort and behaviour of 6-month-old dairy calves housed in a semi-opened shelter to develop animal-based indicators for assessing animal thermal comfort. The ultimate purpose was to further exploit the use of those indicators to prevent thermal stress by providing appropriate care to the animals. Measurements were taken for winter and summer seasons. Results showed that season significantly influenced (P?≤?0.01) the lying down behaviour of calves by reducing the time spent lying, from 679.9 min in winter to 554.1 min in summer. Moreover, season had a significant influence (P?≤?0.01) on feeding behaviour. In detail, the total length of feeding periods was shorter in winter, 442.1 min in comparison to 543.5 min in summer. Time spent drinking increased significantly (P?≤?0.001), from 11.9 min in winter to 26.9 min in summer. Furthermore, season had a significant influence (P?≤?0.001) on self grooming behaviour which was 5.5 times longer in duration in winter than in summer (1,336 s vs 244 s). It was concluded that calves’ thermal comfort is affected by seasonal and climate variations and that this can be assessed by measuring behaviour with animal-based indicators, such as lying down, resting, standing up, feeding, rumination, drinking and self grooming. The indicators developed may be a useful tool to prevent animal thermal stress by providing appropriate housing and handling to calves under seasonal and climate challenge.