Bond of Samuel Leighton and Samuel Shapleigh to the Harvard Corporation, Aug. 23, 1785

Shapleigh and Leighton's signatures have been cut out from the bottom of this document. It was "signed, sealed and delivered" in the presence of Benjamin Stevens and Ebenezer Marriner.

Bond of Samuel Shapleigh and Thomas Adams to the Harvard Corporation, Aug. 15, 1789

Shapleigh and Adams' signatures have been cut out from the bottom of this document. It was "signed, sealed and delivered" in the presence of Thomas Gray and Darius Shaw.

Bond of Samuel Shapleigh and unknown co-signatory to the Harvard Corporation, Aug. 15, 1789

Shapleigh and the unknown co-signatory's signatures have been cut out from the bottom of this document. It was "signed, sealed and delivered" in the presence of Owen Warland and William Wahan.

Bond of Samuel Shapleigh to Ebenezer Bradish, July 1, 1793

Although it is known that Bradish was a tavern keeper in Cambridge, the circumstances precipitating this bond are unclear. Shapleigh's name has been cut out from the bottom of the document. It was "signed, sealed and delivered" in the presence of John Warland and Raham Richardson. Annotations on the verso indicate payments made in 1795 and 1796.

John Oldham counterbond to James Clarke & Richard Moores, 1722 May 14

This legal document, a counterbond, was created on May 14, 1722 and involved John Oldham, James Clark, and Richard Moores. All three men were residents of Cambridge at the time of its creation. The document specifies Oldham's financial obligations to Clark, a cordwainer, and Moores, a tailor and was "Sign[ed], sealed & [delivered] in the presence of Nathaniel Sparhawk and Noah Sparkhawk." The document also refers to the "trustees for the town of Cambridge" Spencer Shipps, Nathaniel Sparhawk and John Dickson.

Deed of feoffment for property in Cambridge, Massachusetts: from Thomas Sweetman to Michael Spencer, 1677 December 10

In this deed of feoffment, written on Dec. 10, 1677, Thomas Sweetman agreed to sell his dwelling house, barn, and orchard to his son-in-law, Michael Spencer, for the cost of eighty pounds sterling. The property was located in Cambridge, Massachusetts, on what was then the northwest corner of the grounds of Harvard College, and was sold "together with the wood lot upon the rocks and cow commons belonging to it." The deed specifies that both Sweetman and his wife Isabel were to be allowed to occupy the property until their deaths, and further explains that Spencer and his family were already living in the dwelling house, occupying three rooms. The document was signed, sealed, and delivered in the presence of Daniel Gookin, Jr. and John Bridgham. It was also signed by Thomas Sweetman.

No more compulsory engagement. The emancipation of German security policy. OSW Commentary no. 57, 2011-07-18

Germany’s stance on Libya at the UN Security Council and its later decision not to take part in the military intervention gave rise to heated controversy both in Germany and abroad. At home, this was criticised as “an enormous mistake of historic impact”1; while abroad this raised questions about Germany’s willingness to co-operate with its key Western allies. With its decision on Libya, Germany sealed the process of making its security policy independent from the stances of the US and France. It thus ceased to feel any compulsion to provide not only military engagement but also political support for overseas operations initiated by its key allies, even if these are legitimised by the UN Security Council. Germany’s stance, apart from finishing off a certain process, is also setting a starting point for a discussion inside Germany about its military engagement in international security policy. This will bring about a more assertive and selective approach to cooperation with NATO and the EU’s Common Security and Defence Policy.

