Letter from Thomas Buckley & Co.,

One letter thanking Tudor for his assistance with Rio de Janeiro port authorities.

Account books of Thomas Cradock, 1786-1818 (inclusive)

Account books listing patients, medicines administered, and fees charged by Dr. Thomas Cradock (1752-1821), primarily in Maryland, from 1786 to 1818. In addition to recording names, Cradock occasionally noted demographic information, the patient's location, or their occupation: from 1813 to 1816, he treated Richard Gent, a free African-American man; in 1813, he attended to John Bell, who lived in the Foggy Bottom neighborhood of Washington, D.C. Cradock further noted if the patient was a slave and the name of his or her owner. He would also administer care on behalf of corporate entities, such as Powhatan Factory, which apparently refused him payment. He also sometimes included a diagnosis: in the cases of a Mr. Rowles and Mrs. Violet West, he administered unspecified medicines for gonorrhea at a cost of ten dollars. Commonly prescribed drugs included emetics, cathartics, and anodynes. Cradock also provided smallpox vaccination for his patients. He accepted both cash and payment-in-kind. Tipped into the first volume is an envelope containing a letter from the Medical and Chirurgical Faculty of Maryland to Mrs. Thomas Craddock in 1899 requesting a loan of portrait of Dr. Thomas Craddock [sic]. The three volumes also each contain an index to patient names.

Non-Viral Gene Therapy to Cells of the bovine Intervertebral Disc

Background. Low back pain is an increasing global health problem, which is associated with intervertebral disc (IVD) damage and degeneration. Major changes occur in the nucleus pulposus (NP), with the degradation of the extracellular matrix (ECM).1 Further studies showed that growth factors from transforming growth factor β (TGFβ) and bone morphogenic proteins (BMP) family may induce chondrogenic differentiation of mesenchymal stem cells (MSC).2 Focusing on non-viral gene therapies and their possible translation into the clinics, we investigated if GDF6 (syn. BMP13 or CDMP2) can induce regeneration of degraded NP. We hypothesized that IVD transfected with plasmid over-expressing GDF6 also up-regulates other NP- and chondrogenic cell markers and enhances ECM deposition. Methods. Bovine nucleus pulposus (bNPC) and annulus fibrosus cells (bAFC) were harvested from bovine coccygeal IVD. Primary cells were then electroporized with plasmid GDF6 (Origene, vector RG211366) by optimizing parameters using the Neon Transfection system (Life Technologies, Basel). After transfection, cells were cultured in 2D monolayer or 3D alginate beads for 7, 14 or 21 days. Transfection efficiency of pGDF6 was analyzed by immunohistochemistry and fluorescent microscopy. Cell phenotype was quantified by real-time RT-PCR. To test a non-viral gene therapy applied directly to 3D whole organ culture, coccygeal bovine IVDs were harvested as previously described. Bovine IVDs were transfected by injection of plasmid GDF6 into the center. Electroporation was performed with ECM830 Square Wave Electroporation System (Harvard Apparatus, MA) using 2-needle array electrode or tweezertrodes. 72 h after tranfection discs were fixed and cryosectioned and analyzed by immunofluorescence against GDF6. Results. RT-PCR and immunohistochemistry confirmed up-regulation of GFP and GDF6 in the primary bNPC/bAFC culture. The GFP-tagged GDF6 protein, however, was not visible, possibly due to failure of dimer formation as a result of fusion structure. Organ IVD culture transfection revealed GDF6 positive staining in the center of the disc using 2-needle array electrode. Results from tweezertrodes did not show any GDF6 positive cells. Conclusion. Non-viral transfection is an appealing approach for gene therapy as it fulfills the translational safety aspects of transiency and lacks the toxic effects of viral transduction. We identified novel parameters to successfully transfect primary bovine IVD cells. For transfection of whole IVD explants electroporation parameters need to be further optimized. Acknowledgements. This project was funded by the Lindenhof Foundation (Funds “Research & Teaching”) Project no. 13-02-F. The imaging part of this study was performed with the facility of the Microscopy Imaging Center (MIC), University of Bern. References. Roughly PJ (2004): Spine (Phila), 29:2691-2699 Clarke LE, McConell JC, Sherratt MJ, Derby B, Richardson SM, Hoyland JA (2014), Arthritis Research & Therapy, 16:R67

