Cation ordering over short range and long range scales in the MgAl2O4-CuAl2O4 series

A multi-analytical approach using electron microprobe analysis, X‑ray structural refinement, and optical absorption spectroscopy was applied to characterize short-range and long-range structures of synthetic spinel single crystals along the MgAl2O4-CuAl2O4 solid-solution series. Site populations, derived from the results of site-scattering refinement and stereochemical analysis, show that the tetrahedrally coordinated site (T) is mainly populated by Mg and Cu2+, while the octahedrally coordinated site (M) is dominated by Al. Crystals also show a significant degree of inversion, i.e., occurrence of Al at T counterbalanced by occurrence of divalent cations at M, which increases slightly from 0.24 to 0.29 for the highest Cu2+ contents. Short-range information derived from optical spectra suggests that the local TCu2+-O distances remain constant at increasing Cu2+ content, whereas local MCu2+-O distances are ca. 0.02 Å shorter in Cu-poor MgAl2O4 spinels as compared to MCu2+-O distances in end-member CuAl2O4. The observed splitting of an absorption band, at ca. 7000 cm–1, caused by electron transitions in TCu2+ as well as the anomalous broadness of an absorption band, at ca. 13 500 cm–1, caused by electron transitions in MCu2+ indicates the occurrence of local Jahn-Teller distortions at T and M. Long-range information, however, shows no violation of Fd3m symmetry. From refinements of our single-crystal XRD data we could for the first time derive for a cubic spinel phase a MCu2+-O distance of 2.080 Å and a TCu2+-O of 1.960 Å. The very limited variations in the unit-cell parameter a from 8.079 to 8.087 Å are mainly related to the disordering of Al. Because of the very similar size of Cu2+ and Mg at the T and M sites, the spinel structure responds to the Cu2+ → Mg substitution by increasing cation disordering in such a manner that mean M-O distances remain constant and the mean T-O distances decrease slightly. This results in increasing length of shared octahedral edges and thereby increase of the octahedral cation-cation repulsion. In line with other studies, the importance of steric factors for controlling the cation distributions in the spinel structure is demonstrated to be valid also in the MgAl2O4-CuAl2O4 solid-solution series

The GINGER Project and status of the ring-laser of LNGS

A ring-laser attached to the Earth measures the absolute angular velocity of the Earth summed to the relativistic precessions, de Sitter and Lense-Thirring. GINGER (Gyroscopes IN GEneral Relativity) is a project aiming at measuring the LenseThirring effect with a ground based detector; it is based on an array of ring-lasers. Comparing the Earth angular velocity measured by IERS and the measurement done with the GINGER array, the Lense-Thirring effect can be evaluated. Compared to the existing space experiments, GINGER provides a local measurement, not the averaged value and it is unnecessary to model the gravitational field. It is a proposal, but it is not far from being a reality. In fact the GrossRing G of the Geodesy Observatory of Wettzell has a sensitivity very close to the necessary one. G ofWettzell is part of the IERS system which provides the measure of the Length Of the DAY (LOD); G provides information on the fast component of LOD. In the last few years, a roadmap toward GINGER has been outlined. The experiment G-GranSasso, financed by the INFN Commission II, is developing instrumentations and tests along the roadmap of GINGER. In this short paper the main activities of G-GranSasso and some results will be presented. The first results of GINGERino will be reported, GINGERino is the large ring-laser installed inside LNGS and now in the commissioning phase. Ring-lasers provide as well important informations for geophysics, in particular the rotational seismology, which is an emerging field of science. GINGERino is one of the three experiments of common interest between INFN and INGV

Targeted metabolomic profiles of piglet plasma reveal physiological changes over the suckling period

