Activation of muscarinic acetylcholine receptors via their allosteric binding sites.

Ligands that bind to the allosteric-binding sites on muscarinic acetylcholine receptors alter the conformation of the classical-binding sites of these receptors and either diminish or increase their affinity for muscarinic agonists and classical antagonists. It is not known whether the resulting conformational change also affects the interaction between the receptors and the G proteins. We have now found that the muscarinic receptor allosteric modulators alcuronium, gallamine, and strychnine (acting in the absence of an agonist) alter the synthesis of cAMP in Chinese hamster ovary (CHO) cells expressing the M2 or the M4 subtype of muscarinic receptors in the same direction as the agonist carbachol. In addition, most of their effects on the production of inositol phosphates in CHO cells expressing the M1 or the M3 muscarinic receptor subtypes are also similar to (although much weaker than) those of carbachol. The agonist-like effects of the allosteric modulators are not observed in CHO cells that have not been transfected with the gene for any of the subtypes of muscarinic receptors. The effects of alcuronium on the formation of cAMP and inositol phosphates are not prevented by the classical muscarinic antagonist quinuclidinyl benzilate. These observations demonstrate for the first time that the G protein-mediated functional responses of muscarinic receptors can be evoked not only from their classical, but also from their allosteric, binding sites. This represents a new mechanism of receptor activation.

Progress toward chemical accuracy in the computer simulation of condensed phase reactions.

We describe a procedure for the generation of chemically accurate computer-simulation models to study chemical reactions in the condensed phase. The process involves (i) the use of a coupled semiempirical quantum and classical molecular mechanics method to represent solutes and solvent, respectively; (ii) the optimization of semiempirical quantum mechanics (QM) parameters to produce a computationally efficient and chemically accurate QM model; (iii) the calibration of a quantum/classical microsolvation model using ab initio quantum theory; and (iv) the use of statistical mechanical principles and methods to simulate, on massively parallel computers, the thermodynamic properties of chemical reactions in aqueous solution. The utility of this process is demonstrated by the calculation of the enthalpy of reaction in vacuum and free energy change in aqueous solution for a proton transfer involving methanol, methoxide, imidazole, and imidazolium, which are functional groups involved with proton transfers in many biochemical systems. An optimized semiempirical QM model is produced, which results in the calculation of heats of formation of the above chemical species to within 1.0 kcal/mol (1 kcal = 4.18 kJ) of experimental values. The use of the calibrated QM and microsolvation QM/MM (molecular mechanics) models for the simulation of a proton transfer in aqueous solution gives a calculated free energy that is within 1.0 kcal/mol (12.2 calculated vs. 12.8 experimental) of a value estimated from experimental pKa values of the reacting species.

Efeito da suplementação com óleo de canola sobre a qualidade da manteiga e muçarela

