1,820 research outputs found

    Multiple agency perspective, family control, and private information abuse in an emerging economy

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    Using a comprehensive sample of listed companies in Hong Kong this paper investigates how family control affects private information abuses and firm performance in emerging economies. We combine research on stock market microstructure with more recent studies of multiple agency perspectives and argue that family ownership and control over the board increases the risk of private information abuse. This, in turn, has a negative impact on stock market performance. Family control is associated with an incentive to distort information disclosure to minority shareholders and obtain private benefits of control. However, the multiple agency roles of controlling families may have different governance properties in terms of investors’ perceptions of private information abuse. These findings contribute to our understanding of the conflicting evidence on the governance role of family control within a multiple agency perspectiv

    Radial Growth of Qilian Juniper on the Northeast Tibetan Plateau and Potential Climate Associations

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    There is controversy regarding the limiting climatic factor for tree radial growth at the alpine treeline on the northeastern Tibetan Plateau. In this study, we collected 594 increment cores from 331 trees, grouped within four altitude belts spanning the range 3550 to 4020 m.a.s.l. on a single hillside. We have developed four equivalent ring-width chronologies and shown that there are no significant differences in their growth-climate responses during 1956 to 2011 or in their longer-term growth patterns during the period AD 1110–2011. The main climate influence on radial growth is shown to be precipitation variability. Missing ring analysis shows that tree radial growth at the uppermost treeline location is more sensitive to climate variation than that at other elevations, and poor tree radial growth is particularly linked to the occurrence of serious drought events. Hence water limitation, rather than temperature stress, plays the pivotal role in controlling the radial growth of Sabina przewalskii Kom. at the treeline in this region. This finding contradicts any generalisation that tree-ring chronologies from high-elevation treeline environments are mostly indicators of temperature changes

    Topologically Protected Quantum State Transfer in a Chiral Spin Liquid

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    Topology plays a central role in ensuring the robustness of a wide variety of physical phenomena. Notable examples range from the robust current carrying edge states associated with the quantum Hall and the quantum spin Hall effects to proposals involving topologically protected quantum memory and quantum logic operations. Here, we propose and analyze a topologically protected channel for the transfer of quantum states between remote quantum nodes. In our approach, state transfer is mediated by the edge mode of a chiral spin liquid. We demonstrate that the proposed method is intrinsically robust to realistic imperfections associated with disorder and decoherence. Possible experimental implementations and applications to the detection and characterization of spin liquid phases are discussed.Comment: 14 pages, 7 figure

    Transition of plasmodium sporozoites into liver stage-like forms is regulated by the RNA binding protein pumilio

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    Many eukaryotic developmental and cell fate decisions that are effected post-transcriptionally involve RNA binding proteins as regulators of translation of key mRNAs. In malaria parasites (Plasmodium spp.), the development of round, non-motile and replicating exo-erythrocytic liver stage forms from slender, motile and cell-cycle arrested sporozoites is believed to depend on environmental changes experienced during the transmission of the parasite from the mosquito vector to the vertebrate host. Here we identify a Plasmodium member of the RNA binding protein family PUF as a key regulator of this transformation. In the absence of Pumilio-2 (Puf2) sporozoites initiate EEF development inside mosquito salivary glands independently of the normal transmission-associated environmental cues. Puf2- sporozoites exhibit genome-wide transcriptional changes that result in loss of gliding motility, cell traversal ability and reduction in infectivity, and, moreover, trigger metamorphosis typical of early Plasmodium intra-hepatic development. These data demonstrate that Puf2 is a key player in regulating sporozoite developmental control, and imply that transformation of salivary gland-resident sporozoites into liver stage-like parasites is regulated by a post-transcriptional mechanism

    Perioperative infusion of low- dose of vasopressin for prevention and management of vasodilatory vasoplegic syndrome in patients undergoing coronary artery bypass grafting-A double-blind randomized study