The suckling phase is a critical period for the piglets due to their incomplete immune system development and their rapid growth rates. In this study, we analysed the metabolomic profiles of piglets over this period. Eighteen piglets (nine males and nine females) from three different litters were included in the study. Body weight was recorded at birth (T0), 12 (T1) and 21 (T2) days after birth. Plasma samples were collected at two critical time points of the suckling phase (T1 and T2) and about 180 metabolites of five different biochemical classes (glycerophospholipids, amino acids, biogenic amines, hexoses and acylcarnitines) were analyzed using a target metabolomics approach based on Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). Metabolites whose levels could discriminate the plasma profiles at T1 and T2 were identified using the sparse version of Multilevel Partial Least Squares Discriminant Analysis (sMLPLS-DA), coupled with a stability test based on a Leave One Out (LOO) procedure. The level of twenty-three metabolites differed significantly (P < 0.1; both for stability and the effect size) between the two time points. Higher levels of six acylcarnitine (C14:1, C14:1-OH, C16-OH, C4, C5 and C5-OH), serine, threonine and tyrosine, and one phosphatidylcholine (PC ae C42:3) were observed at T1, whereas one biogenic amine (creatinine), eight phosphatidylcholines including PC aa C30:2, PC ae C30:0, PC ae C32:1, PC ae C38:4, PC ae C40:4, PC ae C42:4, PC ae C42:5 and PC ae C44:6, and four sphingomyelins, including SM (OH) C22:1, SM C16:0, SM C16:1 and SM C18:0, were more abundant at T2. The Metabolite Set Enrichment Analysis and the Pathway Analysis modules suggested a perturbation of the \u201cglycine and serine metabolism\u201d and the \u201csphingolipid metabolism\u201d. Differences of these metabolites between these two time points might be related to the rapid growth and immunological maturation phases of the piglets in this period. Our results provided new information that could describe the biological changes of the piglets over the suckling period. The identified metabolites may be useful markers of the developmental processes occurring in the piglets over this critical pre-weaned phase

Sitagliptin is effective and safe as add-on to insulin in patients with absolute insulin deficiency: a case series

<p>Abstract</p> <p>Introduction</p> <p>It is generally believed that incretin-based therapies are effective in patients possessing certain levels of preserved β-cell function. So far, there are no reports that show the effectiveness of dipeptidyl peptidase-4 inhibitors in patients who absolutely lack the capacity for endogenous insulin secretion.</p> <p>Case presentation</p> <p>This report describes the efficacy of sitagliptin in three Japanese patients (a 91-year-old Japanese woman with type 1 diabetes, a 54-year-old Japanese man with type 2 diabetes and a 30-year-old Japanese man with features of both type 1 and type 2 diabetes) who had no detectable post-meal C-peptide levels. Although they were receiving intensive insulin therapy together with some oral hypoglycemic agents, their glycemic control remained poor. Sitagliptin was added to the ongoing therapeutic regimen to provide better glycemic control. Although these patients had mild hypoglycemia, effective reductions of hemoglobin A1c levels were observed without any adverse events in the liver and kidney during the following 24 weeks. Two of the patients were able to reduce their insulin doses, and one of the patients could discontinue one of the oral hypoglycemic agents. There was no weight gain or gastrointestinal complaints among the three patients. Post-meal C-peptide levels remained undetectable after sitagliptin treatment.</p> <p>Conclusion</p> <p>This report demonstrates that sitagliptin is effective and safe as an add-on therapy to insulin in reducing blood glucose levels in patients who absolutely lack the capacity for endogenous insulin secretion. The improvement seen in glycemic control could not be due to enhanced endogenous insulin secretion, since post-meal C-peptide levels remained undetectable after sitagliptin treatment, but it could be a result of other factors (for example, suppression of glucagon levels). However, the glucagon-suppressive effect of sitagliptin is known to be rather weak and short-lived. Given this background, a novel hypothesis that the glycemic effects of this drug may be caused by mechanisms that are independent of the glucagon-like peptide 1 axis (extra-pancreatic effect) will be discussed.</p

A 1.82 m^2 ring laser gyroscope for nano-rotational motion sensing

We present a fully active-controlled He-Ne ring laser gyroscope, operating in square cavity 1.35 m in side. The apparatus is designed to provide a very low mechanical and thermal drift of the ring cavity geometry and is conceived to be operative in two different orientations of the laser plane, in order to detect rotations around the vertical or the horizontal direction. Since June 2010 the system is active inside the Virgo interferometer central area with the aim of performing high sensitivity measurements of environmental rotational noise. So far, continuous not attempted operation of the gyroscope has been longer than 30 days. The main characteristics of the laser, the active remote-controlled stabilization systems and the data acquisition techniques are presented. An off-line data processing, supported by a simple model of the sensor, is shown to improve the effective long term stability. A rotational sensitivity at the level of ten nanoradiants per squareroot of Hz below 1 Hz, very close to the required specification for the improvement of the Virgo suspension control system, is demonstrated for the configuration where the laser plane is horizontal

