The Use of Patents to Assess National Innovation Systems: Evidences from Spanish Biotechnology

Spain’s economy recorded a high rate of growth from the mid-1990s onwards. At the same time, the resources allocated to Research and Development (R&D) grew at a much faster pace than in other European Union (EU) countries. Spain’s growth recorded an average rate of 2.93% from the early 1990s to 2004. Over the same period, the average growth in the EU was 0.46%. This circumstance, together with several sound policy decisions implemented between 2004 and 2009, ushered in a “golden age of Spanish biotechnology”. In terms of the national patent licenses issued by the Spanish Patent and Trademark Office (SPTO) between 2004 and 2009, the number in biotechnology grew from 84 to 151. However, the current economic situation in Spain, along with a series of political decisions taken over the past two or three years to cut spending on R&D, predicts a sharp downturn in the performance of Spanish biotechnology. This scenario makes Spain one of the best places to study the successes and failures of the management of science and allows transfer this experience to the other international regions. We need to analyze the influence of political decisions as a major factor with a bearing on the quality of science. Using patents as an indicator of scientific development, this paper analyzes the evolution of the biotechnology sector in Spain and its relationship with scientific policy and the management of R&D.

SONIA REGINA PRADO

A dissertação teve como objetivo principal estudar como uma Instituição de Ensino Superior Privada (IES) atuante no Brasil tem crescido pós Lei de Diretrizes e Bases (LDB) de 1996 até 2015, por meio da análise do curso de bacharelado em Administração de Empresas, nas modalidades: presencial, EAD e Flex (semipresencial). Para este fim, foi realizada uma pesquisa exploratória, de caráter qualitativo baseada no método do estudo de caso. Para coleta de evidências foram analisados relatórios corporativos (Annual Report, Relatórios Internos e outros documentos), entrevistas baseadas em roteiro semiestruturado com gestores da IES privada e observações. Dentre os principais achados, verificou-se que as principais estratégicas de crescimento da IES privada estudada se basearam em fusões e aquisições de outras IES, abertura de novos polos de EAD, na abertura de novas unidades próprias, bem como em inovações em várias dimensões da organização. Os programas governamentais de financiamento aos alunos também são fortes contribuintes para este crescimento, como o Fundo de Financiamento ao Estudante do Ensino Superior (FIES) e o Programa Universidade para Todos (Prouni). Com essa nova realidade, o ensino superior privado recebeu incentivo e facilitação para o seu crescimento, a um ritmo acelerado. Consequentemente pode-se concluir que a IES privada estudada adotou as seguintes estratégias de crescimento: Expansão orgânica com fusões/ aquisições de Instituições menores, com desenvolvimento de planos para todos os campi Brasil; Greenfield (por meio de solicitação de autorização de novas unidades e/ou cursos) em cidades sem possibilidades de aquisições/fusões, e aumentando o número de vagas/ matriculas nas unidades já existentes, aderiu aos programas do governo e também cuidou da evasão por meio de: Seguro educacional; gestão preparada para atender necessidades do discente; Sistema de Ensino com currículos integrados nacionalmente; Intercâmbio de alunos e professores entre as diversas unidades em todas as regiões do país e padronização dos processos.

Characterization of a genetically engineered inactivation-resistant coagulation factor VIIIa

Individuals with hemophilia A require frequent infusion of preparations of coagulation factor VIII. The activity of factor VIII (FVIII) as a cofactor for factor IXa in the coagulation cascade is limited by its instability after activation by thrombin. Activation of FVIII occurs through proteolytic cleavage and generates an unstable FVIII heterotrimer that is subject to rapid dissociation of its subunits. In addition, further proteolytic cleavage by thrombin, factor Xa, factor IXa, and activated protein C can lead to inactivation. We have engineered and characterized a FVIII protein, IR8, that has enhanced in vitro stability of FVIII activity due to resistance to subunit dissociation and proteolytic inactivation. FVIII was genetically engineered by deletion of residues 794-1689 so that the A2 domain is covalently attached to the light chain. Missense mutations at thrombin and activated protein C inactivation cleavage sites provided resistance to proteolysis, resulting in a single-chain protein that has maximal activity after a single cleavage after arginine-372. The specific activity of partially purified protein produced in transfected COS-1 monkey cells was 5-fold higher than wild-type (WT) FVIII. Whereas WT FVIII was inactivated by thrombin after 10 min in vitro, IR8 still retained 38% of peak activity after 4 hr. Whereas binding of IR8 to von Willebrand factor (vWF) was reduced 10-fold compared with WT FVIII, in the presence of an anti-light chain antibody, ESH8, binding of IR8 to vWF increased 5-fold. These results demonstrate that residues 1690–2332 of FVIII are sufficient to support high-affinity vWF binding. Whereas ESH8 inhibited WT factor VIII activity, IR8 retained its activity in the presence of ESH8. We propose that resistance to A2 subunit dissociation abrogates inhibition by the ESH8 antibody. The stable FVIIIa described here provides the opportunity to study the activated form of this critical coagulation factor and demonstrates that proteins can be improved by rationale design through genetic engineering technology.