Avaliação da técnica imunohistoquímica como método de deteção da apoptose a nível celular

A apoptose constitui um processo fisiológico de morte celular, caracterizado por alterações morfológicas distintas e mecanismos bioquímicos e moleculares bem definidos. O seu papel de destaque em numerosos eventos biológicos e importantes processos patológicos conduziu a um crescente interesse na investigação dos mecanismos celulares que regulam o processo apoptótico. A aplicação de metodologias capazes de identificar células apoptóticas despoletou um enorme desenvolvimento de técnicas. No entanto, as propriedades demonstradas por estes ensaios nem sempre se aplicam ao estudo de amostras tecidulares, pelo que a escolha dos diferentes métodos deverá ser criteriosamente avaliada, tendo em conta a aplicação pretendida e as alterações morfológicas que se pretendem detetar. Das várias técnicas disponíveis para deteção da apoptose em tecidos, muitos investigadores recomendam o método TUNEL, o qual se baseia na marcação de produtos endonucleossómicos resultantes da fragmentação do DNA. Outros métodos histoquímicos também disponíveis incluem a deteção do citocromo c, libertado da mitocôndria ou a deteção das proteínas pró e anti-apoptóticas, Bax, Bidm e Bcl-2, envolvidas nos mecanismos intrínsecos da apoptose. Mais recentemente, a marcação de produtos específicos resultantes da clivagem de proteínas alvo pelas caspases, tem vindo a ser considerada uma abordagem promissora. Como principal objectivo deste trabalho pretendeu-se avaliar a técnica imunohistoquímica como método de deteção da apoptose a nível celular, em tecidos animais, tendo por base o método TUNEL, o qual permite a deteção de fragmentos de DNA. Os resultados obtidos permitiram concluir que, apesar do método TUNEL possuir as suas limitações ao nível da sensibilidade e especificidade, o mesmo constitui um mecanismo imunohistoquímico útil na deteção de células apoptóticas. Contudo, segundo opinião de vários autores, adverte-se para a necessidade da aplicação de pelo menos dois métodos imunohistoquímicos como forma de validar a ocorrência do processo apoptótico, razão pela qual se optou pela deteção do citocromo c citosólico como método complementar, uma vez que a sua libertação para o espaço citosólico se encontra implicada na ativação da apoptose.

Genetically engineered silk and genipin-enhanced fibrin hydrogel for annulus fibrosus repair

INTRODUCTION: Around 80% of people are affected by low back pain at least once in their life, often caused by trauma provoking intervertebral disc (IVD) herniation and/or IVD degeneration. Apart from some promising approaches for nucleus pulposus repair, so far no treatment or repair is available for the outer fibrous tissue, annulus fibrosus (AF). We aimed for sealing and repairing an AF injury in a bovine IVD organ culture model in vitro over 14 days under different loading conditions. For this purpose, a silk fleece composite from Bombyx mori silk was combined with genipin-enhanced fibrin hydrogel [1]. METHODS: Bovine IVDs of 12-17 months old animals were isolated by first removing all surrounding tissue, followed by cutting out the IVDs [2]. Culturing of discs occurred in high glucose Dulbecco's Modified Eagle Medium (HG-DMEM) supplemented with 5% serum as previously described. On the next day, injury was induced using a 2mm biopsy punch (Polymed, Switzerland). The formed cavity was filled with (0.4%) genipin-enhanced human based fibrin hydrogel (35- 55mg/mL human fibrinogen, Baxter, Austria) and sealed with a silk fleece-membrane composite (Spintec Engineering, Germany). Different culture conditions were applied: free swelling, static diurnal load of 0.2MPa for 8h/d and complex loading at 0.2MPa compression combined with ± 2° torsion at 0.2Hz for 8h/d. Complex loading was applied by a custom built 2 degree of freedom bioreactor [3]. After 14 days of culture cell activity was determined with resazurin assay. Additionally, glycosaminoglycan (dimethyl-methylene blue), DNA (Hoechst) and collagen content (hydroxy-proline) were determined. Finally, real-time qPCR of major IVD marker genes was performed. RESULTS: The silk seal closing the injury site could successfully withstand the forces of all three loading conditions with no misplacement over the two weeks’ culture. Nevertheless, disc height of the repaired discs did not significantly differ from the injured group. The disc phenotype could be maintained as demonstrated by biochemical analysis of gene expression, cell activity, DNA-, collagen- and GAG content. The silk itself was evaluated to be highly biocompatible for hMSC, as revealed by cytotoxicity assays. DISCUSSION & CONCLUSIONS: The silk can be considered a highly-elastic and biocompatible material for AF closure and the genipin-enhanced fibrin hydrogel has also good biomechanical properties. However, the cyto-compatibility of genipin seems rather poor and other hydrogels and/or cross-linkers should be looked into. REFERENCES: 1 C.C. Guterl et al. (2014) Characterization of Mechanics and Cytocompatibility of Fibrin Genipin Annulus Fibrosus Sealant with the Addition of Cell Adhesion Molecules, Tissue Eng Part A 2 S.C. Chan, B. Gantenbein-Ritter (2012) Preparation of intact bovine tail intervertebral discs for organ culture, J Vis Exp 3 B Gantenbein et al. (2015) Organ Culture Bioreactors - Platforms to Study Human Intervertebral Disc Degeneration and Regenerative Therapy, Curr Stem Cell Res Ther [epub ahead of print] ACKNOWLEDGEMENTS: This project is supported by the Gebert Rüf Stiftung project # GRS-028/13.

