On the effects of exothermicity and endothermicity upon the temperature fields in a partially-filled porous channel

Forced convection of heat in a two-dimensional channel, partially filled by a porous insert is considered. This system is assumed under fully developed conditions and constant wall heat flux. Further, the fluid and solid phases can feature internal heat generation (exothermicity) and consumption (endothermicity). Analytical solutions are developed for the solid and fluid temperature fields by applying local thermal non-equilibrium (LTNE) conditions and the Darcy-Brinkman model of momentum transport. Two existing interface models (Models A and B) are employed to describe the thermal boundary conditions at the porous-fluid interface. The developed solutions for the temperature fields are compared to those found by applying the local thermal equilibrium (LTE) assumption and, therefore, the validity of the LTE is examined. This is done for a wide range of pertinent parameters including Biot number, conductivity ratio, Darcy number and thickness of the porous insert. It is found that the thermal behaviour of the investigated partially filled system is influenced by the heat sources in both solid and fluid phase. It is further shown that the LTE approach remains an acceptable assumption only for some specific regions of the parametric space. Furthermore, the occurrence of temperature gradient bifurcation on the surface of the porous-fluid interface is examined. It is demonstrated that this effect is highly sensitive to the intensity of the energy sources

Socio-Economic Differences in Food Group and Nutrient Intakes Among Young Women in Ireland

The present study aimed to investigate socio-economic disparities in food and nutrient intakes among young Irish women. A total of 221 disadvantaged and seventy-four non-disadvantaged women aged 18–35 years were recruited. Diet was assessed using a diet history protocol. Of the total population, 153 disadvantaged and sixty-three non-disadvantaged women were classified as plausible dietary reporters. Food group intakes, nutrient intakes and dietary vitamin and mineral concentrations per MJ of energy consumed were compared between the disadvantaged and non-disadvantaged populations, as was compliance with dietary fibre, macronutrient and micronutrient intake guidelines. The disadvantaged women had lower intakes than the non-disadvantaged women of fruit, vegetables, fish, breakfast cereals, low-fat milk and wholemeal bread (all P,0·001), yogurt (P¼0·001), low-fat spread (P¼0·002) and fresh meat (P¼0·003). They also had higher intakes of butter, processed red meats, white bread, sugar-sweetened beverages, fried potatoes and potato-based snacks (all P,0·001) and full-fat milk (P¼0·014). Nutritionally, the disadvantaged women had higher fat, saturated fat and refined sugar intakes; lower dietary fibre, vitamin and mineral intakes; and lower dietary vitamin and mineral densities per MJ than their more advantaged peers. Non-achievement of carbohydrate (P¼0·017), fat (P,0·001), saturated fat (P,0·001), refined sugar (P,0·001), folate (P¼0·050), vitamin C (P,0·001), vitamin D (P¼0·047) and Ca (P¼0·019) recommendations was more prevalent among the disadvantaged women. Both groups showed poor compliance with Fe and Na guidelines. We conclude that the nutritional deficits present among these socially disadvantaged women are significant, but may be potentially ameliorated by targeted food-based interventions

Virtual Screening of Histone Lysine Demethylase(JMJD2) identifies new inhibitors

The JmjC domain-containing proteins are hydroxylases that confer posttranslational modifications on histone tails, by removing methylation marks on methylated lysine residues. This serves to either promote or repress gene transcription. The JMJD2A-D family members include the enzyme Jumonji domain 2C (JMJD2C), which specifically demethylates di- and trimethylated histone H3 at Lys 9 or Lys 36.[1] Dysregulation of JMJD2C has been implicated in prostate, colonic, and breast cancer as the demethylase can modify the expression levels of oncogenes.[2] The goal of the present study was to identify potent and selective small-molecule inhibitors of JMJD2C, to be used as chemical biology tools to further investigate the role of JMJD2C in cell proliferation and survival. Using high-resolution crystal structures of the JMJD2 subfamily members as templates, we have performed a small molecule virtual docking screen. From the ~3 million molecules that were docked, this experiment identified 21 compounds as possible leads. These compounds were tested against JMJD2C in enzymatic assays and here we report an overall hit rate of 76%, with 8 compounds demonstrating an IC50 of 176μM to 1.18μM. A molecule containing a salicylate core was selected as a candidate for optimization and thus far we have completed several rounds of iterative target-specific compound docking, hybrid molecule design, compound synthesis and in vitro characterization. Notably, our method demonstrated a substantial increase in potency when we linked two docked fragments together and further derivatized this new scaffold, through which we have successfully derived a 65nM inhibitor of JMJD2C. A compound representing the inhibitor scaffold has been co-crystallized with JMJD2A to a resolution of 2.4 Å. In the crystal structure each asymmetric unit contains two JMJD2A monomers, each bound to a single inhibitor molecule. This complex-structure superposes well with the docked pose for the hybrid series of compounds. We are now focusing our efforts on identifying an inhibitor that is selective for the JMJD2 family over other JmjC domain-containing proteins

