Abstract:
Biochemical studies with human cord blood-derived PEPs now show that Ras and the class Ib enzyme of the phosphatidylinositol-3 kinase (PI3K) family, PI3K gamma, are activated in response to minimal Epo concentrations. Surprisingly, three structurally different PI3K inhibitors block Ras, MEK and Erk activation in PEPs by Epo. Furthermore, Erk activation in PEPs is insensitive to the inhibition of Raf kinases but suppressed upon PKC inhibition. In contrast, Erk activation induced by stem cell factor, which activates c-Kit in the same cells, is sensitive to Raf inhibition and insensitive to PI3K and PKC inhibitors.These unexpected findings contrast with previous results in human primary cells using Epo at supraphysiological concentrations and open new doors to eventually understanding how low Epo concentrations mediate the moderate proliferation of erythroid progenitors under homeostatic blood oxygen levels. They indicate that the basal activation of MEKs and Erks in PEPs by minimal concentrations of Epo does not occur through the classical cascade Shc/Grb2/Sos/Ras/Raf/MEK/Erk. Instead, MEKs and Erks are signal mediators of PI3K, probably the recently described PI3K gamma, through a Raf-independent signaling pathway which requires PKC activity. It is likely that higher concentrations of Epo that are induced by hypoxia, for example, following blood loss, lead to additional mitogenic signals which greatly accelerate erythroid progenitor proliferation.Erythropoietin (Epo) is a multifunctional cytokine [1-4]. It has been known for a long time as a crucial regulator during all stages of definitive erythropoiesis. More recently, Epo was shown to have an important role in the survival of neurons after stress and injury [5-7]. Epo drives not only the proliferation of already committed early erythroid progenitor cells (burst-forming unit-erythroid; BFU-E), but also, and prominently, the proliferation and differentiation of later stage cells (colony-forming unit-erythroid; CFU-E

Abstract:
Background Dendritic cells (DCs) are the sentinels of the mammalian immune system, characterized by a complex maturation process driven by pathogen detection. Although multiple studies have described the analysis of activated DCs by transcriptional profiling, recent findings indicate that mRNAs are also regulated at the translational level. A systematic analysis of the mRNAs being translationally regulated at various stages of DC activation was performed using translational profiling, which combines sucrose gradient fractionation of polysomal-bound mRNAs with DNA microarray analysis. Results Total and polysomal-bound mRNA populations purified from immature, 4 h and 16 h LPS-stimulated human monocyte-derived DCs were analyzed on Affymetrix microarrays U133 2.0. A group of 375 transcripts was identified as translationally regulated during DC-activation. In addition to several biochemical pathways related to immunity, the most statistically relevant biological function identified among the translationally regulated mRNAs was protein biosynthesis itself. We singled-out a cluster of 11 large ribosome proteins mRNAs, which are disengaged from polysomes at late time of maturation, suggesting the existence of a negative feedback loop regulating translation in DCs and linking ribosomal proteins to immuno-modulatory function. Conclusion Our observations highlight the importance of translation regulation during the immune response, and may favor the identification of novel protein networks relevant for immunity. Our study also provides information on the potential absence of correlation between gene expression and protein production for specific mRNA molecules present in DCs.

Abstract:
The squeezed limit of the three-point function of cosmological perturbations is a powerful discriminant of different models of the early Universe. We present a conceptually simple and complete framework to relate any primordial bispectrum in this limit to late time observables, such as the CMB temperature bispectrum and the scale-dependent halo bias. We employ a series of convenient coordinate transformations to capture the leading non-linear effects of cosmological perturbation theory on these observables. This makes crucial use of Fermi Normal Coordinates and their conformal generalization, which we introduce here and discuss in detail. As an example, we apply our formalism to standard slow-roll single-field inflation. We show explicitly that Maldacena's results for the squeezed limits of the scalar bispectrum [proportional to (ns-1) in comoving gauge] and the tensor-scalar-scalar bispectrum lead to no deviations from a Gaussian universe, except for projection effects. In particular, the primordial contributions to the squeezed CMB bispectrum and scale dependent halo bias vanish, and there are no primordial "fossil" correlations between long-wavelength tensor perturbations and small-scale perturbations. The contributions to observed correlations are then only due to projection effects such as gravitational lensing and redshift perturbations.

Abstract:
The leading locally observable effect of a long-wavelength metric perturbation corresponds to a tidal field. We derive the tidal field induced by scalar, vector, and tensor perturbations, and use second order perturbation theory to calculate the effect on the locally measured small-scale density fluctuations. For sub-horizon scalar perturbations, we recover the standard perturbation theory result ($F_2$ kernel). For tensor modes of wavenumber $k_L$, we find that effects persist for $k_L\tau \gg 1$, i.e. even long after the gravitational wave has entered the horizon and redshifted away, i.e. it is a "fossil" effect. We then use these results, combined with the "ruler perturbations" of arXiv:1204.3625, to predict the observed distortion of the small-scale matter correlation function induced by a long-wavelength tensor mode. We also estimate the observed signal in the B mode of the cosmic shear from a gravitational wave background, including both tidal (intrinsic alignment) and projection (lensing) effects. The non-vanishing tidal effect in the $k_L\tau \gg 1$ limit significantly increases the intrinsic alignment contribution to shear B modes, especially at low redshifts $z \lesssim 2$.