Nitrogen isotopic composition and chemical composition of altered oceanic crust from ODP Legs 129 and 185

Knowledge of the subduction input flux of nitrogen (N) in altered oceanic crust (AOC) is critical in any attempt to mass-balance N across arc-trench systems on a global or individual-margin basis. We have employed sealed-tube, carrier-gas-based methods to examine the N concentrations and isotopic compositions of AOC. Analyses of 53 AOC samples recovered on DSDP/ODP legs from the North and South Pacific, the North Atlantic, and the Antarctic oceans (with larger numbers of samples from Site 801 outboard of the Mariana trench and Site 1149 outboard of the Izu trench), and 14 composites for the AOC sections at Site 801, give N concentrations of 1.3 to 18.2 ppm and d15N_air of -11.6? to +8.3?, indicating significant N enrichment probably during the early stages of hydrothermal alteration of the oceanic basalts. The N-d15N modeling for samples from Sites 801 and 1149 (n=39) shows that the secondary N may come from (1) the sedimentary N in the intercalated sediments and possibly overlying sediments via fluid-sediment/rock interaction, and (2) degassed mantle N2 in seawater via alteration-related abiotic reduction processes. For all Site 801 samples, weak correlation of N and K2O contents indicates that the siting of N in potassic alteration phases strongly depends on N availability and is possibly influenced by highly heterogeneous temperature and redox conditions during hydrothermal alteration. The upper 470-m AOC recovered by ODP Legs 129 and 185 delivers approximately 800 kg/km N annually into the Mariana margin. If the remaining less-altered oceanic crust (assuming 6.5 km, mostly dikes and gabbros) has MORB-like N of 1.5 ppm, the entire oceanic crust transfers 5100 kg/km N annually into that trench. This N input flux is twice as large as the annual N input of 2500 kg/km in seafloor sediments subducting into the same margin, demonstrating that the N input in oceanic crust, and its isotopic consequences, must be considered in any assessment of convergent margin N flux.

(Table 1) Summary of basalt unit thickness, vesicularity, number of flow units, and average porosity at ODP Site 135-839

