A Statistical Analysis of RNA Folding Algorithms Through Thermodynamic Parameter Perturbation

Computational RNA secondary structure prediction is rather well established. However, such prediction algorithms always depend on a large number of experimentally measured parameters. Here, we study how sensitive structure prediction algorithms are to changes in these parameters. We find that already for changes corresponding to the actual experimental error to which these parameters have been determined 30% of the structure are falsly predicted and the ground state structure is preserved under parameter perturbation in only 5% of all cases. We establish that base pairing probabilities calculated in a thermal ensemble are a viable though not perfect measure for the reliability of the prediction of individual structure elements. A new measure of stability using parameter perturbation is proposed, and its limitations discussed.Comment: 6 pages, 3 figures, 1 table submitted to Nucleic Acids Researc

Solar electric space mission analysis Progress report, 1 Jun. - 31 Dec. 1966

Characteristics and trajectory analysis of solar electric propulsion space missions - Mars orbiter and Jupiter flyb

Aerospace systems and mission analysis research Status report, 1 Apr. - 31 Dec. 1966

Systems and mission analysis of solar electric propulsion for solar system exploratio

Deaths Exceed Births in Most of Europe, But Not in the United States

In this brief, authors Kenneth Johnson, Layton Fields, and Dudley Poston, Jr. present important new findings about the diminishing number of births compared to deaths in Europe and the United States from their recent article in Population and Development Review. Their research focuses on the prevalence and dynamics of natural decrease in subareas of Europe and the United States in the first decade of the twenty-first century using counties (United States) or county-equivalents (Europe). The authors report that 58 percent of the 1,391 counties of Europe had more deaths than births during that period compared to just 28 percent of the 3,137 U.S. counties. Natural decrease is more widespread in Europe because its population is older, fertility rates are lower, and there are fewer women of child-bearing age. Natural decrease is a major policy concern because it drains the demographic resilience from a region, diminishing its economic viability and competitiveness. The implications of the recent European immigrant surge for natural decrease are uncertain, but the authors’ analysis suggests that natural decrease is likely to remain widespread in Europe for the foreseeable future

Aerospace systems and mission analysis research - Solar electric space mission analysis Final report

Mission analysis for solar electric propelled spacecraft on Mars Orbiter, Jupiter flyby, and asteroid belt exploration trajectorie

MULTIPLE STRUCTURAL BREAKS IN AUSTRALIA’S MACROECONOMIC DATA: AN APPLICATION OF THE LUMSDAINE AND PAPELL TEST

This paper employs all available annual time series data to endogenously determine the timing of structural breaks for 10 macroeconomic variables in the Australian economy. The ADF (Augmented Dickey and Fuller) test and the LP (Lumsdaine and Papell, 1997) test are used to examine the time series properties of the data. The ADF test results provide no evidence against the unit root null hypothesis in all ten macroeconomic variables. After accounting for the two most significant structural breaks in the data impacting on both the intercept and trend, the results from the LP test indicate that the null of at least one unit root is rejected for four of the variables under investigation at the 10 per cent level or better. We also found that the dates of structural breaks in most cases point to: (a) the oil/wages shock occurring in the 1973-1975 period, (b) the 1990-1991 recession; (c) the culmination of financial deregulation and innovation in the late 1980s; and (d) the 1997 Asian crisis.Unit roots Hypothesis, structural breaks, and Australian economy

A national register for surveillance of inherited disorders: beta thalassaemia in the United Kingdom

OBJECTIVE: To demonstrate the value of a national register for surveillance of services for an inherited disorder. METHODS: Data from the United Kingdom Thalassaemia Register and the United Kingdom Register of Prenatal Diagnosis for Haemoglobin Disorders were combined in a database; these registers include all fetuses known to have been diagnosed with beta thalassaemia major, beta thalassaemia intermedia, or haemoglobin E/beta thalassaemia in the United Kingdom. Data were extracted to show outcomes (selective abortion or live birth) of all fetuses and the status of those born with a disorder (alive, dead, successful bone marrow transplant, or lost to follow-up) by parents' region of residence and ethnicity. FINDINGS: At the end of 1999 the register included 1074 patients, 807 of whom were alive and residing in the United Kingdom. A successful bone marrow transplant has been performed for 117 out of 581 (20%) patients born since 1975. Residents of Pakistani origin are now the main group at risk in the United Kingdom, replacing residents of Cypriot origin. This has led to a marked shift in the need for services from the south-east of England to the Midlands and the north of England. Despite the acceptability of prenatal diagnosis, the proportion of affected births remains 50% higher than would be expected, reflecting a widespread failure to deliver timely screening and counselling to carriers. Even though effective treatment is available the annual number of deaths is rising, indicating that better tolerated treatments are needed. CONCLUSION: A national diagnosis register is a powerful instrument for monitoring the treatment and prevention of inherited disorders and for highlighting correctable shortcomings. In view of the increasing possibilities for genetic screening there is a strong case for central funding for such databases within modern health services

Missense mutations in the perforin (PRF1) gene as a cause of hereditary cancer predisposition

Perforin, a pore-forming toxin released from secretory granules of NK cells and CTLs, is essential for their cytotoxic activity against infected or cancerous target cells. Bi-allelic loss-of-function mutations in the perforin gene are invariably associated with a fatal immunoregulatory disorder, familial haemophagocytic lymphohistiocytosis type 2 (FHL2), in infants. More recently, it has also been recognized that partial loss of perforin function can cause disease in later life, including delayed onset FHL2 and haematological malignancies. Herein we report a family in which a wide range of systemic inflammatory and neoplastic manifestations have occurred across three generations. We found that disease was linked to two missense perforin gene mutations (encoding A91V, R410W) that cause protein misfolding and partial loss of activity. These cases link the partial loss of perforin function with some solid tumours that are known to be controlled by the immune system, as well as haematological cancers. Our findings also demonstrate that perforin gene mutations can contribute to hereditary cancer predisposition

Heterogeneity in a spontaneous mouse lung carcinoma: selection and characterisation of stable metastatic variants.

The development and characterisation of a new epithelial model for the experimental investigation of metastasis is described. A tissue culture cell line CMT64 was established from a spontaneous alveolar lung carcinoma of a 17 month old female C57BL/ICRF at mouse (Franks et al., 1976). Subcutaneous inoculation of cells produces local tumours which give rise to a small number of lung metastases within three weeks. Four different tissue culture sublines CMT167, 170, 175 and 181 with increased metastatic ability were selected from pooled lung metastases by culture, mouse inoculation and reselection from lung metastases through four culture/inoculation cycles. These sublines are themselves heterogeneous and clones derived from them display marked differences in metastatic behaviour. Both CMT64 and its sublines have remained relatively stable in morphology and behavior since their origin, are fairly well differentiated, produce basal lamina even in metastases, and metastasise rapidly and preferentially to the lung after subcutaneous and intravenous inoculation in both syngeneic C57 and Nu/Nu mice (Franks & Layton, 1984). The expression of the metastatic potential of these cells is strongly influenced by the age and immune status of the host. The CMT64 system is a particularly useful model for experimental metastasis studies