48 research outputs found
Influenza D Virus: A Potential Threat for Humans?
Influenza D virus (IDV) is a novel influenza virus first isolated from swine in 2011 in Oklahoma. Several studies have isolated IDV in cattle from multiple geographic areas, suggesting that cattle could be a possible primary natural reservoir for the virus. To date, few studies have been performed on human samples and there is no conclusive evidence that IDV has the ability to infect humans. This serological study aimed to assess the prevalence of antibodies against IDV in the human population. The IDV used in the serological analysis was influenza D/bovine/Oklahoma/660/2013. The human serum samples, collected in Italy between 2005 and 2017, were randomly selected from the laboratory serum bank and tested by the haemagglutination inhibition (HI) assay. HI positivity has been confirmed using the virus neutralization (VN) assay. Based on HI positivity (HI titers ≥ 10), a low prevalence (5%–10%) was observed between 2005 and 2007. There has been a sharp increase since 2008, resulting in two main peaks in 2009–2010 and 2013–2014, a finding confirmed by the statistical trend analysis. The same pattern and trends can be seen with higher HI titers of >20 and ≥40. The prevalence of antibodies against IDV has increased in the human population in Italy from 2005 to 2017. Low prevalence values between 2005 and 2007 suggest that IDV most probably circulated before its detection in 2011, and perhaps even before 2005. In Italy, IDV has been shown to circulate among swine and bovine herds. It is, therefore, possible that prevalence peaks in humans follow the infection epidemics in animals and do not to persist in the population, resembling a spillover event from the animal reservoir and showing that the virus may not circulate consistently in the human population. However, IDV seemed to have the ability to elicit an immune response in humans
Replication, Virulence, and Pathogenesis of Influenza Viruses
Influenza D virus (IDV) is a novel influenza virus that infects cattle and swine, with cattle as its primary host species. The goal of our first study was to investigate the replication and transmission of bovine IDV in guinea pigs. Following direct intranasal inoculation of animals, the virus was detected in nasal washes of infected animals during the first 7 days post-infection. High viral titers were obtained from nasal turbinates and lung tissues of directly inoculated animals. Further, bovine IDV was able to transmit from the infected guinea pigs to sentinel animals by means of contact and not by aerosol dissemination under the experimental conditions tested in this study. Despite exhibiting no clinical signs, infected guinea pigs developed seroconversion and the viral antigen was detected in lungs of animals by immunohistochemistry. The observation that bovine IDV replicated in the respiratory tract of guinea pigs was similar to observations described previously in studies of gnotobiotic calves and pigs experimentally infected with bovine IDV but different from those described previously in experimental infections in ferrets and swine with a swine IDV, which supported virus replication only in the upper respiratory tract and not in the lower respiratory tract, including lung. Our study established that guinea pigs could be used as an animal model for studying this newly emerging influenza virus. Influenza D virus isolated from the cattle and swine populations from North America and Eurasia shares 50% homology to the human influenza C virus. The goal of our second study was to investigate the replication kinetics and virulence of bovine and swine influenza D isolates (96-98% homology), in comparison to human influenza C in guinea pigs. Despite the similarity, both bovine and swine IDVs differ antigenically and genetically and belong to two different lineages. Guinea pigs upon intranasal inoculation of D/bovine/660/Oklahoma/2013 (bovine IDV), D/swine/1334/Oklahoma/2011 (swine IDV) and C/ Victoria/2012 (human ICV) did not exhibit any clinical signs. However, all the infected animals seroconverted at 7 days post-infection (dpi). Guinea pigs infected with ICV did not shed the virus in nasal washes at 1 dpi and only 2/8 shed virus at 3 dpi. In contrast, in bovine IDV infected group, 9/10 animals shed the