Helix packing of lactose permease in Escherichia coli studied by site-directed chemical cleavage.

Biotinylated lactose permease from Escherichia coli containing a single-cysteine residue at position 330 (helix X) or at position 147, 148, or 149 (helix V) was purified by avidin-affinity chromatography and derivatized with 5-(alpha-bromoacetamido)-1,10-phenanthroline-copper [OP(Cu)]. Studies with purified, OP(Cu)-labeled Leu-330 --> Cys permease in dodecyl-beta-D-maltopyranoside demonstrate that after incubation in the presence of ascorbate, cleavage products of approximately 19 and 6-8 kDa are observed on immunoblots with anti-C-terminal antibody. Remarkably, the same cleavage products are observed with permease embedded in the native membrane. Comparison with the C-terminal half of the permease expressed independently as a standard indicates that the 19-kDa product results from cleavage near the cytoplasmic end of helix VII, whereas the 6- to 8-kDa fragment probably results from fragmentation near the cytoplasmic end of helix XI. Results are entirely consistent with a tertiary-structure model of the C-terminal half of the permease derived from earlier site-directed fluorescence and site-directed mutagenesis studies. Similar studies with OP(Cu)-labeled Cys-148 permease exhibit cleavage products at approximately 19 kDa and at 15-16 kDa. The larger fragment probably reflects cleavage at a site near the cytoplasmic end of helix VII, whereas the 15- to 16-kDa fragment is consistent with cleavage near the cytoplasmic end of helix VIII. When OP(Cu) is moved 100 degrees to position 149 (Val-149 --> Cys permease), a single product is observed at 19 kDa, suggesting fragmentation at the cytoplasmic end of helix VII. However, when the reagent is moved 100 degrees in the other direction to position 147 (Gly-147 --> Cys permease), cleavage is not observed. The results suggest that helix V is in close proximity to helices VII and VIII with position 148 in the interface between the helices, position 149 facing helix VII, and position 147 facing the lipid bilayer.

The report of the committee about Harvard Coledge: presented to the Generall Court held the 3 of (3) month, 1654

Two folio-sized leaves with a handwritten draft of the May 3, 1654 report of a General Court Committee authorized to investigate the financial state of Harvard College. The report responds directly to eight questions raised in the September 10, 1653 Order of the General Court that established the Committee. The report provides summaries of Harvard's income sources and disbursements, offers recommendations regarding the President's salary and the allowances for the academic Fellows, steward, butler, and cook, and indicates specific contributions from local towns.

Student notebook of James Varney, 1721-1725

The bound notebook contains academic texts copied by Harvard student James Varney in the early 1720s. The texts are written tête-bêche (where both ends of the volume are used to begin writing). The front paste-down endpaper reads 'James Varney his book 1724,' and the rear paste-down endpaper reads 'Joseph Lovett' [AB 1728].

