Metabolism of Alzheimer beta-amyloid precursor protein: regulation by protein kinase A in intact cells and in a cell-free system.

Various compounds that affect signal transduction regulate the relative utilization of alternative processing pathways for the beta-amyloid precursor protein (beta APP) in intact cells, increasing the production of nonamyloidogenic soluble beta APP (s beta APP) and decreasing that of amyloidogenic beta-amyloid peptide. In a recent study directed toward elucidating the mechanisms underlying phorbol ester-stimulated s beta APP secretion from cells, it was demonstrated that protein kinase C increases the formation from the trans-Golgi network (TGN) of beta APP-containing secretory vesicles. Here we present evidence that forskolin increases s beta APP production from intact PC12 cells, and protein kinase A stimulates formation from the TGN of beta APP-containing vesicles. Although protein kinase A and protein kinase C converge at the level of formation from the TGN of beta APP-containing vesicles, additional evidence indicates that the regulatory mechanisms involved are distinct.

Curtin-Hammett versus non-Curtin-Hammett frameworks is optimizing the enantioselective binolam/titanium(IV)-catalyzed cyanobenzoylation of aldehydes: Part 2

Extensive experimental and computational studies have been carried out on the enantioselective titanium(IV)-catalyzed cyanobenzoylation of aldehydes using 1:n Binolam:Ti(OiPr)4 mixtures as precatalysts, with the purpose of identifying the key mechanistic aspects governing enantioselectivity. HCN and isopropyl benzoate were detected in the reacting mixtures. This, as well as the reaction’s response to the presence of an exogenous base, and the failure to react in the presence of Binol:Ti(OiPr)4 mixtures, led us to propose not a direct cyanobenzoylation but an indirect process involving enantioselective hydrocyanation followed by O-benzoylation. Computational work provided positive evidence for the intervention of both indirect and direct cyanobenzoylation routes, the former being faster. However, the standard Curtin–Hammett-based optimization search ended with unsatisfactory results. Experimental and computational DFT studies (B3LYP/6-31G*) led us to conclude that: (1) the overall cyanobenzoylation of aldehydes catalyzed by 1:n Binolam:Ti(OiPr)4 mixtures involves an enantioselective hydrocyanation followed by an stereochemically inert O-benzoylation; (2) the initial complexes prevailing in a 1:1 Binolam:Ti(OiPr)4 mixture are the solvated mononuclear monomer 5·2(iPrOH) and solvated dinuclear dimer 9·2(iPrOH), whereas 9·2(iPrOH) is the major component in a 1:2 or higher 1:n mixture; (3) since the slowest step is that of benzoylation of ligated iPrOH which yields the actual catalysts 5–9, the catalytic system fits into a non-Curtin–Hammett framework, the final products deriving from a kinetic quench of the competing routes; and (4) accordingly, catalysis by 1:1 Binolam:Ti(OiPr)4 mixtures should involve cyanobenzoylations promoted by mononuclear 5, contaminated with those promoted by some dinuclear open dimer 9, whereas cyanobenzoylations catalyzed by a 1:2 and higher 1:n mixtures should be the result of catalysis promoted by the large amounts of dinuclear open dimer 9.

An introduction to alysidal algebra (IV)

Purpose – Deontical impure systems are systems whose object set is formed by an s-impure set, whose elements are perceptuales significances (relative beings) of material and/or energetic objects (absolute beings) and whose relational set is freeways of relations, formed by sheaves of relations going in two-way directions and at least one of its relations has deontical properties such as permission, prohibition, obligation and faculty. The paper aims to discuss these issues. Design/methodology/approach – Mathematical and logical development of human society ethical and normative structure. Findings – Existence of relations with positive imperative modality (obligation) would constitute the skeleton of the system. Negative imperative modality (prohibition) would be the immunological system of protection of the system. Modality permission the muscular system, that gives the necessary flexibility. Four theorems have been formulated based on Gödel's theorem demonstrating the inconsistency or incompleteness of DISs. For each constructed systemic conception can happen to it one of the two following things: either some allowed responses are not produced or else some forbidden responses are produced. Responses prohibited by the system are defined as nonwished effects. Originality/value – This paper is a continuation of the four previous papers and is developed the theory of deontical impure systems.

A VLT/FLAMES survey for massive binaries in Westerlund 1. IV. Wd1-5 – binary product and a pre-supernova companion for the magnetar CXOU J1647-45?

