Dynamic aberrant NF-κB spurs tumorigenesis: A new model encompassing the microenvironment

Recently it was discovered that a transient activation of transcription factor NF-κB can give cells properties essential for invasiveness and cancer initiating potential. In contrast, most oncogenes to date were characterized on the basis of mutations or by their constitutive overexpression. Study of NF-κB actually leads to a far more dynamic perspective on cancer: tumors caused by diverse oncogenes apparently evolve into cancer after loss of feedback regulation for NF-κB. This event alters the cellular phenotype and the expression of hormonal mediators, modifying signals between diverse cell types in a tissue. The result is a disruption of stem cell hierarchy in the tissue, and pervasive changes in the microenvironment and immune response to the malignant cells

EFFECT OF PYROLYSIS PARAMETERS ON SILICON CARBIDE-FORMING COMPOSITE MIXTURES

High-performance ceramics are often used for reusable spacecraft Thermal Protection Systems (TPS). Pre-ceramic polymers provide a suitable route for fabricating silicon carbide (SiC)–based TPS. It is known that different phases of SiC form upon pyrolysis depending on the temperature. This research investigates the effects of pyrolysis temperature and nucleation aids on SiC forming pre-ceramic polymers and how they influence the final phases. It is possible that the addition of seed powders consisting of microscale and nanoscale SiC powders can aid growth of crystalline SiC at lower temperatures and influence the final composition in mixtures of SiC-forming polymers with crystalline SiC powders and graphite. For this research, pre-ceramic polymer mixtures with various nucleation aids were cured slowly in a furnace and pyrolyzed at various temperatures into a ceramic. The effects of temperature were investigated for six different sample configurations: pure polymer sample, micron crystalline SiC powder layer with polymer fill, nano SiC powder with polymer fill, micron SiC powder and polymer mixture (85 wt%), 3D printed amorphous carbon-loaded polylactic acid layer with SiC polymer fill, and crystalline graphite mixed with a UV-curable polymer (65 wt.%) mixed with SiC polymer. Material characterization was conducted via SEM to identify the phases. These results can improve processing procedures for these ceramics with better strength and thermal diffusivity for TPS.Ensign, United States NavyApproved for public release. Distribution is unlimited

The major genetic determinants of HIV-1 control affect HLA class I peptide presentation.

Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA-viral peptide interaction as the major factor modulating durable control of HIV infection

Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study

International audienc