Millisecond solar radio bursts in the metric wavelength range

A study and classification of super-short structures (SSSs) recorded during metric type IV bursts is presented. The most important property of SSSs is their duration, at half power ranging from 4-50 ms, what is up to 10 times shorter than spikes at corresponding frequencies. The solar origin of the SSSs is confirmed by one-to-one correspondence between spectral recordings of Artemis-IV1 and high time resolution single frequency measurements of the TSRS2. We have divided the SSSs in the following categories: 1. Broad-Band SSSs: They were partitioned in two subcategories, the SSS-Pulses and Drifting SSSs; 2. Narrow-band: They appear either as Spike-Like SSSs or as Patch-Like SSSs; 3. Complex SSS: They consist of the absorption-emission segments and were morphologically subdivided into Rain-drop Bursts (narrow-band emission head and a broad-band absorption tail) and Blinkers.Comment: Recent Advances in Astronomy and Astrophysics: 7th International Conference of the Hellenic Astronomical Society. AIP Conference Proceedings, Volume 848, pp. 224-228 (2006

Integrated functional and spatial profiling of tumour immune responses induced by immunotherapy: the iPROFILER platform

Background: Cancer immunotherapy elicits functional activation and changes in immune cell distribution in cancer. Tumour heterogeneity is a reason for treatment failure but is difficult to capture in experimental settings. This proof-of-principle study describes the integrated functional and digital spatial profiling platform iPROFILER to capture in-situ immune activation patterns with high precision. Materials and methods: iPROFILER combines an algorithm-based image analysis approach for spatial profiling with functional analyses of patient-derived tumour fragments (PDTFs). This study utilized a folate receptor 1 (FOLR1)xCD3 bispecific antibody in dual-affinity re-targeting (DART) format as a tool for inducing T-cell responses in patient tumour samples, and an in-depth investigation of the immune perturbations induced in the tumour microenvironment was performed. Results: Ex-vivo DART stimulation induces upregulation of multiple activation markers in CD4+ and CD8+ T-cell populations and secretion of pro-inflammatory cytokines in FOLR1-positive tumour specimens. This response was reduced or absent in tissue samples that did not express FOLR1. Immunological responses were driven by a strong induction of interferon gamma (IFNγ) and IFNγ-induced chemokines suggestive of activation of cytotoxic or Th1-like T cells. Ex-vivo DART treatment led to a numerical increase in effector T cells and an upregulation of immune activation markers in the tumour microenvironment as captured by digital image analysis. Analysis of immune activation in tumour and stromal regions further supported the potential of the platform to measure local differences in cell-type-specific activation patterns. Conclusions: iPROFILER effectively combines functional and spatial readouts to investigate immune responses ex vivo in human tumour samples. Keywords: Ex-vivo models; computer-assisted image processing; digital pathology; immunotherapy; tumour biomarkers; tumour microenvironment

Characterization of CDKN2A(p16) methylation and impact in colorectal cancer: systematic analysis using pyrosequencing

Background The aim of this study is to analyse CDKN2A methylation using pyrosequencing on a large cohort of colorectal cancers and corresponding non-neoplastic tissues. In a second step, the effect of methylation on clinical outcome is addressed. Methods Primary colorectal cancers and matched non-neoplastic tissues from 432 patients underwent CDKN2A methylation analysis by pyrosequencing (PyroMarkQ96). Methylation was then related to clinical outcome, microsatellite instability (MSI), and BRAF and KRAS mutation. Different amplification conditions (35 to 50 PCR cycles) using a range of 0-100% methylated DNA were tested. Results Background methylation was at most 10% with ≥35 PCR cycles. Correlation of observed and expected values was high, even at low methylation levels (0.02%, 0.6%, 2%). Accuracy of detection was optimal with 45 PCR cycles. Methylation in normal mucosa ranged from 0 to >90% in some cases. Based on the maximum value of 10% background, positivity was defined as a ≥20% difference in methylation between tumor and normal tissue, which occurred in 87 cases. CDKN2A methylation positivity was associated with MSI (p = 0.025), BRAF mutation (p < 0.0001), higher tumor grade (p < 0.0001), mucinous histology (p = 0.0209) but not with KRAS mutation. CDKN2A methylation had an independent adverse effect (p = 0.0058) on prognosis. Conclusion The non-negligible CDKN2A methylation of normal colorectal mucosa may confound the assessment of tumor-specific hypermethylation, suggesting that corresponding non-neoplastic tissue should be used as a control. CDKN2A methylation is robustly detected by pyrosequencing, even at low levels, suggesting that this unfavorable prognostic biomarker warrants investigation in prospective studies

