501 research outputs found

    The stubborn non-probabilist : "negation incoherence" and a new way to block the Dutch Book argument

    Get PDF
    We rigorously specify the class of nonprobabilistic agents which are, we argue, immune to the classical Dutch Book argument. We also discuss the notion of expected value used in the argument as well as sketch future research connecting our results to those concerning incoherence measures

    Improving corporate governance in state-owned corporations in China: which way forward?

    Get PDF
    This article discusses corporate governance in China. It outlines the basic agency problem in Chinese listed companies and questions the effectiveness of the current mechanisms employed to improve their standards of governance. Importantly, it considers alternative means through which corporate practice in China can be brought into line with international expectations and stresses the urgency with which this task must be tackled. It concludes that regulators in China must construct a corporate governance model which is compatible with its domestic setting and not rush to adopt governance initiatives modelled on those in cultures which are fundamentally different in the hope of also reproducing their success

    Augmented TLR2 Expression on Monocytes in both Human Kawasaki Disease and a Mouse Model of Coronary Arteritis

    Get PDF
    BACKGROUND: Kawasaki disease (KD) of unknown immunopathogenesis is an acute febrile systemic vasculitis and the leading cause of acquired heart diseases in childhood. To search for a better strategy for the prevention and treatment of KD, this study compared and validated human KD immunopathogenesis in a mouse model of Lactobacillus casei cell wall extract (LCWE)-induced coronary arteritis. METHODS: Recruited subjects fulfilled the criteria of KD and were admitted for intravenous gamma globulin (IVIG) treatment at the Kaohsiung Chang Gung Memorial Hospital from 2001 to 2009. Blood samples from KD patients were collected before and after IVIG treatment, and cardiovascular abnormalities were examined by transthoracic echocardiography. Wild-type male BALB/c mice (4-week-old) were intraperitoneally injected with LCWE (1 mg/mL) to induce coronary arteritis. The induced immune response in mice was examined on days 1, 3, 7, and 14 post injections, and histopathology studies were performed on days 7 and 14. RESULTS: Both human KD patients and LCWE-treated mice developed coronary arteritis, myocarditis, valvulitis, and pericarditis, as well as elevated plasma levels of interleukin (IL)-2, IL-6, IL-10, monocyte chemoattractant protein (MCP)-1, and tumor necrosis factor (TNF)-α in acute phase. Most of these proinflammatory cytokines declined to normal levels in mice, whereas normal levels were achieved in patients only after IVIG treatment, with a few exceptions. Toll-like receptor (TLR)-2, but not TLR4 surface enhancement on circulating CD14+ monocytes, was augmented in KD patients before IVIG treatment and in LCWE-treated mice, which declined in patients after IVIG treatment. CONCLUSION: This result suggests that that not only TLR2 augmentation on CD14+ monocytes might be an inflammatory marker for both human KD patients and LCWE-induced CAL mouse model but also this model is feasible for studying therapeutic strategies of coronary arteritis in human KD by modulating TLR2-mediated immune activation on CD14+ monocytes

    DNA topoisomerases participate in fragility of the oncogene RET

    Get PDF
    Fragile site breakage was previously shown to result in rearrangement of the RET oncogene, resembling the rearrangements found in thyroid cancer. Common fragile sites are specific regions of the genome with a high susceptibility to DNA breakage under conditions that partially inhibit DNA replication, and often coincide with genes deleted, amplified, or rearranged in cancer. While a substantial amount of work has been performed investigating DNA repair and cell cycle checkpoint proteins vital for maintaining stability at fragile sites, little is known about the initial events leading to DNA breakage at these sites. The purpose of this study was to investigate these initial events through the detection of aphidicolin (APH)-induced DNA breakage within the RET oncogene, in which 144 APHinduced DNA breakpoints were mapped on the nucleotide level in human thyroid cells within intron 11 of RET, the breakpoint cluster region found in patients. These breakpoints were located at or near DNA topoisomerase I and/or II predicted cleavage sites, as well as at DNA secondary structural features recognized and preferentially cleaved by DNA topoisomerases I and II. Co-treatment of thyroid cells with APH and the topoisomerase catalytic inhibitors, betulinic acid and merbarone, significantly decreased APH-induced fragile site breakage within RET intron 11 and within the common fragile site FRA3B. These data demonstrate that DNA topoisomerases I and II are involved in initiating APH-induced common fragile site breakage at RET, and may engage the recognition of DNA secondary structures formed during perturbed DNA replication

