Enhancement Factor for Gas Absorption in a Finite Liquid Layer. Part 1: Instantaneous Reaction in a Liquid in Plug Flow

An approximate analysis of gas absorption with instantaneous reaction in a liquid layer of finite thickness in plug flow is presented. An approximate solution to the enhancement factor for the case of unequal diffusivities between the dissolved gas and the liquid reactant has been derived and validated by numerical simulation. Depending on the diffusivity ratio of the liquid reactant to the dissolved gas (?), the enhancement factor tends to be either lower or higher than the prediction of the classical enhancement factor equation based on the penetration theory (Ei,pen) at Fourier numbers typically larger than 0.1. An empirical correlation valid for all Fourier numbers is proposed to allow a quick estimation of the enhancement factor, which describes the prediction of the approximate solution and the simulation data with a relative error below 5?% under the investigated conditions (? = 0.34, Ei,pen = 21000).

Enhancement Factor for Gas Absorption in a Finite Liquid Layer. Part 2: First- and Second-Order Reactions in a Liquid in Plug Flow

Gas absorption accompanied by an irreversible chemical reaction of first-order or second-order in a liquid layer of finite thickness in plug flow has been investigated. The analytical solution to the enhancement factor has been derived for the case of a first-order reaction, and the exact solution to the enhancement factor has been obtained via numerical simulation for the case of a second-order reaction. The enhancement factor in both cases is presented as a function of the Fourier number and tends to deviate from the prediction of the existing enhancement factor expressions based on the penetration theory at Fourier numbers above 0.1 due to the absence of a well-mixed bulk region in the liquid layer. Approximate enhancement factor expressions that describe the analytical and exact solutions with an accuracy of 5?% and 9?%, respectively, have been proposed.

CD11b+ bone marrow-derived monocytes are the major leukocyte subset responsible for retinal capillary leukostasis in experimental diabetes in mouse and express high levels of CCR5 in the circulation

We investigated the phenotype of cells involved in leukostasis in the early stages of streptozotocin-induced diabetes in mice by direct observation and by adoptive transfer of calcein-AM-labeled bone marrow-derived leukocytes from syngeneic mice. Retinal whole mounts, confocal microscopy, and flow cytometry ex vivo and scanning laser ophthalmoscopy in vivo were used. Leukostasis in vivo and ex vivo in retinal capillaries was increased after 2 weeks of diabetes (Hb A(1c), 14.2 ± 1.2) when either donor or recipient mice were diabetic. Maximum leukostasis occurred when both donor and recipient were diabetic. CD11b(+), but not Gr1(+), cells were preferentially entrapped in retinal vessels (fivefold increase compared with nondiabetic mice). In diabetic mice, circulating CD11b(+) cells expressed high levels of CCR5 (P = 0.04), whereas spleen (P = 0.0001) and retinal (P = 0.05) cells expressed increased levels of the fractalkine chemokine receptor. Rosuvastatin treatment prevented leukostasis when both recipient and donor were treated but not when donor mice only were treated. This effect was blocked by treatment with mevalonate. We conclude that leukostasis in early diabetic retinopathy involves activated CCR5(+)CD11b(+) myeloid cells (presumed monocytes). However, leukostasis also requires diabetes-induced changes in the endothelium, because statin therapy prevented leukostasis only when recipient mice were treated. The up-regulation of the HMG-CoA reductase pathway in the endothelium is the major metabolic dysregulation promoting leukostasis.

Isolation of a bone marrow-derived stem cell line with high proliferation potential and its application for preventing acute fatal liver failure

Transplantation of hepatocytes or hepatocyte-like cells of extrahepatic origin is a promising strategy for treatment of acute and chronic liver failure. We examined possible utility of hepatocyte-like cells induced from bone marrow cells for such a purpose. Clonal cell lines were established from the bone marrow of two different rat strains. One of these cell lines, rBM25/S3 cells, grew rapidly (doubling time, approximately 24 hours) without any appreciable changes in cell properties for at least 300 population doubling levels over a period of 300 days, keeping normal diploid karyotype. The cells expressed CD29, CD44, CD49b, CD90, vimentin, and fibronectin but not CD45, indicating that they are of mesenchymal cell origin. When plated on Matrigel with hepatocyte growth factor and fibroblast growth factor-4, the cells efficiently differentiated into hepatocyte-like cells that expressed albumin, cytochrome P450 (CYP) 1A1, CYP1A2, glucose 6-phosphatase, tryptophane-2,3-dioxygenase, tyrosine aminotransferase, hepatocyte nuclear factor (HNF)1 alpha, and HNF4alpha. Intrasplenic transplantation of the differentiated cells prevented fatal liver failure in 90%-hepatectomized rats. In conclusion, a clonal stem cell line derived from adult rat bone marrow could differentiate into hepatocyte-like cells, and transplantation of the differentiated cells could prevent fatal liver failure in 90%-hepatectomized rats. The present results indicate a promising strategy for treating human fatal liver diseases.

