Ultrafast laser physics continues to advance at a rapid pace, driven primarily by the development of more powerful and sophisticated diode-pumping sources, the development of new laser materials, and ...new laser and amplification approaches such as optical parametric chirped-pulse amplification. The rapid development of high average power cryogenic laser sources seems likely to play a crucial role in realizing the long-sought goal of powerful ultrafast sources that offer concomitant high peak and average powers. In this paper, we review the optical, thermal, thermo-optic and laser parameters important to cryogenic laser technology, recently achieved laser and laser materials progress, the progression of cryogenic laser technology, discuss the importance of cryogenic laser technology in ultrafast laser science, and what advances are likely to be achieved in the near-future.
Although Rat-1 fibroblasts expressing c-myc constitutively are unable to arrest growth in low serum, their numbers do not increase in culture because of substantial cell death. We show this cell ...death to be dependent upon expression of c-myc protein and to occur by apoptosis. Regions of the c-myc protein required for induction of apoptosis overlap with regions necessary for cotransformation, autoregulation, and inhibition of differentiation, suggesting that the apoptotic function of c-myc protein is related to its other functions. Moreover, cells with higher levels of c-myc protein are more prone to cell death upon serum deprivation. Finally, we demonstrate that deregulated c-myc expression induces apoptosis in cells growth arrested by a variety of means and at various points in the cell cycle.
Receptor interacting protein 1 (RIP140) has recently been demonstrated to be a key player in the regulation of skeletal muscle mitochondrial content. We have shown that β-guanadinopropionic acid ...(β-GPA) feeding reduces RIP140 protein content and mRNA levels concomitant with increases in mitochondrial content (Williams DB, Sutherland LN, Bomhof MR, Basaraba SA, Thrush AB, Dyck DJ, Field CJ, Wright DC. Am J Physiol Endocrinol Metab 296: E1400-E1408, 2009). Since β-GPA feeding reduces high-energy phosphate levels and activates AMPK, alterations reminiscent of exercise, we hypothesized that exercise training would reduce RIP140 protein content. We further postulated that an acute bout of exercise, or interventions known to induce the expression of mitochondrial enzymes or genes involved in mitochondrial biogenesis, would result in decreases in nuclear RIP140 content. Two weeks of daily swim training increased markers of mitochondrial content in rat skeletal muscle independent of reductions in RIP140 protein. Similarly, high-intensity exercise training in humans failed to reduce RIP140 content despite increasing skeletal muscle mitochondrial enzymes. We found that 6 wk of daily 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) injections had no effect on RIP140 protein content in rat skeletal muscle while RIP140 content from LKB1 knockout mice was unaltered despite reductions in mitochondria. An acute bout of exercise, AICAR treatment, and epinephrine injections increased the mRNA levels of PGC-1α, COXIV, and lipin1 independent of decreases in nuclear RIP140 protein. Surprisingly these interventions increased RIP140 mRNA expression. In conclusion our results demonstrate that decreases in RIP140 protein content are not required for exercise and AMPK-dependent increases in skeletal muscle mitochondrial content, nor do acute perturbations alter the cellular localization of RIP140 in parallel with the induction of genes involved in mitochondrial biogenesis.
Increased survival in children with critical congenital heart disease (CHD) has raised interest in the neurodevelopmental sequelae of these lesions. This investigation is part of an institutional ...effort to examine the neurodevelopment of 5-year-old children following repair or palliation of CHD.
We performed a battery of neuropsychological tests on a sample of 243 children between 1998 and 2001.
In the sample as a whole, mean full-scale (FSIQ), verbal (VIQ), and performance (PIQ) IQ scores were in the normal range (96.8+/-15.9, 97.8+/-14.6, and 96.3+/-17.1, respectively). Anatomic, demographic, and perioperative factors were assessed for impact on neurodevelopment. In multiple regression analysis, lower socioeconomic status (SES) and the diagnosis of velocardiofacial syndrome (VCFS) predicted a lower FSIQ (P=0.01, and P=0.001, respectively). A single ventricle diagnosis (P=0.06), longer postoperative ICU stay (P=0.08), and cumulative duration of hypothermic circulatory arrest (HCA) (P=0.09) approached significance as predictors of lower FSIQ.