Context. The first soft gamma-ray repeater was discovered over three decades ago, and was subsequently identified as a magnetar, a class of highly magnetised neutron star. It has been hypothesised that these stars power some of the brightest supernovae known, and that they may form the central engines of some long duration gamma-ray bursts. However there is currently no consenus on the formation channel(s) of these objects. Aims. The presence of a magnetar in the starburst cluster Westerlund 1 implies a progenitor with a mass ≥40 M⊙, which favours its formation in a binary that was disrupted at supernova. To test this hypothesis we conducted a search for the putative pre-SN companion. Methods. This was accomplished via a radial velocity survey to identify high-velocity runaways, with subsequent non-LTE model atmosphere analysis of the resultant candidate, Wd1-5. Results. Wd1-5 closely resembles the primaries in the short-period binaries, Wd1-13 and 44, suggesting a similar evolutionary history, although it currently appears single. It is overluminous for its spectroscopic mass and we find evidence of He- and N-enrichement, O-depletion, and critically C-enrichment, a combination of properties that is difficult to explain under single star evolutionary paradigms. We infer a pre-SN history for Wd1-5 which supposes an initial close binary comprising two stars of comparable (~ 41 M⊙ + 35 M⊙) masses. Efficient mass transfer from the initially more massive component leads to the mass-gainer evolving more rapidly, initiating luminous blue variable/common envelope evolution. Reverse, wind-driven mass transfer during its subsequent WC Wolf-Rayet phase leads to the carbon pollution of Wd1-5, before a type Ibc supernova disrupts the binary system. Under the assumption of a physical association between Wd1-5 and J1647-45, the secondary is identified as the magnetar progenitor; its common envelope evolutionary phase prevents spin-down of its core prior to SN and the seed magnetic field for the magnetar forms either in this phase or during the earlier episode of mass transfer in which it was spun-up. Conclusions. Our results suggest that binarity is a key ingredient in the formation of at least a subset of magnetars by preventing spin-down via core-coupling and potentially generating a seed magnetic field. The apparent formation of a magnetar in a Type Ibc supernova is consistent with recent suggestions that superluminous Type Ibc supernovae are powered by the rapid spin-down of these objects.

Mabayi region, Burundi, 1994, Defense Mapping Agency (DMA) Series Z724, Sheet 4675-IV (Raster Image)

This layer is a georeferenced raster image of the United States Defense Mapping Agency (DMA) Series Z724, Burundi, 1:50,000 Topographic Line Map (TLM) Series sheet map entitled: Mabayi. Printed in: 1994. Covers portions of Mabayi region, Burundi. Sheet: 4675-IV. Edition statement: Ed. 1 - DMA. The image inside the map neatline is georeferenced to the surface of the earth and fit to World Geodetic System (1984) coordinates. All map collar information is also available as part of the raster image. Burundi 1:50:000 Series Z724 maps are in English and French (legends also include Rundi). Each source map in the series is printed in color at a scale of 1:50,000. Series source sheets were published in 1994-1995 by the United States Defense Mapping Agency, Hydrographic/Topographic Center. The source map was scanned and georeferenced for Harvard University's Center for Geographic Analysis' AfricaMap project by East View Cartographic. Individual TLM sheets covering Burundi (40 sheets in total) were selected from the TLM worldwide series. DMA Topographic Line Map series maps are typical topographic maps portraying both natural and manmade features. They show and name works of nature, such as mountains, valleys, lakes, rivers, vegetation, etc. They also identify the principal works of humans, such as roads, railroads, boundaries, transmission lines, major buildings, etc. Relief is shown with standard contour intervals of 20 meters, with some sheets having supplemental meter contours, form lines, hachures, shading, and/or spot heights. Depths shown by bathymetric isolines. Please pay close attention to map collar information on projections, spheroid, compilation dates, legend information, and keys to grid numbering and other numbers which appear inside the neatline.

