A versatile facility for the calibration of X-ray polarimeters with polarized and unpolarized controlled beams

We devised and built a versatile facility for the calibration of the next generation X-ray polarimeters with unpolarized and polarized radiation. The former is produced at 5.9 keV by means of a Fe55 radioactive source or by X-ray tubes, while the latter is obtained by Bragg diffraction at nearly 45 degrees. Crystals tuned with the emission lines of X-ray tubes with molybdenum, rhodium, calcium and titanium anodes are employed for the efficient production of highly polarized photons at 2.29, 2.69, 3.69 and 4.51 keV respectively. Moreover the continuum emission is exploited for the production of polarized photons at 1.65 keV and 2.04 keV and at energies corresponding to the higher orders of diffraction. The photons are collimated by means of interchangeable capillary plates and diaphragms, allowing a trade-off between collimation and high fluxes. The direction of the beam is accurately arranged by means of high precision motorized stages, controlled via computer so that long and automatic measurements can be done. Selecting the direction of polarization and the incidence point we can map the response of imaging devices to both polarized and unpolarized radiation. Changing the inclination of the beam we can study the systematic effects due to the focusing of grazing incidence optics and the feasibility of instruments with large field of view.Comment: 12 pages, 11 figure

From the Amelioration of a NADP+-dependent Formate Dehydrogenase to the Discovery of a New Enzyme: Round Trip from Theory to Practice

NADP+-dependent formate dehydrogenases (FDHs) are biotechnologically relevant enzymes for cofactors regeneration in industrial processes employing redox biocatalysts. Their effective applicability is however hampered by the low cofactor and substrate affinities of the few enzymes described so far. After different efforts to ameliorate the previously studied GraFDH from the acidobacterium Granulicella mallensis MP5ACTX8, an enzyme having double (NAD+ and NADP+) cofactor specificity, we started over our search with the advantage of hindsight. We identified and characterized GraFDH2, a novel highly active FDH, which proved to be a good NAD+-dependent catalyst. A rational engineering approach permitted to switch its cofactor specificity, producing an enzyme variant that displays a 10-fold activity improvement over the wild-type enzyme with NADP+. Such variant resulted to be one of the best performing enzyme among the NADP+-dependent FDHs reported so far in terms of catalytic performance

Association between a common missense variant in LOXL3 gene and the risk of non-syndromic cleft palate

To investigate possible association between functional common variants in the lysyl oxidase like 3 gene and non-syndromic cleft palate we selected a common missense variant p.Ile615Phe (rs17010021), which was predicted to have a probably damaging effect on the lysyl oxidase like 3 enzyme. We genotyped 258 non-syndromic cleft palate case-parent triads of European origin and tested genetic association using the transmission disequilibrium test and log-linear regression analyses of genotypic relative risks and of parent-of-origin effects. The observed genotype frequency in parents was in Hardy-Weinberg equilibrium. Compared with wild-type Ile/Ile homozygotes, the relative risks for Phe/Phe homozygote infants was 6.87 (P value 3.0 × 10-3 ), while that for Ile/Phe heterozygotes was not significant. Assuming an autosomal recessive model, the relative risks for Phe/Phe genotype resulted 10.54 (P value 2.9 × 10-5 ), with a 3.6% population attributable risk. No parent-of-origin effect was observed. The identification in lysyl oxidase like 3 of a missense variant which under a recessive model associates with 10-fold increased risk of non-syndromic cleft palate supports the hypothesis that the genetic etiology of this congenital anomaly includes relatively uncommon recessive variants with moderate penetrance and located in genes which are also involved in syndromes that include cleft palate as part of the phenotype. Our findings require functional validation and replication in a larger independent genetic association study

Ultrastructural analysis of collagen fibril diameter distribution in cleft lip

Objective: A preliminary study to determine collagen fibril diameter (CF-ED) distribution on medial and lateral sides of cleft lip (CL). Material and Methods: Tissue samples from medial and lateral sides of CL were fixed in 2.5% glutaraldehyde and 1% osmium tetroxide and embedded in Araldite CY212 resin for transmission electron microscopy. The analysis of CF-ED was performed using the ImageJ program. To characterize the packaging of collagen fibrils (CFs) in the two tissues, we estimated the collagen number density (CF-ND) and fibril-area-fraction (FAF). Differences in measurements across the two sides were calculated using Wilcoxon signed-rank test. Results: The CF-ED was statistically significantly (p < 0.001) smaller on the medial side (45.69 ± 7.89 nm) than on the lateral side (54.18 ± 7.62 nm). The medial side had a higher CF-ND and a higher percentage of FAF than the lateral side. Conclusion: Our finding of a smaller CF-ED and higher CF-ND and FAF for the medial side suggests possible differences in size and distribution of CFs between medial and lateral sides of CL. This finding provides knowledge toward underlying tissue biomechanics that may help reconstruction of perioral tissue scaffolds, ultimately resulting in better treatment of patients with oral clefts

