Golden Apples of Deceit

Do you recall the myth about the Golden Apples of Deceit? It seems instructive to me during these trying, tense technological times. Atalanta had been warned by the god Apollo that she would lose herself if ever she married so she determined not to.

Analysis of Factor VIII polymorphic markers as a means for carrier detection in Brazilian families with haemophilia A

Haemophilia A is an X-linked, recessively inherited bleeding disorder of varying severity, which results from the deficiency of procoagulant factor VIII f(8). Linkage diagnosis using polymorphic markers in the f8 gene is widely used to detect carriers. The objective of this study was to verify the informativeness of three polymorphic markers in the Brazilian population, to evaluate the usefulness of such markers in carrier detection procedures. Sixty-three unrelated healthy volunteers and 10 haemophilic families were studied. Two microsatellite repeats and one HindIII RFLP markers were used. Carrier and non-carrier status could be determined in 80% of females investigated. Intron 13 markers presented the highest heterozygosity rate (79%) followed by intron 22 (68%) and intron 19 (57%). When all three markers were used together, linkage analysis informativeness increased significantly. We conclude that these markers are suitable for carrier detection in the Brazilian population and we recommend their use in combination to maximize diagnostic efficiency.

The Sicilian coinage of Henry VI - mint attributions reconsidered

The Sicilian Coinage of the Hohenstaufen has been studied since the 17th century. Today, with the splendid Medieval European Coinage 14 at our hands, scholars are still struggling when it comes to mint attributions for Henry’s Sicilian denari and taris: Palermo or Messina? Palermo and Messina? The coin finds from Monte Iato (PA) may shed light on this old problem: by starting from one coin type alone and examining the different subtypes and variants, we can catch a glimpse of the way coinage was organised in Sicily at the end of the 12th century.

Coexpression of factor VIII heavy and light chain adeno-associated viral vectors produces biologically active protein

We are interested in using recombinant adeno-associated viral vectors in the treatment of hemophilia A. Because of the size constraints of recombinant adeno-associated viral vectors, we delivered the heavy and light chains of the human factor 8 (hFVIII) cDNA independently by using two separate vectors. Recombinant AAV vectors were constructed that utilized the human elongation factor 1α promoter, a human growth factor polyadenylation signal, and the cDNA sequences encoding either the heavy or light chain of hFVIII. Portal vein injections of each vector alone, a combination of both vectors, or a hFIX control vector were performed in C57BL/6 mice. An ELISA specific for the light chain of hFVIII demonstrated very high levels (2–10 μg/ml) of protein expression in animals injected with the light chain vector alone or with both vectors. We utilized a chromogenic assay in combination with an antibody specific to hFVIII to determine the amount of biologically active hFVIII in mouse plasma. In animals injected with both the heavy and light chain vectors, greater than physiological levels (200–400 ng/ml) of biologically active hFVIII were produced. This suggests that coexpression of the heavy and light chains of hFVIII may be a feasible approach for treatment of hemophilia A.

Short-term correction of factor VIII deficiency in a murine model of hemophilia A after delivery of adenovirus murine factor VIII in utero

Development of in utero gene transfer approaches may provide therapies for genetic disorders with perinatal morbidity. In hemophilia A, prenatal and postnatal bleeding may be catastrophic, and modest increments in factor VIII (FVIII) activity are therapeutic. We performed transuterine i.p. gene transfer at day 15 of gestation in a murine model of hemophilia A. Normal, carrier (XHX), and FVIII-deficient (XHY and XHXH) fetuses injected with adenoviral vectors carrying luciferase or β-galactosidase reporter genes showed high-level gene expression with 91% fetal survival. The live-born rates of normal and FVIII-deficient animals injected in utero with adenovirus murine FVIII (3.3 × 105 plaque-forming units) was 87%. FVIII activity in plasma was 50.7 ± 10.5% of normal levels at day 2 of life, 7.2 ± 2.2% by day 15 of life, and no longer detectable at day 21 of life in hemophilic animals. Injection of higher doses of murine FVIII adenovirus at embryonic day 15 produced supranormal levels of FVIII activity in the neonatal period. PCR analysis identified viral genomes primarily in the liver, intestine, and spleen, although adenoviral DNA was detected in distal tissues when higher doses of adenovirus were administered. These studies show that transuterine i.p. injection of adenoviral vectors produces therapeutic levels of circulating FVIII throughout the neonatal period. The future development of efficient and persisting vectors that produce long-term gene expression may allow for in utero correction of genetic diseases originating in the fetal liver, hematopoietic stem cells, as well as other tissues.

[Admittatur of Henry Gardner (Harvard AB 1798)], 1794 August 13

Published copy of the 1790 College Laws, in a modern hardcover binding, with the admittatur of undergraduate Henry Gardner signed by President Joseph Willard on August 13, 1794.

Diary of Henry Flynt, 1723-1747

This diary, effectively a commonplace book, documents Flynt's daily activities and personal reflections from 1723 to 1747. Many entries concern his dealings with family members, business associates, acquaintances, ministers, and political officials. The diary includes a list of books Flynt loaned to others from 1723 to 1743 and detailed financial entries from 1724 to 1747. These entries provide information about the costs of goods and services, as well as Flynt's consumption habits; they detail where he traveled, what he ate and drank (including, apparently, many pounds of almonds), what he read, and many other aspects of daily life. The diary also contains entries related to Flynt's land holdings and other investments, as well as copies of meeting minutes from several sessions of the Harvard Board of Overseers.