Cytoskeletal elements in mammalian spermiogenesis and spermatozoa.

Identification of the cytoskeletal elements and their role in the formation as well as the maintenance of head membrane compartmentalization is a much debated issue in mammalian spermatozoa. Data which have emerged during the last ten years are summarized. Those which have converged in a common opinion, such as the distribution of actin in mammalian spermiogenesis, are distinguished from those which have to be confirmed, such as the role of actin related proteins and actin in mature spermatozoa.     

Expression of polysialylated neural cell adhesion molecule by proliferating cells in the subependymal layer of the adult rat, in its rostral extension and in the olfactory bulb

The highly sialylated isoform of the neural cell adhesion molecule is thought to be expressed predominantly in the developing nervous system, where it is implicated in a variety of dynamic events linked to neural morphogenesis. It has become increasingly evident, however, that this "embryonic" neural cell adhesion molecule isoform continues to be expressed in certain adult neuronal systems, and in particular, in those that can undergo structural plasticity. In the present study, we performed light microscopic immunocytochemistry with an antibody specific for polysialylated neural cell adhesion molecule and confirmed our earlier observations [Bonfanti L. et al. (1992) Neuroscience 49, 419-436] showing polysialylated neural cell adhesion molecule-immunoreactive cells in the subependymal layer of the lateral ventricle of the adult rat, a region where cell proliferation continues into the postnatal period. In addition, we used an antibody raised against the proliferating cell nuclear antigen and found that proliferating cells continue to be visible in this area, even in the adult. Double immunolabeling showed that many of these newly generated cells displayed high polysialylated neural cell adhesion molecule immunoreactivity. Cells from a portion of the subependymal layer migrate to the olfactory bulb and contribute to the continual replacement of its granule neurons [Luskin M. B. (1993) Neuron 11, 173-189]. We found polysialylated neural cell adhesion molecule-immunoreactive cells all along the pathway purported to be followed by the newly generated cells to their final destination and in neurons corresponding to granular and periglomerular cells in the olfactory bulb. Our present observations thus support the contention that polysialylation is a feature of neurons capable of dynamic change and may contribute to the molecular mechanisms permitting cell proliferation and migration not only during development but also in the adult.     

miRNA Expression Profiling in Subcutaneous Adipose Tissue of Monozygotic Twins Discordant for HIV Infection: Validation of Differentially Expressed miRNA and Bioinformatic Analysis

Combined AntiRetroviral Treatments (cARTs) used for HIV infection may result in varied metabolic complications, which in some cases, may be related to patient genetic factors, particularly microRNAs. The use of monozygotic twins, differing only for HIV infection, presents a unique and powerful model for the controlled analysis of potential alterations of miRNAs regulation consequent to cART treatment. Profiling of 2578 mature miRNA in the subcutaneous (SC) adipose tissue and plasma of monozygotic twins was investigated by the GeneChip^® miRNA 4.1 array. Real-time PCR and ddPCR experiments were performed in order to validate differentially expressed miRNAs. Target genes of deregulated miRNAs were predicted by the miRDB database (prediction score > 70) and enrichment analysis was carried out with g:Profiler. Processes in SC adipose tissue most greatly affected by miRNA up-regulation included (i) macromolecular metabolic processes, (ii) regulation of neurogenesis, and (iii) protein phosphorylation. Furthermore, KEGG analysis revealed miRNA up-regulation involvement in (i) insulin signaling pathways, (ii) neurotrophin signaling pathways, and (iii) pancreatic cancer. By contrast, miRNA up-regulation in plasma was involved in (i) melanoma, (ii) p53 signaling pathways, and (iii) focal adhesion. Our findings suggest a mechanism that may increase the predisposition of HIV⁺ patients to insulin resistance and cancer.     

Frequency dependence on bias current in 5 GHz CMOS VCOs: impact on tuning range and flicker noise upconversion

The tuning curve of an LC-tuned voltage-controlled oscillator (VCO) substantially deviates from the ideal curve 1//spl radic/(LC(V)) when a varactor with an abrupt C(V) characteristic is adopted and the full oscillator swing is applied directly across the varactor. The tuning curve becomes strongly dependent on the oscillator bias current. As a result, the practical tuning range is reduced and the upconverted flicker noise of the bias current dominates the 1/f/sup 3/ close-in phase noise, even if the waveform symmetry has been assured. A first-order estimation of the tuning curve for MOS-varactor-tuned VCOs is provided. Based on this result, a simplified phase-noise model for double cross-coupled VCOs is derived. This model can be easily adapted to cover other LC-tuned oscillator topologies. The theoretical analyses are experimentally validated with a 0.25 /spl mu/m CMOS fully integrated VCO for 5 GHz wireless LAN receivers. By eliminating the bias current generator in a second oscillator, the close-in phase noise improves by 10 dB and features -70 dBc/Hz at 10 kHz offset. The 1/f/sup 2/ noise is -132 dBc/Hz at 3 MHz offset. The tuning range spans from 4.6 to 5.7 GHz (21%) and the current consumption is 2.9 mA.     

