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Micro-Electro-Mechanical Systems (MEMS) gyroscopes are inertial sensors for the measurement of angular rates. They have a variety of applications from consumer electronics to drones and the need of stability against environmental fluctuations, such as temperature, is a key factor in order to avoid expensive calibration procedures. Frequency Modulation (FM) has been recently proposed as an innovative working principle for MEMS gyroscopes and as the desired solution in terms of stability against environmental fluctuations. In this paper, the FM working principle is formalized for the three-axial case for the first time and the governing equations are derived both in the idealized case of a point-mass gyroscope and in the real case of a distributed-mass gyroscope. Moreover, the mechanical structure of the first three-axial MEMS FM gyroscope is proposed and studied. Preliminary experimental measurements prove the validity of both the model and the simulations results employed during the design process. The proposed structure overcomes lots of the constraints of the surface micromachining fabrication processes and represents an important step towards the development of a new class of MEMS gyroscopes.

The evaluation of microwave (MW) imaging radar capabilities in non-destructive tests to detect internal structures or defects in the inner volume of thermal insulation coating has been carried out. The MW imaging with high spatial resolution has been performed with holographic subsurface radar operated in the frequency range from 22.2 to 26.2 GHz. The investigation of this non-destructive testing (NDT) technology is important to evaluate the feasibility for quality check of assembled polyurethane sandwich parts for thermal insulation. The samples of polyurethane foam thermal insulation have been fabricated in collaboration with a manufacturing industry of household appliances to have a representative set of real defects. The images obtained are of high quality and easy to be interpreted as they reveal the shapes and plane positions of the defect into samples with thickness up to 90 mm.

Surface deformation monitoring provides unique data for observing and measuring the performance of producing hydrocarbon reservoirs, for Enhanced Oil Recovery (EOR) and for Carbon Capture and Storage (CCS). To this end, radar interferometry (InSAR), particularly multi-interferogram Persistent Scatterer (PS) techniques, such as PSInSAR™, are innovative, valuable and cost-effective tools. Depending on reservoir characteristics and depth, oil or gas production can induce surface subsidence or, in the cases of EOR and CCS, ground heave, potentially triggering fault reactivation and in some cases threatening well integrity. Mapping the surface effects of fault reactivation, due to either fluid extraction or injection, usually requires the availability of hundreds of measurement points per square km with millimeter-level precision, which is time consuming and expensive to obtain using traditional monitoring techniques, but can be readily obtained with InSAR data. Moreover, advanced InSAR techniques developed in the last decade are capable of providing millimeter precision, comparable to optical leveling, and a high spatial density of displacement measurements over long periods of time, without the need for installing equipment or otherwise accessing the study area. Until recently, a limitation to the application of InSAR was the relatively long revisiting time (24 or 35 days) of the previous generation of C-band satellites (ERS1-2, Envisat, Radarsat). However, a new generation of X-band radar satellites (TerraSAR-X and the COSMO-SkyMed constellation), which have been operational since 2008, are providing significant improvements. TerraSAR-X has a repeat cycle of 11 days, while the joint use of two sensors of the COSMO-SkyMed constellation have an effective repeat cycle of just 8 days. With the launch of the fourth satellite of the constellation, in 2010, COSMO-SkyMed will have an effective revisiting time of just 4 days, allowing “near real-time” applications. Indeed, by combining two acquisition geometries (e.g. data acquired along ascending and descending orbits), it will be possible, on average, to have a new scene over the area of interest every other day. Additional advantages of the new X-band satellites are: A higher sensitivity to target displacement and a higher spatial resolution (the density of measurement points can be increased by an order of magnitude, possibly exceeding 2,500 PS/km2). In this paper, we present some examples of the application of X-band SAR data to reservoir monitoring. Special attention will be given to CCS projects where InSAR data could become a “standard” monitoring tool. The paper will highlight the technical features of the new sensors, the possible synergy between TerraSAR-X and COSMOSkyMed data, as well as the importance of a careful analysis of atmospheric disturbances affecting SAR data covering the area of interest, in order to retrieve high quality displacement data. Finally, some conclusions will be drawn supporting recommendations about future CCS monitoring programs.