Abstract:
Nucleic acid sensing by cells is a key feature of antiviral responses, which generally result in type-I Interferon production and tissue protection. However, detection of double-stranded RNAs in virus-infected cells promotes two concomitant and apparently conflicting events. The dsRNA-dependent protein kinase (PKR) phosphorylates translation initiation factor 2-alpha (eIF2α) and inhibits protein synthesis, whereas cytosolic DExD/H box RNA helicases induce expression of type I-IFN and other cytokines. We demonstrate that the phosphatase-1 cofactor, growth arrest and DNA damage-inducible protein 34 (GADD34/Ppp1r15a), an important component of the unfolded protein response (UPR), is absolutely required for type I-IFN and IL-6 production by mouse embryonic fibroblasts (MEFs) in response to dsRNA. GADD34 expression in MEFs is dependent on PKR activation, linking cytosolic microbial sensing with the ATF4 branch of the UPR. The importance of this link for anti-viral immunity is underlined by the extreme susceptibility of GADD34-deficient fibroblasts and neonate mice to Chikungunya virus infection.

Abstract:
We study the renormalization of a non-magnetic impurity's scattering potential due to the presence of a massless collective spin mode at a ferromagnetic quantum critical point. To this end, we compute the lowest order vertex corrections in two- and three-dimensional systems, for arbitrary scattering angle and frequency of the scattered fermions, as well as band curvature. We show that only for backward scattering in D=2 does the lowest order vertex correction diverge logarithmically in the zero frequency limit. In all other cases, the vertex corrections approach a finite (albeit possibly large) value in the zero frequency limit. We demonstrate that vertex corrections are strongly suppressed with increasing curvature of the fermionic bands. Moreover, we show how the frequency dependence of vertex corrections varies with the scattering angle. We also discuss the form of higher order ladder vertex corrections and show that they can be classified according to the zero-frequency limit of the lowest order vertex correction. We show that even in those cases where the latter is finite, summing up an infinite series of ladder vertex diagrams can lead to a strong enhancement (or divergence) of the impurity's scattering potential. Finally, we suggest that the combined frequency and angular dependence of vertex corrections might be experimentally observable via a combination of frequency dependent and local measurements, such as scanning tunneling spectroscopy on ordered impurity structures, or measurements of the frequency dependent optical conductivity.

Abstract:
We study the Kondo screening of a single magnetic impurity inside a non-magnetic quantum corral located on the surface of a metallic host system. We show that the spatial structure of the corral's eigenmodes lead to a spatially dependent Kondo effect whose signatures are spatial variations of the Kondo temperature, $T_K$. Moreover, we predict that the Kondo screening is accompanied by the formation of multiple Kondo resonances with characteristic spatial patterns. Our results open new possibilities to manipulate and explore the Kondo effect by using quantum corrals.

Abstract:
Seven electronic databases were searched for all relevant randomised clinical trials. Data were extracted and validated by both authors, tabulated and summarised narratively. The methodological quality was assessed with the Jadad score.Seven trials met our inclusion criteria. Without exception, their findings suggest that Ukrain has curative effects on a range of cancers. However, the methodological quality of most studies was poor. In addition, the interpretation of several trials was impeded by other problems.The data from randomised clinical trials suggest Ukrain to have potential as an anticancer drug. However, numerous caveats prevent a positive conclusion, and independent rigorous studies are urgently needed.Ukrain (NSC-631570) is a semi-synthetic compound derived from the common weed, greater celandine (Chelidonium majus L.). This plant contains a range of alkaloids, most notably chelidonine, also known as benzophenanthridine alkaloid. A leaflet distributed to patients at the Bristol Cancer Help Centre, United Kingdom, describes Ukrain as " the only known product, which at present does not also destroy healthy cells, and which reduces tumors and boosts the immune system..." [1]. Ukrain is most commonly administered intravenously and consists of one molecule thiophosphoric acid conjugated to three molecules of chelidonine. It has drug licenses in several states of the former Soviet Union.Research on Ukrain started about 20 years ago. Meanwhile, numerous in-vitro studies [2-37] animal experiments [38-83], case reports [84-97], and case series [98-108] have emerged. Collectively, these data suggest that Ukrain has anticancer activity in a wide range of cell lines, which could be of clinical value. Whether or not this translates into clinical effectiveness and whether or not Ukrain does indeed cure some type of cancer or improves their prognosis can best be decided on the basis of randomised clinical trials (RCTs). This systematic review is aimed at summarising a

Abstract:
Bifurcation diagrams and plots of Lyapunov exponents in the $r$--$\Omega$ --plane for Duffing--type oscillators $$\ddot x +2r\dot x +V'(x,\Omega t) =0$$ exhibit a regular pattern of repeating selfsimilar ``tongues'' with complex internal structure. We demonstrate here that this behaviour is easily understood qualitatively and quantitatively from the Poincar\'e map of the system in action--angle variables. This map approaches the {\it one dimensional} form $$\varphi_{n+1} = A + C \e^{-r T} \cos \varphi_n, \ \ T= \pi / \Omega$$ provided $\e^{-r T}$ (but not necessarily $C \e^{- r T}$), $r$ and $\Omega$ are small. We derive asymptotic (for $r$, $\Omega$ small) formulae for $A$ and $C$ for a special class of potentials $V$. We argue that these special cases contain all the information needed to treat the general case of potentials which obey $V'' \ge 0$ at all times. The essential tools of the derivation are the use of action--angle variables, the adiabatic approximation and the introduction of a nonoscillating reference solution of Duffing's equation, with respect to which the action-angle variables have to be determined. These allow the explicit construction of the Poincar\'e map in powers of $\e^{-rT}$. To first order, we obtain the $\varphi$--map, which survives asymptotically. To {\it second} order we obtain the two--dimensional $I$--$\varphi$--map. In $I$--direction it contracts by a factor $\e^{-rT}$ upon each iteration.

Abstract:
The problem of an apparent inconsistency between the fission rates derived on the basis of Bohr-Wheeler's transition-state method and Kramers' dynamical model of nuclear fission, first pointed out by Strutinsky in 1973, is revisited. The study is based on studying the features of individual trajectories on the fission path.