Challenges in the human genome project

The purpose and scope of the human genome project are discussed. Basic biological concepts underlying the project are reviewed. The two processes-logic and experimentation-used to understand DNA sequences are compared, and the process of obtaining the sequence is described. Two problem areas in this collaboration between biologists and computer scientists are examined. They arise from differences in training that can make communication difficult, and nomenclature problems     

Alliance and Dropout in Family Therapy for Adolescents With Behavior Problems: Individual and Systemic Effects.

This study examined the relationship between alliance and retention in family therapy. Alliance was examined at the individual (parent and adolescent) and family levels (within-family differences). Participants were 34 families who received functional family therapy for the treatment of adolescent (aged 12-18 years) behavior problems. Families were classified as treatment dropouts (n=14) or completers (n=20). Videotapes of the first sessions were rated to identify parent and adolescent alliances with the therapist. Results demonstrated that individual parent and adolescent alliances did not predict retention. However, as hypothesized, dropout cases had significantly higher unbalanced alliances (parent minus adolescent) than did completer cases. These findings highlight the importance of alliances in functional family therapy and suggest that how the alliance operates in conjoint family therapy may be a function of systemic rather than of individual processes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Limitations and benefits of cooperative proxy caching

Cooperating proxy caches are groups of HTTP proxy servers that organize to share cached objects. This paper develops analytical models for proxy cooperation which use speedup in user response time as the performance metric. Speedup expressions are derived for the cooperation upper bound, a proxy mesh, and a three-level proxy hierarchy. The equations compare fundamental design approaches by separating the proxy organization for object delivery from the mechanism for object discovery. Discovery mechanisms analyzed for the mesh and hierarchy models include ideal discovery, Internet cache protocol (ICP) query, and distributed metadata directories. Equations are evaluated using parameter estimates from experiments and from analysis of cache trace logs. Results indicate that proxy cooperation is marginally viable from the standpoint of average user response time, and that the miss penalty for the hierarchy renders it less viable than the mesh. Proxy cooperation can, however, reduce the variability in user response time and the number of long delays. A trace-driven simulation shows that caching constraints have little effect on cooperation performance due to request filtering by lower level caches.     

Pigmentation phenotypes of variant extension locus alleles result from point mutations that alter MSH receptor function

Coat colors in the chestnut horse, the yellow Labrador retriever, the red fox, and one type of yellow mouse are due to recessive alleles at the extension locus. Similarly, dominant alleles at this locus are often responsible for dark coat colors in mammals, such as the melanic form of the leopard, Panthera pardus. We show here that the murine extension locus encodes the melanocyte-stimulating hormone (MSH) receptor. In mice, the recessive yellow allele (e) results from a frameshift that produces a prematurely terminated, nonfunctioning receptor. The sombre (Eso and Eso-3J) and tobacco darkening (Etob) alleles, which both have dominant melanizing effects, results from point mutations that produce hyperactive MSH receptors. The Eso-3J receptor is constitutively activated, while the Etob receptor remains hormone responsive and produces a greater activation of its effector, adenylyl cyclase, than does the wild-type allele.     

Hypothermic ischaemia of the liver: a re-perfusion phenomenon

BACKGROUND: The effects of hypothermic injury to the liver were investigated on an isolated perfusion circuit by comparing porcine livers with varying degrees of preservation injury. METHODS: A group of unstored livers (n = 5) were compared to livers stored in University of Wisconsin (UW) solution for 18 h (n = 5), and a group of livers stored in Hartmann's solution for 18 h (n = 5). RESULTS: We observed that the degree of platelet sequestration was directly related to the severity of the preservation injury. After 2 h of isolated liver perfusion, the perfusate platelet count fell from 148 +/- 14 x 10(9)/L to 84 +/- 13 x 10(9)/L for control livers. In comparison for livers stored in UW solution, the platelet count fell from 173 +/- 43 x 10(9)/L to 61 +/- 14 x 10(9)/L representing a 64.8% fall, while for those stored in Hartmann's solution, an even more profound fall from 152 +/- 36 x 10(9)/L to 19 +/- 9 x 10(9)/L (87.5% fall) was observed. The difference between the UW-stored and Hartmann's-stored livers was significant (P < 0.05). However, using this model, the degree of leukocyte sequestration did not differentiate the groups. Both histological and ultrastructural examination of liver biopsies taken immediately following revascularization demonstrated that for mild degrees of preservation injury following hypothermic storage, changes occur to the sinusoidal lining cells well before changes to the parenchymal elements. CONCLUSIONS: These findings substantiate the hypothesis that the primary injury associated with hypothermia involves the sinusoidal lining cells (non-parenchymal elements), that it is predominantly a reperfusion phenomenon and that efforts at improving preservation should therefore be targeted primarily at these cells and not the hepatocytes.     

Superior vena cava syndrome after heart transplantation: percutaneous treatment of a complication of bicaval anastomoses

The aims of this study were to establish a working rabbit heart model of regional myocardial ischaemia in which electrophysiologic parameters and arrhythmogenesis could be correlated and to explore the mechanisms underlying the antiarrhythmic activity of lignocaine. Monophasic action-potential duration (MAPD90), effective refractory period (ERP), and conduction delay were measured at three ventricular sites in isolated hearts paced at 3.3 Hz. The hearts were treated before and throughout 30 min of ischaemia and 15 min of reperfusion with a vehicle or 20 microM lignocaine. In both groups, ischaemia produced a similar shortening in MAPD90. Lignocaine decreased ERP shortening during ischaemia from -56+/-4 to -32+/-6 ms. An ischaemia-induced increase in conduction delay was greater in the lignocaine than the control group (49+/-7 vs. 11+/-2 ms). Ischaemia-induced dispersion of repolarisation was reduced by lignocaine from 66+/-4 to 32+/-7 ms, and dispersion of refractoriness was decreased from 57+/-6 to 16+/-3 ms. Lignocaine decreased inducibility of ventricular fibrillation (VF) during ischaemia from 86 to 25%. We conclude that, in this model, the antiarrhythmic activity of lignocaine during regional ischaemia is associated with an increase in ischaemia-induced conduction delay and reduced dispersion of repolarisation and refractoriness.