Measuring Gravito-magnetic Effects by Multi Ring-Laser Gyroscope

We propose an under-ground experiment to detect the general relativistic effects due to the curvature of space-time around the Earth (de Sitter effect) and to rotation of the planet (dragging of the inertial frames or Lense-Thirring effect). It is based on the comparison between the IERS value of the Earth rotation vector and corresponding measurements obtained by a tri-axial laser detector of rotation. The proposed detector consists of six large ring-lasers arranged along three orthogonal axes. In about two years of data taking, the 1% sensitivity required for the measurement of the Lense-Thirring drag can be reached with square rings of 6 $m$ side, assuming a shot noise limited sensitivity ($20 prad/s/\sqrt{Hz}$). The multi-gyros system, composed of rings whose planes are perpendicular to one or the other of three orthogonal axes, can be built in several ways. Here, we consider cubic and octahedron structures. The symmetries of the proposed configurations provide mathematical relations that can be used to study the stability of the scale factors, the relative orientations or the ring-laser planes, very important to get rid of systematics in long-term measurements, which are required in order to determine the relativistic effects.Comment: 24 pages, 26 Postscript figure

Frequency-modulated electromagnetic neural stimulation (FREMS) as a treatment for symptomatic diabetic neuropathy: results from a double-blind, randomised, multicentre, long-term, placebo-controlled clinical trial

AIMS/HYPOTHESIS: The aim was to evaluate the efficacy and safety of transcutaneous frequency-modulated electromagnetic neural stimulation (frequency rhythmic electrical modulation system, FREMS) as a treatment for symptomatic peripheral neuropathy in patients with diabetes mellitus. METHODS: This was a double-blind, randomised, multicentre, parallel-group study of three series, each of ten treatment sessions of FREMS or placebo administered within 3 weeks, 3 months apart, with an overall follow-up of about 51 weeks. The primary endpoint was the change in nerve conduction velocity (NCV) of deep peroneal, tibial and sural nerves. Secondary endpoints included the effects of treatment on pain, tactile, thermal and vibration sensations. Patients eligible to participate were aged 18-75 years with diabetes for ≥ 1 year, HbA(1c) <11.0% (97 mmol/mol), with symptomatic diabetic polyneuropathy at the lower extremities (i.e. abnormal amplitude, latency or NCV of either tibial, deep peroneal or sural nerve, but with an evocable potential and measurable NCV of the sural nerve), a Michigan Diabetes Neuropathy Score ≥ 7 and on a stable dose of medications for diabetic neuropathy in the month prior to enrolment. Data were collected in an outpatient setting. Participants were allocated to the FREMS or placebo arm (1:1 ratio) according to a sequence generated by a computer random number generator, without block or stratification factors. Investigators digitised patients' date of birth and site number into an interactive voice recording system to obtain the assigned treatment. Participants, investigators conducting the trial, or people assessing the outcomes were blinded to group assignment. RESULTS: Patients (n = 110) with symptomatic neuropathy were randomised to FREMS (n = 54) or placebo (n = 56). In the intention-to-treat population (50 FREMS, 51 placebo), changes in NCV of the three examined nerves were not different between FREMS and placebo (deep peroneal [means ± SE]: 0.74 ± 0.71 vs 0.06 ± 1.38 m/s; tibial: 2.08 ± 0.84 vs 0.61 ± 0.43 m/s; and sural: 0.80 ± 1.08 vs -0.91 ± 1.13 m/s; FREMS vs placebo, respectively). FREMS induced a significant reduction in day and night pain as measured by a visual analogue scale immediately after each treatment session, although this beneficial effect was no longer measurable 3 months after treatment. Compared with the placebo group, in the FREMS group the cold sensation threshold was significantly improved, while non-significant differences were observed in the vibration and warm sensation thresholds. No relevant side effects were recorded during the study. CONCLUSIONS/INTERPRETATION: FREMS proved to be a safe treatment for symptomatic diabetic neuropathy, with immediate, although transient, reduction in pain, and no effect on NCV. TRIAL REGISTRATION: ClinicalTrials.gov NCT01628627. FUNDING: The clinical trial was sponsored by Lorenz Biotech (Medolla, Italy), lately Lorenz Lifetech (Ozzano dell'Emilia, Italy)

The GINGER Project

GINGER (Gyroscopes IN General Relativity) is a project aiming at measuring the Lense-Thirring effect, at 1% level, with an experiment on earth. It is based on an array of ring-lasers, which are the most sensitive inertial sensors to measure the rotation rate of the Earth. The GINGER project is still under discussion; the experiment G-GranSasso is an R&amp;D experiment financed by INFN Group II, it is studying the key points of GINGER and at the same time developing prototypes. In the following the signal coming out of a ring-laser and the present sensitivity are described.The prototypes GP2 and GINGERino and the preliminary results are reported. This project is inter-disciplinary since ring-lasers provide informations for the fast variation of the earth rotation rate, they are used for the rotational seismology and for top sensitivity angle metrology