Sample records for h-1 heliac
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Helicons, History, High Technology and Heliacs
NASA Astrophysics Data System (ADS)
Boswell, Rod
1998-11-01
Helicon waves depend basically on the Hall effect and propagate between the ion and electron gyro frequencies: they are whistlers masquerading under another name hence their history goes back to the great war and subsequently involved such people as Appleton, Hartree and Storey. Considerable experimental and theoretical research was carried out on linear propagation during the 1960's and at the end of the decade it was discovered that the wave could actually heat the plasma electrons and increase the ionisation rate considerably. Nothing much happened during the 1970's but in the early 1980's it was realised that this high density source could be used for processing thin films and an increasing number of papers were published, which continues to this day. The first experiments on using helicons to create and heat toroidal plasmas were carried out at the end of the 1980's in a small heliac. Recent experiments with helicon excitation in the large heliac H1 at the ANU have shown that the ion temperature increases with the wave power. This mystery is being actively investigated.
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Global Alfvén eigenmodes in the H-1 heliac
NASA Astrophysics Data System (ADS)
Hole, M. J.; Blackwell, B. D.; Bowden, G.; Cole, M.; Könies, A.; Michael, C.; Zhao, F.; Haskey, S. R.
2017-12-01
Recent upgrades in H-1 power supplies have enabled the operation of the H-1 experiment at higher heating powers than previously attainable. A heating power scan in mixed hydrogen/helium plasmas reveals a change in mode activity with increasing heating power. At low power (< 50 kW) modes with beta-induced Alfvén eigenmode frequency scaling are observed. At higher power modes consistent with an analysis of nonconventional global Alfvén eigenmodes (GAEs) are observed, the subject of this work. We have computed the mode continuum, and identified GAE structures using the ideal MHD solver CKA and the gyrokinetic code EUTERPE. An analytic model for ICRH-heated minority ions is used to estimate the fast ion temperature from the hydrogen species. Linear growth rate scans using a local flux surface stability calculation, LGRO, are performed. These studies demonstrate drive from the radial spatial gradient of circulating particles whose speed is significantly less than the Alfvén speed, and are resonant with the mode through harmonics of the Fourier decomposition of the strongly shaped heliac magnetic field. They reveal drive is possible with a small ({n}f/{n}0< 0.2) hot energetic tail of the hydrogen species, for which {T}f> 300 {eV}. Local linear growth rate scans are also complemented with global calculations from CKA and EUTERPE. These qualitatively confirm the findings from the LGRO study, and show that the inclusion of finite Larmor radius effects can reduce the growth rate by a factor of up to ten, and increases the marginal stability fast ion temperature by a factor of two. Finally, a study of damping of the global mode with the thermal plasma is conducted, computing continuum damping , and the damping arising from finite Larmor radius and parallel electric fields (via resistivity). We find that continuum damping is of order 0.1% for the configuration studied. A similar calculation in the cylindrical plasma model produces a frequency 35% higher and a damping 30% of
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The ancient Armenian calendars' connection with the celestial bodies
NASA Astrophysics Data System (ADS)
Broutian, G. H.
2015-07-01
The two oldest Armenian calendars - the Haykian and Protohaykian calendars were connected with observations of celestial bodies. Particularly since 2341 B.C. the heliacal rising of the first star of Orion was used to determine the day of the main holiday - Nawasard. Before that the observations of the same star were used in Protohaykian calendar to determine both the beginning and the end of the year. The year was determined as the duration of visibility of the star Betelgeuse. The year started with the heliacal rising of this star and ended with its heliacal setting. The remaining duration was considered to be out of the year. There are also evidences in Armenian medieval literary sources concerning the observations of heliacal rising and setting of Pleiades. An attempt was made to substantiate that the large symbol carved on the rock platform of the small hill in Metzamor also concerns to the Pleiades and shows the direction of heliacal rising of Pleiades.
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Sui, Jinyu; Yang, Dawei; Qiao, Chuanling; Xu, Huiyang; Xu, Bangfeng; Wu, Yunpu; Yang, Huanliang; Chen, Yan; Chen, Hualan
2016-07-19
Eurasian avian-like H1N1 (EA H1N1) swine influenza viruses are prevalent in pigs in Europe and Asia, but occasionally cause human infection, which raises concern about their pandemic potential. Here, we produced a whole-virus inactivated vaccine with an EA H1N1 strain (A/swine/Guangxi/18/2011, SW/GX/18/11) and evaluated its efficacy against homologous H1N1 and heterologous H1N1 and H1N2 influenza viruses in mice. A strong humoral immune response, which we measured by hemagglutination inhibition (HI) and virus neutralization (VN), was induced in the vaccine-inoculated mice upon challenge. The inactivated SW/GX/18/11 vaccine provided complete protection against challenge with homologous SW/GX/18/11 virus in mice and provided effective protection against challenge with heterologous H1N1 and H1N2 viruses with distinctive genomic combinations. Our findings suggest that this EA H1N1 vaccine can provide protection against both homologous H1N1 and heterologous H1N1 or H1N2 virus infection. As such, it is an excellent vaccine candidate to prevent H1N1 swine influenza. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Ferreira, Vitor F; da Rocha, David R; da Silva, Fernando C; Ferreira, Patrícia G; Boechat, Núbia A; Magalhães, Jorge L
2013-03-01
The triazoles represent a class of five-membered heterocyclic compounds of great importance for the preparation of new drugs with diverse biological activities because they may present several structural variations with the same numbers of carbon and nitrogen atoms. Due to the success of various triazoles that entered the pharmaceutical market and are still being used in medicines, many companies and research groups have shown interest in developing new methods of synthesis and biological evaluation of potential uses for these compounds. In this review, the authors explored aspects of patents for the 1H-1,2,3-, 2H-1,2,3-, 1H-1,2,4- and 4H-1,2,4-triazole families, including prototypes being considered in clinical studies between 2008 and 2011. The triazoles have been studied for over a century as an important class of heterocyclic compounds and still attract considerable attention due to their broad range of biological activities. More recently, there has been considerable interest in the development of novel triazoles with anti-inflammatory, antiplatelet, antimicrobial, antimycobacterial, antitumoral and antiviral properties and activity against several neglected diseases. This review emphasizes recent perspective and advances in the therapeutically active 1H-1,2,3-, 2H-1,2,3-, 1H-1,2,4- and 4H-1,2,4-triazole derivative patents between 2008 and 2011, covering the development of new chemical entities and new pharmaceuticals. Many studies have focused on these compounds as target structures and evaluated them in several biological targets. The preparation of 1H-1,2,3-, 2H-1,2,3-, 1H-1,2,4- and 4H-1,2,4-triazole derivatives brings to light several issues. There is a need to find new, more efficient preparations for these triazoles that take into consideration current issues in green chemistry, energy saving and sustainability. New diseases are discovered and new viruses and bacteria continue to challenge mankind, so it is imperative to find new prototypes for these
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Photoperiod-H1 (Ppd-H1) Controls Leaf Size1[OPEN
Digel, Benedikt; Tavakol, Elahe; Verderio, Gabriele; Xu, Xin
2016-01-01
Leaf size is a major determinant of plant photosynthetic activity and biomass; however, it is poorly understood how leaf size is genetically controlled in cereal crop plants like barley (Hordeum vulgare). We conducted a genome-wide association scan for flowering time, leaf width, and leaf length in a diverse panel of European winter cultivars grown in the field and genotyped with a single-nucleotide polymorphism array. The genome-wide association scan identified PHOTOPERIOD-H1 (Ppd-H1) as a candidate gene underlying the major quantitative trait loci for flowering time and leaf size in the barley population. Microscopic phenotyping of three independent introgression lines confirmed the effect of Ppd-H1 on leaf size. Differences in the duration of leaf growth and consequent variation in leaf cell number were responsible for the leaf size differences between the Ppd-H1 variants. The Ppd-H1-dependent induction of the BARLEY MADS BOX genes BM3 and BM8 in the leaf correlated with reductions in leaf size and leaf number. Our results indicate that leaf size is controlled by the Ppd-H1- and photoperiod-dependent progression of plant development. The coordination of leaf growth with flowering may be part of a reproductive strategy to optimize resource allocation to the developing inflorescences and seeds. PMID:27457126
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Photoperiod-H1 (Ppd-H1) Controls Leaf Size.
Digel, Benedikt; Tavakol, Elahe; Verderio, Gabriele; Tondelli, Alessandro; Xu, Xin; Cattivelli, Luigi; Rossini, Laura; von Korff, Maria
2016-09-01
Leaf size is a major determinant of plant photosynthetic activity and biomass; however, it is poorly understood how leaf size is genetically controlled in cereal crop plants like barley (Hordeum vulgare). We conducted a genome-wide association scan for flowering time, leaf width, and leaf length in a diverse panel of European winter cultivars grown in the field and genotyped with a single-nucleotide polymorphism array. The genome-wide association scan identified PHOTOPERIOD-H1 (Ppd-H1) as a candidate gene underlying the major quantitative trait loci for flowering time and leaf size in the barley population. Microscopic phenotyping of three independent introgression lines confirmed the effect of Ppd-H1 on leaf size. Differences in the duration of leaf growth and consequent variation in leaf cell number were responsible for the leaf size differences between the Ppd-H1 variants. The Ppd-H1-dependent induction of the BARLEY MADS BOX genes BM3 and BM8 in the leaf correlated with reductions in leaf size and leaf number. Our results indicate that leaf size is controlled by the Ppd-H1- and photoperiod-dependent progression of plant development. The coordination of leaf growth with flowering may be part of a reproductive strategy to optimize resource allocation to the developing inflorescences and seeds. © 2016 American Society of Plant Biologists. All rights reserved.
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Carter, Donald M.; Bloom, Chalise E.; Nascimento, Eduardo J. M.; Marques, Ernesto T. A.; Craigo, Jodi K.; Cherry, Joshua L.; Lipman, David J.
2013-01-01
Individuals <60 years of age had the lowest incidence of infection, with ∼25% of these people having preexisting, cross-reactive antibodies to novel 2009 H1N1 influenza. Many people >60 years old also had preexisting antibodies to novel H1N1. These observations are puzzling because the seasonal H1N1 viruses circulating during the last 60 years were not antigenically similar to novel H1N1. We therefore hypothesized that a sequence of exposures to antigenically different seasonal H1N1 viruses can elicit an antibody response that protects against novel 2009 H1N1. Ferrets were preinfected with seasonal H1N1 viruses and assessed for cross-reactive antibodies to novel H1N1. Serum from infected ferrets was assayed for cross-reactivity to both seasonal and novel 2009 H1N1 strains. These results were compared to those of ferrets that were sequentially infected with H1N1 viruses isolated prior to 1957 or more-recently isolated viruses. Following seroconversion, ferrets were challenged with novel H1N1 influenza virus and assessed for viral titers in the nasal wash, morbidity, and mortality. There was no hemagglutination inhibition (HAI) cross-reactivity in ferrets infected with any single seasonal H1N1 influenza viruses, with limited protection to challenge. However, sequential H1N1 influenza infections reduced the incidence of disease and elicited cross-reactive antibodies to novel H1N1 isolates. The amount and duration of virus shedding and the frequency of transmission following novel H1N1 challenge were reduced. Exposure to multiple seasonal H1N1 influenza viruses, and not to any single H1N1 influenza virus, elicits a breadth of antibodies that neutralize novel H1N1 even though the host was never exposed to the novel H1N1 influenza viruses. PMID:23115287
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Comparative pathology of pigs infected with Korean H1N1, H1N2, or H3N2 swine influenza A viruses.
Lyoo, Kwang-Soo; Kim, Jeong-Ki; Jung, Kwonil; Kang, Bo-Kyu; Song, Daesub
2014-09-24
The predominant subtypes of swine influenza A virus (SIV) in Korea swine population are H1N1, H1N2, and H3N2. The viruses are genetically close to the classical U.S. H1N1 and triple-reassortant H1N2 and H3N2 viruses, respectively. Comparative pathogenesis caused by Korean H1N1, H1N2, and H3N2 SIV was evaluated in this study. The H3N2 infected pigs had severe scores of gross and histopathological lesions at post-inoculation days (PID) 2, and this then progressively decreased. Both the H1N1 and H1N2 infected pigs lacked gross lesions at PID 2, but they showed moderate to severe pneumonia on PID 4, 7 and 14. The pigs infected with H1N1 had significant scores of gross and histopathological lesions when compared with the other pigs infected with H1N2, H3N2, and mock at PID 14. Mean SIV antigen-positive scores were rarely detected for pigs infected with H1N2 and H3N2 from PID 7, whereas a significantly increased amount of viral antigens were found in the bronchioles and alveolar epithelium of the H1N1infected pigs at PID 14. We demonstrated that Korean SIV subtypes had different pulmonary pathologic patterns. The Korean H3N2 rapidly induced acute lung lesions such as broncho-interstitial pneumonia, while the Korean H1N1 showed longer course of infection as compared to other strains.
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Nfon, Charles; Berhane, Yohannes; Pasick, John; Embury-Hyatt, Carissa; Kobinger, Gary; Kobasa, Darwyn; Babiuk, Shawn
2012-01-01
There is a critical need to have vaccines that can protect against emerging pandemic influenza viruses. Commonly used influenza vaccines are killed whole virus that protect against homologous and not heterologous virus. Using chickens we have explored the possibility of using live low pathogenic avian influenza (LPAI) A/goose/AB/223/2005 H1N1 or A/WBS/MB/325/2006 H1N2 to induce immunity against heterologous highly pathogenic avian influenza (HPAI) A/chicken/Vietnam/14/2005 H5N1. H1N1 and H1N2 replicated in chickens but did not cause clinical disease. Following infection, chickens developed nucleoprotein and H1 specific antibodies, and reduced H5N1 plaque size in vitro in the absence of H5 neutralizing antibodies at 21 days post infection (DPI). In addition, heterologous cell mediated immunity (CMI) was demonstrated by antigen-specific proliferation and IFN-γ secretion in PBMCs re-stimulated with H5N1 antigen. Following H5N1 challenge of both pre-infected and naïve controls chickens housed together, all naïve chickens developed acute disease and died while H1N1 or H1N2 pre-infected chickens had reduced clinical disease and 70-80% survived. H1N1 or H1N2 pre-infected chickens were also challenged with H5N1 and naïve chickens placed in the same room one day later. All pre-infected birds were protected from H5N1 challenge but shed infectious virus to naïve contact chickens. However, disease onset, severity and mortality was reduced and delayed in the naïve contacts compared to directly inoculated naïve controls. These results indicate that prior infection with LPAI virus can generate heterologous protection against HPAI H5N1 in the absence of specific H5 antibody.
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Nfon, Charles; Berhane, Yohannes; Pasick, John; Embury-Hyatt, Carissa; Kobinger, Gary; Kobasa, Darwyn; Babiuk, Shawn
2012-01-01
There is a critical need to have vaccines that can protect against emerging pandemic influenza viruses. Commonly used influenza vaccines are killed whole virus that protect against homologous and not heterologous virus. Using chickens we have explored the possibility of using live low pathogenic avian influenza (LPAI) A/goose/AB/223/2005 H1N1 or A/WBS/MB/325/2006 H1N2 to induce immunity against heterologous highly pathogenic avian influenza (HPAI) A/chicken/Vietnam/14/2005 H5N1. H1N1 and H1N2 replicated in chickens but did not cause clinical disease. Following infection, chickens developed nucleoprotein and H1 specific antibodies, and reduced H5N1 plaque size in vitro in the absence of H5 neutralizing antibodies at 21 days post infection (DPI). In addition, heterologous cell mediated immunity (CMI) was demonstrated by antigen-specific proliferation and IFN-γ secretion in PBMCs re-stimulated with H5N1 antigen. Following H5N1 challenge of both pre-infected and naïve controls chickens housed together, all naïve chickens developed acute disease and died while H1N1 or H1N2 pre-infected chickens had reduced clinical disease and 70–80% survived. H1N1 or H1N2 pre-infected chickens were also challenged with H5N1 and naïve chickens placed in the same room one day later. All pre-infected birds were protected from H5N1 challenge but shed infectious virus to naïve contact chickens. However, disease onset, severity and mortality was reduced and delayed in the naïve contacts compared to directly inoculated naïve controls. These results indicate that prior infection with LPAI virus can generate heterologous protection against HPAI H5N1 in the absence of specific H5 antibody. PMID:23240067
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Kirisawa, Rikio; Ogasawara, Yoshitaka; Yoshitake, Hayato; Koda, Asuka; Furuya, Tokujiro
2014-11-01
From 2010 to 2013 in Japan, we isolated 11 swine influenza viruses (SIVs) from pigs showing respiratory symptoms. Sequence and phylogenetic analyses showed that 6 H1N1 viruses originated from the pandemic (H1N1) 2009 (pdm 09) virus and the other 5 viruses were reassortants between SIVs and pdm 09 viruses, representing 4 genotypes. Two H1N2 viruses contained H1 and N2 genes originated from Japanese H1N2 SIV together with internal genes of pdm 09 viruses. Additionally, 1 H1N2 virus contained a further NP gene originating from Japanese H1N2 SIV. One H1N1 virus contained only the H1 gene originating from Japanese H1 SIV in a pdm 09 virus background. One H3N2 virus contained H3 and N2 genes originating from Japanese H3N2 SIV together with internal genes of pdm 09 virus. The results indicate that pdm 09 viruses are distributed widely in the Japanese swine population and that several reassortments with Japanese SIVs have occurred.
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Chen, Yan; Zhang, Jian; Qiao, Chuanling; Yang, Huanliang; Zhang, Ying; Xin, Xiaoguang; Chen, Hualan
2013-01-01
The pandemic A/H1N1 influenza viruses emerged in both Mexico and the United States in March 2009, and were transmitted efficiently in the human population. They were transmitted occasionally from humans to other mammals including pigs, dogs and cats. In this study, we report the isolation and genetic analysis of novel viruses in pigs in China. These viruses were related phylogenetically to the pandemic 2009 H1N1 influenza viruses isolated from humans and pigs, which indicates that the pandemic virus is currently circulating in swine populations, and this hypothesis was further supported by serological surveillance of pig sera collected within the same period. Furthermore, we isolated another two H1N1 viruses belonging to the lineages of classical swine H1N1 virus and avian-like swine H1N1 virus, respectively. Multiple genetic lineages of H1N1 viruses are co-circulating in the swine population, which highlights the importance of intensive surveillance for swine influenza in China. Copyright © 2012 Elsevier B.V. All rights reserved.
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Antigenic variation of H1N1, H1N2 and H3N2 swine influenza viruses in Japan and Vietnam.
Takemae, Nobuhiro; Nguyen, Tung; Ngo, Long Thanh; Hiromoto, Yasuaki; Uchida, Yuko; Pham, Vu Phong; Kageyama, Tsutomu; Kasuo, Shizuko; Shimada, Shinichi; Yamashita, Yasutaka; Goto, Kaoru; Kubo, Hideyuki; Le, Vu Tri; Van Vo, Hung; Do, Hoa Thi; Nguyen, Dang Hoang; Hayashi, Tsuyoshi; Matsuu, Aya; Saito, Takehiko
2013-04-01
The antigenicity of the influenza A virus hemagglutinin is responsible for vaccine efficacy in protecting pigs against swine influenza virus (SIV) infection. However, the antigenicity of SIV strains currently circulating in Japan and Vietnam has not been well characterized. We examined the antigenicity of classical H1 SIVs, pandemic A(H1N1)2009 (A(H1N1)pdm09) viruses, and seasonal human-lineage SIVs isolated in Japan and Vietnam. A hemagglutination inhibition (HI) assay was used to determine antigenic differences that differentiate the recent Japanese H1N2 and H3N2 SIVs from the H1N1 and H3N2 domestic vaccine strains. Minor antigenic variation between pig A(H1N1)pdm09 viruses was evident by HI assay using 13 mAbs raised against homologous virus. A Vietnamese H1N2 SIV, whose H1 gene originated from a human strain in the mid-2000s, reacted poorly with post-infection ferret serum against human vaccine strains from 2000-2010. These results provide useful information for selection of optimal strains for SIV vaccine production.
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Swine flu; H1N1 type A influenza ... The H1N1 virus is now considered a regular flu virus. It is one of the three viruses included in the regular (seasonal) flu vaccine . You cannot get H1N1 flu virus from ...
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Histone HIST1H1C/H1.2 regulates autophagy in the development of diabetic retinopathy.
Wang, Wenjun; Wang, Qing; Wan, Danyang; Sun, Yue; Wang, Lin; Chen, Hong; Liu, Chengyu; Petersen, Robert B; Li, Jianshuang; Xue, Weili; Zheng, Ling; Huang, Kun
2017-05-04
Autophagy plays critical and complex roles in many human diseases, including diabetes and its complications. However, the role of autophagy in the development of diabetic retinopathy remains uncertain. Core histone modifications have been reported involved in the development of diabetic retinopathy, but little is known about the histone variants. Here, we observed increased autophagy and histone HIST1H1C/H1.2, an important variant of the linker histone H1, in the retinas of type 1 diabetic rodents. Overexpression of histone HIST1H1C upregulates SIRT1 and HDAC1 to maintain the deacetylation status of H4K16, leads to upregulation of ATG proteins, then promotes autophagy in cultured retinal cell line. Histone HIST1H1C overexpression also promotes inflammation and cell toxicity in vitro. Knockdown of histone HIST1H1C reduces both the basal and stresses (including high glucose)-induced autophagy, and inhibits high glucose induced inflammation and cell toxicity. Importantly, AAV-mediated histone HIST1H1C overexpression in the retinas leads to increased autophagy, inflammation, glial activation and neuron loss, similar to the pathological changes identified in the early stage of diabetic retinopathy. Furthermore, knockdown of histone Hist1h1c by siRNA in the retinas of diabetic mice significantly attenuated the diabetes-induced autophagy, inflammation, glial activation and neuron loss. These results indicate that histone HIST1H1C may offer a novel therapeutic target for preventing diabetic retinopathy.
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H1N1-associated acute retinitis.
Rifkin, Lana; Schaal, Shlomit
2012-06-01
To present the first reported case of bilateral H(1)N(1)-associated acute retinitis and its successful treatment. Interventional case report. A 41-year-old HIV-positive male presented with acute vision loss, panuveitis, and retinitis. A diagnostic and therapeutic vitrectomy with intravitreal injection of vancomycin and ganciclovir and endolaser was performed. One month later, the patient returned with similar symptoms in the fellow eye and underwent the same procedure. ELISA immunoassay revealed H(1)N(1) antibodies in both the vitreous and serum. PCR for herpes viruses included HSV, CMV, and VZV. Bacterial and fungal cultures were negative. On 1-year follow-up, the vision remained 20/20 in both eyes without evidence of recurrent inflammation. H(1)N(1) should be included in the differential diagnosis of any patient with a history of recent influenza A (H(1)N(1)) infection and acute retinitis. H(1)N(1) may carry a better prognosis than other viruses causing acute retinitis.
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Yang, Huanliang; Chen, Yan; Shi, Jianzhong; Guo, Jing; Xin, Xiaoguang; Zhang, Jian; Wang, Dayan; Shu, Yuelong; Qiao, Chuanling; Chen, Hualan
2011-09-28
Influenza A (H1N1) virus has caused human influenza outbreaks in a worldwide pandemic since April 2009. Pigs have been found to be susceptible to this influenza virus under experimental and natural conditions, raising concern about their potential role in the pandemic spread of the virus. In this study, we generated a high-growth reassortant virus (SC/PR8) that contains the hemagglutinin (HA) and neuraminidase (NA) genes from a novel H1N1 isolate, A/Sichuan/1/2009 (SC/09), and six internal genes from A/Puerto Rico/8/34 (PR8) virus, by genetic reassortment. The immunogenicity and protective efficacy of this reassortant virus were evaluated at different doses in a challenge model using a homologous SC/09 or heterologous A/Swine/Guangdong/1/06(H1N2) virus (GD/06). Two doses of SC/PR8 virus vaccine elicited high-titer serum hemagglutination inhibiting (HI) antibodies specific for the 2009 H1N1 virus and conferred complete protection against challenge with either SC/09 or GD/06 virus, with reduced lung lesions and viral shedding in vaccine-inoculated animals compared with non-vaccinated control animals. These results indicated for the first time that a high-growth SC/PR8 reassortant H1N1 virus exhibits properties that are desirable to be a promising vaccine candidate for use in swine in the event of a pandemic H1N1 influenza. Copyright © 2011 Elsevier B.V. All rights reserved.
