Frequent clonal loss of heterozygosity but scarcity of microsatellite instability at chromosomal breakpoint cluster regions in adult leukemias.

Microsatellites are important highly polymorphic genetic markers dispersed in the human genome. Using a panel of 22 (CA)n repeat microsatellite markers mapped to recurrent breakpoint cluster regions specifically involved in leukemia, we investigated 114 adult leukemias (25 acute lymphocytic leukemia [ALL], 32 acute myeloid leukemia [AML], 36 chronic lymphocytic leukemia [CLL], and 21 chronic myeloid leukemia [CML] in chronic phase) for somatic mutations at these loci. In each patient, DNA from fresh leukemia samples was analyzed alongside normal constitutive DNA from buccal epithelium. We detected loss of heterozygosity (LOH) in 81 of 114 patients (ALL 16/25, AML 25/32, CLL 30/36, CML 10/21). Deletions were most often seen in ALL at 11q23 and 19p13; in AML at 8q22 and 11q23; in CLL at 13q14.3, 11q13, and 11q23; and in CML at 3q26. Only six deletions were reported in 74 karyotypes analyzed, whereas in these same cases, 91 LOH events were detected by microsatellites. Of 26 leukemias with a normal karyotype, 16 nevertheless showed at least one LOH by microsatellite analysis. Replication errors were found in 10 of 114 patients (8.8%). Thus, microsatellite instability is rare in leukemia in contrast to many solid tumors. Our findings suggest that in adult leukemia, LOH may be an important genetic event in addition to typical chromosomal translocations. LOH may point to the existence of tumor suppressor genes involved in leukemogenesis to a degree that has hitherto been underestimated.

Audit report on America’s Agricultural Industrial Heritage Landscape, Inc., d/b/a Silos and Smokestacks National Heritage Area (Silos and Smokestacks), in Waterloo, Iowa for the years ended December 31, 2006 and 2005

Audit report on America’s Agricultural Industrial Heritage Landscape, Inc., d/b/a Silos and Smokestacks National Heritage Area (Silos and Smokestacks), in Waterloo, Iowa for the years ended December 31, 2006 and 2005

Implementation study of a clinical prediction score to rule out cardiogenic chest pain in community: Cluster randomized trial

1.1 Fundamentals Chest pain is a common complaint in primary care patients (1 to 3% of all consultations) (1) and its aetiology can be miscellaneous, from harmless to potentially life threatening conditions. In primary care practice, the most prevalent aetiologies are: chest wall syndrome (43%), coronary heart disease (12%) and anxiety (7%) (2). In up to 20% of cases, potentially serious conditions as cardiac, respiratory or neoplasic diseases underlie chest pain. In this context, a large number of laboratory tests are run (42%) and over 16% of patients are referred to a specialist or hospitalized (2).¦A cardiovascular origin to chest pain can threaten patient's life and investigations run to exclude a serious condition can be expensive and involve a large number of exams or referral to specialist -­‐ often without real clinical need. In emergency settings, up to 80% of chest pains in patients are due to cardiovascular events (3) and scoring methods have been developed to identify conditions such as coronary heart disease (HD) quickly and efficiently (4-­‐6). In primary care, a cardiovascular origin is present in only about 12% of patients with chest pain (2) and general practitioners (GPs) need to exclude as safely as possible a potential serious condition underlying chest pain. A simple clinical prediction rule (CPR) like those available in emergency settings may therefore help GPs and spare time and extra investigations in ruling out CHD in primary care patients. Such a tool may also help GPs reassure patients with more common origin to chest pain.

Efeitos da Interação Conjunta da Volatilidade das Taxas de Juro e da Dívida nas Decisões de Investimento: Evidências nas Empresas Portuguesas do Setor Industrial

Focalizando, essencialmente, sobre os efeitos da interação. conjunta da volatildade das taxas de juro e da dívida nas decisões de investimento das empresas portuguesas, listadas na Euronext Lisbon, e considerando a composição de dados em séries temporais empilhadas, extraímos 291 observações completas, durante o período de 1999 a 2009. Os resultados encontrados mostram que uma maior exposição ao risco da dívida das empresas portuguesas depende do nível de endividamento. As empresas moderadamente endividadas e amantes do risco não diminuem os seus investimentos, quando se verifica uma maior volatilidade do risco da dívida. Por outro lado, as empresas sobreendividadas e inimigas do risco respondem perante a uma maior volatilidade do risco da dívida, diminuindo os seus investimentos. Além disso, descobrimos que as empresas portuguesas reduzem os seus investimentos face a uma maior volatilidade das taxas de juro. Entretanto, fomos surpreendidos que as empresas portuguesas não reduzem os seus investimentos, face a um efeito marginal das taxas de juro. Este resultado sugere que, o benefício fiscal resultante do efeito de reavaliação da dívida (Lensink et al., 2001), é mais relevante para as empresas sobreendividadas, uma vez que podem atenuar o efeito dos encargos financeiros (Bo e Sterken, 2002).

Identification of the biosynthetic gene cluster for the Pseudomonas aeruginosa antimetabolite L-2-amino-4-methoxy-trans-3-butenoic acid.

L-2-amino-4-methoxy-trans-3-butenoic acid (AMB) is a potent antibiotic and toxin produced by Pseudomonas aeruginosa. Using a novel biochemical assay combined with site-directed mutagenesis in strain PAO1, we have identified a five-gene cluster specifying AMB biosynthesis, probably involving a thiotemplate mechanism. Overexpression of this cluster in strain PA7, a natural AMB-negative isolate, led to AMB overproduction.

Credit rationing and crowding out during the Industrial Revolution: Evidence from Hoare's Bank, 1702-1862

Crowding-out during the British Industrial Revolution has long been one of the leadingexplanations for slow growth during the Industrial Revolution, but little empirical evidence exists to support it. We argue that examinations of interest rates are fundamentally misguided, and that the eighteenth- and early nineteenth-century private loan market balanced through quantity rationing. Using a unique set of observations on lending volume at a London goldsmith bank, Hoare s, we document the impact of wartime financing on private credit markets. We conclude that there is considerable evidence that government borrowing, especially during wartime, crowded out private credit.

Factor prices and productivity growth during the British Industrial Revolution

This paper presents new estimates of total factor productivity growth in Britain for the period1770 1860. We use the dual technique and argue that the estimates we derive from factorprices are of similar quality to quantity-based calculations. Our results provide further evidence,calculated on the basis of an independent set of sources, that productivity growth duringthe British Industrial Revolution was relatively slow. The Crafts Harley view of theIndustrial Revolution is thus reinforced. Our preferred estimates suggest a modest accelerationafter 1800.