A new perturbative expansion of the time evolution operator associated with a quantum system

A novel expansion of the evolution operator associated with a -- in general, time-dependent -- perturbed quantum Hamiltonian is presented. It is shown that it has a wide range of possible realizations that can be fitted according to computational convenience or to satisfy specific requirements. As a remarkable example, the quantum Hamiltonian describing a laser-driven trapped ion is studied in detail.Comment: 32 pages; modified version with examples of my previous paper quant-ph/0404056; to appear on the J. of Optics B: Quantum and Semiclassical Optics, Special Issue on 'Optics and Squeeze Transformations after Einstein

The immunomodulator PSK induces in vitro cytotoxic activity in tumour cell lines via arrest of cell cycle and induction of apoptosis

Background Protein-bound polysaccharide (PSK) is derived from the CM-101 strain of the fungus Coriolus versicolor and has shown anticancer activity in vitro and in in vivo experimental models and human cancers. Several randomized clinical trials have demonstrated that PSK has great potential in adjuvant cancer therapy, with positive results in the adjuvant treatment of gastric, esophageal, colorectal, breast and lung cancers. These studies have suggested the efficacy of PSK as an immunomodulator of biological responses. The precise molecular mechanisms responsible for its biological activity have yet to be fully elucidated.Methods The in vitro cytotoxic anti-tumour activity of PSK has been evaluated in various tumour cell lines derived from leukaemias, melanomas, fibrosarcomas and cervix, lung, pancreas and gastric cancers. Tumour cell proliferation in vitro was measured by BrdU incorporation and viable cell count. Effect of PSK on human peripheral blood lymphocyte (PBL) proliferation in vitro was also analyzed. Studies of cell cycle and apoptosis were performed in PSK-treated cells.Results PSK showed in vitro inhibition of tumour cell proliferation as measured by BrdU incorporation and viable cell count. The inhibition ranged from 22 to 84%. Inhibition mechanisms were identified as cell cycle arrest, with cell accumulation in G0/G1 phase and increase in apoptosis and caspase-3 expression. These results indicate that PSK has a direct cytotoxic activity in vitro, inhibiting tumour cell proliferation. In contrast, PSK shows a synergistic effect with IL-2 that increases PBL proliferation.Conclusion These results indicate that PSK has cytotoxic activity in vitro on tumour cell lines. This new cytotoxic activity of PSK on tumour cells is independent of its previously described immunomodulatory activity on NK cells.AGL was supported by FIS Postdoctoral Research Contract CP03/00111. Studies were partially supported by a grant from Kureha Chemical Industry (Japan)

Sustained proliferation in cancer: mechanisms and novel therapeutic targets

Proliferation is an important part of cancer development and progression. This is manifest by altered expression and/or activity of cell cycle related proteins. Constitutive activation of many signal transduction pathways also stimulates cell growth. Early steps in tumor development are associated with a fibrogenic response and the development of a hypoxic environment which favors the survival and proliferation of cancer stem cells. Part of the survival strategy of cancer stem cells may manifested by alterations in cell metabolism. Once tumors appear, growth and metastasis may be supported by overproduction of appropriate hormones (in hormonally dependent cancers), by promoting angiogenesis, by undergoing epithelial to mesenchymal transition, by triggering autophagy, and by taking cues from surrounding stromal cells. A number of natural compounds (e.g., curcumin, resveratrol, indole-3-carbinol, brassinin, sulforaphane, epigallocatechin-3-gallate, genistein, ellagitannins, lycopene and quercetin) have been found to inhibit one or more pathways that contribute to proliferation (e.g., hypoxia inducible factor 1, nuclear factor kappa B, phosphoinositide 3 kinase/Akt, insulin-like growth factor receptor 1, Wnt, cell cycle associated proteins, as well as androgen and estrogen receptor signaling). These data, in combination with bioinformatics analyses, will be very important for identifying signaling pathways and molecular targets that may provide early diagnostic markers and/or critical targets for the development of new drugs or drug combinations that block tumor formation and progression

Phenolic, polysaccharidic and lipidic fractions of mushrooms from northeast Portugal: chemical compounds with antioxidant properties

Mushrooms do not constitute a significant portion of the human diet, but their consumption continues to increase due to their functional benefits and presence of bioactive compounds. Some of those compounds can be found in the phenolic, polysaccharidic and lipidic fractions of edible and inedible species. Herein, those fractions of five wild mushrooms (Coprinopsis atramentaria, Lactarius bertillonii, Lactarius vellereus, Rhodotus palmatus and Xerocomus chrysenteron) from Northeast Portugal were studied for their chemical composition and antioxidant properties. Protocatechuic, p-hydroxybenzoic, p-coumaric and cinnamic acids were found in the phenolic fraction, ramnose, xylose, fucose, arabinose, fructose, glucose, manose, mannitol, sucrose, maltose and trehalose were quantified in polysaccharidic fraction, linoleic and stearic (only in Lactarius sp.) acids, and β- and γ-tocopherols were the main compounds in the lipidic fraction. C. atramentaria and X. chrysenteron phenolic fractions gave the highest free radical scavenging activity, reducing properties and lipid peroxidation inhibition in brain homogenates, which is in agreement with its highest content in total phenolics. Furthermore, among the polysaccharidic fractions C. atramentaria also gave the highest antioxidant activity, which is accordingly with its highest total polysaccharides content and sugars obtained after hydrolysis.The authors are grateful to Fundação para a Ciência e a Tecnologia (FCT, Portugal) and COMPETE/QREN/EU (research project PTDC/AGR-ALI/110062/2009) for financial support. L. Barros (BPD/4609/2008) and S.A. Heleno (BD/70304/2010) also thank FCT, POPH-QREN and FSE. The GIP-USAL is financially supported by the Spanish Ministerio de Ciencia e Innovación through the Consolider-Ingenio 2010 Programme (FUN-C-FOOD, CSD2007-00063), and Junta de Castilla y León (Grupo de Investigación de Excelencia, GR133)