On the filling factor of emitting material in the upper atmosphere of ε Eri (K2 V)

The emission measure distribution in the upper transition region and corona of e Eri is derived from observed emission-line fluxes. Theoretical emission measure distributions are calculated assuming that the radiation losses are balanced by the net conductive flux. We discuss how the area factor of the emitting regions as a function of temperature can be derived from a comparison between these emission measure distributions. It is found that the filling factor varies from ~0.2 in the mid-transition region to ~1.0 in the inner corona. The sensitivity of these results to the adopted ion fractions, the iron abundance and other parameters is discussed. The area factors found are qualitatively similar to the observed structure of the solar atmosphere, and can be used to constrain two-component models of the chromosphere. Given further observations, the method could be applied to investigate the trends in filling factors with indicators of stellar activity.

Sca-1+ progenitors derived from embryonic stem cells differentiate into endothelial cells capable of vascular repair after arterial injury

Embryonic stem cells possess the ability to differentiate into endothelium. The ability to produce large volumes of endothelium from embryonic stem cells could provide a potential therapeutic modality for vascular injury. We describe an approach that selects endothelial cells using magnetic beads that may be used therapeutically to treat arterial injury.

Wild-type Measles Virus Infection Upregulates Poliovirus Receptor-Related 4 and Causes Apoptosis in Brain Endothelial Cells by Induction of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand

Small numbers of brain endothelial cells (BECs) are infected in children with neurologic complications of measles virus (MV) infection. This may provide a mechanism for virus entry into the central nervous system, but the mechanisms are unclear. Both in vitro culture systems and animal models are required to elucidate events in the endothelium. We compared the ability of wild-type (WT), vaccine, and rodent-adapted MV strains to infect, replicate, and induce apoptosis in human and murine brain endothelial cells (HBECs and MBECs, respectively). Mice also were infected intracerebrally. All MV stains productively infected HBECs and induced the MV receptor PVRL4. Efficient WT MV production also occurred in MBECs. Extensive monolayer destruction associated with activated caspase 3 staining was observed in HBECs and MBECs, most markedly with WT MV. Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL), but not Fas ligand, was induced by MV infection. Treatment of MBECs with supernatants from MV-infected MBEC cultures with an anti-TRAIL antibody blocked caspase 3 expression and monolayer destruction. TRAIL was also expressed in the endothelium and other cell types in infected murine brains. This is the first demonstration that infection of low numbers of BECs with WT MV allows efficient virus production, induction of TRAIL, and subsequent widespread apoptosis.

A posteriori-derived dietary patterns and retinal vessel caliber in an elderly population

Purpose. To examine the association between a posteriori–derived dietary patterns (DP) and retinal vessel caliber in an elderly population.

Methods. This was a cross-sectional study of 288 elderly adults (>65 years) who participated in the European Eye study (EUREYE) Northern Irish cohort. DP were extracted using principal component analysis from completed food frequency questionnaires. Semi-automated computer grading was used to determine the mean retinal vessel diameters (central retinal arteriole equivalent [CRAE] and central retinal venule equivalent [CRVE]) from digitized visual field one images using a standard measurement protocol.

Results. Three major DP were identified in this population, which accounted for 21% of the total variance: a “healthy” pattern with high factor loadings for oily fish, fruits and vegetables, and olive oil; an “unhealthy” pattern with high factor loadings for red and processed meat, refined grains, eggs, butter, sugar and sweets; and a “snack and beverage” pattern with high factor loading for pizza, nuts, and coffee. Multivariable linear regression analysis indicated no significant association between major identified DP and mean CRAE or CRVE in all models.

Conclusions. This is the first study to investigate associations between a posteriori–derived DP and retinal vessel caliber. There was no evidence of a relationship between extracted DP and retinal vessel measurements in this population. However, it is possible that potentially important relationships exist between single nutrients or foods and vessel diameters that cannot be identified using a DP approach. Further studies to examine the role of dietary factors in the microcirculation are required.