Mathematical notebook, and commonplace book, circa 1689-1769

Manuscript notebook, possibly kept by Harvard students, containing 17th century English transcriptions of arithmetic and geometry texts, one of which is dated 1689-1690; 18th century transcriptions from John Ward’s “The Young Mathematician’s Guide”; and notes on physics lectures delivered by John Winthrop, the Hollis Professor of Mathematics and Natural Philosophy at Harvard from 1738 to 1779. The notebook also contains 18th century reading notes on Henry VIII, Tudor succession, and English history from Daniel Neal’s “The History of the Puritans” and David Hume’s “History of England,” and notes on Ancient history, taken mainly from Charles Rollin’s “The Ancient History of the Egyptians, Carthaginians, Assyrians, Babylonians, Medes and Persians, Macedonians and Grecians.” Additionally included are an excerpt from Plutarch’s “Lives” and transcriptions of three articles from “The Gentleman’s Magazine, and Historical Chronicle,” published in 1769: “A Critique on the Works of Ovid”; a book review of “A New Voyage to the West-Indies”; and “Genuine Anecdotes of Celebrated Writers, &.” The flyleaf contains the inscription “Semper boni aliquid operis facito ut diabolus te semper inveniat occupatum,” a variation on a quote of Saint Jerome that translates approximately as “Always good to do some work so that the devil may always find you occupied.” In the seventeenth and eighteenth centuries, Harvard College undergraduates often copied academic texts and lecture notes into personal notebooks in place of printed textbooks. Winthrop used Ward’s textbook in his class, while the books of Hume, Neal, and Rollin were used in history courses taught at Harvard in the 18th century.

Jamaica, 1763 (Image 1 of 4) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: This map of the island of Jamaica; laid down from the papers and under the direction of Henry Moore, Esqr.; His Majesty's Lieutenant Governor and Commander in Chief of that island, in the years 1756, 57, 58, 59, 60 & 61; & from a great number of actual surveys performed by the publishers is humbly inscribed by his lordship's most obedient & most humble servants, Thos. Craskell, engineer, Jas. Simpson, surveyor. It was published by D. Fournier in 1763. Scale [ca 1:200,000]. This layer is image 1 of 4 total images of the four sheet map, representing the southwest portion of the map.The image inside the map neatline is georeferenced to the surface of the earth and fit to the Jamaica Grid projected 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 towns, villages, and other human settlements, roads, drainage, selected buildings, ground cover, shoreline features, 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.

Jamaica, 1763 (Image 2 of 4) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: This map of the island of Jamaica; laid down from the papers and under the direction of Henry Moore, Esqr.; His Majesty's Lieutenant Governor and Commander in Chief of that island, in the years 1756, 57, 58, 59, 60 & 61; & from a great number of actual surveys performed by the publishers is humbly inscribed by his lordship's most obedient & most humble servants, Thos. Craskell, engineer, Jas. Simpson, surveyor. It was published by D. Fournier in 1763. Scale [ca 1:200,000]. This layer is image 2 of 4 total images of the four sheet map, representing the southeast portion of the map. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Jamaica Grid projected 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 towns, villages, and other human settlements, roads, drainage, selected buildings, ground cover, shoreline features, 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.

Jamaica, 1763 (Image 3 of 4) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: This map of the island of Jamaica; laid down from the papers and under the direction of Henry Moore, Esqr.; His Majesty's Lieutenant Governor and Commander in Chief of that island, in the years 1756, 57, 58, 59, 60 & 61; & from a great number of actual surveys performed by the publishers is humbly inscribed by his lordship's most obedient & most humble servants, Thos. Craskell, engineer, Jas. Simpson, surveyor. It was published by D. Fournier in 1763. Scale [ca 1:200,000]. This layer is image 3 of 4 total images of the four sheet map, representing the northeast portion of the map. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Jamaica Grid projected 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 towns, villages, and other human settlements, roads, drainage, selected buildings, ground cover, shoreline features, 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.

Jamaica, 1763 (Image 4 of 4) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: This map of the island of Jamaica; laid down from the papers and under the direction of Henry Moore, Esqr.; His Majesty's Lieutenant Governor and Commander in Chief of that island, in the years 1756, 57, 58, 59, 60 & 61; & from a great number of actual surveys performed by the publishers is humbly inscribed by his lordship's most obedient & most humble servants, Thos. Craskell, engineer, Jas. Simpson, surveyor. It was published by D. Fournier in 1763. Scale [ca 1:200,000]. This layer is image 4 of 4 total images of the four sheet map, representing the northwest portion of the map. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Jamaica Grid projected 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 towns, villages, and other human settlements, roads, drainage, selected buildings, ground cover, shoreline features, 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.