The genotype of the human cancer cell: implications for risk analysis

An extremely large database describes genotypes associated with the human cancer phenotype and genotypes of human populations with genetic predisposition to cancer. Aspects of this database are examined from the perspective of risk analysis, and the following conclusions and hypotheses are proposed: (1) The genotypes of human cancer cells are characterized by multiple mutated genes. Each type of cancer is characterized by a set of mutated genes, a subset from a total of more than 80 genes, that varies between tissue types and between different tumors from the same tissue. No single cancer-associated gene nor carcinogenic pathway appears suitable as an overall indicator whose induction serves as a quantitative marker for risk analysis. (2) Genetic defects that predispose human populations to cancer are numerous and diverse, and provide a model for associating cancer rates with induced genetic changes. As these syndromes contribute significantly to the overall cancer rate, risk analysis should include an estimation of the effect of putative carcinogens on individuals with genetic predisposition. (3) Gene activation and inactivation events are observed in the cancer genotype at different frequencies, and the potency of carcinogens to induce these events varies significantly. There is a paradox between the observed frequency for induction of single mutational events in test systems and the frequency of multiple events in a single cancer cell, suggesting events are not independent. Quantitative prediction of cancer risk will depend on identifying rate-limiting events in carcinogenesis. Hyperproliferation and hypermutation may be such events. (4) Four sets of data suggest that hypermutation may be an important carcinogenic process. Current mechanisms of risk analysis do not properly evaluate the potency of putative carcinogens to induce the hypermutable state or to increase mutation in hypermutable cells. (5) High-dose exposure to carcinogens in model systems changes patterns of gene expression and may induce protective effects through delay in cell progression and other processes that affect mutagenesis and toxicity. Paradigms in risk analysis that require extrapolation over wide ranges of exposure levels may be flawed mechanistically and may underestimate carcinogenic effects of test agents at environmental levels. Characteristics of the human cancer genotype suggest that approaches to risk analysis must be broadened to consider the multiplicity of carcinogenic pathways and the relative roles of hyperproliferation and hypermutation. Further, estimation of risk to general human populations must consider effects on hypersusceptible individuals. The extrapolation of effects over wide exposure levels is an imprecise process.     

Moving on and moving up: The experience of households who resell public sector dwellings

The long‐term consequences of the sale of public sector dwellings to sitting tenants are under‐researched; in particular, the experience of tenant purchasers in the housing market subsequent to purchase is little known. This paper reports research designed to fill this gap in knowledge. Over 200 tenants who had bought their dwelling from the Scottish Special Housing Association and subsequently resold on the open market were traced using the Register fo Sasines and the Land Register and interviewed. Most had made considerable capital gains on resale and had used some of the realised capital to trade up in the housing market. They were, on average, slightly more affluent and younger than sitting tenant purchasers generally; they represented a group of households who were privileged within the public sector through living as tenants in the best stock and who were enabled by the Right to Buy to convert that good luck into hard cash and move into mainstream owner occupation. This good luck compounded the advantaged position vis‐à‐vis other tenants that they enjoyed in the labour market.     

Perceptions of elder abuse and help-seeking patterns among African-American, Caucasian American, and Korean-American elderly women

Thirteen scenarios were used to measure and compare the perceptions of elder abuse and help-seeking behaviors of African-American, Caucasian American, and Korean-American elderly women. Significant group differences existed in their perceptions of elder abuse with regard to six scenarios, and the Korean-American women were substantially less likely to perceive a given situation as abusive than the other groups. The three groups also showed significant differences in their intended use of formal and informal sources of help in the case of elder abuse.     

Jitter reduction through feedback for picosecond pulsed InGaAsPlasers

Following a comparison of picosecond-pulse generation techniques, feedback schemes are reported for the generation of picosecond pulse trains with improved jitter for both multicontact and conventional single-contact InGaAsP-InP lasers. Subpicosecond jitter is achieved for Q-switched laser sources using a novel optoelectronic feedback scheme. The use of resonant electrical feedback is shown to improve the timing jitter of gain-switched pulses by up to six times. Pulse-to-pulse timing jitter as low as 250 fs is demonstrated for a hybrid of optical and electrical feedback schemes. Limits for timing jitter in diode lasers are established for optoelectronic, electrical, and optical feedback schemes, and the key picosecond pulse generation schemes are compared in terms of timing jitter for the first time     

Atmospheric Chemistry of 2-Ethyl Acrolein

The atmospheric oxidation of the unsaturated aldehyde 2-ethyl acrolein, CH₂=C(C₂H₅)CHO, has been studied in laboratory experiments involving the reaction of ozone with 2-ethyl acrolein in the dark (with cyclohexane added to scavenge the hydroxyl radical), and the sunlight irradiation of 2-ethyl acrolein with NO in air. The major carbonyl products of the 2-ethyl acrolein reaction with ozone are formaldehyde, acetaldehyde, and the dicarbonyl ethylglyoxal, CH₃CH₂COCHO. Sunlight irradiation of 2-ethyl acrolein and NO led to the formation of three carbonyls (formaldehyde, acetaldehyde, and ethylglyoxal) and three peroxyacyl nitrates, (RC(O)OONO₂), including PAN (R = CH₃), PPN (R = C₂H₅), and the unsaturated compound EPAN (R = CH₂=C(C₂H₅)). Mechanisms are outlined for the reactions of ozone and of the hydroxyl radical with 2-ethyl acrolein. These mechanisms are consistent with the observed carbonyl and peroxyacyl nitrate products. Thermal decomposition, a major atmospheric removal process for peroxyacyl nitrates, has been studied for EPAN. The decomposition rate of EPAN relative to that of PAN is 0.59–0.73 at 292–294 K and 1 atm of air. Atmospheric implications of these results are discussed.     

Feedstock aids microPIM parts production: Tiny cogs test the imagination of powder professionals as small parts demand ever-finer materials…

With commercially available PIM feedstock reportedly unable to fulfill the requirements for the microPIM components under investigation, researchers at the Institute for Materials Research III (IMR) in Karlsruhe, Germany, have developed new binder systems for feedstock based on both nanoceramic and ultrafine metallic powders. In the case of ceramics (zirconia) the powders can be as fine as 300 nm, and for metals in the 3μm-5μm particle size range. The powders are used to develop PIM gearwheels (Figure 1) and other components for a demonstrator micro annular gear pump design (Figure 2); however, the technology is also said to be applicable to micro gears used in watches.     

On the "adiabatic approximation" for design of control laws for linear, time-varying systems

Control laws are often designed for linear time-varying processes by solving the algebraic Riccati equation for the optimum control law at each instant of time. Such designs may be called "adiabatic approximations." Although they are not optimum, they can result in closed loop systems which perform well. The stability of systems designed using the adiabatic approximation can be assessed by the "second method of Lyapunov." Stability is assured if a readily computed test matrixF, which depends on the rate of change of the parameters of the system, is negative-definite.