The Covenant of Sinai - the Revelation of God\u27s Mercy. A Theology of the Covenant in the Book of Exodus

Događaj Izlaska je zikkarôn - spomenčin i tvori čin vjere Židova. Savez Božji je središnji čin tog događaja spasenja. U Knjizi Izlaska opisivanje sklapanja Saveza (19 - 34) djelo je više redaktora nastalo na temelju višestoljetnih predaja. Postojao je jedan kratki temeljni tekst (Grundschrift) najbolje sačuvan u jahvističkom prikazu sklapanja Saveza. Savez je protumačen kao milosrdni Jahvin čin prema svome narodu zbog danih obećanja Abrahamu i njegovu potomstvu. Elohist je obogatio tekst prikazom misterija Božje prisutnosti i djelovanja u povijesti. Deuteronomistička predaja kroz više redakcija protumačila je Savez kao trajni čin Božjeg milosrđa i umetnula Deset zapovijedi kao dokument Saveza, a zadnji svećenički redaktor dodao je i Knjigu saveza. Svećenički prikaz u opis Saveza unio je potrebu svetosti, svetišta i kulta. Mojsije je u tekstu privilegiran u susretu s Jahvom i posrednik je Saveza. Savez je povezan i s teologijom stvaranja. Slavlje Saveza prikazano je slikom gozbe i obredom krvi kojim je izraženo zajedništvo života naroda sa živim Bogom. Subota je božanska ustanova i znak je vječnog Saveza. Prekršaj Saveza (Izl 32) reinterpretacija je vjerskog i narodnog raskola iz vremena Jeroboama I. Mojsije je zagovornik oproštenja pred Jahvom jer milosrđe pripada biti Jahvina identiteta. Oproštenje je u funkciji obnovljenog Saveza koji je u biti objava Božjeg milosrđa i interpretacija prve istine Dekaloga.The event of the exodus, as depicted in the Book of Exodus, is zikkarôn a memorial and constitutes the faith of Jews. God\u27s covenant is the central act of the redempting experience. The narrative of the Covenant at Mount Sinai in the Book of Exodus (chapters 19-34) is the work of several redactors who reshaped centuries old traditions. Contemporary researchers of the Old Testament assume the existence of a brief fundamental text (Grundschrift) which is best preserved in the Yahwistic account of the covenant narrative. In it, the covenant is explained as Yahweh\u27s merciful act in favor of his people, based on promises granted to Abraham and his progeny. The Elohist redactor enriched the text by presenting the mystery of God\u27s presence and activity in the his- ton/ of God\u27s people. Deuteronomic redaction interprets the covenant as an enduring action of God\u27s mercy and inserted the Ten Commandments as a Document of the Covenant, while the final redactor added the Book of the Covenant. Priestly account of the Covenant Code included the indispensability of holiness, the central shrine and worship. Moses was entrusted with performing the encounter with Yahweh and to mediate the covenant. The making of the covenant is related to the theology of creation. It is depicted in the form of a banquet and the sprinkling of blood which reflects Israel\u27s life fellowship with the living God. The Shabbat is the eternal sign of the covenant. The golden calf episode (Ex 32) is a reinterpretation of national and religious schism during the reign of Jeroboam I. In this episode Moses intercedes with Yahweh to forgive his people\u27s sin. Mercy is an integral part of Yahweh\u27s very selfhood. The forgiveness leads to restoration of the covenant which in essence is the revelation of God\u27s mercy and interpretation of the first Commandment which strongly asserts that Yahweh is the only deity for Israel

The preference for Europe: public opinion about European integration since 1952

To determine how public opinion matters for the politics of European integration, we need to know what Europeans say about Europe. Yet, despite a proliferation of analyses of public support for Europe, fundamental questions remain. First, does aggregate opinion reflect a single preference for Europe? Second, is the content of opinions similar across countries? Third, have opinions about Europe become more structured over time? Finally, what are the long-term dynamics in opinions about Europe? To answer these questions, we construct a new dataset of historical public opinion since 1952 in France, Germany, Italy, and the United Kingdom. Over the long run, aggregate opinion toward Europe reflects one dominant underlying dimension and its content is similar across countries. We examine the trends in support for Europe

High CD8+ T Cell Activation Marks a Less Differentiated HIV-1 Specific CD8+ T Cell Response that Is Not Altered by Suppression of Viral Replication

