<b><i>Topoisomerase 1</i></b> Promoter Variants and Benefit from Irinotecan in Metastatic Colorectal Cancer Patients

Objective: Topoisomerase 1 (topo-1) is an important target for the treatment of metastatic colorectal cancer (CRC). The aim of the present study was to evaluate the correlation between topo-1 single-nucleotide polymorphisms (SNPs) and clinical outcome in metastatic CRC (mCRC) patients. Methods: With the use of specific software (PROMO 3.0), we performed an in silico analysis of topo-1 promoter SNPs; the rs6072249 and rs34282819 SNPs were included in the study. DNA was extracted from 105 mCRC patients treated with FOLFIRI ± bevacizumab in the first line. SNP genotyping was performed by real-time PCR. Genotypes were correlated with clinical parameters (objective response rate, progression-free survival, and overall survival). Results: No single genotype was significantly associated with clinical variables. The G allelic variant of rs6072249 topo-1 SNP is responsible for GC factor and X-box-binding protein transcription factor binding. The same allelic variant showed a nonsignificant trend toward a shorter progression-free survival (GG, 7.5 months; other genotypes, 9.3 months; HR 1.823, 95% CI 0.8904-3.734; p = 0.1). Conclusion: Further analyses are needed to confirm that the topo-1 SNP rs6072249 and transcription factor interaction could be a part of tools to predict clinical outcome in mCRC patients treated with irinotecan-based regimens

Modelling of an intersubband quantum confined Stark effect in Ge quantum wells for mid-infrared photonics

: In this work we theoretically investigate quantum confined Stark effect of intersubband transitions in asymmetric Ge/SiGe quantum wells for intensity modulation in the mid-infrared. Our calculations show that extinction ratios up to 1 dB and modulation speeds of several tens of GHz could be obtained in 100 µm long waveguides

Seesaw mechanism, baryon asymmetry and neutrinoless double beta decay

A simplified but very instructive analysis of the seesaw mechanism is here performed. Assuming a nearly diagonal Dirac neutrino mass matrix, we study the forms of the Majorana mass matrix of right-handed neutrinos, which reproduce the effective mass matrix of left-handed neutrinos. As a further step, the important effect of a non diagonal Dirac neutrino mass matrix is explored. The corresponding implications for the baryogenesis via leptogenesis and for the neutrinoless double beta decay are reviewed. We propose two distinct models where the baryon asymmetry is enhanced.Comment: 21 pages, RevTex. Revise

A comparative analysis of denoising algorithms for extragalactic imaging surveys

Aims. We present a comprehensive analysis of the performance of noise-reduction (denoising) algorithms to determine whether they provide advantages in source detection, mitigating noise on extragalactic survey images. Methods. The methods we analyze here are representative of different algorithmic families: Perona-Malik filtering, bilateral filter, total variation denoising, structure-texture image decomposition, non-local means, wavelets, and block-matching We tested the algorithms on simulated images of extragalactic fields with resolution and depth typical of the Hubble, Spitzer, and Euclid Space Telescopes, and of ground-based instruments. After choosing their best internal parameters configuration, we assessed their performance as a function of resolution, background level, and image type, in addition to testing their ability to preserve the objects fluxes and shapes. Finally, we analyze, in terms of completeness and purity, the catalogs that were extracted after applying denoising algorithms on a simulated Euclid Wide Survey VIS image and on real H160 and K-band (HAWK-I) observations of the CANDELS GOODS-South field. Results. Denoising algorithms often outperform the standard approach of filtering with the point spread function (PSF) of the image. Applying structure-texture image decomposition, Perona-Malik filtering, the total variation method by Chambolle, and bilateral filtering on the Euclid-VIS image, we obtain catalogs that are both more pure and complete by 0.2 magnitude than those based on the standard approach. The same result is achieved with the structure-texture image decomposition algorithm applied on the H160 image. The relative advantage of denoising techniques with respect to PSF filtering rises with increasing depth. Moreover, these techniques better preserve the shape of the detected objects with respect to PSF smoothing. Conclusions. Denoising algorithms provide significant improvements in the detection of faint objects and enhance the scientific return of current and future extragalactic surveys. We identify the most promising denoising algorithms among the 20 techniques considered in this study

Bilateral diaphragmatic paralysis after kidney surgery

A 57-year-old woman underwent an enucleoresection of her right kidney angiomyolipoma. Two weeks later she was admitted to our hospital because of dyspnea at rest with orthopnea. The chest x-ray showed the elevation of both hemidiaphragms and the measurement of the sniff transdiaphragmatic pressure confirmed the diagnosis of bilateral diaphragmatic paralysis. A diaphragm paralysis can be ascribed to several causes, i.e. trauma, compressive events, inflammations, neuropathies, or it can be idiopathic. In this case, it was very likely that the patient suffered from post-surgery neuralgic amyotrophy. To our knowledge, there are only a few reported cases of neuralgic amyotrophy, also known as Parsonage- Turner Syndrome, which affects only the phrenic nerve as a consequence of a surgery in an anatomically distant site