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Carter, Donald M; Lu, Hai-Rong; Bloom, Chalise E; Crevar, Corey J; Cherry, Joshua L; Lipman, David J; Ross, Ted M
2012-01-01
During the 2009 influenza pandemic, individuals over the age of 60 had the lowest incidence of infection with approximately 25% of these people having pre-existing, cross-reactive antibodies to novel 2009 H1N1 influenza isolates. It was proposed that older people had pre-existing antibodies induced by previous 1918-like virus infection(s) that cross-reacted to novel H1N1 strains. Using antisera collected from a cohort of individuals collected before the second wave of novel H1N1 infections, only a minority of individuals with 1918 influenza specific antibodies also demonstrated hemagglutination-inhibition activity against the novel H1N1 influenza. In this study, we examined human antisera collected from individuals that ranged between the ages of 1 month and 90 years to determine the profile of seropositive influenza immunity to viruses representing H1N1 antigenic eras over the past 100 years. Even though HAI titers to novel 2009 H1N1 and the 1918 H1N1 influenza viruses were positively associated, the association was far from perfect, particularly for the older and younger age groups. Therefore, there may be a complex set of immune responses that are retained in people infected with seasonal H1N1 that can contribute to the reduced rates of H1N1 influenza infection in older populations.
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Higher titers of some H5N1 and recent human H1N1 and H3N2 influenza viruses in Mv1 Lu vs. MDCK cells
2011-01-01
Background The infectivity of influenza A viruses can differ among the various primary cells and continuous cell lines used for such measurements. Over many years, we observed that all things equal, the cytopathic effects caused by influenza A subtype H1N1, H3N2, and H5N1 viruses were often detected earlier in a mink lung epithelial cell line (Mv1 Lu) than in MDCK cells. We asked whether virus yields as measured by the 50% tissue culture infectious dose and plaque forming titer also differed in MDCK and Mv1 Lu cells infected by the same influenza virus subtypes. Results The 50% tissue culture infectious dose and plaque forming titer of many influenza A subtype H1N1, H3N2, and H5N1 viruses was higher in Mv1 Lu than in MDCK cells. Conclusions The yields of influenza subtype H1N1, H3N2, and H5N1 viruses can be higher in Mv1 Lu cells than in MDCK cells. PMID:21314955
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... turn Javascript on. Feature: Flu 2009 H1N1 Flu Vaccine Facts Past Issues / Fall 2009 Table of Contents ... H1N1 flu vaccine. 1 The 2009 H1N1 flu vaccine is safe and well tested. Clinical trials conducted ...
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Liu, Wallace H.; Roemer, Sarah C.; Port, Alex M.; Churchill, Mair E. A.
2012-01-01
Anti-silencing function 1 (Asf1) and Chromatin Assembly Factor 1 (CAF-1) chaperone histones H3/H4 during the assembly of nucleosomes on newly replicated DNA. To understand the mechanism of histone H3/H4 transfer among Asf1, CAF-1 and DNA from a thermodynamic perspective, we developed and employed biophysical approaches using full-length proteins in the budding yeast system. We find that the C-terminal tail of Asf1 enhances the interaction of Asf1 with CAF-1. Surprisingly, although H3/H4 also enhances the interaction of Asf1 with the CAF-1 subunit Cac2, H3/H4 forms a tight complex with CAF-1 exclusive of Asf1, with an affinity weaker than Asf1–H3/H4 or H3/H4–DNA interactions. Unlike Asf1, monomeric CAF-1 binds to multiple H3/H4 dimers, which ultimately promotes the formation of (H3/H4)2 tetramers on DNA. Thus, transition of H3/H4 from the Asf1-associated dimer to the DNA-associated tetramer is promoted by CAF-1-induced H3/H4 oligomerization. PMID:23034810
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Kakita, Veera Mohana Rao; Rachineni, Kavitha; Hosur, Ramakrishna V
2017-07-21
The present manuscript focuses on fast and simultaneous determination of 1 H- 1 H and 1 H- 19 F scalar couplings in fluorinated complex steroid molecules. Incorporation of broadband PSYCHE homonuclear decoupling in the indirect dimension of zero-quantum filtered diagonal experiments (F1-PSYCHE-DIAG) suppresses 1 H- 1 H scalar couplings; however, it retains 1 H- 19 F scalar couplings (along F1 dimension) for the 19 F coupled protons while preserving the pure-shift nature for 1 H resonances uncoupled to 19 F. In such cases, along the direct dimensions, 1 H- 1 H scalar coupling multiplets deconvolute and they appear as duplicated multiplets for the 19 F coupled protons, which facilitates unambiguous discrimination of 19 F coupled 1 H chemical sites from the others. Further, as an added advantage, data acquisition has been accelerated by invoking the known ideas of spectral aliasing in the F1-PSYCHE-DIAG scheme and experiments demand only ~10 min of spectrometer times. Copyright © 2017 John Wiley & Sons, Ltd.
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Van Reeth, Kristien; Brown, Ian H; Dürrwald, Ralf; Foni, Emanuela; Labarque, Geoffrey; Lenihan, Patrick; Maldonado, Jaime; Markowska-Daniel, Iwona; Pensaert, Maurice; Pospisil, Zdenek; Koch, Guus
2008-05-01
Avian-like H1N1 and human-like H3N2 swine influenza viruses (SIV) have been considered widespread among pigs in Western Europe since the 1980s, and a novel H1N2 reassortant with a human-like H1 emerged in the mid 1990s. This study, which was part of the EC-funded 'European Surveillance Network for Influenza in Pigs 1', aimed to determine the seroprevalence of the H1N2 virus in different European regions and to compare the relative prevalences of each SIV between regions. Laboratories from Belgium, the Czech Republic, Germany, Italy, Ireland, Poland and Spain participated in an international serosurvey. A total of 4190 sow sera from 651 farms were collected in 2002-2003 and examined in haemagglutination inhibition tests against H1N1, H3N2 and H1N2. In Belgium, Germany, Italy and Spain seroprevalence rates to each of the three SIV subtypes were high (> or =30% of the sows seropositive) to very high (> or =50%), except for a lower H1N2 seroprevalence rate in Italy (13.8%). Most sows in these countries with high pig populations had antibodies to two or three subtypes. In Ireland, the Czech Republic and Poland, where swine farming is less intensive, H1N1 was the dominant subtype (8.0-11.7% seropositives) and H1N2 and H3N2 antibodies were rare (0-4.2% seropositives). Thus, SIV of H1N1, H3N2 and H1N2 subtype are enzootic in swine producing regions of Western Europe. In Central Europe, SIV activity is low and the circulation of H3N2 and H1N2 remains to be confirmed. The evolution and epidemiology of SIV throughout Europe is being further monitored through a second 'European Surveillance Network for Influenza in Pigs'.
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Webber, Amy L; Elena, Bénédicte; Griffin, John M; Yates, Jonathan R; Pham, Tran N; Mauri, Francesco; Pickard, Chris J; Gil, Ana M; Stein, Robin; Lesage, Anne; Emsley, Lyndon; Brown, Steven P
2010-07-14
A disaccharide is a challenging case for high-resolution (1)H solid-state NMR because of the 24 distinct protons (14 aliphatic and 10 OH) having (1)H chemical shifts that all fall within a narrow range of approximately 3 to 7 ppm. High-resolution (1)H (500 MHz) double-quantum (DQ) combined rotation and multiple pulse sequence (CRAMPS) solid-state NMR spectra of beta-maltose monohydrate are presented. (1)H-(1)H DQ-SQ CRAMPS spectra are presented together with (1)H (DQ)-(13)C correlation spectra obtained with a new pulse sequence that correlates a high-resolution (1)H DQ dimension with a (13)C single quantum (SQ) dimension using the refocused INEPT pulse-sequence element to transfer magnetization via one-bond (13)C-(1)H J couplings. Compared to the observation of only a single broad peak in a (1)H DQ spectrum recorded at 30 kHz magic-angle spinning (MAS), the use of DUMBO (1)H homonuclear decoupling in the (1)H DQ CRAMPS experiment allows the resolution of distinct DQ correlation peaks which, in combination with first-principles chemical shift calculations based on the GIPAW (Gauge Including Projector Augmented Waves) plane-wave pseudopotential approach, enables the assignment of the (1)H resonances to the 24 distinct protons. We believe this to be the first experimental solid-state NMR determination of the hydroxyl OH (1)H chemical shifts for a simple sugar. Variable-temperature (1)H-(1)H DQ CRAMPS spectra reveal small increases in the (1)H chemical shifts of the OH resonances upon decreasing the temperature from 348 K to 248 K.
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26 CFR 1.1033(h)-1 - Effective date.
Code of Federal Regulations, 2010 CFR
2010-04-01
... 26 Internal Revenue 11 2010-04-01 2010-04-01 true Effective date. 1.1033(h)-1 Section 1.1033(h)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Common Nontaxable Exchanges § 1.1033(h)-1 Effective date. Except as provided otherwise in...
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Qi, Li; Pujanauski, Lindsey M; Davis, A Sally; Schwartzman, Louis M; Chertow, Daniel S; Baxter, David; Scherler, Kelsey; Hartshorn, Kevan L; Slemons, Richard D; Walters, Kathie-Anne; Kash, John C; Taubenberger, Jeffery K
2014-11-18
Zoonotic avian influenza virus infections may lead to epidemics or pandemics. The 1918 pandemic influenza virus has an avian influenza virus-like genome, and its H1 hemagglutinin was identified as a key mammalian virulence factor. A chimeric 1918 virus expressing a contemporary avian H1 hemagglutinin, however, displayed murine pathogenicity indistinguishable from that of the 1918 virus. Here, isogenic chimeric avian influenza viruses were constructed on an avian influenza virus backbone, differing only by hemagglutinin subtype expressed. Viruses expressing the avian H1, H6, H7, H10, and H15 subtypes were pathogenic in mice and cytopathic in normal human bronchial epithelial cells, in contrast to H2-, H3-, H5-, H9-, H11-, H13-, H14-, and H16-expressing viruses. Mouse pathogenicity was associated with pulmonary macrophage and neutrophil recruitment. These data suggest that avian influenza virus hemagglutinins H1, H6, H7, H10, and H15 contain inherent mammalian virulence factors and likely share a key virulence property of the 1918 virus. Consequently, zoonotic infections with avian influenza viruses bearing one of these hemagglutinins may cause enhanced disease in mammals. Influenza viruses from birds can cause outbreaks in humans and may contribute to the development of pandemics. The 1918 pandemic influenza virus has an avian influenza virus-like genome, and its main surface protein, an H1 subtype hemagglutinin, was identified as a key mammalian virulence factor. In a previous study, a 1918 virus expressing an avian H1 gene was as virulent in mice as the reconstructed 1918 virus. Here, a set of avian influenza viruses was constructed, differing only by hemagglutinin subtype. Viruses with the avian H1, H6, H7, H10, and H15 subtypes caused severe disease in mice and damaged human lung cells. Consequently, infections with avian influenza viruses bearing one of these hemagglutinins may cause enhanced disease in mammals, and therefore surveillance for human infections
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Qi, Li; Pujanauski, Lindsey M.; Davis, A. Sally; Schwartzman, Louis M.; Chertow, Daniel S.; Baxter, David; Scherler, Kelsey; Hartshorn, Kevan L.; Slemons, Richard D.; Walters, Kathie-Anne; Kash, John C.
2014-01-01
ABSTRACT Zoonotic avian influenza virus infections may lead to epidemics or pandemics. The 1918 pandemic influenza virus has an avian influenza virus-like genome, and its H1 hemagglutinin was identified as a key mammalian virulence factor. A chimeric 1918 virus expressing a contemporary avian H1 hemagglutinin, however, displayed murine pathogenicity indistinguishable from that of the 1918 virus. Here, isogenic chimeric avian influenza viruses were constructed on an avian influenza virus backbone, differing only by hemagglutinin subtype expressed. Viruses expressing the avian H1, H6, H7, H10, and H15 subtypes were pathogenic in mice and cytopathic in normal human bronchial epithelial cells, in contrast to H2-, H3-, H5-, H9-, H11-, H13-, H14-, and H16-expressing viruses. Mouse pathogenicity was associated with pulmonary macrophage and neutrophil recruitment. These data suggest that avian influenza virus hemagglutinins H1, H6, H7, H10, and H15 contain inherent mammalian virulence factors and likely share a key virulence property of the 1918 virus. Consequently, zoonotic infections with avian influenza viruses bearing one of these hemagglutinins may cause enhanced disease in mammals. PMID:25406382
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Lessler, Justin; Santos, Thais dos; Aguilera, Ximena; Brookmeyer, Ron; Cummings, Derek AT
2010-01-01
In late April 2009 the emergence of 2009 pandemic influenza A (H1N1pdm) virus was detected in humans. From its detection through July 18th, 2009, confirmed cases of H1N1pdm in the Americas were periodically reported to the Pan-American Health Organization (PAHO) by member states. Because the Americas span much of the world’s latitudes, this data provides an excellent opportunity to examine variation in H1N1pdm transmission by season. Using reports from PAHO member states from April 26th, 2009 through July 18th, 2009, we characterize the early spread of the H1N1 pandemic in the Americas. For a geographically representative sample of member states we estimate the reproductive number (R) of H1N1pdm over the reporting period. The association between these estimates and latitude, temperature, humidity and population age structure was estimated. Estimates of the peak reproductive number of H1N1pdm ranged from 1.3 (for Panama, Colombia) to 2.1 (for Chile). We found that reproductive number estimates were most associated with latitude in both univariate and multivariate analyses. To the extent that latitude is a proxy for seasonal changes in climate and behavior, this association suggests a strong seasonal component to H1N1pdm transmission. However, the reasons for this seasonality remain unclear. PMID:20847900
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Mesman, Annelies W; Westerhuis, Brenda M; Ten Hulscher, Hinke I; Jacobi, Ronald H; de Bruin, Erwin; van Beek, Josine; Buisman, Annemarie M; Koopmans, Marion P; van Binnendijk, Robert S
2016-09-01
Pre-existing immunity played a significant role in protection during the latest influenza A virus H1N1 pandemic, especially in older age groups. Structural similarities were found between A(H1N1)2009 and older H1N1 virus strains to which humans had already been exposed. Broadly cross-reactive antibodies capable of neutralizing the A(H1N1)2009 virus have been implicated in this immune protection in adults. We investigated the serological profile of a group of young children aged 9 years (n=55), from whom paired blood samples were available, just prior to the pandemic wave (March 2009) and shortly thereafter (March 2010). On the basis of A(H1N1)2009 seroconversion, 27 of the 55 children (49 %) were confirmed to be infected between these two time points. Within the non-infected group of 28 children (51 %), high levels of seasonal antibodies to H1 and H3 HA1 antigens were detected prior to pandemic exposure, reflecting past infection with H1N1 and H3N2, both of which had circulated in The Netherlands prior to the pandemic. In some children, this reactivity coincided with specific antibody reactivity against A(H1N1)2009. While these antibodies were not able to neutralize the A(H1N1)2009 virus, they were able to mediate antibody-dependent cellular cytotoxicity (ADCC) in vitro upon interaction with the A(H1N1)2009 virus. This finding suggests that cross-reactive antibodies could contribute to immune protection in children via ADCC.
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Genetic Characterization of H1N1 and H1N2 Influenza A Viruses Circulating in Ontario Pigs in 2012.
Grgić, Helena; Costa, Marcio; Friendship, Robert M; Carman, Susy; Nagy, Éva; Poljak, Zvonimir
2015-01-01
The objective of this study was to characterize H1N1 and H1N2 influenza A virus isolates detected during outbreaks of respiratory disease in pig herds in Ontario (Canada) in 2012. Six influenza viruses were included in analysis using full genome sequencing based on the 454 platform. In five H1N1 isolates, all eight segments were genetically related to 2009 pandemic virus (A(H1N1)pdm09). One H1N2 isolate had hemagglutinin (HA), polymerase A (PA) and non-structural (NS) genes closely related to A(H1N1)pdm09, and neuraminidase (NA), matrix (M), polymerase B1 (PB1), polymerase B2 (PB2), and nucleoprotein (NP) genes originating from a triple-reassortant H3N2 virus (tr H3N2). The HA gene of five Ontario H1 isolates exhibited high identity of 99% with the human A(H1N1)pdm09 [A/Mexico/InDRE4487/09] from Mexico, while one Ontario H1N1 isolate had only 96.9% identity with this Mexican virus. Each of the five Ontario H1N1 viruses had between one and four amino acid (aa) changes within five antigenic sites, while one Ontario H1N2 virus had two aa changes within two antigenic sites. Such aa changes in antigenic sites could have an effect on antibody recognition and ultimately have implications for immunization practices. According to aa sequence analysis of the M2 protein, Ontario H1N1 and H1N2 viruses can be expected to offer resistance to adamantane derivatives, but not to neuraminidase inhibitors.
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Genetic Characterization of H1N1 and H1N2 Influenza A Viruses Circulating in Ontario Pigs in 2012
Grgić, Helena; Costa, Marcio; Friendship, Robert M.; Carman, Susy; Nagy, Éva; Poljak, Zvonimir
2015-01-01
The objective of this study was to characterize H1N1 and H1N2 influenza A virus isolates detected during outbreaks of respiratory disease in pig herds in Ontario (Canada) in 2012. Six influenza viruses were included in analysis using full genome sequencing based on the 454 platform. In five H1N1 isolates, all eight segments were genetically related to 2009 pandemic virus (A(H1N1)pdm09). One H1N2 isolate had hemagglutinin (HA), polymerase A (PA) and non-structural (NS) genes closely related to A(H1N1)pdm09, and neuraminidase (NA), matrix (M), polymerase B1 (PB1), polymerase B2 (PB2), and nucleoprotein (NP) genes originating from a triple-reassortant H3N2 virus (tr H3N2). The HA gene of five Ontario H1 isolates exhibited high identity of 99% with the human A(H1N1)pdm09 [A/Mexico/InDRE4487/09] from Mexico, while one Ontario H1N1 isolate had only 96.9% identity with this Mexican virus. Each of the five Ontario H1N1 viruses had between one and four amino acid (aa) changes within five antigenic sites, while one Ontario H1N2 virus had two aa changes within two antigenic sites. Such aa changes in antigenic sites could have an effect on antibody recognition and ultimately have implications for immunization practices. According to aa sequence analysis of the M2 protein, Ontario H1N1 and H1N2 viruses can be expected to offer resistance to adamantane derivatives, but not to neuraminidase inhibitors. PMID:26030614
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Ion chemistry of 1H-1,2,3-triazole.
Ichino, Takatoshi; Andrews, Django H; Rathbone, G Jeffery; Misaizu, Fuminori; Calvi, Ryan M D; Wren, Scott W; Kato, Shuji; Bierbaum, Veronica M; Lineberger, W Carl
2008-01-17
A combination of experimental methods, photoelectron-imaging spectroscopy, flowing afterglow-photoelectron spectroscopy and the flowing afterglow-selected ion flow tube technique, and electronic structure calculations at the B3LYP/6-311++G(d,p) level of density functional theory (DFT) have been employed to study the mechanism of the reaction of the hydroxide ion (HO-) with 1H-1,2,3-triazole. Four different product ion species have been identified experimentally, and the DFT calculations suggest that deprotonation by HO- at all sites of the triazole takes place to yield these products. Deprotonation of 1H-1,2,3-triazole at the N1-H site gives the major product ion, the 1,2,3-triazolide ion. The 335 nm photoelectron-imaging spectrum of the ion has been measured. The electron affinity (EA) of the 1,2,3-triazolyl radical has been determined to be 3.447 +/- 0.004 eV. This EA and the gas-phase acidity of 2H-1,2,3-triazole are combined in a negative ion thermochemical cycle to determine the N-H bond dissociation energy of 2H-1,2,3-triazole to be 112.2 +/- 0.6 kcal mol-1. The 363.8 nm photoelectron spectroscopic measurements have identified the other three product ions. Deprotonation of 1H-1,2,3-triazole at the C5 position initiates fragmentation of the ring structure to yield a minor product, the ketenimine anion. Another minor product, the iminodiazomethyl anion, is generated by deprotonation of 1H-1,2,3-triazole at the C4 position, followed by N1-N2 bond fission. Formation of the other minor product, the 2H-1,2,3-triazol-4-ide ion, can be rationalized by initial deprotonation of 1H-1,2,3-triazole at the N1-H site and subsequent proton exchanges within the ion-molecule complex. The EA of the 2H-1,2,3-triazol-4-yl radical is 1.865 +/- 0.004 eV.
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Sensitivity of influenza rapid diagnostic tests to H5N1 and 2009 pandemic H1N1 viruses.
Sakai-Tagawa, Yuko; Ozawa, Makoto; Tamura, Daisuke; Le, Mai thi Quynh; Nidom, Chairul A; Sugaya, Norio; Kawaoka, Yoshihiro
2010-08-01
Simple and rapid diagnosis of influenza is useful for making treatment decisions in the clinical setting. Although many influenza rapid diagnostic tests (IRDTs) are available for the detection of seasonal influenza virus infections, their sensitivity for other viruses, such as H5N1 viruses and the recently emerged swine origin pandemic (H1N1) 2009 virus, remains largely unknown. Here, we examined the sensitivity of 20 IRDTs to various influenza virus strains, including H5N1 and 2009 pandemic H1N1 viruses. Our results indicate that the detection sensitivity to swine origin H1N1 viruses varies widely among IRDTs, with some tests lacking sufficient sensitivity to detect the early stages of infection when the virus load is low.
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NASA Astrophysics Data System (ADS)
Niu, Chunhuan; Jin, Bo; Shang, Yu; Liu, Qiangqiang; Peng, Rufang
2018-04-01
4-Amino-1,2,4-triazolium 1'-hydroxy-1H,1'H-5,5'-bitetrazol-1-olate (ATHBTO) was synthesized by reacting 4-amino-1,2,4-triazole (AT) and 1H,1‧H-5,5‧-bistetrazole-1,1‧-diolate dihydrate (H2BTO.2H2O). Its crystal structure was characterized through single-crystal X-ray diffraction. Meanwhile, FTIR, 1H NMR, 13C NMR, and elemental analysis were also introduced to analyze its composition. The thermal stability was investigated by differential scanning calorimetry, thermogravimetric analysis, and thermogravimetric tandem infrared spectrum. Results indicated that ATHBTO exhibited excellent resistance to thermal decompositions reaching 511.4 K and had a 64.6% mass loss between 475.7 and 552.3 K. The kinetics parameters were calculated by Kissinger's method and Ozawa-Doyle's method. Moreover, according to the Kamlet-Jacobs formula, the calculated detonation velocity and detonation pressure of ATHBTO attained 8218 m/s and 28.69 GPa, respectively.
