994 resultados para combination class


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Natural drug discovery represents an area of research with vast potential. The investigation into the use of naturally-occurring peptides as potential therapeutic agents provides a new “chemical space” for the procurement of drug leads. Intensive and systematic studies on the broad-spectrum antimicrobial peptides found in amphibian skin secretions are of particular interest in the quest for new antibiotics to treat multiple drug-resistant bacterial infections. Here we report the molecular cloning of the biosynthetic precursor-encoding cDNAs and respective mature peptides representing a novel group of antimicrobial peptides from the skin secretions of representative species of phyllomedusine leaf frogs: the Central American red-eyed leaf frog (Agalychnis callidryas), the South American orange-legged leaf frog (Phyllomedusa hypochondrialis) and the Giant Mexican leaf frog, (Pachymedusa dacnicolor). Each novel peptide possessed the highly-conserved sequence, LGMIPL/VAISAISA/SLSKLamide, and each exhibited activity against the Gram-positive bacterium, Staphylococcus aureus and the yeast, Candida albicans, but all were devoid of haemolytic effects at concentrations up to and including the MICs for both organisms. The novel peptide group were named medusins, derived from the name of the hylid frog sub-family, Phyllomedusinae, to which all species investigated belong. These data clearly demonstrate that comparative studies of the skin secretions of phyllomedusine frogs can continue to produce novel peptides that have the potential to be leads in the development of new and effective antimicrobials.

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Dermot Bolger's The Journey Home (1990) narrates an often hyperbolic and overblown diatribe against a litany of social and political ills, which elicited frequently critical responses to the novel from reviewers. Yet Bolger's seminal work remains both popular and controversial because of its capacity to shock and upbraid the false morality of Irish society--a society that the author considered to be riven by class inequalities and official abuses. Bolger employs sexual abuse as a metonym for political corruption in the novel, and this essay explores The Journey Home's surreal story of youth in a working-class Dublin suburb in light of more recent revelations of Ireland's legacy of institutional sexual abuse.

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ABSTRACT: Bone-seeking radionuclides including samarium-153 ethylene diamine tetramethylene phosphonate and strontium-89 have been used for decades in the palliation of pain from bone metastases especially from prostate cancer. Emerging evidence of improved survival in metastatic castration-resistant prostate cancer (CRPC) with the first-in-class a-radionuclide, radium-223 (Ra) has rekindled interest in the role of bone-seeking radionuclide therapy.We review the literature for randomized controlled trials of bone-seeking radionuclides and explore some of the issues regarding the optimal use of these agents. In particular, we discuss dose, dose rate, radiobiology, and quality of radiation and postulate on potential future directions in particular combination schedules. ß-Emitting, bone-seeking radionuclides have proven ability to control pain in prostate cancer metastatic to bone with pain response rates in the order of 60% to 70% when used as single agents. Most of the published trials were underpowered to detect differences in survival; however, there is evidence of the potential for disease modification when these agents are used in combination with chemotherapy or in multiple cycles.Data from the recent phase III ALSYMPCA trial that compared Ra to placebo in symptomatic CRPC demonstrate a significant improvement in median overall survival of 3.6 months for patients with symptomatic CRPC metastatic to bone treated with 6 cycles of the a-emitting radionuclide Ra compared with placebo. The success of Ra in improving survival in CRPC will lead this agent to become part of the treatment paradigm for this disease, and with such an excellent safety profile, Ra has huge potential in combination strategies as well as for use earlier in the natural history of metastatic prostate cancer.

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The MaRINET project aims to build a synergy in the European marine renewable energy development infrastructure network, involving a total of 28 partners across the union. Its scope extends from small to large scale testing, in both tank and field. The main activities of the project are to standardize test procedures, to provide centralized free access for European technology developers, and to innovate for improving test infrastructures and techniques.
This paper presents the work carried in this last part, which focuses on research objectives identified to be current challenges for industrial development. They are distributed in 6 topics. On the one hand are issues that concern directly one of the 3 types of energy scoped in the project: wave, tidal, and offshore wind energy. Two examples are the real time estimation of incident waves, and the measurement of turbulence in tidal flows. On the other hand, collaborative effort is drawn on aspects that are common to those technologies: electrical components, environmental monitoring, and dedicated moorings.

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In this paper, the envelope-tracking technique is exploited to boost average efficiency of the newly introduced broadband Inverse Class-E power amplifier. A 2.26 GHz - 20.5 dBm - 3 V power amplifier was designed, constructed, and measured. For a multi-carrier input signal with 10 dB peak-to-average ratio, the average PAE was increased from 5.7% to 54.5%. © 2008 IEEE.

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Experimental assessments of the modified power-combining Class-E amplifier are described. The technique used to combine the output of individual power amplifiers (PAs) into an unbalanced load without the need for bulky transformers permits the use of small RF chokes useful for the deployment in the EER transmitter. The modified output load network of the PA results in excellent 50 dBc and 46 dBc second and third-harmonic suppressions, dispensing the need for additional lossy filtering block. Operating from a 3.2 V dc supply voltage, the PA exhibits 64% drain efficiency at 24 dBm output power. Over a wide bandwidth of 350 MHz, drain efficiency of better than 60% at output power higher than 22 dBm were achieved. © 2010 IEICE Institute of Electronics Informati.

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Analysis and synthesis of the new Class-EF power amplifier (PA) are presented in this paper. The proposed circuit offers means to alleviate some of the major issues faced by existing Class-EF and Class-EF PAs, such as (1) substantial power losses due to parasitic resistance of the large inductor in the Class-EF load network, (2) unpredictable behaviour of practical lumped inductors and capacitors at harmonic frequencies, and (3) deviation from ideal Class-EF operation mode due to detrimental effects of device output inductance at high frequencies. The transmission-line load network of the Class-EF PA topology elaborated in this paper simultaneously satisfies the Class-EF optimum impedance requirements at fundamental frequency, second, and third harmonics as well as simultaneously providing matching to the circuit optimum load resistance for any prescribed system load resistance. Furthermore, an elegant solution using an open and short-circuit stub arrangement is suggested to overcome the problem encountered in the mm-wave IC realizations of the Class-EF PA load network due to lossy quarter-wave line. © 2010 IEICE Institute of Electronics Informati.