Genetic selection strategies: computer modeling

There are four primary factors to consider in genetic selection strategies: 1) accuracy of selection, 2) selection intensity, 3) effective population size, and 4) mating system. Current theory indicates that optimum response to selection is achieved by maximizing the first three factors and using a mating systems that allows optimization of reproductive characteristics in dam lines and production characteristics in sire lines. However, with limited resources, compromises among the first three factors are needed. Simulations are useful for examining those compromises. Unrealistic simplifying assumptions are necessary for analytic theoretical results and thus do not address real world breeding problems. Using simulations, the relationship between selection accuracy, which is increased by use of family selection indices or Best Linear Unbiased Prediction (BLUP), and response to selection was examined. Results show that those procedures place a great restriction on effective population size, which offsets most of their advantage, i.e., there is too little emphasis on effective population size. A revision of the methodology and a reappraisal of the results of selection theory for optimization of genetic response is required. Another relationship that is of fundamental importance in breeding programs is that between selection intensity and effective population size. Analytical results for the additive case have been developed but have never been extended to heterotic traits. A gene level simulation program was developed to examine that relationship. Results show that the optimal selection strategy depends on the trait being selected. For additive traits and in the short term (20 generations), one should maximize selection intensity. For heterotic traits, an intermediate proportion (25% of each sex) gives optimal response. In all breeding strategies, primary attention must be given to the rate of inbreeding, which is increased by increasing either accuracy of selection or selection intensity. Inbreeding reduces response to selection in two ways. First, for both additive and nonadditive traits, inbreeding is a measure of the amount of random genetic drift that has occurred. Genetic drift causes loss of favorable alleles. Once lost, those alleles can never be recovered and thus genetic drift lowers the selection limit. Second, for heterotic traits, inbreeding results in a depression of the mean caused by directional dominance.     

Polymerase chain reaction amplification analyses of clonality in T-cell malignancy including peripheral T-cell lymphoma

Clonality in T-cell malignancy was investigated using T-cell receptor (TcR) V beta 1-20 family primers and polymerase chain reaction amplification (PCR) of cDNA prepared from tissue biopsies and blood involved with tumour. Secondary PCR amplification of the VDJ joints of primary PCR products was performed to distinguish clonal from polyclonal products, and clonal V beta gene products were confirmed by direct PCR sequencing in the majority of cases. In eight T-cell malignancies including T-cell acute lymphoblastic leukaemia (T-ALL) and T-cell chronic lymphocytic leukaemia (T-CLL) shown to be clonal by Southern blot analysis, one or two primary PCR products were identified and shown to be clonal. In five cases of peripheral T-cell lymphoma (PTCL) all V beta 1-20 families were identified after primary PCR amplification, and clonal products were identified in two cases after secondary amplification; TcR V beta clonal families could not be demonstrated in the remaining three cases. These data were in agreement with previous Southern blot analysis of these cases, and confirmed the presence of reactive T cells in PTCL as well as providing further evidence for the genotypic heterogeneity of this entity. In the remaining case, a blood lymphocytosis, primary PCR amplification produced predominant TcR V beta 6 and V beta 12 family products, of which the V beta 6 family proved clonal after secondary PCR amplification. There was no evidence for overrepresentation of TCR V beta families by the tumour populations in this study, furthermore the data confirm the involvement of reactive cells in T-cell malignancy and the genetic heterogeneity of PTCL.     

Tissue fixation security in transosseous rotator cuff repairs: a mechanical comparison of simple versus mattress sutures

The primary purpose of this investigation was to compare tissue fixation security by simple sutures versus mattress sutures in transosseous rotator cuff repair. These two repair techniques were each performed in 17 human cadaver shoulders, with two bone tunnels being used for the repair by two simple sutures and two other bone tunnels being used for the repair by one mattress suture. The repairs were loaded to failure in a servohydraulic materials test system. Rotator cuff repair by simple sutures was found to be significantly stronger than repair by mattress sutures (P = .0007). The average ultimate load to failure for the simple suture construct (189.62 N) was 39.72% greater than that for the mattress suture construct (135.71 N). Most of the failures occurred by suture breakage at the knot. Load-sharing by multiple suture tails and multiple knots in the simple suture configuration likely contributed to its superior strength characteristics compared with the mattress suture configuration.     

Barriers to Increased Engineering Graduate Enrollments: Counterforces and Their Implementation

This paper highlights the role of the faculty member in recruiting students currently enrolled in B.S. programs in engineering and the sciences into full-time pursuit of a graduate-level engineering degree. The faculty member is demonstrated to be in a unique position to influence such students, providing strong counterforces to a confluence of attitudes and pressures experienced during the B.S. experience which effectively create a barrier to full-time engineering graduate study. We analyze this barrier via the method of force field analysis, and demonstrate that effective recruitment into full-time graduate study must be based on a four-fold strategy of education, expectations, improved B.S. experience and better control of the B.S. environment. Approaches to implement these strategies are discussed.     

Shear numbers of protein beta-barrels: definition refinements and statistics

The original definition of shear number for a beta-barrel is not unique if it contains one or more uneven beta-bulges. We define the shear number of a beta-barrel as the minimal change of residue numbers in the backbone direction for all closed paths on the beta-barrel. We also discuss how to overcome some computational difficulties. It is pointed out that some closed beta-sheets should not be considered as beta-barrels. The pertinent statistics obtained from a representative list of the Protein Data Bank entries are summarized. All beta-barrels have positive shear numbers, i.e. they are right-twisted. The shear numbers of most beta-barrels are even, but exceptions do exist. The sizes of beta-ladders in a beta-barrel vary significantly. Most beta-barrels contain uneven beta-bulges, which may have important biological functions.     

Diminished levels of insulin-like growth factor-I in lungs in streptozotocin-induced diabetes: relation to nutritional status and growth

It is yet unknown whether the impaired nutritional status of streptozotocin-induced diabetic rats influences changes in levels of insulin-like growth factor-I (IGF-I) in this experimental model of diabetes. To explore this possibility, simultaneous studies were undertaken of rats made diabetic by streptozotocin (75 mg/kg body wt, intraperitoneally) and undernourished control rats with similar somatic growth rate (determined by body weight gain), in comparison with normal controls. Serum IGF-I levels were diminished in the untreated diabetic and undernourished control animals, but more so in the diabetic group. Lung IGF-I levels (per lung and per lung DNA) and DNA contents were diminished to similar degrees in the untreated diabetic animals and the undernourished control group. Lung dry weights of the diabetic rats were greater than those of the undernourished control group, such that lung IGF-I/100 mg tissue dry wt in the former was significantly lower than in the latter group. Insulin treatment of the diabetic rats restored their body weights, serum and lung IGF-I levels, and DNA contents to normal control values. Lung IGF-I levels in the diabetic rats correlated strongly with serum glucose (r = .75) and body weight (r = .79), and moderately with lung weight (r = .43) and lung DNA (r = .58). These findings suggest that the diminished lung IGF-I levels in streptozotocin-induced diabetes may be related to the impaired nutritional status and/or somatic growth of the experimental animals, and that this relationship may be responsible, at least in part, for the diminished lung cellular proliferation observed in experimental diabetic animals.