Age estimations of calcareous nannofossil biohorizons of the middle Paleocene to early Eocene at ODP Site 208-1262 (Table 1, Appendix B)

Over the last several decades debates on the 'tempo and mode' of evolution have centered on the question whether morphological evolution preferentially occurs gradually or punctuated, i.e., with long periods of stasis alternating with short periods of rapid morphological change and generation of new species. Another major debate is focused on the question whether long-term evolution is driven by, or at least strongly influenced by changes in the environment, or by interaction with other life forms. Microfossils offer a unique opportunity to obtain the large datasets as well as the precision in dating of subsequent samples to study both these questions.We present high-resolution analyses of selected calcareous nannofossils from the deep-sea section recovered at ODP Site 1262 (Leg 208) in the South-eastern Atlantic. The studied section encompasses nannofossil Zones NP4-NP12 (equivalent to CP3-CP10) and Chrons C27r-C24n. We document more than 70 biohorizons occurring over an about 10 Myr time interval, (~62.5 Ma to ~52.5 Ma), and discuss their reliability and reproducibility with respect to previous data, thus providing an improved biostratigraphic framework, which we relate to magnetostratigraphic information, and present for two possible options of a new Paleocene stratigraphic framework based on cyclostratigraphy. This new framework enabled us to tentatively reconstruct steps in the evolution of early Paleogene calcareous nannoplankton through documentation of transitional morphotypes between genera and/or species and of the phylogenetic relations between the genera Fasciculithus, Heliolithus, Discoasteroides and Discoaster, as well as between Rhomboaster and Tribrachiatus. The exceptional record provided by the continuous, composite sequence recovered at Walvis Ridge allows us to describe the mode of evolution among calcareous nannoplankton: new genera and/or new species usually originated through branching of lineages via gradual, but relatively rapid, morphological transitions, as documented by the presence of intermediate forms between the end-member ancestral and descendant forms. Significant modifications in the calcareous nannofossil assemblages are often "related" to significant changes in environmental conditions, but the appearance of structural innovations and radiations within a single genus also occurred during "stable" environmental conditions. These lines of evidence suggest that nannoplankton evolution is not always directly triggered by stressed environmental conditions but could be also driven by endogenous biotic control.

The works of Thomas Middleton, now first collected,

Imperfect: frontpiece wanting. cf. v.1, p. 4211.

The twelve moneths and Christmas Day, from 'Fantastickes.'

Printed at the Thistle Press to designs executed by Bruce Rogers.

Report to the President by the Emergency Board created June 23, 1948 by Executive order 9971 pursuant to Section 10 of the Railway Labor Act : to investigate and report upon a dispute between the Grand Trunk Western Railroad Co., Chesapeake and Ohio Railway Co., Wabash Railroad and the Ann Arbor Railroad Co. and certain of its employees represented by the National Maritime Union of America, N.M.B. cases A-2801, A-2802, A-2803, A-2804, Detroit, Michigan, July 20, 1948.

Signed: Robert G. Simmons, chairman, Thomas F. Gallagher, member, Joseph L. Miller, member.

Memoir of Maj.-Gen. George H. Thomas,

Mode of access: Internet.

Analyses of demographic, attitudinal and behavioral characteristics of participants in the diagnostic inspection demonstration projects. Volume IV - appendices. Part B.

National Highway Traffic Safety Administration, Washington, D.C.

The diary of Dr. Thomas Cartwright, bishop of Chester; commencing at the time of his elevation to that see, August M.DC.LXXXVI,; and terminating with the visitation of St. Mary Magdalene college, Oxford, October M.DC.LXXXVII.

Mode of access: Internet.

Procès des trois Anglais, Robert-Thomas Wilson, John-Ely Hutchinson, Michel Bruce, et autres, accusés d'avoir facilité l'évation de Lavalette.

Mode of access: Internet.