virus in nasal washes at 1 dpi, while the swine IDV group (8/8) began to shed the virus only at 3 dpi. Hence, the disparity in the virus-shedding pattern of swine IDV could be an adaptation lag due to the subtle difference in receptor binding specificity and virus tropism. Deep RNA sequencing of viral genomes in the nasal washes, receptor binding preference, and structural modeling of receptor binding domain of hemagglutinin-esterase fusion protein are currently underway to identify the key factors and mechanisms involved in the differential replication kinetics, viral tropism, pathogenesis of the bovine and swine influenza D viruses. Further, our third project was aimed at developing a good primary culture system from swine for studying the virulence and pathogenesis. Influenza viruses are a group of respiratory pathogens that have evolved into four different types: A, B, C, and D. One common feature is that all four types are capable of replication and transmission among pigs. Human respiratory primary epithelial cell culture has been recently utilized to examine the replication and pathogenesis of influenza A viruses. However, little has been made in the development of the autologous cell culture system from swine to study influenza viruses. Here we describe the development of primary epithelial cells from swine nasal turbinates, trachea and lungs and determine their utility in the replication of four types of influenza viruses. Phenotypic characterization using immunocytochemistry coupled with flow cytometry analysis showed that cytokeratin was expressed at high levels in swine nasal turbinates, trachea, and lung cells, while the relatively low abundance of other epithelial cell markers (desmin, α-SMA, and vimentin) was detected. In addition, all three swine cells were found able to undergo the polarization as measured by trans-epithelial electrical resistance (TEER) and expression of tight junction proteins including claudin-1, -3, Zona occludens protein -1 (ZO-1) and occludin-1. These results strongly suggest that the developed swine primary cells possess common characteristics of epithelial cells. Furthermore, sialic acid receptor profile analysis through lectin binding assay with Sambucus Nigra Lectin (SNA) and Maackia Amurensis Lectin II (MAL-II) demonstrated that three swine primary epithelial cells expressed higher levels of alpha 2,6 linkage sialic acid (SNA) than alpha 2,3 linkage sialic acid receptors (MAL-II). Finally, all three primary cells supported the replication of Influenza A, B, C and D viruses to an appreciable level, but virus type-dependent replication kinetics were observed. Overall, these swine respiratory primary cells showed epithelial phenotype and are suitable for studying the comparative biology and pathobiology of four types of influenza viruses
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Tomorrow's College: The Future of Higher Education
Jeffrey Selingo, an author, reporter, and editor at large of The Chronicle of Higher Education, presented a talk on the future of higher education at Columbia University. Sree Sreenivasan, Columbia's Chief Digital Officer, introduced the talk
Emerging Threats of Highly Pathogenic Avian Influenza A (H5N1) in US Dairy Cattle: Understanding Cross-Species Transmission Dynamics in Mammalian Hosts
The rapid geographic spread of the highly pathogenic avian influenza (HPAI) A(H5N1) virus in poultry, wild birds, and other mammalian hosts, including humans, raises significant health concerns globally. The recent emergence of HPAI A(H5N1) in agricultural animals such as cattle and goats indicates the ability of the virus to breach unconventional host interfaces, further expanding the host range. Among the four influenza types—A, B, C, and D, cattle are most susceptible to influenza D infection and serve as a reservoir for this seven-segmented influenza virus. It is generally thought that bovines are not hosts for other types of influenza viruses, including type A. However, this long-standing viewpoint has been challenged by the recent outbreaks of HPAI A(H5N1) in dairy cows in the United States. To date, HPAI A(H5N1) has spread into fourteen states, affecting 299 dairy herds and causing clinical symptoms such as reduced appetite, fever, and a sudden drop in milk production. Infected cows can also transmit the disease through raw milk. This review article describes the current epidemiological landscape of HPAI A(H5N1) in US dairy cows and its interspecies transmission events in other mammalian hosts reported across the globe. The review also discusses the viral determinants of tropism, host range, adaptative mutations of HPAI A(H5N1) in various mammalian hosts with natural and experimental infections, and vaccination strategies. Finally, it summarizes some immediate questions that need to be addressed for a better understanding of the infection biology, transmission, and immune response of HPAI A(H5N1) in bovines