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Chiapponi, Chiara; Moreno, Ana; Barbieri, Ilaria; Merenda, Marianna; Foni, Emanuela
2012-09-01
In Europe, three major swine influenza viral (SIV) subtypes (H1N1, H1N2 and H3N2) have been isolated in pigs. Developing a test that is able to detect and identify the subtype of the circulating strain rapidly during an outbreak of respiratory disease in the pig population is of essential importance. This study describes two multiplex RT-PCRs which distinguish the haemagglutinin (HA) gene and the neuraminidase (NA) gene of the three major subtypes of SIV circulating in Europe. The HA PCR was able to identify the lineage (avian or human) of the HA of H1 subtypes. The analytical sensitivity of the test, considered to be unique, was assessed using three reference viruses. The detection limit corresponded to 1×10(-1) TCID(50)/200μl for avian-like H1N1, 1×10(0) TCID(50)/200μl for human-like H1N2 and 1×10(1) TCID(50)/200μl for H3N2 SIV. The multiplex RT-PCR was first carried out on a collection of 70 isolated viruses showing 100% specificity and then on clinical samples, from which viruses had previously been isolated, resulting in an 89% positive specificity of the viral subtype. Finally, the test was able to identify the viral subtype correctly in 56% of influenza A positive samples, from which SIV had not been isolated previously. It was also possible to identify mixed viral infections and the circulation of a reassortant strain before performing genomic studies. Copyright © 2012 Elsevier B.V. All rights reserved.
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USDA-ARS?s Scientific Manuscript database
The pandemic H1N1 virus of 2009 (2009 H1N1) continues to cause illness worldwide, primarily in younger age groups. To better understand the pathogenesis of these viruses in mammals, we used a mouse model to evaluate the relative virulence of selected 2009 H1N1 viruses and compared them to a represe...
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NASA Astrophysics Data System (ADS)
Psarski, Maciej; Marczak, Jacek; Celichowski, Grzegorz; Sobieraj, Grzegorz B.; Gumowski, Konrad; Zhou, Feng; Liu, Weimin
2012-10-01
Nature inspires the design of synthetic materials with superhydrophobic properties, which can be used for applications ranging from self-cleaning surfaces to microfluidic devices. Their water repellent properties are due to hierarchical (micrometer- and nanometre-scale) surface morphological structures, either made of hydrophobic substances or hydrophobized by appropriate surface treatment. In this work, the efficiency of two surface treatment procedures, with a hydrophobic fluoropolymer, synthesized and deposited from 1H,1H,2H,2H-perfluorooctyltrichlorosilane (PFOTS) is investigated. The procedures involved reactions from the gas and liquid phases of the PFOTS/hexane solutions. The hierarchical structure is created in an epoxy nanocomposite surface, by filling the resin with alumina nanoparticles and micron-sized glass beads and subsequent sandblasting with corundum microparticles. The chemical structure of the deposited fluoropolymer was examined using XPS spectroscopy. The topography of the modified surfaces was characterized using scanning electron microscopy (SEM), and atomic force microscopy (AFM). The hydrophobic properties of the modified surfaces were investigated by water contact and sliding angles measurements. The surfaces exhibited water contact angles of above 150° for both modification procedures, however only the gas phase modification provided the non-sticking behaviour of water droplets (sliding angle of 3°). The discrepancy is attributed to extra surface roughness provided by the latter procedure.
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Pichyangkul, Sathit; Krasaesub, Somporn; Jongkaewwattana, Anan; Thitithanyanont, Arunee; Wiboon-ut, Suwimon; Yongvanitchit, Kosol; Limsalakpetch, Amporn; Kum-Arb, Utaiwan; Mongkolsirichaikul, Duangrat; Khemnu, Nuanpan; Mahanonda, Rangsini; Garcia, Jean-Michel; Mason, Carl J.; Walsh, Douglas S.; Saunders, David L.
2014-01-01
We studied cross-reactive antibodies against avian influenza H5N1 and 2009 pandemic (p) H1N1 in 200 serum samples from US military personnel collected before the H1N1 pandemic. Assays used to measure antibodies against viral proteins involved in protection included a hemagglutination inhibition (HI) assay and a neuraminidase inhibition (NI) assay. Viral neutralization by antibodies against avian influenza H5N1 and 2009 pH1N1 was assessed by influenza (H5) pseudotyped lentiviral particle-based and H1N1 microneutralization assays. Some US military personnel had cross-neutralizing antibodies against H5N1 (14%) and 2009 pH1N1 (16.5%). The odds of having cross-neutralizing antibodies against 2009 pH1N1 were 4.4 times higher in subjects receiving more than five inactivated whole influenza virus vaccinations than those subjects with no record of vaccination. Although unclear if the result of prior vaccination or disease exposure, these pre-existing antibodies may prevent or reduce disease severity. PMID:24277784
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Busquets, Núria; Segalés, Joaquim; Córdoba, Lorena; Mussá, Tufaria; Crisci, Elisa; Martín-Valls, Gerard E; Simon-Grifé, Meritxell; Pérez-Simó, Marta; Pérez-Maíllo, Monica; Núñez, Jose I; Abad, Francesc X; Fraile, Lorenzo; Pina, Sonia; Majó, Natalia; Bensaid, Albert; Domingo, Mariano; Montoya, María
2010-01-01
The recent pandemic caused by human influenza virus A(H1N1) 2009 contains ancestral gene segments from North American and Eurasian swine lineages as well as from avian and human influenza lineages. The emergence of this A(H1N1) 2009 poses a potential global threat for human health and the fact that it can infect other species, like pigs, favours a possible encounter with other influenza viruses circulating in swine herds. In Europe, H1N1, H1N2 and H3N2 subtypes of swine influenza virus currently have a high prevalence in commercial farms. To better assess the risk posed by the A(H1N1) 2009 in the actual situation of swine farms, we sought to analyze whether a previous infection with a circulating European avian-like swine A/Swine/Spain/53207/2004 (H1N1) influenza virus (hereafter referred to as SwH1N1) generated or not cross-protective immunity against a subsequent infection with the new human pandemic A/Catalonia/63/2009 (H1N1) influenza virus (hereafter referred to as pH1N1) 21 days apart. Pigs infected only with pH1N1 had mild to moderate pathological findings, consisting on broncho-interstitial pneumonia. However, pigs inoculated with SwH1N1 virus and subsequently infected with pH1N1 had very mild lung lesions, apparently attributed to the remaining lesions caused by SwH1N1 infection. These later pigs also exhibited boosted levels of specific antibodies. Finally, animals firstly infected with SwH1N1 virus and latter infected with pH1N1 exhibited undetectable viral RNA load in nasal swabs and lungs after challenge with pH1N1, indicating a cross-protective effect between both strains. © INRA, EDP Sciences, 2010.
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Lichtscheidl, Alejandro G.; Janicke, Michael T.; Scott, Brian L.; ...
2015-08-21
The synthesis and full characterization, including Nuclear Magnetic Resonance (NMR) data ( 1H, 13C{ 1H} and 119Sn{ 1H}), for a series of Me 3SnX (X = O-2,6-tBu 2C 6H 3 (1), (Me 3Sn)N(2,6- iPr 2C 6H 3) (3), NH-2,4,6- tBu 3C 6H 2 (4), N(SiMe 3) 2 (5), NEt 2, C 5Me 5 (6), Cl, Br, I, and SnMe 3) compounds in benzene-d 6, toluene-d 8, dichloromethane-d 2, chloroform-d 1, acetonitrile-d 3, and tetrahydrofuran-d 8 are reported. The X-ray crystal structures of Me 3Sn(O-2,6- tBu 2C 6H 3) (1), Me 3Sn(O-2,6- iPr 2C 6H 3) (2), and (Me 3Sn)(NH-2,4,6- tBumore » 3C 6H 2) (4) are also presented. As a result, these compiled data complement existing literature data and ease the characterization of these compounds by routine NMR experiments.« less
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Code of Federal Regulations, 2010 CFR
2010-10-01
... 42 Public Health 1 2010-10-01 2010-10-01 false Applicability. 52h.1 Section 52h.1 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS SCIENTIFIC PEER REVIEW OF RESEARCH GRANT APPLICATIONS AND RESEARCH AND DEVELOPMENT CONTRACT PROJECTS § 52h.1 Applicability. (a) This part...
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Bauer, Katja; Richter, Martina; Wutzler, Peter; Schmidtke, Michaela
2009-04-01
In the flu season 2005/2006 amantadine-resistant human influenza A viruses (FLUAV) of subtype H3N2 circulated in Germany. This raises questions on the neuraminidase inhibitor (NAI) susceptibility of FLUAV. To get an answer, chemiluminescence-based neuraminidase inhibition assays were performed with 51 H1N1, H1N2, and H3N2 FLUAV isolated in Germany from 2001 to 2005/2006. According to the mean IC(50) values (0.38-0.91 nM for oseltamivir and 0.76-1.13 nM for zanamivir) most H1N1 and H3N2 FLUAV were NAI-susceptible. But, about four times higher zanamivir concentrations were necessary to inhibit neuraminidase activity of H1N2 viruses. Two H1N1 isolates were less susceptible to both drugs in NA inhibition as well as virus yield reduction assays. Results from sequence analysis of viral hemagglutinin and neuraminidase genes and evolutionary analysis of N2 gene revealed (i) different subclades for N2 in H1N2 and H3N2 FLUAV that could explain the differences in zanamivir susceptibility among these viruses and (ii) specific amino acid substitutions in the neuraminidase segment of the two less NAI-susceptible H1N1 isolates. One H3N2 was isolate proved to be a mixture of a NA deletion mutant and full-length NA viruses.
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Minns, F C; Mhuineachain, A Ni; van Beek, E J R; Ritchie, G; Hill, A; Murchison, J T
2015-09-01
To review, phenotype and assess potential prognostic value of initial chest X-ray findings in patients with H1N1 influenza during seasonal outbreaks of 2009 and 2010, in comparison with non-H1N1, community acquired pneumonia (CAP). We retrospectively identified 72 patients admitted to hospital with pneumonia during the seasons of 2009 and 2010. H1N1 cases were confirmed by virology PCR. Presenting chest X-rays were jointly read by 2 radiologists, who were 'blinded' to further patient details and divided into 6 zones. Total number of opacified zones, the pattern and distribution of changes and length of hospital stay were recorded. Patients with H1N1 demonstrated more opacified zones (mean of 2.9 compared with 2.0; p=0.006), which were bilateral in two-thirds compared with a quarter of those with non-H1N1 CAP (p=0.001). H1N1 radiographs were more likely to be 'patchy' versus 'confluent' changes of non-H1N1 CAP (p=0.03) and more often demonstrated peripheral distribution (p=0.01). H1N1 patients tended to stay in hospital longer (not significant; p=0.08). A positive correlation existed between number of affected zones and length of inpatient stay, which was statistically significant for the cohorts combined (p=0.02). The findings were the same for the two evaluated seasons. H1N1 patients demonstrated more extensive disease, which was more likely bilateral, 'patchy', and peripheral in distribution. With increasing global cases of H1N1, knowledge of the typical findings of the H1N1 presenting chest X-ray may assist with early triage of patients, particularly where rapid viral testing is not available. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
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NASA Astrophysics Data System (ADS)
Wang, Yong-Tao; Lü, Lin-Rui; Tang, Gui-Mei
2018-03-01
Two new benzimidazole salts, namely, [H2IBI]2+ 2X (X = NO3- (1), ClO4- (2) [IBI = 2-((1H-imidazol-1-yl)methyl)-1H-benzimidazole], were grown through reacting IBI and two different inorganic acids by slow evaporation method, respectively. Compounds 1 and 2 have been characterized by single-crystal X-ray diffraction, IR, UV-Vis, and thermogravimetric analyses (TGA). In both compounds, a set of hydrogen bonds (C/Nsbnd H⋯O) can be clearly observed, through which a three-dimensional framework will be generated. The luminescent spectra show the emission peaks in compounds 1 and 2 are found at 375 and 371 nm, respectively. By comparison with the free IBI, the emission maxima of compounds 1 and 2 are obviously red-shifted about 67 and 63 nm, respectively.
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Identification of swine H1N2/pandemic H1N1 reassortant influenza virus in pigs, United States.
Ali, Ahmed; Khatri, Mahesh; Wang, Leyi; Saif, Yehia M; Lee, Chang-Won
2012-07-06
In October and November 2010, novel H1N2 reassortant influenza viruses were identified from pigs showing mild respiratory signs that included cough and depression. Sequence and phylogenetic analysis showed that the novel H1N2 reassortants possesses HA and NA genes derived from recent H1N2 swine isolates similar to those isolated from Midwest. Compared to the majority of reported reassortants, both viruses preserved human-like host restrictive and putative antigenic sites in their HA and NA genes. The four internal genes, PB2, PB1, PA, and NS were similar to the contemporary swine triple reassortant viruses' internal genes (TRIG). Interestingly, NP and M genes of the novel reassortants were derived from the 2009 pandemic H1N1. The NP and M proteins of the two isolates demonstrated one (E16G) and four (G34A, D53E, I109T, and V313I) amino acid changes in the M2 and NP proteins, respectively. Similar amino acid changes were also noticed upon incorporation of the 2009 pandemic H1N1 NP in other reassortant viruses reported in the U.S. Thus the role of those amino acids in relation to host adaptation need to be further investigated. The reassortments of pandemic H1N1 with swine influenza viruses and the potential of interspecies transmission of these reassortants from swine to other species including human indicate the importance of systematic surveillance of swine population to determine the origin, the prevalence of similar reassortants in the U.S. and their impact on both swine production and public health. Copyright © 2012 Elsevier B.V. All rights reserved.
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O'Donnell, Christopher D.; Wright, Amber; Vogel, Leatrice N.; Wei, Chih-Jen; Nabel, Gary J.
2012-01-01
Compared to seasonal influenza viruses, the 2009 pandemic H1N1 (pH1N1) virus caused greater morbidity and mortality in children and young adults. People over 60 years of age showed a higher prevalence of cross-reactive pH1N1 antibodies, suggesting that they were previously exposed to an influenza virus or vaccine that was antigenically related to the pH1N1 virus. To define the basis for this cross-reactivity, ferrets were infected with H1N1 viruses of variable antigenic distance that circulated during different decades from the 1930s (Alaska/35), 1940s (Fort Monmouth/47), 1950s (Fort Warren/50), and 1990s (New Caledonia/99) and challenged with 2009 pH1N1 virus 6 weeks later. Ferrets primed with the homologous CA/09 or New Jersey/76 (NJ/76) virus served as a positive control, while the negative control was an influenza B virus that should not cross-protect against influenza A virus infection. Significant protection against challenge virus replication in the respiratory tract was observed in ferrets primed with AK/35, FM/47, and NJ/76; FW/50-primed ferrets showed reduced protection, and NC/99-primed ferrets were not protected. The hemagglutinins (HAs) of AK/35, FM/47, and FW/50 differ in the presence of glycosylation sites. We found that the loss of protective efficacy observed with FW/50 was associated with the presence of a specific glycosylation site. Our results suggest that changes in the HA occurred between 1947 and 1950, such that prior infection could no longer protect against 2009 pH1N1 infection. This provides a mechanistic understanding of the nature of serological cross-protection observed in people over 60 years of age during the 2009 H1N1 pandemic. PMID:22674976
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O'Donnell, Christopher D; Wright, Amber; Vogel, Leatrice N; Wei, Chih-Jen; Nabel, Gary J; Subbarao, Kanta
2012-08-01
Compared to seasonal influenza viruses, the 2009 pandemic H1N1 (pH1N1) virus caused greater morbidity and mortality in children and young adults. People over 60 years of age showed a higher prevalence of cross-reactive pH1N1 antibodies, suggesting that they were previously exposed to an influenza virus or vaccine that was antigenically related to the pH1N1 virus. To define the basis for this cross-reactivity, ferrets were infected with H1N1 viruses of variable antigenic distance that circulated during different decades from the 1930s (Alaska/35), 1940s (Fort Monmouth/47), 1950s (Fort Warren/50), and 1990s (New Caledonia/99) and challenged with 2009 pH1N1 virus 6 weeks later. Ferrets primed with the homologous CA/09 or New Jersey/76 (NJ/76) virus served as a positive control, while the negative control was an influenza B virus that should not cross-protect against influenza A virus infection. Significant protection against challenge virus replication in the respiratory tract was observed in ferrets primed with AK/35, FM/47, and NJ/76; FW/50-primed ferrets showed reduced protection, and NC/99-primed ferrets were not protected. The hemagglutinins (HAs) of AK/35, FM/47, and FW/50 differ in the presence of glycosylation sites. We found that the loss of protective efficacy observed with FW/50 was associated with the presence of a specific glycosylation site. Our results suggest that changes in the HA occurred between 1947 and 1950, such that prior infection could no longer protect against 2009 pH1N1 infection. This provides a mechanistic understanding of the nature of serological cross-protection observed in people over 60 years of age during the 2009 H1N1 pandemic.
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Code of Federal Regulations, 2010 CFR
2010-04-01
... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Example. 1.642(h)-5 Section 1.642(h)-5 Internal... TAXES Estates, Trusts, and Beneficiaries § 1.642(h)-5 Example. The application of section 642(h) may be... deductions 14,800 It also has a capital loss of $5,000. (b) Under section 642(h)(1), an unused net operating...
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Code of Federal Regulations, 2012 CFR
2012-04-01
... employment of H-1B, H-1B1, and E-3 nonimmigrants and how do employers apply for H-1B, H-1B1, and E-3 visas... Requirements for Employers Seeking To Employ Nonimmigrants on H-1b Visas in Specialty Occupations and as Fashion Models, and Requirements for Employers Seeking To Employ Nonimmigrants on H-1b1 and E-3 Visas in...
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Code of Federal Regulations, 2013 CFR
2013-04-01
... employment of H-1B, H-1B1, and E-3 nonimmigrants and how do employers apply for H-1B, H-1B1, and E-3 visas... Requirements for Employers Seeking To Employ Nonimmigrants on H-1b Visas in Specialty Occupations and as Fashion Models, and Requirements for Employers Seeking To Employ Nonimmigrants on H-1b1 and E-3 Visas in...
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Code of Federal Regulations, 2014 CFR
2014-04-01
... employment of H-1B, H-1B1, and E-3 nonimmigrants and how do employers apply for H-1B, H-1B1, and E-3 visas... Requirements for Employers Seeking To Employ Nonimmigrants on H-1b Visas in Specialty Occupations and as Fashion Models, and Requirements for Employers Seeking To Employ Nonimmigrants on H-1b1 and E-3 Visas in...
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Code of Federal Regulations, 2011 CFR
2011-04-01
... employment of H-1B, H-1B1, and E-3 nonimmigrants and how do employers apply for H-1B, H-1B1, and E-3 visas... Requirements for Employers Seeking To Employ Nonimmigrants on H-1b Visas in Specialty Occupations and as Fashion Models, and Requirements for Employers Seeking To Employ Nonimmigrants on H-1b1 and E-3 Visas in...
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Code of Federal Regulations, 2010 CFR
2010-04-01
... employment of H-1B, H-1B1, and E-3 nonimmigrants and how do employers apply for H-1B, H-1B1, and E-3 visas... Requirements for Employers Seeking To Employ Nonimmigrants on H-1b Visas in Specialty Occupations and as Fashion Models, and Requirements for Employers Seeking To Employ Nonimmigrants on H-1b1 and E-3 Visas in...
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Teledyne H1RG, H2RG, and H4RG Noise Generator
NASA Technical Reports Server (NTRS)
Rauscher, Bernard J.
2015-01-01
This paper describes the near-infrared detector system noise generator (NG) that we wrote for the James Webb Space Telescope (JWST) Near Infrared Spectrograph (NIRSpec). NG simulates many important noise components including; (1) white "read noise", (2) residual bias drifts, (3) pink 1/f noise, (4) alternating column noise, and (5) picture frame noise. By adjusting the input parameters, NG can simulate noise for Teledyne's H1RG, H2RG, and H4RG detectors with and without Teledyne's SIDECAR ASIC IR array controller. NG can be used as a starting point for simulating astronomical scenes by adding dark current, scattered light, and astronomical sources into the results from NG. NG is written in Python-3.4.
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Flick, H; Drescher, M; Prattes, J; Tovilo, K; Kessler, H H; Vander, K; Seeber, K; Palfner, M; Raggam, R B; Avian, A; Krause, R; Hoenigl, M
2014-02-01
Reliable and rapid diagnosis of influenza A H1N1 is essential to initiate appropriate antiviral therapy and preventive measures. We analysed the differences in clinical presentation and laboratory parameters between emergency department patients with PCR-confirmed H1N1 influenza infection (n = 199) and those with PCR-negative influenza-like illness (ILI; n = 252). Cough, wheezing, leucopenia, eosinopenia and a lower C-reactive protein remained significant predictors of H1N1 influenza. Proposed combinations of clinical symptoms with simple laboratory parameters (e.g. reported or measured fever and either cough or leucocytes <8.5 × 10(9) /L) were clearly superior to currently used official ILI case definitions that use clinical criteria alone. © 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.
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Ambati, Aditya; Valentini, Davide; Montomoli, Emanuele; Lapini, Guilia; Biuso, Fabrizio; Wenschuh, Holger; Magalhaes, Isabelle; Maeurer, Markus
2015-01-01
A high content peptide microarray containing the entire influenza A virus [A/California/08/2009(H1N1)] proteome and haemagglutinin proteins from 12 other influenza A subtypes, including the haemagglutinin from the [A/South Carolina/1/1918(H1N1)] strain, was used to gauge serum IgG epitope signatures before and after Pandemrix® vaccination or H1N1 infection in a Swedish cohort during the pandemic influenza season 2009. A very narrow pattern of pandemic flu-specific IgG epitope recognition was observed in the serum from individuals who later contracted H1N1 infection. Moreover, the pandemic influenza infection generated IgG reactivity to two adjacent epitopes of the neuraminidase protein. The differential serum IgG recognition was focused on haemagglutinin 1 (H1) and restricted to classical antigenic sites (Cb) in both the vaccinated controls and individuals with flu infections. We further identified a novel epitope VEPGDKITFEATGNL on the Ca antigenic site (251–265) of the pandemic flu haemagglutinin, which was exclusively recognized in serum from individuals with previous vaccinations and never in serum from individuals with H1N1 infection (confirmed by RNA PCR analysis from nasal swabs). This epitope was mapped to the receptor-binding domain of the influenza haemagglutinin and could serve as a correlate of immune protection in the context of pandemic flu. The study shows that unbiased epitope mapping using peptide microarray technology leads to the identification of biologically and clinically relevant target structures. Most significantly an H1N1 infection induced a different footprint of IgG epitope recognition patterns compared with the pandemic H1N1 vaccine. PMID:25639813
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Treatment and Prevention of Pandemic H1N1 Influenza.
Rewar, Suresh; Mirdha, Dashrath; Rewar, Prahlad
2015-01-01
Swine influenza is a respiratory infection common to pigs worldwide caused by type A influenza viruses, principally subtypes H1N1, H1N2, H2N1, H3N1, H3N2, and H2N3. Swine influenza viruses also can cause moderate to severe illness in humans and affect persons of all age groups. People in close contact with swine are at especially high risk. Until recently, epidemiological study of influenza was limited to resource-rich countries. The World Health Organization declared an H1N1 pandemic on June 11, 2009, after more than 70 countries reported 30,000 cases of H1N1 infection. In 2015, incidence of swine influenza increased substantially to reach a 5-year high. In India in 2015, 10,000 cases of swine influenza were reported with 774 deaths. The Centers for Disease Control and Prevention recommend real-time polymerase chain reaction as the method of choice for diagnosing H1N1. Antiviral drugs are the mainstay of clinical treatment of swine influenza and can make the illness milder and enable the patient to feel better faster. Antiviral drugs are most effective when they are started within the first 48 hours after the clinical signs begin, although they also may be used in severe or high-risk cases first seen after this time. The Centers for Disease Control and Prevention recommends use of oseltamivir (Tamiflu, Genentech) or zanamivir (Relenza, GlaxoSmithKline). Prevention of swine influenza has 3 components: prevention in swine, prevention of transmission to humans, and prevention of its spread among humans. Because of limited treatment options, high risk for secondary infection, and frequent need for intensive care of individuals with H1N1 pneumonia, environmental control, including vaccination of high-risk populations and public education are critical to control of swine influenza out breaks. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
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40 CFR 721.5540 - 1H,3H,5H-oxazolo [3,4-c] oxazole, dihydro-7a-methyl-.