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    Preoperative medication by inhibitors of angiotensin-converting enzyme (ACE) in coronary artery patients predisposes to vasoplegic shock early after coronary artery bypass grafting. Although in the majority of the cases this shock is mild, in some of them it appears as a situation, "intractable" to high-catecholamine dose medication. In this study we examined the possible role of prophylactic infusion of low-dose vasopressin, during and for the four hours post-bypass after cardiopulmonary bypass, in an effort to prevent this syndrome. In addition, we studied the influence of infused vasopressin on the hemodynamics of the patients, as well as on the postoperative urine-output and blood-loss. In our study 50 patients undergoing coronary artery bypass grafting were included in a blind-randomized basis. Two main criteria were used for the eligibility of patients for coronary artery bypass grafting: ejection fraction between 30-40%, and patients receiving ACE inhibitors, at least for four weeks preoperatively. The patients were randomly divided in two groups, the group A who were infused with 0.03 IU/min vasopressin and the group B who were infused with normal saline intraoperativelly and for the 4 postoperative hours. Measurements of mean artery pressure (MAP), central venous pressure (CVP), systemic vascular resistance (SVR), ejection fracture (EF), heart rate (HR), mean pulmonary artery pressure (MPAP), cardiac index (CI) and pulmonary vascular resistance (PVR) were performed before, during, and after the operation. The requirements of catecholamine support, the urine-output, the blood-loss, and the requirements in blood, plasma and platelets for the first 24 hours were included in the data collected. The incidence of vasodilatory shock was significantly lower (8% vs 20%) in group A and B respectively (p = 0,042). Generally, the mortality was 12%, exclusively deriving from group B. Postoperatively, significant higher values of MAP, CVP, SVR and EF were recorded in the patients of group A, compared to those of group B. In group A norepinephrine was necessary in fewer patients (p = 0.002) and with a lower mean dose (p = 0.0001), additive infusion of epinephrine was needed in fewer patients (p = 0.001), while both were infused for a significant shorter infusion-period (p = 0.0001). Vasopressin administration (for group A) was associated with a higher 24 hour diuresis) (0.0001)

    The R337H mutation in TP53 and breast cancer in Brazil

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    <p>Abstract</p> <p>Background</p> <p>Germline mutations in p53 are associated with the Li-Fraumeni Syndrome which is characterized by childhood cancers, including pediatric adrenal cortical carcinomas and early onset breast cancer. The high incidence of adrenal cortical carcinomas in southern Brazil is mostly attributed to the <it>R337H </it>mutation in <it>TP53</it>. The relatively high population frequency of this mutation in southern Brazil, along with the clustering of early onset breast cancer in Li-Frameni families, suggests this mutation may also be a low-penetrance breast cancer susceptibility polymorphism.</p> <p>Methods</p> <p>We undertook this study to evaluate the frequency of the <it>R337H </it>mutation in breast cancer patients from Rio de Janeiro, Brazil. <it>R337H </it>mutation status was determined in 390 unselected breast cases and 324 controls identified from clinics in Rio de Janeiro, Brazil using a PCR-based assay.</p> <p>Results</p> <p>Two of the breast cancer cases (0.5%) and none of the controls carried the mutation. Both cases had an early age at diagnosis (< 40 years old) and a family history of breast and other cancers.</p> <p>Conclusions</p> <p>These data suggest genetic screening of young onset breast cancer patients should include testing for the <it>R337H </it>mutation.</p

    Development and validation of a repharsed phase- HPLC method for simultaneous determination of rosiglitazone and glimepiride in combined dosage forms and human plasma