Source as a controlling factor on the quality and interpretation of sediment magnetic records from the northern North Atlantic

Magnetic properties of eight particle size ranges from nine locations in Iceland and 26 locations in southern Greenland reveal the importance of source variation for our understanding of paleomagnetic and environmental magnetic records in the marine environment. These terrestrial samples show varying degrees of particle size dependence with all samples showing that the silt fraction possesses greater concentrations of ferrimagnetic minerals than either clay or sand. Fine pseudo-single domain (PSD) size magnetic grains dominate the magnetic assemblage of all Icelandic fractions. In contrast, Greenlandic samples possess greater variation in magnetic grain size; only fine silt and clay are as magnetically fine as the Icelandic PSD grains, while Greenlandic silts and sands are dominated by coarser PSD and multi-domain grains. These observations from potential marine sediment sources suggest that the silt size fraction is a likely driver for much of the concentration-dependent parameters derived from bulk magnetic records and that the magnetic grain size of the silt fraction can be used to discriminate between Icelandic and Greenlandic sources. Using these results to examine magnetic grain size records from marine sediment cores collected across the northern North Atlantic suggests that source, not just transport-controlled physical grain-size, has a significant impact on determining the magnetic grain size at a particular location. Homogeneity of magnetic grain size in Icelandic sediments at least partially explains the consistent quality of paleomagnetic records derived from cores surrounding Iceland and their ability to buffer large environmental changes. © 2013 Elsevier B.V.

Stimulation of cholesteryl ester synthesis in human monocyte-derived macrophages by low-density lipoproteins from type 1 (insulin-dependent) diabetic patients:the influence of non-enzymatic glycosylation of low-density lipoproteins

Diabetes mellitus is an independent risk factor in the development of atherosclerosis. In this study we aimed to demonstrate whether there is an abnormal interaction between low-density lipoproteins from diabetic patients and human macrophages. We measured cholesteryl ester synthesis and cholesteryl ester accumulation in human monocyte-derived macrophages (obtained from non-diabetic donors) incubated with low density lipoproteins from Type 1 (insulin-dependent) diabetic patients in good or fair glycaemic control. Low density lipoproteins from the diabetic patients stimulated more cholesteryl ester synthesis than low density lipoproteins from non-diabetic control subjects (7.19 +/- 1.19 vs 6.11 +/- 0.94 nmol/mg cell protein/20 h, mean +/- SEM, p less than 0.05). The stimulation of cholesteryl ester synthesis by low density lipoproteins isolated from diabetic patients was paralleled by a significant increase in intracellular cholesteryl ester accumulation (p less than 0.02). There were no significant differences in the lipid composition of low density lipoproteins between the diabetic and control groups. Non-enzymatic glycosylation of low density lipoproteins was higher in the diabetic group (p less than 0.01) and correlated significantly with cholesteryl ester synthesis (r = 0.58). Similarly, low-density lipoproteins obtained from non-diabetic subjects and glycosylated in vitro stimulated more cholesteryl ester synthesis in macrophages than control low density lipoproteins. The increase in cholesteryl ester synthesis and accumulation by cells exposed to low density lipoproteins from diabetic patients seems to be mediated by an increased uptake of these lipoproteins by macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)

Macrophages Control Vascular Stem/Progenitor Cell Plasticity Through Tumor Necrosis Factor-α-Mediated Nuclear Factor-κB Activation

Objective: Vascular lineage differentiation of stem/progenitor cells can contribute to both tissue repair and exacerbation of vascular diseases such as in vein grafts. The role of macrophages in controlling vascular progenitor differentiation is largely unknown and may play an important role in graft development. This study aims to identify the role of macrophages in vascular stem/progenitor cell differentiation and thereafter elucidate the mechanisms that are involved in the macrophage- mediated process.

Approach and Results: We provide in vitro evidence that macrophages can induce endothelial cell (EC) differentiation of the stem/progenitor cells while simultaneously inhibiting their smooth muscle cell differentiation. Mechanistically, both effects were mediated by macrophage-derived tumor necrosis factor-α (TNF-α) via TNF-α receptor 1 and canonical nuclear factor-κB activation. Although the overexpression of p65 enhanced EC (or attenuated smooth muscle cell) differentiation, p65 or TNF-α receptor 1 knockdown using lentiviral short hairpin RNA inhibited EC (or rescued smooth muscle cell) differentiation in response to TNF-α. Furthermore, TNF-α–mediated EC differentiation was driven by direct binding of nuclear factor-κB (p65) to specific VE-cadherin promoter sequences. Subsequent experiments using an ex vivo decellularized vessel scaffold confirmed an increase in the number of ECs and reduction in smooth muscle cell marker expression in the presence of TNF-α. The lack of TNF-α in a knockout mouse model of vein graft decreased endothelialization and significantly increased thrombosis formation.

Conclusions: Our study highlights the role of macrophages in directing vascular stem/progenitor cell lineage commitment through TNF-α–mediated TNF-α receptor 1 and nuclear factor-κB activation that is likely required for endothelial repair in vascular diseases such as vein graft.

