143 research outputs found

    Portfolio Optimization Using SPEA2 with Resampling

    Get PDF
    Proceeding of: Intelligent Data Engineering and Automated Learning – IDEAL 2011: 12th International Conference, Norwich, UK, September 7-9, 2011The subject of financial portfolio optimization under real-world constraints is a difficult problem that can be tackled using multiobjective evolutionary algorithms. One of the most problematic issues is the dependence of the results on the estimates for a set of parameters, that is, the robustness of solutions. These estimates are often inaccurate and this may result on solutions that, in theory, offered an appropriate risk/return balance and, in practice, resulted being very poor. In this paper we suggest that using a resampling mechanism may filter out the most unstable. We test this idea on real data using SPEA2 as optimization algorithm and the results show that the use of resampling increases significantly the reliability of the resulting portfolios.The authors acknowledge financial support granted by the Spanish Ministry of Science under contract TIN2008-06491-C04-03 (MSTAR) and Comunidad de Madrid (CCG10- UC3M/TIC-5029).Publicad

    ОЦІНКА ЯКОСТІ НАДАННЯ МЕДИЧНИХ ПОСЛУГ СЕРЕДНІМ МЕДИЧНИМ ПЕРСОНАЛОМ В УМОВАХ ПРИВАТНОГО МЕДИЧНОГО ЦЕНТРУ

    Get PDF
    The article analyzes the literature and classifies the quality of the nursing staff, according to which the analysis of the quality of the nurses of Private Medical Ophthalmologic Center «Professor Zahurskyi Eye Surgery Center» for 2015 and suggests the ways to improve the optimization of the medical staff to achieve better treatment outcomes and satisfaction of patients.У статті проведено аналіз літератури з даної проблеми та класифіковано показники якості роботи середнього медичного персоналу. Проведено аналіз якості роботи медичних сестер приватного медичного офтальмологічного центру ТОВ «Центр хірургії ока професора Загурського» за 2015 р. та запропоновано шляхи вдосконалення та оптимізації роботи медичного персоналу для досягнення кращих результатів лікування та задоволеності пацієнтів.

    ПРОБЛЕМИ ПРОФЕСІЙНОЇ ЗАХВОРЮВАНОСТІ СЕРЕД ФАРМАЦЕВТИЧНИХ ПРАЦІВНИКІВ

    Get PDF
    The article presents the experience of investigation of pharmacists’morbidity in some countries of the world. Basic factors influencing on the structure and level of pharmacists’morbidity were determined.У статті проаналізовано досвід вивчення захворюваності аптечних працівників у деяких зарубіжних країнах. Визначено основні чинники, що впливають на рівень та структуру захворюваності аптечних працівників

    Somatic Mutations of the Immunoglobulin Framework Are Generally Required for Broad and Potent HIV-1 Neutralization

    Get PDF
    Broadly neutralizing antibodies (bNAbs) to HIV-1 can prevent infection and are therefore of great importance for HIV-1 vaccine design. Notably, bNAbs are highly somatically mutated and generated by a fraction of HIV-1-infected individuals several years after infection. Antibodies typically accumulate mutations in the complementarity determining region (CDR) loops, which usually contact the antigen. The CDR loops are scaffolded by canonical framework regions (FWRs) that are both resistant to and less tolerant of mutations. Here, we report that in contrast to most antibodies, including those with limited HIV-1 neutralizing activity, most bNAbs require somatic mutations in their FWRs. Structural and functional analyses reveal that somatic mutations in FWR residues enhance breadth and potency by providing increased flexibility and/or direct antigen contact. Thus, in bNAbs, FWRs play an essential role beyond scaffolding the CDR loops and their unusual contribution to potency and breadth should be considered in HIV-1 vaccine design

    DNA damage alters DNA polymerase δ to a form that exhibits increased discrimination against modified template bases and mismatched primers

    Get PDF
    Human DNA polymerase δ (Pol δ4), a key enzyme in chromosomal replication, is a heterotetramer composed of the p125, p50, p68 and p12 subunits. Genotoxic agents such as UV and alkylating chemicals trigger a DNA damage response in which Pol δ4 is converted to a trimer (Pol δ3) by degradation of p12. We show that Pol δ3 has altered enzymatic properties: it is less able to perform translesion synthesis on templates containing base lesions (O6-MeG, 8-oxoG, an abasic site or a thymine-thymine dimer); a greater proofreading activity; an increased exonuclease/polymerase activity ratio; a decreased tendency for the insertion of wrong nucleotides, and for the extension of mismatched primers. Overall, our findings indicate that Pol δ3 exhibits an enhanced ability for the detection of errors in both primers and templates over its parent enzyme. These alterations in Pol δ3 show that p12 plays a major role in Pol δ4 catalytic functions, and provides significant insights into the rationale for the conversion of Pol δ4 to Pol δ3 in the cellular response to DNA damage

