An atomic mechanism for the boson peak in metallic glasses

The boson peak in metallic glasses is modeled in terms of local structural shear rearrangements. Using Eshelby's solution of the corresponding elasticity theory problem (J. D. Eshelby, Proc. Roy. Soc. A241, 376 (1957)), one can calculate the saddle point energy of such a structural rearrangement. The neighbourhood of the saddle point gives rise to soft resonant vibrational modes. One can calculate their density, their kinetic energy, their fourth order potential term and their coupling to longitudinal and transverse sound waves.Comment: 9 pages, 7 figures, 31 references, contribution to 11th International Workshop on Complex Systems, Andalo (Italy), March 200

In Search of Differential Inhibitors of Aldose Reductase

Aldose reductase, classified within the aldo-keto reductase family as AKR1B1, is an NADPH dependent enzyme that catalyzes the reduction of hydrophilic as well as hydrophobic aldehydes. AKR1B1 is the first enzyme of the so-called polyol pathway that allows the conversion of glucose into sorbitol, which in turn is oxidized to fructose by sorbitol dehydrogenase. The activation of the polyol pathway in hyperglycemic conditions is generally accepted as the event that is responsible for a series of long-term complications of diabetes such as retinopathy, cataract, nephropathy and neuropathy. The role of AKR1B1 in the onset of diabetic complications has made this enzyme the target for the development of molecules capable of inhibiting its activity. Virtually all synthesized compounds have so far failed as drugs for the treatment of diabetic complications. This failure may be partly due to the ability of AKR1B1 to reduce alkenals and alkanals, produced in oxidative stress conditions, thus acting as a detoxifying agent. In recent years we have proposed an alternative approach to the inhibition of AKR1B1, suggesting the possibility of a differential inhibition of the enzyme through molecules able to preferentially inhibit the reduction of either hydrophilic or hydrophobic substrates. The rationale and examples of this new generation of aldose reductase differential inhibitors (ARDIs) are presented

Pathways of 4-hydroxy-2-nonenal detoxification in a human astrocytoma cell line

One of the consequences of the increased level of oxidative stress that often characterizes the cancer cell environment is the abnormal generation of lipid peroxidation products, above all 4-hydroxynonenal. The contribution of this aldehyde to the pathogenesis of several diseases is well known. In this study, we characterized the ADF astrocytoma cell line both in terms of its pattern of enzymatic activities devoted to 4-hydroxynonenal removal and its resistance to oxidative stress induced by exposure to hydrogen peroxide. A comparison with lens cell lines, which, due to the ocular function, are normally exposed to oxidative conditions is reported. Our results show that, overall, ADF cells counteract oxidative stress conditions better than normal cells, thus confirming the redox adaptation demonstrated for several cancer cells. In addition, the markedly high level of NADP+-dependent dehydrogenase activity acting on the glutahionyl-hydroxynonanal adduct detected in ADF cells may promote, at the same time, the detoxification and recovery of cell-reducing power in these cells

Evidence for treatment with estradiol for women with SARS-CoV-2 infection

Background: Given that an individual’s age and gender are strongly predictive of coronavirus disease 2019 (COVID-19) outcomes, do such factors imply anything about preferable therapeutic options? Methods: An analysis of electronic health records for a large (68,466-case), international COVID-19 cohort, in 5-year age strata, revealed age-dependent sex differences. In particular, we surveyed the effects of systemic hormone administration in women. The primary outcome for estradiol therapy was death. Odds ratios (ORs) and Kaplan-Meier survival curves were analyzed for 37,086 COVID-19 women in two age groups: pre- (15–49 years) and peri-/post-menopausal (> 50 years). Results: The incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is higher in women than men (by about + 15%) and, in contrast, the fatality rate is higher in men (about + 50%). Interestingly, the relationships between these quantities are linked to age: pre-adolescent girls and boys had the same risk of infection and fatality rate, while adult premenopausal women had a significantly higher risk of infection than men in the same 5-year age stratum (about 16,000 vs. 12,000 cases). This ratio changed again in peri- and postmenopausal women, with infection susceptibility converging with men. While fatality rates increased continuously with age for both sexes, at 50 years, there was a steeper increase for men. Thus far, these types of intricacies have been largely neglected. Because the hormone 17ß-estradiol influences expression of the human angiotensin-converting enzyme 2 (ACE2) protein, which plays a role in SARS-CoV-2 cellular entry, propensity score matching was performed for the women’s sub-cohort, comparing users vs. non-users of estradiol. This retrospective study of hormone therapy in female COVID-19 patients shows that the fatality risk for women > 50 years receiving estradiol therapy (user group) is reduced by more than 50%; the OR was 0.33, 95% CI [0.18, 0.62] and the hazard ratio (HR) was 0.29, 95% CI [0.11,0.76]. For younger, pre-menopausal women (15–49 years), the risk of COVID-19 fatality is the same irrespective of estradiol treatment, probably because of higher endogenous estradiol levels. Conclusions: As of this writing, still no effective drug treatment is available for COVID-19; since estradiol shows such a strong improvement regarding fatality in COVID-19, we suggest prospective studies on the potentially more broadly protective roles of this naturally occurring hormone

