Superconducting gravity gradiometer mission. Volume 1: Study team executive summary

An executive summary is presented based upon the scientific and engineering studies and developments performed or directed by a Study Team composed of various Federal and University activities involved with the development of a three-axis Superconducting Gravity Gradiometer integrated with a six-axis superconducting accelerometer. This instrument is being developed for a future orbital mission to make precise global gravity measurements. The scientific justification and requirements for such a mission are discussed. This includes geophysics, the primary mission objective, as well as secondary objectives, such as navigation and tests of fundamental laws of physics, i.e., a null test of the inverse square law of gravitation and tests of general relativity. The instrument design and status along with mission analysis, engineering assessments, and preliminary spacecraft concepts are discussed. In addition, critical spacecraft systems and required technology advancements are examined. The mission requirements and an engineering assessment of a precursor flight test of the instrument are discussed

Bohr sets and multiplicative diophantine approximation

In two dimensions, Gallagher's theorem is a strengthening of the Littlewood conjecture that holds for almost all pairs of real numbers. We prove an inhomogeneous fibre version of Gallagher's theorem, sharpening and making unconditional a result recently obtained conditionally by Beresnevich, Haynes and Velani. The idea is to find large generalised arithmetic progressions within inhomogeneous Bohr sets, extending a construction given by Tao. This precise structure enables us to verify the hypotheses of the Duffin--Schaeffer theorem for the problem at hand, via the geometry of numbers

Birch's theorem with shifts

A famous result due to Birch (1961) provides an asymptotic formula for the number of integer points in an expanding box at which given rational forms of the same degree simultaneously vanish, subject to a geometric condition. We present the first inequalities analogue of Birch's theorem

A note on rational points near planar curves

Under fairly natural assumptions, Huang counted the number of rational points lying close to an arc of a planar curve. He obtained upper and lower bounds of the correct order of magnitude, and conjectured an asymptotic formula. In this note, we establish the conjectured asymptotic formula

Stem cells and the origin of gliomas: A historical reappraisal with molecular advancements.

The biology of both normal and tumor development clearly possesses overlapping and parallel features. Oncogenes and tumor suppressors are relevant not only in tumor biology, but also in physiological developmental regulators of growth and differentiation. Conversely, genes identified as regulators of developmental biology are relevant to tumor biology. This is particularly relevant in the context of brain tumors, where recent evidence is mounting that the origin of brain tumors, specifically gliomas, may represent dysfunctional developmental neurobiology. Neural stem cells are increasingly being investigated as the cell type that originally undergoes malignant transformation - the cell of origin - and the evidence for this is discussed

Immune-Mediated Drug Induced Liver Injury: A Multidisciplinary Approach

This thesis presents an approach to expose relationships between immune mediated drug induced liver injury (IMDILI) and the three-dimensional structural features of toxic drug molecules and their metabolites. The series of analyses test the hypothesis that drugs which produce similar patterns of toxicity interact with targets within common toxicological pathways and that activation of the underlying mechanisms depends on structural similarity among toxic molecules. Spontaneous adverse drug reaction (ADR) reports were used to identify cases of IMDILI. Network map tools were used to compare the known and predicted protein interactions with each of the probe drugs to explore the interactions that are common between the drugs. The IMDILI probe set was then used to develop a pharmacophore model which became the starting point for identifying potential toxicity targets for IMDILI. Pharmacophore screening results demonstrated similarities between the probe IMDILI set of drugs and Toll-Like Receptor 7 (TLR7) agonists, suggesting TLR7 as a potential toxicity target. This thesis highlights the potential for multidisciplinary approaches in the study of complex diseases. Such approaches are particularly helpful for rare diseases where little knowledge is available, and may provide key insights into mechanisms of toxicity that cannot be gleaned from a single disciplinary study

Effective applications of microcomputer-based management information and decision support systems for small and medium sized enterprises

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.Firstly, this thesis reviews the literature on the application of microcomputer-based Management Information Systems (MISs) and Decision Support Systems (DSS) to Small and Medium sized Enterprises (SMEs). It is found that the hardware platform today is already sufficient for SMEs. However, information regarding successful implementation of MISs for SMEs is scarce and largely fragmented. DSS requires more focused and dedicated use of information to support managerial decision making. Unfortunately, the development of DSSs for SMEs is even more backward. Yet, there is an emerging need for SMEs today because business operations have become more sophisticated under intensified competition. With this scenario in mind, the author undertook intensive questionnaire and case surveys to find out the current development and trends for the effective applications of MISs and DSSs. In 1987, the author was awarded the Oshikawa Fellowship by Asian Productivity Organisation in Tokyo and started the present research. 446 completed questionnaire survey sheets from U.K. and Hang Kong have been received and analysed. 67 SMEs and related organisations in 6 developing/developed countries were also visited. This forms the knowledge for the development of expert systems (ES) for effective applications of MIS. The approach for DSS is based on a carefully selected business game which has most of the common business decision parameters. Intensive experiment with over 100 subjects was conducted in running the game, with an average time contribution of about 20 hours/person. The findings are again consolidated and structured into an ES. Longitudinal research was conducted in 5 representative SMEs. With the use of action learning and participation of the researcher, more in-depth firsthand information were obtained and analysed. These form part of the input to the ES as well. Both ES have been validated and further improved. The experimenters find these as keys to develop MIS/DSS for SMEs. A marketing plan is suggested to launch these two products so that they can become more easily available. Finally, recommendations are made on the effective use of the ES and for further development

Immune-Mediated Drug Induced Liver Injury: A Multidisciplinary Approach

This thesis presents an approach to expose relationships between immune mediated drug induced liver injury (IMDILI) and the three-dimensional structural features of toxic drug molecules and their metabolites. The series of analyses test the hypothesis that drugs which produce similar patterns of toxicity interact with targets within common toxicological pathways and that activation of the underlying mechanisms depends on structural similarity among toxic molecules. Spontaneous adverse drug reaction (ADR) reports were used to identify cases of IMDILI. Network map tools were used to compare the known and predicted protein interactions with each of the probe drugs to explore the interactions that are common between the drugs. The IMDILI probe set was then used to develop a pharmacophore model which became the starting point for identifying potential toxicity targets for IMDILI. Pharmacophore screening results demonstrated similarities between the probe IMDILI set of drugs and Toll-Like Receptor 7 (TLR7) agonists, suggesting TLR7 as a potential toxicity target. This thesis highlights the potential for multidisciplinary approaches in the study of complex diseases. Such approaches are particularly helpful for rare diseases where little knowledge is available, and may provide key insights into mechanisms of toxicity that cannot be gleaned from a single disciplinary study

The US Health Care System and Lagging Life Expectancy: A Case Study

Life expectancy in the United States fares poorly in international comparisons. Its low ranking is often blamed on a poor performance by the health care system rather than on behavioral factors. This paper compares mortality trends from prostate cancer in the United States to those in other developed countries. Prostate cancer is chosen because it can be detected at an early stage, because effective treatments are available, and because it is less heavily influenced by behavioral factors than most other chronic diseases. We find that, after the introduction of the PSA screening test for prostate cancer, mortality from the disease declined significantly faster in the United States than in the set of comparison countries. Trends in incidence and survival rates support the interpretation that the US health care system has worked very effectively to reduce mortality from this important disease. A brief consideration of breast cancer suggests that similar processes may have been at work among women