Formerly bile-farmed bears as a model of accelerated ageing

Bear bile-farming is common in East and Southeast Asia and this farming practice often results in irreversible health outcomes for the animals. We studied long-term effects of chronic bacterial and sterile hepatobiliary inflammation in 42 Asiatic black bears (Ursus thibetanus) rescued from Vietnamese bile farms. The bears were examined under anesthesia at least twice as part of essential medical interventions. All bears were diagnosed with chronic low-grade sterile or bacterial hepatobiliary inflammation along with pathologies from other systems. Our main finding was that the chronic low-grade inflammatory environment associated with bile extraction in conjunction with the suboptimal living conditions on the farms promoted and accelerated the development of age-related pathologies such as chronic kidney disease, obese sarcopenia, cardiovascular remodeling, and degenerative joint disease. Through a biomimetic approach, we identified similarities with inflammation related to premature aging in humans and found significant deviations from the healthy ursid phenotype. The pathological parallels with inflammageing and immuno-senescence induced conditions in humans suggest that bile-farmed bears may serve as animal models to investigate pathophysiology and deleterious effects of lifestyle-related diseases

Different Pattern of Immunoglobulin Gene Usage by HIV-1 Compared to Non-HIV-1 Antibodies Derived from the Same Infected Subject

A biased usage of immunoglobulin (Ig) genes is observed in human anti-HIV-1 monoclonal antibodies (mAbs) resulting probably from compensation to reduced usage of the VH3 family genes, while the other alternative suggests that this bias usage is due to antigen requirements. If the antigen structure is responsible for the preferential usage of particular Ig genes, it may have certain implications for HIV vaccine development by the targeting of particular Ig gene-encoded B cell receptors to induce neutralizing anti-HIV-1 antibodies. To address this issue, we have produced HIV-1 specific and non-HIV-1 mAbs from an infected individual and analyzed the Ig gene usage. Green-fluorescence labeled virus-like particles (VLP) expressing HIV-1 envelope (Env) proteins of JRFL and BaL and control VLPs (without Env) were used to select single B cells for the production of 68 recombinant mAbs. Ten of these mAbs were HIV-1 Env specific with neutralizing activity against V3 and the CD4 binding site, as well as non-neutralizing mAbs to gp41. The remaining 58 mAbs were non-HIV-1 Env mAbs with undefined specificities. Analysis revealed that biased usage of Ig genes was restricted only to anti-HIV-1 but not to non-HIV-1 mAbs. The VH1 family genes were dominantly used, followed by VH3, VH4, and VH5 among anti-HIV-1 mAbs, while non-HIV-1 specific mAbs preferentially used VH3 family genes, followed by VH4, VH1 and VH5 families in a pattern identical to Abs derived from healthy individuals. This observation suggests that the biased usage of Ig genes by anti-HIV-1 mAbs is driven by structural requirements of the virus antigens rather than by compensation to any depletion of VH3 B cells due to autoreactive mechanisms, according to the gp120 superantigen hypothesis

Pre-Clinical Evaluation of a 213Bi-Labeled 2556 Antibody to HIV-1 gp41 Glycoprotein in HIV-1 Mouse Models as a Reagent for HIV Eradication

Any strategy for curing HIV infection must include a method to eliminate viral-infected cells. Based on our earlier proof-of-principle results targeting HIV-1 infected cells with radiolabeled antibody (mAb) to gp41 viral antigen, we embarked on identifying a suitable candidate mAb for preclinical development.Among the several human mAbs to gp41 tested, mAb 2556 was found to have high affinity, reactivity with multimeric forms of gp41 present on both the surface of virus particles and cells expressing HIV-1 Env, and recognition of a highly conserved epitope of gp41 shared by all HIV-1 subtypes. Also, mAb 2556 was the best in competition with HIV-1+ serum antibodies, which is an extremely important consideration for efficacy in the treatment of HIV patients. When radiolabeled with alpha-emitting radionuclide 213-Bismuth ((213)Bi) - (213)Bi-2556 efficiently and specifically killed ACH-2 human lymphocytes chronically infected with HIV-1, and HIV-1 infected human peripheral blood mononuclear cells (hPBMCs). The number of binding sites for (213)Bi-2556 on the surface of the infected cells was >10(6). The in vivo experiments were performed in two HIV-1 mouse models--splenic and intraperitoneal. In both models, the decrease in HIV-1 infected hPBMCs from the spleens and peritoneum, respectively, was dose-dependent with the most pronounced killing of hPBMCs observed in the 100 µCi (213)Bi-2556 group (P = 0.01). Measurement of the blood platelet counts and gross pathology of the treated mice demonstrated the lack of toxicity for (213)Bi-2556.We describe the preclinical development of a novel radiolabeled mAb reagent that could potentially be part of an HIV eradication strategy that is ready for translation into the clinic as the next step in its development. As viral antigens are very different from "self" human antigens - this approach promises high selectivity, increased efficacy and low toxicity, especially in comparison to immunotoxins