LINE-1 methylation in cleft lip tissues:influence of infant MTHFR c.677C&gt;T genotype

Objective: To investigate the influence of MTHFR c.677C&gt;T genotype on LINE-1 methylation in lateral and medial tissues from cleft lip (CL). Methods: Forty-five consecutive non-syndromic cleft lip with or without cleft palate (nsCL/P) cases were included in the study. Genomic DNA was extracted from tissues at both sides of cleft lip, and LINE-1 methylation was detected by bisulfite conversion and pyrosequencing. MTHFR c.677C&gt;T genotyping was carried out using the TaqMan genotyping assay. Results: LINE-1 methylation level was significantly higher on medial side of cleft lip compared with lateral side (p&nbsp;=&nbsp;0.001). This difference was not significantly influenced by the case's sex or cleft type. However, MTHFR c.677C&gt;T genotyping revealed that the difference in LINE-1 methylation across cleft lip was restricted to carriers of C allele of MTHFR c.677C&gt;T and was not apparent in TT homozygous cases (p&nbsp;=&nbsp;0.027). Conclusion: This integrated analysis supports the previous finding of differences in DNA methylation across the two sides of cleft lip and further suggests a possible role of MTHFR c.677C&gt;T genotype in establishing this difference

Re-testing the JET-X Flight Module No. 2 at the PANTER facility

The Joint European X-ray Telescope (JET-X) was the core instrument of the Russian Spectrum-X-gamma space observatory. It consisted of two identical soft X-ray (0.3 - 10 keV) telescopes with focusing optical modules having a measured angular resolution of nearly 15 arcsec. Soon after the payload completion, the mission was cancelled and the two optical flight modules (FM) were brought to the Brera Astronomical Observatory where they had been manufactured. After 16 years of storage, we have utilized the JET-X FM2 to test at the PANTER X-ray facility a prototype of a novel X-ray polarimetric telescope, using a Gas Pixel Detector (GPD) with polarimetric capabilities in the focal plane of the FM2. The GPD was developed by a collaboration between INFN-Pisa and INAF-IAPS. In the first phase of the test campaign, we have re-tested the FM2 at PANTER to have an up-to-date characterization in terms of angular resolution and effective area, while in the second part of the test the GPD has been placed in the focal plane of the FM2. In this paper we report the results of the tests of the sole FM2, using an unpolarized X-ray source, comparing the results with the calibration done in 1996.Comment: Author's accepted manuscript posted to arXiv.org as permitted by Springer's Self-Archiving Policy. The final publication is available at http://rd.springer.com/article/10.1007%2Fs10686-013-9365-

The Gas Pixel Detector as an X-ray photoelectric polarimeter with a large field of view

The Gas Pixel Detector (GPD) is a new generation device which, thanks to its 50 um pixels, is capable of imaging the photoelectrons tracks produced by photoelectric absorption in a gas. Since the direction of emission of the photoelectrons is strongly correlated with the direction of polarization of the absorbed photons, this device has been proposed as a polarimeter for the study of astrophysical sources, with a sensitivity far higher than the instruments flown to date. The GPD has been always regarded as a focal plane instrument and then it has been proposed to be included on the next generation space-borne missions together with a grazing incidence optics. Instead in this paper we explore the feasibility of a new kind of application of the GPD and of the photoelectric polarimeters in general, i.e. an instrument with a large field of view. By means of an analytical treatment and measurements, we verify if it is possible to preserve the sensitivity to the polarization for inclined beams, opening the way for the measurement of X-ray polarization for transient astrophysical sources. While severe systematic effects arise for inclination greater than about 20 degrees, methods and algorithms to control them are discussed.Comment: 11 pages, 8 figure

HSP 27 aspossible prognostic factor in patients with oral squamous cell carcinoma.

