Abstract
Traditionally available handheld dosemeters are generally sensitive to only one type of radiation: neutrons or photons. Some dosemeters also rely on very specific attenuation correlations ...between response and dose, are not scalable in size and multiple dosemeters are required to characterise mixed-particle fields. The research presented here serves as a proof-of-concept for a method to simultaneously measure dose rates from neutrons and photons using a particle discriminating organic scintillation detector without the need for spectral deconvolution. The method was compared with traditional instruments and to simulation. Isotopic photon dose rates measured with this method were within 4% of simulated truth, whereas fission spectrum neutron dose rates were measured within 21%. Measurements of dose rates from both particles agree with simulated truth better than traditional instruments. This new method allows for measurement of dose equivalent from both neutrons and photons with a single instrument and no reliance on spectral deconvolution.
The basement membrane (BM) is a layer of specialized extracellular matrix that surrounds normal prostate glands and preserves tissue integrity. Lack or discontinuity of the BM is a prerequisite for ...tumor cell invasion into interstitial spaces, thus favoring metastasis. Therefore, BM maintenance represents a barrier against cancer development and progression. In the study, we show that miR-205 participates in a network involving ΔNp63α, which is essential for maintenance of the BM in prostate epithelium. At the molecular level, ΔNp63α is able to enhance miR-205 transcription by binding to its promoter, whereas the microRNA can post-transcriptionally limit the amount of ΔNp63α protein, mostly by affecting ΔNp63α proteasomal degradation rather than through a canonical miRNA/target interaction. Functionally, miR-205 is able to control the deposition of laminin-332 and its receptor integrin-β4. Hence, pathological loss of miR-205, as widely observed in prostate cancer, may favor tumorigenesis by creating discontinuities in the BM. Here we demonstrate that therapeutic replacement of miR-205 in prostate cancer (PCa) cells can restore BM deposition and 3D organization into normal-like acinar structures, thus hampering cancer progression.
The CUPID-0 experiment searches for double beta decay using cryogenic calorimeters with double (heat and light) read-out. The detector, consisting of 24 ZnSe crystals 95 Formula omitted enriched in ...Formula omittedSe and two natural ZnSe crystals, started data-taking in 2017 at Laboratori Nazionali del Gran Sasso. We present the search for the neutrino-less double beta decay of Formula omittedSe into the 0 Formula omitted, 2 Formula omitted and 2 Formula omitted excited states of Formula omittedKr with an exposure of 5.74 kg Formula omittedyr (2.24 Formula omitted10 Formula omitted emitters Formula omittedyr). We found no evidence of the decays and set the most stringent limits on the widths of these processes: Formula omitted( Formula omittedSe Formula omittedKr Formula omitted)8.55 Formula omitted10 Formula omitted yr Formula omitted, Formula omitted ( Formula omitted Se Formula omitted Kr Formula omitted) Formula omitted yr Formula omitted, Formula omitted( Formula omittedSe Formula omittedKr Formula omitted)8.25 Formula omitted10 Formula omitted yr Formula omitted (90 Formula omitted credible interval).
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
IV methylprednisolone (IVMP) has been used to treat relapses in patients with relapsing-remitting (RR) MS, but its effect on disease progression is not known. Furthermore, there are no data on the ...impact of IVMP on T1 black holes or whole-brain atrophy.
To determine the effect of IVMP on MRI measures of the destructive pathology in patients with RR-MS and secondarily to determine the effect of IVMP on disability progression in patients with RR-MS.
The authors conducted a randomized, controlled, single-blind, phase II clinical trial of IVMP in patients with RR-MS. Eighty-eight patients with RR-MS with baseline Expanded Disability Status Scale (EDSS) scores of < or =5.5 were randomly assigned to regular pulses of IVMP (1 g/day for 5 days with an oral prednisone taper) or IVMP at the same dose schedule only for relapses (IVMP for relapses) and followed without other disease-modifying drug therapy for 5 years. Pulsed IVMP was given every 4 months for 3 years and then every 6 months for the subsequent 2 years. Patients had quantitative cranial MRI scans at study entry and after 5 years and standardized clinical assessments every 4 to 6 months.
Eighty-one of 88 patients completed the trial as planned, and treatment was well tolerated. Baseline demographic, clinical, and MRI measures were well matched in the two study arms. Patients on the pulsed IVMP arm received more MP than patients on the control arm of the study (p < 0.0001). Mean change in T1 black hole volume favored pulsed IVMP therapy (+1.3 vs +5.2 mL; p < 0.0001), as did mean change in brain parenchymal volume (+2.6 vs -74.5 mL; p = 0.003). There was no significant difference between treatment arms in the change in T2 volume or annual relapse rate during the study. However, there was significantly more EDSS score worsening in the control group, receiving IVMP only for relapses. There was a 32.2% reduction (p </= 0.0001) in the probability of sustained EDSS score worsening in the pulsed MP arm compared with the relapse treatment arm. At the end of the study, EDSS was better in the pulsed MP group (1.7 vs 3.4; p < 0.0001). Prolonged treatment with pulsed IVMP was safe and well tolerated; only two patients dropped out for toxic side effects over 5 years.