Host Range, Biology, and Species Specificity of Seven-Segmented Influenza Viruses—A Comparative Review on Influenza C and D
Other than genome structure, influenza C (ICV), and D (IDV) viruses with seven-segmented genomes are biologically different from the eight-segmented influenza A (IAV), and B (IBV) viruses concerning the presence of hemagglutinin–esterase fusion protein, which combines the function of hemagglutinin and neuraminidase responsible for receptor-binding, fusion, and receptor-destroying enzymatic activities, respectively. Whereas ICV with humans as primary hosts emerged nearly 74 years ago, IDV, a distant relative of ICV, was isolated in 2011, with bovines as the primary host. Despite its initial emergence in swine, IDV has turned out to be a transboundary bovine pathogen and a broader host range, similar to influenza A viruses (IAV). The receptor specificities of ICV and IDV determine the host range and the species specificity. The recent findings of the presence of the IDV genome in the human respiratory sample, and high traffic human environments indicate its public health significance. Conversely, the presence of ICV in pigs and cattle also raises the possibility of gene segment interactions/virus reassortment between ICV and IDV where these viruses co-exist. This review is a holistic approach to discuss the ecology of seven-segmented influenza viruses by focusing on what is known so far on the host range, seroepidemiology, biology, receptor, phylodynamics, species specificity, and cross-species transmission of the ICV and IDV
Mg-rikas alumiinisilikaattien synteesi ja alkalin aktivointi
AbstractAlkali-activated materials (AAMs) are alternative cementitious materials with lower carbon footprints compared to traditional Portland cement (PC). In addition to Ca, Si, and Al, the precursors used in the preparation of AAMs can sometimes include considerable amounts of Mg, so that Mg significantly influences the structure and properties of AAMs. When compared to Ca, Si, and Al, relatively few studies have focused on the role of Mg in AAMs. This thesis deals with alkali activation of Mg-rich aluminosilicate precursors with the following objectives: 1) preparation, characterization, and estimation of alkaline reactivity of Na-Mg aluminosilicate glasses; 2) synthesis of AAMs from Na-Mg aluminosilicate glasses and their detailed characterization to understand the fate of Mg; and 3) estimation of the potential of phlogopite as a Mg-rich raw material for alkali activation.The structural study of Na-Mg aluminosilicate glasses indicates that the higher cationic field strength (CFS) of Mg than Na makes Mg preferable as a network modifier, whereas Na acts as a charge compensator. Alkaline reactivity studies of Na-Mg aluminosilicate glasses reveal that as Mg replaces Na in glasses, the reactivity of the glasses increases initially, attains a maximum, and then drops. This trend can be explained by the interplay between glass depolymerization and optical basicity: depolymerization dictates the glass reactivity initially, while the effect of optical basicity dominates at later stages. Detailed structural study of AAMs prepared from Na-Mg aluminosilicate glasses indicates that Mg in AAMs exists as an amorphous magnesium silicate (AMS) phase, but the existence of this phase is not well documented in the literature. The driving force for AMS formation is the high CFS of Mg, which leads to effective stabilization of the depolymerized silicate species. The absence of hydrotalcite-group phases from these AAMs is due to the depletion of Al by zeolite production. The assessment of phlogopite mineral as a Mg-rich precursor for alkali activation indicates that untreated phlogopite is highly inert. However, thermal treatment could enhance the alkaline reactivity of phlogopite.Original papersOriginal papers are not included in the electronic version of the dissertation.Sreenivasan, H., Kinnunen, P., Adesanya, E., Patanen, M., Kantola, A. M., Telkki, V.