Spillover and diffraction sidelobe contamination in a double-shielded experiment for mapping Galactic synchrotron emission

We have analyzed observations from a radioastronomical experiment to survey the sky at decimetric wavelengths along with feed pattern measurements in order to account for the level of ground contamination entering the sidelobes. A major asset of the experiment is the use of a wire mesh fence around the rim-halo shielded antenna with the purpose of levelling out and reducing this source of stray radiation for zenith-centered 1-rpm circular scans. We investigate the shielding performance of the experiment by means of a geometric diffraction model in order to predict the level of the spillover and diffraction sidelobes in the direction of the ground. Using 408 MHz and 1465 MHz feed measurements, the model shows how a weakly-diffracting and unshielded antenna configuration becomes strongly-diffracting and double-shielded as far-field diffraction effects give way to near-field ones. Due to the asymmetric response of the feeds, the orientation of their radiation fields with respect to the secondary must be known a priori before comparing model predictions with observational data. By adjusting the attenuation coefficient of the wire mesh the model is able to reproduce the amount of differential ground pick-up observed during test measurements at 1465 MHz.Comment: 14 pages, 17 eps + 1 gif figures and 4 Tables. Accepted for publication in A&AS. Fig.7 available at full resolution from http://www.das.inpe.br/~tello/publications.ht

A radio continuum survey of the southern sky at 1420 MHz. Observations and data reduction

We describe the equipment, observational method and reduction procedure of an absolutely calibrated radio continuum survey of the South Celestial Hemisphere at a frequency of 1420 MHz. These observations cover the area 0h < R.A. < 24h for declinations less than -10 degree. The sensitivity is about 50 mK T_B (full beam brightness) and the angular resolution (HPBW) is 35.4', which matches the existing northern sky survey at the same frequency.Comment: 9 pages with 9 figures, A&A, in pres

Autoantibody Profiling for Lung Cancer Screening Longitudinal Retrospective Analysis of CT Screening Cohorts

Recommendations for lung cancer screening present a tangible opportunity to integrate predictive blood-based assays with radiographic imaging. This study compares performance of autoantibody markers from prior discovery in sample cohorts from two CT screening trials. One-hundred eighty non-cancer and 6 prevalence and 44 incidence cancer cases detected in the Mayo Lung Screening Trial were tested using a panel of six autoantibody markers to define a normal range and assign cutoff values for class prediction. A cutoff for minimal specificity and best achievable sensitivity were applied to 256 samples drawn annually for three years from 95 participants in the Kentucky Lung Screening Trial. Data revealed a discrepancy in quantile distribution between the two apparently comparable sample sets, which skewed the assay’s dynamic range towards specificity. This cutoff offered 43% specificity (102/237) in the control group and accurately classified 11/19 lung cancer samples (58%), which included 4/5 cancers at time of radiographic detection (80%), and 50% of occult cancers up to five years prior to diagnosis. An apparent ceiling in assay sensitivity is likely to limit the utility of this assay in a conventional screening paradigm. Pre-analytical bias introduced by sample age, handling or storage remains a practical concern during development, validation and implementation of autoantibody assays. This report does not draw conclusions about other logical applications for autoantibody profiling in lung cancer diagnosis and management, nor its potential when combined with other biomarkers that might improve overall predictive accuracy

Differentiation of human induced pluripotent stem cells towards notochordal-like cells: the role of tissue source

