1,254 research outputs found
Ramp rate abatement for wind energy integration in microgrids
This study analyses the performance of a battery storage system in abating the ramp rates of the power produced by a wind turbine. This approach can reduce the wind power fluctuations that are typical of small size wind farms and promote the wind energy integration in microgrids. Production data was generated from actual wind measurements over one year, and the capability of ramp abatement by varying battery capacity, battery power rating and ramp rate thresholds was investigated. The effect on battery degradation due to charge-discharge cycling required by the smoothing service was also estimated. Results suggest that good smoothing performance can be achieved with a wide range of power-capacity combinations, but the lifetime of the storage system can be as low as one year if its capacity is small
Targeting CDK6 and BCL2 Exploits the MYB Addiction of Ph+ Acute Lymphoblastic Leukemia
Philadelphia chromosome–positive acute lymphoblastic leukemia (Phþ ALL) is currently treated with BCR-ABL1 tyrosine kinase inhibitors (TKI) in combination with chemotherapy. However, most patients develop resistance to TKI through BCR-ABL1–dependent and –independent mechanisms. Newly developed TKI can target Phþ ALL cells with BCR-ABL1–dependent resistance; however, overcoming BCR-ABL1–independent mechanisms of resistance remains challenging because transcription factors, which are difficult to inhibit, are often involved. We show here that (i) the growth of Phþ ALL cell lines and primary cells is highly dependent on MYB-mediated transcriptional upregulation of CDK6, cyclin D3, and BCL2, and (ii) restoring their expression in MYB-silenced Phþ ALL cells rescues their impaired proliferation and survival. Levels of MYB and CDK6 were highly correlated in adult Phþ ALL (P ¼ 0.00008). Moreover, Phþ ALL cells exhibited a specific requirement for CDK6 but not CDK4 expression, most likely because, in these cells, CDK6 was predominantly localized in the nucleus, whereas CDK4 was almost exclusively cytoplasmic. Consistent with their essential role in Phþ ALL, pharmacologic inhibition of CDK6 and BCL2 markedly suppressed proliferation, colony formation, and survival of Phþ ALL cells ex vivo and in mice. In summary, these findings provide a proof-of-principle, rational strategy to target the MYB addiction of Phþ ALL. © 2017 American Association for Cancer Research
Sorafenib and Thyroid Cancer
Sorafenib (Nexavar) is a multikinase inhibitor, which has demonstrated both anti-proliferative and anti-angiogenic properties in vitro and in vivo, inhibiting the activity of targets present in the tumor cell [c-RAF (proto-oncogene serine/threonine-protein kinase), BRAF, V600EBRAF, c-KIT, and FMS-like tyrosine kinase 3] and in tumor vessels (c-RAF, vascular endothelial growth factor receptor-2, vascular endothelial growth factor receptor-3, and platelet-derived growth factor receptor β). For several years, sorafenib has been approved for the treatment of hepatocellular carcinoma and advanced renal cell carcinoma. After previous studies showing that sorafenib was able to inhibit oncogenic RET mutants, V600EBRAF, and angiogenesis and growth of orthotopic anaplastic thyroid cancer xenografts in nude mice, some clinical trials demonstrated the effectiveness of sorafenib in advanced thyroid cancer. Currently, the evaluation of the clinical safety and efficacy of sorafenib for the treatment of advanced thyroid cancer is ongoing. This article reviews the anti-neoplastic effect of sorafenib in thyroid cancer. Several completed (or ongoing) studies have evaluated the long-term efficacy and tolerability of sorafenib in patients with papillary and medullary aggressive thyroid cancer. The results suggest that sorafenib is a promising therapeutic option in patients with advanced thyroid cancer that is not responsive to traditional therapeutic strategies
Evaluation of safety and efficacy of DNA vaccines against bovine herpesvirus-1 (BoHV-1) in calves.
Four DNA vaccines against BoHV-1 were evaluated for their efficacy in calves. Twelve animals were divided into four groups which were injected with four different DNA vaccines: pVAX-tgD (Vaccine A); pVAX-tgD co-immunised with pVAX-48CpG (Vaccine B); pVAX-UbiLacl-tgD-L (Vaccine C); pVAX-UbiLacl-tgD-L co-immunised with pVAX-48CpG (Vaccine D). Three additional calves were given the plasmid vector and served as controls. Ninety days after the first vaccination all calves were challenge infected with BoHV-1.
All animals developed a severe form of infections bovine rhinotracheitis. Only the calves given the pVAX-tgD co-immunised with pVAX-48CpG (Vaccine B) developed humoral antibodies against BoHV-1 between 56 and 90 days after the first vaccination, whereas in calves of other groups and in the controls, antibodies appeared only after the infection. In the calves vaccinated with either pVAX-tgD (Vaccine A) or pVAX-tgD combined with pVAX-48CpG (Vaccine B), BoHV-1-specific IFN-gamma secreting cells were detected in PBMCs 90 days after the first vaccination and their number increased after challenge exposure. In the other groups the IFN-gamma secreting cells were detected after virus infection and at low values
Macroparasite fauna of alien grey squirrels (Sciurus carolinensis): composition, variability and implications for native species.