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    <p>Abstract</p> <p>Background</p> <p>Rosiglitazone (ROZ) and glimepiride (GLM) are antidiabetic agents used in the treatment of type 2 diabetes mellitus. A survey of the literature reveals that only one spectrophotometric method has been reported for the simultaneous determination of ROS and GLM in pharmaceutical preparations. However the reported method suffers from the low sensitivity, for this reason, our target was to develop a simple sensitive HPLC method for the simultaneous determination of ROZ and GLM in their combined dosage forms and plasma.</p> <p>Results</p> <p>A simple reversed phase high performance liquid chromatographic (RP-HPLC) method was developed and validated for the simultaneous determination of Rosiglitazone (ROS) and Glimepiride (GLM) in combined dosage forms and human plasma. The separation was achieved using a 150 mm × 4.6 mm i.d., 5 μm particle size Symmetry<sup>® </sup>C18 column. Mobile phase containing a mixture of acetonitrile and 0.02 M phosphate buffer of pH 5 (60: 40, V/V) was pumped at a flow rate of 1 mL/min. UV detection was performed at 235 nm using nicardipine as an internal standard. The method was validated for accuracy, precision, specificity, linearity, and sensitivity. The developed and validated method was successfully used for quantitative analysis of Avandaryl™ tablets. The chromatographic analysis time was approximately 7 min per sample with complete resolution of ROS (t<sub>R </sub>= 3.7 min.), GLM (t<sub>R </sub>= 4.66 min.), and nicardipine (t<sub>R</sub>, 6.37 min). Validation studieswas performed according to ICH Guidelines revealed that the proposed method is specific, rapid, reliable and reproducible. The calibration plots were linear over the concentration ranges 0.10-25 μg/mL and 0.125-12.5 μg/mL with LOD of 0.04 μg/mL for both compounds and limits of quantification 0.13 and 0.11 μg/mL for ROS and GLM respectively.</p> <p>Conclusion</p> <p>The suggested method was successfully applied for the simultaneous analysis of the studied drugs in their co-formulated tablets and human plasma. The mean percentage recoveries in Avandaryl™ tablets were 100.88 ± 1.14 and 100.31 ± 1.93 for ROS and GLM respectively. Statistical comparison of the results with those of the reference method revealed good agreement and proved that there were no significant difference in the accuracy and precision between the two methods respectively. The interference likely to be introduced from some co-administered drugs such as glibenclamide, gliclazide, metformine, pioglitazone and nateglinide was investigated.</p

    The Echinococcus canadensis (G7) genome: A key knowledge of parasitic platyhelminth human diseases

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    Background: The parasite Echinococcus canadensis (G7) (phylum Platyhelminthes, class Cestoda) is one of the causative agents of echinococcosis. Echinococcosis is a worldwide chronic zoonosis affecting humans as well as domestic and wild mammals, which has been reported as a prioritized neglected disease by the World Health Organisation. No genomic data, comparative genomic analyses or efficient therapeutic and diagnostic tools are available for this severe disease. The information presented in this study will help to understand the peculiar biological characters and to design species-specific control tools. Results: We sequenced, assembled and annotated the 115-Mb genome of E. canadensis (G7). Comparative genomic analyses using whole genome data of three Echinococcus species not only confirmed the status of E. canadensis (G7) as a separate species but also demonstrated a high nucleotide sequences divergence in relation to E. granulosus (G1). The E. canadensis (G7) genome contains 11,449 genes with a core set of 881 orthologs shared among five cestode species. Comparative genomics revealed that there are more single nucleotide polymorphisms (SNPs) between E. canadensis (G7) and E. granulosus (G1) than between E. canadensis (G7) and E. multilocularis. This result was unexpected since E. canadensis (G7) and E. granulosus (G1) were considered to belong to the species complex E. granulosus sensu lato. We described SNPs in known drug targets and metabolism genes in the E. canadensis (G7) genome. Regarding gene regulation, we analysed three particular features: CpG island distribution along the three Echinococcus genomes, DNA methylation system and small RNA pathway. The results suggest the occurrence of yet unknown gene regulation mechanisms in Echinococcus. Conclusions: This is the first work that addresses Echinococcus comparative genomics. The resources presented here will promote the study of mechanisms of parasite development as well as new tools for drug discovery. The availability of a high-quality genome assembly is critical for fully exploring the biology of a pathogenic organism. The E. canadensis (G7) genome presented in this study provides a unique opportunity to address the genetic diversity among the genus Echinococcus and its particular developmental features. At present, there is no unequivocal taxonomic classification of Echinococcus species; however, the genome-wide SNPs analysis performed here revealed the phylogenetic distance among these three Echinococcus species. Additional cestode genomes need to be sequenced to be able to resolve their phylogeny.Fil: Maldonado, Lucas Luciano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Assis, Juliana. Fundación Oswaldo Cruz; BrasilFil: Gomes Araújo, Flávio M.. Fundación Oswaldo Cruz; BrasilFil: Salim, Anna C. M.. Fundación Oswaldo Cruz; BrasilFil: Macchiaroli, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Cucher, Marcela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Camicia, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Fox, Adolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Rosenzvit, Mara Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Oliveira, Guilherme. Instituto Tecnológico Vale; Brasil. Fundación Oswaldo Cruz; BrasilFil: Kamenetzky, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentin

