Electron anti-neutrinos at the Glashow resonance (GR, at $E_{\bar \nu_e} \sim6.3$ PeV) have an enhanced probability to be detected. With three neutrinosdetected by IceCube in the (1-2) PeV energy range at present, one would expectthat about 1 to 4 GR $\bar\nu_e$ should have been detected. The high-energy$\sim 8.7$ PeV muon neutrino detected by IceCube may not be a GR event. If so,we expect to detect 50 to 70 GR $\bar\nu_e$, then one would have a "missingGlashow-resonance problem". This would suggest (1) that $p\gamma$ interactionrather than $pp$ interaction is the dominant channel to produce the observedIceCube high-energy neutrinos, (2) that multi-pion $p\gamma$ interactions aresuppressed, and (3) that the magnetic field and photon energy density in the$p\gamma$ emission region is such that significant $\mu^+$ cooling occursbefore decaying, yet $\pi^+$'s essentially do not cool before decaying.
We have studied the Earth matter effect on the oscillation of upward goingGeV neutrinos by taking into account the three active neutrino flavors. Forneutrino energy in the range 3 to 12 GeV we observed three distinct resonantpeaks for the oscillation process $\nu_e\leftrightarrow \nu_{\mu,\tau}$ inthree \textit{distinct} densities. However, according to the most realisticdensity profile of the Earth, the second peak at neutrino energy 6.18 GeVcorresponding to the density $6.6\,g/cm^3$ does not exist. So the resonance atthis energy can not be of MSW-type. For the calculation of observed flux ofthese GeV neutrinos on Earth, we considered two different flux ratios at thesource, the standard scenario with the flux ratio $1:2:0$ and the muon dampedscenario with $0:1:0$. It is observed that at the detector while the standardscenario gives the observed flux ratio $1:1:1$, the muon damped scenario has adifferent ratio. For muon damped case with $E_{\nu} 20$ GeV, we get the average$\Phi_{\nu_e}\sim 0$ and $\Phi_{\nu_\mu}\simeq \Phi_{\nu_\tau}\simeq 0.45$. Theupcoming PINGU will be able to shed more light on the nature of the resonancein these GeV neutrinos and hopefully will also be able to discriminate amongdifferent processes of neutrino production at the source in GeV energy range.
Thermal burn injuries in patients who are alcohol-intoxicated result in greater morbidity and mortality. Murine models combining ethanol and localized thermal burn injury reproduce the systemic toxicity seen in human subjects, which consists of both acute systemic cytokine production with multiple organ dysfunction, as well as a delayed systemic immunosuppression. However, the exact mechanisms for these acute and delayed effects are unclear. These studies sought to define the role of the lipid mediator platelet-activating factor in the acute and delayed effects of intoxicated burn injury. Combining ethanol and thermal burn injury resulted in increased enzymatic platelet-activating factor generation in a keratinocyte cell line in vitro, human skin explants ex vivo, as well as in murine skin in vivo. Further, the acute increase in inflammatory cytokines, such as IL-6, and the systemic immunosuppressive effects of intoxicated thermal burn injury were suppressed in mice lacking platelet-activating factor receptors. Together, these studies provide a potential mechanism and treatment strategies for the augmented toxicity and immunosuppressive effects of thermal burn injury in the setting of acute ethanol exposure, which involves the pleotropic lipid mediator platelet-activating factor.
Activation of the hedgehog pathway is causative of virtually all sporadic and Gorlin syndrome-related basal cell carcinomas (BCCs), with loss of function of Ptc1 being the most common genomic lesion. Sporadic BCCs also overexpress Dsg2, a desmosomal cadherin normally found in the basal layer. Using a mouse model of Gorlin syndrome (Ptc1 +/lacZ mice), we found that overexpressing Dsg2 in the basal layer (K14-Dsg2/Ptc1 +/lacZ mice) or the superficial epidermis (Inv-Dsg2/Ptc1 +/lacZ mice) resulted in increased spontaneous BCC formation at 3 and 6 months, respectively. The tumors did not show loss of heterozygosity of Ptc1, despite high levels of Gli1 and phosphorylated Stat3. A panel of sporadic human BCCs showed increased staining of both Dsg2 and phosphorylated Stat3 in all nine samples. Overexpression of Dsg2 in ASZ001 cells, a Ptc1 -/- BCC cell line, induced Stat3 phosphorylation and further increased Gli1 levels, in both an autocrine and paracrine manner. Three different Stat3 inhibitors reduced viability and Gli1 expression in ASZ001 cells but not in HaCaT cells. Conversely, stimulation of Stat3 in ASZ001 cells with IL-6 increased Gli1 expression. Our results indicate that Dsg2 enhances canonical hedgehog signaling downstream of Ptc1 to promote BCC development through the activation of phosphorylated Stat3 and regulation of Gli1 expression.
Despite the advancement in diagnostic modalities of sepsis, it is still a leading cause of morbidity and mortality. Differentiation between sepsis and non-infectious disease states remains a diagnostic challenge. Procalcitonin (PCT) is useful for the diagnosis of sepsis but it varies in cut-off ranges at different clinical settings. The aim of this study was to correlate serum PCT levels with cultures and to evaluate the best cut-off values with high sensitivity and specificity for PCT.