623 research outputs found

    Social and alternative banking: project selection and monitoring after the New Basel Capital Accord

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    Any economic activity calls for the exercise of moral judgement. There are some economic activities that actively promote collective benefit as a primary or secondary aim, and there are others that aim to increase the value of a firm. Investment decisions always have collective impact, but collective returns may be ignored or considered less important in company management if the objective is the maximisation of shareholder wealth. The allocative function exercised by banks in their credit activity may take this into account. Some banks nowadays focus on social profile, while others integrate the traditional approach with this new sensibility. But unfortunately banking regulations governing stability and soundness of the financial system make no mention of the social profile. The New Basel Capital Accord was an opportunity to recognise that bank's objectives may not consist only of the maximisation of shareholder wealth. But it was a missed opportunity, in that it gave advantages to traditional commercial banks and not to banks focussing on collective goals. This paper puts forward proposals for integrating the Basel II framework with profiles of collective bank credit policy. Social credit evaluation methods could help to identify those ethical banks which are more successful in meeting collective objectives. A sustainable credit appraisal methodology could have been examined by the Basel Committee and could have incentivated sustainable banking by giving it specific advantages.social banking, alternative banking, socially responsible investing, investments appraisal, Basel II, new capital accord

    Variable domain N-linked glycosylation and negative surface charge are key features of monoclonal ACPA: implications for B-cell selection

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    Autoreactive B cells have a central role in the pathogenesis of rheumatoid arthritis (RA), and recent findings have proposed that anti-citrullinated protein autoantibodies (ACPA) may be directly pathogenic. Herein, we demonstrate the frequency of variable-region glycosylation in single-cell cloned mAbs. A total of 14 ACPA mAbs were evaluated for predicted N-linked glycosylation motifs in silico and compared to 452 highly-mutated mAbs from RA patients and controls. Variable region N-linked motifs (N-X-S/T) were strikingly prevalent within ACPA (100%) compared to somatically hypermutated (SHM) RA bone marrow plasma cells (21%), and synovial plasma cells from seropositive (39%) and seronegative RA (7%). When normalized for SHM, ACPA still had significantly higher frequency of N-linked motifs compared to all studied mAbs including highly-mutated HIV broadly-neutralizing and malaria-associated mAbs. The Fab glycans of ACPA-mAbs were highly sialylated, contributed to altered charge, but did not influence antigen binding. The analysis revealed evidence of unusual B-cell selection pressure and SHM-mediated decreased in surface charge and isoelectric point in ACPA. It is still unknown how these distinct features of anti-citrulline immunity may have an impact on pathogenesis. However, it is evident that they offer selective advantages for ACPA+ B cells, possibly also through non-antigen driven mechanisms

    Therapeutic efficacy of antibodies lacking FcgammaR against lethal Dengue virus infection Is due to neutralizing potency and blocking of enhancing antibodies

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    <div><p>Dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS) are life-threatening complications following infection with one of the four serotypes of dengue virus (DENV). At present, no vaccine or antiviral therapies are available against dengue. Here, we characterized a panel of eight human or mouse-human chimeric monoclonal antibodies (MAbs) and their modified variants lacking effector function and dissected the mechanism by which some protect against antibody-enhanced lethal DENV infection. We found that neutralizing modified MAbs that recognize the fusion loop or the A strand epitopes on domains II and III of the envelope protein, respectively, act therapeutically by competing with and/or displacing enhancing antibodies. By analyzing these relationships, we developed a novel <em>in vitro</em> suppression-of-enhancement assay that predicts the ability of modified MAbs to act therapeutically against antibody-enhanced disease <em>in vivo</em>. These studies provide new insight into the biology of DENV pathogenesis and the requirements for antibodies to treat lethal DENV disease.</p> </div

    Understanding the differential hygienic behavior towards drone brood in Apis mellifera colonies from Argentina