Classification and Properties of Supershort Solar Radio Bursts

Characteristics of supershort structures (SSSs) occurring in the metric solar type IV radio bursts are described. The most important property of SSSs is their duration, which, at half-power, ranges from 4 to 60 ms and is thus much shorter than generally expected for the bursts in the metric range. The comparison of the distributions of SSS durations with those of the spikes confirms that these are completely different classes of bursts. Our analysis is focused on the frequency range 200-450 MHz, providing us with the one-to-one identification of individual SSSs in single-frequency records of the INAF-Trieste Astronomical Observatory (Italy) and in the high-resolution spectral data of Artemis IV (Greece). The analysis reveals a number of different bursts that are classified as simple broadband, simple narrowband, and complex SSSs. The diversity of SSSs has a resemblance to the variety of the well-known metric radio bursts characterized by a 1 s timescale

RADIO EVIDENCE OF BREAK-OUT RECONNECTION?

We reconsider the 2003 October 28 X17 flare/coronal mass ejection (CME), studying the five minutes immediately before the impulsive flare phase (not discussed in previous work). To this aim we examine complementary dynamic radio spectrograms, single frequency polarimeter records, radio images, space-based longitudinal field magnetograms, and ultraviolet images. We find widely distributed faint and narrowband meter wave radio sources located outside active regions but associated with the boundaries of magnetic flux connectivity cells, inferred from the potential extrapolation of the observed photospheric longitudinal field as a model for coronal magnetic field structures. The meter wave radio sources occur during the initial decimeter wave effects, which are well known to be associated with filament destabilization in the flaring active region (here NOAA 10486). Antiochos et al. predict in their break-out model for CME initiation that "... huge phenomena ... may be controlled by detailed plasma processes that occur in relatively tiny regions." They suggest that the expected faint energy release "... on long field lines far away from any neutral line ... may be detectable in radio/microwave emission from nonthermal particles..." In this paper, we describe meter wave sources whose properties correctly coincide with the quoted predictions of the break-out reconnection model of the CME initiation

Combining visibilities from the Giant Meterwave Radio Telescope and the Nancay Radio Heliograph: High dynamic range snapshot images of the solar corona at 327 MHz

We report first results from an ongoing program of combining visibilities from the Giant Meterwave Radio Telescope (GMRT) and the Nancay Radio Heliograph (NRH) to produce composite snapshot images of the sun at meter wavelengths. We describe the data processing, including a specific multi-scale CLEAN algorithm. We present results of a) simulations for two models of the sun at 327 MHz, with differing complexity b) observations of a complex noise storm on the sun at 327 MHz on Aug 27 2002. Our results illustrate the capacity of this method to produce high dynamic range snapshot images when the solar corona has structures with scales ranging from the image resolution of 49" to the size of the whole sun. We find that we cannot obtain reliable snapshot images for complex objects when the visibilities are sparsely sampled.Comment: Accepted for publication in Astronomy & Astrophysics. Version with high resolution figures available from ftp://ftp.iucaa.ernet.in/in.coming/gmrtnr

CD8+ lymphocytes/ tumour-budding index: an independent prognostic factor representing a ‘pro-/anti-tumour' approach to tumour host interaction in colorectal cancer

