During future, large scale CO2 geological storage in saline aquifers, fluid pressure is expected to rise as a consequence of CO2 injection, but the pressure build up will have to stay below specified ...values to ensure a safe and long term containment of the CO2 in the storage site. The pressure build up is the result of two different effects. The first effect is a local overpressure around the injectors, which is due to the high CO2 velocities around the injectors, and which can be mitigated by adding CO2 injectors. The second effect is a regional scale pressure build up that will take place if the storage aquifer is closed or if the formation water that flows away from the pressurised area is not large enough to compensate volumetrically the CO2 injection. This second effect cannot be mitigated by adding additional injectors. In the first section of this paper, we review some major global and regional assessments of CO2 storage capacities in deep saline aquifers, in term of mass and storage efficiency. These storage capacities are primarily based on a volumetric approach: storage capacity is the volumetric sum of the CO2 that can be stored through various trapping mechanisms. We then discuss in Section 2 storage efficiencies derived from a pressure build up approach, as stated in the CO2STORE final report (Chadwick A. et al. (eds) (2008) Best Practice for the Storage of CO2 in Saline Aquifers, Observations and Guidelines from the SACS and CO2STORE Projects, Keyworth, Nottingham, BGS Occasional Publication No. 14) and detailed by Van der Meer and Egberts (van der Meer L.G.H., Egberts P.J.P. (2008) A General Method for Calculating Subsurface CO2 Storage Capacity, OTC Paper 19309, presented at the OTC Conference held in Houston, Texas, USA, 5-8 May). A quantitative range of such storage efficiency is presented, based on a review of orders of magnitudes of pore and water compressibilities and allowable pressure increase. To illustrate the relevance of this approach, it is applied to the Utsira aquifer in the North Sea. In Sections 3 and 4, we discuss possible effects that may lead to higher or lower CO2 storage efficiencies. Water production appears to be an attractive strategy in order to address regional scale pressure build up and, consequently, to increase the storage capacity. Following these quantitative applications, we recommend to evaluate the CO2 storage capacities of an aquifer, during a screening study for ranking purposes, using a pressure and compressibility formula rather than a volumetric approach, in order to avoid large overestimation of the aquifer storage capacity. Further studies are naturally required to validate the storage capacities at a qualification stage.
Au cours d’opérations à grande échelle de stockage géologique de CO2 dans des aquifères salins, la pression des fluides dans les formations va augmenter, mais devra rester sous des limites définies par des contraintes d’intégrité des sites de stockage. La hausse de pression est la conséquence de deux effets distincts. Premièrement, la pression augmente localement autour des injecteurs de CO2 pour permettre l’injection du CO2 dans les nappes. Cet effet peut être contrôlé en ajoutant des injecteurs de CO2. Deuxièmement, la pression va augmenter à une échelle régionale, soit parce que l’aquifère est fermée, soit parce que le flux d’eau s’échappant de la zone pressurisée ne compense pas volumétriquement le CO2 injecté. Ce second effet ne peut pas être maîtrisé en augmentant le nombre d’injecteurs. Dans la première section du papier, nous discutons sur des évaluations mondiales ou régionales de capacités de stockage du CO2 en aquifère, tant du point de vue de la quantité que de l’efficacité de stockage. Ces capacités sont principalement basées sur une approche volumétrique : la capacité de stockage est la somme des volumes de CO2 pouvant être stockés par différents processus de piégeage. Dans la seconde section, nous présentons les efficacités de stockage calculées par une approche en pression, telles qu’établies dans le rapport final du projet CO2STORE (Chadwick A. et al. (eds) (2008) Best Practice for the Storage of CO2 in Saline Aquifers, Observations and Guidelines from the SACS and CO2STORE Projects, Keyworth, Nottingham, BGS Occasional Publication No. 14) et explicitées par Van der Meer et Egberts (van der Meer L.G.H., Egberts P.J.P. (2008) A General Method for Calculating Subsurface CO2 Storage Capacity, OTC Paper 19309, presented at the OTC Conference held in Houston, Texas, USA, 5-8 May). Une gamme d’efficacités de stockage est présentée, basée sur une revue des ordres de grandeur des compressibilités de pore et de l’eau de formation et des augmentations de pression admissibles. Pour illustrer l’importance de cette approche, elle est appliquée au cas de l’Utsira, dans la Mer du Nord. Dans les sections 3 et 4, les effets pouvant conduire à une augmentation ou une réduction des efficacités de stockage sont discutés. L’extraction d’eau de formation apparaît être une stratégie attractive pour relaxer les surpressions lors de stockage et donc augmenter la capacité de stockage d’un aquifère. En conséquence des applications numériques effectuées, il est recommandé, lors d’études de screening sur les capacités de stockage de nappes, d’établir la capacité de stockage sur la base d’une formule de compressibilité et de pressurisation plutôt que par une approche volumétrique intégrant différents processus de piégeage local du CO2. Ceci doit permettre d’éviter une surestimation importante des capacités de stockage. Des études complémentaires sont ensuite nécessaires pour valider les capacités de stockage lors d’une phase de qualification.