Mutambara region, Burundi, 1994, Defense Mapping Agency (DMA) Series Z724, Sheet 4772-IV (Raster Image)

This layer is a georeferenced raster image of the United States Defense Mapping Agency (DMA) Series Z724, Burundi, 1:50,000 Topographic Line Map (TLM) Series sheet map entitled: Mutambara. Printed in: 1994. Covers portions of Mutambara region, Burundi. Sheet: 4772-IV. Edition statement: Ed. 1 - DMA. The image inside the map neatline is georeferenced to the surface of the earth and fit to World Geodetic System (1984) coordinates. All map collar information is also available as part of the raster image. Burundi 1:50:000 Series Z724 maps are in English and French (legends also include Rundi). Each source map in the series is printed in color at a scale of 1:50,000. Series source sheets were published in 1994-1995 by the United States Defense Mapping Agency, Hydrographic/Topographic Center. The source map was scanned and georeferenced for Harvard University's Center for Geographic Analysis' AfricaMap project by East View Cartographic. Individual TLM sheets covering Burundi (40 sheets in total) were selected from the TLM worldwide series. DMA Topographic Line Map series maps are typical topographic maps portraying both natural and manmade features. They show and name works of nature, such as mountains, valleys, lakes, rivers, vegetation, etc. They also identify the principal works of humans, such as roads, railroads, boundaries, transmission lines, major buildings, etc. Relief is shown with standard contour intervals of 20 meters, with some sheets having supplemental meter contours, form lines, hachures, shading, and/or spot heights. Depths shown by bathymetric isolines. Please pay close attention to map collar information on projections, spheroid, compilation dates, legend information, and keys to grid numbering and other numbers which appear inside the neatline.

Mwaro region, Burundi, 1994, Defense Mapping Agency (DMA) Series Z724, Sheet 4773-IV (Raster Image)

This layer is a georeferenced raster image of the United States Defense Mapping Agency (DMA) Series Z724, Burundi, 1:50,000 Topographic Line Map (TLM) Series sheet map entitled: Mwaro. Printed in: 1994. Covers portions of Mwaro region, Burundi. Sheet: 4773-IV. Edition statement: Ed. 1 - DMA. The image inside the map neatline is georeferenced to the surface of the earth and fit to World Geodetic System (1984) coordinates. All map collar information is also available as part of the raster image. Burundi 1:50:000 Series Z724 maps are in English and French (legends also include Rundi). Each source map in the series is printed in color at a scale of 1:50,000. Series source sheets were published in 1994-1995 by the United States Defense Mapping Agency, Hydrographic/Topographic Center. The source map was scanned and georeferenced for Harvard University's Center for Geographic Analysis' AfricaMap project by East View Cartographic. Individual TLM sheets covering Burundi (40 sheets in total) were selected from the TLM worldwide series. DMA Topographic Line Map series maps are typical topographic maps portraying both natural and manmade features. They show and name works of nature, such as mountains, valleys, lakes, rivers, vegetation, etc. They also identify the principal works of humans, such as roads, railroads, boundaries, transmission lines, major buildings, etc. Relief is shown with standard contour intervals of 20 meters, with some sheets having supplemental meter contours, form lines, hachures, shading, and/or spot heights. Depths shown by bathymetric isolines. Please pay close attention to map collar information on projections, spheroid, compilation dates, legend information, and keys to grid numbering and other numbers which appear inside the neatline.

Bukeye region, Burundi, 1994, Defense Mapping Agency (DMA) Series Z724, Sheet 4774-IV (Raster Image)

This layer is a georeferenced raster image of the United States Defense Mapping Agency (DMA) Series Z724, Burundi, 1:50,000 Topographic Line Map (TLM) Series sheet map entitled: Bukeye. Printed in: 1994. Covers portions of Bukeye region, Burundi. Sheet: 4774-IV. Edition statement: Ed. 1 - DMA. The image inside the map neatline is georeferenced to the surface of the earth and fit to World Geodetic System (1984) coordinates. All map collar information is also available as part of the raster image. Burundi 1:50:000 Series Z724 maps are in English and French (legends also include Rundi). Each source map in the series is printed in color at a scale of 1:50,000. Series source sheets were published in 1994-1995 by the United States Defense Mapping Agency, Hydrographic/Topographic Center. The source map was scanned and georeferenced for Harvard University's Center for Geographic Analysis' AfricaMap project by East View Cartographic. Individual TLM sheets covering Burundi (40 sheets in total) were selected from the TLM worldwide series. DMA Topographic Line Map series maps are typical topographic maps portraying both natural and manmade features. They show and name works of nature, such as mountains, valleys, lakes, rivers, vegetation, etc. They also identify the principal works of humans, such as roads, railroads, boundaries, transmission lines, major buildings, etc. Relief is shown with standard contour intervals of 20 meters, with some sheets having supplemental meter contours, form lines, hachures, shading, and/or spot heights. Depths shown by bathymetric isolines. Please pay close attention to map collar information on projections, spheroid, compilation dates, legend information, and keys to grid numbering and other numbers which appear inside the neatline.