A longitudinal comparison of emotional, behavioral and attention problems in autistic and typically developing children

Background Mental health problems are elevated in autistic individuals but there is limited evidence on the developmental course of problems across childhood. We compare the level and growth of anxious-depressed, behavioral and attention problems in an autistic and typically developing (TD) cohort. Methods Latent growth curve models were applied to repeated parent-report Child Behavior Checklist data from age 2–10 years in an inception cohort of autistic children (Pathways, N = 397; 84% boys) and a general population TD cohort (Wirral Child Health and Development Study; WCHADS; N = 884, 49% boys). Percentile plots were generated to quantify the differences between autistic and TD children. Results Autistic children showed elevated levels of mental health problems, but this was substantially reduced by accounting for IQ and sex differences between the autistic and TD samples. There was small differences in growth patterns; anxious-depressed problems were particularly elevated at preschool and attention problems at late childhood. Higher family income predicted lower base-level on all three dimensions, but steeper increase of anxious-depressed problems. Higher IQ predicted lower level of attention problems and faster decline over childhood. Female sex predicted higher level of anxious-depressed and faster decline in behavioral problems. Social-affect autism symptom severity predicted elevated level of attention problems. Autistic girls' problems were particularly elevated relative to their same-sex non-autistic peers. Conclusions Autistic children, and especially girls, show elevated mental health problems compared to TD children and there are some differences in predictors. Assessment of mental health should be integrated into clinical practice for autistic children

Duration of Treatment for Pseudomonas aeruginosa Bacteremia : a Retrospective Study

Introduction: There is no consensus regarding optimal duration of antibiotic therapy for Pseudomonas aeruginosa bacteremia. We aimed to evaluate the impact of short antibiotic course. Methods: We present a retrospective multicenter study including patients with P. aeruginosa bacteremia during 2009-2015. We evaluated outcomes of patients treated with short (6-10 days) versus long (11-15 days) antibiotic courses. The primary outcome was a composite of 30-day mortality or bacteremia recurrence and/or persistence. Univariate and inverse probability treatment-weighted (IPTW) adjusted multivariate analysis for the primary outcome was performed. To avoid immortal time bias, the landmark method was used. Results: We included 657 patients; 273 received a short antibiotic course and 384 a long course. There was no significant difference in baseline characteristics of patients. The composite primary outcome occurred in 61/384 patients in the long-treatment group (16%) versus 32/273 in the short-treatment group (12%) (p = 0.131). Mortality accounted for 41/384 (11%) versus 25/273 (9%) of cases, respectively. Length of hospital stay was significantly shorter in the short group [median 13 days, interquartile range (IQR) 9-21 days, versus median 15 days, IQR 11-26 days, p = 0.002]. Ten patients in the long group discontinued antibiotic therapy owing to adverse events, compared with none in the short group. On univariate and multivariate analyses, duration of therapy was not associated with the primary outcome. Conclusions: In this retrospective study, 6-10 days of antibiotic course for P. aeruginosa bacteremia were as effective as longer courses in terms of survival and recurrence. Shorter therapy was associated with reduced length of stay and less drug discontinuation

A Major Role of the RecFOR Pathway in DNA Double-Strand-Break Repair through ESDSA in Deinococcus radiodurans

In Deinococcus radiodurans, the extreme resistance to DNA–shattering treatments such as ionizing radiation or desiccation is correlated with its ability to reconstruct a functional genome from hundreds of chromosomal fragments. The rapid reconstitution of an intact genome is thought to occur through an extended synthesis-dependent strand annealing process (ESDSA) followed by DNA recombination. Here, we investigated the role of key components of the RecF pathway in ESDSA in this organism naturally devoid of RecB and RecC proteins. We demonstrate that inactivation of RecJ exonuclease results in cell lethality, indicating that this protein plays a key role in genome maintenance. Cells devoid of RecF, RecO, or RecR proteins also display greatly impaired growth and an important lethal sectoring as bacteria devoid of RecA protein. Other aspects of the phenotype of recFOR knock-out mutants paralleled that of a ΔrecA mutant: ΔrecFOR mutants are extremely radiosensitive and show a slow assembly of radiation-induced chromosomal fragments, not accompanied by DNA synthesis, and reduced DNA degradation. Cells devoid of RecQ, the major helicase implicated in repair through the RecF pathway in E. coli, are resistant to γ-irradiation and have a wild-type DNA repair capacity as also shown for cells devoid of the RecD helicase; in contrast, ΔuvrD mutants show a markedly decreased radioresistance, an increased latent period in the kinetics of DNA double-strand-break repair, and a slow rate of fragment assembly correlated with a slow rate of DNA synthesis. Combining RecQ or RecD deficiency with UvrD deficiency did not significantly accentuate the phenotype of ΔuvrD mutants. In conclusion, RecFOR proteins are essential for DNA double-strand-break repair through ESDSA whereas RecJ protein is essential for cell viability and UvrD helicase might be involved in the processing of double stranded DNA ends and/or in the DNA synthesis step of ESDSA