We perform a comparison of different approaches to star-galaxy classification using the broad-band photometric data from Year 1 of the Dark Energy Survey.
Pro-inflammatory cytokines contribute to the cachexia associated with pancreatic cancer and stimulate the acute phase response which has been associated with shortened survival in such patients. ...Polymorphisms of cytokine genes may influence their production. The present study examined the effect of a polymorphism of the interleukin (IL)-1b gene upon the inflammatory state and survival in pancreatic cancer. Genomic DNA was obtained from 64 patients with pancreatic cancer and 101 healthy controls. Using the polymerase chain reaction and subsequent TaqI restriction enzyme digestion the subject's genotype for a diallelic polymorphism of the interleukin-1b gene was established. IL-1b production by peripheral blood mononuclear cells and serum C-reactive protein (CRP) levels from patients were also examined and survival noted. Patients homozygous for allele 2 of the IL-1b gene had significantly shorter survival than other groups (P = 0.0001). These patients also exhibited higher IL-1b production (P = 0.022). Possession of allele 2 was also associated with significantly shorter survival (median 144 vs 256 days, P = 0.034) and significantly higher CRP level (P = 0.0003). The possession of a genotype resulting in increased IL-1b production was associated with shortened survival and increased serum CRP level. This may reflect the role of IL-1b in inducing an acute phase protein response and cachexia in cancer or may be related to changes in tumour phenotype.
Forest harvest results in the removal of a large reservoir of terrestrial carbon with potential significant effects on net CO
2 emissions, but concomitant effects on other atmospheric trace gas ...fluxes are poorly understood.
We measured CO
2, CH
4 and N
2O fluxes between soils and the atmosphere over 3 years at a recently harvested site under
Pinus radiata on a volcanic soil of high-fertility status using replicated, large, in situ chambers to enclose three harvest residue treatments. Temporal changes in CO
2 and N
2O emissions were also measured over a wider harvested area using small chambers. The residue (slash) treatments were a control (‘no-slash’), ‘normal-slash’ typical of the site and ‘high-slash’ (three times normal-slash). Mass loss was inversely related to all size categories of slash, and averaged 98% for litter and 34% for large wood (76–120
mm diameter). C:N ratios generally declined as a result of increased N concentrations. Overall, CO
2-C production was significantly higher (
P
=
0.02) in the ‘normal-slash’ (by 27%) and ‘high-slash’ (by 72%) than in the ‘no-slash’ treatments. An interaction between treatment and time explained (
P
=
0.05) the CO
2-C flux data better than did the interaction between treatment and soil moisture (
P
=
0.07). Evidence from small-chamber CO
2-C flux data collected over a wider area before and after harvest suggested little apparent effect of soil disturbance during harvest. Averaged over 3 years, the annual CO
2-C efflux from the large chambers was 8.3
±
1.1
Mg
ha
−1.
Methane uptake was apparently depressed by surface soil disturbance during harvest, because it increased after harvest by 70% in the ‘normal-slash’ and ‘high-slash’ treatments to average 12
±
1
kg CH
4 ha
−1
year
−1. Neither NH
4
+ nor NO
3
−-N concentrations had any measurable effect on CH
4 uptake. Despite the high N fertility of the harvest site, N
2O emissions were low overall (0.56
±
0.17
kg N
2O-N ha
−1
year
−1) and differed little between treatments, apart from a spike shortly after harvest.
Overall, during the time frame of the first commitment period under the Kyoto Protocol, the three greenhouse gases (CO
2, CH
4 and N
2O) contributed 87, −1 and 14%, respectively, to combined emissions on a CO
2-equivalent basis from this fertile harvest site.
Pathologic obliterative bronchiolitis (OB)/Bronchiolitis obliterans syndrome (pathologic OB/BOS) is the major obstacle to long‐term survival post‐lung transplantation (LT). Our group has demonstrated ...that pulmonary hypertension (PH) complicates the course of chronic inflammatory lung diseases that have similarities to pathologic OB/BOS and that vascular remodeling of the bronchial circulation occurs during BOS. Consequently, we hypothesized that PH is associated with pathologic OB/BOS and may result from a vasculopathy of the allograft pulmonary circulation.