BACKGROUND: The tumour-host interaction at the invasive front of colorectal cancer, including the epithelial-mesenchymal transition and its hallmark 'tumour budding', is an important area of investigation in terms of prognosis. The aim of this study was to determine the prognostic impact of a 'pro-/anti-tumour' approach defined by an established 'pro-tumour' (tumour budding) and host-related 'anti-tumour' factor of the adaptive immunological microenvironment (CD8+ lymphocytes). METHODS: Double immunostaining for CK22/CD8 on whole tissue sections (n=279; Cohort 1) and immunohistochemistry for CD8+ using tissue microarrays (n=191; Cohort 2) was carried out. Tumour buds, CD8+ and CD8+ T-lymphocytes : tumour buds indices were evaluated per high-power field. RESULTS: In Cohort 1, a low-CD8+/ buds index was associated with lymph node metastasis (P>0.001), vascular invasion (P=0.009), worse survival in univariate (P>0.001) and multivariable (P>0.001) analysis, and furthermore in lymph node-negative patients (P=0.002). In Cohort 2, the CD8+/ buds index was associated with T stage (P>0.001), N stage (P=0.041), vascular invasion (P=0.005) and survival in patients with TNM stage II (P=0.019), stage III (P=0.004), and adjuvantly untreated (P=0.009) and treated patients (P>0.001). CONCLUSION: The CD8+ lymphocyte : tumour-budding index is an independent prognostic factor in colorectal cancer and a promising approach for a future prognostic score for patients with this disease

Reproducibility of tumor budding assessment in pancreatic cancer based on a multicenter interobserver study.

Tumor budding has been reported to be an independent prognostic factor in pancreatic ductal adenocarcinoma (PDAC). Its use in daily diagnostics would improve the prognostic stratification of patients. We performed a multicenter interobserver study to test various budding assessment methods for their reproducibility. Two serial sections of 50 resected, treatment-naïve PDACs were stained for Hematoxylin and Eosin (H&amp;E) and pancytokeratin. Tumor budding was scored by independent observers at five participating centers in Switzerland, Germany, and Canada. Pathologists assessed tumor budding on a digital platform comparing H&amp;E with pancytokeratin staining in 10 high-power fields (10HPF) and one HPF hotspot (1HPF). Additionally, tumor budding was assessed in one H&amp;E hotspot at × 20 magnification, as suggested by the International Tumor Budding Consensus Conference (ITBCC). Correlation coefficients for bud counts between centers ranged from r = 0.58648 to r = 0.78641 for H&amp;E and from r = 0.69288 to r = 0.81764 for pancytokeratin. The highest interobserver agreement across all centers was observed for pancytokeratin 10HPFs (ICC = 0.6). ICC values were 0.49, 0.48, 0.41, and 0.4 for H&amp;E in 1HPF hotspot, H&amp;E in 10HPFs, pancytokeratin in 1HPF, and H&amp;E in one hotspot at ×20, respectively (ITBCC method). This interobserver study reveals a range between moderately poor to moderate agreement levels between pathologists for the different tumor budding assessment methods in PDAC. Acceptable levels of agreement were reached with the pancytokeratin 10HPF method, which can thus be recommended for the assessment of tumor budding in PDAC resection specimens. To improve the levels of interobserver agreement, the implementation of machine learning applications should be considered

Prognostic impact of the expression of putative cancer stem cell markers CD133, CD166, CD44s, EpCAM, and ALDH1 in colorectal cancer

The aim of this study was to elucidate the prognostic impact of putative cancer stem cell markers CD133, CD166, CD44s, EpCAM, and aldehyde dehydrogenase-1 (ALDH1) in colorectal cancer

Coordinated Cellular Neighborhoods Orchestrate Antitumoral Immunity at the Colorectal Cancer Invasive Front.

Antitumoral immunity requires organized, spatially nuanced interactions between components of the immune tumor microenvironment (iTME). Understanding this coordinated behavior in effective versus ineffective tumor control will advance immunotherapies. We re-engineered co-detection by indexing (CODEX) for paraffin-embedded tissue microarrays, enabling simultaneous profiling of 140 tissue regions from 35 advanced-stage colorectal cancer (CRC) patients with 56 protein markers. We identified nine conserved, distinct cellular neighborhoods (CNs)-a collection of components characteristic of the CRC iTME. Enrichment of PD-1+CD4+ T cells only within a granulocyte CN positively correlated with survival in a high-risk patient subset. Coupling of tumor and immune CNs, fragmentation of T cell and macrophage CNs, and disruption of inter-CN communication was associated with inferior outcomes. This study provides a framework for interrogating how complex biological processes, such as antitumoral immunity, occur through concerted actions of cells and spatial domains