-V., Huttula, M., Cao, W., Provis, J. L., & Illikainen, M. (2020). Field Strength of Network-Modifying Cation Dictates the Structure of (Na-Mg) Aluminosilicate Glasses. Frontiers in Materials, 7. https://doi.org/10.3389/fmats.2020.00267Self-archived versionSreenivasan, H., Cao, W., Hu, Y., Xiao, Q., Shakouri, M., Huttula, M., Provis, J. L., Illikainen, M., & Kinnunen, P. (2020). Towards designing reactive glasses for alkali activation: Understanding the origins of alkaline reactivity of Na-Mg aluminosilicate glasses. PLOS ONE, 15(12), e0244621. https://doi.org/10.1371/journal.pone.0244621Self-archived versionSreenivasan, H., Adesanya, E., Niu, H., Perumal, P., Kantola, A. M., Telkki, V.-V., Huttula, M., Cao, W., Provis, J. L., Illikainen, M., & Kinnunen, P. (2021). Evidence of formation of an amorphous magnesium silicate (AMS) phase during alkali activation of (Na-Mg) aluminosilicate glasses. Cement and Concrete Research, 145, 106464. https://doi.org/10.1016/j.cemconres.2021.106464Self-archived versionSreenivasan, H., Kinnunen, P., Heikkinen, E.-P., & Illikainen, M. (2017). Thermally treated phlogopite as magnesium-rich precursor for alkali activation purpose. Minerals Engineering, 113, 47–54. https://doi.org/10.1016/j.mineng.2017.08.003TiivistelmäAlkali -aktivoidut materiaalit (AAM) ovat vaihtoehtoisia sementtimateriaaleja, joilla on pienempi hiilijalanjälki verrattuna perinteiseen portland -sementtiin (PC). Ca: n, Si: n ja Al: n lisäksi esiasteissa (joita käytetään AAM: ien valmistukseen) voi joskus olla huomattava määrä Mg: tä, ja tämä johtaa siihen, että Mg vaikuttaa merkittävästi AAM: ien rakenteeseen ja ominaisuuksiin. Verrattuna Ca, Si ja Al, on ollut suhteellisen vähän tutkimuksia, joissa keskitytään Mg: n rooliin AAM: issä. Tämä opinnäytetyö käsittelee Mg-rikkaiden alumiinisilikaattiesiasteiden alkaliaktivaatiota seuraavilla tavoitteilla: 1) Na-Mg-alumiinisilikaattilasien alkalisen reaktiivisuuden valmistelu, karakterisointi ja arviointi; 2) synteesi AAM: istä Na-Mg-alumiinisilikaattilasista ja niiden yksityiskohtainen karakterisointi Mg: n kohtalon ymmärtämiseksi; 3) Flogopiitin potentiaalin arviointi Mg-rikkaana raaka-aineena alkalin aktivoimiseksi.Na-Mg-alumiinisilikaattilasien rakennetutkimus osoittaa, että Mg: n korkeamman kationisen kentänvoimakkuuden (CFS) takia Na: n vuoksi Mg on edullinen verkon muokkaajana, kun taas Na toimii varauksen kompensoijana. Na-Mg-alumiinisilikaattilasien alkaliset reaktiivisuustutkimukset paljastavat, että kun Mg korvaa Na: n lasissa, lasien reaktiivisuus kasvaa aluksi ja saavuttaa maksimin, minkä jälkeen se laskee. Tämä suuntaus voidaan selittää lasin depolymeroinnin ja optisen emäksisyyden välisellä vuorovaikutuksella: depolymerointi sanelee aluksi lasin reaktiivisuuden, kun taas optisen emäksisyyden vaikutus hallitsee myöhemmässä vaiheessa. Yksityiskohtainen rakenteellinen tutkimus AAM: ista, jotka on valmistettu Na-Mg-alumiinisilikaattilasista, osoittaa, että Mg AAM-yhdisteissä esiintyy amorfisena magnesiumsilikaatti (AMS) -faasina, jonka olemassaoloa ei ole hyvin dokumentoitu kirjallisuudessa. AMS: n muodostumisen liikkeellepaneva voima on Mg: n korkea CFS, mikä johtaa depolymeroitujen silikaattilajien tehokkaaseen vakautumiseen. Hydrotaltsiittiryhmän faasien puuttuminen näistä AAM: ista on havaittu johtuvan Al: n ehtymisestä zeoliittituotannolla. Flogopiittimineraalin arviointi Mg-rikkaana esiasteena alkalin aktivoitumiselle osoittaa, että käsittelemätön flogopiitti on erittäin inertti. Lämpökäsittely voi kuitenkin parantaa flogopiitin emäksistä reaktiivisuutta.OsajulkaisutOsajulkaisut eivät sisälly väitöskirjan elektroniseen versioon.Sreenivasan, H., Kinnunen, P., Adesanya, E., Patanen, M., Kantola, A. M., Telkki, V.