Experimental characterization of pull-in parameters for an electrostatically actuated cantilever

MEMS-NEMS applications extensively use micro-nano cantilever structures as actuation system, thanks to their intrinsically simple end efficient configuration. Under the action of an electrostatic actuation voltage the can- tilever deflects, until it reaches the maximum value of the electrostatic actuation voltage, namely the pull-in voltage. This limits its operating point and is a critical issue for the switching of the actuator. The present work aims to experimentally measure the variation of the pull-in voltage and the tip deflection for different geometri- cal parameters of an electrostatically actuated cantilever. First, by relying on a nonlinear differential model from the literature, we designed and built a macro-scale cantilever switch, which can be simply adapted to different configurations. Second, we experimentally investigated the effect of the free length of the suspended electrode, and of the gap from the ground, on the pull-in response. The experimental results always showed a close agree- ment with the analytical predictions, with a maximum relative error lower that 10% for the pull-in voltage, and a relative difference lower than 18% for the pull-in deflection

Current treatment approaches in CML.

Take home messages Five tyrosine kinase inhibitors are available, the treatment strategy is still challenging. Baseline risk, comorbidities, and patient and physician expectations play a pivotal role. Treatment-free remission is a new opportunity

Comparative study of imiquimod 3.75% vs. photodynamic therapy for actinic keratosis of the scalp

Background/purpose: To assess efficacy, tolerability, adverse effects, recurrence, and aesthetic results of imiquimod 3.75% vs. photodynamic therapy with 5-aminolaevulinic acid (MAL-PDT) for actinic keratosis (AK). Methods: A small randomized, intraindividual right-left pilot study for AK treatment of multiple scalp lesions was performed. Patients were treated with imiquimod and subsequently MAL-PDT (on opposite sides of the scalp) 14 days apart. Study end points were evaluated with clinical and dermoscopic examinations at 1, 3, 6, and 12 months. Results: Nine male bald patients were enrolled. Imiquimod achieved a slightly higher overall clearance rate than MAP-PDT (68.1% vs 56.5%). According to AK degree of severity, clearance rates were greater for degree I and III with imiquimod (68.8%, 64.5% and 75% with imiquimod vs. 48%, 69.8%, and 66.7% for MAL-PDT, respectively). At 12 months, a slightly higher total recurrence rate was noted for imiquimod compared with MAL-PDT (9.9% vs. 8.6%); new lesions were 2 degree I for imiquimod and 4 degree I for MAL-PDT. For both treatments, pain was moderate/strong (even if MAL-PDT seems to be less tolerable) adverse effects are common and transient; aesthetic results excellent. Conclusion: Both imiquimod and MAL-PDT were effective in the reduction in the number of AK. In the long-term, both present a good effectiveness maintained over time with excellent aesthetic results. A combination or sequential therapy could optimize the management of the cancerization field

Adjustment and transformation strategies of ItalPoS Permanent GNSS Network

A private network of 133 Global Navigation Satellite Systems (GNSS) permanent sites, named ItalPoS (Italian Positioning Service) and uniformly covering the entire Italian territory, was established in April 2006 by the Italian Division of Leica Geosystems S.p.A. This network also involves several GPS stations of the INGV (Italian National Institute of Geophysics and Volcanology) RING (Real-time Integrated National Gps) network and GPS stations from other public and private bodies. Indeed Leica Geosystems contributed with its experience and its products to these networks which currently fulfil the national coverage where there are no ItalPoS stations. For instance, the purpose of the ItalPoS network is mainly GNSS data distribution in terms of real time corrections and RINEX files for the post-processing. In order to compute and distribute to private and scientific users a set of adjusted coordinates of the ItalPoS network in the IGS05 and ETRF89-2000 reference frames, a dataset of RINEX of about 120 GPS permanent sites was created and processed, using the distributed sessions approach, by means of Gamit/Globk 10.3 GPS data processor, also using some SOPAC (Scripps Orbits and Permanent Array Center) and EUREF (European Permanent Network) solutions to improve the reference frame definition and the internal constraints. This paper describes all the strategies adopted to estimate coordinates and velocities of the ItalPoS Network in IGS05 and in ETRF89-2000 reference frames in the whole Italian territory

