A Decade Of Starspot Activity On The Eclipsing Short-Period RS Canum Venaticorum Star WY Cancri: 1988-1997

We present optical photometry of the short-period eclipsing RS CVn system WY Cancri for the years 1988–1997. For each light curve, we model the distortion waves in order to study the behavior of starspots in this system. After removing the spot effects f

Japanese Purchases, Exchange Rates, and Speculation in Residential Real Estate Markets

Several luxury single-family home markets in Hawaii have experienced significant price movements in 1987 and 1988, along with a tremendous influx of Japanese buyers. Most noteworthy is the Waialae-Kahala neighborhood in Honolulu, where average price increases of over 60% in the past two years have occurred. This surge in prices has stimulated a great deal of speculative interest. The purpose of this article is to examine the effect of exchange rates (yen/dollar) and Japanese buyers on selected residential market prices and turnover. Using the most exhaustive and complete data set available in Hawaii covering 1986 through early 1988, hedonic pricing models as well as descriptive statistics are used to examine the effects of strong foreign interest in local housing submarkets.

Propulsion and Space Vehicle Systems Analysis Program Tensor I, volume I Technical report no. 341

Computer program for space vehicle and propulsion systems analysi

Transcription Factor Phox2 Upregulates Expression of Norepinephrine Transporter and Dopamine β-Hydroxylase in Adult Rat Brains

Degeneration of the noradrenergic locus coeruleus (LC) in aging and neurodegenerative diseases is well documented. Slowing or reversing this effect may have therapeutic implications. Phox2a and Phox2b are homeodomain transcriptional factors that function as determinants of the noradrenergic phenotype during embryogenesis. In the present study, recombinant lentiviral eGFP-Phox2a and -Phox2b (vPhox2a and vPhox2b) were constructed to study the effects of Phox2a/2b over-expression on dopamine β-hydroxylase (DBH) and norepinephrine transporter (NET) levels in central noradrenergic neurons. Microinjection of vPhox2 into the LC of adult rats significantly increased Phox2 mRNA levels in the LC region. Over-expression of either Phox2a or Phox2b in the LC was paralleled by significant increases in mRNA and protein levels of DBH and NET in the LC. Similar increases in DBH and NET protein levels were observed in the hippocampus following vPhox2 microinjection. In the frontal cortex, only NET protein levels were significantly increased by vPhox2 microinjection. Over-expression of Phox2 genes resulted in a significant increase in BrdU-positive cells in the hippocampal dentate gyrus. The present study demonstrates an upregulatory effect of Phox2a and Phox2b on the expression of DBH and NET in noradrenergic neurons of rat brains, an effect not previously shown in adult animals. Phox2 genes may play an important role in maintaining the function of the noradrenergic neurons after birth, and regulation of Phox2 gene expression may have therapeutic utility in aging or disorders involving degeneration of noradrenergic neurons

Evidence for Oxidative Stress and Defective Antioxidant Response in Guinea Pigs with Tuberculosis

The development of granulomatous inflammation with caseous necrosis is an important but poorly understood manifestation of tuberculosis in humans and some animal models. In this study we measured the byproducts of oxidative stress in granulomatous lesions as well as the systemic antioxidant capacity of BCG vaccinated and non-vaccinated guinea pigs experimentally infected with Mycobacterium tuberculosis. In non-vaccinated guinea pigs, oxidative stress was evident within 2 weeks of infection as measured by a decrease in the serum total antioxidant capacity and blood glutathione levels accompanied by an increase in malondialdehyde, a byproduct of lipid peroxidation, within lesions. Despite a decrease in total and reduced blood glutathione concentrations, there was an increase in lesion glutathione by immunohistochemistry in response to localized oxidative stress. In addition there was an increase in the expression of the host transcription factor nuclear erythroid 2 p45-related factor 2 (Nrf2), which regulates several protein and non-proteins antioxidants, including glutathione. Despite the increase in cytoplasmic expression of Nrf2, immunohistochemical staining revealed a defect in Nrf2 nuclear translocation within granulomatous lesions as well as a decrease in the expression of the Nrf2-regulated antioxidant protein NQO1. Treating M. tuberculosis–infected guinea pigs with the antioxidant drug N-acetyl cysteine (NAC) partially restored blood glutathione concentrations and the serum total antioxidant capacity. Treatment with NAC also decreased spleen bacterial counts, as well as decreased the lung and spleen lesion burden and the severity of lesion necrosis. These data suggest that the progressive oxidative stress during experimental tuberculosis in guinea pigs is due in part to a defect in host antioxidant defenses, which, we show here, can be partially restored with antioxidant treatment. These data suggest that the therapeutic strategies that reduce oxidant-mediated tissue damage may be beneficial as an adjunct therapy in the treatment and prevention of tuberculosis in humans

Uptake and Accumulation of Oxidized Low-Density Lipoprotein during Mycobacterium tuberculosis Infection in Guinea Pigs

The typical host response to infection of humans and some animals by M. tuberculosis is the accumulation of reactive oxygen species generating inflammatory cells into discrete granulomas, which frequently develop central caseous necrosis. In previous studies we showed that infection of immunologically naïve guinea pigs with M. tuberculosis leads to localized and systemic oxidative stress that results in a significant depletion of serum total antioxidant capacity and the accumulation of malondialdehyde, a bi-product of lipid peroxidation. Here we show that in addition, the generation of excessive reactive oxygen species in vivo resulted in the accumulation of oxidized low density lipoproteins (OxLDL) in pulmonary and extrapulmonary granulomas, serum and lung macrophages collected by bronchoalveolar lavage. Macrophages from immunologically naïve guinea pigs infected with M. tuberculosis also had increased surface expression of the type 1 scavenger receptors CD36 and LOX1, which facilitate the uptake of oxidized host macromolecules including OxLDL. Vaccination of guinea pigs with Bacillus Calmette Guerin (BCG) prior to aerosol challenge reduced the bacterial burden as well as the intracellular accumulation of OxLDL and the expression of macrophage CD36 and LOX1. In vitro loading of guinea pig lung macrophages with OxLDL resulted in enhanced replication of bacilli compared to macrophages loaded with non-oxidized LDL. Overall, this study provides additional evidence of oxidative stress in M. tuberculosis infected guinea pigs and the potential role OxLDL laden macrophages have in supporting intracellular bacilli survival and persistence