New Hubble Space Telescope Discoveries of Type Ia Supernovae at z > 1: Narrowing Constraints on the Early Behavior of Dark Energy

We have discovered 21 new Type Ia supernovae (SNe Ia) with the Hubble Space Telescope (HST) and have used them to trace the history of cosmic expansion over the last 10 billion years. These objects, which include 13 spectroscopically confirmed SNe Ia at z > 1, were discovered during 14 epochs of reimaging of the GOODS fields North and South over two years with the Advanced Camera for Surveys on HST. Together with a recalibration of our previous HST-discovered SNe Ia, the full sample of 23 SNe Ia at z > 1 provides the highest-redshift sample known. Combined with previous SN Ia datasets, we measured H(z) at discrete, uncorrelated epochs, reducing the uncertainty of H(z>1) from 50% to under 20%, strengthening the evidence for a cosmic jerk--the transition from deceleration in the past to acceleration in the present. The unique leverage of the HST high-redshift SNe Ia provides the first meaningful constraint on the dark energy equation-of-state parameter at z >1. The result remains consistent with a cosmological constant (w(z)=-1), and rules out rapidly evolving dark energy (dw/dz >>1). The defining property of dark energy, its negative pressure, appears to be present at z>1, in the epoch preceding acceleration, with ~98% confidence in our primary fit. Moreover, the z>1 sample-averaged spectral energy distribution is consistent with that of the typical SN Ia over the last 10 Gyr, indicating that any spectral evolution of the properties of SNe Ia with redshift is still below our detection threshold.Comment: typos, references corrected, minor additions to exposition 82 pages, 17 figures, 6 tables. Data also available at: http://braeburn.pha.jhu.edu/~ariess/R06. Accepted, Astrophysical Journal vol. 656 for March 10, 200

Millimetre observations of a sample of high-redshift obscured quasars

We present observations at 1.2 mm with MAMBO-II of a sample of z>~2 radio-intermediate obscured quasars, as well as CO observations of two sources with the Plateau de Bure Interferometer. Five out of 21 sources (24%) are detected at a significance of >=3sigma. Stacking all sources leads to a statistical detection of = 0.96+-0.11 mJy and stacking only the non-detections also yields a statistical detection, with = 0.51+-0.13 mJy. This corresponds to a typical far-infrared luminosity L_FIR~4x10^12 Lsol. If the far-infrared luminosity is powered entirely by star-formation, and not by AGN-heated dust, then the characteristic inferred star-formation rate is ~700 Msol yr-1. This far-infrared luminosity implies a dust mass of M_dust~3x10^8 Msol. We estimate that such large dust masses on kpc scales can plausibly cause the obscuration of the quasars. We present dust SEDs for our sample and derive a mean SED for our sample. This mean SED is not well fitted by clumpy torus models, unless additional extinction and far-infrared re-emission due to cool dust are included. There is a hint that the host galaxies of obscured quasars must have higher far-infrared luminosities and cool-dust masses and are therefore often found at an earlier evolutionary phase than those of unobscured quasars. For one source at z=2.767, we detect the CO(3-2) transition, with S_CO Delta nu=630+-50 mJy km s-1, corresponding to L_CO(3-2)= 3.2x10^7 Lsol, or L'_CO(3-2)=2.4x10^10 K km s-1 pc2. For another source at z=4.17, the lack of detection of the CO(4-3) line yields a limit of L'_CO(4-3)<1x10^10 K km s-1 pc2. Molecular gas masses, gas depletion timescales and gas-to-dust ratios are estimated (Abridged).Comment: Accepted by ApJ, 25 pages, 11 figures, 4 table