A sociedade está cada vez mais exigente com relação à qualidade dos produtos consumidos e se preocupa com os benefícios para a saúde. Neste contexto, objetivou-se avaliar o efeito da inclusão de níveis de óleo de canola na dieta de vacas sobre amanteiga e muçarela, buscando produtos mais saudáveis para o consumo humano. Foram utilizadas 18 vacas Holandesas, em estágio intermediário de lactação, com produção média de 22 (± 4) Kg de leite/ dia, as quais foram distribuídas em dois quadrados latinos 3x3 contemporâneos e receberam as dietas experimentais: T1- Controle (0% de inclusão de óleo); T2- 3% de inclusão de óleo de canola e T3- 6% de inclusão de óleo de canola. O perfil lipídico foi determinado através de cromatografia gasosa, além da avaliação de qualidade nutricional, realizada através de equações utilizando os ácidos graxos obtidos no perfil lipídico, análises físico-químicas determinadas pela metodologia do Instituto Adolfo Lutz e análises microbiológicas. Houveram problemas durante processamento do leite, gerando alterações de tecnologia de fabricação do produto manteiga, obtendo-se outro produto, o creme de leite, ao invés de manteiga, além de prejuízos na qualidade microbiológicas do creme de leite e muçarela. A inclusão de óleo de canola na dieta em lactação reduziu quadraticamente os ácidos graxos de cadeia curta e proporcionou aumento quadrático dos ácidos graxos de cadeia longa, dos ácidos graxos insaturados e ácidos graxos monoinsaturados na muçarela. A relação ácidos graxos saturados/ ácidos graxos insaturados (AGS/ AGI) e a relação ômega-6/ômega-3, assim como os índices de aterogenicidade e trombogenicidade, na muçarela, reduziram linearmente 25,68%, 31,35%; 32,12% e 21,78%, respectivamente, quando comparando T1 e T3. No creme de leite, houve redução linear dos ácidos graxos de cadeia curta e média, bem como, os ácidos graxos saturados e a relação ácidos graxos saturados/ ácidos graxos insaturados (AGS/ AGI) em 41,07%; 23,82%; 15,91% e 35,59%, respectivamente, enquanto os ácidos graxos de cadeia longa, ácidos graxos insaturados e ácidos graxos monoinsaturados aumentaram linearmente 41,40%; 28,24% e 32,07%, nesta ordem, quando comparando T1 com T3. Os índices de aterogenicidade e trombogenicidade reduziram de forma linear, enquanto o índice h/H (razão ácidos graxos hipocolesterolêmicos e hipercolesterolêmicos) aumentou linearmente. A composição físico-química de ambos derivados e o rendimento da muçarela não apresentaram efeito significativo com a inclusão do óleo de canola, exceto a proteína bruta da muçarela que apresentou aumento linear e a gordura do creme de leite que apresentou efeito quadrático. As análises microbiológicas mostram contagens muito elevadas de microrganismos, sugerindo que os produtos não apresentam qualidade microbiológica, decorrente da ausência do processo de pasteurização do creme e da baixa eficiência do tratamento térmico aplicado ao leite destinado a produção da muçarela. Conclui-se que a adição de óleo de canola na dieta de vacas lactantes proporciona muçarela e creme de leite mais saudáveis para o consumo humano, pois apresentaram perfil lipídico mais rico em ácidos graxos insaturados, além da série ômega-3 e ácido oleico, entretanto, devido a problemas de processamento, estes produtos obtidos, não estão aptos ao consumo devido à ausência de qualidade microbiológica.

Principales puntos de convergencia entre las escuelas hegemónicas de teoría económica y sociológica desde la Ilustración escocesa hasta nuestros días

This research aims to show the main points of convergence between hegemonic schools of economic and sociological theory from the Scottish Enlightenment until today. To this end, on the one hand, we set three basic families of economic thought (the mainstream, the Austrian school and Marxism); and, on the other, we divide the history of sociology in five major generations (pioneers, founders, institutionalizers, compilers and constructivist). Subsequently, we set five historical periods as reference to our respective chapters and compare, within each of them, the theoretical contributions from these two areas. Thus, in the first chapter, called "the liberal parenthesis", we consider the relationship between the classical school of economics and the pioneers and founders of sociology. In the second, entitled "the social question" we analyze, on the one hand, the theoretical consistency of both the neoclassical school, as Austrian, with the principles defended by the institutionalizers of sociology; and, on the other, the influence of Karl Marx, as founder of sociology and classical economist, in the work of Soviet revolutionary theorists. In chapter three, called the "new industrial state", we demonstrate the theoretical proximity between both Keynesianism and the Austrian school of economics, with the doctrine defended by the generation of compilers in sociology. The fourth chapter, entitled "second industrial divide", refers to the similarities between the theoretical contributions of the monetarist Chicago school and the Austrian school with sociological constructivism. Finally, chapter five, the "global market", shows that the two hegemonic schools in economics, "integrated model", and sociology, "analytical sociology", are composed of the same three schools of thought: the rational choice, the neo-institutionalism and network approach. Thus, we can conclude that, if we look at their respective areas of influence, during this historical period occurs an manifest agreement between the theoretical contributions from the economic and sociological fields.

Condensados de Bose-Einstein em redes óticas: a transição superfluido-isolante de Mott em redes hexagonais e a classe de universalidade superfluido-vidro de Bose em 3D