In patients with RR-MS, treatment with pulses of IVMP slows development of T1 black holes, prevents or delays whole-brain atrophy, and prevents or delays disability progression. A phase III study of IVMP pulses is warranted.
Abstract
The TRISTAN project is the upgrade of the KATRIN experiment designed for the search of sterile neutrinos by replacing the current KATRIN detector with a multipixel SDD (Silicon Drift ...Detector) matrix. We have characterized SDDs response to electrons using a SEM (Scanning Electron Microscope) as an electron source and a Geant4-based simulation whose output is processed with an empirical function to reproduce data. We have crosschecked this model by reconstructing backscattering measurements obtained using a radioactive electron source.
Comparison of analog and digital pulse-shape-discrimination systems Sosa, C.S.; Flaska, M.; Pozzi, S.A.
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
08/2016, Letnik:
826, Številka:
C
Journal Article
Recenzirano
Odprti dostop
Pulse shape discrimination (PSD) performance of two optimized PSD systems (one digital and one analog) is compared in this work. One system uses digital charge integration, while the other system ...uses analog zero crossing. Measurements were conducted with each PSD system using the CAEN V1720 (250MHz) data acquisition system. An organic-liquid scintillator, coupled to a photo-multiplier tube, was used to detect neutrons and gamma rays from a Cf-252 spontaneous-fission source. The PSD performance of both systems was optimized and quantified using a traditional figure-of-merit (FOM) approach. FOM's were found for three, 300 keVee light-output bins, spanning from 100 to 1000keVee, and one larger bin from 100 to 1800keVee. Digital PSD outperformed analog PSD in the lowest light-output bin by approximately 50%, and by 11% for the highest light-output bin.
This study evaluated the mechanical behavior of different configurations of the All-on-4 treatment concept designed with straight short (6-mm-length), straight standard (11-mm-length), or tilted ...standard (30-degree angled; 11-mm-length) posterior implants.
The All-on-4 configurations were performed in atrophic mandible models and consisted of anterior straight standard and posterior tilted standard implants (H1 model), anterior straight standard and posterior straight short implants (H2 model), and anterior and posterior straight standard implants (H3 model). Three oblique forces of 100 N were simulated in the posterior region of the prosthetic bar. The values of stress were obtained for the ductile materials using the von Mises equivalent stress (σ
) criteria. The stress peaks in the peri-implant bone crest were measured by the maximum (σ
) and minimum (σ
) principal stresses. The two-way analysis of variance (two-way ANOVA) and Tukey post hoc tests determined significant differences (P < .01) of stress values among the ductile materials (implant and prosthetic components).
The use of tilted standard posterior implants (H1 model) showed the lowest values of σ
and σ
in the posterior region of the peri-implant bone area. On the other hand, the use of straight short (H2 model) or straight standard (H3 model) posterior implants significantly reduced the von Mises mean stresses in the bar screws, abutments, and abutment screws (P < .01).
The higher odds of technical failures (screw fracture/loosening) may be expected when the All-on-4 configuration is performed with tilted standard posterior implants. Also, peri-implant bone overload may occur when the All-on-4 design is performed with straight short or straight standard posterior implants in atrophic mandibles.
Localization and modeling of radioactive contaminations is a challenge that ultra-low background experiments are constantly facing. These are fundamental steps both to extract scientific results and ...to further reduce the background of the detectors. Here we present an innovative technique based on the analysis of
α
-
α
delayed coincidences in
232
Th and
238
U decay chains, developed to investigate the contaminations of the ZnSe crystals in the CUPID-0 experiment. This method allows to disentangle surface and bulk contaminations of the detectors relying on the different probability to tag delayed coincidences as function of the
α
decay position.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Dysregulated cell cycling is a universal hallmark of cancer and is often mediated by abnormal activation of cyclin-dependent kinases (CDKs) and their cyclin partners. Over-expression of individual ...complexes are reported in multiple myeloma (MM), making them attractive therapeutic targets. In this study, we investigate the preclinical activity of a novel small-molecule multi-CDK inhibitor, AT7519, in MM. We show the anti-MM activity of AT7519 displaying potent cytotoxicity and apoptosis; associated with in vivo tumor growth inhibition and prolonged survival. At the molecular level, AT7519 inhibited RNA polymerase II (RNA pol II) phosphorylation, a CDK9, 7 substrate, associated with decreased RNA synthesis confirmed by ³H Uridine incorporation. In addition, AT7519 inhibited glycogen synthase kinase 3β (GSK-3β) phosphorylation; conversely pretreatment with a selective GSK-3 inhibitor and shRNA GSK-3β knockdown restored MM survival, suggesting the involvement of GSK-3β in AT7519-induced apoptosis. GSK-3β activation was independent of RNA pol II dephosphorylation confirmed by α-amanitin, a specific RNA pol II inihibitor, showing potent inhibition of RNA pol II phosphorylation without corresponding effects on GSK-3β phosphorylation. These results offer new insights into the crucial, yet controversial role of GSK-3β in MM and show significant anti-MM activity of AT7519, providing the rationale for its clinical evaluation in MM. Oncogene (2010) 29, 2325-2336; doi: 10.1038/onc.2009.510; published online 25 January 2010 Keywords: myeloma; cyclin-dependent kinase; GSK-3β; RNA pol II
PDF