Code of Federal Regulations, 2010 CFR
2010-07-01
... 40 Protection of Environment 30 2010-07-01 2010-07-01 false 1H,3H,5H-oxazolo [3,4-c] oxazole... Specific Chemical Substances § 721.5540 1H,3H,5H-oxazolo [3,4-c] oxazole, dihydro-7a-methyl-. (a) Chemical substances and significant new uses subject to reporting. (1) The chemical substance identified as 1H,3H,5H...
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[Swine-origin influenza H1N1/California--passions and facts].
Gendon, Iu Z
2010-01-01
Analysis of pandemic caused by swine influenza virus H1N1/California showed moderate virulence of this virus compared to pandemic viruses, which caused pandemics in 1918, 1957, and 1968. During seasonal influenza epidemic in countries of southern hemisphere (June-August 2009) despite on circulation of H1N1/California strain, epidemics was caused by human influenza viruses H3N2 and H1N1. It was concluded that strain H1N1/California could not be attributed to pandemic strains of influenza viruses.
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Outbreaks of pandemic (H1N1) 2009 and seasonal influenza A (H3N2) on cruise ship.
Ward, Kate A; Armstrong, Paul; McAnulty, Jeremy M; Iwasenko, Jenna M; Dwyer, Dominic E
2010-11-01
To determine the extent and pattern of influenza transmission and effectiveness of containment measures, we investigated dual outbreaks of pandemic (H1N1) 2009 and influenza A (H3N2) that had occurred on a cruise ship in May 2009. Of 1,970 passengers and 734 crew members, 82 (3.0%) were infected with pandemic (H1N1) 2009 virus, 98 (3.6%) with influenza A (H3N2) virus, and 2 (0.1%) with both. Among 45 children who visited the ship's childcare center, infection rate for pandemic (H1N1) 2009 was higher than that for influenza A (H3N2) viruses. Disembarked passengers reported a high level of compliance with isolation and quarantine recommendations. We found 4 subsequent cases epidemiologically linked to passengers but no evidence of sustained transmission to the community or passengers on the next cruise. Among this population of generally healthy passengers, children seemed more susceptible to pandemic (H1N1) 2009 than to influenza (H3N2) viruses. Intensive disease control measures successfully contained these outbreaks.
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NASA Astrophysics Data System (ADS)
Chen, Xuchong; Jin, Shouwen; Zhang, Huan; Xiao, Xiao; Liu, Bin; Wang, Daqi
2017-09-01
Cocrystallization of the imidazole derivatives, L1-L3, with a series of organic acids gave a total of five molecular salts with the compositions: (imidazole): (DL-10-camphorsulfonic acid) [(HL1+)·(cpsa-), cpsa- = DL-10-camphorsulfonate] (1), (imidazole): (3,5-dihydroxybenzoic acid) [(HL1+) · (3,5-dba-), 3,5-dba- = 3,5-dihydroxybenzoate] (2), (imidazole): (isophthalic acid): H2O [(HL1)+·(Hmpa)-·H2O, Hmpa- = hydrogenisophthalate] (3), (benzimidazole): (butane-1,2,3,4-tetracarboxylic acid) [(HL2+)·(H3bta -), H3bta- = trihydrogen butane-1,2,3,4-tetracarboxylate] (4), and (benzimidazole)2: 1-(2-(1H-benzimidazol-1-yl)ethyl)-1H-benzimidazole: (5-nitrosalicylic acid)2 [(L2)2·(H2L3)2+·(5-nsa-)2, 5-nsa- = 5-nitrosalicylate], (5). The five salts have been characterized by XRD technique, IR, and EA, and the melting points of all the salts were also reported. And their structural and supramolecular aspects are fully analyzed. The result reveals that among the five investigated crystals the ring N in the imidazole moieties are protonated when the organic acids are ionized, and the crystal packing is interpreted in terms of the strong Nsbnd H⋯O H-bond from the imidazole and the ionized acids. In addition to the Nsbnd H⋯O H-bond, the Osbnd H⋯O H-bonds were also established at the salts 2-5, compound 1 has the additional Nsbnd H⋯S H-bonds. Further analysis of the crystal packing of the salts displayed that a different family of additional CHsbnd O/CH2sbnd O/CH3sbnd O, CHsbnd S, CHsbnd π, NHsbnd π, and πsbnd π associations contribute to the stabilization and expansion of the total 3D framework structures. For the coexistence of the various weak interactions these structures had homo or hetero supramolecular synthons or both. Some classical supramolecular synthons, such as R12(4), R22(7), and R22(8) usually observed in crystals of organic acids with imidazole, were again shown to be involved in constructing most of these hydrogen bonding networks.
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NASA Astrophysics Data System (ADS)
Wang, Chengyun; Zuo, Xiaoxi; Zhao, Minkai; Xiao, Xin; Yu, Le; Nan, Junmin
2016-03-01
1H,1H,5H-Perfluoropentyl-1,1,2,2-tetrafluoroethylether (F-EAE) mixed with ethylene carbonate (EC), diethyl carbonate (DEC), and lithium hexafluorophosphate (LiPF6) is evaluated as a co-solvent high-potential electrolyte of LiNi1/3Co1/3Mn1/3O2/graphite batteries. Linear sweep voltammetry (LSV) and cyclic voltammetry (CV) indicate that the EC/DEC-based electrolyte with F-EAE possesses a high oxidation potential (>5.2 V vs. Li/Li+) and excellent film-forming characteristics. With 40 wt% F-EAE in the electrolyte, the capacity retention of the LiNi1/3Co1/3Mn1/3O2/graphite pouch cells that are cycled between 3.0 and 4.5 V is significantly improved from 28.8% to 86.8% after 100 cycles. In addition, electrochemical impedance spectroscopy (EIS) of three-electrode pouch cells, scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS) are used to characterize the effects of F-EAE on the enhanced capacity retention. It is demonstrated that F-EAE facilitates the formation of a stable surface electrolyte interface (SEI) layer with low impedance on the anode and effectively suppresses an increase in the charge-transfer resistance on the cathode. These results suggest that F-EAE can serve as an alternative electrolyte solvent for 4.5 V high voltage rechargeable lithium-ion batteries.
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H7N9 Influenza Virus Is More Virulent in Ferrets than 2009 Pandemic H1N1 Influenza Virus.
Yum, Jung; Ku, Keun Bon; Kim, Hyun Soo; Seo, Sang Heui
2015-12-01
The novel H7N9 influenza virus has been infecting humans in China since February 2013 and with a mortality rate of about 40%. This study compared the pathogenicity of the H7N9 and 2009 pandemic H1N1 influenza viruses in a ferret model, which shows similar symptoms to those of humans infected with influenza viruses. The H7N9 influenza virus caused a more severe disease than did the 2009 pandemic H1N1 influenza virus. All of the ferrets infected with the H7N9 influenza virus had died by 6 days after infection, while none of those infected with the 2009 pandemic H1N1 influenza virus died. Ferrets infected with the H7N9 influenza virus had higher viral titers in their lungs than did those infected with the 2009 pandemic H1N1 influenza virus. Histological findings indicated that hemorrhagic pneumonia was caused by infection with the H7N9 influenza virus, but not with the 2009 pandemic H1N1 influenza virus. In addition, the lung tissues of ferrets infected with the H7N9 influenza virus contained higher levels of chemokines than did those of ferrets infected with the 2009 pandemic H1N1 influenza virus. This study suggests that close monitoring is needed to prevent human infection by the lethal H7N9 influenza virus.
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Guo, Ying; Han, Shengli; Cao, Jingjing; Liu, Qi; Zhang, Tao
2014-12-01
It has been reported that the histamine H1 receptor (H(1)R) gene is up-regulated in patients with allergic rhinitis and H(1)R expression level strongly correlates with the severity of allergy symptoms. Drugs for therapy should avoid allergy symptoms, especially for patients with over-expressed H(1)R. Therefore, screening of the components which could induce H(1)R activation is urgently needed for drug safety evaluation. Homoharringtonine injection is a preparation for acute nonlymphocytic leukemia, which is approved by China Food and Drug Administration (CFDA) and US Food and Drug Administration. However, severely adverse reactions often occur with intravenous injection of the preparation. In present study, an H(1)R/CMC model was applied for capturing membrane retained components which could induce H(1)R activation. Retention components were enriched and analyzed by H(1)R/CMC-HPLC/MS. Homoharringtonine was recognized, separated and identified in homoharringtonine injection. Ca(2+) flux assay and p-IP3R expression founded that homoharringtonine retained by the H1 R/CMC model increased phosphorylation of IP3R and promoted cytosolic free Ca(2+) elevation in a dose-dependent manner which further verified the activity of homoharringtonine in activating the H1 R. In conclusion, homoharringtonine was screened and identified as a potential allergic factor. This provides an indication that a patient with over-expressed H1 R should be aware of possible allergic reaction when applying homoharringtonine injection. Copyright © 2014 John Wiley & Sons, Ltd.
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Yasui, Fumihiko; Itoh, Yasushi; Ikejiri, Ai; Kitabatake, Masahiro; Sakaguchi, Nobuo; Munekata, Keisuke; Shichinohe, Shintaro; Hayashi, Yukiko; Ishigaki, Hirohito; Nakayama, Misako; Sakoda, Yoshihiro; Kida, Hiroshi; Ogasawara, Kazumasa; Kohara, Michinori
2016-11-28
H5N1 highly pathogenic avian influenza (H5N1 HPAI) virus causes elevated mortality compared with seasonal influenza viruses like H1N1 pandemic influenza (H1N1 pdm) virus. We identified a mechanism associated with the severe symptoms seen with H5N1 HPAI virus infection. H5N1 HPAI virus infection induced a decrease of dendritic cell number in the splenic extrafollicular T-cell zone and impaired formation of the outer layers of B-cell follicles, resulting in insufficient levels of antibody production after infection. However, in animals vaccinated with a live recombinant vaccinia virus expressing the H5 hemagglutinin, infection with H5N1 HPAI virus induced parafollicular dendritic cell accumulation and efficient antibody production. These results indicate that a recombinant vaccinia encoding H5 hemagglutinin gene does not impair dendritic cell recruitment and can be a useful vaccine candidate.
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Defense.gov - Special Report - H1N1 Flu: Facing the H1N1 Flu
Learned WASHINGTON, Nov. 6, 2009 - Senior medical officials who successfully slowed the spread of H1N1 flu Crucial To Fleet Readiness NORFOLK (NNS) -- Commands and medical clinics throughout U.S. Fleet Forces , Ghana. Story» Naval Medical Center Portsmouth Works to Immunize Against Flu PORTSMOUTH, Va., Dec. 15
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Saliba, Elie; Evangelinos, Minoas; Gournas, Christos; Corrillon, Florent; Georis, Isabelle; André, Bruno
2018-03-23
The yeast Target of Rapamycin Complex 1 (TORC1) plays a central role in controlling growth. How amino acids and other nutrients stimulate its activity via the Rag/Gtr GTPases remains poorly understood. We here report that the signal triggering Rag/Gtr-dependent TORC1 activation upon amino-acid uptake is the coupled H + influx catalyzed by amino-acid/H + symporters. H + -dependent uptake of other nutrients, ionophore-mediated H + diffusion, and inhibition of the vacuolar V-ATPase also activate TORC1. As the increase in cytosolic H + elicited by these processes stimulates the compensating H + -export activity of the plasma membrane H + -ATPase (Pma1), we have examined whether this major ATP-consuming enzyme might be involved in TORC1 control. We find that when the endogenous Pma1 is replaced with a plant H + -ATPase, H + influx or increase fails to activate TORC1. Our results show that H + influx coupled to nutrient uptake stimulates TORC1 activity and that Pma1 is a key actor in this mechanism. © 2018, Saliba et al.
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Common mechanisms of inhibition for the Na+/glucose (hSGLT1) and Na+/Cl−/GABA (hGAT1) cotransporters
Hirayama, Bruce A; Díez-Sampedro, Ana; Wright, Ernest M
2001-01-01
Electrophysiological methods were used to investigate the interaction of inhibitors with the human Na+/glucose (hSGLT1) and Na+/Cl−/GABA (hGAT1) cotransporters. Inhibitor constants were estimated from both inhibition of substrate-dependent current and inhibitor-induced changes in cotransporter conformation. The competitive, non-transported inhibitors are substrate derivatives with inhibition constants from 200 nM (phlorizin) to 17 mM (esculin) for hSGLT1, and 300 nM (SKF89976A) to 10 mM (baclofen) for hGAT1. At least for hSGLT1, values determined using either method were proportional over 5-orders of magnitude. Correlation of inhibition to structure of the inhibitors resulted in a pharmacophore for glycoside binding to hSGLT1: the aglycone is coplanar with the pyranose ring, and binds to a hydrophobic/aromatic surface of at least 7×12Å. Important hydrogen bond interactions occur at five positions bordering this surface. In both hSGLT1 and hGAT1 the data suggests that there is a large, hydrophobic inhibitor binding site ∼8Å from the substrate binding site. This suggests an architectural similarity between hSGLT1 and hGAT1. There is also structural similarity between non-competitive and competitive inhibitors, e.g., phloretin is the aglycone of phlorizin (hSGLT1) and nortriptyline resembles SKF89976A without nipecotic acid (hGAT1). Our studies establish that measurement of the effect of inhibitors on presteady state currents is a valid non-radioactive method for the determination of inhibitor binding constants. Furthermore, analysis of the presteady state currents provide novel insights into partial reactions of the transport cycle and mode of action of the inhibitors. PMID:11588102
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Zeng, Xianying; Chen, Pucheng; Liu, Liling; Deng, Guohua; Li, Yanbing; Shi, Jianzhong; Kong, Huihui; Feng, Huapeng; Bai, Jie; Li, Xin; Shi, Wenjun; Tian, Guobin; Chen, Hualan
2016-05-01
The Goose/Guangdong-lineage H5 viruses have evolved into diverse clades and subclades based on their hemagglutinin (HA) gene during their circulation in wild birds and poultry. Since late 2013, the clade 2.3.4.4 viruses have become widespread in poultry and wild bird populations around the world. Different subtypes of the clade 2.3.4.4 H5 viruses, including H5N1, H5N2, H5N6, and H5N8, have caused vast disease outbreaks in poultry in Asia, Europe, and North America. In this study, we developed a new H5N1 inactivated vaccine by using a seed virus (designated as Re-8) that contains the HA and NA genes from a clade 2.3.4.4 virus, A/chicken/Guizhou/4/13(H5N1) (CK/GZ/4/13), and its six internal genes from the high-growth A/Puerto Rico/8/1934 (H1N1) virus. We evaluated the protective efficacy of this vaccine in chickens challenged with one H5N1 clade 2.3.2.1b virus and six different subtypes of clade 2.3.4.4 viruses, including H5N1, H5N2, H5N6, and H5N8 strains. In the clade 2.3.2.1b virus DK/GX/S1017/13-challenged groups, half of the vaccinated chickens shed virus through the oropharynx and two birds (20%) died during the observation period. All of the control chickens shed viruses and died within 6 days of infection with challenge virus. All of the vaccinated chickens remained healthy following challenge with the six clade 2.3.4.4 viruses, and virus shedding was not detected from any of these birds; however, all of the control birds shed viruses and died within 4 days of challenge with the clade 2.3.4.4 viruses. Our results indicate that the Re-8 vaccine provides protection against different subtypes of clade 2.3.4.4 H5 viruses.
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Outbreaks of Pandemic (H1N1) 2009 and Seasonal Influenza A (H3N2) on Cruise Ship
Ward, Kate A.; Armstrong, Paul; Iwasenko, Jenna M.; Dwyer, Dominic E.
2010-01-01
To determine the extent and pattern of influenza transmission and effectiveness of containment measures, we investigated dual outbreaks of pandemic (H1N1) 2009 and influenza A (H3N2) that had occurred on a cruise ship in May 2009. Of 1,970 passengers and 734 crew members, 82 (3.0%) were infected with pandemic (H1N1) 2009 virus, 98 (3.6%) with influenza A (H3N2) virus, and 2 (0.1%) with both. Among 45 children who visited the ship’s childcare center, infection rate for pandemic (H1N1) 2009 was higher than that for influenza A (H3N2) viruses. Disembarked passengers reported a high level of compliance with isolation and quarantine recommendations. We found 4 subsequent cases epidemiologically linked to passengers but no evidence of sustained transmission to the community or passengers on the next cruise. Among this population of generally healthy passengers, children seemed more susceptible to pandemic (H1N1) 2009 than to influenza (H3N2) viruses. Intensive disease control measures successfully contained these outbreaks. PMID:21029531
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Infrared predissociation spectroscopy of M+ (C6H6)(1-4)(H2O)(1-2)Ar(0-1) cluster ions, M = Li, Na.
Beck, Jordan P; Lisy, James M
2011-05-05
Infrared predissociation (IRPD) spectra of Li(+)(C(6)H(6))(1-4)(H(2)O)(1-2)Ar(0-1) and Na(+)(C(6)H(6))(2-4)(H(2)O)(1-2)Ar(1) are presented along with ab initio calculations. The results indicate that the global minimum energy structure for Li(+)(C(6)H(6))(2)(H(2)O)(2) has each water forming a π-hydrogen bond with the same benzene molecule. This bonding motif is preserved in Li(+)(C(6)H(6))(3-4)(H(2)O)(2)Ar(0-1) with the additional benzene ligands binding to the available free OH groups. Argon tagging allows high-energy Li(+)(C(6)H(6))(2-4)(H(2)O)(2)Ar isomers containing water-water hydrogen bonds to be trapped and detected. The monohydrated, Li(+) containing clusters contain benzene-water interactions with varying strength as indicated by shifts in OH stretching frequencies. The IRPD spectra of M(+)(C(6)H(6))(1-4)(H(2)O)(1-2)Ar are very different for lithium-bearing versus sodium-bearing cluster ions emphasizing the important role of ion size in determining the most favorable balance of competing noncovalent interactions.
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Hasegawa, Shunji; Hirano, Reiji; Hashimoto, Kunio; Haneda, Yasuhiro; Shirabe, Komei; Ichiyama, Takashi
2011-02-01
The number of human cases of pandemic H1N1 influenza viral infection has increased in Japan since April 2009, as it has worldwide. This virus is widespread in the Yamaguchi prefecture in western Japan, where most infected children exhibited respiratory symptoms. Bronchial asthma is thought to be one of the risk factors that exacerbate respiratory symptoms of pandemic H1N1-infected patients, but the pathogenesis remains unclear. We retrospectively investigated the records of 33 children with pandemic H1N1 influenza viral infection who were admitted to our hospital between October and December 2009 and analyzed their clinical features. The percentage of children with asthma attack, with or without abnormal findings on chest radiographs (pneumonia, atelectasis, etc.), caused by pandemic H1N1 influenza infection was significantly higher than that of children with asthma attack and 2008-2009 seasonal influenza infection. Of the 33 children in our study, 22 (66.7%) experienced an asthma attack. Among these children, 20 (90.9%) did not receive long-term management for bronchial asthma, whereas 7 (31.8%) were not diagnosed with bronchial asthma and had experienced their first asthma attack. However, the severity of the attack did not correlate with the severity of the pulmonary complications of pandemic H1N1 influenza viral infection. The pandemic H1N1 influenza virus greatly increases the risk of lower respiratory tract complications such as asthma attack, pneumonia, and atelectasis, when compared to the seasonal influenza virus. Furthermore, our results suggest that pandemic H1N1 influenza viral infection can easily induce a severe asthma attack, pneumonia, and atelectasis in atopic children without any history of either an asthma attack or asthma treatment. © 2011 John Wiley & Sons A/S.
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26 CFR 1.642(h)-4 - Allocation.
Code of Federal Regulations, 2010 CFR
2010-04-01
... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Allocation. 1.642(h)-4 Section 1.642(h)-4...) INCOME TAXES Estates, Trusts, and Beneficiaries § 1.642(h)-4 Allocation. The carryovers and excess deductions to which section 642(h) applies are allocated among the beneficiaries succeeding to the property...
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Yu, Hai; Zhang, Peng-Chao; Zhou, Yan-Jun; Li, Guo-Xin; Pan, Jie; Yan, Li-Ping; Shi, Xiao-Xiao; Liu, Hui-Li; Tong, Guang-Zhi
2009-08-21
As pigs are susceptible to both human and avian influenza viruses, they have been proposed to be intermediate hosts or mixing vessels for the generation of pandemic influenza viruses through reassortment or adaptation to the mammalian host. In this study, we reported avian-like H1N1 and novel ressortant H1N2 influenza viruses from pigs in China. Homology and phylogenetic analyses showed that the H1N1 virus (A/swine/Zhejiang/1/07) was closely to avian-like H1N1 viruses and seemed to be derived from the European swine H1N1 viruses, which was for the first time reported in China; and the two H1N2 viruses (A/swine/Shanghai/1/07 and A/swine/Guangxi/13/06) were novel ressortant H1N2 influenza viruses containing genes from the classical swine (HA, NP, M and NS), human (NA and PB1) and avian (PB2 and PA) lineages, which indicted that the reassortment among human, avian, and swine influenza viruses had taken place in pigs in China and resulted in the generation of new viruses. The isolation of avian-like H1N1 influenza virus originated from the European swine H1N1 viruses, especially the emergence of two novel ressortant H1N2 influenza viruses provides further evidence that pigs serve as intermediate hosts or "mixing vessels", and swine influenza virus surveillance in China should be given a high priority.
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Trebbien, Ramona; Bragstad, Karoline; Larsen, Lars Erik; Nielsen, Jens; Bøtner, Anette; Heegaard, Peter M H; Fomsgaard, Anders; Viuff, Birgitte; Hjulsager, Charlotte Kristiane
2013-09-18
The influenza A virus subtypes H1N1, H1N2 and H3N2 are the most prevalent subtypes in swine. In 2003, a reassorted H1N2 swine influenza virus (SIV) subtype appeared and became prevalent in Denmark. In the present study, the reassortant H1N2 subtype was characterised genetically and the infection dynamics compared to an "avian-like" H1N1 virus by an experimental infection study. Sequence analyses were performed of the H1N2 virus. Two groups of pigs were inoculated with the reassortant H1N2 virus and an "avian-like" H1N1 virus, respectively, followed by inoculation with the opposite subtype four weeks later. Measurements of HI antibodies and acute phase proteins were performed. Nasal virus excretion and virus load in lungs were determined by real-time RT-PCR. The phylogenetic analysis revealed that the reassorted H1N2 virus contained a European "avian-like" H1-gene and a European "swine-like" N2-gene, thus being genetically distinct from most H1N2 viruses circulating in Europe, but similar to viruses reported in 2009/2010 in Sweden and Italy. Sequence analyses of the internal genes revealed that the reassortment probably arose between circulating Danish "avian-like" H1N1 and H3N2 SIVs. Infected pigs developed cross-reactive antibodies, and increased levels of acute phase proteins after inoculations. Pigs inoculated with H1N2 exhibited nasal virus excretion for seven days, peaking day 1 after inoculation two days earlier than H1N1 infected pigs and at a six times higher level. The difference, however, was not statistically significant. Pigs euthanized on day 4 after inoculation, had a high virus load in all lung lobes. After the second inoculation, the nasal virus excretion was minimal. There were no clinical sign except elevated body temperature under the experimental conditions. The "avian-like" H1N2 subtype, which has been established in the Danish pig population at least since 2003, is a reassortant between circulating swine "avian-like" H1N1 and H3N2. The Danish
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2013-01-01
Background The influenza A virus subtypes H1N1, H1N2 and H3N2 are the most prevalent subtypes in swine. In 2003, a reassorted H1N2 swine influenza virus (SIV) subtype appeared and became prevalent in Denmark. In the present study, the reassortant H1N2 subtype was characterised genetically and the infection dynamics compared to an “avian-like” H1N1 virus by an experimental infection study. Methods Sequence analyses were performed of the H1N2 virus. Two groups of pigs were inoculated with the reassortant H1N2 virus and an “avian-like” H1N1 virus, respectively, followed by inoculation with the opposite subtype four weeks later. Measurements of HI antibodies and acute phase proteins were performed. Nasal virus excretion and virus load in lungs were determined by real-time RT-PCR. Results The phylogenetic analysis revealed that the reassorted H1N2 virus contained a European “avian-like” H1-gene and a European “swine-like” N2-gene, thus being genetically distinct from most H1N2 viruses circulating in Europe, but similar to viruses reported in 2009/2010 in Sweden and Italy. Sequence analyses of the internal genes revealed that the reassortment probably arose between circulating Danish “avian-like” H1N1 and H3N2 SIVs. Infected pigs developed cross-reactive antibodies, and increased levels of acute phase proteins after inoculations. Pigs inoculated with H1N2 exhibited nasal virus excretion for seven days, peaking day 1 after inoculation two days earlier than H1N1 infected pigs and at a six times higher level. The difference, however, was not statistically significant. Pigs euthanized on day 4 after inoculation, had a high virus load in all lung lobes. After the second inoculation, the nasal virus excretion was minimal. There were no clinical sign except elevated body temperature under the experimental conditions. Conclusions The “avian-like” H1N2 subtype, which has been established in the Danish pig population at least since 2003, is a reassortant
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Canine susceptibility to human influenza viruses (A/pdm 09H1N1, A/H3N2 and B).