We conducted a single‐center, retrospective study and examined the presence of PH and vasculopathy in patients with pathologic OB/BOS. Fifty‐two pathologic specimens post‐LT were recovered from January 10, 1997 to January 5, 2007 and divided into two groups, those with and without pathologic OB/BOS.PH was defined as a mean pulmonary artery pressure (mPAP) > 25 mmHg by right heart catheterization (RHC) or right ventricular systolic pressure (RVSP) ≥45 mmHg by transthoracic echocardiogram (TTE).
PH was more prevalent in those LT recipients with pathologic OB/BOS (72% vs. 0%, p = 0.003). Furthermore, pulmonary arteriopathy and venopathy were more prevalent in patients with pathologic OB/BOS (84% vs. 4%, p < 0.0001, and 77% vs. 35%, p = 0.004, respectively).
PH is common in LT recipients with pathologic OB/BOS and is associated with a vasculopathy of the allograft pulmonary circulation.
Pulmonary hypertension is common in lung transplants with bronchiolitis obliterans, associated with vasculopathy in the pulmonary circulation.
Impaired insulin action is a key feature of type 2 diabetes and is also found, to a more extreme degree, in familial syndromes of insulin resistance. Although inherited susceptibility to insulin ...resistance may involve the interplay of several genetic loci, no clear examples of interactions among genes have yet been reported. Here we describe a family in which five individuals with severe insulin resistance, but no unaffected family members, were doubly heterozygous with respect to frameshift/premature stop mutations in two unlinked genes, PPARG and PPP1R3A these encode peroxisome proliferator activated receptor γ, which is highly expressed in adipocytes, and protein phosphatase 1, regulatory subunit 3, the muscle-specific regulatory subunit of protein phosphatase 1, which are centrally involved in the regulation of carbohydrate and lipid metabolism, respectively. That mutant molecules primarily involved in either carbohydrate or lipid metabolism can combine to produce a phenotype of extreme insulin resistance provides a model of interactions among genes that may underlie common human metabolic disorders such as type 2 diabetes.
CPPs (cell-penetrating peptides) facilitate the cellular uptake of covalently attached oligonucleotides, proteins and other macromolecules, but the mechanism of their uptake is disputed. Two models ...are proposed: direct movement through the phospholipid bilayer and endocytic uptake. Mitochondria are a good model system to distinguish between these possibilities, since they have no vesicular transport systems. Furthermore, CPP-mediated delivery of macromolecules to the mitochondrial matrix would be a significant breakthrough in the study of mitochondrial function and dysfunction, and could also lead to new therapies for diseases caused by mitochondrial damage. Therefore we investigated whether two CPPs, penetratin and Tat, could act as mitochondrial delivery vectors. We also determined whether conjugation of the lipophilic cation TPP (triphenylphosphonium) to penetratin or Tat facilitated their uptake into mitochondria, since TPP leads to uptake of attached molecules into mitochondria driven by the membrane potential. Neither penetratin nor Tat, nor their TPP conjugates, are internalized by isolated mitochondria, indicating that these CPPs cannot cross mitochondrial phospholipid bilayers. Tat and TPP-Tat are taken up by cells, but they accumulate in endosomes and do not reach mitochondria. We conclude that CPPs cannot cross mitochondrial phospholipid bilayers, and therefore cannot deliver macromolecules directly to mitochondria. Our findings shed light on the mechanism of uptake of CPPs by cells. The lack of direct movement of CPPs through mitochondrial phospholipid bilayers, along with the observed endosomal accumulation of Tat and TPP-Tat in cells, makes it unlikely that CPPs enter cells by direct membrane passage, and instead favours cellular uptake via an endocytic pathway.