Children with CHD, on the whole, appear to be performing within the average range in terms of intellectual abilities. Lower SES and VCFS are associated with lower IQ scores. Trends toward worse outcomes were observed in single ventricle patients, biventricular patients with longer postrepair ICU stays, and patients subjected to longer periods of HCA.
Angiosperm stigmas have long been known to exhibit high levels of peroxidase activity when they are mature and most receptive to pollen but the biological function of stigma peroxidases is not known. ...A novel stigma-specific class III peroxidase gene, SSP (stigma-specific peroxidase) expressed exclusively in the stigmas of Senecio squalidus L. (Asteraceae) has recently been identified. Expression of SSP is confined to the specialized secretory cells (papillae) that compose the stigma epidermis. The literature on stigma peroxidases and hypotheses on their function(s) is reviewed here before further characterization of SSP and an attempt to determine its function are described. It is shown that SSP is localized to cytoplasmic regions of stigmatic papillae and also to the surface of these cells, possibly as a component of the pellicle, a thin layer of condensed protein typical of 'dry' stigmas. Enzyme assays on recombinant SSP showed it to be a peroxidase with a preference for diphenolic substrates (ABTS and TMB) and a pH optimum of ~4.5. In such assays the peroxidase activity of SSP was low when compared with horseradish peroxidase. To explore the function of SSP and other stigmatic peroxidases, levels of reactive oxygen species (ROS) in stigmas of S. squalidus were investigated. Relatively large amounts of ROS, principally H₂O₂, were detected in S. squalidus stigmas where most ROS/H₂O₂ was localized to the stigmatic papillae, the location of SSP. These observations are discussed in the context of possible functions for SSP, other peroxidases, and ROS in the stigmas of angiosperms.
Targeting the interaction of proteins with weak binding affinities or low solubility represents a particular challenge for drug screening. The NanoLuc
® Binary Technology (NanoBiT
®) was originally ...developed to detect protein-protein interactions in live mammalian cells. Here we report the successful translation of the NanoBit cellular assay into a biochemical, cell-free format using mammalian cell lysates. We show that the assay is suitable for the detection of both strong and weak protein interactions such as those involving the binding of RAS oncoproteins to either RAF or phosphoinositide 3-kinase (PI3K) effectors respectively, and that it is also effective for the study of poorly soluble protein domains such as the RAS binding domain of PI3K. Furthermore, the RAS interaction assay is sensitive and responds to both strong and weak RAS inhibitors. Our data show that the assay is robust, reproducible, cost-effective, and can be adapted for small and large-scale screening approaches. The NanoBit Biochemical Assay offers an attractive tool for drug screening against challenging protein-protein interaction targets, including the interaction of RAS with PI3K.
An unsaturated-zone transport model was used to examine the transport and fate of metolachlor applied to an agricultural site in Maryland, USA. The study site was instrumented to collect data on ...soil-water content, soil-water potential, ground water levels, major ions, pesticides, and nutrients from the unsaturated zone during 2002-2004. The data set was enhanced with site-specific information describing weather, soils, and agricultural practices. The Root Zone Water Quality Model was used to simulate physical, chemical, and biological processes occurring in the unsaturated zone. Model calibration to bromide tracer concentrations indicated flow occurred through the soil matix. Simulated recharge rates were within the measured range of values. The pesticide transport model was calibrated to the intensive data collection period (2002-2004), and the calibrated model was then used to simulate the period 1984 through 2004 to examine the impact of sustained agricultural management practices on the concentrations of metolachlor and its degradates at the study site. Simulation results indicated that metolachlor degrades rapidly in the root zone but that the degradates are transported to depth in measurable quantities. Simulations indicated that degradate transport is strongly related to the duration of sustained use of metolachlor and the extent of biodegradation.