Macrophage migration inhibitory factor (MIF) expression in human malignant gliomas contributes to immune escape and tumour progression

Macrophage migration inhibitory factor (MIF), which inhibits apoptosis and promotes angiogenesis, is expressed in cancers suppressing immune surveillance. Its biological role in human glioblastoma is, however, only poorly understood. We examined in-vivo expression of MIF in 166 gliomas and 23 normal control brains by immunohistochemistry. MIF immunoreactivity was enhanced in neoplastic astrocytes in WHO grade II glioma and increased significantly in higher tumour grades (III-IV). MIF expression was further assessed in 12 glioma cell lines in vitro. Quantitative RT-PCR showed that MIF mRNA expression was elevated up to 800-fold in malignant glioma cells compared with normal brain. This translated into high protein levels as assessed by immunoblotting of total cell lysates and by ELISA-based measurement of secreted MIF. Wild-type p53-retaining glioma cell lines expressed higher levels of MIF, which may be connected with the previously described role of MIF as a negative regulator of wild-type p53 signalling in tumour cells. Stable knockdown of MIF by shRNA in glioma cells significantly increased tumour cell susceptibility towards NK cell-mediated cytotoxicity. Furthermore, supernatant from mock-transfected cells, but not from MIF knockdown cells, induced downregulation of the activating immune receptor NKG2D on NK and CD8+ T cells. We thus propose that human glioma cell-derived MIF contributes to the immune escape of malignant gliomas by counteracting NK and cytotoxic T-cell-mediated tumour immune surveillance. Considering its further cell-intrinsic and extrinsic tumour-promoting effects and the availability of small molecule inhibitors, MIF seems to be a promising candidate for future glioma therapy.

Heme oxygenase-1 derived carbon monoxide permits maturation of myeloid cells

Critical functions of the immune system are maintained by the ability of myeloid progenitors to differentiate and mature into macrophages. We hypothesized that the cytoprotective gas molecule carbon monoxide (CO), generated endogenously by heme oxygenases (HO), promotes differentiation of progenitors into functional macrophages. Deletion of HO-1, specifically in the myeloid lineage (Lyz-Cre:Hmox1(flfl)), attenuated the ability of myeloid progenitors to differentiate toward macrophages and decreased the expression of macrophage markers, CD14 and macrophage colony-stimulating factor receptor (MCSFR). We showed that HO-1 and CO induced CD14 expression and efficiently increased expansion and differentiation of myeloid cells into macrophages. Further, CO sensitized myeloid cells to treatment with MCSF at low doses by increasing MCSFR expression, mediated partially through a PI3K-Akt-dependent mechanism. Exposure of mice to CO in a model of marginal bone marrow transplantation significantly improved donor myeloid cell engraftment efficiency, expansion and differentiation, which corresponded to increased serum levels of GM-CSF, IL-1α and MCP-1. Collectively, we conclude that HO-1 and CO in part are critical for myeloid cell differentiation. CO may prove to be a novel therapeutic agent to improve functional recovery of bone marrow cells in patients undergoing irradiation, chemotherapy and/or bone marrow transplantation.

Novel titania sol-gel derived film for luminescence-based oxygen sensing.

A novel method for the preparation of titania sol–gel derived oxygen sensors based on the ruthenium(II) dye, [Ru(bpy)3]2+, is described. A titania sol–gel paste film was cast onto microscope slides, and the dye ion-paired to the deprotonated, hydroxylated groups on the film's surface from an aqueous solution of the dye at pH 11. The resulting sensor film is extremely oxygen sensitive, with a PO2 (S = 1/2) value (i.e. the partial pressure of oxygen required in order to reduce the original, oxygen free, luminescence intensity by 50%) of 0.011 atm. The sensor undergoes 95% response to oxygen in 4 s, and shows 95% recovery of its luminescence in argon within 7 s.

HPV16 Down-Regulates the Insulin-Like Growth Factor Binding Protein 2 to Promote Epithelial Invasion in Organotypic Cultures

Cervical cancer is a multi-stage disease caused by human papillomaviruses (HPV) infection of cervical epithelial cells, but the mechanisms regulating disease progression are not clearly defined. Using 3-dimensional organotypic cultures, we demonstrate that HPV16 E6 and E7 proteins alter the secretome of primary human keratinocytes resulting in local epithelial invasion. Mechanistically, absence of the IGF-binding protein 2 (IGFBP2) caused increases in IGFI/II signalling and through crosstalk with KGF/FGFR2b/AKT, cell invasion. Repression of IGFBP2 is mediated by histone deacetylation at the IGFBP2 promoter and was reversed by treatment with histone deacetylase (HDAC) inhibitors. Our in vitro findings were confirmed in 50 invasive cancers and 79 cervical intra-epithelial neoplastic lesions caused by HPV16 infection, where IGFBP2 levels were reduced with increasing disease severity. In summary, the loss of IGFBP2 is associated with progression of premalignant disease, and sensitises cells to pro-invasive IGF signalling, and together with stromal derived factors promotes epithelial invasion.