Background Conduction disturbances and arrhythmias characterize the cardiac feature of myotonic dystrophy type 1 (MD1), and a myocardial involvement has been suggested as part of the cardiac disease. The aim of the study was to investigate the role of novel ultrasonic techniques, such as integrated backscatter (IBS) and color Doppler myocardial imaging (CDMI), in the assessment of the subclinical functional and structural myocardial involvement in patients with MD1. Methods Thirty-one patients with MD1 (MD1 group) without known heart failure were evaluated and compared with 31 healthy, age-matched controls. In all patients, 19 conventional and 28 new echocardiographic parameters (14 tissue Doppler, 10 CDMI, and 4 IBS indexes) were analyzed. Results In regard to ultrastructural left ventricular (LV) properties, a significantly higher IBS echointensity was found at the septum level in the MD1 group, with a statistically significant correlation with MPI (myocardial performance index) ( r = 0.34; P = .05) and PR interval duration ( r = 0.40; P = .05). In regard to LV systolic function, the MD1 group showed an early alteration of systolic function compared with controls, evidenced by a significant higher MPI and lower peak strain, strain rate, and cyclic variation index (CVI). In regard to LV diastolic function, the MD1 group showed an early alteration of diastolic function compared with controls, evidenced by lower tissue Doppler imaging, E/A, and E/A strain rate, with a statistically significant inverse correlation to the muscular disability rating scale. On receiver operating characteristic curve analysis, MPI and CVI showed the highest discriminating ability to differentiate the hearts of patients with MD1 from healthy subjects. Conclusion Highly sensitive ultrasonic techniques can detect early functional and structural alterations of the LV myocardium in patients with MD1.

It is well known that type 1 diabetes mellitus (T1DM) is a complex genetic disease resulting from the autoimmune destruction of pancreatic beta cells. Several genes have been associated with susceptibility and/or protection for T1DM, but the disease risk is mostly influenced by genes located in the class II region of the major histocompatibility complex. The attraction of leukocytes to tissues is essential for inflammation and the beginning of autoimmune reaction. The process is controlled by chemokines, which are chemotactic cytolines. Some studies have shown that CCR2-64I and CCR5-Delta 32 might be important for protection of susceptibility to some immunologically-mediated disorders. In the present study, we demonstrate the lack of association between CCR2-64I and CCR5-Delta 32 gene polymorphism and TIDM and we describe a new method for a simple and more precise genotyping of the CCR2 gene.

The autoimmune polyendocrine syndrome type II (APS-II) is characterized by the association of autoimmune Addison's disease with thyroid autoimmune diseases or type-1 diabetes mellitus. 21-Hydroxylase autoantibodies enable the accurate diagnosis of autoimmune Addison's disease and, in patients with other endocrine autoimmune diseases, identify subjects at high risk for clinical adrenal insufficiency. 17 alpha-Hydroxylase (17OH) and side-chain-cleavage enzyme (P450scc) are target autoantigens of steroid-cell autoantibodies, and in women with Addison's disease, 17OH autoantibodies and P450scc autoantibodies are markers of increased risk for premature ovarian failure. Thyroperoxidase autoantibodies, thyroglobulin autoantibodies, H+/K(+)-ATPase autoantibodies, and GAD65 autoantibodies are frequently detected in patients with isolated Addison's or APS-II. Screening for other organ-specific autoimmune diseases should be performed in every patient with at least one major disease component of APS-II.

A series of novel optically active α-amino acids, containing a pyrazole ring, which can be regarded as building blocks for peptidomimetics, have been prepared starting from readily available α-amino acids. The synthetic strategy employed allows the regio- and stereoselective preparation of 1,3- or 1,5-substituted pyrazolyl rings. The pyrazole containing peptidomimetics can be considered as analogues of peptides with a cis amide bond.