Outer-Disk Populations in NGC 7793: Evidence for Stellar Radial Migration

We analyzed the radial surface brightness profile of the spiral galaxy NGC 7793 using HST/ACS images from the GHOSTS survey and a new HST/WFC3 image across the disk break. We used the photometry of resolved stars to select distinct populations covering a wide range of stellar ages. We found breaks in the radial profiles of all stellar populations at 280" (~5.1 kpc). Beyond this disk break, the profiles become steeper for younger populations. This same trend is seen in numerical simulations where the outer disk is formed almost entirely by radial migration. We also found that the older stars of NGC 7793 extend significantly farther than the underlying HI disk. They are thus unlikely to have formed entirely at their current radii, unless the gas disk was substantially larger in the past. These observations thus provide evidence for substantial stellar radial migration in late-type disks.Comment: 8 pages, 6 figure. Accepted for publication in Ap

Van Gogh-like 2 is essential for the architectural patterning of the mammalian biliary tree.

Background &amp; AimsIn the developing liver, bipotent epithelial progenitor cells known as hepatoblasts undergo lineage segregation to form the two major epithelial cell types, hepatocytes that constitute the bulk of the liver parenchyma and biliary epithelial cells (cholangiocytes) which comprise the bile duct, a complex tubular network which is critical for normal liver function. Notch and TGFβ signalling promote the formation of a sheet of biliary epithelial cells, the ductal plate that organises into discontinuous tubular structures. How these structures elongate and connect to form a continuous duct remains undefined. We aimed to define the mechanisms by which the ductal plate transitions from simple sheet of epithelial cells to a complex and connected bile duct.MethodsBy combining single cell RNA sequencing from embryonic mouse livers with genetic tools and organoid models we functionally dissected the role of planar cell polarity in duct patterning.ResultsWe show that the planar cell polarity protein, VANGL2 is expressed late in intrahepatic bile duct development and patterns the formation of cell-cell contacts between biliary cells. The patterning of these cell contacts regulates the normal polarisation of the actin cytoskeleton within biliary cells and loss of Vangl2-function results in the abnormal distribution of cortical actin remodelling resulting in the failure of bile duct formation.ConclusionsPlanar cell polarity is a critical step in the post-specification sculpture of the bile duct and is essential for establishing normal tissue architecture.Impact and ImplicationsHuman disease and mouse models have allowed us to define how the mammalian biliary lineage is specified during liver development. Once this relatively simple epithelium has formed though, how it undergoes morphogenesis to form a complex and branched structure is not clear. Similar to other branched tissues such as the liver and kidney the bile ducts use planar cell polarity signalling to coordinate cell movements; however how these biochemical signals are linked to ductular patterning remains unclear. Here we show that the core planar cell polarity protein, VANGL2 patterns how cell-cell contacts form in the mammalian bile duct and how ductular cells transmit confluent mechanical changes along the length of a duct. This work sheds light on how biological tubes are pattered across mammalian tissues (including within the liver) and will be important in how we promote ductular growth in patients where the duct is mis-patterned or poorly formed

Mesenchymal stromal cells facilitate neutrophil-trained immunity by reprogramming hematopoietic stem cells

Novel therapeutics are urgently needed to prevent opportunistic infections in immunocompromised individuals undergoing cancer treatments or other immune-suppressive therapies. Trained immunity is a promising strategy to reduce this burden of disease. We previously demonstrated that mesenchymal stromal cells (MSCs) preconditioned with a class A CpG oligodeoxynucleotide (CpG-ODN), a Toll-like receptor 9 (TLR9) agonist, can augment emergency granulopoiesis in a murine model of neutropenic sepsis. Here, we used a chimeric mouse model to demonstrate that MSCs secrete paracrine factors that act on lineage-negative c-kit+ hematopoietic stem cells (HSCs), leaving them “poised” to enhance emergency granulopoiesis months after transplantation. Chimeric mice developed from HSCs exposed to conditioned media from MSCs and CpG-ODN-preconditioned MSCs showed significantly higher bacterial clearance and increased neutrophil granulopoiesis following lung infection than control mice. By Cleavage Under Targets and Release Using Nuclease (CUT&RUN) chromatin sequencing, we identified that MSC-conditioned media leaves H3K4me3 histone marks in HSCs at genes involved in myelopoiesis and in signaling persistence by the mTOR pathway. Both soluble factors and extracellular vesicles from MSCs mediated these effects on HSCs and proteomic analysis by mass spectrometry revealed soluble calreticulin as a potential mediator. In summary, this study demonstrates that trained immunity can be mediated by paracrine factors from MSCs to induce neutrophil-trained immunity by reprogramming HSCs for long-lasting functional changes in neutrophil-mediated antimicrobial immunity