A mesoscopic approach to diffusion phenomena in mixtures

The mesosocpic concept is applied to the theory of mixtures. The aim is to investigate the diffusion phenomenon from a mesoscopic point of view. The domain of the field quantities is extended by the set of mesoscopic variables, here the velocities of the components. Balance equations on this enlarged space are the equations of motion for the mesoscopic fields. Moreover, local distribution functions of the velocities are introduced as a statistical element, and an equation of motion for this distribution function is derived. From this equation of motion differential equations for the diffusion fluxes, and also for higher order fluxes are obtained. These equations are of balance type, as it is postulated in Extended Thermodynamics. The resulting evolution equation for the diffusion flux generalizes the Fick's law

Regulated Deficit Irrigation of \u27Montmorency\u27 Tart Cherry

Regulated deficit irrigation (RDI) is the strategy of reducing irrigation rates during a specific period of growth and development, with the objective of conserving water and managing plant growth while maintaining or improving yield and fruit quality. Mature tart cherry (Prunus cerasus L. \u27Montmorency\u27) trees in a commercial orchard were subjected to a range of irrigation deficits from pit hardening to harvest during the 2007 and 2008 seasons. Irrigation treatments replaced from 62% to 96% of ETc, during that period. Midday stem water potential measurements were significantly different among treatments before harvest. However, fresh weight yield at harvest did not differ significantly among irrigation treatments in either year (P-value=0.64). In 2008 the amount of undersized fruit eliminated during packout was significantly higher in the treatments replacing 61% and 68% of ETc than in the control (P-value\u3c0.0001), but only amounted to 2.0% and 1.4% of total yields, respectively. This small increase in undersized fruit did not significantly affect packout. Fruit quality measurements, such as soluble solids concentration and chroma of whole intact fruit, increased with the severity of the irrigation deficit. Visible surface bark damage from mechanical harvesting appeared less severe as deficit levels increased. Return bloom was not significantly affected by irrigation treatments

Exploitation of the Second Law: Coleman–Noll and Liu Procedure in Comparison

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich.This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.A comparison is made between two classical methods for the exploitation of the second law of thermodynamics: the Coleman–Noll and the Liu procedure. On the example of a rigid heat conductor with general entropy flux, it is shown that the two procedures are equivalent. This equivalence is demonstrated in the case of a state space including the wanted fields, only, as well as in the case of gradients being relevant for constitutive equations, too. Also, the possible importance of an internal variable or an internal degree of freedom is considered

PD-L1 is not constitutively expressed on tasmanian devil facial tumor cells but is strongly upregulated in response to IFN-gamma and can be expressed in the tumor microenvironment

The devil facial tumor disease (DFTD) is caused by clonal transmissible cancers that have led to a catastrophic decline in the wild Tasmanian devil (Sarcophilus harrisii) population. The first transmissible tumor, now termed devil facial tumor 1 (DFT1), was first discovered in 1996 and has been continually transmitted to new hosts for at least 20 years. In 2015, a second transmissible cancer [devil facial tumor 2 (DFT2)] was discovered in wild devils, and the DFT2 is genetically distinct and independent from the DFT1. Despite the estimated 136,559 base pair substitutions and 14,647 insertions/deletions in the DFT1 genome as compared to two normal devil reference genomes, the allograft tumors are not rejected by the host immune system. Additionally, genome sequencing of two sub-strains of DFT1 detected greater than 15,000 single-base substitutions that were found in only one of the DFT1 sub-strains, demonstrating the transmissible tumors are evolving and that generation of neoantigens is likely ongoing. Recent evidence in human clinical trials suggests that blocking PD-1:PD-L1 interactions promotes antitumor immune responses and is most effective in cancers with a high number of mutations. We hypothesized that DFTD cells could exploit the PD-1:PD-L1 inhibitory pathway to evade antitumor immune responses. We developed recombinant proteins and monoclonal antibodies (mAbs) to provide the first demonstration that PD-1 binds to both PD-L1 and PD-L2 in a non-placental mammal and show that PD-L1 is upregulated in DFTD cells in response to IFN-γ. Immunohistochemistry showed that PD-L1 is rarely expressed in primary tumor masses, but low numbers of PD-L1+ non-tumor cells were detected in the microenvironment of several metastatic tumors. Importantly, in vitro testing suggests that PD-1 binding to PD-L1 and PD-L2 can be blocked by mAbs, which could be critical to understanding how the DFT allografts evade the immune system.Andrew S. Flies, A. Bruce Lyons, Lynn M. Corcoran, Anthony T. Papenfuss, James M. Murphy, Graeme W. Knowles, Gregory M. Woods and John D. Haybal