The relationship of elevated T cell activation to altered T cell differentiation profiles, each defining features of HIV-1 infection, has not been extensively explored. We hypothesized that anti-retroviral suppression of T cell activation levels would lead to alterations in the T cell differentiation of total and HIV-1 specific CD8+ T cell responses among recently HIV-1 infected adults.We performed a longitudinal study simultaneously measuring T cell activation and maturation markers on both total and antigen-specific T cells in recently infected adults: prior to treatment; after the initiation of HAART; and after treatment was halted. Prior to treatment, HIV-1 Gag-specific CD8+ T cells were predominantly of a highly activated, intermediate memory (CD27+CD28-) phenotype, while CMV pp65-specific CD8+ T cells showed a late memory (CD27-CD28-), low activation phenotype. Participants with the highest fraction of late memory (CD27-CD28-) HIV-1-specific CD8+ T cells had higher CD4+ T cell counts (rho = +0.74, p = 0.004). In turn, those with the highest fraction of intermediate memory (CD27+ CD28-) HIV-1 specific CD8+ T cells had high total CD8+ T cell activation (rho = +0.68, p = 0.01), indicating poorer long-term clinical outcomes. The HIV-1 specific T cell differentiation profile was not readily altered by suppression of T cell activation following HAART treatment.A more differentiated, less activated HIV-1 specific CD8+ T cell response may be clinically protective. Anti-retroviral treatment initiated two to four months after infection lowered T cell activation but had no effect on the differentiation profile of the HIV-1-specific response. Intervention during the first month of acute infection may be required to shift the differentiation phenotype of HIV-1 specific responses to a more clinically favorable profile

Tim-3 expression defines a novel population of dysfunctional T cells with highly elevated frequencies in progressive HIV-1 infection

Progressive loss of T cell functionality is a hallmark of chronic infection with human immunodeficiency virus 1 (HIV-1). We have identified a novel population of dysfunctional T cells marked by surface expression of the glycoprotein Tim-3. The frequency of this population was increased in HIV-1–infected individuals to a mean of 49.4 ± SD 12.9% of CD8+ T cells expressing Tim-3 in HIV-1–infected chronic progressors versus 28.5 ± 6.8% in HIV-1–uninfected individuals. Levels of Tim-3 expression on T cells from HIV-1–infected inviduals correlated positively with HIV-1 viral load and CD38 expression and inversely with CD4+ T cell count. In progressive HIV-1 infection, Tim-3 expression was up-regulated on HIV-1–specific CD8+ T cells. Tim-3–expressing T cells failed to produce cytokine or proliferate in response to antigen and exhibited impaired Stat5, Erk1/2, and p38 signaling. Blocking the Tim-3 signaling pathway restored proliferation and enhanced cytokine production in HIV-1–specific T cells. Thus, Tim-3 represents a novel target for the therapeutic reversal of HIV-1–associated T cell dysfunction

Granulocyte colony-stimulating factors for febrile neutropenia prophylaxis following chemotherapy: systematic review and meta-analysis

Background: Febrile neutropenia (FN) occurs following myelosuppressive chemotherapy and is associated with morbidity, mortality, costs, and chemotherapy reductions and delays. Granulocyte colony-stimulating factors (G-CSFs) stimulate neutrophil production and may reduce FN incidence when given prophylactically following chemotherapy. Methods: A systematic review and meta-analysis assessed the effectiveness of G-CSFs (pegfilgrastim, filgrastim or lenograstim) in reducing FN incidence in adults undergoing chemotherapy for solid tumours or lymphoma. G-CSFs were compared with no primary G-CSF prophylaxis and with one another. Nine databases were searched in December 2009. Meta-analysis used a random effects model due to heterogeneity. Results: Twenty studies compared primary G-CSF prophylaxis with no primary G-CSF prophylaxis: five studies of pegfilgrastim; ten of filgrastim; and five of lenograstim. All three G-CSFs significantly reduced FN incidence, with relative risks of 0.30 (95% CI: 0.14 to 0.65) for pegfilgrastim, 0.57 (95% CI: 0.48 to 0.69) for filgrastim, and 0.62 (95% CI: 0.44 to 0.88) for lenograstim. Overall, the relative risk of FN for any primary G-CSF prophylaxis versus no primary G-CSF prophylaxis was 0.51 (95% CI: 0.41 to 0.62). In terms of comparisons between different G-CSFs, five studies compared pegfilgrastim with filgrastim. FN incidence was significantly lower for pegfilgrastim than filgrastim, with a relative risk of 0.66 (95% CI: 0.44 to 0.98). Conclusions: Primary prophylaxis with G-CSFs significantly reduces FN incidence in adults undergoing chemotherapy for solid tumours or lymphoma. Pegfilgrastim reduces FN incidence to a significantly greater extent than filgrastim