Song, Daesub; Kim, Hyekwon; Na, Woonsung; Hong, Minki; Park, Seong-Jun; Moon, Hyoungjoon; Kang, Bokyu; Lyoo, Kwang-Soo; Yeom, Minjoo; Jeong, Dae Gwin; An, Dong-Jun; Kim, Jeong-Ki
2015-02-01
We investigated the infectivity and transmissibility of the human seasonal H3N2, pandemic (pdm) H1N1 (2009) and B influenza viruses in dogs. Dogs inoculated with human seasonal H3N2 and pdm H1N1 influenza viruses exhibited nasal shedding and were seroconverted against the viruses; this did not occur in the influenza B virus-inoculated dogs. Transmission of human H3N2 virus between dogs was demonstrated by observing nasal shedding and seroconversion in naïve dogs after contact with inoculated dogs. The seroprevalence study offered evidence of human H3N2 infection occurring in dogs since 2008. Furthermore, serological evidence of pdm H1N1 influenza virus infection alone and in combination with canine H3N2 virus was found in the serum samples collected from field dogs during 2010 and 2011. Our results suggest that dogs may be hosts for human seasonal H3N2 and pdm H1N1 influenza viruses. © 2015 The Authors.
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Vincent, Amy L; Ma, Wenjun; Lager, Kelly M; Gramer, Marie R; Richt, Juergen A; Janke, Bruce H
2009-10-01
H1 influenza A viruses that were distinct from the classical swine H1 lineage were identified in pigs in Canada in 2003–2004; antigenic and genetic characterization identified the hemagglutinin (HA) as human H1 lineage. The viruses identified in Canadian pigs were human lineage in entirety or double (human–swine) reassortants. Here, we report the whole genome sequence analysis of four human-like H1 viruses isolated from U.S. swine in 2005 and 2007. All four isolates were characterized as triple reassortants with an internal gene constellation similar to contemporary U.S. swine influenza virus (SIV), with HA and neuraminidase (NA) most similar to human influenza virus lineages. A 2007 human-like H1N1 was evaluated in a pathogenesis and transmission model and compared to a 2004 reassortant H1N1 SIV isolate with swine lineage HA and NA. The 2007 isolate induced disease typical of influenza virus and was transmitted to contact pigs; however, the kinetics and magnitude differed from the 2004 H1N1 SIV. This study indicates that the human-like H1 SIV can efficiently replicate and transmit in the swine host and now co-circulates with contemporary SIVs as a distinct genetic cluster of H1 SIV.
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Ling, Man To; Tu, Wenwei; Han, Yan; Mao, Huawei; Chong, Wai Po; Guan, Jing; Liu, Ming; Lam, Kwok Tai; Law, Helen K W; Peiris, J S Malik; Takahashi, K; Lau, Yu Lung
2012-01-01
Mannose-binding lectin (MBL) is a pattern-recognition molecule, which functions as a first line of host defense. Pandemic H1N1 (pdmH1N1) influenza A virus caused massive infection in 2009 and currently circulates worldwide. Avian influenza A H9N2 (H9N2/G1) virus has infected humans and has the potential to be the next pandemic virus. Antiviral function and immunomodulatory role of MBL in pdmH1N1 and H9N2/G1 virus infection have not been investigated. In this study, MBL wild-type (WT) and MBL knockout (KO) murine models were used to examine the role of MBL in pdmH1N1 and H9N2/G1 virus infection. Our study demonstrated that in vitro, MBL binds to pdmH1N1 and H9N2/G1 viruses, likely via the carbohydrate recognition domain of MBL. Wild-type mice developed more severe disease, as evidenced by a greater weight loss than MBL KO mice during influenza virus infection. Furthermore, MBL WT mice had enhanced production of proinflammatory cytokines and chemokines compared with MBL KO mice, suggesting that MBL could upregulate inflammatory responses that may potentially worsen pdmH1N1 and H9N2/G1 virus infections. Our study provided the first in vivo evidence that MBL may be a risk factor during pdmH1N1 and H9N2/G1 infection by upregulating proinflammatory response.
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Lyoo, K S; Na, W; Phan, L V; Yoon, S W; Yeom, M; Song, D; Jeong, D G
2017-12-01
Since the emergence of highly pathogenic avian influenza (HPAI) H5N1 in Asia, the haemagglutinin (HA) gene of this virus lineage has continued to evolve in avian populations, and H5N1 lineage viruses now circulate concurrently worldwide. Dogs may act as an intermediate host, increasing the potential for zoonotic transmission of influenza viruses. Virus transmission and pathologic changes in HPAI clade 1.1.2 (H5N1)-, 2.3.2.1c (H5N1)- and 2.3.4.4 (H5N6)-infected dogs were investigated. Mild respiratory signs and antibody response were shown in dogs intranasally infected with the viruses. Lung histopathology showed lesions that were associated with moderate interstitial pneumonia in the infected dogs. In this study, HPAI H5N6 virus replication in dogs was demonstrated for the first time. Dogs have been suspected as a "mixing vessel" for reassortments between avian and human influenza viruses to occur. The replication of these three subtypes of the H5 lineage of HPAI viruses in dogs suggests that dogs could serve as intermediate hosts for avian-human influenza virus reassortment if they are also co-infected with human influenza viruses. © 2017 Blackwell Verlag GmbH.
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Benzene-1,4-diol–5-(1H-imidazol-1-yl)pyrimidine (1/1)
Jiang, Yan-Ke; Hou, Gui-Ge
2011-01-01
The asymmetric unit of title compound, C7H6N4·C6H6O2, contains one 5-(1H-imidazol-1-yl)pyrimidine molecule and two half benzene-1,4-diol molecules; the benzene-1,4-diol molecules are located on individual inversion centers. In the pyrimidine molecule, the imidazole ring is twisted with respect to the pyrimidine ring at a dihedral angle of 25.73 (7)°. In the crystal, O—H⋯N hydrogen bonds link the molecules to form supramolecular chains. π–π stacking is also observed in the crystal, the centroid–centroid distance between parallel imdazole rings being 3.5543 (16) Å. PMID:22220081
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Nang, Nguyen Tai; Song, Byung Min; Kang, Young Myong; Kim, Heui Man; Kim, Hyun Soo; Seo, Sang Heui
2012-01-01
Please cite this paper as: Nang et al. (2013) Live attenuated H5N1 vaccine with H9N2 internal genes protects chickens from infections by both Highly Pathogenic H5N1 and H9N2 Influenza Viruses. Influenza and Other Respiratory Viruses 7(2) 120–131. Background The highly pathogenic H5N1 and H9N2 influenza viruses are endemic in many countries around the world and have caused considerable economic loss to the poultry industry. Objectives We aimed to study whether a live attenuated H5N1 vaccine comprising internal genes from a cold‐adapted H9N2 influenza virus could protect chickens from infection by both H5N1 and H9N2 viruses. Methods We developed a cold‐adapted H9N2 vaccine virus expressing hemagglutinin and neuraminidase derived from the highly pathogenic H5N1 influenza virus using reverse genetics. Results and Conclusions Chickens immunized with the vaccine were protected from lethal infections with homologous and heterologous H5N1 or H9N2 influenza viruses. Specific antibody against H5N1 virus was detected up to 11 weeks after vaccination (the endpoint of this study). In vaccinated chickens, IgA and IgG antibody subtypes were induced in lung and intestinal tissue, and CD4+ and CD8+ T lymphocytes expressing interferon‐gamma were induced in the splenocytes. These data suggest that a live attenuated H5N1 vaccine with cold‐adapted H9N2 internal genes can protect chickens from infection with H5N1 and H9N2 influenza viruses by eliciting humoral and cellular immunity. PMID:22487301
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Ling, Man To; Tu, Wenwei; Han, Yan; Mao, Huawei; Chong, Wai Po; Guan, Jing; Liu, Ming; Lam, Kwok Tai; Law, Helen K. W.; Peiris, J. S. Malik; Takahashi, K.
2012-01-01
Background. Mannose-binding lectin (MBL) is a pattern-recognition molecule, which functions as a first line of host defense. Pandemic H1N1 (pdmH1N1) influenza A virus caused massive infection in 2009 and currently circulates worldwide. Avian influenza A H9N2 (H9N2/G1) virus has infected humans and has the potential to be the next pandemic virus. Antiviral function and immunomodulatory role of MBL in pdmH1N1 and H9N2/G1 virus infection have not been investigated. Methods. In this study, MBL wild-type (WT) and MBL knockout (KO) murine models were used to examine the role of MBL in pdmH1N1 and H9N2/G1 virus infection. Results. Our study demonstrated that in vitro, MBL binds to pdmH1N1 and H9N2/G1 viruses, likely via the carbohydrate recognition domain of MBL. Wild-type mice developed more severe disease, as evidenced by a greater weight loss than MBL KO mice during influenza virus infection. Furthermore, MBL WT mice had enhanced production of proinflammatory cytokines and chemokines compared with MBL KO mice, suggesting that MBL could upregulate inflammatory responses that may potentially worsen pdmH1N1 and H9N2/G1 virus infections. Conclusions. Our study provided the first in vivo evidence that MBL may be a risk factor during pdmH1N1 and H9N2/G1 infection by upregulating proinflammatory response. PMID:22080095
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Noisumdaeng, Pirom; Pooruk, Phisanu; Prasertsopon, Jarunee; Assanasen, Susan; Kitphati, Rungrueng; Auewarakul, Prasert; Puthavathana, Pilaipan
2014-04-01
Six recombinant vaccinia viruses containing HA, NA, NP, M or NS gene insert derived from a highly pathogenic avian influenza H5N1 virus, and the recombinant vaccinia virus harboring plasmid backbone as the virus control were constructed. The recombinant proteins were characterized for their expression and subcellular locations in TK(-) cells. Antibodies to the five recombinant proteins were detected in all 13 sequential serum samples collected from four H5N1 survivors during four years of follow-up; and those directed to rVac-H5 HA and rVac-NA proteins were found in higher titers than those directed to the internal proteins as revealed by indirect immunofluorescence assay. Although all 28 non-H5N1 subjects had no neutralizing antibodies against H5N1 virus, they did have cross-reactive antibodies to those five recombinant proteins. A significant increase in cross-reactive antibody titer to rVac-H5 HA and rVac-NA was found in paired blood samples from patients infected with the 2009 pandemic virus. Copyright © 2014 Elsevier Inc. All rights reserved.
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Opriessnig, Tanja; Gauger, Phillip C; Gerber, Priscilla F; Castro, Alessandra M M G; Shen, Huigang; Murphy, Lita; Digard, Paul; Halbur, Patrick G; Xia, Ming; Jiang, Xi; Tan, Ming
2018-01-01
Swine influenza A viruses (IAV-S) found in North American pigs are diverse and the lack of cross-protection among heterologous strains is a concern. The objective of this study was to compare a commercial inactivated A/H1N1/pdm09 (pH1N1) vaccine and two novel subunit vaccines, using IAV M2 ectodomain (M2e) epitopes as antigens, in a growing pig model. Thirty-nine 2-week-old IAV negative pigs were randomly assigned to five groups and rooms. At 3 weeks of age and again at 5 weeks of age, pigs were vaccinated intranasally with an experimental subunit particle vaccine (NvParticle/M2e) or a subunit complex-based vaccine (NvComplex/M2e) or intramuscularly with a commercial inactivated vaccine (Inact/pH1N1). At 7 weeks of age, the pigs were challenged with pH1N1 virus or sham-inoculated. Necropsy was conducted 5 days post pH1N1 challenge (dpc). At the time of challenge one of the Inact/pH1N1 pigs had seroconverted based on IAV nucleoprotein-based ELISA, Inact/pH1N1 pigs had significantly higher pdm09H1N1 hemagglutination inhibition (HI) titers compared to all other groups, and M2e-specific IgG responses were detected in the NvParticle/M2e and the NvComplex/M2e pigs with significantly higher group means in the NvComplex/M2e group compared to SHAMVAC-NEG pigs. After challenge, nasal IAV RNA shedding was significantly reduced in Inact/pH1N1 pigs compared to all other pH1N1 infected groups and this group also had reduced IAV RNA in oral fluids. The macroscopic lung lesions were characterized by mild-to-severe, multifocal-to-diffuse, cranioventral dark purple consolidated areas typical of IAV infection and were similar for NvParticle/M2e, NvComplex/M2e and SHAMVAC-IAV pigs. Lesions were significantly less severe in the SHAMVAC-NEG and the Inact/pH1N1pigs. Under the conditions of this study, a commercial Inact/pH1N1 specific vaccine effectively protected pigs against homologous challenge as evidenced by reduced clinical signs, virus shedding in nasal secretions and oral fluids
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Gauger, Phillip C.; Gerber, Priscilla F.; Castro, Alessandra M. M. G.; Shen, Huigang; Murphy, Lita; Digard, Paul; Halbur, Patrick G.; Xia, Ming; Jiang, Xi; Tan, Ming
2018-01-01
Swine influenza A viruses (IAV-S) found in North American pigs are diverse and the lack of cross-protection among heterologous strains is a concern. The objective of this study was to compare a commercial inactivated A/H1N1/pdm09 (pH1N1) vaccine and two novel subunit vaccines, using IAV M2 ectodomain (M2e) epitopes as antigens, in a growing pig model. Thirty-nine 2-week-old IAV negative pigs were randomly assigned to five groups and rooms. At 3 weeks of age and again at 5 weeks of age, pigs were vaccinated intranasally with an experimental subunit particle vaccine (NvParticle/M2e) or a subunit complex-based vaccine (NvComplex/M2e) or intramuscularly with a commercial inactivated vaccine (Inact/pH1N1). At 7 weeks of age, the pigs were challenged with pH1N1 virus or sham-inoculated. Necropsy was conducted 5 days post pH1N1 challenge (dpc). At the time of challenge one of the Inact/pH1N1 pigs had seroconverted based on IAV nucleoprotein-based ELISA, Inact/pH1N1 pigs had significantly higher pdm09H1N1 hemagglutination inhibition (HI) titers compared to all other groups, and M2e-specific IgG responses were detected in the NvParticle/M2e and the NvComplex/M2e pigs with significantly higher group means in the NvComplex/M2e group compared to SHAMVAC-NEG pigs. After challenge, nasal IAV RNA shedding was significantly reduced in Inact/pH1N1 pigs compared to all other pH1N1 infected groups and this group also had reduced IAV RNA in oral fluids. The macroscopic lung lesions were characterized by mild-to-severe, multifocal-to-diffuse, cranioventral dark purple consolidated areas typical of IAV infection and were similar for NvParticle/M2e, NvComplex/M2e and SHAMVAC-IAV pigs. Lesions were significantly less severe in the SHAMVAC-NEG and the Inact/pH1N1pigs. Under the conditions of this study, a commercial Inact/pH1N1 specific vaccine effectively protected pigs against homologous challenge as evidenced by reduced clinical signs, virus shedding in nasal secretions and oral fluids
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Information Entropy Analysis of the H1N1 Genetic Code
NASA Astrophysics Data System (ADS)
Martwick, Andy
2010-03-01
During the current H1N1 pandemic, viral samples are being obtained from large numbers of infected people world-wide and are being sequenced on the NCBI Influenza Virus Resource Database. The information entropy of the sequences was computed from the probability of occurrence of each nucleotide base at every position of each set of sequences using Shannon's definition of information entropy, [ H=∑bpb,2( 1pb ) ] where H is the observed information entropy at each nucleotide position and pb is the probability of the base pair of the nucleotides A, C, G, U. Information entropy of the current H1N1 pandemic is compared to reference human and swine H1N1 entropy. As expected, the current H1N1 entropy is in a low entropy state and has a very large mutation potential. Using the entropy method in mature genes we can identify low entropy regions of nucleotides that generally correlate to critical protein function.
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Perez, Daniel Roberto; Sorrell, Erin; Angel, Matthew; Ye, Jianqiang; Hickman, Danielle; Pena, Lindomar; Ramirez-Nieto, Gloria; Kimble, Brian; Araya, Yonas
2009-08-24
On June 11, 2009 the World Health Organization (WHO) declared a new H1N1 influenza pandemic. This pandemic strain is as transmissible as seasonal H1N1 and H3N2 influenza A viruses. Major concerns facing this pandemic are whether the new virus will replace, co-circulate and/or reassort with seasonal H1N1 and/or H3N2 human strains. Using the ferret model, we investigated which of these three possibilities were most likely favored. Our studies showed that the current pandemic virus is more transmissible than, and has a biological advantage over, prototypical seasonal H1 or H3 strains.
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Howells, Fleur M; Uhlmann, Anne; Temmingh, Henk; Sinclair, Heidi; Meintjes, Ernesta; Wilson, Don; Stein, Dan J
2014-03-01
Methamphetamine (MA) use has been shown to decrease n-acetyl-aspartate (NAA), a marker of neuronal integrity and viability, on (1)H magnetic resonance spectroscopy ((1)H-MRS). However, little work has compared (1)H-MRS in MA dependent individuals and MA dependent individuals with MA induced psychotic disorder (MAP). Twenty six participants with MA dependence (sixteen without psychosis, ten with psychosis - MAP) and nineteen healthy controls underwent 2D-chemical shift imaging (1)H-MRS, which included voxels in the anterior cingulate cortices (ACC), dorsolateral prefrontal cortices (DLPFC), and frontal white matter. We compared metabolite concentrations relative to phosphocreatine+creatine (PCr+Cr) for n-acetyl-aspartate (NAA), n-acetyl-aspartate+n-acetyl-aspartyl-glutamate (NAA+NAAG), glutamate (Glu), glutamate+glutamine (Glu+Gln), myo-inositol, and glycerophosphocholine+phosphocholine (GPC+PCh) across groups. The MA groups showed significantly decreased relative NAA metabolite concentrations for right ACC and right DLPFC, compared with control group. The MA dependent group only showed significantly decreased choline metabolites for right DLPFC, compared with control group. The MAP group's relative NAA metabolite concentrations were significantly correlated with age of initial use and duration of MA use, these correlates were not apparent in MA dependent group. MA use is associated with decreased neuronal integrity and viability, specifically in the right ACC and right DLPFC. MA dependence showed active neurodegeneration in the right DLPFC, this was not apparent in the MAP group and may be related to the use of antipsychotic medication in the MAP group. The effects of MA use in MAP suggest that age of initial use presents a mismatch of neuronal plasticity, in frontal white vs. gray matter and duration of use relates to decreased neuronal integrity and viability. Further study is warranted from this initial study of (1)H-MRS in MAP, in particular longitudinal
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26 CFR 301.6323(h)-1 - Definitions.
Code of Federal Regulations, 2010 CFR
2010-04-01
... 26 Internal Revenue 18 2010-04-01 2010-04-01 false Definitions. 301.6323(h)-1 Section 301.6323(h)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) PROCEDURE AND ADMINISTRATION PROCEDURE AND ADMINISTRATION Collection General Provisions § 301.6323(h)-1 Definitions. (a...
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Ma, Jingjiao; Shen, Huigang; Liu, Qinfang; Bawa, Bhupinder; Qi, Wenbao; Duff, Michael; Lang, Yuekun; Lee, Jinhwa; Yu, Hai; Bai, Jianfa; Tong, Guangzhi; Hesse, Richard A.; Richt, Jürgen A.
2014-01-01
ABSTRACT At least 10 different genotypes of novel reassortant H3N2 influenza viruses with 2009 pandemic H1N1 [A(H1N1)pdm09] gene(s) have been identified in U.S. pigs, including the H3N2 variant with a single A(H1N1)pdm09 M gene, which has infected more than 300 people. To date, only three genotypes of these viruses have been evaluated in animal models, and the pathogenicity and transmissibility of the other seven genotype viruses remain unknown. Here, we show that three H3N2 reassortant viruses that contain 3 (NP, M, and NS) or 5 (PA, PB2, NP, M, and NS) genes from A(H1N1)pdm09 were pathogenic in pigs, similar to the endemic H3N2 swine virus. However, the reassortant H3N2 virus with 3 A(H1N1)pdm09 genes and a recent human influenza virus N2 gene was transmitted most efficiently among pigs, whereas the reassortant H3N2 virus with 5 A(H1N1)pdm09 genes was transmitted less efficiently than the endemic H3N2 virus. Interestingly, the polymerase complex of reassortant H3N2 virus with 5 A(H1N1)pdm09 genes showed significantly higher polymerase activity than those of endemic and reassortant H3N2 viruses with 3 A(H1N1)pdm09 genes. Further studies showed that an avian-like glycine at position 228 at the hemagglutinin (HA) receptor binding site is responsible for inefficient transmission of the reassortant H3N2 virus with 5 A(H1N1)pdm09 genes. Taken together, our results provide insights into the pathogenicity and transmissibility of novel reassortant H3N2 viruses in pigs and suggest that a mammalian-like serine at position 228 in the HA is critical for the transmissibility of these reassortant H3N2 viruses. IMPORTANCE Swine influenza is a highly contagious zoonotic disease that threatens animal and public health. Introduction of 2009 pandemic H1N1 virus [A(H1N1)pdm09] into swine herds has resulted in novel reassortant influenza viruses in swine, including H3N2 and H1N2 variants that have caused human infections in the United States. We showed that reassortant H3N2 influenza
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Singh, Ashona; Soliman, Mahmoud E
2015-01-01
This study embarks on a comprehensive description of the conformational contributions to resistance of neuraminidase (N1) in H1N1 and H5N1 to oseltamivir, using comparative multiple molecular dynamic simulations. The available data with regard to elucidation of the mechanism of resistance as a result of mutations in H1N1 and H5N1 neuraminidases is not well established. Enhanced post-dynamic analysis, such as principal component analysis, solvent accessible surface area, free binding energy calculations, and radius of gyration were performed to gain a precise insight into the binding mode and origin of resistance of oseltamivir in H1N1 and H5N1 mutants. Three significant features reflecting resistance in the presence of mutations H274Y and I222K, of the protein complexed with the inhibitor are: reduced flexibility of the α-carbon backbone; an improved ΔEele of ~15 (kcal/mol) for H1N1 coupled with an increase in ΔGsol (~13 kcal/mol) from wild-type to mutation; a low binding affinity in comparison with the wild-type of ~2 (kcal/mol) and ~7 (kcal/mol) with respect to each mutation for the H5N1 systems; and reduced hydrophobicity of the overall surface structure due to an impaired hydrogen bonding network. We believe the results of this study will ultimately provide a useful insight into the structural landscape of neuraminidase-associated binding of oseltamivir. Furthermore, the results can be used in the design and development of potent inhibitors of neuraminidases. PMID:26257512
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Singh, Ashona; Soliman, Mahmoud E
2015-01-01
This study embarks on a comprehensive description of the conformational contributions to resistance of neuraminidase (N1) in H1N1 and H5N1 to oseltamivir, using comparative multiple molecular dynamic simulations. The available data with regard to elucidation of the mechanism of resistance as a result of mutations in H1N1 and H5N1 neuraminidases is not well established. Enhanced post-dynamic analysis, such as principal component analysis, solvent accessible surface area, free binding energy calculations, and radius of gyration were performed to gain a precise insight into the binding mode and origin of resistance of oseltamivir in H1N1 and H5N1 mutants. Three significant features reflecting resistance in the presence of mutations H274Y and I222K, of the protein complexed with the inhibitor are: reduced flexibility of the α-carbon backbone; an improved ΔEele of ~15 (kcal/mol) for H1N1 coupled with an increase in ΔGsol (~13 kcal/mol) from wild-type to mutation; a low binding affinity in comparison with the wild-type of ~2 (kcal/mol) and ~7 (kcal/mol) with respect to each mutation for the H5N1 systems; and reduced hydrophobicity of the overall surface structure due to an impaired hydrogen bonding network. We believe the results of this study will ultimately provide a useful insight into the structural landscape of neuraminidase-associated binding of oseltamivir. Furthermore, the results can be used in the design and development of potent inhibitors of neuraminidases.