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    Brood diseases of Apis mellifera colonies constitute a main problem of beekeeping worldwide. Worker bees display a social health mechanism that consists in detecting, uncapping and removing dead or diseased brood from the hive: the hygienic behavior (CH). These activities are induced by olfactory cues and have been described as associated to hygiene of brood parasitized by Varroa destructor. This mite have preference for drone brood, but the efficiency of CH towards their cells is significantly lower compared with cells of worker brood, being left uninspected by workers. Some authors suggest that a possible cause of the CH differences is due to the cell wax cap of drone brood (thicker than worker cells) acting as a barrier to volatile compounds and obstructing disease detection. The aims of this research were to study the differential CH towards worker and drone brood belonging to highly hygienic colonies from Argentina, and to explore the importance of drone cell wax cap as an interfering factor in the transmission of chemical signals. To this end, removal percentages of pin-killed worker and drone brood were recorded and an innovative cell wax cap exchange was implemented in three different treatments: pin-killed worker pupa with a healthy drone cell wax cap; a healthy worker pupa with a pin-killed drone cell wax cap; and a healthy worker pupa covered with a healthy drone cell wax cap (control). Results showed a greater removal towards worker cells than drone cells. For the cell wax cap exchange experiment, we found that the removal of pin-killed worker pupae covered with healthy drone cell wax cap was significantly high, while the removal of healthy worker pupae covered with pin-killed drone opercula was low. These preliminary results confirms a differential behavior between both type of brood cells and suggests that the cell wax cap of drone brood is not interfering the detection of chemical compounds from the diseased brood by worker bees, regardless the thickness. This work contributes to a better understanding of the detection activity of different types of diseased brood and provides information useful to control strategies of varroosis and other brood diseases.Fil: Dowd, D. Duggan. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Genética; ArgentinaFil: Muntaabski, Irina. Instituto Nacional de Tecnologia Agropecuaria. Centro de Investigacion En Ciencias Veterinarias y Agronomicas. Instituto de Agrobiotecnologia y Biologia Molecular. Grupo Vinculado Instituto de Genetica "ewald A. Favret" Al Iabimo | Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Pque. Centenario. Instituto de Agrobiotecnologia y Biologia Molecular. Grupo Vinculado Instituto de Genetica "ewald A. Favret" Al Iabimo.; ArgentinaFil: Russo, R. M.. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Genética; ArgentinaFil: Landi, L.. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación de Recursos Naturales. Instituto de Recursos Biológicos; ArgentinaFil: Lanzavecchia, S. B.. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Genética; ArgentinaFil: Cladera, J. L.. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Genética; ArgentinaFil: Palacio, M. A.. Instituto Nacional de Tecnología Agropecuaria; ArgentinaFil: Bedascarrabure, E.. Instituto Nacional de Tecnologia Agropecuaria. Centro de Investigacion de Agroindustria. Instituto de Ingeniería Rural.; ArgentinaFil: Scannapieco, Alejandra Carla. Instituto Nacional de Tecnologia Agropecuaria. Centro de Investigacion En Ciencias Veterinarias y Agronomicas. Instituto de Agrobiotecnologia y Biologia Molecular. Grupo Vinculado Instituto de Genetica "ewald A. Favret" Al Iabimo | Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Pque. Centenario. Instituto de Agrobiotecnologia y Biologia Molecular. Grupo Vinculado Instituto de Genetica "ewald A. Favret" Al Iabimo.; ArgentinaFil: Liendo, María Clara. Instituto Nacional de Tecnologia Agropecuaria. Centro de Investigacion En Ciencias Veterinarias y Agronomicas. Instituto de Agrobiotecnologia y Biologia Molecular. Grupo Vinculado Instituto de Genetica "ewald A. Favret" Al Iabimo | Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Pque. Centenario. Instituto de Agrobiotecnologia y Biologia Molecular. Grupo Vinculado Instituto de Genetica "ewald A. Favret" Al Iabimo.; Argentina46th Apimondia International Apicultural Congress: Beekeeping together within agricultureQuébecCanadáInternational Federation of Beekeepers' AssociationsCanadian Honey Counci

    Emerging Approaches to DNA Data Storage: Challenges and Prospects

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    With the total amount of worldwide data skyrocketing, the global data storage demand is predicted to grow to 1.75 × 1014GB by 2025. Traditional storage methods have difficulties keeping pace given that current storage media have a maximum density of 103GB/mm3. As such, data production will far exceed the capacity of currently available storage methods. The costs of maintaining and transferring data, as well as the limited lifespans and significant data losses associated with current technologies also demand advanced solutions for information storage. Nature offers a powerful alternative through the storage of information that defines living organisms in unique orders of four bases (A, T, C, G) located in molecules called deoxyribonucleic acid (DNA). DNA molecules as information carriers have many advantages over traditional storage media. Their high storage density, potentially low maintenance cost, ease of synthesis, and chemical modification make them an ideal alternative for information storage. To this end, rapid progress has been made over the past decade by exploiting user-defined DNA materials to encode information. In this review, we discuss the most recent advances of DNA-based data storage with a major focus on the challenges that remain in this promising field, including the current intrinsic low speed in data writing and reading and the high cost per byte stored. Alternatively, data storage relying on DNA nanostructures (as opposed to DNA sequence) as well as on other combinations of nanomaterials and biomolecules are proposed with promising technological and economic advantages. In summarizing the advances that have been made and underlining the challenges that remain, we provide a roadmap for the ongoing research in this rapidly growing field, which will enable the development of technological solutions to the global demand for superior storage methodologies

