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21.
For complex genetic diseases involving incomplete penetrance, genetic heterogeneity, and multiple disease genes, it is often difficult to determine the molecular variant(s) responsible for the disease pathogenesis. Linkage and association studies may help identify genetic regions and molecular variants suspected of being directly responsible for disease predisposition or protection, but, especially for complex diseases, they are less useful for determining when a predisposing molecular variant has been identified. In this paper, we expand upon the simple concept that if a genetic factor predisposing to disease has been fully identified, then a parent homozygous for this factor should transmit either of his/her copies at random to any affected children. Closely linked markers are used to determine identity by descent values in affected sib pairs from a parent homozygous for a putative disease predisposing factor. The expected deviation of haplotype sharing from 50%, when not all haplotypes carrying this factor are in fact equally predisposing, has been algebraically determined for a single locus general disease model. Equations to determine expected sharing for multiple disease alleles or multiple disease locus models have been formulated. The recessive case is in practice limiting and therefore can be used to estimate the maximum proportion of putative susceptibility haplotypes which are in fact predisposing to disease when the mode of inheritance of a disease is unknown. This method has been applied to 27 DR3/DR3 parents and 50 DR4/DR4 parents who have at least 2 children affected with insulin dependent diabetes mellitus (IDDM). The transmission of both DR3 and DR4 haplotypes is statistically different from 50% (P < 0.05 and P < 0.001, respectively). An upper estimate for the proportion of DR3 haplotypes associated with a high IDDM susceptibility is 49%, and for DR4 haplotypes 38%. Our results show that the joint presence of non-Asp at DQ beta position 57 and Arg at DQ alpha position 52, which has been proposed as a strong IDDM predisposing factor, is insufficient to explain the HLA component of IDDM predisposition. 相似文献
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It is well known that low levels of light element impurities, such as oxygen and nitrogen, can significantly modify phase
equilibria in conventional titanium alloys. However, although the role of nitrogen and oxygen as alpha stabilizers is well
established, little quantitative work exists in ternary and higher order systems. Moreover the effect of such elements on
equilibria with phases other than cx-and P-Ti is often unknown. The problems in measuring light elements at the microscopic
level adds to the difficulty of establishing partitioning, and old axioms are often transferred to new alloys with little
evidence that they are applicable. As part of a current program on titanium alloys, phase diagram modeling has been performed
for a variety of titanium alloys with additions of oxygen and nitrogen. This paper presents results for the system Ti-Al-V-O-(N,C)
with particular reference to the O additions to the commercially important alloy Ti-6A1-4V.
This paper was presented at the International Phase Diagram Prediction Symposium sponsored by the ASM/MSD Thermodynamics and
Phase Equilibria Committee at Materials Week, October 21–23,1991, in Cincinnati, OH. The symposium was organized by John Morral,
University of Connecticut, and Philip Nash, Illinois Institute of Technology. 相似文献
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Christine Di Massimo Paul A. Lant Aidan Saunders Gary A. Montague Ming T. Tham A. Julian Morris 《Journal of chemical technology and biotechnology (Oxford, Oxfordshire : 1986)》1992,53(3):265-277
The last decade has seen the development of a number of approaches for estimating those variables which are difficult to measure on-line in industrial process situations. Whilst a range of techniques is available, a common element is the use of process knowledge in the form of a system model. In the case of bioprocess systems, although a large range of models has been presented in the literature, their use in estimation schemes on an industrial scale has been limited. A number of reasons can be identified for their low level of utilisation. Of particular significance is the uncertainty which exists in quantifying system performance and the process-model mismatch which inevitably results. The level of ‘pre-defined model’ uncertainty, together with the knowledge gained during the course of the fermentation, serves to dictate estimator structure. The paper considers a range of estimation strategies and contrasts, through industrial applications, their performance characteristics and utility. 相似文献
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Communication between patients with breast cancer and health care providers. Determinants and implications 总被引:1,自引:0,他引:1
C Lerman M Daly WP Walsh N Resch J Seay A Barsevick L Birenbaum T Heggan G Martin 《Canadian Metallurgical Quarterly》1993,72(9):2612-2620
BACKGROUND: This study evaluated the perceptions of patients with breast cancer of their medical interactions with providers. The determinants and psychological consequences of communication problems also were examined. METHODS: Ninety-seven patients with Stage I or II breast cancer completed a set of validated questionnaires before initiating postoperative therapy. Data on psychological distress were collected at baseline and 3-month follow-up, and multivariate models were fit to explain the relationship between pretreatment communication problems and subsequent psychological distress. Data on clinical variables were abstracted from medical records. RESULTS: A substantial proportion of patients (84%) reported difficulties communicating with the medical team. Communication problems were more common among patients who were less optimistic about their disease and had less assertive coping styles. Patient-reported communication problems were associated with increased anxiety, depression anger, and confusion at the 3-month follow-up. The association between communication problems and mood disturbance remained significant, although small, after adjusting for baseline mood disturbance, demographic, clinical, and coping style variables. CONCLUSION: Interventions that enhance communication between patients with breast cancer and their providers may improve patients' psychological adjustment to treatment. Conversely, interventions that lower distress and modify coping style may enhance communication. 相似文献
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1. The classical ATP sensitive K+ (K(ATP)) channels are composed of a sulphonylurea receptor (SUR) and an inward rectifying K+ channel subunit (BIR/Kir6.2). They are the targets of vasorelaxant agents called K+ channel openers, such as pinacidil and nicorandil. 2. In order to examine the tissue selectivity of pinacidil and nicorandil, in vitro, we compared the effects of these agents on cardiac type (SUR2A/Kir6.2) and vascular smooth muscle type (SUR2B/Kir6.2) of the K(ATP) channels heterologously expressed in HEK293T cells, a human embryonic kidney cell line, by using the patch-clamp method. 3. In the cell-attached recordings (145 mM K+ in the pipette), pinacidil and nicorandil activated a weakly inwardly-rectifying, glibenclamide-sensitive 80 pS K+ channel in both the transfected cells. 4. In the whole-cell configuration, pinacidil showed a similar potency in activating the SUR2B/Kir6.2 and SUR2A/Kir6.2 channels (EC50 of approximately 2 and approximately 10 microM, respectively). On the other hand, nicorandil activated the SUR2B/Kir6.2 channel > 100 times more potently than the SUR2A/Kir6.2 (EC50 of approximately 10 microM and > 500 microM, respectively). 5. Thus, nicorandil, but not pinacidil, preferentially activates the K(ATP) channels containing SUR2B. Because SUR2A and SUR2B are diverse only in 42 amino acids at their C-terminal ends, it is strongly suggested that this short part of SUR2B may play a critical role in the action of nicorandil on the vascular type classical K(ATP) channel. 相似文献
30.
AM Moody WP Mayles JM Bliss RP A'Hern JR Owen J Regan B Broad JR Yarnold 《Canadian Metallurgical Quarterly》1994,33(2):106-112
A prospective assessment of late changes in breast appearance in 559 patients after tumour excision and radiotherapy for early breast cancer noted a strong association with breast size. Only 3/48 (6%) patients with small breasts developed moderate or severe late changes compared with 94/423 (22%) with medium sized breasts and 34/88 (39%) patients with large breasts (p < 0.001). One possibility is that greater radiation changes are related to greater dose inhomogeneity in women with large breasts. To explore this hypothesis, radiation dose distributions were assessed in a separate group of 37 women in whom three-level transverse computer tomographic images of the breast in the treatment position were available. A significant correlation was found between breast size and dose inhomogeneity which may account for the marked changes in breast appearance reported in women with large breasts. 相似文献