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Phthalazin-1(2H)-one–picric acid (1/1)
Yathirajan, H. S.; Narayana, B.; Swamy, M. T.; Sarojini, B. K.; Bolte, Michael
2008-01-01
The geometric parameters of the title compound, C8H6N2O·C6H3N3O7, are in the usual ranges. The three nitro groups are almost coplanar with the aromatic picrate ring [dihedral angles 10.2 (2)°, 7.62 (16) and 8.08 (17)°]. The molecular conformation of the picric acid is stabilized by an intramolecular O—H⋯O hydrogen bond. The phthalazin-1(2H)-one molecules are connected via N—H⋯O hydrogen bonds, forming centrosymmetric dimers. PMID:21200682
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Outbreak of pandemic influenza A/H1N1 2009 in Nepal.
Adhikari, Bal Ram; Shakya, Geeta; Upadhyay, Bishnu Prasad; Prakash Kc, Khagendra; Shrestha, Sirjana Devi; Dhungana, Guna Raj
2011-03-23
The 2009 flu pandemic is a global outbreak of a new strain of H1N1 influenza virus. Pandemic influenza A (H1N1) 2009 has posed a serious public health challenge world-wide. Nepal has started Laboratory diagnosis of Pandemic influenza A/H1N1 from mid June 2009 though active screening of febrile travellers with respiratory symptoms was started from April 27, 2009. Out of 609 collected samples, 302 (49.6%) were Universal Influenza A positive. Among the influenza A positive samples, 172(28.3%) were positive for Pandemic influenza A/H1N1 and 130 (21.3%) were Seasonal influenza A. Most of the pandemic cases (53%) were found among young people with ≤ 20 years. Case Fatality Ratio for Pandemic influenza A/H1N1 in Nepal was 1.74%. Upon Molecular characterization, all the isolated pandemic influenza A/H1N1 2009 virus found in Nepal were antigenically and genetically related to the novel influenza A/CALIFORNIA/07/2009-LIKE (H1N1)v type. The Pandemic 2009 influenza virus found in Nepal were antigenically and genetically related to the novel A/CALIFORNIA/07/2009-LIKE (H1N1)v type.
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Phipps, Kara L.; Marshall, Nicolle; Tao, Hui; Danzy, Shamika; Onuoha, Nina; Steel, John
2017-01-01
ABSTRACT Reassortment of gene segments between coinfecting influenza A viruses (IAVs) facilitates viral diversification and has a significant epidemiological impact on seasonal and pandemic influenza. Since 1977, human IAVs of H1N1 and H3N2 subtypes have cocirculated with relatively few documented cases of reassortment. We evaluated the potential for viruses of the 2009 pandemic H1N1 (pH1N1) and seasonal H3N2 lineages to reassort under experimental conditions. Results of heterologous coinfections with pH1N1 and H3N2 viruses were compared to those obtained following coinfection with homologous, genetically tagged, pH1N1 viruses as a control. High genotype diversity was observed among progeny of both coinfections; however, diversity was more limited following heterologous coinfection. Pairwise analysis of genotype patterns revealed that homologous reassortment was random while heterologous reassortment was characterized by specific biases. pH1N1/H3N2 reassortant genotypes produced under single-cycle coinfection conditions showed a strong preference for homologous PB2-PA combinations and general preferences for the H3N2 NA, pH1N1 M, and H3N2 PB2 except when paired with the pH1N1 PA or NP. Multicycle coinfection results corroborated these findings and revealed an additional preference for the H3N2 HA. Segment compatibility was further investigated by measuring chimeric polymerase activity and growth of selected reassortants in human tracheobronchial epithelial cells. In guinea pigs inoculated with a mixture of viruses, parental H3N2 viruses dominated but reassortants also infected and transmitted to cage mates. Taken together, our results indicate that strong intrinsic barriers to reassortment between seasonal H3N2 and pH1N1 viruses are few but that the reassortants formed are attenuated relative to parental strains. IMPORTANCE The genome of IAV is relatively simple, comprising eight RNA segments, each of which typically encodes one or two proteins. Each viral protein
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H1- and H2-receptor characterization in the tracheal circulation of sheep.
Webber, S. E.; Salonen, R. O.; Widdicombe, J. G.
1988-01-01
1. The effects of histamine, the specific H1-agonist SKF 71481-A2 and the H2-agonist dimaprit were examined on tracheal vascular resistance in sheep anaesthetized with pentobarbitone. Tracheal vascular resistance was determined by perfusing the cranial tracheal arteries at constant flows and measuring inflow pressures. Changes in tracheal smooth muscle tone were also measured. 2. Histamine and SKF 71481-A2 contracted the tracheal smooth muscle and this effect was blocked by the H1-antagonist mepyramine. Stimulation of H2-receptors with dimaprit had no effect on tracheal smooth muscle tone. 3. Histamine had a complex action on the tracheal vasculature producing either a triphasic change (early dilatation then constriction followed by late dilatation) or just a constriction. SKF 71481-A2 always produced a biphasic change in vascular resistance (dilatation followed by constriction). Dimaprit dilated the tracheal vasculature. 4. The late dilatation produced by histamine in some sheep was blocked by bilateral cervical vagotomy but the mechanism for this effect is not known. No other responses to histamine, SKF 71481-A2 or dimaprit were affected by vagotomy. 5. The vasoconstriction produced by histamine and SKF 71481-A2 was antagonized by mepyramine indicating a H1-receptor-mediated effect. Cimetidine had no effect on the vasoconstriction to histamine suggesting a lack of involvement of H2-receptors. 6. The vasodilatation produced by histamine and SKF 71481-A2 was also antagonized by mepyramine, again suggesting a H1-receptor-mediated action. Cimetidine had no effect on the vasodilator response to histamine indicating no involvement of H2-receptors in this response. 7. The dilator effect of dimaprit was antagonized by cimetidine suggesting this effect was mediated by H2-receptors. 8. We conclude that H1-receptors in the various parts of the sheep tracheal vasculature can cause increases and decreases in total tracheal vascular resistance; that H2-receptors decrease
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26 CFR 31.3406(h)-1 - Definitions.
Code of Federal Regulations, 2010 CFR
2010-04-01
... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Definitions. 31.3406(h)-1 Section 31.3406(h)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) EMPLOYMENT TAXES AND... Income Tax at Source § 31.3406(h)-1 Definitions. (a) In general. For purposes of section 3406 and the...
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Kang, Xiao-ping; Jiang, Tao; Li, Yong-qiang; Lin, Fang; Liu, Hong; Chang, Guo-hui; Zhu, Qing-yu; Qin, E-de; Qin, Cheng-feng; Yang, Yin-hui
2010-06-02
A duplex real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay was improved for simultaneous detection of highly pathogenic H5N1 avian influenza virus and pandemic H1N1 (2009) influenza virus, which is suitable for early diagnosis of influenza-like patients and for epidemiological surveillance. The sensitivity of this duplex real-time RT-PCR assay was 0.02 TCID50 (50% tissue culture infective dose) for H5N1 and 0.2 TCID50 for the pandemic H1N1, which was the same as that of each single-target RT-PCR for pandemic H1N1 and even more sensitive for H5N1 with the same primers and probes. No cross reactivity of detecting other subtype influenza viruses or respiratory tract viruses was observed. Two hundred and thirty-six clinical specimens were tested by comparing with single real-time RT-PCR and result from the duplex assay was 100% consistent with the results of single real-time RT-PCR and sequence analysis.
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Quiroga, Jairo; Portilla, Jaime; Cobo, Justo; Glidewell, Christopher
2010-01-01
(3Z)-3-{1-[(5-Phenyl-1H-pyrazol-3-yl)amino]ethylidene}-4,5-dihydrofuran-2(3H)-one, C(15)H(15)N(3)O(2), (I), and the stoichiometric adduct (3Z)-3-{1-[(5-methyl-1H-pyrazol-3-yl)amino]ethylidene}-4,5-dihydrofuran-2(3H)-one-6-(2-hydroxyethyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7(4H)-one (1/1), C(10)H(13)N(3)O(2).C(10)H(13)N(3)O(2), (II), in which the two components have the same composition but different constitutions, are formed in the reactions of 2-acetyl-4-butyrolactone with 5-amino-3-phenyl-1H-pyrazole and 5-amino-3-methyl-1H-pyrazole, respectively. In each compound, the furanone component contains an intramolecular N-H...O hydrogen bond. The molecules of (I) are linked into a chain by a single intermolecular N-H...O hydrogen bond, while in (II), a combination of one O-H...N hydrogen bond, within the selected asymmetric unit, and two N-H...O hydrogen bonds link the molecular components into a ribbon containing alternating centrosymmetric R(4)(4)(20) and R(6)(6)(22) rings.
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Sokolova, T M; Poloskov, V V; Shuvalov, A N; Rudneva, I A; Timofeeva, T A
2018-03-01
In culture of THP-1 cells differentiated into macrophages with PMA (THP-PMA macrophages) infected with influenza viruses of subtypes H1, H5 and H9, we measured the expression of TLR7 and RIG1 receptor genes, sensors of viral RNA and ribonucleoprotein, and the levels of production of inflammatory cytokines IL-1β, TNFα, IL-10, and IFNα. The sensitivity and inflammatory response of THP-PMA macrophages to pandemic influenza A virus H1N1pdm09 and avian influenza H5N2 and H9N2 viruses correlate with the intracellular level of their viral RNA and activation of the RIG1 gene. Abortive infection is accompanied by intensive macrophage secretion of TNFα, IL-1β, and toxic factors inducing cell death. Activity of endosomal TLR7 receptor gene changed insignificantly in 24 h after infection and significantly decreased in 48 and 72 h under the action of H5N2 and H9N2, which correlated with manifestation of the cytopathogenic effect of these viruses. H5N2 and H9N2 avian viruses in THP-PMA macrophages are strong activators of the expression of the gene of the cytoplasmic RIG1 receptor 24 and 48 h after infection, and the pandemic virus H1N1pdm09 is a weak stimulator of RIG1 gene. Avian influenza H5N2 and H9N2 viruses are released by rapid induction of the inflammatory response in macrophages. At the late stages of infection, we observed a minor increase in IL-10 secretion in macrophages and, probably, the polarization of a part of the population in type M2. The studied influenza A viruses are weak inductors of IFN in THP-PMA macrophages. In the culture medium of THP-PMA macrophages infected with H9N2 and H5N2 viruses, MTT test revealed high levels of toxic factors causing the death of Caco-2 cells. In contrast to avian viruses, pandemic virus H1N1pdm09 did not induce production of toxic factors.
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Ma, Wenjun; Liu, Qinfang; Qiao, Chuanling; del Real, Gustavo; García-Sastre, Adolfo; Webby, Richard J; Richt, Jürgen A
2014-03-11
The 2009 pandemic H1N1 virus (pH1N1) was derived through reassortment of North American triple reassortant and Eurasian avian-like swine influenza viruses (SIVs). To date, when, how and where the pH1N1 arose is not understood. To investigate viral reassortment, we coinfected cell cultures and a group of pigs with or without preexisting immunity with a Eurasian H1N1 virus, A/Swine/Spain/53207/2004 (SP04), and a North American triple reassortant H1N1 virus, A/Swine/Kansas/77778/2007 (KS07). The infected pigs were cohoused with one or two groups of contact animals to investigate viral transmission. In coinfected MDCK or PK15 continuous cell lines with KS07 and SP04 viruses, more than 20 different reassortant viruses were found. In pigs without or with preexisting immunity (immunized with commercial inactivated swine influenza vaccines) and coinfected with both viruses, six or seven reassortant viruses, as well as the parental viruses, were identified in bronchoalveolar lavage fluid samples from the lungs. Interestingly, only one or two viruses transmitted to and were detected in contact animals. No reassortant containing a gene constellation similar to that of pH1N1 virus was found in either coinfected cells or pigs, indicating that the reassortment event that resulted in the generation of this virus is a rare event that likely involved specific viral strains and/or a favorable, not-yet-understood environment. IMPORTANCE The 2009 pandemic-like H1N1 virus could not be reproduced either in cell cultures or in pigs coinfected with North American triple reassortant H1N1 and Eurasian H1N1 swine influenza viruses. This finding suggests that the generation of the 2009 pandemic H1N1 virus by reassortment was a rare event that likely involved specific viral strains and unknown factors. Different reassortant viruses were detected in coinfected pigs with and without preexisting immunity, indicating that host immunity plays a relevant role in driving viral reassortment of
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Monastyrskyi, Andrii; Kyle, Dennis E.; Manetsch, Roman
2015-01-01
Infectious diseases are the second leading cause of deaths in the world with malaria being responsible for approximately the same amount of deaths as cancer in 2012. Despite the success in malaria prevention and control measures decreasing the disease mortality rate by 45% since 2000, the development of single-dose therapeutics with radical cure potential is required to completely eradicate this deadly condition. Targeting multiple stages of the malaria parasite is becoming a primary requirement for new candidates in antimalarial drug discovery and development. Recently, 4(1H)-pyridone, 4(1H)-quinolone, 1,2,3,4-tetrahydroacridone, and phenoxyethoxy-4(1H)-quinolone chemotypes have been shown to be antimalarials with blood stage activity, liver stage activity, and transmission blocking activity. Advancements in structure-activity relationship and structure-property relationship studies, biological evaluation in vitro and in vivo, as well as pharmacokinetics of the 4(1H)-pyridone and 4(1H)-quinolone chemotypes will be discussed. PMID:25116582
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NASA Astrophysics Data System (ADS)
Kuz'mina, L. G.; Navasardyan, M. A.; Mikhailov, A. A.
2017-11-01
X-ray diffraction study of two crystalline modifications of C2H5O-C6H3(OH)-CH=N-C6H4-CH3 ( 1a, sp. gr. P21/ n, and 1b, sp. gr. C2/c) and C3H7O-C6H3(OH)-CH=N-C6H4-C4H9 ( 2, sp. gr. P212121) has been performed. The 1a crystal structure contains two independent molecules. The molecules are conformationally nonrigid with respect to the mutual rotation of benzene rings; the dihedral angles between their planes are 29.19° and 26.00° in the independent molecules of 1a, 18.72° in the molecule of 1b, and 50.35° in the molecule of 2. The crystal packing of the compounds is discussed.
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Matusiak, Agnieszka; Kuczer, Mariola; Czarniewska, Elżbieta; Rosiński, Grzegorz; Kowalik-Jankowska, Teresa
2014-09-01
Mono- and polynuclear copper(II) complexes of the alloferon 1 with point mutations (H1A) A(1)GVSGH(6)GQH(9)GVH(12)G (Allo1A) and (H9A) H(1)GVSGH(6)GQA(9)GVH(12)G (Allo9A) have been studied by potentiometric, UV-visible, CD, EPR spectroscopic and mass spectrometry (MS) methods. To obtain a complete complex speciation different metal-to-ligand molar ratios ranging from 1:1 to 4:1 for Allo1A and to 3:1 for Allo9A were studied. The presence of the His residue in first position of the peptide chain changes the coordination abilities of the Allo9A peptide in comparison to that of the Allo1A. Imidazole-N3 atom of N-terminal His residue of the Allo9A peptide forms stable 6-membered chelate with the terminal amino group. Furthermore, the presence of two additional histidine residues in the Allo9A peptide (H(6),H(12)) leads to the formation of the CuL complex with 4N {NH2,NIm-H(1),NIm-H(6),NIm-H(12)} binding site in wide pH range (5-8). For the Cu(II)-Allo1A system, the results demonstrated that at physiological pH7.4 the predominant complex the CuH-1L consists of the 3N {NH2,N(-),CO,NIm} coordination mode. The inductions of phenoloxidase activity and apoptosis in vivo in Tenebrio molitor cells by the ligands and their copper(II) complexes at pH7.4 were studied. The Allo1A, Allo1K peptides and their copper(II) complexes displayed the lowest hemocytotoxic activity while the most active was the Cu(II)-Allo9A complex formed at pH7.4. The results may suggest that the N-terminal-His(1) and His(6) residues may be more important for their proapoptotic properties in insects than those at positions 9 and 12 in the peptide chain. Copyright © 2014 Elsevier Inc. All rights reserved.
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40 CFR 721.10171 - 1H-benz(e)indolium, 1,1,2,3-tetramethyl-, 4-methylbenzenesulfonic acid (1:1).
Code of Federal Regulations, 2010 CFR
2010-07-01
... 40 Protection of Environment 30 2010-07-01 2010-07-01 false 1H-benz(e)indolium, 1,1,2,3... SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10171 1H-benz(e)indolium, 1,1,2,3... reporting. (1) The chemical substance identified as 1H-benz(e)indolium, 1,1,2,3-tetramethyl-, 4...
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Influenza A(H1N1)pdm09 during air travel
Neatherlin, John; Cramer, Elaine H.; Dubray, Christine; Marienau, Karen J.; Russell, Michelle; Sun, Hong; Whaley, Melissa; Hancock, Kathy; Duong, Krista K.; Kirking, Hannah L.; Schembri, Christopher; Katz, Jacqueline M.; Cohen, Nicole J.; Fishbein, Daniel B.
2015-01-01
Summary The global spread of the influenza A(H1N1)pdm09 virus (pH1N1) associated with travelers from North America during the onset of the 2009 pandemic demonstrates the central role of international air travel in virus migration. To characterize risk factors for pH1N1 transmission during air travel, we investigated travelers and airline employees from four North American flights carrying ill travelers with confirmed pH1N1 infection. Of 392 passengers and crew identified, information was available for 290 (74%) passengers were interviewed. Overall attack rates for acute respiratory infection and influenza-like illness 1–7 days after travel were 5.2% and 2.4% respectively. Of 43 individuals that provided sera, 4 (9.3%) tested positive for pH1N1 antibodies, including 3 with serologic evidence of asymptomatic infection. Investigation of novel influenza aboard aircraft may be instructive. However, beyond the initial outbreak phase, it may compete with community-based mitigation activities, and interpretation of findings will be difficult in the context of established community transmission. PMID:23523241
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A(H1N1)pdm09 influenza infection: vaccine inefficiency.
Friedman, Nehemya; Drori, Yaron; Pando, Rakefet; Glatman-Freedman, Aharona; Sefty, Hanna; Bassal, Ravit; Stein, Yaniv; Shohat, Tamy; Mendelson, Ella; Hindiyeh, Musa; Mandelboim, Michal
2017-05-16
The last influenza pandemic, caused by the swine A(H1N1)pdm09 influenza virus, began in North America at 2009. Since then, the World Health Organization (WHO) recommended integration of the swine-based virus A/California/07/2009 strain in yearly vaccinations. Yet, infections with A(H1N1)pdm09 have continued in subsequent years. The reasons for this are currently unknown. During the 2015-2016 influenza season, we noted an increased prevalence of A(H1N1)pdm09 influenza virus infection in Israel. Our phylogenetic analysis indicated that the circulating A(H1N1)pdm09 strains belonged to 6B.1 and 6B.2 clades and differed from the vaccinating strain, with approximately 18 amino acid differences found between the circulating strains and the immunizing A/California/07/2009 strain. Hemmaglutination inhibition (HI) assays demonstrated higher antibodies titer against the A/California/07/2009 vaccinating strain as compared to the circulating Israeli strains. We thus suggest that the current vaccination was not sufficiently effective and propose inclusion of the current circulating A(H1N1)pdm09 influenza viruses in the annual vaccine composition.
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Kobayashi, Miho; Takayama, Ikuyo; Kageyama, Tsutomu; Tsukagoshi, Hiroyuki; Saitoh, Mika; Ishioka, Taisei; Yokota, Yoko; Kimura, Hirokazu; Tashiro, Masato; Kozawa, Kunihisa
2013-12-01
We isolated a novel influenza virus A(H1N2) strain from a pig on January 13, 2012, in Gunma Prefecture, Japan. Phylogenetic analysis showed that the strain was a novel type of double-reassortant virus derived from the swine influenza virus strains H1N1pdm09 and H1N2, which were prevalent in Gunma at that time.
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NASA Technical Reports Server (NTRS)
Richter, OTTO-G.
1993-01-01
The original Revised Shapley-Ames (RSA) galaxy sample of almost 1300 galaxies has been augmented with further bright galaxies from the RSA appendix as well as newer galaxy catalogs. A complete and homogeneous, strictly magnitude-limited all-sky sample of 2345 galaxies brighter than 13.4 in apparent blue magnitude was formed. New 21 cm H1 line observations for more than 600 RSA galaxies have been combined with all previously available H1 data from the literature. This new extentise data act allows detailed tests of widely accepted 'standard' reduction and analysis techniques.
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González-Padilla, Jazmin E; Rosales-Hernández, Martha C; Padilla-Martínez, Itzia I; García-Báez, Efren V; Rojas-Lima, Susana; Salazar-Pereda, Veronica
2014-01-01
Molecules of 1,2-bis(4-bromophenyl)-1H-benzimidazole, C19H12Br2N2, (I), and 2-(4-bromophenyl)-1-(4-nitrophenyl)-1H-benzimidazole, C19H12BrN3O2, (II), are arranged in dimeric units through C-H...N and parallel-displaced π-stacking interactions favoured by the appropriate disposition of N- and C-bonded phenyl rings with respect to the mean benzimidazole plane. The molecular packing of the dimers of (I) and (II) arises by the concurrence of a diverse set of weak intermolecular C-X...D (X = H, NO2; D = O, π) interactions.
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Early Detection of Pandemic (H1N1) 2009, Bangladesh
Rahman, Mustafizur; Al Mamun, Abdullah; Haider, Mohammad Sabbir; Zaman, Rashid Uz; Karmakar, Polash Chandra; Nasreen, Sharifa; Muneer, Syeda Mah-E; Homaira, Nusrat; Goswami, Doli Rani; Ahmed, Be-Nazir; Husain, Mohammad Mushtuq; Jamil, Khondokar Mahbuba; Khatun, Selina; Ahmed, Mujaddeed; Chakraborty, Apurba; Fry, Alicia; Widdowson, Marc-Alain; Bresee, Joseph; Azim, Tasnim; Alamgir, A.S.M.; Brooks, Abdullah; Hossain, Mohamed Jahangir; Klimov, Alexander; Rahman, Mahmudur; Luby, Stephen P.