Gihofi region, Burundi, 1994, Defense Mapping Agency (DMA) Series Z724, Sheet 4872-IV (Raster Image)

This layer is a georeferenced raster image of the United States Defense Mapping Agency (DMA) Series Z724, Burundi, 1:50,000 Topographic Line Map (TLM) Series sheet map entitled: Gihofi. Printed in: 1994. Covers portions of Gihofi region, Burundi. Sheet: 4872-IV. Edition statement: Ed. 1 - DMA. The image inside the map neatline is georeferenced to the surface of the earth and fit to World Geodetic System (1984) coordinates. All map collar information is also available as part of the raster image. Burundi 1:50:000 Series Z724 maps are in English and French (legends also include Rundi). Each source map in the series is printed in color at a scale of 1:50,000. Series source sheets were published in 1994-1995 by the United States Defense Mapping Agency, Hydrographic/Topographic Center. The source map was scanned and georeferenced for Harvard University's Center for Geographic Analysis' AfricaMap project by East View Cartographic. Individual TLM sheets covering Burundi (40 sheets in total) were selected from the TLM worldwide series. DMA Topographic Line Map series maps are typical topographic maps portraying both natural and manmade features. They show and name works of nature, such as mountains, valleys, lakes, rivers, vegetation, etc. They also identify the principal works of humans, such as roads, railroads, boundaries, transmission lines, major buildings, etc. Relief is shown with standard contour intervals of 20 meters, with some sheets having supplemental meter contours, form lines, hachures, shading, and/or spot heights. Depths shown by bathymetric isolines. Please pay close attention to map collar information on projections, spheroid, compilation dates, legend information, and keys to grid numbering and other numbers which appear inside the neatline.

Musongati region, Burundi, 1994, Defense Mapping Agency (DMA) Series Z724, Sheet 4873-IV (Raster Image)

This layer is a georeferenced raster image of the United States Defense Mapping Agency (DMA) Series Z724, Burundi, 1:50,000 Topographic Line Map (TLM) Series sheet map entitled: Musongati. Printed in: 1994. Covers portions of Musongati region, Burundi. Sheet: 4873-IV. Edition statement: Ed. 1 - DMA. The image inside the map neatline is georeferenced to the surface of the earth and fit to World Geodetic System (1984) coordinates. All map collar information is also available as part of the raster image. Burundi 1:50:000 Series Z724 maps are in English and French (legends also include Rundi). Each source map in the series is printed in color at a scale of 1:50,000. Series source sheets were published in 1994-1995 by the United States Defense Mapping Agency, Hydrographic/Topographic Center. The source map was scanned and georeferenced for Harvard University's Center for Geographic Analysis' AfricaMap project by East View Cartographic. Individual TLM sheets covering Burundi (40 sheets in total) were selected from the TLM worldwide series. DMA Topographic Line Map series maps are typical topographic maps portraying both natural and manmade features. They show and name works of nature, such as mountains, valleys, lakes, rivers, vegetation, etc. They also identify the principal works of humans, such as roads, railroads, boundaries, transmission lines, major buildings, etc. Relief is shown with standard contour intervals of 20 meters, with some sheets having supplemental meter contours, form lines, hachures, shading, and/or spot heights. Depths shown by bathymetric isolines. Please pay close attention to map collar information on projections, spheroid, compilation dates, legend information, and keys to grid numbering and other numbers which appear inside the neatline.

Karuzi region, Burundi, 1994, Defense Mapping Agency (DMA) Series Z724, Sheet 4874-IV (Raster Image)