INTRODUCTION: Notochordal cells (NCs) are linked to a healthy intervertebral disc (IVD), and they are considered an exciting target for cell-based therapy. However, NCs are scarcely available as they are lost early in life, and attempts at in vivoexpansion have failed because NCs lose their specific phenotype. The production of Notochordal-like cells (NLCs) from human induced pluripotent stem cells (iPSCs) is a viable alternative. However, current attempts have been challenged by the low differentiation efficiency into the NC lineage. Therefore, the aim of this study was to build on the tissue-specific epigenetic memory of hiPSCs derived from IVD progenitor cells (TIE2+-cells) to improve hiPSC differentiation towards mature, matrix-producing NLCs. METHODS: hiPSCs were generated from TIE2⁺ cells of three adult donors. As a comparison, donormatched minimally invasive peripheral blood mononuclear (PBM) cell-derived iPSCs were used. Firstly, the iPSCs were differentiated into mesendodermal progenitors by Wnt pathway activation (N2B27 medium + 3µM CHIR99021)¹. Thereafter, the cells were further driven towards the NClineage by transfection with synthetic NOTO mRNA¹ and further matured using a 3D pellet culture in discogenic medium containing 10ng/mL TGF-β1. Read-out parameters included cell morphology, gene and protein expression and matrix deposition. RESULTS: Both TIE2⁺ and PBM cell-derived hiPSC showed successful differentiation towards mesendodermal progenitor cells following Wnt activation on day 2, indicated by the cells moving out of the colonies after CHIR stimulation. Accordingly, a decreased gene expression of pluripotency markers (OCT4, SOX2, NANOG), and upregulation of Wnt-target genes (LEF1, NODAL) and mesendodermal markers (TBXT, FOXA2, TBX6) was observed compared to mTESR1 controls. This was confirmed by immuno-stains for FOXA2 and TBXT. At day 3, we confirmed a 9-fold increase in NOTO mRNA levels after transfection in all donor lines. At day 28, the appearance of vacuolated NLCs was observed in both TIE2⁺ and PBM cell-derived pellet cultures confirming successful commitment towards the NC-lineage. Interestingly, while DMMB-assay detected GAG deposition in both lines, a significant increase in GAG content was seen in the TIE2⁺ cell-derived pellets. DISCUSSION & CONCLUSIONS: Tissue-specific TIE2⁺ cell-derived iPSCs may allow for an improved iPSNLC differentiation efficiency, indicated by the increased potency for deposition of GAG-rich matrix. Detailed analysis of the phenotypic markers and matrix deposited at the end of the 28 day maturation is ongoing to further document the phenotype of these iPS-NLCs. Delineating which epigenetic features are retained after reprogramming of these two cell lines, could shed light on the differences in their differentiation capacity. REFERENCES: ¹Colombier et al., 202

Consensus guidelines for the management of radiation dermatitis and coexisting acne-like rash in patients receiving radiotherapy plus EGFR inhibitors for the treatment of squamous cell carcinoma of the head and neck

Background: Radiation dermatitis occurs to some degree in most patients receiving radiotherapy, with or without chemotherapy. Patients with squamous cell carcinoma of the head and neck (SCCHN) who receive radiotherapy in combination with epidermal growth factor receptor (EGFR) inhibitors, such as cetuximab, may develop a characteristic acne-like rash in addition to dermatitis. Design: An advisory board of 11 experienced radiation oncologists, medical oncologists and dermatologists discussed the management options for skin reactions in patients receiving EGFR inhibitors and radiotherapy for SCCHN. Skin toxicity was categorised according to the National Cancer Institute—Common Terminology Criteria for Adverse Events (version 3) grading. Results: Both general and grade-specific approaches for the management of dermatitis in this patient group are presented. It was concluded that where EGFR inhibitor-related acne-like rash and dermatitis coexist within irradiated fields, management should be based on the grade of dermatitis: for grade 1 (or no dermatitis), treatment recommendations for EGFR-related acne-like rash outside irradiated fields should be followed; for grades 2 and above, treatment recommendations for dermatitis were proposed. Conclusions: This paper presents comprehensive consensus guidelines for the treatment of dermatitis in patients with SCCHN receiving EGFR inhibitors in combination with radiotherap

Axonal Localization of Integrins in the CNS Is Neuronal Type and Age Dependent.