    Exceptionally potent human monoclonal antibodies are effective for prophylaxis and therapy of tetanus in mice

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    Human monoclonal antibodies were used here to study the mechanism of neuron intoxication by tetanus neurotoxin and to evaluate them as a safe preventive and therapeutic substitute of hyperimmune sera for tetanus in mice. By screening memory B cells of immune donors, we selected two monoclonal antibodies specific for tetanus neurotoxin with exceptionally high neutralizing activities, which were extensively characterized both structurally and functionally. We found that these antibodies interfere with the binding and translocation of the neurotoxin into neurons by interacting with two epitopes, whose definition pinpoints crucial events in the cellular pathogenesis of tetanus. This information explains the unprecedented neutralization ability of these antibodies, which were found to be exceptionally potent in preventing experimental tetanus when injected in mice long before the neurotoxin. Moreover, their Fab derivatives neutralized tetanus neurotoxin in post-exposure experiments, suggesting their potential therapeutic use via intrathecal injection. As such, these human monoclonal antibodies, as well as their Fab derivatives, meet all requirements for being considered for prophylaxis and therapy of human tetanus and are ready for clinical trials

    Longitudinal landscapes of serum antibody repertoires after influenza infection and vaccination

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    Vaccination is the most effective means of infectious disease prevention. Despite its success, however, we still lack a clear understanding of vaccine responses in humans. For example, influenza vaccines still leave a large fraction of population vulnerable. Over the past decade, single B-cell analysis and next-generation sequencing (NGS) technologies have become invaluable tools for studying the antibody repertoire to influenza. Such studies have led to discoveries of broadly-neutralizing antibodies (bNAbs), which can neutralize across multiple strains of influenza virus, promoting the notion of designing a universal vaccine that will elicit such antibodies. One of such isolated bNAbs, called FI6, showed remarkable ability to neutralize all of the influenza A virus strains through targeting the conserved epitope in the stem of hemagglutinin (HA). However, it remains unclear whether such bNAbs actually play a role in conferring protection against influenza since antibody proteins (not B-cells) need to circulate at physiologically relevant concentrations in serum to have implications in protection. Using high-resolution proteomics coupled with NGS, we quantitatively determined the serological antibody repertoire to CA09 HA (H1) at the individual clonotype-level in a donor (whom FI6 was isolated from) following influenza infection (in 2010 with pandemic CA09) and vaccination across five years (2010-2014 with seasonal flu vaccine). We analyzed the temporal changes of head-targeting and stem-binding antibodies, illustrating the gradual increase of stem-targeting antibodies following repeated exposures to CA09 HA. Following vaccination in 2014, \u3e60% of the repertoire consisted of one single clonotype of stem-binding antibody that was present at very low abundance in 2010. Our data demonstrate that the repetitive exposure to influenza skews the serological repertoire toward antibodies that target conserved epitopes, and these antibodies continue to be boosted every time the same epitopes are encountered. Once elicited, stem-binding antibodies displayed a tendency to persist in serum across multiple years while head-specific antibodies decayed quicker. The differential longevity of stem-binding and head-specific antibodies presented here has direct implications for the design of the future universal vaccine

    watch dog detector for beam diagnostic in hadrontherapy application

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    The "Watch Dog" is a beam monitor designed for medical accelerators, that will be installed at the end of the CNAO (Centro Nazionale di Adroterapia Oncologica) extraction lines. Its main goal is to achieve a real time monitoring of the beam position during patient treatments; the system can generate an interlock signal in case the measured quantity is out of the nominal range. In this paper the Watch Dog is described, and preliminary tests are presented

    SARS-like WIV1-CoV poised for human emergence

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    The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome (MERS)-CoV highlights the continued risk of cross-species transmission leading to epidemic disease. This manuscript describes efforts to extend surveillance beyond sequence analysis, constructing chimeric and full-length zoonotic coronaviruses to evaluate emergence potential. Focusing on SARS-like virus sequences isolated from Chinese horseshoe bats, the results indicate a significant threat posed by WIV1-CoV. Both full-length and chimeric WIV1-CoV readily replicated efficiently in human airway cultures and in vivo, suggesting capability of direct transmission to humans. In addition, while monoclonal antibody treatments prove effective, the SARS-based vaccine approach failed to confer protection. Together, the study indicates an ongoing threat posed by WIV1-related viruses and the need for continued study and surveillance
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