Generating mice with targeted mutations.

Journal ArticleMutational analysis is one of the most informative approaches available for the study of complex biological processes. It has been particularly successful in the analysis of the biology of bacteria, yeast, the nematode worm Caenorhabditis elegans and the fruit fly Drosophila melanogaster. Extension of this approach to the mouse, through informative, was far less successful relative to what has been achieved with these simpler model organisms. This is because it is not numerically practical in mice to use random mutagenesis to isolate mutations that affect a specified biological process of interest. Nonetheless, biological phenomena such as a sophisticated immune response, cancer, vascular disease or higher-order cognitive function, to mention just a few, must analyzed in organisms that show such phenomena, and for this reason geneticists and other researchers have turned to the mouse. Gene targeting, the means for creating mice with designed mutations in almost any gene, was developed as an alternative to the impractical use of random mutgenesis for pursing genetic analysis in the mouse. Now gene targeting has advanced the genomic manipulations possible in mice to a level that can be matched only in far simple organisms such as bacteria and yeast

High Resolution Observations using Adaptive Optics: Achievements and Future Needs

Over the last few years, several interesting observations were obtained with the help of solar Adaptive Optics (AO). In this paper, few observations made using the solar AO are enlightened and briefly discussed. A list of disadvantages with the current AO system are presented. With telescopes larger than 1.5m are expected during the next decade, there is a need to develop the existing AO technologies for large aperture telescopes. Some aspects of this development are highlighted. Finally, the recent AO developments in India are also presented

Can We Observe Weak Anomalous Couplings of Heavy Quarks Through Three Jet Events?

The rates and corresponding jet distributions for the decay $Z\to b\bar bg$ and the process $e^+e^-\to t\bar tg$ may be sensitive to anomalous dipole-like couplings of heavy quarks to the photon and $Z$. In the $b$-quark case, after updating our previous analysis on the constraints imposed by current experiments on $Zb\bar b$ anomalous couplings, we show that the variation of these couplings within their presently allowed ranges leads to rather minor modifications to the Standard Model expectations for $Z\to b\bar bg$ observables. In the $t$-quark case, significant deviations from the Standard Model predictions for $t\bar tg$ production at the Next Linear Collider are possible.Comment: 26 pages with 9 embedded figures; gzipped, uuencoded postscript file. To obtain a copy of this paper send e-mail to [email protected]

On the heating mix of ITER (invited paper)

This paper considers the heating mix of ITER for the two main scenarios. Presently, 73MWof absorbed power are foreseen in the mix 20/33/20 for ECH, NBI and ICH. Given a sufficient edge stability, Q = 10 the goal of scenario 2 can be reached with 40MW power irrespective of the heating method but depends sensitively inter alia on the H-mode pedestal temperature, the density profile shape and on the characteristics of impurity transport. ICH preferentially heats the ions and would contribute specifically with Q 0.5, and strong off-axis current drive (CD). The findings presented here are based on revised CD efficiencies γ for ECCD and a detailed benchmark of several CD codes. With ECCD alone, the goals of scenario 4 can hardly be reached. Efficient off-axisCDis only possible with NBI.With beams, inductive discharges with fni > 0.8 can be maintained for 3000 s. The conclusion of this study is that the present heating mix of ITER is appropriate. It provides the necessary actuators to induce in a flexible way the best possible scenarios. The development risks of NBI at 1MeV can be reduced by operation at 0.85MeV

Cardiopulmonary, Histologic, and Inflammatory Effects of Intravenous Na2S After Blunt Chest Trauma-Induced Lung Contusion in Mice

