Paul–Straubel–Kingdon trap for true zero-point confinement of an individual ion and reservoir

A modification of the Paul–Straubel trap previously described by us may profitably be operated in a Paul–Straubel–Kingdon (PSK) mode during the initial loading of an individual ion into the trap. Thereby the coating of the trap ring electrode by the atomic beam directed upon it in earlier experiments is eliminated, as is the ionization of an already trapped ion. Coating created serious problems as it spot-wise changed the work function of the ring electrode, which caused large, uncontrolled dc fields in the trap center that prevented zero-point confinement. Operating the Paul–Straubel trap with a small negative bias on the ring electrode wire is all that is required to realize the PSK mode. In this mode the tiny ring trap in the center of the long, straight wire section is surrounded by a second trapping well shaped like a long, thin-walled cylindrical shell and extending to the end-caps. There, ions may be conveniently created in this well without danger of coating the ring with barium. In addition, the long second well is useful as a multi-ion reservoir.

Fully competent dendritic cells as inducers of T cell anergy in autoimmunity

Mature immunologically competent dendritic cells are the most efficient antigen-presenting cells that powerfully activate T cells and initiate and sustain immune responses. Indeed, dendritic cells are able to efficiently capture antigens, express high levels of costimulatory molecules, and produce the combination of cytokines required to create a powerful immune response. They are also considered to be important in initiating autoimmune disease by efficiently presenting autoantigens to self-reactive T cells that, in this case, will mount a pathogenic autoimmune reaction. Triggering T cells is not a simple on–off procedure, as T cell receptor responds to minor changes in ligand with gradations of T cell activation and effector functions. These “misfit” peptides have been called Altered Peptide Ligands, and have been shown to have important biological significance. Here, we show that fully capable dendritic cells may present, upon natural antigen processing, a self-epitope with Altered Peptide Ligands features that can unexpectedly induce anergy in a human autoreactive T cell clone. These results indicate that presentation of a self-epitope by immunologically competent dendritic cells does not always mean “danger” and show a mechanism involved in the fine balance between activation and tolerance induction in humans.

Global warming in the twenty-first century: An alternative scenario

A common view is that the current global warming rate will continue or accelerate. But we argue that rapid warming in recent decades has been driven mainly by non-CO2 greenhouse gases (GHGs), such as chlorofluorocarbons, CH4, and N2O, not by the products of fossil fuel burning, CO2 and aerosols, the positive and negative climate forcings of which are partially offsetting. The growth rate of non-CO2 GHGs has declined in the past decade. If sources of CH4 and O3 precursors were reduced in the future, the change in climate forcing by non-CO2 GHGs in the next 50 years could be near zero. Combined with a reduction of black carbon emissions and plausible success in slowing CO2 emissions, this reduction of non-CO2 GHGs could lead to a decline in the rate of global warming, reducing the danger of dramatic climate change. Such a focus on air pollution has practical benefits that unite the interests of developed and developing countries. However, assessment of ongoing and future climate change requires composition-specific long-term global monitoring of aerosol properties.

Direct toxicity of nonsteroidal antiinflammatory drugs for renal medullary cells

Antipyretic analgesics, taken in large doses over a prolonged period, cause a specific form of kidney disease, characterized by papillary necrosis and interstitial scarring. Epidemiological evidence incriminated mixtures of drugs including aspirin (ASA), phenacetin, and caffeine. The mechanism of toxicity is unclear. We tested the effects of ASA, acetaminophen (APAF, the active metabolite of phenacetin), caffeine, and other related drugs individually and in combination on mouse inner medullary collecting duct cells (mIMCD3). The number of rapidly proliferating cells was reduced by ≈50% by 0.5 mM ASA, salicylic acid, or APAF. The drugs had less effect on confluent cells, which proliferate slowly. Thus, the slow in vivo turnover of IMCD cells could explain why clinical toxicity requires very high doses of these drugs over a very long period. Caffeine greatly potentiated the effect of acetaminophen, pointing to a potential danger of the mixture. Cyclooxygenase (COX) inhibitors, indomethacin and NS-398, did not reduce cell number except at concentrations greatly in excess of those that inhibit COX. Therefore, COX inhibition alone is not toxic. APAF arrests most cells in late G1 and S and produces a mixed form of cell death with both oncosis (swollen cells and nuclei) and apoptosis. APAF is known to inhibit the synthesis of DNA and cause chromosomal aberrations due to inhibition of ribonucleotide reductase. Such effects of APAF might account for renal medullary cell death in vivo and development of uroepithelial tumors from surviving cells that have chromosomal aberrations.

The challenge of contracting for technological information

Contracting to provide technological information (TI) is a significant challenge. TI is an unusual commodity in five ways. (i) TI is difficult to count and value; conventional indicators, such as patents and citations, hardly indicate value. TI is often sold at different prices to different parties. (ii) To value TI, it may be necessary to “give away the secret.” This danger, despite nondisclosure agreements, inhibits efforts to market TI. (iii) To prove its value, TI is often bundled into complete products, such as a computer chip or pharmaceutical product. Efficient exchange, by contrast, would involve merely the raw information. (iv) Sellers’ superior knowledge about TI’s value make buyers wary of overpaying. (v) Inefficient contracts are often designed to secure rents from TI. For example, licensing agreements charge more than marginal cost. These contracting difficulties affect the way TI is produced, encouraging self-reliance. This should be an advantage to large firms. However, small research and development firms spend more per employee than large firms, and nonprofit universities are major producers. Networks of organizational relationships, particularly between universities and industry, are critical in transmitting TI. Implicit barter—money for guidance—is common. Property rights for TI are hard to establish. Patents, quite suitable for better mousetraps, are inadequate for an era when we design better mice. Much TI is not patented, and what is patented sets fuzzy demarcations. New organizational forms are a promising approach to contracting difficulties for TI. Webs of relationships, formal and informal, involving universities, start-up firms, corporate giants, and venture capitalists play a major role in facilitating the production and spread of TI.

Virus-mediated gene transfer into hippocampal CA1 region restores long-term potentiation in brain-derived neurotrophic factor mutant mice.

Long-term potentiation (LTP) has been shown to be impaired in mice deficient in the brain-derived neurotrophic factor (BDNF) gene, as well as in a number of other knockout animals. Despite its power the gene-targeting approach is always fraught with the danger of looking at the cumulative direct and indirect effects of the absence of a particular gene rather than its immediate function. The re-expression of a specific gene at a selective time point and at a specific site in gene-defective mutants presents a potent procedure to overcome this limitation and to evaluate the causal relationship between the absence of a particular gene and the impairment of a function in gene-defective animals. Here we demonstrate that the re-expression of the BDNF gene in the CA1 region almost completely restores the severely impaired LTP in hippocampal slices of BDNF-deficient mice. The results therefore provide strong evidence for the direct involvement of BDNF in the process of LTP.