Classical lissencephaly (LIS) is a neuronal migration disorder resulting in brain malformation, epilepsy and mental retardation. Deletions or mutations of LIS1 on 17p13.3 and mutations in XLIS (DCX) ...on Xq22.3–q23 produce LIS. Direct DNA sequencing of LIS1 and XLIS was performed in 25 children with sporadic LIS and no deletion of LIS1 by fluorescence in situ hybridization. Mutations of LIS1 were found by sequencing (n = 8) and Southern blot (n = 2) in a total of 10 patients (40%) of both sexes and mutations of XLIS in five males (20%). Combined with previous data, deletions or mutations of these two genes account for ∼76% of isolated LIS. These data demonstrate that LIS1 and XLIS mutations cause the majority of, though not all, human LIS. The mutations in LIS1 were predicted to result in protein truncation in six of eight patients and splice site mutations in two, all of which disrupt one or more of the seven WD40 repeats contained in the LIS1 protein. Point mutations in XLIS identified the C-terminal serine/proline-rich region as potentially important for protein function. The patients with mutations were included in a genotype-phenotype analysis of 32 subjects with deletions or other mutations of these two genes. Whereas the brain malformation due to LIS1 mutations was more severe over the parietal and occipital regions, XLIS mutations produced the reverse gradient, which was more severe over the frontal cortex. The distinct LIS patterns suggest that LIS1 and XLIS may be part of overlapping, but distinct, signaling pathways that promote neuronal migration.
ABSTRACT
We present direct constraints on galaxy intrinsic alignments (IAs) using the Dark Energy Survey Year 3 (DES Y3), the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), and its ...precursor, the Baryon Oscillation Spectroscopic Survey (BOSS). Our measurements incorporate photometric red sequence (redMaGiC) galaxies from DES with median redshift z ∼ 0.2–1.0, luminous red galaxies from eBOSS at z ∼ 0.8, and also an SDSS-III BOSS CMASS sample at z ∼ 0.5. We measure two-point IA correlations, which we fit using a model that includes lensing, magnification, and photometric redshift error. Fitting on scales 6 Mpc h−1 < rp < 70 Mpc h−1, we make a detection of IAs in each sample, at 5σ–22σ (assuming a simple one-parameter model for IAs). Using these red samples, we measure the IA–luminosity relation. Our results are statistically consistent with previous results, but offer a significant improvement in constraining power, particularly at low luminosity. With this improved precision, we see detectable dependence on colour between broadly defined red samples. It is likely that a more sophisticated approach than a binary red/blue split, which jointly considers colour and luminosity dependence in the IA signal, will be needed in future. We also compare the various signal components at the best-fitting point in parameter space for each sample, and find that magnification and lensing contribute $\sim 2\!-\!18~{{\ \rm per\ cent}}$ of the total signal. As precision continues to improve, it will certainly be necessary to account for these effects in future direct IA measurements. Finally, we make equivalent measurements on a sample of emission-line galaxies from eBOSS at z ∼ 0.8. We constrain the non-linear alignment amplitude to be $A_1=0.07^{+0.32}_{-0.42}$ (|A1| < 0.78 at 95 per cent CL).
The striking emergence of an epidemic of HIV-related renal disease in patients with end-stage renal disease provided the rationale for the exploration of whether HIV-1 directly infects renal ...parenchymal cells. Renal glomerular and tubular epithelial cells contain HIV-1 mRNA and DNA, indicating infection by HIV-1. In addition, circularized viral DNA, a marker of recent nuclear import of full-length, reverse-transcribed RNA, was detected in the biopsies, suggesting active replication in renal tissue. Infiltrating infected leukocytes harbored more viral mRNA than renal epithelium. Identification of this novel reservoir suggests that effectively targeting the kidney with antiretrovirals may be critical for patients who are seropositive with renal disease. Thus, renal epithelium constitutes a unique and previously unrecognized cell target for HIV-1 infection.
Many industrial processes, such as power stations and ore smelters discharge large outflows of “waste” heat in off-gasses rich in CO
2. There is, however, rapidly growing interest in the mitigation ...of this CO
2, including using it to enhance the growth of microalgae for producing biodiesel. The use of off-gas to support ponds that act as microalgae incubators could represent a significant benefit to an industry’s operational economics and the environment. However, many generators of off-gases, particularly those related to mining, are located in regions, such as in South America, Northern Europe and Canada that experience long periods of temperatures well below those optimal for microalgae growth. Under these conditions, utilization of the heat in the off-gas to maintain water temperatures in microalgae ponds represents a new approach to beneficially exploit this otherwise waste energy. A dynamic model for a distributed temperature profile of a microalgae incubator pond bubbled through with off-gas was, therefore, developed using energy conservation laws. Simulations were carried out to evaluate pond temperatures in response to changes in gas flow rate and temperature, as well as annual variations in air temperatures and solar radiation. The results demonstrate the feasibility of significantly extending the operation of a microalgae production facility through the year beyond what would be possible without the use of the off-gas.
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