A varactor configuration minimizing the amplitude-to-phase noise conversion in VCOs

Amplitude-to-phase-noise conversion due to varactors can severely limit the close-in phase noise performance in LC-tuned oscillators. This work proposes a rigorous analysis of this phenomenon, which highlights the fundamental limitations of single-ended tuned and differentially tuned diode varactor configurations. The back-to-back varactor topology is identified as a suitable solution to linearize the tank capacitance. The amplitude to phase noise conversion is greatly attenuated and the 1/f/sup 3/ phase noise is drastically reduced, without impairing the achievable tuning range. These results are validated through circuit simulations in an existing 0.35-/spl mu/m CMOS technology.     

A 2.5-GHz DDFS-PLL With 1.8-MHz Bandwidth in 0.35-$mu$m CMOS

A wideband frequency synthesizer architecture is presented. The proposed topology employs a direct digital frequency synthesizer (DDFS) to control the output frequency of an offset-PLL. In this way, the synthesizer features a very fine frequency resolution, 24 Hz, as in delta-sigma fractional-N PLLs, but without being affected by the quantization-induced phase noise. This, in turn, allows enlarging the loop bandwidth. The frequency synthesizer is designed to be employed as a direct modulator for Bluetooth transmitter in a low-cost 0.35-mum CMOS technology. At 2.5GHz it achieves 1.8-MHz bandwidth, while the settling time within 30ppm for an 80-MHz step is 3 mus. The integrated phase noise gives less than 1 degree of rms phase error and the worst-case spur is 48dBc at 1 MHz, well below the specifications. Power dissipation is 120 mW for the PLL core, 50 mW for the DDFS plus DACs, and 19 mW for the GFSK modulator.     

Derivation of imperfect interface models coupling damage and temperature

In this paper we introduce a model describing a layered structure composed by two thermoelastic adherents and a thin adhesive subject to a degradation process. By an asymptotic expansion method, we derive a model of imperfect interface coupling damage and temperature evolution. Moreover, assuming that the behaviour of the adhesive is ruled by two different regimes, one in traction and one in compression, we derive a second limit model where unilateral contact conditions on the interface are also included.     

Social media adoption in Italian firms. Opportunities and challenges for lagging regions

Social media are an important growth opportunity for firms, especially small-sized ones operating in peripheral and lagging regions. In this paper, we investigate not only whether firms are able to take this opportunity, but also if they are able to face the challenge of adopting social media at a professional level to obtain a significant economic impact, measured in terms of exporting activities. Exploring the Italian case, our empirical study indicates that smaller firms in lagging areas are more likely to adopt social media but at the same time less likely to use them at a professional level. This reflects poor strategic targets of social media adoption and lower probabilities of entering international markets.     

Parameters associated with residual insulin secretion during the first year of disease in children and adolescents with Type 1 diabetes mellitus

Factors associated with residual insulin secretion and spontaneous remission in Type 1 diabetic patients are important in the evaluation of treatment aimed at modifying the natural history of Type 1 DM. We investigated the effect of parameters at onset on residual beta cell function in 215 Type 1 DM children and adolescents. Blood gas analysis, HLA, GAD and IA-2 antibodies before the start of insulin treatment were recorded for each patient. Residual C-peptide secretion was assessed by the glucagon test, and parameters of metabolic control (HbA1c and insulin dose U kg(-1) day(-1)) were examined at disease onset and after 3, 6, and 12 months. Residual C-peptide secretion throughout the first year of disease was significantly reduced in patients with disease onset before age 5. Multiple regression analysis showed that low pH at onset showed a significant and independent association with reduced C-peptide at 3 months (p = 0.02) and that the detection of GAD antibodies had a significant independent association with decreased C-peptide secretion at 6 months of follow-up (p = 0.02). Insulin requirement was higher in the youngest patients group and in patients with GAD antibodies. Spontaneous insulin remission (HbA1c <6% and insulin <0.3 U kg(-1) day(-1)) occurred in 22/192 (11%) patients at 3 months of follow-up, in 15/190 (8%) patients at 6 months and in 8/169 (5%) patient at 12 months. Remission was more prevalent in older patients (p = 0.01) and in patients without detectable GAD antibodies: (14/64 vs 8/128, p = 0.001). Sex, IA-2 antibodies and HLA DR were not independently associated with C-peptide secretion, insulin requirement or remission in the first year of Type 1 DM. This study confirms the association of young age, severe acidosis at disease onset, and GAD antibodies with decreased residual beta-cell function and spontaneous remission during the first year of insulin treatment. These factors should be considered in trials evaluating therapies to retain beta-cell function and induce remission at and after disease onset.