Call for meeting regarding I. B. Seixas offering himself as hazzan

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Letter from Abraham Touro to Moses B. Seixas

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Women in the congregation in the days of Hazan I. B. Seixas

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Letter to K. K. S. I. from K. K. B'nai Jeshurun, asking to borrow seforim and ornaments for the consecration of the synagogue

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Letter of B. S. Judah, presenting Tebah cloth, etc. for escaba for his grandfather

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Letter from B. S. Judah, declining to act as hatan bereshit

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Volatile constituents of Clausena willdenovii: Structures of the furanoterpenes α-clausenan, diclausenan A and diclausenan B

Four furanoid terpenic compounds, α-clausenan, rosefuran (γ-clausenan) and diclausenans A and B, were isolated from the essential oil of the leaves of Clausena willdenovii. Their structures were determined by chemical and spectral data. The occurrence of a high concentration of rosefuran is noteworthy. Selenium dioxide oxidation of diclausenan gave an unusual product, identified as an epoxy-dicarbonyl compound.

Notice of election of B. Nathan and S. Lazarus

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SOCS3 expression induced by PIM2 requires PKC and PI3K signaling

Initiation of proinflammatory host immunity in response to infection represents as a key event in effective control and containment of the pathogen at the site of infection as well as in elicitation of robust immune memory responses. In the current investigation, we demonstrate that an integral cell wall antigen of the mycobacterial envelope, Phosphatidyl-myo-inositol dimannosides (PIM2) triggers Suppressor of cytokine signaling (SOCS) 3 expression in macrophages in a Toll-like receptor 2 (TLR2)-MyD88 dependent manner. Data derived from signaling perturbations suggest the involvement of phosphoinositide-3 kinase (PI3K) and protein kinase C (PKC) signaling pathways during PIM2 induced SOCS3 expression. Further, pharmacological inhibition of ERK1/2, but not of p38 MAP kinase or JNK abrogated the induced expression of SOCS3. The PIM2 induced activation of ERK1/2 was dependent on the activation of PI3K or PKC signaling which in turn regulated p65 nuclear factor -kappa B (NF-kappa B) nuclear translocation. Overall, current study delineates the role for PI3K-PKC axis and ERK1/2 signaling as key signaling events during PIM2 induced SOCS3 expression in macrophages.

A Proof of Convergence of the B-RED and P-RED Algorithms for Random Early Detection

In [8], we recently presented two computationally efficient algorithms named B-RED and P-RED for random early detection. In this letter, we present the mathematical proof of convergence of these algorithms under general conditions to local minima.

The mast cell as a regulator of atherosclerotic plaque stability

Atherosclerosis is an inflammatory disease progressing over years via the accumulation of cholesterol in arterial intima with subsequent formation of atherosclerotic plaques. The stability of a plaque is determined by the size of its cholesterol-rich necrotic lipid core and the thickness of the fibrous cap covering it. The strength and thickness of the cap are maintained by smooth muscle cells and the extracellular matrix produced by them. A plaque with a large lipid core and a thin cap is vulnerable to rupture that may lead to acute atherothrombotic events, such as myocardial infarction and stroke. In addition, endothelial erosion, possibly induced by apoptosis of endothelial cells, may lead to such clinical events. One of the major causes of plaque destabilization is inflammation induced by accumulated and modified lipoproteins, and exacerbated by local aberrant shear stress conditions. Macrophages, T-lymphocytes and mast cells infiltrate particularly into the plaque’s shoulder regions prone to atherothrombotic events, and they are present at the actual sites of plaque rupture and erosion. Two major mechanisms of plaque destabilization induced by inflammation are extracellular matrix remodeling and apoptosis. Mast cells are bone marrow-derived inflammatory cells that as progenitors upon chemotactic stimuli infiltrate the target tissues, such as the arterial wall, differentiate in the target tissues and mediate their effects via the release of various mediators, typically in a process called degranulation. The released preformed mast cell granules contain proteases such as tryptase, chymase and cathepsin G bound to heparin and chondroitin sulfate proteoglycans. In addition, various soluble mediators such as histamine and TNF-alpha are released. Mast cells also synthesize many mediators such as cytokines and lipid mediators upon activation. Mast cells are capable of increasing the level of LDL cholesterol in the arterial intima by increasing accumulation and retention of LDL and by decreasing removal of cholesterol by HDL in vitro. In addition, by secreting proinflammatory mediators and proteases, mast cells may induce plaque destabilization by inducing apoptosis of smooth muscle and endothelial cells. Also in vivo data from apoE-/- and ldlr-/- mice suggest a role for mast cells in the progression of atherosclerosis. Furthermore, mast cell-deficient mice have become powerful tools to study the effects of mast cells in vivo. In this study, evidence suggesting a role for mast cells in the regulation of plaque stability is presented. In a mouse model genetically susceptible to atherosclerosis, mast cell deficiency (ldlr-/-/KitW-sh/W-sh mice) was associated with a less atherogenic lipid profile, a decreased level of lipid accumulation in the aortic arterial wall and a decreased level of vascular inflammation as compared to mast-cell competent littermates. In vitro, mast cell chymase-induced smooth muscle cell apoptosis was mediated by inhibition of NF-kappaB activity, followed by downregulation of bcl-2, release of cytochrome c, and activation of caspase-8, -9 and -3. Mast cell-induced endothelial cell apoptosis was mediated by chymase and TNF-alpha, and involved chymase-mediated degradation of fibronectin and vitronectin, and inactivation of FAK- and Akt-mediated survival signaling. Subsequently, mast cells induced inhibition of NF-kappaB activity and activation of caspase-8 and -9. In addition, possible mast cell protease-mediated mechanisms of endothelial erosion may include degradation of fibronectin and VE-cadherin. Thus, the present results suggest a role for mast cells in destabilization of atherosclerotic plaques.