    Temperature, recreational fishing and diapause egg connections : dispersal of spiny water fleas (Bythotrephes longimanus)

    Get PDF
    © The Author(s), 2011. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License. The definitive version was published in Biological Invasions 13 (2011): 2513-2531, doi:10.1007/s10530-011-0078-8.The spiny water flea (Bythotrephes longimanus) is spreading from Great Lakes coastal waters into northern inland lakes within a northern temperature-defined latitudinal band. Colonization of Great Lakes coastal embayments is assisted by winds and seiche surges, yet rapid inland expansion across the northern states comes through an overland process. The lack of invasions at Isle Royale National Park contrasts with rapid expansion on the nearby Keweenaw Peninsula. Both regions have comparable geology, lake density, and fauna, but differ in recreational fishing boat access, visitation, and containment measures. Tail spines protect Bythotrephes against young of the year, but not larger fish, yet the unusual thick-shelled diapausing eggs can pass through fish guts in viable condition. Sediment traps illustrate how fish spread diapausing eggs across lakes in fecal pellets. Trillions of diapausing eggs are produced per year in Lake Michigan and billions per year in Lake Michigamme, a large inland lake. Dispersal by recreational fishing is linked to use of baitfish, diapausing eggs defecated into live wells and bait buckets, and Bythothephes snagged on fishing line, anchor ropes, and minnow seines. Relatively simple measures, such as on-site rinsing of live wells, restricting transfer of certain baitfish species, or holding baitfish for 24 h (defecation period), should greatly reduce dispersal.Study of Lakes Superior and Michigan was funded from NSF OCE-9726680 and OCE-9712872 to W.C.K., OCE-9712889 to J. Churchill. Geographic survey sampling and Park studies in the national parks during 2008-2010 were funded by a grant from the National Park Service Natural Resource Preservation Program GLNF CESU Task Agreement No. J6067080012

    Saliva levels of Abeta1-42 as potential biomarker of Alzheimer's disease: a pilot study

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Simple, non-invasive tests for early detection of degenerative dementia by use of biomarkers are urgently required. However, up to the present, no validated extracerebral diagnostic markers for the early diagnosis of Alzheimer disease (AD) are available. The clinical diagnosis of probable AD is made with around 90% accuracy using modern clinical, neuropsychological and imaging methods. A biochemical marker that would support the clinical diagnosis and distinguish AD from other causes of dementia would therefore be of great value as a screening test. A total of 126 samples were obtained from subjects with AD, and age-sex-matched controls. Additionally, 51 Parkinson's disease (PD) patients were used as an example of another neurodegenerative disorder. We analyzed saliva and plasma levels of β amyloid (Aβ) using a highly sensitive ELISA kit.</p> <p>Results</p> <p>We found a small but statistically significant increase in saliva Aβ<sub>42 </sub>levels in mild AD patients. In addition, there were not differences in saliva concentration of Aβ<sub>42 </sub>between patients with PD and healthy controls. Saliva Aβ<sub>40 </sub>expression was unchanged within all the studied sample. The association between saliva Aβ<sub>42 </sub>levels and AD was independent of established risk factors, including age or Apo E, but was dependent on sex and functional capacity.</p> <p>Conclusions</p> <p>We suggest that saliva Aβ<sub>42 </sub>levels could be considered a potential peripheral marker of AD and help discrimination from other types of neurodegenerative disorders. We propose a new and promising biomarker for early AD.</p

    Mesozoic fossils (>145 Mya) suggest the antiquity of the subgenera of Daphnia and their coevolution with chaoborid predators