    HIV therapy by a combination of broadly neutralizing antibodies in humanized mice

    Get PDF
    Human antibodies to human immunodeficiency virus-1 (HIV-1) can neutralize a broad range of viral isolates in vitro and protect non-human primates against infection. Previous work showed that antibodies exert selective pressure on the virus but escape variants emerge within a short period of time. However, these experiments were performed before the recent discovery of more potent anti-HIV-1 antibodies and their improvement by structure-based design. Here we re-examine passive antibody transfer as a therapeutic modality in HIV-1-infected humanized mice. Although HIV-1 can escape from antibody monotherapy, combinations of broadly neutralizing antibodies can effectively control HIV-1 infection and suppress viral load to levels below detection. Moreover, in contrast to antiretroviral therapy the longer half-life of antibodies led to control of viraemia for an average of 60 days after cessation of therapy. Thus, combinations of potent monoclonal antibodies can effectively control HIV-1 replication in humanized mice, and should be re-examined as a therapeutic modality in HIV-1-infected individuals

    Mutator Suppression and Escape from Replication Error–Induced Extinction in Yeast

    Get PDF
    Cells rely on a network of conserved pathways to govern DNA replication fidelity. Loss of polymerase proofreading or mismatch repair elevates spontaneous mutation and facilitates cellular adaptation. However, double mutants are inviable, suggesting that extreme mutation rates exceed an error threshold. Here we combine alleles that affect DNA polymerase δ (Pol δ) proofreading and mismatch repair to define the maximal error rate in haploid yeast and to characterize genetic suppressors of mutator phenotypes. We show that populations tolerate mutation rates 1,000-fold above wild-type levels but collapse when the rate exceeds 10−3 inactivating mutations per gene per cell division. Variants that escape this error-induced extinction (eex) rapidly emerge from mutator clones. One-third of the escape mutants result from second-site changes in Pol δ that suppress the proofreading-deficient phenotype, while two-thirds are extragenic. The structural locations of the Pol δ changes suggest multiple antimutator mechanisms. Our studies reveal the transient nature of eukaryotic mutators and show that mutator phenotypes are readily suppressed by genetic adaptation. This has implications for the role of mutator phenotypes in cancer

    On the Zwitterionic Nature of Gas-Phase Peptides and Protein Ions

    Get PDF
    Determining the total number of charged residues corresponding to a given value of net charge for peptides and proteins in gas phase is crucial for the interpretation of mass-spectrometry data, yet it is far from being understood. Here we show that a novel computational protocol based on force field and massive density functional calculations is able to reproduce the experimental facets of well investigated systems, such as angiotensin II, bradykinin, and tryptophan-cage. The protocol takes into account all of the possible protomers compatible with a given charge state. Our calculations predict that the low charge states are zwitterions, because the stabilization due to intramolecular hydrogen bonding and salt-bridges can compensate for the thermodynamic penalty deriving from deprotonation of acid residues. In contrast, high charge states may or may not be zwitterions because internal solvation might not compensate for the energy cost of charge separation

    Balancing repair and tolerance of DNA damage caused by alkylating agents

    Get PDF
    Alkylating agents constitute a major class of frontline chemotherapeutic drugs that inflict cytotoxic DNA damage as their main mode of action, in addition to collateral mutagenic damage. Numerous cellular pathways, including direct DNA damage reversal, base excision repair (BER) and mismatch repair (MMR), respond to alkylation damage to defend against alkylation-induced cell death or mutation. However, maintaining a proper balance of activity both within and between these pathways is crucial for a favourable response of an organism to alkylating agents. Furthermore, the response of an individual to alkylating agents can vary considerably from tissue to tissue and from person to person, pointing to genetic and epigenetic mechanisms that modulate alkylating agent toxicity

    Learning Effective Dispatching Rules For Batch Processor Scheduling

    No full text
    Batch processor scheduling, where machines can process multiple jobs simultaneously, is frequently harder than its unit-capacity counterpart because an effective scheduling procedure must not only decide how to group the individual jobs into batches, but also determine the sequence in which the batches are to be processed. We extend a previously developed genetic learning approach to automatically discover effective dispatching policies for several batch scheduling environments, and show that these rules yield good system performance. Computational results show the competitiveness of the learned rules with existing rules for different performance measures. The autonomous learning approach addresses a growing practical need for rapidly developing effective dispatching rules for these environments by automating the discovery of effective job dispatching procedures
    corecore