Methodology for preparing a series of novel α-amino-acids and their derivatives containing an isoxazole ring as a substituent is presented. The synthesis starts from a readily available l -serine derivative from which, depending on the synthetic strategy, it is possible to obtain isoxazol-3-yl or isoxazol-5-yl amino-acid precursors.

The synthesis of tri-functionalized orthogonally protected CRAB templates based on the triazine skeleton are described together with some protocols for the preparation of families of diversomers using a parallel synthesis approach.

A stereospecific syntheses of optically active pyrazoles and isoxazoles from L-proline is described. The procedure presented is based on readily available materials and can be used for preparing new conformationally restricted pyrazole-containing amino acids.

Enantiospecific syntheses of optically active amino acids containing an oxazole moiety are described. Two different strategies for their insertion in a peptidomimetic chain are also discussed. The procedures presented are based on materials readily available in multigram quantities.

Analysis of the MICA gene revealed a trinucleotide repeat (GCT) microsatellite polymorphism within the transmembrane region. So far, seven alleles of the exon 5 of the MICA gene, which consist of 4, 5, 6, 7, 9, and 10 repetitions of GCT or five repetitions of GCT with an additional nucleotide insertion (GGCT), have been identified. These alleles have been accordingly named A4, A5, A6, A7, A9, A10, and A5.1, and the sizes are, respectively, 179 bp, 182 bp, 186 bp, 189 bp, 194 bp, 197 bp, and 185 bp. We analyzed 1100 Italian subjects for MICA exon 5 microsatellite polymorphism. A new peak corresponding to 191-bp size was observed in one individual, and we confirmed the presence of new polymorphism in exon 5 by sequencing, which consisted of eight GCT repeats. We named this allele, as a current nomenclature, MICA8.

We measured fasting serum levels of type I procollagen C-terminal propeptide (PICP), insulin-like growth factor-I (IGF-I), and IGF binding protein-3 (IGFBP-3) in obese children and adolescents (obese subjects [OS]) to evaluate their relationship to growth, gender, pubertal stage, and weight excess (WE). The influence of insulin, growth hormone (GH), and weight loss was also studied. The study population consisted of 244 OS and 236 normal-weight subjects (NWS) matched for age, gender, and pubertal stage. At stage I, OS had a higher standard deviation score (SDS) for height than NWS of both genders. During the prepubertal phase, growth velocity (GV) was greater in OS than in NWS of both genders, but it was lower in female OS at stage II and male OS at stage III. PICP increased in puberty, with a more rapid decrease later in female OS and NWS; prepubertal values were higher in OS but were reduced at pubertal stage IV to V in comparison to NWS. Stepwise multiple regression analysis demonstrated that GV was the only anthropological variable correlating with PICP. IGF-I serum values increased significantly in puberty and were higher in OS than in NWS at stage I for both genders. IGFBP-3 values of OS exceeded those of NWS at stages I to III in males and I to II in females. No difference was observed for males versus females in each group, nor was any difference observed for the IGF-I IGFBP-3 molar ratio between the two groups. Using stepwise analysis, a positive correlation between IGF-I and IGFBP-3 was observed in prepubertal but not in pubertal NWS. Fasting insulin values correlated with IGFBP-3 in OS, accounting for 24.8% of the variation in prepubertal subjects and 17.1% in pubertal subjects. No such correlation was observed in NWS. In prepubertal NWS, PICP and SDS of body mass index (BMI) correlated with IGF-I, accounting for 12.9% of the variation, and SDS of BNII correlated with IGFBP-3, explaining 27.8% of the variation. In prepubertal OS, no such correlations could be observed, but PICP and SDS of BMI accounted for 14.3% of the variation in the IGF-I IGFBP-3 molar ratio. A significant reduction of IGFBP-3 and an increase of the IGF-I IGFBP-3 molar ratio were detected after weight loss in 40 OS. In conclusion, we demonstrated that IGF-I and IGFBP-3 are influenced by age, gender, sexual development, and nutritional status. Also, an influence of insulin on IGFBP-3 serum levels was observed in OS. The relations of IGF-I to PICP in NWS and of the IGF-I IGFBP-3 molar ratio to PICP in OS support the concept of IGF-I influence on skeletal growth. The increased IGFBP-3 serum values in OS suggest a possible role in controlling the growth stimulus induced by nutritional status.