The Role of Information and Financial Reporting in Corporate Governance and Debt Contracting

We review recent literature on the role of financial reporting transparency in reducing governance-related agency conflicts among managers, directors, and shareholders, as well as in reducing agency conflicts between shareholders and creditors, and offer researchers some suggested avenues for future research. Key themes include the endogenous nature of debt contracts and governance mechanisms with respect to information asymmetry between contracting parties, the heterogeneous nature of the informational demands of contracting parties, and the heterogeneous nature of the resulting governance and debt contracts. We also emphasize the role of a commitment to financial reporting transparency in facilitating informal multiperiod contracts among managers, directors, shareholders, and creditors

Management Forecast Credibility and Underreaction to News

In this paper, we first document evidence of underreaction to management forecast news. We then hypothesize that the credibility of the forecast influences the magnitude of this underreaction. Relying on evidence that more credible forecasts are associated with a larger reaction in the short window around the management forecasts and a smaller post-management forecast drift in returns, we show that the magnitude of the underreaction is smaller for firms that provide more credible forecasts. Our paper contributes to the literature by providing out-of-sample evidence of the drift in returns documented in the post-earnings-announcement drift literature, with the credibility of the news being one explanation for the phenomenon.Sloan School of ManagementWharton SchoolDeloitte Foundatio

Willow supply strategies to energy plants

The main objective of this study was to develop minimum cost supply strategies for willow to energy plants (two plant sizes: 0.5 and 30 MWe, two energy conversion technologies: combustion and gasification). Time span between harvest and energy conversion varied from 1 to 12 months. For a realistic comparison, different supply chains were based on the same initial characteristics (i.e., moisture content 50% wb at harvest) and final fuel specifications at the energy plant (moisture content 20% wb, particle size chips or chunks). Cost calculations were based on the integral cost calculation method and were presented for all process steps. The main conclusion was that the time span between harvest and energy conversion and the size and conversion technology of the energy plant largely influence the design of the supply chain and consequently the supply costs. The fuel supply costs ranged from 17.6 to 26.1 ECU/t DM (where DM stands for oven dry matter) or 0.010 to 0.023 ECU/kWh. The cost reduction which could be achieved by choosing the minimum cost chain design could be as high as 45% or 14.4 ECU/t DM. Generally, the strategy of minimum costs for supply of fuel to an energy plant running all year round on willow was as follows: … for farmers who should supply their willow within 6 months after harvest: harvest as chips, forced drying at the farm and transport (if necessary); … for farmers who should supply their willow beyond 6 months after harvest: harvest as chunks or stems, natural drying near the willow field, transport (if necessary) and central chipping (if applicable)

Drying characteristics of willow chips and stems

In supply chains of willow (Salix viminalis) biomass to energy plants, drying is advisable in order to enable safe long-term storage, increase boiler efficiency and reduce gaseous emissions. To gain insight into the drying process, drying characteristics of willow chips and stems were investigated experimentally in a drying installation. The drying process was modelled with a diffusion equation. The effective water diffusivity Deffwas assumed to be a simple algebraic function of the dimensionless moisture concentration m:Deff =D0ma, with D0being the initial diffusivity, and a an empirical exponent. Drying of a chip and of a stem without bark could be successfully described with a diffusion equation for a plane sheet and a cylinder, respectively. Drying of a stem with bark could be successfully described as drying of a stem without bark surrounded by a thin layer (bark) with a much lower diffusivity. Compared to a chip, a stem without bark dried approximately 10 times slower from fresh state to equilibrium moisture content, mainly due to the larger diffusion distance of the stem. A stem with bark dried approximately 10 times slower than a stem without bark due to the low diffusivity of the bark

On optimisation of agri chains by dynamic programming

A methodology for optimisation of agri chains by dynamic programming (DP) is presented which explicitly deals with the appearance and quality of products. In agri chains, a product can be characterised by two types of states, namely appearance and quality states. Appearance states are influenced by handling actions. Quality states are influenced by processing, transportation and storage actions. The concept of chain optimisation by DP is elaborated. Chain optimisation refers to the construction of optimal routes defining which actors in the chain should perform which actions at which process conditions at minimum integral costs. Models describing quality development of a product as a function of the process conditions can be included into the DP methodology. The DP methodology has been implemented into a software tool and is illustrated with a case for an agri chain of willow biomass fuel to an energy plant. (C) 2002 Elsevier Science B.V. All rights reserved