Estudamos transições de fases quânticas em gases bosônicos ultrafrios aprisionados em redes óticas. A física desses sistemas é capturada por um modelo do tipo Bose-Hubbard que, no caso de um sistema sem desordem, em que os átomos têm interação de curto alcance e o tunelamento é apenas entre sítios primeiros vizinhos, prevê a transição de fases quântica superfluido-isolante de Mott (SF-MI) quando a profundidade do potencial da rede ótica é variado. Num primeiro estudo, verificamos como o diagrama de fases dessa transição muda quando passamos de uma rede quadrada para uma hexagonal. Num segundo, investigamos como a desordem modifica essa transição. No estudo com rede hexagonal, apresentamos o diagrama de fases da transição SF-MI e uma estimativa para o ponto crítico do primeiro lobo de Mott. Esses resultados foram obtidos usando o algoritmo de Monte Carlo quântico denominado Worm. Comparamos nossos resultados com os obtidos a partir de uma aproximação de campo médio e com os de um sistema com uma rede ótica quadrada. Ao introduzir desordem no sistema, uma nova fase emerge no diagrama de fases do estado fundamental intermediando a fase superfluida e a isolante de Mott. Essa nova fase é conhecida como vidro de Bose (BG) e a transição de fases quântica SF-BG que ocorre nesse sistema gerou muitas controvérsias desde seus primeiros estudos iniciados no fim dos anos 80. Apesar dos avanços em direção ao entendimento completo desta transição, a caracterização básica das suas propriedades críticas ainda é debatida. O que motivou nosso estudo, foi a publicação de resultados experimentais e numéricos em sistemas tridimensionais [Yu et al. Nature 489, 379 (2012), Yu et al. PRB 86, 134421 (2012)] que violam a lei de escala $\\phi= u z$, em que $\\phi$ é o expoente da temperatura crítica, $z$ é o expoente crítico dinâmico e $ u$ é o expoente do comprimento de correlação. Abordamos essa controvérsia numericamente fazendo uma análise de escalonamento finito usando o algoritmo Worm nas suas versões quântica e clássica. Nossos resultados demonstram que trabalhos anteriores sobre a dependência da temperatura de transição superfluido-líquido normal com o potencial químico (ou campo magnético, em sistemas de spin), $T_c \\propto (\\mu-\\mu_c)^\\phi$, estavam equivocados na interpretação de um comportamento transiente na aproximação da região crítica genuína. Quando os parâmetros do modelo são modificados de maneira a ampliar a região crítica quântica, simulações com ambos os modelos clássico e quântico revelam que a lei de escala $\\phi= u z$ [com $\\phi=2.7(2)$, $z=3$ e $ u = 0.88(5)$] é válida. Também estimamos o expoente crítico do parâmetro de ordem, encontrando $\\beta=1.5(2)$.

Notebook, 1710-1711

Paper notebook with the handwritten notes written in both Latin and English.

Notes : manuscript, [16---17--]

Notes on and excerpts of materials used by Harvard undergraduates in the 17th and early 18th cent.; including Prolegomena de arte in genere; William Brattle's A compendium of logick; Alexander Richardson's In dialecticam brevis commentatio; Grammatica hebraea; and other works.

Theses of 1663

Handwritten document written in Latin and dated August 1663 purported to be the Harvard College Commencement Theses of 1663, but considered by John Noble of the Colonial Society of Massachusetts to be a contemporary parody. Noble notes of the 1663 Theses, that "there seems to be no reason to doubt that this is a genuine, original manuscript of the date which it bears," but describes it as a "blaze of literary and scholastic pyrotechnics" that suggests it was created satirically (John Noble, "Harvard Theses of 1663" in the Publications of the Colonial Society, Volume V: Transactions, April 1898, pages 322-339).

Delft, Netherlands, ca. 1695 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Delfi Batavorum vernacule Delft, F. de Wit excudit. It was published ca. 1695. Scale [ca. 1:3,800]. Covers a portion of Delft, Netherlands. Map in Latin and Dutch. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Dutch National Grid: RD (Rijksdriehoekstelsel) GCS Amersfoort (Bessel 1841) coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, drainage, built-up areas and selected buildings, fortifications, ground cover, and more. Includes also index.This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of originators, ground condition dates, scales, and map purposes.

Dordrecht, Netherlands, ca. 1695 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Dordracum vulgo Dortt, F. de Wit excudit. It was published ca. 1695. Scale [ca. 1:4,830]. Covers a portion of Dordrecht, Netherlands. Map in Latin and Dutch.The image inside the map neatline is georeferenced to the surface of the earth and fit to the Dutch National Grid: RD (Rijksdriehoekstelsel) GCS Amersfoort (Bessel 1841) coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, drainage, built-up areas and selected buildings, fortifications, ground cover, and more. Includes also index.This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of originators, ground condition dates, scales, and map purposes.