Summary. HSP27 belongs to the Heat shock protein (HSP) family, which plays essential functions in cells under physiological conditions and prevents stressinduced cellular damage. The aim of this study was to investigate the biological role of HSP27 in oral tumorigenesis. Materials and methods: Seventy-nine cases of oral squamous cell carcinoma and 10 cases of normal mucosa were analysed for HSP27 expression by immunohistochemistry. Moreover, the western blot analysis was performed on two cases of normal mucosa and five cases of OSCC. Results: Normal oral mucosa showed a suprabasal expression of HSP27. Twenty-four cases of SCC (30.7%) showed a diffuse staining for HSP27, and 48 cases (60.3%) showed instead a decrease in staining, which was diffuse, homogeneous, or with alternation of positive and negative areas in a single tumor (“mosaic” pattern). Only 7 cases of OSCC (7.5%) were completely negative for HSP27. Frequency of lymph node metastases was higher in HSP27-negative tumours (3/7, 42.8%) than in HSP-reduced (16/48, 33.3%) or positive ones (5/26, 19.2%). Regard staging, stages I and II had a higher score than stages III and IV (stage I > stage II > stage III > stage IV). There was also a statistically significant correlation between HSP27 expression and grade: HSP27 expression was reduced in poorly differentiated tumours (P < 0.05). When analysed for prognostic significance, patients with negative/reduced HSP27 expression had poorer survival rates than the group with positive HSP27 expression (P < 0.05). The statistical analysis of these findings showed no significant correlation between HSP27 expression, sex, and tumour size. Conclusion: Cases with reduced expression were more aggressive and poorly differentiated. These data suggest that HSP27 expression may be useful in order to identify cases of oral squamous cell carcinoma with more aggressive and invasive phenotype providing novel diagnostic and prognostic information on individual patient survival with oral cancers

An X-ray polarimeter for hard X-ray optics

Development of multi-layer optics makes feasible the use of X-ray telescope at energy up to 60-80 keV: in this paper we discuss the extension of photoelectric polarimeter based on Micro Pattern Gas Chamber to high energy X-rays. We calculated the sensitivity with Neon and Argon based mixtures at high pressure with thick absorption gap: placing the MPGC at focus of a next generation multi-layer optics, galatic and extragalactic X-ray polarimetry can be done up till 30 keV.Comment: 12 pages, 7 figure

A pilot study employing hepatic intra-arterial irinotecan injection of drug-eluting beads as salvage therapy in liver metastatic colorectal cancer patients without extrahepatic involvement: The first southern Italy experience

Background: The main aim of this prospective study was to evaluate the efficacy of drug-eluting beads with irinotecan (DEBIRI) for liver metastases from colorectal cancer. Secondary aims were to evaluate survival and toxicity. Methods: Twenty-five patients with metastases in &lt;50% of the liver and without extrahepatic involvement were enrolled. Treatment response assessment was performed by multidetector contrast enhancement computed tomography (MDCT) with evaluation of the enhancement pattern of the target lesion and tumor response rates according to modified Response Evaluation Criteria in Solid Tumors (mRECIST, Version 1.1). All adverse events were recorded by the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events, Version 3.0. Associations of tumor response and variables were calculated using the chi-squared test. Overall survival (OS) was calculated using the Kaplan–Meier method. Comparisons were made using the log-rank test. Results: According to mRECIST, complete response (CR) was observed in 21.8% of patients, partial response (PR) in 13%, stable disease (SD) in 52.2% and progressive disease (PD) in 13% of patients. Response rate (RR = CR + PR) was 34.8%. No associations between treatment response and variables such as Dukes’ classification, grading and Kras status were found (P&gt;0.05). The median OS was 37 months (95% CI: 13.881 to 60.119). Cox regression model showed that neither site, Dukes’ classification, grading, Kras status nor number of chemotherapy treatments pre-DEBIRI influenced the OS. The log-rank test showed no statistically significant difference in OS among patients who underwent 1, 2 or 3 DEBIRI treatments (χ2=2.831, P=0.09). In our study, the main toxicities included postembolization syndrome (PES), hypertransaminasemia and fever. Conclusion: The favorable tumor response and the favorable toxicity profile make DEBIRI treatment a potential third-line therapy. Although further larger studies are needed to confirm these data, we can state that DEBIRI is an attractive emerging treatment in these patients