    Immunological imbalance between IFN-³ and IL-10 levels in the sera of patients with the cardiac form of Chagas disease

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    The immune response is crucial for protection against disease; however, immunological imbalances can lead to heart and digestive tract lesions in chagasic patients. Several studies have evaluated the cellular and humoral immune responses in chagasic patients in an attempt to correlate immunological findings with clinical forms of Chagas disease. Moreover, immunoglobulins and cytokines are important for parasitic control and are involved in lesion genesis. Here, cytokine and IgG isotype production were studied, using total epimastigote antigen on sera of chagasic patients with indeterminate (IND, n = 27) and cardiac (CARD, n = 16) forms of the disease. Samples from normal, uninfected individuals (NI, n = 30) were use as controls. The results showed that sera from both IND and CARD patients contained higher levels of Trypanosoma cruzi-specific IgG1 (IgG1) antibodies than sera from NI. No difference in IgG2 production levels was observed between NI, IND and CARD patients, nor was a difference in IL-10 and IFN-³ production detected in the sera of IND, CARD and NI patients. However, IND patients displayed a positive correlation between IL-10 and IFN-³ levels in serum, while CARD patients showed no such correlation, indicating an uncontrolled inflammatory response in CARD patients. These findings support the hypothesis that a lack of efficient regulation between IFN-³ and IL-10 productions in CARD patients may lead to cardiac immunopathology.CNP

    Disruption of the MDM2–p53 interaction strongly potentiates p53-dependent apoptosis in cisplatin-resistant human testicular carcinoma cells via the Fas/FasL pathway

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    Wild-type p53 has a major role in the response and execution of apoptosis after chemotherapy in many cancers. Although high levels of wild-type p53 and hardly any TP53 mutations are found in testicular cancer (TC), chemotherapy resistance is still observed in a significant subgroup of TC patients. In the present study, we demonstrate that p53 resides in a complex with MDM2 at higher cisplatin concentrations in cisplatin-resistant human TC cells compared with cisplatin-sensitive TC cells. Inhibition of the MDM2–p53 interaction using either Nutlin-3 or MDM2 RNA interference resulted in hyperactivation of the p53 pathway and a strong induction of apoptosis in cisplatin-sensitive and -resistant TC cells. Suppression of wild-type p53 induced resistance to Nutlin-3 in TC cells, demonstrating the key role of p53 for Nutlin-3 sensitivity. More specifically, our results indicate that p53-dependent induction of Fas membrane expression (∼threefold) and enhanced Fas/FasL interactions at the cell surface are important mechanisms of Nutlin-3-induced apoptosis in TC cells. Importantly, an analogous Fas-dependent mechanism of apoptosis upon Nutlin-3 treatment is executed in wild-type p53 expressing Hodgkin lymphoma and acute myeloid leukaemia cell lines. Finally, we demonstrate that Nutlin-3 strongly augmented cisplatin-induced apoptosis and cell kill via the Fas death receptor pathway. This effect is most pronounced in cisplatin-resistant TC cells
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