An inflatable drill-string packer was used at Site 839 to measure the bulk in-situ permeability within basalts cored in Hole 839B. The packer was inflated at two depths, 398.2 and 326.9 mbsf; all on-board information indicated that the packer mechanically closed off the borehole, although apparently the packer hydraulically sealed the borehole only at 398.2 mbsf. Two pulse tests were run at each depth, two constant-rate injection tests were run at the first set, and four were run at the second. Of these, only the constant-rate injection tests at the first set yielded a permeability, calculated as ranging from 1 to 5 * 10**-12 m**2. Pulse tests and constant-rate injection tests for the second set did not yield valid data. The measured permeability is an upper limit; if the packer leaked during the experiments, the basalt would be less permeable. In comparison, permeabilities measured at other Deep Sea Drilling Project and Ocean Drilling Program sites in pillow basalts and flows similar to those measured in Hole 839B are mainly about 10**-13 to 10**-14 m**2. Thus, if our results are valid, the basalts at Site 839 are more permeable than ocean-floor basalts investigated elsewhere. Based on other supporting evidence, we consider these results to be a valid measure of the permeability of the basalts. Temperature data and the geochemical and geotechnical properties of the drilled sediments all indicate that the site is strongly affected by fluid flow. The heat flow is very much less than expected in young oceanic basalts, probably a result of rapid fluid circulation through the crust. The geochemistry of pore fluids is similar to that of seawater, indicating seawater flow through the sediments, and sediments are uniformly underconsolidated for their burial depth, again indicating probable fluid flow. The basalts are highly vesicular. However, the vesicularity can only account for part of the average porosity measured on the neutron porosity well log; the remainder of the measured porosity is likely present as voids and fractures within and between thin-bedded basalts. Core samples, together with porosity, density, and resistivity well-log data show locations where the basalt section is thin bedded and probably has from 15% to 35% void and fracture porosity. Thus, the measured permeability seems reasonable with respect to the high measured porosity. Much of the fluid flow at Site 839 could be directed through highly porous and permeable zones within and between the basalt flows and in the sediment layer just above the basalt. Thus, the permeability measurements give an indication of where and how fluid flow may occur within the oceanic crust of the Lau Basin.

(Table 1) Sr-isotope values of representative sediment samples from ODP sites at the Costa Rica margin

Two sealed borehole hydrologic observatories (CORKs) were installed in two active hydrogeochemical systems at the Costa Rica subduction zone to investigate the relationship between tectonics, fluid flow, and fluid composition. The observatories were deployed during Ocean Drilling Program (ODP) Leg 205 at Site 1253, ~ 0.2 km seaward of the trench, in the upper igneous basement, and at Site 1255, ~ 0.5 km landward of the trench, in the décollement. Downhole instrumentation was designed to monitor formation fluid flow rates, composition, pressure, and temperature. The two-year records collected by this interdisciplinary effort constitute the first co-registered hydrological, chemical, and physical dataset from a subduction zone, providing critical information on the average and transient state of the subduction thrust and upper igneous basement. The continuous records at ODP Site 1253 show that the uppermost igneous basement is highly permeable hosting an average fluid flow rate of 0.3 m/yr, and indicate that the fluid sampled in the basement is a mixture between seawater (~ 50%) and a subduction zone fluid originating within the forearc (~ 50%). These results suggest that the uppermost basement serves as an efficient pathway for fluid expelled from the forearc that should be considered in models of subduction zone hydrogeology and deformation. Three transients in fluid flow rates were observed along the décollement at ODP Site 1255, two of which coincided with stepwise increases in formation pressure. These two transients are the result of aseismic slip dislocations that propagated up-dip from the seismogenic zone over the course of ~ 2 weeks terminating before reaching ODP Site 1255 and the trench. The nature and temporal behavior of strain and the associated hydrological response during these slow slip events may be an analog for the response of the seaward part of the subduction prism during or soon after large subduction zone earthquakes.

Total cross sections of nuclei for 280 Mev neutrons.

The measurement of 28O-Mev neutron cross sections of various nuclei is described. The neutron beam used results from 340-Mev protons in the 184-in. cyclotron striking a 2-in. Be target. The neutron detector consists of a double coincidence anthracene scintillation counter telescope which counts recoil protons scattered at 15 deg from a paraffin cylinder placed in the collimated neutron beam. A 2-in. Cu absorber placed between the counters assures that only protons of energy greater than 250 Mev are counted. The cross sections for all nuclei measured from Li to Pb are smaller than the corresponding cross sections measured at 90 Mev by factors between 0.5 and 0.6.

Preliminary official statement dated February 4, 1993 : State of Illinois : $100,000,000 Build Illinois bonds (Sales tax revenue bonds) : Series R.

Cover title.