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>The timescale of the origins of <it>Daphnia </it>O. F. Mueller (Crustacea: Cladocera) remains controversial. The origin of the two main subgenera has been associated with the breakup of the supercontinent Pangaea. This vicariance hypothesis is supported by reciprocal monophyly, present day associations with the former Gondwanaland and Laurasia regions, and mitochondrial DNA divergence estimates. However, previous multilocus nuclear DNA sequence divergence estimates at < 10 Million years are inconsistent with the breakup of Pangaea. We examined new and existing cladoceran fossils from a Mesozoic Mongolian site, in hopes of gaining insights into the timescale of the evolution of <it>Daphnia</it>.</p> <p>Results</p> <p>We describe new fossils of ephippia from the Khotont site in Mongolia associated with the Jurassic-Cretaceous boundary (about 145 MYA) that are morphologically similar to several modern genera of the family Daphniidae, including the two major subgenera of <it>Daphnia</it>, i.e., <it>Daphnia </it>s. str. and <it>Ctenodaphnia</it>. The daphniid fossils co-occurred with fossils of the predaceous phantom midge (Chaoboridae).</p> <p>Conclusions</p> <p>Our findings indicate that the main subgenera of <it>Daphnia </it>are likely much older than previously known from fossils (at least 100 MY older) or from nuclear DNA estimates of divergence. The results showing co-occurrence of the main subgenera far from the presumed Laurasia/Gondwanaland dispersal barrier shortly after formation suggests that vicariance from the breakup of Pangaea is an unlikely explanation for the origin of the main subgenera. The fossil impressions also reveal that the coevolution of a dipteran predator (Chaoboridae) with the subgenus <it>Daphnia </it>is much older than previously known -- since the Mesozoic.</p

    Better Few than Hungry: Flexible Feeding Ecology of Collared Lemurs Eulemur collaris in Littoral Forest Fragments

    Get PDF
    Frugivorous primates are known to encounter many problems to cope with habitat degradation, due to the fluctuating spatial and temporal distribution of their food resources. Since lemur communities evolved strategies to deal with periods of food scarcity, these primates are expected to be naturally adapted to fluctuating ecological conditions and to tolerate a certain degree of habitat changes. However, behavioral and ecological strategies adopted by frugivorous lemurs to survive in secondary habitats have been little investigated. Here, we compared the behavioral ecology of collared lemurs (Eulemur collaris) in a degraded fragment of littoral forest of south-east Madagascar, Mandena, with that of their conspecifics in a more intact habitat, Sainte Luce.Lemur groups in Mandena and in Sainte Luce were censused in 2004/2007 and in 2000, respectively. Data were collected via instantaneous sampling on five lemur groups totaling 1,698 observation hours. The Shannon index was used to determine dietary diversity and nutritional analyses were conducted to assess food quality. All feeding trees were identified and measured, and ranging areas determined via the minimum convex polygon. In the degraded area lemurs were able to modify several aspects of their feeding strategies by decreasing group size and by increasing feeding time, ranging areas, and number of feeding trees. The above strategies were apparently able to counteract a clear reduction in both food quality and size of feeding trees.Our findings indicate that collared lemurs in littoral forest fragments modified their behavior to cope with the pressures of fluctuating resource availability. The observed flexibility is likely to be an adaptation to Malagasy rainforests, which are known to undergo periods of fruit scarcity and low productivity. These results should be carefully considered when relocating lemurs or when selecting suitable areas for their conservation

    p53 mutations in human cutaneous melanoma correlate with sun exposure but are not always involved in melanomagenesis

    Get PDF
    In melanoma, the relationship between sun exposure and the origin of mutations in either the N-ras oncogene or the p53 tumour-suppressor gene is not as clear as in other types of skin cancer. We have previously shown that mutations in the N-ras gene occur more frequently in melanomas originating from sun-exposed body sites, indicating that these mutations are UV induced. To investigate whether sun exposure also affects p53 in melanoma, we analysed 81 melanoma specimens for mutations in the p53 gene. The mutation frequency is higher than thus far reported: 17 specimens (21%) harbour one or more p53 mutations. Strikingly, 17 out of 22 mutations in p53 are of the C:G to T:A or CC:GG to TT:AA transitional type, strongly suggesting an aetiology involving UV exposure. Interestingly, the p53 mutation frequency in metastases was much lower than in primary tumours. In the case of metastases, a role for sun exposure was indicated by the finding that the mutations are present exclusively in skin metastases and not in internal metastases. Together with a relatively frequent occurrence of silent third-base pair mutations in primary melanomas, this indicates that the p53 mutations, at least in these tumours, have not contributed to melanomagenesis and may have originated after establishment of the primary tumour. 1999 Cancer Research Campaig
    corecore