50 research outputs found
Effective Dissipation and Turbulence in Spectrally Truncated Euler Flows
A new transient regime in the relaxation towards absolute equilibrium of the
conservative and time-reversible 3-D Euler equation with high-wavenumber
spectral truncation is characterized. Large-scale dissipative effects, caused
by the thermalized modes that spontaneously appear between a transition
wavenumber and the maximum wavenumber, are calculated using fluctuation
dissipation relations. The large-scale dynamics is found to be similar to that
of high-Reynolds number Navier-Stokes equations and thus to obey (at least
approximately) Kolmogorov scaling.Comment: 4 pages, 5 figures new version with only 4 figures; title changed;
manuscript changed; accepted by PR
Electric dipole polarizability of Ca
The electric dipole strength distribution in Ca between 5 and 25 MeV
has been determined at RCNP, Osaka, from proton inelastic scattering
experiments at very forward angles. Combined with total photoabsorption data at
higher excitation energy, this enables an extraction of the electric dipole
polarizability (Ca) = 1.92(17) fm. Together with
the measured in Ca, it provides a stringent test of
modern theoretical approaches, including coupled cluster calculations with
chiral effective field theory interactions and state-of-the art energy density
functionals. The emerging picture is that for this medium-mass region dipole
polarizabilities are well described theoretically, with important constraints
for the neutron skin in Ca and related equation of state quantities.Comment: 6 pages, 3 figure
Genetic polymorphisms of MMP1, MMP3 and MMP7 gene promoter and risk of colorectal adenoma
BACKGROUND: Matrix metalloproteinases (MMP) have been shown to play a role in colorectal cancer (CRC). More recently, MMP1, MMP3 and MMP7 functional gene promoter polymorphisms have been found to be associated with CRC occurrence and prognosis. To document the role of MMP polymorphisms in the early step of colorectal carcinogenesis, we investigated their association with colorectal adenoma risk in a case-control study comprising 295 patients with large adenomas (LA), 302 patients with small adenomas (SA) and 568 polyp-free (PF) controls. METHODS: Patients were genotyped using automated fragment analysis for MMP1 -1607 ins/del G and MMP3 -1612 ins/delA (MMP3.1) polymorphisms and allelic discrimination assay for MMP3 -709 A/G (MMP3.2) and MMP7 -181 A/G polymorphisms. Association between MMP genotypes and colorectal adenomas was first tested for each polymorphism separately and then for combined genotypes using the combination test. Adjustment on relevant variables and estimation of odds ratios were performed using unconditional logistic regression. RESULTS: No association was observed between the polymorphisms and LA when compared to PF or SA. When comparing SA to PF controls, analysis revealed a significant association between MMP3 -1612 ins/delA polymorphism and SA with an increased risk associated with the 6A/6A genotype (OR = 1.67, 95%CI: 1.20–2.34). Using the combination test, the best association was found for MMP3.1-MMP1 (p = 0.001) with an OR of 1.88 (95%CI: 1.08–3.28) for the combined genotype 2G/2G-6A/6A estimated by logistic regression. CONCLUSION: These data show a relation between MMP1 -1607 ins/del G and MMP3 -1612 ins/delA combined polymorphisms and risk of SA, suggesting their potential role in the early steps of colorectal carcinogenesis
Mepolizumab as the first targeted treatment for eosinophilic granulomatosis with polyangiitis: a review of current evidence and potential place in therapy
Paola Faverio,1,2 Giulia Bonaiti,1,2 Francesco Bini,3 Adriano Vaghi,3 Alberto Pesci1,2 1School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy; 2Respiratory Unit, San Gerardo Hospital, ASST di Monza, Monza, Italy; 3ASST-Rhodense, UOC Pneumologia, Garbagnate Milanese, Milan, Italy Abstract: Mepolizumab is an anti-interleukin-5 (IL-5) humanized monoclonal antibody that binds to free IL-5. It induces bone marrow eosinophil maturation arrest and decreases eosinophil progenitors and subsequent maturation in the blood and bronchial mucosa. Its use has been extensively studied in severe eosinophilic asthma at a dose of 100 mg subcutaneously (SC) every 4 weeks and, more recently, in other hypereosinophilic syndromes. Eosinophilic granulomatosis with polyangiitis (EGPA) is an eosinophilic vasculitis that may involve multiple organs. Characteristic clinical manifestations are asthma, sinusitis, transient pulmonary infiltrates and neuropathy. Among the numerous pathways involved in the pathogenesis of EGPA, the Th-2 phenotype has a main role, as suggested by the prominence of the asthmatic component, in triggering the release of key cytokines for the activation, maturation and survival of eosinophils. In particular, IL-5 is highly increased in active EGPA and its inhibition can represent a potential therapeutic target. In this scenario, mepolizumab may play a therapeutic role. After some positive preliminary observations on the use of mepolizumab in small case series of EGPA patients with refractory or relapsing disease despite standard of care treatment, a randomized controlled trial was published in 2017. Mepolizumab at a dose of 300 mg administered by SC injection every 4 weeks proved effective in prolonging the period of remission of the disease, allowing for reduced steroid use. The positive results of this study, which met both of the primary endpoints, led to the approval in the USA of mepolizumab in adult patients with EGPA by the Food and Drug Administration in 2017. Therefore, mepolizumab can be officially considered as an add-on therapy with steroid-sparing effect in cases of relapsing or refractory EGPA. However, the most appropriate dose and duration of therapy still need to be determined. Future studies on larger multinational populations with prolonged follow-up are warranted. Keywords: mepolizumab, eosinophilic granulomatosis with polyangiitis, Churg–Strauss syndrom
Linkage of familial breast cancer to chromosome 17q21 may not be restricted to early-onset disease.
Lod scores for linkage between familial breast and ovarian cancer and markers on chromosome 17q21 are more frequently positive among families with disease diagnosed at younger ages than they are among older-onset families, suggesting that linkage is restricted to early-onset disease. However, for late-onset cases, the relative probability of sporadic rather than inherited disease is higher than previously suggested. If this correction is made, then later-onset families are much less informative; linkage heterogeneity based on age at onset is no longer significant; and for the sample of families as a whole, linkage is significant at a recombination fraction since demonstrated to be close to the correct local. There is probably more than one gene for inherited breast cancer, but heterogeneity may not be due to age at disease onset
Penetrance of Parkinson disease in glucocerebrosidase gene mutation carriers
Glucocerebrosidase (GBA) gene mutations represent a strong risk factor for Parkinson disease (PD). PD penetrance in GBA mutation carriers, which represents a key issue for genetic counseling, especially for relatives of patients with Gaucher disease (GD), is unknown. Our objective was to estimate PD penetrance in a familial study of GBA mutation carriers
Mode III threshold under Rolling Contact Fatigue and development of a test gearbox for planet gears: Conference Proceedings
This paper is on the assessment for Mode III crack propagation under the influence of primarily Rolling Contact Fatigue (RCF) in integrated thin-rimmed planetary gears and its integrated bearings, and the design and development of a test gearbox for the full-scale testing of such a 3-gear train planet gears layout. It is in response to the ‘Innovative DEsign for Reliable PLANEt bearings’ (IDERPLANE) research project which will address the concern of high RCF in planetary gear bearings in the epicyclic modules of aerospace applications such as Geared turbofans (GTFs) and Main gearboxes (MGBs) in aircrafts. The project is part of the Clean Sky 2 Horizon 2020 call, and its consortium is headed by the Politecnico di Milano