2012-01-01
To explore Bangladesh’s ability to detect novel influenza, we examined a series of laboratory-confirmed pandemic (H1N1) 2009 cases. During June–July 2009, event-based surveillance identified 30 case-patients (57% travelers); starting July 29, sentinel sites identified 252 case-patients (1% travelers). Surveillance facilitated response weeks before the spread of pandemic (H1N1) 2009 infection to the general population. PMID:22257637
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Miller, Paula E; Rambachan, Aksharananda; Hubbard, Roderick J; Li, Jiabai; Meyer, Alison E; Stephens, Peter; Mounts, Anthony W; Rolfes, Melissa A; Penn, Charles R
2012-01-01
The influenza A (H1N1) pandemic swept across the globe from April 2009 to August 2010 affecting millions. Many WHO Member States relied on antiviral drugs, specifically neuraminidase inhibitors (NAIs) oseltamivir and zanamivir, to treat influenza patients in critical condition. Such drugs have been found to be effective in reducing severity and duration of influenza illness, and likely reduced morbidity during the pandemic. However, it is less clear whether NAIs used during the pandemic reduced H1N1 mortality. Country-level data on supply of oseltamivir and zanamivir were used to predict H1N1 mortality (per 100,000 people) from July 2009 to August 2010 in forty-two WHO Member States. Poisson regression was used to model the association between NAI supply and H1N1 mortality, with adjustment for economic, demographic, and health-related confounders. After adjustment for potential confounders, each 10% increase in kilograms of oseltamivir, per 100,000 people, was associated with a 1.6% reduction in H1N1 mortality over the pandemic period (relative rate (RR) = 0.84 per log increase in oseltamivir supply). While the supply of zanamivir was considerably less than that of oseltamivir in each Member State, each 10% increase in kilogram of active zanamivir, per 100,000, was associated with a 0.3% reduction in H1N1 mortality (RR = 0.97 per log increase). While there are limitations to the ecologic nature of these data, this analysis offers evidence of a protective relationship between antiviral drug supply and influenza mortality and supports a role for influenza antiviral use in future pandemics.
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Petrie, Joshua G; Parkhouse, Kaela; Ohmit, Suzanne E; Malosh, Ryan E; Monto, Arnold S; Hensley, Scott E
2016-12-15
During the 2013-2014 influenza season, nearly all circulating 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09) strains possessed an antigenically important mutation in hemagglutinin (K166Q). Here, we performed hemagglutination-inhibition (HAI) assays, using sera collected from 382 individuals prior to the 2013-2014 season, and we determined whether HAI titers were associated with protection from A(H1N1)pdm09 infection. Protection was associated with HAI titers against an A(H1N1)pdm09 strain possessing the K166Q mutation but not with HAI titers against the current A(H1N1)pdm09 vaccine strain, which lacks this mutation. These data indicate that contemporary A(H1N1)pdm09 strains are antigenically distinct from the current A(H1N1)pdm09 vaccine strain. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.
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Kobayashi, Miho; Takayama, Ikuyo; Kageyama, Tsutomu; Tsukagoshi, Hiroyuki; Saitoh, Mika; Ishioka, Taisei; Yokota, Yoko; Kimura, Hirokazu; Tashiro, Masato
2013-01-01
We isolated a novel influenza virus A(H1N2) strain from a pig on January 13, 2012, in Gunma Prefecture, Japan. Phylogenetic analysis showed that the strain was a novel type of double-reassortant virus derived from the swine influenza virus strains H1N1pdm09 and H1N2, which were prevalent in Gunma at that time. PMID:24274745
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Molecular structure studies of (1S,2S)-2-benzyl-2,3-dihydro-2-(1H-inden-2-yl)-1H-inden-1-ol
Zhang, Tao; Paluch, Krzysztof; Scalabrino, Gaia; Frankish, Neil; Healy, Anne-Marie; Sheridan, Helen
2015-01-01
The single enantiomer (1S,2S)-2-benzyl-2,3-dihydro-2-(1H-inden-2-yl)-1H-inden-1-ol (2), has recently been synthesized and isolated from its corresponding diastereoisomer (1). The molecular and crystal structures of this novel compound have been fully analyzed. The relative and absolute configurations have been determined by using a combination of analytical tools including X-ray crystallography, X-ray Powder Diffraction (XRPD) analysis and Nuclear Magnetic Resonance (NMR) spectroscopy. PMID:25750458
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26 CFR 1.643(h)-1 - Distributions by certain foreign trusts through intermediaries.
Code of Federal Regulations, 2010 CFR
2010-04-01
... intermediaries. 1.643(h)-1 Section 1.643(h)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Estates, Trusts, and Beneficiaries § 1.643(h)-1... section, FT is deemed to have distributed XYZ stock with a value of 85X to C on December 1, 2001. (h...
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Xu, Jiarong; Yang, Deji; Huang, Dongyan; Xu, Jiaping; Liu, Shichao; Lin, Huixing; Zhu, Haodan; Liu, Bao; Lu, Chengping
2013-03-01
Swine influenza (SI) is an acute respiratory infectious disease of swine caused by swine influenza virus (SIV). SIV is not only an important respiratory pathogen in pigs but also a potent threat to human health. Here, we report the construction of a recombinant swinepox virus (rSPV/H3-2A-H1) co-expressing hemagglutinin (HA1) of SIV subtypes H1N1 and H3N2. Immune responses and protection efficacy of the rSPV/H3-2A-H1 were evaluated in guinea pigs. Inoculation of rSPV/H3-2A-H1 yielded neutralizing antibodies against SIV H1N1 and H3N2. The IFN-γ and IL-4 concentrations in the supernatant of lymphocytes stimulated with purified SIV HA1 antigen were significantly higher (P < 0.01) than those of the control groups. Complete protection of guinea pigs against SIV H1N1 or H3N2 challenge was observed. No SIV shedding was detected from guinea pigs vaccinated with rSPV/H3-2A-H1 after challenge. Most importantly, the guinea pigs immunized with rSPV/H3-2A-H1 did not show gross and micrographic lung lesions. However, the control guinea pigs experienced distinct gross and micrographic lung lesions at 7 days post-challenge. Our data suggest that the recombinant swinepox virus encoding HA1 of SIV H1N1 and H3N2 might serve as a promising candidate vaccine for protection against SIV H1N1 and H3N2 infections.
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Pandemic (H1N1) 2009 Cases, Buenos Aires, Argentina
Querci, Marcia; Marcone, Débora; Videla, Cristina; Martínez, Alfredo; Bonvehi, Pablo; Carballal, Guadalupe
2010-01-01
To determine clinical and virologic characteristics of pandemic (H1N1) 2009 in Buenos Aires, Argentina, we conducted real-time reverse transcription–PCR on samples from patients with influenza-like illness, June 11–30, 2009. Of 513 patients tested, 54% were positive for influenza virus subtype H1N1. Infection rate was lowest for patients ≥60 years of age. PMID:20113568
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Dash, Sandeep Kumar; Kumar, Manoj; Kataria, Jag Mohan; Nagarajan, Shanmugasundaram; Tosh, Chakradhar; Murugkar, Harshad V; Kulkarni, Diwakar D
2016-06-01
Low pathogenic avian influenza H9N2 and highly pathogenic avian influenza H5N1 viruses continue to co-circulate in chickens. Prior infection with low pathogenic avian influenza can modulate the outcome of H5N1 infection. In India, low pathogenic H9N2 and highly pathogenic H5N1 avian influenza viruses are co-circulating in poultry. Herein, by using chickens with prior infection of A/chicken/India/04TI05/2012 (H9N2) virus we explored the outcome of infection with H5N1 virus A/turkey/India/10CA03/2012 natural PB1 gene reassortant from H9N2. Four groups (E1-E4) of SPF chickens (n = 6) prior inoculated with 10(6) EID50 of H9N2 virus were challenged with 10(6) EID50 of H5N1 natural reassortant (PB1-H9N2) virus at days 1 (group E1); 3 (group E2); 7 (group E3) and 14 (group E4) post H9N2 inoculation. The survival percentage in groups E1-E4 was 0, 100, 66.6 and 50%, respectively. Virus shedding periods for groups E1-E4 were 3, 4, 7 and 9 days, respectively post H5N1 challenge. Birds of group E1 and E2 were shedding both H9N2 and H5N1 viruses and mean viral RNA copy number was higher in oropharyngeal swabs than cloacal swabs. In group, E3 and E4 birds excreted only H5N1 virus and mean viral RNA copy number was higher in most cloacal swabs than oral swabs. These results indicate that prior infection with H9N2 virus could protect from lethal challenge of reassortant H5N1 virus as early as with three days prior H9N2 inoculation and protection decreased in groups E3 and E4 as time elapsed. However, prior infection with H9N2 did not prevent infection with H5N1 virus and birds continue to excrete virus in oropharyngeal and cloacal swabs. Amino acid substitution K368E was found in HA gene of excreted H5N1 virus of group E3. Hence, concurrent infection can also cause emergence of viruses with mutations leading to virus evolution. The results of this study are important for the surveillance and epidemiological data analysis where both H9N2 and H5N1 viruses are co
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Kapczynski, Darrell R.; Tumpey, Terrence M.; Hidajat, Rachmat; Zsak, Aniko; Chrzastek, Klaudia; Tretyakova, Irina; Pushko, Peter
2016-01-01
Highly pathogenic avian influenza (HPAI) viruses, especially H5N1 strains, represent a public health threat and cause widespread morbidity and mortality in domestic poultry. Recombinant virus-like particles (VLPs) represent a promising novel vaccine approach to control avian influenza including HPAI strains. Influenza VLPs contain viral hemagglutinin (HA), which can be expressed in cell culture within highly immunogenic VLPs that morphologically and antigenically resemble influenza virions, except VLPs are non-infectious. Here we describe a recombinant VLP containing HA proteins derived from three distinct clades of H5N1 viruses as an experimental, broadly protective H5 avian influenza vaccine. A baculovirus vector was configured to co-express the H5 genes from recent H5N1 HPAI isolates A/chicken/Germany/2014 (clade 2.3.4.4), A/chicken/West Java/Subang/29/2007 (clade 2.1.3) and A/chicken/Egypt/121/2012 (clade 2.2.1). Co-expression of these genes in Sf9 cells along with influenza neuraminidase (NA) and retrovirus gag genes resulted in production of triple-clade H555 VLPs that exhibited hemagglutination activity and morphologically resembled influenza virions. Vaccination of chickens with these VLPs resulted in induction of serum antibody responses and efficient protection against experimental challenges with three different viruses including the recent U.S. H5N8 HPAI isolate. We conclude that these novel triple-clade VLPs represent a feasible strategy for simultaneously evoking protective antibodies against multiple variants of H5 influenza virus. PMID:26868083
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Deblanc, C; Gorin, S; Quéguiner, S; Gautier-Bouchardon, A V; Ferré, S; Amenna, N; Cariolet, R; Simon, G
2012-05-25
Swine influenza virus (SIV) and Mycoplasma hyopneumoniae (Mhp) are widespread in farms and are major pathogens involved in the porcine respiratory disease complex (PRDC). The aim of this experiment was to compare the pathogenicity of European avian-like swine H1N1 and European human-like reassortant swine H1N2 viruses in naïve pigs and in pigs previously infected with Mhp. Six groups of SPF pigs were inoculated intra-tracheally with either Mhp, or H1N1, or H1N2 or Mhp+H1N1 or Mhp+H1N2, both pathogens being inoculated at 21 days intervals in these two last groups. A mock-infected group was included. Although both SIV strains induced clinical signs when singly inoculated, results indicated that the H1N2 SIV was more pathogenic than the H1N1 virus, with an earlier shedding and a greater spread in lungs. Initial infection with Mhp before SIV inoculation increased flu clinical signs and pathogenesis (hyperthermia, loss of appetite, pneumonia lesions) due to the H1N1 virus but did not modify significantly outcomes of H1N2 infection. Thus, Mhp and SIV H1N1 appeared to act synergistically, whereas Mhp and SIV H1N2 would compete, as H1N2 infection led to the elimination of Mhp in lung diaphragmatic lobes. In conclusion, SIV would be a risk factor for the severity of respiratory disorders when associated with Mhp, depending on the viral subtype involved. This experimental model of coinfection with Mhp and avian-like swine H1N1 is a relevant tool for studying the pathogenesis of SIV-associated PRDC and testing intervention strategies for the control of the disease. Copyright © 2012 Elsevier B.V. All rights reserved.
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Pandemic influenza A (H1N1) 2009 vaccine: an update.
Goel, M K; Goel, M; Khanna, P; Mittal, K
2011-01-01
The world witnessed a the first influenza pandemic in this century and fourth overall since first flu pandemic was reported during the World War I. The past experiences with influenza viruses and this pandemic of H1N1 place a consider-able strain on health services and resulted in serious illnesses and a large number of deaths. Develop-ing countries were declared more likely to be at risk from the pandemic effects, as they faced the dual problem of highly vulnerable populations and limited resources to respond H1N1. The public health experts agreed that vaccination is the most effective ways to mitigate the negative effects of the pandemic. The vaccines for H1N1 virus have been used in over 40 countries and administered to over 200 million people helped in a great way and on August 10, 2010, World Health Organization (WHO) announced H1N1 to be in postpandemic period. But based on knowledge about past pandemics, the H1N1 (2009) virus is expected to continue to circulate as a seasonal virus and may undergo some agenic-variation. As WHO strongly recommends vaccination, vigilance for regular updating of the composition of influenza vaccines, based on an assessment of the future impact of circulating viruses along with safety surveillance of the vaccines is necessary. This review has been done to take a stock of the currently available H1N1 vaccines and their possible use as public health intervention in the postpandemic period.
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Wang, Shufen; Yuan, Jiuchuang; Li, Huixing; Chen, Maodu
2017-08-02
In order to study the dynamics of the reaction H( 2 S) + NaH(X 1 Σ + ) → Na( 2 S) + H 2 (X 1 Σ g + ), a new potential energy surface (PES) for the ground state of the NaH 2 system is constructed based on 35 730 ab initio energy points. Using basis sets of quadruple zeta quality, multireference configuration interaction calculations with Davidson correction were carried out to obtain the ab initio energy points. The neural network method is used to fit the PES, and the root mean square error is very small (0.00639 eV). The bond lengths, dissociation energies, zero-point energies and spectroscopic constants of H 2 (X 1 Σ g + ) and NaH(X 1 Σ + ) obtained on the new NaH 2 PES are in good agreement with the experiment data. On the new PES, the reactant coordinate-based time-dependent wave packet method is applied to study the reaction dynamics of H( 2 S) + NaH(X 1 Σ + ) → Na( 2 S) + H 2 (X 1 Σ g + ), and the reaction probabilities, integral cross-sections (ICSs) and differential cross-sections (DCSs) are obtained. There is no threshold in the reaction due to the absence of an energy barrier on the minimum energy path. When the collision energy increases, the ICSs decrease from a high value at low collision energy. The DCS results show that the angular distribution of the product molecules tends to the forward direction. Compared with the LiH 2 system, the NaH 2 system has a larger mass and the PES has a larger well at the H-NaH configuration, which leads to a higher ICS value in the H( 2 S) + NaH(X 1 Σ + ) → Na( 2 S) + H 2 (X 1 Σ g + ) reaction. Because the H( 2 S) + NaH(X 1 Σ + ) → Na( 2 S) + H 2 (X 1 Σ g + ) reaction releases more energy, the product molecules can be excited to a higher vibrational state.
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Identification of reassortant pandemic H1N1 influenza virus in Korean pigs.
Han, Jae Yeon; Park, Sung Jun; Kim, Hye Kwon; Rho, Semi; Nguyen, Giap Van; Song, Daesub; Kang, Bo Kyu; Moon, Hyung Jun; Yeom, Min Joo; Park, Bong Kyun
2012-05-01
Since the 2009 pandemic human H1N1 influenza A virus emerged in April 2009, novel reassortant strains have been identified throughout the world. This paper describes the detection and isolation of reassortant strains associated with human pandemic influenza H1N1 and swine influenza H1N2 (SIV) viruses in swine populations in South Korea. Two influenza H1N2 reassortants were detected, and subtyped by PCR. The strains were isolated using Madin- Darby canine kidney (MDCK) cells, and genetically characterized by phylogenetic analysis for genetic diversity. They consisted of human, avian, and swine virus genes that were originated from the 2009 pandemic H1N1 virus and a neuraminidase (NA) gene from H1N2 SIV previously isolated in North America. This identification of reassortment events in swine farms raises concern that reassortant strains may continuously circulate within swine populations, calling for the further study and surveillance of pandemic H1N1 among swine.
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Park, Ji Hun; Kim, Ji Yup; Cho, Woo Kyung; Choi, Insung S
2014-03-01
Bioinspired silicification attracts a great deal of interest because of its physiologically relevant, mild conditions for hydrolysis and condensation of silica precursors, which makes the bioinspired approach superior to the conventional sol–gel process, particularly when dealing with biological entities. However, the morphological control of silica structures with incorporation of functional groups in the bioinspired silicilication has been unexplored. In this work, we co-silicificated (1H, 1H, 2H, 2H-perfluorooctyl)triethoxysilane and tetraethyl orthosilicate to investigate the morphological evolution of fluorinated silica structures in the cetyltrimethylammonium bromide-mediated, cysteamine-catalyzed silicification. The generated micrometer-long wormlike and spherical silica structures display superhydrophobicity after film formation. Interestingly, the measurement of dynamic water contact angles shows that the morphological difference leads to a different wetting state, either the self-cleaning or the pinning state of the superhydrophobic surface.
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Inactivation of influenza A virus H1N1 by disinfection process.
Jeong, Eun Kyo; Bae, Jung Eun; Kim, In Seop
2010-06-01
Because any patient, health care worker, or visitor is capable of transmitting influenza to susceptible persons within hospitals, hospital-acquired influenza has been a clinical concern. Disinfection and cleaning of medical equipment, surgical instruments, and hospital environment are important measures to prevent transmission of influenza virus from hospitals to individuals. This study was conducted to evaluate the efficacy of disinfection processes, which can be easily operated at hospitals, in inactivating influenza A virus H1N1 (H1N1). The effects of 0.1 mol/L NaOH, 70% ethanol, 70% 1-propanol, solvent/detergent (S/D) using 0.3% tri (n-butyl)-phosphate and 1.0% Triton X-100, heat, and ethylene oxide (EO) treatments in inactivating H1N1 were determined. Inactivation of H1N1 was kinetically determined by the treatment of disinfectants to virus solution. Also, a surface test method, which involved drying an amount of virus on a surface and then applying the inactivation methods for 1 minute of contact time, was used to determine the virucidal activity. H1N1 was completely inactivated to undetectable levels in 1 minute of 70% ethanol, 70% 1-propanol, and solvent/detergent treatments in the surface tests as well as in the suspension tests. H1N1 was completely inactivated in 1 minute of 0.1 mol/L NaOH treatment in the suspension tests and also effectively inactivated in the surface tests with the log reduction factor of 3.7. H1N1 was inactivated to undetectable levels within 5 minutes, 2.5 minutes, and 1 minute of heat treatment at 70, 80, and 90 degrees C, respectively in the suspension tests. Also, H1N1 was completely inactivated by EO treatment in the surface tests. Common disinfectants, heat, and EO tested in this study were effective at inactivating H1N1. These results would be helpful in implementing effective disinfecting measures to prevent hospital-acquired infections. Copyright 2010 Association for Professionals in Infection Control and Epidemiology, Inc
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Calabi-Yau threefolds with small h1,1's from Fano threefolds
NASA Astrophysics Data System (ADS)
Lee, Nam-Hoon
2017-09-01
We construct Calabi-Yau threefolds with relatively small Hodge numbers h 1 , 1's by smoothing normal crossing varieties, which are obtained from Fano threefolds. We consider over 300 configurations and compute Hodge numbers of Calabi-Yau threefolds. Many of those Hodge pairs (h 1 , 1 ,h 1 , 2) do not overlap with those of Calabi-Yau threefolds constructed in the toric setting.
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Possible Increased Pathogenicity of Pandemic (H1N1) 2009 Influenza Virus upon Reassortment
Schrauwen, Eefje J.A.; Herfst, Sander; Chutinimitkul, Salin; Bestebroer, Theo M.; Rimmelzwaan, Guus F.; Osterhaus, Albert D.M.E.; Kuiken, Thijs
2011-01-01
Since emergence of the pandemic (H1N1) 2009 virus in April 2009, three influenza A viruses—seasonal (H3N2), seasonal (H1N1), and pandemic (H1N1) 2009—have circulated in humans. Genetic reassortment between these viruses could result in enhanced pathogenicity. We compared 4 reassortant viruses with favorable in vitro replication properties with the wild-type pandemic (H1N1) 2009 virus with respect to replication kinetics in vitro and pathogenicity and transmission in ferrets. Pandemic (H1N1) 2009 viruses containing basic polymerase 2 alone or in combination with acidic polymerase of seasonal (H1N1) virus were attenuated in ferrets. In contrast, pandemic (H1N1) 2009 with neuraminidase of seasonal (H3N2) virus resulted in increased virus replication and more severe pulmonary lesions. The data show that pandemic (H1N1) 2009 virus has the potential to reassort with seasonal influenza viruses, which may result in increased pathogenicity while it maintains the capacity of transmission through aerosols or respiratory droplets. PMID:21291589
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Terahertz Spectroscopy of CrH (X 6Σ+) and AlH (X 1Σ+)
NASA Astrophysics Data System (ADS)
Halfen, D. T.; Ziurys, L. M.
2016-12-01
New laboratory measurements of hydrides have been carried out using terahertz direct absorption spectroscopy. Spin components of the N=2≤ftarrow 1 transition of the free radical CrH (X 6Σ+) have been recorded in the range 730-734 GHz, as well as a new measurement of the J=2≤ftarrow 1 line of AlH (X 1Σ+) near 755 GHz. Both species were created in an AC discharge of H2, argon, and metal vapor. For CrH, the chromium source was Cr(CO)6, while AlH was produced from Al(CH3)3. The J=4.5≤ftarrow 3.5 and 3.5≤ftarrow 2.5 fine-structure components were recorded for CrH, each which consists of resolved proton hyperfine doublets. For AlH, the two main quadrupole components, F=4.5≤ftarrow 3.5 and 3.5≤ftarrow 2.5, of the J=2≤ftarrow 1 transition were observed as blended features. These data were analyzed with previous 1≤ftarrow 0 millimeter/submillimeter measurements with 6Σ and 1Σ Hamiltonians for chromium and aluminum hydrides, respectively, and rotational, fine-structure (CrH only), and hyperfine constants were derived. The new measurements have resulted in refined spectroscopic parameters for both species, as well as direct measurement of the respective 2≤ftarrow 1 rotational transitions. This work also resolves a 10 MHz discrepancy in the frequency of the AlH line. CrH and AlH have already been observed in the photospheres of stars via their electronic transitions. These data will facilitate their discovery at submillimeter/terahertz wavelengths in circumstellar envelopes and perhaps in diffuse clouds.
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26 CFR 31.3121(h)-1 - American employer.
Code of Federal Regulations, 2010 CFR
2010-04-01
... 26 Internal Revenue 15 2010-04-01 2010-04-01 false American employer. 31.3121(h)-1 Section 31.3121(h)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) EMPLOYMENT....3121(h)-1 American employer. (a) The term “American employer” means an employer which is (1) the United...
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Moon, Jong Taik; Jeon, Ji Young; Park, Hang Ah; Noh, Young-Soo; Lee, Kyung-Tae; Kim, Jungahn; Choo, Dong Joon; Lee, Jae Yeol
2010-01-15
3,4-Diphenyl-substituted 1H-furan-2,5-dione and 1H-pyrrole-2,5-dione derivatives were synthesized and evaluated for the inhibitory activities on LPS-induced PGE(2) production in RAW 264.7 macrophage cells. Both 1H-furan-2,5-dione and 1H-pyrrole-2,5-dione rings as main scaffolds were easily obtained using one of three synthetic methods. Among the compounds investigated, 1H-3-(4-sulfamoylphenyl)-4-phenyl-pyrrole-2,5-dione (6l) showed a strong inhibitory activity (IC(50)=0.61microM) of PGE(2) production. Copyright 2009 Elsevier Ltd. All rights reserved.