IL-2 Immunotherapy to Recently HIV-1 Infected Adults Maintains the Numbers of IL-17 Expressing CD4+ T (TH17) Cells in the Periphery

Little is known about the manipulation of IL-17 producing CD4+ T cells (TH17) on a per-cell basis in humans in vivo. Previous studies on the effects of IL-2 on IL-17 secretion in non-HIV models have shown divergent results. We hypothesized that IL-2 would mediate changes in IL-17 levels among recently HIV-1-infected adults receiving anti-retroviral therapy. We measured cytokine T cell responses to CD3/CD28, HIV-1 Gag, and CMV pp65 stimulation, and changes in multiple CD4+ T cell subsets. Those who received IL-2 showed a robust expansion of naive and total CD4+ T cell counts and T-reg counts. However, after IL-2 treatment, the frequency of TH17 cells declined, while counts of TH17 cells did not change due to an expansion of the CD4+ naïve T cell population (CD27+CD45RA+). Counts of HIV-1 Gag-specific T cells declined modestly, but CMV pp65 and CD3/CD28 stimulated populations did not change. Hence, in contrast with recent studies, our results suggest IL-2 is not a potent in vivo regulator of TH17 cell populations in HIV-1 disease. However, IL-2-mediated T-reg expansions may selectively reduce responses to certain antigen-specific populations, such as HIV-1 Gag

First Sagittarius A* Event Horizon Telescope Results. I. The Shadow of the Supermassive Black Hole in the Center of the Milky Way

We present the first Event Horizon Telescope (EHT) observations of Sagittarius A* (Sgr A*), the Galactic center source associated with a supermassive black hole. These observations were conducted in 2017 using a global interferometric array of eight telescopes operating at a wavelength of λ = 1.3 mm. The EHT data resolve a compact emission region with intrahour variability. A variety of imaging and modeling analyses all support an image that is dominated by a bright, thick ring with a diameter of 51.8 \ub1 2.3 μas (68% credible interval). The ring has modest azimuthal brightness asymmetry and a comparatively dim interior. Using a large suite of numerical simulations, we demonstrate that the EHT images of Sgr A* are consistent with the expected appearance of a Kerr black hole with mass ∼4 7 106 M☉, which is inferred to exist at this location based on previous infrared observations of individual stellar orbits, as well as maser proper-motion studies. Our model comparisons disfavor scenarios where the black hole is viewed at high inclination (i > 50\ub0), as well as nonspinning black holes and those with retrograde accretion disks. Our results provide direct evidence for the presence of a supermassive black hole at the center of the Milky Way, and for the first time we connect the predictions from dynamical measurements of stellar orbits on scales of 103-105 gravitational radii to event-horizon-scale images and variability. Furthermore, a comparison with the EHT results for the supermassive black hole M87* shows consistency with the predictions of general relativity spanning over three orders of magnitude in central mass

A Comparison of Mathematical Models for Polarization of Single Eukaryotic Cells in Response to Guided Cues

Polarization, a primary step in the response of an individual eukaryotic cell to a spatial stimulus, has attracted numerous theoretical treatments complementing experimental studies in a variety of cell types. While the phenomenon itself is universal, details differ across cell types, and across classes of models that have been proposed. Most models address how symmetry breaking leads to polarization, some in abstract settings, others based on specific biochemistry. Here, we compare polarization in response to a stimulus (e.g., a chemoattractant) in cells typically used in experiments (yeast, amoebae, leukocytes, keratocytes, fibroblasts, and neurons), and, in parallel, responses of several prototypical models to typical stimulation protocols. We find that the diversity of cell behaviors is reflected by a diversity of models, and that some, but not all models, can account for amplification of stimulus, maintenance of polarity, adaptation, sensitivity to new signals, and robustness