This layer is a georeferenced raster image of the United States Defense Mapping Agency (DMA) Series Z724, Burundi, 1:50,000 Topographic Line Map (TLM) Series sheet map entitled: Karuzi. Printed in: 1994. Covers portions of Karuzi region, Burundi. Sheet: 4874-IV. Edition statement: Ed. 1 - DMA. The image inside the map neatline is georeferenced to the surface of the earth and fit to World Geodetic System (1984) coordinates. All map collar information is also available as part of the raster image. Burundi 1:50:000 Series Z724 maps are in English and French (legends also include Rundi). Each source map in the series is printed in color at a scale of 1:50,000. Series source sheets were published in 1994-1995 by the United States Defense Mapping Agency, Hydrographic/Topographic Center. The source map was scanned and georeferenced for Harvard University's Center for Geographic Analysis' AfricaMap project by East View Cartographic. Individual TLM sheets covering Burundi (40 sheets in total) were selected from the TLM worldwide series. DMA Topographic Line Map series maps are typical topographic maps portraying both natural and manmade features. They show and name works of nature, such as mountains, valleys, lakes, rivers, vegetation, etc. They also identify the principal works of humans, such as roads, railroads, boundaries, transmission lines, major buildings, etc. Relief is shown with standard contour intervals of 20 meters, with some sheets having supplemental meter contours, form lines, hachures, shading, and/or spot heights. Depths shown by bathymetric isolines. Please pay close attention to map collar information on projections, spheroid, compilation dates, legend information, and keys to grid numbering and other numbers which appear inside the neatline.

Cankuzo region, Burundi, 1994, Defense Mapping Agency (DMA) Series Z724, Sheet 4974-IV (Raster Image)

This layer is a georeferenced raster image of the United States Defense Mapping Agency (DMA) Series Z724, Burundi, 1:50,000 Topographic Line Map (TLM) Series sheet map entitled: Cankuzo. Printed in: 1994. Covers portions of Cankuzo region, Burundi. Sheet: 4974-IV. Edition statement: Ed. 1 - DMA. The image inside the map neatline is georeferenced to the surface of the earth and fit to World Geodetic System (1984) coordinates. All map collar information is also available as part of the raster image. Burundi 1:50:000 Series Z724 maps are in English and French (legends also include Rundi). Each source map in the series is printed in color at a scale of 1:50,000. Series source sheets were published in 1994-1995 by the United States Defense Mapping Agency, Hydrographic/Topographic Center. The source map was scanned and georeferenced for Harvard University's Center for Geographic Analysis' AfricaMap project by East View Cartographic. Individual TLM sheets covering Burundi (40 sheets in total) were selected from the TLM worldwide series. DMA Topographic Line Map series maps are typical topographic maps portraying both natural and manmade features. They show and name works of nature, such as mountains, valleys, lakes, rivers, vegetation, etc. They also identify the principal works of humans, such as roads, railroads, boundaries, transmission lines, major buildings, etc. Relief is shown with standard contour intervals of 20 meters, with some sheets having supplemental meter contours, form lines, hachures, shading, and/or spot heights. Depths shown by bathymetric isolines. Please pay close attention to map collar information on projections, spheroid, compilation dates, legend information, and keys to grid numbering and other numbers which appear inside the neatline.

Kirundo region, Burundi, 1994, Defense Mapping Agency (DMA) Series Z724, Sheet 4875-IV (Raster Image)

This layer is a georeferenced raster image of the United States Defense Mapping Agency (DMA) Series Z724, Burundi, 1:50,000 Topographic Line Map (TLM) Series sheet map entitled: Kirundo. Printed in: 1994. Covers portions of Kirundo region, Burundi. Sheet: 4875-IV. Edition statement: Ed. 1 - DMA. The image inside the map neatline is georeferenced to the surface of the earth and fit to World Geodetic System (1984) coordinates. All map collar information is also available as part of the raster image. Burundi 1:50:000 Series Z724 maps are in English and French (legends also include Rundi). Each source map in the series is printed in color at a scale of 1:50,000. Series source sheets were published in 1994-1995 by the United States Defense Mapping Agency, Hydrographic/Topographic Center. The source map was scanned and georeferenced for Harvard University's Center for Geographic Analysis' AfricaMap project by East View Cartographic. Individual TLM sheets covering Burundi (40 sheets in total) were selected from the TLM worldwide series. DMA Topographic Line Map series maps are typical topographic maps portraying both natural and manmade features. They show and name works of nature, such as mountains, valleys, lakes, rivers, vegetation, etc. They also identify the principal works of humans, such as roads, railroads, boundaries, transmission lines, major buildings, etc. Relief is shown with standard contour intervals of 20 meters, with some sheets having supplemental meter contours, form lines, hachures, shading, and/or spot heights. Depths shown by bathymetric isolines. Please pay close attention to map collar information on projections, spheroid, compilation dates, legend information, and keys to grid numbering and other numbers which appear inside the neatline.

Novel particulate BCG-loaded delivery system for mucosal immunization against tuberculosis

Tese de doutoramento, Farmácia (Tecnologia Farmacêutica), Universidade de Lisboa, Faculdade de Farmácia, 2016