General stereospecific syntheses of the optically active title compounds are described. The procedures presented are based on readily available starting materials, such as piperazine alcohols, and can be arranged for multigram quantities.

Cyclic β-amino alcohols 1–4 derived from natural α-amino acids were used as chiral ligands in oxazaborolidine reduction of ketones. The processes were carried out in the presence of various achiral tertiary amine: better resuts are achieved by N , N -diethylaniline.

A procedure for the preparation of optically active (2 R ,5 S )- and (2 S ,5 S )-2-Carboxy-1,4-diaza-[4.3.0]bicyclononane is described. The method is based on the reduction of diketopiperazines obtained from cyclization of Pro-L-Ser or Pro-D-Ser and occurs without loss of enantiomeric purity. The synthesis is based on readily available starting materials and can be easily arranged for multigram scale preparations.

The N-Boc derivatives of (2S,3S,4R,6E)-2-amino-3-hydroxy-4-methyl-6-octenoic acid and (2S,4R)-2-amino-4-methyl-hexanoic acid have been prepared using the acetonide of D-Serine aldehyde 1 as a formyl glycine equivalent. The stereochemistry of the y-branch was introduced by reaction of (E)-crotyltrimethylsilane with 1 in the presence of TiCl4 followed by elaboration of the terminal double bond and further transformation of the Serine hydroxymethyl group into a carboxylic acid.

Starting from l -serine and l -threonine, (S)-diphenyl-(2,2-dimethyl-1,3-oxazolidin-4-yl)-methanol and (4S,5R)-diphenyl-(2,2-dimethyl-5-methyl-1,3-oxazolidin-4-yl)-methanol were prepared in good yields. The use of these compounds as very efficient chiral catalysts for the enantioselective addition of diethylzinc to aldehydes is described. This paper reports the first example of the use of oxazolidine methanols in asymmetric synthesis.

Autoantibodies are an important marker of human autoimmune diseases and the development of simple, precise and reproducible immunoassays to detect autoantibodies is important to our understanding of human autoimmunity. GAD65 autoantibodies occur frequently in insulin-dependent diabetic patients and is a useful marker for IDDM. A RIA to detect immunoreactive GAD65 has not been described. In the present study we describe a semi-automated fluid-phase immunoassay for the rapid detection of GAD65 autoantibodies in human serum. We also developed a sensitive RIA to determine immunoreactive human GAD65 in biological fluids and in vitro cell systems. Using in vitro translated recombinant human GAD65 in a multiwell-adapted procedure, our GAD65Ab RIA combines high specificity and sensitivity with a high capacity to analyze a large number of samples. In this report the three critical steps in the GAD65Ab RIA, DNA preparation, in vitro translation and immunoprecipitation, have been optimized. In our RIA, GAD65Ab were detected in 116/155 (75%) new onset Swedish IDDM children and in 1/85 (1.2%) healthy controls. In an immunoassay to detect autoantibodies against the proinsulin converting enzyme 2 (PC-2) no such antibodies were detected in IDDM patients. In the GAD65 RIA the lower detection limit was 2 ng/ml (31 fmol/ml). Our data demonstrate that autoantigen radioligands produced by in vitro translation are useful in RIA for autoantibodies and autoantigens in studies of human autoimmunity.