Electron energy distributions and transport coefficients in N2 in E times B fields

Using the concept of energy-dependent effective field intensity, electron transport coefficients in nitrogen have been determined in E times B fields (E = electric field intensity, B = magnetic flux density) by the numerical solution of the Boltzmann transport equation for the energy distribution of electrons. It has been observed that as the value of B/p (p = gas pressure) is increased from zero, the perpendicular drift velocity increased linearly at first, reaches a maximum value, and then decreases with increasing B/p. In general, the electron mean energy is found to be a function of Eavet/p( Eavet = averaged effective electric field intensity) only, but the other transport coefficients, such as transverse drift velocity, perpendicular drift velocity, and the Townsend ionization coefficient, are functions of both E/p and B/p.

Nuclear Import Mechanisms of STAT and NF-kB Transcription Factors

The eukaryotic cell nucleoplasm is separated from the cytoplasm by the nuclear envelope. This compartmentation of eukaryotic cells requires that all nuclear proteins must be transported from the cytoplasm into the nucleus. Transport of macromolecules between the nucleus and the cytoplasm occurs through nuclear pore complexes (NPCs). Proteins to be targeted into the nucleus by the classical nuclear import system contain nuclear localization signals (NLSs), which are recognized by importin alpha, the NLS receptor. Importin alpha binds to importin beta, which docks the importin-cargo complex on the cytoplasmic side of the NPC and mediates the movement of the complex into the nucleus. Presently six human importin alpha isoforms have been identified. Transcription factors are among the most important regulators of gene expression in eukaryotic organisms. Transcription factors bind to specific DNA sequences on target genes and modulate the activity of the target gene. Many transcription factors, including signal transducers and activators of transcription (STAT) and nuclear factor kB (NF-kB), reside in the cytoplasm in an inactive form, and upon activation they are rapidly transported into the nucleus. In the nucleus STATs and NF-kB regulate the activity of genes whose products are critical in controlling numerous cellular and organismal processes, such as inflammatory and immune responses, cell growth, differentiation and survival. The aim of this study was to investigate the nuclear import mechanisms of STAT and NF-kB transcription factors. This work shows that STAT1 homodimers and STAT1/STAT2 heterodimers bind specifically and directly to importin alpha5 molecule via unconventional dimer-specific NLSs. Importin alpha molecules have two regions, which have been shown to directly interact with the amino acids in the NLS of the cargo molecule. The Arm repeats 2-4 comprise the N-terminal NLS binding site and Arm repeats 7-8 the C-terminal NLS binding site. In this work it is shown that the binding site for STAT1 homodimers and STAT1/STAT2 heterodimers is composed of Arm repeats 8 and 9 of importin alpha5 molecule. This work demonstrates that all NF-kB proteins are transported into the nucleus by importin alpha molecules. In addition, NLS was identified in RelB protein. The interactions between NF-kB proteins and importin alpha molecules were found to be directly mediated by the NLSs of NF-kB proteins. Moreover, we found that p50 binds to the N-terminal and p65 to the C-terminal NLS binding site of importin alpha3. The results from this thesis work identify previously uncharacterized mechanisms in nuclear import of STAT and NF-kB. These findings provide new insights into the molecular mechanisms regulating the signalling cascades of these important transcription factors from the cytoplasm into the nucleus to the target genes.