Multiorgan spread and pathogenesis of influenza infection with three human influenza A viruses was studied in mice. Mouse-adapted viruses A/Dunedin/4/73(H3N2), A/Mississippi/1/85(H3N2), and ...A/PR/8/34(H1N1) differed considerably in virulence (p.f.u./LD
50
): 79,000 p.f.u. for Dunedin, 5,000 p.f.u. for Mississippi, and 65 p.f.u. for PR/8, which qualified Dunedin as low virulent, Mississippi as intermediate, and PR/8 as highly virulent. All three viruses were detected in lungs, heart, and thymus by cultivation and RT-PCR. Moreover, vRNA of all viruses was found in liver and spleen, of Dunedin and PR/8 also in kidneys and that of Dunedin and Mississippi in blood. Only vRNA of Dunedin was demonstrated in brain. Lung damage accompanied by histopathological changes and thymus reduction were most extensive after infection with the highly virulent virus PR/8. We assume that the ability to spread to multiple organs may be a more common property of influenza viruses in mammalian hosts than previously believed.
Axillary lymph node dissection (ALND) has traditionally been the principal method for evaluating axillary lymph node status in breast cancer patients. In the past decades sentinel lymph nodes biopsy ...after lymphatic mapping has been used to stage the disease. The majority of sentinel lymph nodes (SLN) positive patients do not have additional metastases in non-sentinel nodes (non-SLN) after additional ALND. These patients are exposed to the morbidity of ALND without any benefit from additional axillary clearence. In the present study we would like to asses the criteria for selecting those patients, who have high risk for non-SLN metastases in the axilla in cases of positive SLN. In this retrospective analysis, clinical and pathologic data from 163 patients who underwent SLN biopsy followed by ALND were collected. Following clinical and pathological characteristics were analyzed to predict the likehood of non-SLN metastases: age, staging, histologic type and grading of the tumors, hormonal receptor status, HER-2 receptor status and Ki-67 protein, angioinvasion, metastases in SLN and non-SLN. Relative frequencies of individual characteristics between sample groups were statistically tested by Chi-square test at significance level p=0.5, when sample sizes in groups were small (≤5) by Fisher´s exact test. Metastasis in SLN were present in 67 (41%) of patients, 48 patients (29,4%) had metastasis also in non-SLN. The ratio between non-SLN positive / non-SLN negative lymph nodes in patients with positive SLN increases with the stage of the disease, the difference between values for the pT1c and pT2 stadium was statistically significant (p = 0.0296). The same applies to grading, but the differences were not significant (p>0.05). We could not find significant differences for angioinvasion of the tumor, probably for small number of patients with angioinvasion (p>0.05).Only the stage of the tumor was shown to be significant in predicting the metastasis in non-SLN in our group of breast cancer patients with positive SLN Nearly 80% of the patients of 70 years and older displayed no benefit from axillary staging, because of negative SLN as well as non-SLN, although thanks to the small sample size this was not a statistically significant result. Furthermore, current recommendations for axillary staging in breast cancer patients are discussed.
Avian influenza A viruses (IAVs) are able to overcome the interspecies barrier and adapt to the new non-avian host. The process of adaptation requires the adaptive changes of IAV genome resulting in ...amino acid substitutions. The aim of this work was the description of amino acid substitutions in avian influenza A viruses (IAVs) occurring during their adaptation to equine host. Today, viruses of the equine influenza H3N8 subtype, first isolated in 1963, represent a single genetic lineage of IAV causing a respiratory disease in horses. We compared the amino acid sequences of the conserved proteins PB2, PB1, PA, NP, M1, M2, NS1 and NEP of equine influenza H3N8 subtype IAV with sequences of avian viruses, both available in the NCBI's Influenza Virus Resource Database. The amino acid substitutions persisting in equine IAV isolates and occurring in avian IAV at f both hosts.