Altered miRNA expression network in locus coeruleus of depressed suicide subjects

Norepinephrine (NE) is produced primarily by neurons in the locus coeruleus (LC). Retrograde and ultrastructural examinations reveal that the core of the LC and its surrounding region receives afferent projections from several brain areas which provide multiple neurochemical inputs to the LC with changes in LC neuronal firing, making it a highly coordinated event. Although NE and mediated signaling systems have been studied in relation to suicide and psychiatric disorders that increase the risk of suicide including depression, less is known about the corresponding changes in molecular network within LC. In this study, we examined miRNA networks in the LC of depressed suicide completers and healthy controls. Expression array revealed differential regulation of 13 miRNAs. Interaction between altered miRNAs and target genes showed dense interconnected molecular network. Functional clustering of predicated target genes yielded stress induced disorders that collectively showed the complex nature of suicidal behavior. In addition, 25 miRNAs were pairwise correlated specifically in the depressed suicide group, but not in the control group. Altogether, our study revealed for the first time the involvement of LC based dysregulated miRNA network in disrupting cellular pathways associated with suicidal behavior

Low Dose Aerosol Fitness at the Innate Phase of Murine Infection Better Predicts Virulence amongst Clinical Strains of Mycobacterium tuberculosis

Background: Evaluation of a quick and easy model to determine the intrinsic ability of clinical strains to generate active TB has been set by assuming that this is linked to the fitness of Mycobacterium tuberculosis strain at the innate phase of the infection. Thus, the higher the bacillary load, the greater the possibility of inducting liquefaction, and thus active TB, once the adaptive response is set. Methodology/Principal Findings: The virulence of seven clinical Mycobacterium tuberculosis strains isolated in Spain was tested by determining the bacillary concentration in the spleen and lung of mice at weeks 0, 1 and 2 after intravenous (IV) inoculation of 10 4 CFU, and by determining the growth in vitro until the stationary phase had been reached. Cord distribution automated analysis showed two clear patterns related to the high and low fitness in the lung after IV infection. This pattern was not seen in the in vitro fitness tests, which clearly favored the reference strain (H37Rv). Subsequent determination using a more physiological low-dose aerosol (AER) inoculation with 10 2 CFU showed a third pattern in which the three best values coincided with the highest dissemination capacity according to epidemiological data. Conclusions/Significance: The fitness obtained after low dose aerosol administration in the presence of the innate immune response is the most predictive factor for determining the virulence of clinical strains. This gives support to a mechanism o

A genome-wide DNA methylation study in colorectal carcinoma

<p>Abstract</p> <p>Background</p> <p>We performed a genome-wide scan of 27,578 CpG loci covering 14,475 genes to identify differentially methylated loci (DML) in colorectal carcinoma (CRC).</p> <p>Methods</p> <p>We used Illumina's Infinium methylation assay in paired DNA samples extracted from 24 fresh frozen CRC tissues and their corresponding normal colon tissues from 24 consecutive diagnosed patients at a tertiary medical center.</p> <p>Results</p> <p>We found a total of 627 DML in CRC covering 513 genes, of which 535 are novel DML covering 465 genes. We also validated the Illumina Infinium methylation data for top-ranking genes by non-bisulfite conversion q-PCR-based methyl profiler assay in a subset of the same samples. We also carried out integration of genome-wide copy number and expression microarray along with methylation profiling to see the functional effect of methylation. Gene Set Enrichment Analysis (GSEA) showed that among the major "gene sets" that are hypermethylated in CRC are the sets: "inhibition of adenylate cyclase activity by G-protein signaling", "Rac guanyl-nucleotide exchange factor activity", "regulation of retinoic acid receptor signaling pathway" and "estrogen receptor activity". Two-level nested cross validation showed that DML-based predictive models may offer reasonable sensitivity (around 89%), specificity (around 95%), positive predictive value (around 95%) and negative predictive value (around 89%), suggesting that these markers may have potential clinical application.</p> <p>Conclusion</p> <p>Our genome-wide methylation study in CRC clearly supports most of the previous findings; additionally we found a large number of novel DML in CRC tissue. If confirmed in future studies, these findings may lead to identification of genomic markers for potential clinical application.</p

The High-Resolution Coronal Imager, Flight 2.1

The third flight of the High-Resolution Coronal Imager (Hi-C 2.1) occurred on May 29, 2018; the Sounding Rocket was launched from White Sands Missile Range in New Mexico. The instrument has been modified from its original configuration (Hi-C 1) to observe the solar corona in a passband that peaks near 172 Å, and uses a new, custom-built low-noise camera. The instrument targeted Active Region 12712, and captured 78 images at a cadence of 4.4 s (18:56:22 – 19:01:57 UT; 5 min and 35 s observing time). The image spatial resolution varies due to quasi-periodic motion blur from the rocket; sharp images contain resolved features of at least 0.47 arcsec. There are coordinated observations from multiple ground- and space-based telescopes providing an unprecedented opportunity to observe the mass and energy coupling between the chromosphere and the corona. Details of the instrument and the data set are presented in this paper