-V., Huttula, M., Cao, W., Provis, J. L., & Illikainen, M. (2020). Field Strength of Network-Modifying Cation Dictates the Structure of (Na-Mg) Aluminosilicate Glasses. Frontiers in Materials, 7. https://doi.org/10.3389/fmats.2020.00267Rinnakkaistallennettu versioSreenivasan, H., Cao, W., Hu, Y., Xiao, Q., Shakouri, M., Huttula, M., Provis, J. L., Illikainen, M., & Kinnunen, P. (2020). Towards designing reactive glasses for alkali activation: Understanding the origins of alkaline reactivity of Na-Mg aluminosilicate glasses. PLOS ONE, 15(12), e0244621. https://doi.org/10.1371/journal.pone.0244621Rinnakkaistallennettu versioSreenivasan, H., Adesanya, E., Niu, H., Perumal, P., Kantola, A. M., Telkki, V.-V., Huttula, M., Cao, W., Provis, J. L., Illikainen, M., & Kinnunen, P. (2021). Evidence of formation of an amorphous magnesium silicate (AMS) phase during alkali activation of (Na-Mg) aluminosilicate glasses. Cement and Concrete Research, 145, 106464. https://doi.org/10.1016/j.cemconres.2021.106464Rinnakkaistallennettu versioSreenivasan, H., Kinnunen, P., Heikkinen, E.-P., & Illikainen, M. (2017). Thermally treated phlogopite as magnesium-rich precursor for alkali activation purpose. Minerals Engineering, 113, 47–54. https://doi.org/10.1016/j.mineng.2017.08.003Academic dissertation to be presented with the assent of the Doctoral Training Committee of Technology and Natural Sciences of the University of Oulu for public defence in the OP-Pohjola auditorium (L6), Linnanmaa, on 8 October 2021, at 12 noonAbstract
Alkali-activated materials (AAMs) are alternative cementitious materials with lower carbon footprints compared to traditional Portland cement (PC). In addition to Ca, Si, and Al, the precursors used in the preparation of AAMs can sometimes include considerable amounts of Mg, so that Mg significantly influences the structure and properties of AAMs. When compared to Ca, Si, and Al, relatively few studies have focused on the role of Mg in AAMs. This thesis deals with alkali activation of Mg-rich aluminosilicate precursors with the following objectives: 1) preparation, characterization, and estimation of alkaline reactivity of Na-Mg aluminosilicate glasses; 2) synthesis of AAMs from Na-Mg aluminosilicate glasses and their detailed characterization to understand the fate of Mg; and 3) estimation of the potential of phlogopite as a Mg-rich raw material for alkali activation.
The structural study of Na-Mg aluminosilicate glasses indicates that the higher cationic field strength (CFS) of Mg than Na makes Mg preferable as a network modifier, whereas Na acts as a charge compensator. Alkaline reactivity studies of Na-Mg aluminosilicate glasses reveal that as Mg replaces Na in glasses, the reactivity of the glasses increases initially, attains a maximum, and then drops. This trend can be explained by the interplay between glass depolymerization and optical basicity: depolymerization dictates the glass reactivity initially, while the effect of optical basicity dominates at later stages. Detailed structural study of AAMs prepared from Na-Mg aluminosilicate glasses indicates that Mg in AAMs exists as an amorphous magnesium silicate (AMS) phase, but the existence of this phase is not well documented in the literature. The driving force for AMS formation is the high CFS of Mg, which leads to effective stabilization of the depolymerized silicate species. The absence of hydrotalcite-group phases from these AAMs is due to the depletion of Al by zeolite production. The assessment of phlogopite mineral as a Mg-rich precursor for alkali activation indicates that untreated phlogopite is highly inert. However, thermal treatment could enhance the alkaline reactivity of phlogopite.Tiivistelmä
Alkali -aktivoidut materiaalit (AAM) ovat vaihtoehtoisia sementtimateriaaleja, joilla on pienempi hiilijalanjälki verrattuna perinteiseen portland -sementtiin (PC). Ca: n, Si: n ja Al: n lisäksi esiasteissa (joita käytetään AAM: ien valmistukseen) voi joskus olla huomattava määrä Mg: tä, ja tämä johtaa siihen, että Mg vaikuttaa merkittävästi AAM: ien rakenteeseen ja ominaisuuksiin. Verrattuna Ca, Si ja Al, on ollut suhteellisen vähän tutkimuksia, joissa keskitytään Mg: n rooliin AAM: issä. Tämä opinnäytetyö käsittelee Mg-rikkaiden alumiinisilikaattiesiasteiden alkaliaktivaatiota seuraavilla tavoitteilla: 1) Na-Mg-alumiinisilikaattilasien alkalisen reaktiivisuuden valmistelu, karakterisointi ja arviointi; 2) synteesi AAM: istä Na-Mg-alumiinisilikaattilasista ja niiden yksityiskohtainen karakterisointi Mg: n kohtalon ymmärtämiseksi; 3) Flogopiitin potentiaalin arviointi Mg-rikkaana raaka-aineena alkalin aktivoimiseksi.