Nilotinib: a novel encouraging therapeutic option for chronic myeloid leukemia patients with imatinib resistance or intolerance

Although high rates of complete hematologic and cytogenetic remission have been observed in patients with chronic phase chronic myeloid leukemia (CML) treated with imatinib, a short duration of response with eventual emergence of imatinib resistance has also been reported in a subset of CML patients. The most frequent clinically relevant mechanisms that change imatinib sensitivity in BCR-ABL-transformed cells are mutations within the Abl kinase domain, affecting several of its properties. Crystal structure analysis of the Abl-imatinib complex has proven helpful in identifying potential critical residues that hinder interactions of imatinib with mutated Abl. This has led to the development of a second generation of targeted therapies such as nilotinib and dasatinib, already in phase II clinical trials or SKI-606 and MK-0457 in phase I trials. In this review, we discuss the activity of nilotinib, developed by Novartis using a rational drug design strategy in which imatinib served as the lead compound. Preliminary studies demonstrated that nilotinib has more efficacy than imatinib in inhibiting proliferation of BCR-ABL-dependent cells, a relatively safety profile and clinical efficacy in all phases of CML

Canine placenta histological findings and microvascular density: The histological basis of a negative neonatal outcome?

Placenta is essential for the development of the fetus, and its impaired function can lead to a negative outcome (i.e., neonatal mortality). In dogs, investigations on placenta histology and neonatal outcome in healthy bitches are lacking, and a contribution is provided in this study to emphasize the use of placenta histology in practice. Fifty-one placentas from 11 litters were collected during cesarean section, classified according to the litter size (large (L) or small (S)) and the outcome, this latter as healthy (Group 1) or dead within 7 days (Group 2). The placenta/puppy weight ratio (PPR) was calculated, and specimens were formalin-fixed and paraffin-wax embedded, and on the resulting histological slides, capillary density (CD) was quantified. Among necrosis, calcification, and intravascular leucocytes, only the presence of multifocal-confluent necrosis (significantly more frequent in Group 2) was associated with a higher risk of death within 7 days (odds ratio = 30.7). Mixed logistic regression ruled out the effect on death both of a bitch and cesarean type (programmed vs. emergency). PPR and CD values were associated with litter size; large litters had lower PPR (p < 0.01) and higher CD (p < 0.05) than small litters. The relationship between PPR and CD was negative and significant (p < 0.01). Necrosis was a frequent finding in canine placentas, but only when multifocal-confluent was it associated with a poor outcome. The litter size influenced PPR (lower in L) and CD (higher in L), and this is likely due to the plasticity of placenta adaptation

Spatially restricted expression of PlOtp, a Paracentrotus lividus Orthopedia-related homeobox gene, is correlated with oral ectodermal patterning and skeletal morphogenesis in late-cleavage sea urchin embryos

Several homeobox genes are expressed in the sea urchin embryo but their roles in development have yet to be elucidated. Of particular interest are homologues of homeobox genes that in mouse and Drosophila are involved in patterning the developing central nervous system (CNS). Here, we report the cloning of an orthpedia (Otp)-related gene from Paracentrotus lividus, PlOtp. Otp is a single copy zygotic gene that presents a unique and highly restricted expression pattern. Transcripts were first detected at the mid-gastrula stage in two pairs of oral ectoderm cells located in a ventrolateral position, overlying primary mesenchyme cell (PMC) clusters. Increases in both transcript abundance and the number of Otp-expressing cells were observed at prism and pluteus stages. Otp transcripts are symmetrically distributed in a few ectodermal cells of the oral field. Labelled cells were observed close to sites of active skeletal rod growth (tips of the budding oral and anal arms), and at the juxtaposition of stomodeum and foregut. Chemicals known to perturb PMC patterning along animal-vegetal and oral-aboral axes altered the pattern of Otp expression. Vegetalization by LiCl caused a shift in Otp-expressing cells toward the animal pole, adjacent to shifted PMC aggregates. Nickel treatment induced expression of the Otp gene in an increased number of ectodermal cells, which adopted a radialized pattern. Finally, ectopic expression of Otp mRNA affected patterning along the oral-aboral axis and caused skeletal abnormalities that resembled those exhibited by nickel-treated embryos. From these results, we conclude that the Otp homeodomain gene is involved in short-range cell signalling within the oral ectoderm for patterning the endoskeleton of the larva through epithelial-mesenchymal interactions