The CRISM instrument on MRO collected visible-infrared hyperspectral mapping data (HSP; 180 m/pixel, 262 spectral channels covering 365 to 3937 nm) that covered ∼39% of Mars. Here we present results ...from a new processing pipeline for these data that produces 5° x 5° hyperspectral mapping tiled mosaics that overlap the coverage of recently released multispectral map tile products (version 4 Multispectral Reduced Data Records, MRDRs; 180 m/pixel, 72 spectral channels). These data enable regional investigations into compositional variations that require high spectral resolution or wavelengths not included in MRDRs. In addition to standard processing techniques available in the CRISM Analysis Toolkit (CAT), the pipeline includes a new correction for systematic discrepancies in radiometric calibration between CRISM observing modes, an improved filtering algorithm to remediate noise, and a technique to correct for differences in radiometry among data strips that arise from differences in photometric and atmospheric conditions. Demonstration hyperspectral mapping tiles covering the Mawrth Vallis region were developed and compared with MRDRs and high spatial resolution hyperspectral targeted observations. The new processing pipeline shows an improvement in data quality over standard processing using CAT utilities. Compared to targeted observations (18 or 36 m/pixel, 545 spectral channels), hyperspectral mapping tile mosaics reveal compositional information across a much greater spatial extent at the expense of 5–10 times coarser spatial resolution. In addition, the hyperspectral mapping tile mosaics reveal greater compositional detail in both the spatial and spectral dimensions compared to MRDRs, but with sparser spatial coverage. Sample hyperspectral mapping tile mosaics over the Mawrth Vallis region reveal hydrated silica, Al-bearing smectite, Fe/Mg-bearing smectite, and mixed clays, consistent with compositions previously reported in the literature.
•We present new 5° x 5° hyperspectral mapping tiled mosaics comprised ofCRISM hyperspectral mapping data (HSP; 180 m/pixel, 262 spectral channels).•HSP tile mosaics enable regional investigations into compositional variations that require high spectral resolution.•HSP tile mosaics reveal compositional information across a much greater spatial extant than targeted data and with more spatial and spectral detail than MRDR tiles.•For regional to global-scale investigations, HSP tile mosaics could augment the use of MRDRs by adding critical spectral detail.•For local-scale investigations using CRISM targeted observations, HSP mapping data could add contextual information complementary to that which is available with the MRDRs.
Exercise induces an increase in glucose transport in muscle. As the acute increase in glucose transport reverses, it is replaced by an increase in insulin sensitivity. Interleukin-6 (IL-6) increases ...with exercise and has been reported to activate AMP-activated protein kinase (AMPK). Based on this information, we hypothesized that IL-6 would result in an increase in muscle insulin sensitivity. Rat epitrochlearis and soleus muscles were incubated with 120 ng/ml IL-6. Exposure to IL-6 induced a modest acute increase in glucose transport and was followed 3.5 h later by an increase in insulin sensitivity in epitrochlearis but not soleus muscles. IL-6 also brought about an increase in AMPK phosphorylation in epitrochlearis muscles. We conclude that exposure of fast-twitch muscle to 120 ng/ml IL-6 increases insulin sensitivity by activating AMPK. However, exposure of epitrochlearis muscles to 10 ng/ml IL-6, a concentration >100-fold higher than that attained in plasma during exercise, had no effect on glucose transport or insulin sensitivity. These findings provide evidence that the increases in glucose transport and insulin sensitivity induced by IL-6 are pharmacological rather than physiological effects. We interpret our results as evidence that the increase in IL-6 during exercise does not play a role in the exercise-induced increases in muscle glucose uptake and insulin sensitivity.
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