A very simple procedure for the preparation of chiral optically active N-protected-4-carboxy-1,3-oxazolidine (4-oxaproline) derivatives starting from serine and threonine is described which avoids the use of toxic solvents or reagents. Elaboration of these compounds allows significant improvement in the handling of serine and threonine during the multigram preparation of oligopeptide structures and affords versatile chiral building blocks for the organic synthesis.

Optically active 2-alkyl-2-oxazoline-4-carboxyamides, derived from enantiomeric pure α-amino-β-hydroxy acids, react with aryl- and alkyl sulphonyl chlorides in pyridine affording the corresponding optically active 2-alkyl-2-oxazoline-4-carboxyamido- N -sulphonyl derivatives without appreciable racemization.

An improved synthesis of 2-(2′-pyridyl)-2-aminoalcohols 1a and 1b, in enantiomerically pure form via 1,3-oxazolidine derivatives is presented. Some efficient and selective methods for both the cleavage of the oxazolidine ring and the removal of the N-Boc protecting group are also reported.

Starting from enantiomerically pure serine, a series of (2 R ,5 S ) and (2 S ,5 S )-2-hydroxymethyl-5-alkyl piperazines 1–5 were prepared in good yields without any racemization. The use of these compounds as chiral catalysts for the enantioselective addition of diethylzinc to aldehydes is described. This paper reports the first example of the use of piperazine methanols in asymmetric synthesis.

We determined the natural history of the widespread pancreatic islet beta-cell destruction that precedes the onset of spontaneous putative autoimmune diabetes mellitus in NOD mice. For this purpose, we performed both histological and immunocytochemical examinations of pancreata retrieved from mice at 2 through 30 weeks of age. An overexpression of la antigens was identified on islet beta cells at 4 weeks of age, without evidence of mononuclear cell infiltration. The abnormal expression of la antigens was age-related and was associated with hyperexpression of class I antigens and progressive islet cell histologic damage after 17 weeks of age. Immunocytochemical examination of islet cell infiltrate showed that the number of macrophages did not increase during the early phase of islet cell damage in these mice. The L3T4/Lyt-2 ratio increased after 7 weeks of age, but was 1:1 in the late stage of insulitis. These findings suggest that widespread islet beta-cell destruction is a process that begins primarily with derangements of the pancreatic beta-cell immune pattern, which may trigger a mononuclear cell reaction.

Chiral amino pyridines derived from α-aminoacids were demonstrated to be enantioselective catalysts in the addition of diethylzinc to aldehydes: optically active secondary alcohols in up to 98% ee were obtained in high yields. The temperature dependence of the stereochemical course of the reaction was found to be strictly related to the alkyl structure of the chiral catalyst. The nature of the possible catalytic complex and the origin of temperature effect was thus discussed on the basis of NMR data too.

6-(1S,2S)-6,6-dimethylbicyclo(3.1.1]hept-2-yl)-2-6-(1S,2S)-6, 6-dimethylbicyclo (3.1.1)hept-2-yl-pyridin-2-yl-pyridine (5), 2,9-bis (1S,2S)-6,6-dimethylbicyclo (3.1.1)hept-2-yl-5,6-dihydro-1, 10-phenanthroline (11) and 2,9-bis(1S,2S)-6, 6-dimethylbicyclo(3.1.1]hept-2-yl)-1,10-phenanthroline (12), three new chiral nitrogen ligands of C2 symmetry have been prepared.

Reducing agents prepared from SnCl 2 , chiral diamines and diisobutyl aluminum hydride have been applied to the enantioselective reduction of alkyl phenyl and α-alkynyl ketones. The extent of the ee observed was dependent on the hydrolysis temperature and the structure of the chiral diamine. Hypotheses on possible mechanistic pathways on the basis of stereochemical data and 1 H NMR studies were discussed too.

The synthesis of a series of new optically active pyridine ligands from proline derivatives has been developed for the enantioselective addition of dialkyl zinc compounds to aldehydes. The results obtained indicate that the coordination of a metal atom to the nitrogen of the pyridine ring is essential in determining the stereochemistry of the process.