Introduced hosts populations may benefit of an "enemy release" through impoverishment of parasite communities made of both few imported species and few acquired local ones. Moreover, closely related competing native hosts can be affected by acquiring introduced taxa (spillover) and by increased transmission risk of native parasites (spillback). We determined the macroparasite fauna of invasive grey squirrels (Sciurus carolinensis) in Italy to detect any diversity loss, introduction of novel parasites or acquisition of local ones, and analysed variation in parasite burdens to identify factors that may increase transmission risk for native red squirrels (S. vulgaris). Based on 277 grey squirrels sampled from 7 populations characterised by different time scales in introduction events, we identified 7 gastro-intestinal helminths and 4 parasite arthropods. Parasite richness is lower than in grey squirrel's native range and independent from introduction time lags. The most common parasites are Nearctic nematodes Strongyloides robustus (prevalence: 56.6%) and Trichostrongylus calcaratus (6.5%), red squirrel flea Ceratophyllus sciurorum (26.0%) and Holarctic sucking louse Neohaematopinus sciuri (17.7%). All other parasites are European or cosmopolitan species with prevalence below 5%. S. robustus abundance is positively affected by host density and body mass, C. sciurorum abundance increases with host density and varies with seasons. Overall, we show that grey squirrels in Italy may benefit of an enemy release, and both spillback and spillover processes towards native red squirrels may occur
Measurement of the neutron detection efficiency of a 80% absorber - 20% scintillating fibers calorimeter
The neutron detection efficiency of a sampling calorimeter made of 1 mm
diameter scintillating fibers embedded in a lead/bismuth structure has been
measured at the neutron beam of the The Svedberg Laboratory at Uppsala. A
significant enhancement of the detection efficiency with respect to a bulk
organic scintillator detector with the same thickness is observed.Comment: 10 pages, 7 figure
Towards an embedding of Graph Transformation in Intuitionistic Linear Logic
Linear logics have been shown to be able to embed both rewriting-based
approaches and process calculi in a single, declarative framework. In this
paper we are exploring the embedding of double-pushout graph transformations
into quantified linear logic, leading to a Curry-Howard style isomorphism
between graphs and transformations on one hand, formulas and proof terms on the
other. With linear implication representing rules and reachability of graphs,
and the tensor modelling parallel composition of graphs and transformations, we
obtain a language able to encode graph transformation systems and their
computations as well as reason about their properties
Deadwood in forest stands close to old-growthness under Mediterranean conditions in the Italian Peninsula
Considering that indicators of old-growth features can vary across the European ecoregions, this paper provides some results to identify the distinctive traits of old-growth forests in the Mediterranean ecoregion. Deadwood occurrence as indicator of naturalness is investigated in some remote forest areas that have developed in absence of anthropogenic disturbance over the past few decades. Eleven study sites across the Italian peninsula were elected and records of deadwood were carried out in 1-ha size plots. Deadwood volume, deadwood types and decay stages were inventoried in the selected sites. The amounts of deadwood indicate a large variability among the investigated forest stands: the total volume ranged between 2 and 143 m3ha-1, with an average of 60 m3ha-1. Lying deadwood is the most abundant component of deadwood in the investigated forests, due to the natural mortality occurring in the stands in relation to the processes established in the last decades. On the contrary, stumps are the less represented type of deadwood in almost all the study areas. All the decay classes are present in each study site. The amount of deadwood in Southern Europe, even if lower than that reported for North and Central European countries, could have a different meaning due to the faster decay occurring in Mediterranean forest ecosystems. For this reason, old-growth features and the characteristics of each indicator should be framed and referred to well-defined climatic and biogeographic contexts. Distinctively, under the conditions here investigated, three main deadwood features prove to characterize forest stands close to old-growthness: a ratio of dead to living wood not lower than 10%; lying deadwood much more abundant than the standing one; large range of deadwood size and decay classes across all the deadwood components
Correction of Mutant p63 in EEC Syndrome Using siRNA Mediated Allele-Specific Silencing Restores Defective Stem Cell Function
Ectrodactyly-Ectodermal dysplasia-Clefting (EEC) syndrome is a rare autosomal dominant disease caused by heterozygous mutations in the p63 gene and characterized by limb defects, orofacial clefting, ectodermal dysplasia, and ocular defects. Patients develop progressive total bilateral limbal stem cell deficiency, which eventually results in corneal blindness. Medical and surgical treatments are ineffective and of limited benefit. Oral mucosa epithelial stem cells (OMESCs) represent an alternative source of stem cells capable of regenerating the corneal epithelium and, combined with gene therapy, could provide an attractive therapeutic avenue. OMESCs from EEC patients carrying the most severe p63 mutations (p.R279H and p.R304Q) were characterized and the genetic defect of p.R279H silenced using allele-specific (AS) small interfering RNAs (siRNAs). Systematic screening of locked nucleic acid (LNA)-siRNAs against R279H-p63 allele in (i) stable WT-\u394Np63\u3b1-RFP and R279H-\u394Np63\u3b1-EGFP cell lines, (ii) transient doubly transfected cell lines, and (iii) p.R279H OMESCs, identified a number of potent siRNA inhibitors for the mutant allele, which had no effect on wild-type p63. In addition, siRNA treatment led to longer acquired life span of mutated stem cells compared to controls, less accelerated stem cell differentiation in vitro, reduced proliferation properties, and effective ability in correcting the epithelial hypoplasia, thus giving rise to full thickness stratified and differentiated epithelia. This study demonstrates the phenotypic correction of mutant stem cells (OMESCs) in EEC syndrome by means of siRNA mediated AS silencing with restoration of function. The application of siRNA, alone or in combination with cell-based therapies, offers a therapeutic strategy for corneal blindness in EEC syndrome
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