Influenza A viruses (IAVs) cause acute respiratory infections in humans against which an effective prevention has not yet been developed due to their high variability and broad host specificity. The ...permanent threat of arising new influenza pandemic is represented by avian viruses which after their interspecies transmission can cause a disease with a devastating impact on humans lacking the specific immunity. Since the current vaccines inducing virus-neutralizing (VN) antibodies are targeted at a variable globular part of hemagglutinin (HA), their efficacy is limited and they need permanent updating. On the other hand, conserved IAV antigens such as proton channel M2, membrane protein M1 or nucleoprotein (NP) do not induce VN antibodies, but they do induce heterosubtypic protection resulting in the reduction of virus replication and an improved recovery from the disease. From this point of view recent attention has also been focused on the conserved part of HA, its HA2 glycoprotein (HA2). The main aspects revealing a contribution of HA2 gp to protective immunity are discussed in this review.
The haemagglutinin (HA) of influenza A virus consists of two glycopolypeptides designated HA1 and HA2. Antibodies recognizing HA1 inhibit virus haemagglutination, neutralize virus infectivity and ...provide good protection against infection, but do not cross-react with the HA of other subtypes. Little is known regarding the biological activities of antibodies against HA2. To study the role of antibodies directed against HA2 during influenza virus infection, two vaccinia virus recombinants (rVVs) were used expressing chimeric molecules of HA, in which HA1 and HA2 were derived from different HA subtypes. The KG-11 recombinant expressed HA1 from A/PR/8/34 (H1N1) virus and HA2 from A/NT/60 (H3N2) virus, whilst KG-12 recombinant expressed HA1 from A/NT/60 virus and HA2 from A/PR/8/34 virus. Immunization of BALB/c mice with rVV expressing HA2 of the HA subtype homologous to the challenge virus A/PR/8/34 (H1N1) or A/Mississippi/1/85 (H3N2) did not prevent virus infection, but nevertheless resulted in an increase in mice survival and faster elimination of virus from the lungs. Passive immunization with antibodies purified from mice immunized with rVVs confirmed that antibodies against HA2 were responsible for the described effect on virus infection. Based on the facts that HA2 is a rather conserved part of the HA and that antibodies against HA2, as shown here, may moderate virus infection, future vaccine design should deal with the problem of how to increase the HA2 antibody response.
Four monoclonal antibodies (mAbs) recognizing distinct antigenic sites on the HA2 glycopolypeptide of influenza virus A/Dunedin/4/73 (H3N2) have been tested for in vivo protection. When applied ...intravenously before infection, three of them increased the survival of BALB/c mice infected with 1 LD50 homologous virus. The protection resulted simultaneously in 2 days earlier clearance of virus from the lungs. These three antibodies inhibited the fusion activity of virus in previous in vitro experiments. One of them, specific to N-terminal aa 1-38 of the HA2 glycopolypeptide, was also tested for protection against the heterologous virus A/Mississippi/1/85 (H3N2). Protection similar to that against the homologous virus was observed. The fourth mAb, without fusion-inhibition activity, did not protect mice. It is concluded that antibodies specific to the antigenically conserved HA2 glycopolypeptide that exhibit fusion-inhibition activity can contribute to the protection of infected mice and mediate more effective recovery from infection.