The Space Optical Clocks Project: Development of high-performance transportable and breadboard optical clocks and advanced subsystems

The use of ultra-precise optical clocks in space ("master clocks") will allow for a range of new applications in the fields of fundamental physics (tests of Einstein's theory of General Relativity, time and frequency metrology by means of the comparison of distant terrestrial clocks), geophysics (mapping of the gravitational potential of Earth), and astronomy (providing local oscillators for radio ranging and interferometry in space). Within the ELIPS-3 program of ESA, the "Space Optical Clocks" (SOC) project aims to install and to operate an optical lattice clock on the ISS towards the end of this decade, as a natural follow-on to the ACES mission, improving its performance by at least one order of magnitude. The payload is planned to include an optical lattice clock, as well as a frequency comb, a microwave link, and an optical link for comparisons of the ISS clock with ground clocks located in several countries and continents. Undertaking a necessary step towards optical clocks in space, the EU-FP7-SPACE-2010-1 project no. 263500 (SOC2) (2011-2015) aims at two "engineering confidence", accurate transportable lattice optical clock demonstrators having relative frequency instability below 1\times10^-15 at 1 s integration time and relative inaccuracy below 5\times10^-17. This goal performance is about 2 and 1 orders better in instability and inaccuracy, respectively, than today's best transportable clocks. The devices will be based on trapped neutral ytterbium and strontium atoms. One device will be a breadboard. The two systems will be validated in laboratory environments and their performance will be established by comparison with laboratory optical clocks and primary frequency standards. In this paper we present the project and the results achieved during the first year.Comment: Contribution to European Frequency and Time Forum 2012, Gothenburg, Swede

Surgical site infection after caesarean section. Space for post-discharge surveillance improvements and reliable comparisons

Surgical site infections (SSI) after caesarean section (CS) represent a substantial health system concern. Surveying SSI has been associated with a reduction in SSI incidence. We report the findings of three (2008, 2011 and 2013) regional active SSI surveillances after CS in community hospital of the Latium region determining the incidence of SSI. Each CS was surveyed for SSI occurrence by trained staff up to 30 post-operative days, and association of SSI with relevant characteristics was assessed using binomial logistic regression. A total of 3,685 CS were included in the study. A complete 30 day post-operation follow-up was achieved in over 94% of procedures. Overall 145 SSI were observed (3.9% cumulative incidence) of which 131 (90.3%) were superficial and 14 (9.7%) complex (deep or organ/space) SSI; overall 129 SSI (of which 89.9% superficial) were diagnosed post-discharge. Only higher NNIS score was significantly associated with SSI occurrence in the regression analysis. Our work provides the first regional data on CS-associated SSI incidence, highlighting the need for a post-discharge surveillance which should assure 30 days post-operation to not miss data on complex SSI, as well as being less labour intensive

The sub-TeV transient Gamma-Ray sky: challenges and opportunities

The detection of gravitational waves and neutrinos from astrophysical sources with gamma-ray counterparts officially started the era of Multi-Messenger Astronomy. Their transient and extreme nature implies that monitoring the VHE sky is fundamental to investigate the non-electromagnetic signals. However, the limited effective area of space-borne instruments prevents observations above a few hundred GeV, while the small field of view and low duty cycle of IACTs make them unsuited for extensive monitoring activities and prompt response to transients. Extensive Air Shower arrays (EAS) can provide a large field of view, a wide effective area and a very high duty cycle. Their main difficulty is the distinction between gamma-ray and cosmic-ray initiated air showers, especially below the TeV range. Here we present some case studies stressing the importance that a new EAS array in the Southern Hemisphere will be able to survey the sky from below 100 GeV up to several TeV. In the energy domain between 100 and 400 GeV we expect the strongest electromagnetic signatures of the acceleration of ultra-relativistic particles in sources like SNRs, blazar jets and gamma-ray bursts, as recently proved by IACT observations. This spectral window is also crucial to understand the Universe opacity to high energy radiation, thus providing constraints on the cosmological parameters. We will discuss the implications of VHE radiation on the mechanisms at work and we will focus on the advantages resulting from the ability to monitor the energy window lying between the domain of space-borne detectors and ground-based facilities

Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV

A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7 TeV is presented. The data were collected at the LHC, with the CMS detector, and correspond to an integrated luminosity of 4.6 inverse femtobarns. No significant excess is observed above the background expectation, and upper limits are set on the Higgs boson production cross section. The presence of the standard model Higgs boson with a mass in the 270-440 GeV range is excluded at 95% confidence level.Comment: Submitted to JHE