Kinematics of femtosecond laser-generated plasma expansion: Determination of sub-micron density gradient and collisionality evolution of over-critical laser plasmas

An optical diagnostic based on resonant absorption of laser light in a plasma is introduced and is used for the determination of density scale lengths in the range of 10 nm to >1 μm at the critical surface of an overdense plasma. This diagnostic is also used to extract the plasma collisional frequency, allowing inference of the temporally evolving plasma composition on the tens of femtosecond timescale. This is found to be characterized by two eras: the early time and short scale length expansion (L  0.1λ); this is consistent with a hydrogen plasma decoupling from the bulk target material. Density gradients and plasma parameters on this scale are of importance to plasma mirror optical performance and comment is made on this theme

Kinematics of femtosecond laser-generated plasma expansion : determination of sub-micron density-gradient and collisionality evolution of over-critical laser plasmas

An optical diagnostic based on resonant absorption of laser light in a plasma is introduced and is used for the determination of density scale lengths in the range of 10 nm to >1 μm at the critical surface of an overdense plasma. This diagnostic is also used to extract the plasma collisional frequency, allowing inference of the temporally evolving plasma composition on the tens of femtosecond timescale. This is found to be characterized by two eras: the early time and short scale length expansion (L  0.1λ); this is consistent with a hydrogen plasma decoupling from the bulk target material. Density gradients and plasma parameters on this scale are of importance to plasma mirror optical performance and comment is made on this theme

Activation of β-Catenin by Oncogenic PIK3CA and EGFR Promotes Resistance to Glucose Deprivation by Inducing a Strong Antioxidant Response

Glucose is an essential fuel for cell survival and its availability limits aberrant cellular proliferation. We have hypothesized that specific cancer mutations regulate metabolic response(s) to glucose deprivation (GD). By means of somatic knock-in cellular models, we have analyzed the response to glucose deprivation in cells carrying the frequent delE746-A750EGFR, G13DKRAS or E545KPIK3CA cancer alleles. We demonstrate that, in mammary epithelial cells, glucose has an essential antioxidant function and that these cells are very sensitive to GD. Conversely, isogenic cells carrying the delE746-A750EGFR or the E545KPIK3CA, but not the G13DKRAS allele, display high tolerance to GD by stimulating the expression of anti-oxidant genes (MnSOD and catalase). This adaptive transcriptional response is mediated by the activation of WNT/β-catenin and FOXO4 signalling. Our data highlights a new functional synergism between oncogenic EGFR and PIK3CA with WNT/β-catenin conferring high tolerance to oxidative stress generated by nutrient deprivation

Product–process matrix and complementarity approach

The relationship between different types of innovation is analysed from three different approaches. On the one hand, the distinctive view assumes that the determinants of each type of innovation are different and therefore there is no relationship between them. On the other hand, the integrative view considers that the different types of innovation are complementary. Finally, the product–process matrix framework suggests that the relationship between product innovation and process innovation is substitutive. Using data from Spain belonging to the Technological Innovation Panel (PITEC) for the years 2008, 2009, 2010, 2011 and 2012, we tested which of the three approaches is predominant. To perform the hypothesis test, we used the so-called complementarity approach. We find that there is no unique relation. The nature of the relationship depends on the types of innovation that interact. Our most significant finding is that the relationship between product innovation and process innovation is complementary. This finding contradicts the proposal of the product–process matrix framework. Consequently, the joint implementation of both types of innovation generates a greater impact on the performance of a company than the sum of their separate implementation

HIV/SIV Infection Primes Monocytes and Dendritic Cells for Apoptosis

Subversion or exacerbation of antigen-presenting cells (APC) death modulates host/pathogen equilibrium. We demonstrated during in vitro differentiation of monocyte-derived macrophages and monocyte-derived dendritic cells (DCs) that HIV sensitizes the cells to undergo apoptosis in response to TRAIL and FasL, respectively. In addition, we found that HIV-1 increased the levels of pro-apoptotic Bax and Bak molecules and decreased the levels of anti-apoptotic Mcl-1 and FLIP proteins. To assess the relevance of these observations in the context of an experimental model of HIV infection, we investigated the death of APC during pathogenic SIV-infection in rhesus macaques (RMs). We demonstrated increased apoptosis, during the acute phase, of both peripheral blood DCs and monocytes (CD14+) from SIV+RMs, associated with a dysregulation in the balance of pro- and anti-apoptotic molecules. Caspase-inhibitor and death receptors antagonists prevented apoptosis of APCs from SIV+RMs. Furthermore, increased levels of FasL in the sera of pathogenic SIV+RMs were detected, compared to non-pathogenic SIV infection of African green monkey. We suggest that inappropriate apoptosis of antigen-presenting cells may contribute to dysregulation of cellular immunity early in the process of HIV/SIV infection

Serial blood cytokine and chemokine mRNA and microRNA over 48 h are insult specific in a piglet model of inflammation-sensitized hypoxia-ischaemia.

BACKGROUND: Exposure to inflammation exacerbates injury in neonatal encephalopathy (NE). We hypothesized that brain biomarker mRNA, cytokine mRNA and microRNA differentiate inflammation (E. coli LPS), hypoxia (Hypoxia), and inflammation-sensitized hypoxia (LPS+Hypoxia) in an NE piglet model. METHODS: Sixteen piglets were randomized: (i) LPS 2 μg/kg bolus; 1 μg/kg infusion (LPS; n = 5), (ii) Saline with hypoxia (Hypoxia; n = 6), (iii) LPS commencing 4 h pre-hypoxia (LPS+Hypoxia; n = 5). Total RNA was acquired at baseline, 4 h after LPS and 1, 3, 6, 12, 24, 48 h post-insult (animals euthanized at 48 h). Quantitative PCR was performed for cytokines (IL1A, IL6, CXCL8, IL10, TNFA) and brain biomarkers (ENO2, UCHL1, S100B, GFAP, CRP, BDNF, MAPT). MicroRNA was detected using GeneChip (Affymetrix) microarrays. Fold changes from baseline were compared between groups and correlated with cell death (TUNEL) at 48 h. RESULTS: Within 6 h post-insult, we observed increased IL1A, CXCL8, CCL2 and ENO2 mRNA in LPS+Hypoxia and LPS compared to Hypoxia. IL10 mRNA differentiated all groups. Four microRNAs differentiated LPS+Hypoxia and Hypoxia: hsa-miR-23a, 27a, 31-5p, 193-5p. Cell death correlated with TNFA (R = 0.69; p < 0.01) at 1-3 h and ENO2 (R = -0.69; p = 0.01) at 48 h. CONCLUSIONS: mRNA and miRNA differentiated hypoxia from inflammation-sensitized hypoxia within 6 h in a piglet model. This information may inform human studies to enable triage for tailored neuroprotection in NE. IMPACT: Early stratification of infants with neonatal encephalopathy is key to providing tailored neuroprotection. IL1A, CXCL8, IL10, CCL2 and NSE mRNA are promising biomarkers of inflammation-sensitized hypoxia. IL10 mRNA levels differentiated all three pathological states; fold changes from baseline was the highest in LPS+Hypoxia animals, followed by LPS and Hypoxia at 6 h. miR-23, -27, -31-5p and -193-5p were significantly upregulated within 6 h of a hypoxia insult. Functional analysis highlighted the diverse roles of miRNA in cellular processes