Haarlem, Netherlands, ca. 1695 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Harlemum vulgo Haerlem, F. de Wit excudit. It was published ca. 1695. Scale [ca. 1:3,862]. Covers a portion of Haarlem, Netherlands. Map in Latin and Dutch. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Dutch National Grid: RD (Rijksdriehoekstelsel) GCS Amersfoort (Bessel 1841) coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, drainage, built-up areas and selected buildings, fortifications, canals, ground cover, and more. Includes also index.This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of originators, ground condition dates, scales, and map purposes.

Leiden, Netherlands, ca. 1695 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Lugduni Batavorum vulgo Leyden sic ultimo amplificati delineatio, F. de Wit excudit. It was published ca. 1695. Scale [ca. 1:3,490]. Covers a portion of Leiden, Netherlands. Map in Latin and Dutch.The image inside the map neatline is georeferenced to the surface of the earth and fit to the Dutch National Grid: RD (Rijksdriehoekstelsel) GCS Amersfoort (Bessel 1841) coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, drainage, built-up areas and selected buildings, fortifications, canals, ground cover, and more. Includes also index.This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of originators, ground condition dates, scales, and map purposes.

Switzerland, ca. 1715 (Image 1 of 4) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Nova Helvetiae tabula geographica : illustrissimis et potentissimis cantonibus et rebuspublicis reformatae religionis Tigurinae, Bernensi, Glaronensi, Basiliensi, Scaphusianae, Abbatis Cellanae, dominis suis clementissimis humillime [de]dicata a Ioh. Iacobo Scheuchzero Tigurino med. d. math. prof. It was published by ex officin â Petri Schenkii, in platea vulgo de Warmoesstraat sub signo N. Visschers Athlas ca. 1715. Covers Switzerland. Scale [ca. 1:378,000]. This layer is image 1 of 4 total images of the four sheet source map, representing the northwest portion of the map. Map in Latin and Dutch.The image inside the map neatline is georeferenced to the surface of the earth and fit to the Europe Lambert Conformal Conic coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as drainage, cities and other human settlements, territorial and administrative boundaries, roads, and more. Relief shown pictorially. Includes also illustrations. This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of originators, ground condition dates, scales, and map purposes.

Switzerland, ca. 1715 (Image 2 of 4) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Nova Helvetiae tabula geographica : illustrissimis et potentissimis cantonibus et rebuspublicis reformatae religionis Tigurinae, Bernensi, Glaronensi, Basiliensi, Scaphusianae, Abbatis Cellanae, dominis suis clementissimis humillime [de]dicata a Ioh. Iacobo Scheuchzero Tigurino med. d. math. prof. It was published by ex officin â Petri Schenkii, in platea vulgo de Warmoesstraat sub signo N. Visschers Athlas ca. 1715. Covers Switzerland. Scale [ca. 1:378,000]. This layer is image 2 of 4 total images of the four sheet source map, representing the southwest portion of the map. Map in Latin and Dutch.The image inside the map neatline is georeferenced to the surface of the earth and fit to the Europe Lambert Conformal Conic coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as drainage, cities and other human settlements, territorial and administrative boundaries, roads, and more. Relief shown pictorially. Includes also illustrations. This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of originators, ground condition dates, scales, and map purposes.

Switzerland, ca. 1715 (Image 3 of 4) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Nova Helvetiae tabula geographica : illustrissimis et potentissimis cantonibus et rebuspublicis reformatae religionis Tigurinae, Bernensi, Glaronensi, Basiliensi, Scaphusianae, Abbatis Cellanae, dominis suis clementissimis humillime [de]dicata a Ioh. Iacobo Scheuchzero Tigurino med. d. math. prof. It was published by ex officin â Petri Schenkii, in platea vulgo de Warmoesstraat sub signo N. Visschers Athlas ca. 1715. Covers Switzerland. Scale [ca. 1:378,000]. This layer is image 3 of 4 total images of the four sheet source map, representing the northeast portion of the map. Map in Latin and Dutch.The image inside the map neatline is georeferenced to the surface of the earth and fit to the Europe Lambert Conformal Conic coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as drainage, cities and other human settlements, territorial and administrative boundaries, roads, and more. Relief shown pictorially. Includes also illustrations. This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of originators, ground condition dates, scales, and map purposes.