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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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The formation of zinc ferrite (ZnFe2O4) during the roasting of iron-bearing zinc concentrates requires substantial additional processing to recover the zinc from
this compound by leaching and to eliminate the iron from the leachate. The phase changes that occur in the particles of a
typical industrial zinc sulfide concentrate during roasting in a fluidized bed at 1223 K were investigated by the use of light
microscopy, electron microprobe analysis, and SEM with EDS. The processes which the iron undergoes during its eventual transformation
into ferrite have been clarified by examination of the phases and the morphology of partially roasted marmatitic sphalerite
particles (Zn, Fe)S, and by reference to the known phase equilibria involved in the Zn-Fe-S-0 system. The oxidation of ironbearing
sphalerite occurs in three stages. The first involves the selective diffusion of most of the iron to the particle surface
resulting in the formation of an iron oxide shell enclosing a largely unreacted zinc sulfide kernel. In the second stage,
this kernel is oxidized to form a solid solution of zinc oxide and iron oxide. The iron is initially present in the ferrous
state but, with the disappearance of the sulfide kernel, is oxidized to ferric iron. In the final stage, this dissolved iron
oxide and the iron oxide shell react with the surrounding zinc oxide to form the refractory spinel zinc ferrite. 相似文献
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Kirk C. Valanis 《Canadian Metallurgical Quarterly》2003,129(9):1039-1047
In this paper we derive Newton’s 2nd Law of Motion from the constitutive equation of elasticity of a space-time continuum in four dimensions. This we do by introducing a four-dimensional material continuum with a Minkowskian metric, in analogy with Einstein’s general theory of relativity. The four-continuum is deformable in both space and time. The physics of the deformation is embedded in a variational principle, which is a form-invariant extension of its classical mechanical counterpart in three dimensions, but with the acceleration term absent. General dynamic equations of elasticity in four dimensions are thereby derived. When the constraint of temporal inextensibility (universal time) is introduced, these equations yield readily the dynamic equations of elasticity in three dimensions. The presence of the inertia term in these equations, is a direct consequence of the temporal curvature induced by the deformation of the four-continuum. Newton’s law of motion for rigid bodies follows when the additional constraint of spatial inextensibility is introduced. 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