39 research outputs found

    Spectral projections and resolvent bounds for partially elliptic quadratic differential operators

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    We study resolvents and spectral projections for quadratic differential operators under an assumption of partial ellipticity. We establish exponential-type resolvent bounds for these operators, including Kramers-Fokker-Planck operators with quadratic potentials. For the norms of spectral projections for these operators, we obtain complete asymptotic expansions in dimension one, and for arbitrary dimension, we obtain exponential upper bounds and the rate of exponential growth in a generic situation. We furthermore obtain a complete characterization of those operators with orthogonal spectral projections onto the ground state.Comment: 60 pages, 3 figures. J. Pseudo-Differ. Oper. Appl., to appear. Revised according to referee report, including minor changes to Corollary 1.8. The final publication will be available at link.springer.co

    Automobile shredder residues in Italy: characterization and valorization opportunities

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    At the moment Automobile Shredder Residue (ASR) is usually landfilled worldwide, but European draft Directive 2000/53/CE forces the development of alternative solutions, stating the 95%-wt recovery of an End of Life Vehicle (ELV) weight to be fulfilled by 2015. This work describes two industrial tests, each involving 250-300 t of ELVs, in which different pre-shredding operations were performed. The produced ASR materials underwent an extended characterization and some post-shredding processes, consisting of dimensional, magnetic, electrostatic and densimetric separation phases, were tested on laboratory scale, having as main purpose the enhancement of ASR recovery/recycling and the minimization of the landfilled fraction. The gathered results show that accurate depollution and dismantling operations are mandatory to obtain a high quality ASR material which may be recycled/recovered and partially landfilled according to the actual European Union regulations, with particular concern for Lower Heating Value (LHV), heavy metals content and Dissolved Organic Carbon (DOC) as critical parameters. Moreover post-shredding technical solutions foreseeing minimum economic and engineering efforts, therefore realizable in common European ELVs shredding plants, may lead to multi-purposed (material recovery and thermal valorization) opportunities for ASR reuse/recovery

    Extended investigation of superdeformed bands in 151,152^{151,152}Tb nuclei

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    A detailed study of known and new SD bands in Tb isotopes has been performed with the use of the EUROBALL IV -ray array. The high-statistics data set has allowed for the extension of known SD bands at low and high spins by new -ray transitions. These transitions, as it turns out, correspond to the rotational frequencies where the principal superdeformed gaps (Z=66,N=86) close giving rise to up- or down-bending mechanisms. This enables to attribute the underlying theoretical configurations with much higher confidence as compared to the previous identifications. Five new SD bands have been discovered, three of them assigned to the 152Tb and the two others to the 151Tb nuclei. Nuclear mean-field calculations have been used to interpret the structure of known SD bands as well as of the new ones in terms of nucleonic configurations

    Noncanonical DNA Motifs as Transactivation Targets by Wild Type and Mutant p53

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    Sequence-specific binding by the human p53 master regulator is critical to its tumor suppressor activity in response to environmental stresses. p53 binds as a tetramer to two decameric half-sites separated by 0–13 nucleotides (nt), originally defined by the consensus RRRCWWGYYY (n = 0–13) RRRCWWGYYY. To better understand the role of sequence, organization, and level of p53 on transactivation at target response elements (REs) by wild type (WT) and mutant p53, we deconstructed the functional p53 canonical consensus sequence using budding yeast and human cell systems. Contrary to early reports on binding in vitro, small increases in distance between decamer half-sites greatly reduces p53 transactivation, as demonstrated for the natural TIGER RE. This was confirmed with human cell extracts using a newly developed, semi–in vitro microsphere binding assay. These results contrast with the synergistic increase in transactivation from a pair of weak, full-site REs in the MDM2 promoter that are separated by an evolutionary conserved 17 bp spacer. Surprisingly, there can be substantial transactivation at noncanonical ½-(a single decamer) and ¾-sites, some of which were originally classified as biologically relevant canonical consensus sequences including PIDD and Apaf-1. p53 family members p63 and p73 yielded similar results. Efficient transactivation from noncanonical elements requires tetrameric p53, and the presence of the carboxy terminal, non-specific DNA binding domain enhanced transactivation from noncanonical sequences. Our findings demonstrate that RE sequence, organization, and level of p53 can strongly impact p53-mediated transactivation, thereby changing the view of what constitutes a functional p53 target. Importantly, inclusion of ½- and ¾-site REs greatly expands the p53 master regulatory network

    Multiple Myeloma Treatment in Real-world Clinical Practice : Results of a Prospective, Multinational, Noninterventional Study