Na-Mg-alumiinisilikaattilasien rakennetutkimus osoittaa, että Mg: n korkeamman kationisen kentänvoimakkuuden (CFS) takia Na: n vuoksi Mg on edullinen verkon muokkaajana, kun taas Na toimii varauksen kompensoijana. Na-Mg-alumiinisilikaattilasien alkaliset reaktiivisuustutkimukset paljastavat, että kun Mg korvaa Na: n lasissa, lasien reaktiivisuus kasvaa aluksi ja saavuttaa maksimin, minkä jälkeen se laskee. Tämä suuntaus voidaan selittää lasin depolymeroinnin ja optisen emäksisyyden välisellä vuorovaikutuksella: depolymerointi sanelee aluksi lasin reaktiivisuuden, kun taas optisen emäksisyyden vaikutus hallitsee myöhemmässä vaiheessa. Yksityiskohtainen rakenteellinen tutkimus AAM: ista, jotka on valmistettu Na-Mg-alumiinisilikaattilasista, osoittaa, että Mg AAM-yhdisteissä esiintyy amorfisena magnesiumsilikaatti (AMS) -faasina, jonka olemassaoloa ei ole hyvin dokumentoitu kirjallisuudessa. AMS: n muodostumisen liikkeellepaneva voima on Mg: n korkea CFS, mikä johtaa depolymeroitujen silikaattilajien tehokkaaseen vakautumiseen. Hydrotaltsiittiryhmän faasien puuttuminen näistä AAM: ista on havaittu johtuvan Al: n ehtymisestä zeoliittituotannolla. Flogopiittimineraalin arviointi Mg-rikkaana esiasteena alkalin aktivoitumiselle osoittaa, että käsittelemätön flogopiitti on erittäin inertti. Lämpökäsittely voi kuitenkin parantaa flogopiitin emäksistä reaktiivisuutta
Comparison of Porcine Airway and Intestinal Epithelial Cell Lines for the Susceptibility and Expression of Pattern Recognition Receptors upon Influenza Virus Infection
Influenza viruses infect the epithelial cells of the swine respiratory tract. Cell lines derived from the respiratory tract of pigs could serve as an excellent in vitro model for studying the pathogenesis of influenza viruses. In this study, we examined the replication of influenza viruses in the MK1-OSU cell line, which was clonally derived from pig airway epithelium. MK1-OSU cells expressed both cytokeratin and vimentin proteins and displayed several sugar moieties on the cell membrane. These cells also expressed both Sial2-3Gal and Sial2-6Gal receptors and were susceptible to swine influenza A, but not to human B and C viruses. Interestingly, these cells were also permissive to infection by influenza D virus that utilized 9-O-acetylated glycans. To study the differences in the expression of pattern recognition receptors (PRRs) upon influenza virus infection in the respiratory and digestive tract, we compared the protein expression of various PRRs in MK1-OSU cells with that in the SD-PJEC cell line, a clonally derived cell line from the porcine jejunal epithelium. Toll-like receptor 7 (TLR-7) and melanoma differentiation-associated protein 5 (MDA5) receptors showed decreased expression in influenza A infected MK1-OSU cells, while only TLR-7 expression decreased in SD-PJEC cells. Further research is warranted to study the mechanism behind the virus-mediated suppression of these proteins. Overall, this study shows that the porcine respiratory epithelial cell line, MK1-OSU, could serve as an in-vitro model for studying the pathogenesis and innate immune responses to porcine influenza viruses
The investigation of phase synchronization in the cortex during a fatiguing muscle contraction using EEG
Includes bibliographical references (leaves 140-157)
Application of a Cleavage Fracture Stress Model for Estimating the ASTM E-1921 Reference Temperature of Ferritic Steels from Instrumented Impact Test of CVN Specimens without Precracking
AbstractA recently proposed semi-empirical cleavage fracture stress (CFS) model by the author based on the microscopic cleavage fracture stress, σf, for estimating the ASTM E-1921 reference temperature, T0, of ferritic steels from instrumented impact test (IIT) of Charpy V-notch (CVN) specimens without precracking has been demonstrated for steels with room temperature yield strength in the range 400-750MPa, including irradiated steels. The estimate of T0, based on the CFS model, TQcfs lies within a ± 20°C band, being conservative for most of the steels, but less conservative than TQIGC based on the IGC-procedure. CFS model enhances the validity and utility of the CVN IIT by enabling estimation of design-relevant master curve from unprecracked CVN specimens. In this paper, the method is further applied to some steels (both unirradiated and irradiated) reported in the literature most of which have only IIT data and static tensile data available. The method has also been applied to some IIT test results obtained at IGCAR for 9Cr-1Mo steel in various simulated weld-heat affected zone conditions. The results are compared with TQIGC or other estimates like TQBT or T0, if available