The regenerative ability of CNS axons decreases with age, however, this ability remains largely intact in PNS axons throughout adulthood. These differences are likely to correspond with age-related silencing of proteins necessary for axon growth and elongation. In previous studies, it has been shown that reintroduction of the α9 integrin subunit (tenascin-C receptor, α9) that is downregulated in adult CNS can improve neurite outgrowth and sensory axon regeneration after a dorsal rhizotomy or a dorsal column crush spinal cord lesion. In the current study, we demonstrate that virally expressed integrins (α9, α6, or β1 integrin) in the adult rat sensorimotor cortex and adult red nucleus are excluded from axons following neuronal transduction. Attempts to stimulate transport by inclusion of a cervical spinal injury and thus an upregulation of extracellular matrix molecules at the lesion site, or cotransduction with its binding partner, β1 integrin, did not induce integrin localization within axons. In contrast, virally expressed α9 integrin in developing rat cortex (postnatal day 5 or 10) demonstrated clear localization of integrins in cortical axons revealed by the presence of integrin in the axons of the corpus callosum and internal capsule, as well as in the neuronal cell body. Furthermore, examination of dorsal root ganglia neurons and retinal ganglion cells demonstrated integrin localization both within peripheral nerve as well as dorsal root axons and within optic nerve axons, respectively. Together, our results suggest a differential ability for in vivo axonal transport of transmembrane proteins dependent on neuronal age and subtype

Changes in elastin, elastin binding protein and versican in alveoli in chronic obstructive pulmonary disease

<p>Abstract</p> <p>Background</p> <p>COPD is characterised by loss of alveolar elastic fibers and by lack of effective repair. Elastic fibers are assembled at cell surfaces by elastin binding protein (EBP), a molecular chaperone whose function can be reversibility inhibited by chondroitin sulphate of matrix proteoglycans such as versican. This study aimed to determine if alveoli of patients with mild to moderate COPD contained increased amounts of versican and a corresponding decrease in EBP, and if these changes were correlated with decreases in elastin and FEV₁.</p> <p>Methods</p> <p>Lung samples were obtained from 26 control (FEV₁≥ 80% predicted, FEV₁/VC >0.7) and 17 COPD patients (FEV₁≥ 40% – <80% predicted, FEV₁/VC ≤ 0.7) who had undergone a lobectomy for bronchial carcinoma. Samples were processed for histological and immuno-staining. Volume fractions (<it>V</it>_v) of elastin in alveolar walls and alveolar rims were determined by point counting, and versican and EBP assessed by grading of staining intensities.</p> <p>Results</p> <p>Elastin <it>V</it>v was positively correlated with FEV₁for both the alveolar walls (r = 0.66, p < 0.001) and rims (r = 0.41, p < 0.01). Versican was negatively correlated with FEV₁in both regions (r = 0.30 and 0.32 respectively, p < 0.05), with the highest staining intensities found in patients with the lowest values for FEV₁. Conversely, staining intensities for EBP in alveolar walls and rims and were positively correlated with FEV₁(r = 0.43 and 0.46, p < 0.01).</p> <p>Conclusion</p> <p>Patients with mild to moderate COPD show progressively increased immuno-staining for versican and correspondingly decreased immuno-staining for EBP, with decreasing values of FEV₁. These findings may explain the lack of repair of elastic fibers in the lungs of patients with moderate COPD. Removal of versican may offer a strategy for effective repair.</p

Plant cell division is specifically affected by nitrotyrosine

Virtually all eukaryotic α-tubulins harbour a C-terminal tyrosine that can be reversibly removed and religated, catalysed by a specific tubulin–tyrosine carboxypeptidase (TTC) and a specific tubulin–tyrosine ligase (TTL), respectively. The biological function of this post-translational modification has remained enigmatic. 3-nitro-L-tyrosine (nitrotyrosine, NO2Tyr), can be incorporated into detyrosinated α-tubulin instead of tyrosine, producing irreversibly nitrotyrosinated α-tubulin. To gain insight into the possible function of detyrosination, the effect of NO2Tyr has been assessed in two plant model organisms (rice and tobacco). NO2Tyr causes a specific, sensitive, and dose-dependent inhibition of cell division that becomes detectable from 1 h after treatment and which is not observed with non-nitrosylated tyrosine. These effects are most pronounced in cycling tobacco BY-2 cells, where the inhibition of cell division is accompanied by a stimulation of cell length, and a misorientation of cross walls. NO2Tyr reduces the abundance of the detyrosinated form of α-tubulin whereas the tyrosinated α-tubulin is not affected. These findings are discussed with respect to a model where NO2Tyr is accepted as substrate by TTL and subsequently blocks TTC activity. The irreversibly tyrosinated α-tubulin impairs microtubular functions that are relevant to cell division in general, and cell wall deposition in particular