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    Funding Information: The authors would like to thank all patients and their families and all the EMMOS investigators for their valuable contributions to the study. The authors would like to acknowledge Robert Olie for his significant contribution to the EMMOS study. Writing support during the development of our report was provided by Laura Mulcahy and Catherine Crookes of FireKite, an Ashfield company, a part of UDG Healthcare plc, which was funded by Millennium Pharmaceuticals, Inc, and Janssen Global Services, LLC. The EMMOS study was supported by research funding from Janssen Pharmaceutical NV and Millennium Pharmaceuticals, Inc. Funding Information: The authors would like to thank all patients and their families and all the EMMOS investigators for their valuable contributions to the study. The authors would like to acknowledge Robert Olie for his significant contribution to the EMMOS study. Writing support during the development of our report was provided by Laura Mulcahy and Catherine Crookes of FireKite, an Ashfield company, a part of UDG Healthcare plc, which was funded by Millennium Pharmaceuticals, Inc, and Janssen Global Services, LLC. The EMMOS study was supported by research funding from Janssen Pharmaceutical NV and Millennium Pharmaceuticals, Inc. Funding Information: M.M. has received personal fees from Janssen, Celgene, Amgen, Bristol-Myers Squibb, Sanofi, Novartis, and Takeda and grants from Janssen and Sanofi during the conduct of the study. E.T. has received grants from Janssen and personal fees from Janssen and Takeda during the conduct of the study, and grants from Amgen, Celgene/Genesis, personal fees from Amgen, Celgene/Genesis, Bristol-Myers Squibb, Novartis, and Glaxo-Smith Kline outside the submitted work. M.V.M. has received personal fees from Janssen, Celgene, Amgen, and Takeda outside the submitted work. M.C. reports honoraria from Janssen, outside the submitted work. M. B. reports grants from Janssen Cilag during the conduct of the study. M.D. has received honoraria for participation on advisory boards for Janssen, Celgene, Takeda, Amgen, and Novartis. H.S. has received honoraria from Janssen-Cilag, Celgene, Amgen, Bristol-Myers Squibb, Novartis, and Takeda outside the submitted work. V.P. reports personal fees from Janssen during the conduct of the study and grants, personal fees, and nonfinancial support from Amgen, grants and personal fees from Sanofi, and personal fees from Takeda outside the submitted work. W.W. has received personal fees and grants from Amgen, Celgene, Novartis, Roche, Takeda, Gilead, and Janssen and nonfinancial support from Roche outside the submitted work. J.S. reports grants and nonfinancial support from Janssen Pharmaceutical during the conduct of the study. V.L. reports funding from Janssen Global Services LLC during the conduct of the study and study support from Janssen-Cilag and Pharmion outside the submitted work. A.P. reports employment and shareholding of Janssen (Johnson & Johnson) during the conduct of the study. C.C. reports employment at Janssen-Cilag during the conduct of the study. C.F. reports employment at Janssen Research and Development during the conduct of the study. F.T.B. reports employment at Janssen-Cilag during the conduct of the study. The remaining authors have stated that they have no conflicts of interest. Publisher Copyright: © 2018 The AuthorsMultiple myeloma (MM) remains an incurable disease, with little information available on its management in real-world clinical practice. The results of the present prospective, noninterventional observational study revealed great diversity in the treatment regimens used to treat MM. Our results also provide data to inform health economic, pharmacoepidemiologic, and outcomes research, providing a framework for the design of protocols to improve the outcomes of patients with MM. Background: The present prospective, multinational, noninterventional study aimed to document and describe real-world treatment regimens and disease progression in multiple myeloma (MM) patients. Patients and Methods: Adult patients initiating any new MM therapy from October 2010 to October 2012 were eligible. A multistage patient/site recruitment model was applied to minimize the selection bias; enrollment was stratified by country, region, and practice type. The patient medical and disease features, treatment history, and remission status were recorded at baseline, and prospective data on treatment, efficacy, and safety were collected electronically every 3 months. Results: A total of 2358 patients were enrolled. Of these patients, 775 and 1583 did and did not undergo stem cell transplantation (SCT) at any time during treatment, respectively. Of the patients in the SCT and non-SCT groups, 49%, 21%, 14%, and 15% and 57%, 20%, 12% and 10% were enrolled at treatment line 1, 2, 3, and ≥ 4, respectively. In the SCT and non-SCT groups, 45% and 54% of the patients had received bortezomib-based therapy without thalidomide/lenalidomide, 12% and 18% had received thalidomide/lenalidomide-based therapy without bortezomib, and 30% and 4% had received bortezomib plus thalidomide/lenalidomide-based therapy as frontline treatment, respectively. The corresponding proportions of SCT and non-SCT patients in lines 2, 3, and ≥ 4 were 45% and 37%, 30% and 37%, and 12% and 3%, 33% and 27%, 35% and 32%, and 8% and 2%, and 27% and 27%, 27% and 23%, and 6% and 4%, respectively. In the SCT and non-SCT patients, the overall response rate was 86% to 97% and 64% to 85% in line 1, 74% to 78% and 59% to 68% in line 2, 55% to 83% and 48% to 60% in line 3, and 49% to 65% and 36% and 45% in line 4, respectively, for regimens that included bortezomib and/or thalidomide/lenalidomide. Conclusion: The results of our prospective study have revealed great diversity in the treatment regimens used to manage MM in real-life practice. This diversity was linked to factors such as novel agent accessibility and evolving treatment recommendations. Our results provide insight into associated clinical benefits.publishersversionPeer reviewe

    Characterization ofMedicago populations under cold acclimation by morphological traits and microsatellite (SSR) markers

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    The study was carried on 16 accessions of annual Medicago species (M. truncatula Gaertn. M. ciliaris Krocker., M. aculeata Wild. and M. polymorpha L.). Seedlings of different accessions collected from sites of contrasting altitudes (10 to 1170 m) were subjected to different durations of low temperature regimes. Root to shoot ratios of acclimated and non acclimated plants were compared. Among the 16 accessions studied, 12 were used to assess the degree of genetic polymorphism by SSR microsatellites. Results show that accessions that originated from high altitude had a better root to shoot ratios and so had better ability to cold acclimation than accessions that originated from low altitude (lower ability to cold acclimation). Tests differentiation between species by fisher pair indicates that all species were different from each other. Results show the highest level of homozygosity for all species (> 80 %). Moreover, there were differences between populations of the same species of cold acclimation, which will encourage for a study of association between cold acclimation and molecular polymorphism.Keywords: Cold acclimation, root: shoot ratios, molecular polymorphism, annuals populations, MedicagoAfrican Journal of Biotechnology, Vol 13(27) 2704-271
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