We present a Hubble Space Telescope ultraviolet spectrum of the LINER nucleus of NGC 4579, spanning the wavelength range 1160-3270 A. The data reveal a low-excitation spectrum of narrow (FWHM ~1200 km s^-1^) and broad (FWHM ~ 6600 km s^-1^) emission lines, which provide new diagnostics of the physical conditions within the emission-line regions. A featureless ultraviolet continuum is detected unambiguously, with f<SUB>nu</SUB>) is proportional to ν^-1.0^ over the range 1300-2200 A and ν^-2.4^ over 2200-3000 A. The 2200 A continuum flux is a factor of 3.3 lower than the value reported by Maoz et al. (1995) based on an HST image taken 19 months earlier; this is the first time that UV variability has been discovered in a LINER. The predictions of fast shock models are incompatible with the narrow-line spectrum, because the high-excitation lines produced in fast shocks are weak or absent in NGC 4579. Models of a single slab of gas photoionized by a power-law spectrum do not reproduce the observed line ratios well either, and it appears that the narrow-line region cannot be characterized by a unique value of the ionization parameter. We argue that the narrow-line region is photoionized by the central UV/X-ray source, and that more sophisticated photoionization calculations, incorporating the effects of density and/or ionization stratification and different continuum shapes, can yield results in better agreement with the data.
Abstract Several lines of evidence indicate that major histocompatibility complex class I molecules expressed by target cells can prevent natural killer cell (NK) lysis, possibly by engaging inhibitory receptors expressed by NK cells. On the other hand it is likely that NK cells must be activated to lysis by the recognition of unidentified NK target structures on target cells. To investigate the relationship between positive activation of NK cells by NK target structures versus inhibition by target cell class I molecules, we have examined various NK/target cell interactions for which the expression of inhibitory class I molecules by the target cells is known. The results suggest that specific properties of the target cell other than the absence of class I expression are necessary to activate NK‐mediated lysis. Furthermore, different effector cell populations, i.e. freshly isolated versus interleukin‐2 activated NK cells, differ in their capacity to kill class I‐deficient lymphoblast target cells. In general, class I‐deficient target cells that are resistant to direct lysis by a given NK population can be lysed by the NK cells when the reaction is mediated by antibody‐dependent cellular cytotoxicity (ADCC). Most significantly, all types of NK‐mediated lysis of lymphoblasts, of tumor cells and of almost any target by ADCC can be inhibited by appropriate class I gene expression in the target cell. These results suggest a model in which lysis by NK cells must be triggered by any one of a set of distinct target cell ligands, but that all of these signals can be overruled by class I‐mediated inhibition.
Diterpenes are a structurally diverse class of molecules common in plants, although they are very rarely found in bacteria. We report the identification in Mycobacterium tuberculosis ( Mtb ) of three diterpenes proposed to promote phagolysosome maturation arrest. MS analysis reveals that these diterpenes are novel compounds not previously identified in other organisms. The diterpene with highest abundance in Mtb has a mass fragmentation pattern identical to edaxadiene, which is produced in vitro from geranylgeranyl diphosphate by the enzymes Rv3377c and Rv3378c. A second diterpene found in Mtb has a similar mass spectrum, and is always observed in the same proportion relative to edaxadiene, indicating that it is a side product of the Rv3378c reaction in vivo . We name this second diterpene olefin edaxadiene B. The least abundant of the three diterpenes in Mtb extracts is tuberculosinol, a dephosphorylated side‐product of the edaxadiene pathway intermediate produced by Rv3377c . A frameshift in Rv3377c in Mtb completely eliminates diterpene production, whereas expression of Rv3377c and Rv3378c in the nonpathogenic M. smegmatis is sufficient to produce edaxadiene and edaxadiene B. These studies define the pathway of edaxadiene and edaxadiene B biosynthesis in vivo . Rv3377c and Rv3378c are unique to Mtb and M. bovis , making them candidates for selective therapeutics and diagnostics.
Abstract Fossil fuel alternatives, such as solar energy, are moving to the forefront in a variety of research fields. Polymer‐based organic photovoltaic systems hold the promise for a cost‐effective, lightweight solar energy conversion platform, which could benefit from simple solution processing of the active layer. The function of such excitonic solar cells is based on photoinduced electron transfer from a donor to an acceptor. Fullerenes have become the ubiquitous acceptors because of their high electron affinity and ability to transport charge effectively. The most effective solar cells have been made from bicontinuous polymer–fullerene composites, or so‐called bulk heterojunctions. The best solar cells currently achieve an efficiency of about 5 %, thus significant advances in the fundamental understanding of the complex interplay between the active layer morphology and electronic properties are required if this technology is to find viable application.
The derivation of successful fuel cell technologies requires the development of more effective, cheaper, and poison-resistant electrocatalysts for both the anode (H{sub 2} oxidation in the presence of small amounts of CO from the reforming of carbonaceous fuels) and the cathode (reduction of oxygen in the presence of carried-over fuel). The proposed work is tightly focused on one specific aspect of electrocatalysis; the fundamental role(s) played by nanoscale (1-2 nm thick) oxide (''passive'') films that form on the electrocatalyst surfaces above substrate-dependent, critical potentials, on charge transfer reactions, particularly at elevated temperatures (25 C &lt; T &lt; 200 C). Once the role(s) of these films is (are) adequately understood, we will then use this information to specify, at the molecular level, optimal properties of the passive layer for the efficient electrocatalysis of the oxygen reduction reaction.
No abstract is provided for this article.
The current congestion control paradigm assumes that end users will use a single mandated algorithm. While the work done in this area has proven to be of great value, we need to recognize as a community that this paradigm is clearly inappropriate for future public networks. The reformulation of congestion control for best-effort service is discussed. We are not attempting to design specific new congestion control algorithms. Instead, we are merely trying to articulate the design principles. Many of these principles have been discussed before; however, with ATM currently designing a best-effort service under the name available bit rate (ABR) and the increasing commercialization of the Internet, these issues warrant revisiting. We outline the service model for best-effort service, describe the set of mechanisms available to implement this service model and contrast their various roles. The implications of our findings for future network design are discussed including some well-known examples of congestion control mechanisms.
Community interventions and service programs for grandparents raising grandchildren are being identified and tracked through the Brookdale Grandparent Caregiver Information Project. Based on the first year's examination of 124 such programs, an overview of community intervention effort is provided, with special attention to support groups and comprehensive multi-service programs for grandparent caregivers. Lack of funding and institutional support, and the consequent inability to provide child care, were among key obstacles faced, while sponsorship by health and social service agencies often played a vital role in providing in-kind support and part-time professional staff.
The cost of drug discovery and development is increasing, while the rate of new drug approvals is declining. In contrast to major technological advances with in silico and in vitro screening tools, there have been almost no advances in the tools available for establishing the actions of agents in the complex biochemical networks characteristic of fully assembled living systems. The resulting poor capacity to predict clinical response underlies the high attrition rate of leads at every step of drug development. A potential solution would be provided by kinetic biomarkers (in vivo measurement of fluxes though the key pathways that drive disease processes and therapeutic response). Novel approaches using stable isotope labeling with mass spectrometric analysis have recently emerged for measuring molecular kinetics relevant to drug targets with some applications to drug development. This review discusses the general principles of kinetic biomarkers, providing examples where kinetics have generated meaningful insights into drug activity and highlighting areas where the application of kinetic biomarkers may be particularly useful for future drug discovery and development. Stable isotope mass spectrometric technologies may provide a parallel efficiency for converting molecules into approved drugs with sufficient throughput and reproducibility to maintain pace with the modern engine for generating leads.