Molecular Monitoring of BCR-ABL Transcripts after Allogeneic Stem Cell Transplantation for Chronic Myeloid Leukemia

AbstractThe monitoring of minimal residual disease (MRD) through low sensitivity real-time (RT) polymerase chain reaction (PCR) analysis of BCR-ABL transcripts allows early detection of chronic myeloid leukemia (CML) relapse after allogeneic hematopoietic stem cell transplantation (HSCT). The introduction of more sensitive techniques, such as RT quantitative (Q)-PCR, may lead to an overestimation of the risk of CML relapse. In this study, we reviewed the results of peripheral blood RT Q-PCR in CML patients who underwent allogeneic HSCT from 1983 to 2007. In our laboratory, RT Q-PCR analysis was routinely performed since 2002. Eighty-seven of 189 patients had available RT Q-PCR data; 63 patients had at least 3 RT Q-PCR analyses assessable. Fifty-two of 63 patients (83%) had, at least once, detectable transcript levels, but with an BCR-ABL/ABL ratio <.1% defined as .1% confirmed by the finding of Ph+ cells in bone marrow. No patients with persistent undetectable transcripts relapsed (P = .19). Relapse did not correlate with the number of occurrences o

Experimental and numerical analysis of a liquid aluminium injector for an Al-H2O based hydrogen production system

This paper investigates pressurised injection system for liquid aluminium for a cogeneration system based on the Al–H2O reaction. The reaction produces hydrogen and heat which is used for super-heating vapour for a steam cycle. The aluminium combustion with water generates also alumina as a byproduct; the aluminium oxide can be recycled and transformed back to aluminium. Thus, aluminium can be exploited as energy carrier in order to transport energy from the alumina recycling plant to the place where the cogeneration system is located. The water is also used in a closed loop; indeed, the amount of water produced employing the hydrogen obtained by the proposed system corresponds to the oxidizing water for the Al/H2O reaction. The development of a specific test rig designed for investigating the liquid aluminium injection is presented in this research study. The injector nozzle is investigated by means of numerical thermal and structural analysis. The calculations are compared and validated against the experimental measurements carried out on ad-hoc developed test rig. A good agreement between the numerical results and the experimental values is found and the new design of the nozzle is devised

Questions concerning tyrosine kinase-inhibitor therapy and transplants in chronic phase chronic myeloid leukaemia

In this provocative commentary, we consider several questions posed by the late chronic myeloid leukaemia (CML) expert Prof. Michele Baccarani, which he challenged us to address after his death. He noted only a small proportion of people with chronic phase CML receiving tyrosine kinase-inhibitor (TKI)-therapy are likely to achieve sustained therapy-free remission (TFR) and even fewer are likely to be cured. Persons most likely to fail TKItherapy can be identified at diagnosis or soon after starting TKI-therapy. These persons are likely to need lifetime TKI-therapy with attendant risks of adverse events, cost and psychological consequences. Allogeneic transplants achieve much higher rates of leukaemia-free survival compared with TKI-therapy but are associated with transplant-related adverse events including an almost 20 percent risk of transplant-related deaths within 1 year post-transplant and a compromised quality-of-life because of complications such as chronic graft-versus-host disease. Subject-, disease- and transplant-related co-variates associated with transplant outcomes are known with reasonable accuracy. Not everyone likely to fail TKI-therapy is a transplant candidate. However, in those who candidates are physicians and patients need to weigh benefits and risks of TKI-therapy versus a transplant. We suggest transplants should be more often considered in the metric when counseling people with chronic phase CML unlikely to achieve TFR with TKI-therapy. We question whether we are discounting a possible important therapy intervention; we think so