Background: When used as a pretreatment, hydrogen sulfide (H2S) either attenuated or aggravated lung injury. Therefore, we tested the hypothesis whether posttreatment intravenous Na2S (sulfide) may attenuate lung injury.Methods: After blast wave blunt chest trauma or sham procedure, anesthetized and instrumented mice received continuous intravenous sulfide or vehicle while being kept at 37°C or 32°C core temperature. After 4 hours of pressure-controlled, thoracopulmonary compliance-titrated, lung-protective mechanical ventilation, blood and tissue were harvested for cytokine concentrations, heme oxygenase-1, IκBα, Bcl-Xl, and pBad expression (western blotting), nuclear factor-κB activation (electrophoretic mobility shift assay), and activated caspase-3, cystathionine-β synthase and cystathionine-γ lyase (immunohistochemistry). Results: Hypothermia caused marked bradycardia and metabolic acidosis unaltered by sulfide. Chest trauma impaired thoracopulmonary compliance and arterial Po2, again without sulfide effect. Cytokine levels showed inconsistent response. Sulfide increased nuclear factor-κB activation during normothermia, but this effect was blunted during hypothermia. While histologic lung injury was variable, both sulfide and hypothermia attenuated the trauma-related increase in heme oxygenase-1 expression and activated caspase-3 staining, which coincided with increased Bad phosphorylation and Bcl-Xl expression. Sulfide and hypothermia also attenuated the trauma-induced cystathionine-β synthase and cystathionine-γ lyase expression. Conclusions: Posttreatment sulfide infusion after blunt chest trauma did not affect the impaired lung mechanics and gas exchange but attenuated stress protein expression and apoptotic cell death. This protective effect was amplified by moderate hypothermia. The simultaneous reduction in cystathionine-β synthase and cystathionine-γ lyase expression supports the role of H2S-generating enzymes as an adaptive response during stress states

Spin relaxation in (110) and (001) InAs/GaSb superlattices

We report an enhancement of the electron spin relaxation time (T1) in a (110) InAs/GaSb superlattice by more than an order of magnitude (25 times) relative to the corresponding (001) structure. The spin dynamics were measured using polarization sensitive pump probe techniques and a mid-infrared, subpicosecond PPLN OPO. Longer T1 times in (110) superlattices are attributed to the suppression of the native interface asymmetry and bulk inversion asymmetry contributions to the precessional D'yakonov Perel spin relaxation process. Calculations using a nonperturbative 14-band nanostructure model give good agreement with experiment and indicate that possible structural inversion asymmetry contributions to T1 associated with compositional mixing at the superlattice interfaces may limit the observed spin lifetime in (110) superlattices. Our findings have implications for potential spintronics applications using InAs/GaSb heterostructures.Comment: 4 pages, 2 figure

The association between socio-demographic characteristics and adherence to breast and colorectal cancer screening: Analysis of large sub populations

<p>Abstract</p> <p>Background</p> <p>Populations having lower socioeconomic status, as well as ethnic minorities, have demonstrated lower utilization of preventive screening, including tests for early detection of breast and colorectal cancer.</p> <p>The objective</p> <p>To explore socio-demographic disparities in adherence to screening recommendations for early detection of cancer.</p> <p>Methods</p> <p>The study was conducted by Maccabi Healthcare Services, an Israeli HMO (health plan) providing healthcare services to 1.9 million members. Utilization of breast cancer (BC) and colorectal cancer (CC) screening were analyzed by socio-economic ranks (SERs), ethnicity (Arab vs non-Arab), immigration status and ownership of voluntarily supplemental health insurance (VSHI).</p> <p>Results</p> <p>Data on 157,928 and 303,330 adults, eligible for BC and CC screening, respectively, were analyzed. Those having lower SER, Arabs, immigrants from Former Soviet Union countries and non-owners of VSHI performed fewer cancer screening examinations compared with those having higher SER, non-Arabs, veterans and owners of VSHI (p < 0.001). Logistic regression model for BC Screening revealed a positive association with age and ownership of VSHI and a negative association with being an Arab and having a lower SER. The model for CC screening revealed a positive association with age and ownership of VSHI and a negative association with being an Arab, having a lower SER and being an immigrant. The model estimated for BC and CC screening among females revealed a positive association with age and ownership of VSHI and a negative association with being an Arab, having a lower SER and being an immigrant.</p> <p>Conclusion</p> <p>Patients from low socio-economic backgrounds, Arabs, immigrants and those who do not own supplemental insurance do fewer tests for early detection of cancer. These sub-populations should be considered priority populations for targeted intervention programs and improved resource allocation.</p