Several types of influenza vaccines are available, but due to the highly unpredictable variability of influenza virus surface antigens (hemagglutinin (HA) and neuraminidase) current vaccines are not ...sufficiently effective against broad spectrum of the influenza viruses. An innovative approach to extend the vaccine efficacy is based on the selection of conserved influenza proteins with a potential to induce inter-subtype protection against the influenza A viruses. A promising new candidate for the preparation of broadly protective vaccine may be a highly conserved N-terminal part of HA2 glycopolypeptide (HA2 gp) called fusion peptide. To study its capacity to induce a protective immune response, we immunized mice with the fusion peptide (aa 1-38 of HA2 gp). The protective ability of fusion peptide was compared with the ectodomain aa 2-23 of M2 protein (eM2) that is antigenically conserved and its immunogenic properties have already been well documented. Corresponding peptides (both derived from A/Mississippi/1/85 (H3N2) virus) were synthesized and conjugated to the keyhole limpet hemocyanin (KLH) and used for the immunization of mice. Both antigens induced a significant level of specific antibodies. Immunized mice were challenged with the lethal dose of homologous (H3N2) or heterologous A/PR/8/34 (H1N1) influenza A viruses. Immunization with the fusion peptide led to the 100% survival of mice infected with 1 LD50 of homologous as well as heterologous virus. Survival rate decreased when infectious dose was raised to 2 LD50. The immunization with eM2 induced effective cross-protection of mice infected even with 3 LD50 of both challenge viruses. The lower, but still effective protection induced by the fusion peptide of HA2 gp suggested that besides ectodomain of M2, fusion peptide could also be considered as a part of cross-protective influenza vaccine. To our knowledge, this is the first report demonstrating that active immunization with the conjugated fusion peptide of HA2 gp provided the effective production of antibodies, what contributed to the cross-protection against influenza infection.
Currently, a new trend in development of vaccines against influenza with broader spectrum of efficacy is focused on conserved antigens of influenza virus. The HA2 glycopolypeptide (HA2 gp) is one of ...conserved antigens, potentially suitable as immunogens inducing cross-protection against influenza. We selected two distinct domains of HA2 gp originating from influenza A virus (IAV) of H3 subtype for induction of antiviral immune response: the ectodomain (EHA2) comprising aa 23-185 and the fusion peptide (FP) comprising N-terminal aa 1-38. BALB/c mice were immunized with three doses of EHA2 and FP, respectively, and subsequently challenged with 2 LD50 of IAV of homologous (H3) or heterologous (H7) HA subtype. Both peptides induced significant antibody response and protected mice against the lethal infection. The most efficient protection was achieved with EHA2 against homologous virus.
influenza A virus; cross-protection; HA2 glycopolypeptide; HA2 ectodomain; fusion peptide; mice; vaccine.
Human infections with avian influenza A viruses (IAVs) without or with clinical symptoms of disease were recently reported from several continents, mainly in high risk groups of people, who came into ...the contact with infected domestic birds or poultry. It was shown that avian IAVs are able to infect humans directly without previous adaptation, however, their ability to replicate and to cause a disease in this new host can differ. No spread of these avian IAVs among humans has been documented until now, except for one case described in Netherlands in the February of 2003 in people directly involved in handling IAV (H7N7)-infected poultry. The aim of our work was to examine whether a low pathogenic avian IAV can induce a virus-specific immune response of biological relevancy, in spite of its restricted replication in mammals. As a model we used a low pathogenic virus A/Duck/Czechoslovakia/1956 (H4N6) (A/Duck), which replicated well in MDCK cells and produced plaques on cell monolayers, but was unable to replicate productively in mouse lungs. We examined how the immune system of mice responds to the intranasal application of this non-adapted avian virus. Though we did not prove the infectious virus in lungs of mice following A/Duck application even after its multiple passaging in mice, we detected virus-specific vRNA till day 8 post infection. Moreover, we detected virus-specific mRNA and de novo synthesized viral nucleoprotein (NP) and membrane protein (M1) in lungs of mice on day 2 and 4 after exposure to A/Duck. Virus-specific antibodies in sera of these mice were detectable by ELISA already after a single intranasal dose of A/Duck virus. Not only antibodies specific to the surface glycoprotein hemagglutinin (HA) were induced, but also antibodies specific to the NP and M1 of IAV were detected by Western blot and their titers increased after the second exposure of mice to this virus. Importantly, antibodies neutralizing virus A/Duck were proved in mouse immune sera after the second dose of virus and a slight increase of mRNA expression of immune mediators tumor necrosis factor alpha (TNF-α) and IP10 has been observed in lungs of these mice 48 hr after the infection. These observations correspond to the limited replication ability of the virus in mice and provided an important information about its ability to induce virus-specific antibodies, including those neutralizing virus, even without the previous virus adaptation to the new mammalian host. Such antibodies could consequently influence the immune potential of exposed individuals and their defensive capability against the newly emerged, even more virulent IAV.
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