A comparative analysis of denoising algorithms for extragalactic imaging surveys

We present a comprehensive analysis of the performance of noise-reduction (``denoising'') algorithms to determine whether they provide advantages in source detection on extragalactic survey images. The methods under analysis are Perona-Malik filtering, Bilateral filter, Total Variation denoising, Structure-texture image decomposition, Non-local means, Wavelets, and Block-matching. We tested the algorithms on simulated images of extragalactic fields with resolution and depth typical of the Hubble, Spitzer, and Euclid Space Telescopes, and of ground-based instruments. After choosing their best internal parameters configuration, we assess their performance as a function of resolution, background level, and image type, also testing their ability to preserve the objects fluxes and shapes. We analyze in terms of completeness and purity the catalogs extracted after applying denoising algorithms on a simulated Euclid Wide Survey VIS image, on real H160 (HST) and K-band (HAWK-I) observations of the CANDELS GOODS-South field. Denoising algorithms often outperform the standard approach of filtering with the Point Spread Function (PSF) of the image. Applying Structure-Texture image decomposition, Perona-Malik filtering, the Total Variation method by Chambolle, and Bilateral filtering on the Euclid-VIS image, we obtain catalogs that are both more pure and complete by 0.2 magnitudes than those based on the standard approach. The same result is achieved with the Structure-Texture image decomposition algorithm applied on the H160 image. The advantage of denoising techniques with respect to PSF filtering increases at increasing depth. Moreover, these techniques better preserve the shape of the detected objects with respect to PSF smoothing. Denoising algorithms provide significant improvements in the detection of faint objects and enhance the scientific return of current and future extragalactic surveys.Comment: 30 pages, 55 figures; accepted for publication in A&

Increased levels of RNA oxidation enhance the reversion frequency in aging pro-apoptotic yeast mutants

Despite recent advances in understanding the complexity of RNA processes, regulation of the metabolism of oxidized cellular RNAs and the mechanisms through which oxidized ribonucleotides affect mRNA translation, and consequently cell viability, are not well characterized. We show here that the level of oxidized RNAs is markedly increased in a yeast decapping Kllsm4Δ1 mutant, which accumulates mRNAs, ages much faster that the wild type strain and undergoes regulated-cell-death. We also found that in Kllsm4Δ1 cells the mutation rate increases during chronological life span indicating that the capacity to han- dle oxidized RNAs in yeast declines with aging. Lowering intracellular ROS levels by antioxidants recovers the wild- type phenotype of mutant cells, including reduced amount of oxidized RNAs and lower mutation rate. Since mRNA oxidation was reported to occur in different neurodegen- erative diseases, decapping-deficient cells may represent a useful tool for deciphering molecular mechanisms of cell response to such conditions, providing new insights into RNA modification-based pathogenesis

The First Survey of X-ray Flares from Gamma Ray Bursts Observed by Swift: Temporal Properties and Morphology

We present the first systematic investigation of the morphological and timing properties of flares in GRBs observed by Swift/XRT. We consider a large sample drawn from all GRBs detected by Swift, INTEGRAL and HETE-2 prior to 2006 Jan 31, which had an XRT follow-up and which showed significant flaring. Our sample of 33 GRBs includes long and short, at low and high redshift, and a total of 69 flares. The strongest flares occur in the early phases, with a clear anti-correlation between the flare peak intensity and the flare time of occurrence. Fitting each X-ray flare with a Gaussian model, we find that the mean ratio of the width and peak time is = 0.13+/-0.10, albeit with a large scatter. Late flares at times > 2000 seconds have long durations, Delta t>300 s, and can be very energetic compared to the underlying continuum. We further investigated if there is a clear link between the number of pulses detected in the prompt phase by BAT and the number of X-ray flares detected by XRT, finding no correlation. However, we find that the distribution of intensity ratios between successive BAT prompt pulses and that between successive XRT flares is the same, an indication of a common origin for gamma-ray pulses and X-ray flares. All evidence indicates that flares are indeed related to the workings of the central engine and, within the standard fireball scenario, originate from internal shocks rather than external shocks. While all flares can be explained by long-lasting engine activity, 29/69 flares may also be explained by refreshed shocks. However, 10 can only be explained by prolonged activity of the central engine.Comment: submitted to Ap