The 70 carboxyl-terminal amino acids of nascent secretory proteins are protected from proteolysis by the ribosome and the protein translocation apparatus of the endoplasmic reticulum membrane

We have used proteolysis to examine the environment through which nascent secretory proteins are translocated across the membrane of the endoplasmic reticulum. After solubilization of rough microsomes with detergent, fragments comprised of the approximately 70 carboxyl-terminal amino acids of translocating nascent chains initiated and targeted in vivo were protected from digestion by added proteases. About 40 amino acids of nascent chains were protected from proteolysis by the ribosome; thus, membrane-derived components protect an additional 30 amino acids. Under conditions in which those 30 additional amino acids are protected, only a small set of integral membrane proteins remained associated with the ribosome. These proteins include the Sec61 complex previously identified as the core component of the membrane-bound protein translocation apparatus. These results support the concept of a translocation pore that makes intimate contact with the ribosome and thereby protects nascent chains from proteolytic digestion for an additional, constant length.     

Structure-activity studies of human tumour necrosis factors

The mechanism by which tumour necrosis factors (TNF and lymphotoxin,also called TNFß and TNFß respectively) exerttheir cytotoxic activity on many malignant cells, remains largelyunknown. Furthermore, the broad array of differentiation (geneinduction) and mitogenic activities towards many primary cellsis still a subject of intensive investigation. TNF is an importantmediator in inflammation, immune responses and infection-relatedphenomena and these activities contribute to the severe toxidtyseen when TNF is used as an anticancer agent. The first stepin the mechanism of action is the specific binding of the ligandto its receptors and dissection of the molecular mechanism involvedin this interaction is the subject of this review. The reasonsfor the interest in this aspect are obvious: first, the developmentof strong antagonistic TNF analogues can be useful in dampeningthe potentially lethal or debilitating effects of an overproductionof the cytokine (as in septic shock or rheumatoid arthritis).Secondly, since two distinct TNF receptors exist, constructionof TNF muteins that distinguish between both types may leadto derivatives of this plekrtropic agent with a more restrictedbiological activity pattern. Ideally, one would like to developa TNF mutant that has retained its cytotoxic action on tumourcells without inducing the deleterious systemic toxteity. Suchan optimized TNF molecule could become a potent anticancer agent     

Why models rather than rules give a better account of propositional reasoning: A reply to Bonatti and to O'Brien, Braine, and Yang.

D. P. O'Brien et al (see record 1995-08272-001) argue that the mental model theory of propositional reasoning is easy to refute, and they report 3 experiments that they believe falsify the theory. In contrast, L. Bonatti (see record 1995-08253-001) argues that the model theory is too flexible to be falsified. It is shown that the experiments by O'Brien et al do not refute the model theory and that Bonatti's claims are ill founded. Formal rule theories of propositional reasoning have 3 major weaknesses in comparison with the model theory: (1) They have no decision procedure; (2) they lack predictive power, providing no account of several robust phenomena (e.g., erroneous conclusions tend to be consistent with the premises); and (3) as a class of theories, they are difficult to refute experimentally. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A tractable large-signal dynamic model-application to stronglycoupled distributed feedback lasers

The modulation characteristics of DFB semiconductor lasers have been studied using a transfer matrix method combined with an appropriate rate equation analysis. The model takes into account longitudinal mode spatial hole burning, as well as the nonuniform current injection resulting from the axially varying Fermi voltage, and can be used for the efficient simulation of static, small-signal, and large-signal dynamic properties. The program is applied to the interpretation of experimental data from a strongly coupled InGaAsP/InP DFB laser. The experimental high-frequency properties of this device are well described by the simulations     

The geographic variation of cancer incidence in Ontario

OBJECTIVES: Our objectives were (1) to describe an analysis of the spatial pattern of cancer incidence in Ontario and (2) to discuss the quality of data in the Ontario Cancer Registry with respect to the accuracy of local cancer rates. METHODS: Cancer incidence rates were calculated for 22 cancer sites in 49 counties of Ontario during 1976 to 1986. Capture-recapture methods were used to estimate completeness of case registration, and completeness of residence information was also assessed. Spatial autocorrelation was used in measuring the geographic pattern of incidence rates. Comparisons were also made between sexes and with earlier data from 1966 to 1975. RESULTS: The quality of the geographic data in the registry appeared good, and corrections for incomplete or inaccurate registration had little impact. About one third of the sex-site combinations showed some evidence of spatial patterning in the cancer rate. Particularly strong regional variation was noted for cancers of the stomach, lung, uterus, and prostate. CONCLUSIONS: The analysis revealed a number of cancers with significant spatial patterning of risk. Further work is needed to relate the cancer data to other information on potential life-style and environmental factors.