Analysis of the platypus genome suggests a transposon origin for mammalian imprinting

Comparisons between the platypus and eutherian mammalian genomes provides new insights into how epigenetic imprinting may have evolved in mammalian genomes

Selective CDK9 inhibition overcomes TRAIL resistance by concomitant suppression of cFlip and Mcl-1.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can induce apoptosis in many cancer cells without causing toxicity in vivo. However, to date, TRAIL-receptor agonists have only shown limited therapeutic benefit in clinical trials. This can, most likely, be attributed to the fact that 50% of all cancer cell lines and most primary human cancers are TRAIL resistant. Consequently, future TRAIL-based therapies will require the addition of sensitizing agents that remove crucial blocks in the TRAIL apoptosis pathway. Here, we identify PIK-75, a small molecule inhibitor of the p110α isoform of phosphoinositide-3 kinase (PI3K), as an exceptionally potent TRAIL apoptosis sensitizer. Surprisingly, PI3K inhibition was not responsible for this activity. A kinome-wide in vitro screen revealed that PIK-75 strongly inhibits a panel of 27 kinases in addition to p110α. Within this panel, we identified cyclin-dependent kinase 9 (CDK9) as responsible for TRAIL resistance of cancer cells. Combination of CDK9 inhibition with TRAIL effectively induced apoptosis even in highly TRAIL-resistant cancer cells. Mechanistically, CDK9 inhibition resulted in downregulation of cellular FLICE-like inhibitory protein (cFlip) and Mcl-1 at both the mRNA and protein levels. Concomitant cFlip and Mcl-1 downregulation was required and sufficient for TRAIL sensitization by CDK9 inhibition. When evaluating cancer selectivity of TRAIL combined with SNS-032, the most selective and clinically used inhibitor of CDK9, we found that a panel of mostly TRAIL-resistant non-small cell lung cancer cell lines was readily killed, even at low concentrations of TRAIL. Primary human hepatocytes did not succumb to the same treatment regime, defining a therapeutic window. Importantly, TRAIL in combination with SNS-032 eradicated established, orthotopic lung cancer xenografts in vivo. Based on the high potency of CDK9 inhibition as a cancer cell-selective TRAIL-sensitizing strategy, we envisage the development of new, highly effective cancer therapies.Cell Death and Differentiation advance online publication, 20 December 2013; doi:10.1038/cdd.2013.179

Aldehyde dehydrogenase-1a1 induces oncogene suppressor genes in B cell populations

AbstractThe deregulation of B cell differentiation has been shown to contribute to autoimmune disorders, hematological cancers, and aging. We provide evidence that the retinoic acid-producing enzyme aldehyde dehydrogenase 1a1 (Aldh1a1) is an oncogene suppressor in specific splenic IgG1+/CD19− and IgG1+/CD19+ B cell populations. Aldh1a1 regulated transcription factors during B cell differentiation in a sequential manner: 1) retinoic acid receptor alpha (Rara) in IgG1+/CD19− and 2) zinc finger protein Zfp423 and peroxisome proliferator-activated receptor gamma (Pparg) in IgG1+/CD19+ splenocytes. In Aldh1a1−/− mice, splenic IgG1+/CD19− and IgG1+/CD19+ B cells acquired expression of proto-oncogenic genes c-Fos, c-Jun, and Hoxa10 that resulted in splenomegaly. Human multiple myeloma B cell lines also lack Aldh1a1 expression; however, ectopic Aldh1a1 expression rescued Rara and Znf423 expressions in these cells. Our data highlight a mechanism by which an enzyme involved in vitamin A metabolism can improve B cell resistance to oncogenesis