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H1N1, globalization and the epidemiology of inequality.
Sparke, Matthew; Anguelov, Dimitar
2012-07-01
This paper examines the lessons learned from the 2009 H1N1 pandemic in relation to wider work on globalization and the epidemiology of inequality. The media attention and economic resources diverted to the threats posed by H1N1 were significant inequalities themselves when contrasted with weaker responses to more lethal threats posed by other diseases associated with global inequality. However, the multiple inequalities revealed by H1N1 itself in 2009 still provide important insights into the future of global health in the context of market-led globalization. These lessons relate to at least four main forms of inequality: (1) inequalities in blame for the outbreak in the media; (2) inequalities in risk management; (3) inequalities in access to medicines; and (4) inequalities encoded in the actual emergence of new flu viruses. Copyright © 2011 Elsevier Ltd. All rights reserved.
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Throsby, Mark; van den Brink, Edward; Jongeneelen, Mandy; Poon, Leo L. M.; Alard, Philippe; Cornelissen, Lisette; Bakker, Arjen; Cox, Freek; van Deventer, Els; Guan, Yi; Cinatl, Jindrich; ter Meulen, Jan; Lasters, Ignace; Carsetti, Rita; Peiris, Malik; de Kruif, John; Goudsmit, Jaap
2008-01-01
Background The hemagglutinin (HA) glycoprotein is the principal target of protective humoral immune responses to influenza virus infections but such antibody responses only provide efficient protection against a narrow spectrum of HA antigenic variants within a given virus subtype. Avian influenza viruses such as H5N1 are currently panzootic and pose a pandemic threat. These viruses are antigenically diverse and protective strategies need to cross protect against diverse viral clades. Furthermore, there are 16 different HA subtypes and no certainty the next pandemic will be caused by an H5 subtype, thus it is important to develop prophylactic and therapeutic interventions that provide heterosubtypic protection. Methods and Findings Here we describe a panel of 13 monoclonal antibodies (mAbs) recovered from combinatorial display libraries that were constructed from human IgM+ memory B cells of recent (seasonal) influenza vaccinees. The mAbs have broad heterosubtypic neutralizing activity against antigenically diverse H1, H2, H5, H6, H8 and H9 influenza subtypes. Restriction to variable heavy chain gene IGHV1-69 in the high affinity mAb panel was associated with binding to a conserved hydrophobic pocket in the stem domain of HA. The most potent antibody (CR6261) was protective in mice when given before and after lethal H5N1 or H1N1 challenge. Conclusions The human monoclonal CR6261 described in this study could be developed for use as a broad spectrum agent for prophylaxis or treatment of human or avian influenza infections without prior strain characterization. Moreover, the CR6261 epitope could be applied in targeted vaccine strategies or in the design of novel antivirals. Finally our approach of screening the IgM+ memory repertoire could be applied to identify conserved and functionally relevant targets on other rapidly evolving pathogens. PMID:19079604
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Impact of pandemic (H1N1) 2009 on Australasian critical care units.
Drennan, Kelly; Hicks, Peter; Hart, Graeme
2010-12-01
To identify the resource usage by patients with influenza A H1N1 admitted to Australian and New Zealand intensive care units during the first wave of the pandemic in June, July and August 2009. Data were collected in two separate surveys: the 2007-08 resource and activity survey and the 2009 influenza pandemic survey. Participants comprised 143 of the 189 Australian and New Zealand critical care units identified by the Australian and New Zealand Intensive Care Society Centre for Outcome and Resource Evaluation (ANZICS CORE). Mean length of stay (LOS) and ventilation data for H1N1 patients were reported by the ANZIC Influenza Investigators study from the same units over the same time period. Mean LOS for all ICU admissions was obtained from the ANZICS CORE adult patient database 10-year study. H1N1 patient admissions as a proportion of all ICU admissions; H1N1 patient bed-days as a proportion of total bed-days; ventilation resource usage by H1N1 patients; changes in ICU admissions for elective surgery during the H1N1 pandemic. Over the period June-August 2009, among 30 222 ICU admissions to 133 ICUs contributing data, 704 patients (2.3%) had H1N1 influenza A. Twenty-eight units had no H1N1 patient admissions. The peak of the pandemic in Australia and New Zealand occurred in July 2009, when H1N1 patients represented 3.7% of all ICU admissions for July and 53.5% of all H1N1 patient admissions in the period June-August 2009. We estimate that H1N1 cases required approximately 12.4% of the ventilator resources and used 8.1% of total patient bed-days. During the pandemic, there was a 3.2 percentage-point reduction in elective admissions to public hospitals (from 32.5% to 29.3%). Low rates of admission of H1N1 patients to ICUs during the 2009 pandemic enabled the intensive care system to cope with the large demand when analysed at a jurisdictional level.
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Characteristics and influences of H1N1 communication on college students
Koskan, Alexis; Foster, Caroline; Karlis, Jack; Rose, India; Tanner, Andrea
2014-01-01
Purpose The purpose of this paper is to assess how college students received and responded to H1N1 pandemic emergency preparedness information and to assess college students’ knowledge and attitudes towards H1N1 during the height of the H1N1 epidemic and corresponding public health response to the outbreak. Design/methodology/approach Using a case study approach, the researchers conducted five focus groups at a large Southeastern US university between October 20–29, 2009. Findings In order to effectively communicate emergency preparedness information to college students, universities should rely on interpersonal communication and mediated communication from trusted sources. College students need to understand the health-related emergency, the risk of the emergency, basic steps to avoid it, and only pertinent cues to action. Oversaturation of this information can lead college students to lessen their perceived importance of the disaster prevention information. Research limitations/implications Focus groups were conducted during only two consecutive weeks of the H1N1 epidemic, and snowball sampling may have led to sample bias. Originality/value This research was conducted during the height of the H1N1 pandemic, and is the only study to date that explores college students’ knowledge, attitudes, and behaviors towards H1N1. PMID:25328288
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NASA Astrophysics Data System (ADS)
Banerjee, Amrita; Chakraborty, Sumit; Altan-Bonnet, Nihal; Grebel, Haim
2013-09-01
Infrared (IR) spectroscopy provides fingerprinting of the energy and orientation of molecular bonds. The IR signals are generally weak and require amplification. Here we present a new plasmonic platform, made of freely suspended graphene, which was coating periodic metal structures. Only monolayer thick films were needed for a fast signal recording. We demonstrated unique IR absorption signals of bound proteins: these were the hemagglutinin area (HA1) of swine influenza (H1N1) and the avian influenza (H5N1) viruses bound to their respective tri-saccharides ligand receptors. The simplicity and sensitivity of such approach may find applications in fast monitoring of binding events.
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Cooper, Lynn A.; Subbarao, Kanta
2000-01-01
A simple molecular technique for rapid genotyping was developed to monitor the internal gene composition of currently circulating influenza A viruses. Sequence information from recent H1N1, H3N2, and H5N1 human virus isolates was used to identify conserved regions within each internal gene, and gene-specific PCR primers capable of amplifying all three virus subtypes were designed. Subtyping was based on subtype-specific restriction fragment length polymorphism (RFLP) patterns within the amplified regions. The strategy was tested in a blinded fashion using 10 control viruses of each subtype (total, 30) and was found to be very effective. Once standardized, the genotyping method was used to identify the origin of the internal genes of 51 influenza A viruses isolated from humans in Hong Kong during and immediately following the 1997–1998 H5N1 outbreak. No avian-human or H1-H3 reassortants were detected. Less than 2% (6 of 486) of the RFLP analyses were inconclusive; all were due to point mutations within a restriction site. The technique was also used to characterize the internal genes of two avian H9N2 viruses isolated from children in Hong Kong during 1999. PMID:10878047
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SUV39H1 interacts with HTLV-1 Tax and abrogates Tax transactivation of HTLV-1 LTR
Kamoi, Koju; Yamamoto, Keiyu; Misawa, Aya; Miyake, Ariko; Ishida, Takaomi; Tanaka, Yuetsu; Mochizuki, Manabu; Watanabe, Toshiki
2006-01-01
Background Tax is the oncoprotein of HTLV-1 which deregulates signal transduction pathways, transcription of genes and cell cycle regulation of host cells. Transacting function of Tax is mainly mediated by its protein-protein interactions with host cellular factors. As to Tax-mediated regulation of gene expression of HTLV-1 and cellular genes, Tax was shown to regulate histone acetylation through its physical interaction with histone acetylases and deacetylases. However, functional interaction of Tax with histone methyltransferases (HMTase) has not been studied. Here we examined the ability of Tax to interact with a histone methyltransferase SUV39H1 that methylates histone H3 lysine 9 (H3K9) and represses transcription of genes, and studied the functional effects of the interaction on HTLV-1 gene expression. Results Tax was shown to interact with SUV39H1 in vitro, and the interaction is largely dependent on the C-terminal half of SUV39H1 containing the SET domain. Tax does not affect the methyltransferase activity of SUV39H1 but tethers SUV39H1 to a Tax containing complex in the nuclei. In reporter gene assays, co-expression of SUV39H1 represses Tax transactivation of HTLV-1 LTR promoter activity, which was dependent on the methyltransferase activity of SUV39H1. Furthermore, SUV39H1 expression is induced along with Tax in JPX9 cells. Chromatin immunoprecipitation (ChIP) analysis shows localization of SUV39H1 on the LTR after Tax induction, but not in the absence of Tax induction, in JPX9 transformants retaining HTLV-1-Luc plasmid. Immunoblotting shows higher levels of SUV39H1 expression in HTLV-1 transformed and latently infected cell lines. Conclusion Our study revealed for the first time the interaction between Tax and SUV39H1 and apparent tethering of SUV39H1 by Tax to the HTLV-1 LTR. It is speculated that Tax-mediated tethering of SUV39H1 to the LTR and induction of the repressive histone modification on the chromatin through H3 K9 methylation may be the basis
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Post-translational modifications of linker histone H1 variants in mammals
NASA Astrophysics Data System (ADS)
Starkova, T. Yu; Polyanichko, A. M.; Artamonova, T. O.; Khodorkovskii, M. A.; Kostyleva, E. I.; Chikhirzhina, E. V.; Tomilin, A. N.
2017-02-01
The covalent modifications of the linker histone H1 and the core histones are thought to play an important role in the control of chromatin functioning. Histone H1 variants from K562 cell line (hH1), mouse (mH1) and calf (cH1) thymi were studied by matrix-activated laser desorption/ionization fourier transform ion cyclotron resonance mass-spectroscopy (MALDI-FT-ICR-MS). The proteomics analysis revealed novel post-translational modifications of the histone H1, such as meK34-mH1.4, meK35-cH1.1, meK35-mH1.1, meK75-hH1.2, meK75-hH1.3, acK26-hH1.4, acK26-hH1.3 and acK17-hH1.1. The comparison of the hH1, mH1 and cH1 proteins has demonstrated that the types and positions of the post-translational modifications of the globular domains of the H1.2-H1.4 variants are very conservative. However, the post-translational modifications of the N- and C-terminal tails of H1.2, H1.3 and H1.4 are different. The differences of post-translational modifications in the N- and C-terminal tails of H1.2, H1.3 and H1.4 likely lead to the differences in DNA-H1 and H1-protein interactions.
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26 CFR 1.430(h)(2)-1 - Interest rates used to determine present value.
Code of Federal Regulations, 2010 CFR
2010-04-01
.... 1.430(h)(2)-1 Section 1.430(h)(2)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Certain Stock Options § 1.430(h)(2)-1 Interest... to the interest rates to be applied for a plan year under section 430(h)(2). Section 430(h)(2) and...
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Histone h1 depletion impairs embryonic stem cell differentiation.
Zhang, Yunzhe; Cooke, Marissa; Panjwani, Shiraj; Cao, Kaixiang; Krauth, Beth; Ho, Po-Yi; Medrzycki, Magdalena; Berhe, Dawit T; Pan, Chenyi; McDevitt, Todd C; Fan, Yuhong
2012-01-01
Pluripotent embryonic stem cells (ESCs) are known to possess a relatively open chromatin structure; yet, despite efforts to characterize the chromatin signatures of ESCs, the role of chromatin compaction in stem cell fate and function remains elusive. Linker histone H1 is important for higher-order chromatin folding and is essential for mammalian embryogenesis. To investigate the role of H1 and chromatin compaction in stem cell pluripotency and differentiation, we examine the differentiation of embryonic stem cells that are depleted of multiple H1 subtypes. H1c/H1d/H1e triple null ESCs are more resistant to spontaneous differentiation in adherent monolayer culture upon removal of leukemia inhibitory factor. Similarly, the majority of the triple-H1 null embryoid bodies (EBs) lack morphological structures representing the three germ layers and retain gene expression signatures characteristic of undifferentiated ESCs. Furthermore, upon neural differentiation of EBs, triple-H1 null cell cultures are deficient in neurite outgrowth and lack efficient activation of neural markers. Finally, we discover that triple-H1 null embryos and EBs fail to fully repress the expression of the pluripotency genes in comparison with wild-type controls and that H1 depletion impairs DNA methylation and changes of histone marks at promoter regions necessary for efficiently silencing pluripotency gene Oct4 during stem cell differentiation and embryogenesis. In summary, we demonstrate that H1 plays a critical role in pluripotent stem cell differentiation, and our results suggest that H1 and chromatin compaction may mediate pluripotent stem cell differentiation through epigenetic repression of the pluripotency genes.
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Characterization of H1N1 swine influenza viruses circulating in Canadian pigs in 2009.
Nfon, Charles K; Berhane, Yohannes; Hisanaga, Tamiko; Zhang, Shunzhen; Handel, Katherine; Kehler, Helen; Labrecque, Olivia; Lewis, Nicola S; Vincent, Amy L; Copps, John; Alexandersen, Soren; Pasick, John
2011-09-01
The 2009 pandemic H1N1 (pH1N1), of apparent swine origin, may have evolved in pigs unnoticed because of insufficient surveillance. Consequently, the need for surveillance of influenza viruses circulating in pigs has received added attention. In this study we characterized H1N1 viruses isolated from Canadian pigs in 2009. Isolates from May 2009 were comprised of hemagglutinin and neuraminidase (NA) genes of classical SIV origin in combination with the North American triple-reassortant internal gene (TRIG) cassette, here termed contemporary SIV (conSIV) H1N1. These conSIV H1N1 viruses were contiguous with the North American αH1 cluster, which was distinct from the pH1N1 isolates that were antigenically more related to the γH1 cluster. After the initial isolation of pH1N1 from an Alberta pig farm in early May 2009, pH1N1 was found several times in Canadian pigs. These pH1N1 isolates were genetically and antigenically homogeneous. In addition, H1N1 viruses bearing seasonal human H1 and N1 genes together with the TRIG cassette and an NA encoding an oseltamivir-resistance marker were isolated from pigs. The NS gene of one of these seasonal human-like SIV (shSIV) H1N1 isolates was homologous to pH1N1 NS, implicating reassortment between the two strains. Antigenic cross-reactivity was observed between pH1N1 and conSIV but not with shSIV H1N1. In summary, although there was cocirculation of pH1N1 with conSIV and shSIV H1N1 in Canadian pigs after May 2009, there was no evidence supporting the presence of pH1N1 in pigs prior to May 2009. The possibility for further reassortants being generated exists and should be closely monitored.
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Baker, Nicola; Stone, H. O.; Webster, R. G.
1973-01-01
“Monospecific” antisera to the “fragile” hemaglutinnis of H0N1 (PR8) and H1N1 (FM1) influenza viruses detected an asymmetrical cross-reaction between these two strains that could not be explained by a common neuraminidase. Images PMID:4630797
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Reassortant Avian Influenza A(H5N1) Viruses with H9N2-PB1 Gene in Poultry, Bangladesh
Yamage, Mat; Dauphin, Gwenaëlle; Claes, Filip; Ahmed, Garba; Giasuddin, Mohammed; Salviato, Annalisa; Ormelli, Silvia; Bonfante, Francesco; Schivo, Alessia; Cattoli, Giovanni
2013-01-01
Bangladesh has reported a high number of outbreaks of highly pathogenic avian influenza (HPAI) (H5N1) in poultry. We identified a natural reassortant HPAI (H5N1) virus containing a H9N2-PB1 gene in poultry in Bangladesh. Our findings highlight the risks for prolonged co-circulation of avian influenza viruses and the need to monitor their evolution. PMID:24047513
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H1N1 seasonal influenza virus evolutionary rate changed over time.
Suptawiwat, Ornpreya; Kongchanagul, Alita; Boonarkart, Chompunuch; Auewarakul, Prasert
2018-05-02
It was previously shown that the seasonal H1N1 influenza virus antigenic drift occurred at a slower rate than the seasonal H3N2 virus during the first decade of the 21th century. It was hypothesized that the slower antigenic evolution led to a decrease in average ages of infection, which in turn resulted in lower level of global viral circulation. It is unclear what caused the difference between the two viruses, but a plausible explanation may be related to the fact that the H1N1 virus had been in human population for much longer than the H3N2 virus. This would suggest that H1N1 antigenic drift in an earlier period may have been different from a more recent period. To test this hypothesis, we analyzed seasonal H1N1 influenza sequences during various time periods. In comparison to more recent H1N1 virus, the older H1N1 virus during the first half of the 20th century showed evidences of higher nonsynnonymous/synonymous ration (dN/dS) in its hemagglutinin (HA) gene. We compared amino acid sequence changes in the HA epitopes for each outbreak season and found that there were less changes in later years. Amino acid sequence diversity in the epitopes as measured by sequence entropy became smaller for each passing decade. These suggest that there might be some limit to the antigenic drift. The longer an influenza virus has drifted in human population, the less flexibility it may become. With less flexibility to adapt and escape the host immunity, the virus may have to rely more on younger naïve population. Copyright © 2018 Elsevier B.V. All rights reserved.
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Pittalà, Valeria; Romeo, Giuseppe; Salerno, Loredana; Siracusa, Maria Angela; Modica, Maria; Materia, Luisa; Mereghetti, Ilario; Cagnotto, Alfredo; Mennini, Tiziana; Marucci, Gabriella; Angeli, Piero; Russo, Filippo
2006-01-01
The discovery of a new series of selective and high-affinity alpha(1)-adrenoceptor (alpha(1)-AR) ligands, characterized by a 1H-pyrrolo[2,3-d]-pyrimidine-2,4(3H,7H)-dione system, is described in this paper. Some synthesized compounds, including 20, 22, and 30, displayed affinity in the nanomolar range for alpha(1)-ARs and substantial selectivity with respect to 5-HT(1A) and dopaminergic D(1) and D(2) receptors. Functional assays, performed on selected derivatives, showed antagonistic properties.
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Oseltamivir-resistant pandemic influenza a (H1N1) 2009 viruses in Spain.
Ledesma, Juan; Vicente, Diego; Pozo, Francisco; Cilla, Gustavo; Castro, Sonia Pérez; Fernández, Jonathan Suárez; Ruiz, Mercedes Pérez; Navarro, José María; Galán, Juan Carlos; Fernández, Mirian; Reina, Jordi; Larrauri, Amparo; Cuevas, María Teresa; Casas, Inmaculada; Breña, Pilar Pérez
2011-07-01
Pandemic influenza A (H1N1) 2009 virus appeared in Spain on April 25, 2009 for the first time. This new virus was adamantane-resistant but it was sensitive to neuraminidase (NA) inhibitors oseltamivir and zanamivir. To detect oseltamivir-resistant pandemic influenza A (H1N1) 2009 viruses by the Spanish Influenza Surveillance System (SISS) and a possible spread of oseltamivir-resistant viruses in Spain since starting of the pandemic situation. A total of 1229 respiratory samples taken from 413 severe and 766 non-severe patients with confirmed viral detection of pandemic influenza A (H1N1) 2009 viruses from different Spanish regions were analyzed for the specific detection of the H275Y mutation in NA between April 2009 and May 2010. H275Y NA substitution was found in 8 patients infected with pandemic influenza A (H1N1) 2009 viruses collected in November and December 2009 and in January 2010. All oseltamivir-resistant viruses were detected in severe patients (8/413, 1.93%) who previously received treatment with oseltamivir. Six of these patients were immunocompromised. In Spain, the number of oseltamivir-resistant pandemic influenza A (H1N1) 2009 viruses is until now very low. No evidence for any spread of oseltamivir-resistant H1N1 viruses is achieved in our Country. Copyright © 2011 Elsevier B.V. All rights reserved.
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Vibrational mode frequencies of H2S and H2O adsorbed on Ge(0 0 1)-(2 × 1) surfaces
NASA Astrophysics Data System (ADS)
Hartnett, M.; Fahy, S.
2015-02-01
The equilibrium geometry and vibrational modes of H2S and H2O-terminated Ge(0 0 1)-(2 × 1) surfaces are calculated in a supercell approach using first-principles density functional theory in the local density (LDA), generalized gradient (GGA) approximations and van der Waals (vdW) interactions. Mode frequencies are found using the frozen phonon method. For the H2S-passivated surface, the calculated frequencies in LDA (GGA) are 2429 cm-1 (2490) for the Hsbnd S stretch mode, 712 cm-1 (706) for the Hsbnd S bond bending mode, 377 cm-1 (36) for the Gesbnd S stretch mode and 328 cm-1 (337) for Hsbnd S wag mode. Frequencies for the H2O passivated surface are 3590 cm-1 (3600) for the Hsbnd O stretch mode, 921 cm-1 (947) for the bending mode, 609 cm-1 (559) for the Gesbnd O stretch, 1995 cm-1 (1991) for the Gesbnd H stretch mode, 498 cm-1 (478) for the Gesbnd H bending mode and 342 cm-1 (336) for the Hsbnd O wag mode. The differences between the functionals including vdW terms and the LDA or GGA are less than the differences between LDA and GGA for the vibrational mode frequencies.
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Liu, Chun Li; Huang, Qiu Ying; Meng, Xiang Ru
2016-12-01
The synthesis of coordination polymers or metal-organic frameworks (MOFs) has attracted considerable interest owing to the interesting structures and potential applications of these compounds. It is still a challenge to predict the exact structures and compositions of the final products. A new one-dimensional coordination polymer, catena-poly[[[bis{1-[(1H-benzimidazol-2-yl)methyl]-1H-tetrazole-κN 3 }zinc(II)]-μ-hexane-1,6-dicarboxylato-κ 4 O 1 ,O 1' :O 6 ,O 6' ] monohydrate], {[Zn(C 6 H 8 O 4 )(C 9 H 8 N 6 ) 2 ]·H 2 O} n , has been synthesized by the reaction of Zn(Ac) 2 (Ac is acetate) with 1-[(1H-benzimidazol-2-yl)methyl]-1H-tetrazole (bimt) and adipic acid (H 2 adi) at room temperature. In the polymer, each Zn II ion exhibits an irregular octahedral ZnN 2 O 4 coordination geometry and is coordinated by two N atoms from two symmetry-related bimt ligands and four O atoms from two symmetry-related dianionic adipate ligands. Zn II ions are connected by adipate ligands into a one-dimensional chain which runs parallel to the c axis. The bimt ligands coordinate to the Zn II ions in a monodentate mode on both sides of the main chain. In the crystal, the one-dimensional chains are further connected through N-H...O hydrogen bonds, leading to a three-dimensional supramolecular architecture. In addition, the title polymer exhibits fluorescence, with emissions at 334 and 350 nm in the solid state at room temperature.
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Muñoz-Medina, José Esteban; Sánchez-Vallejo, Carlos Javier; Méndez-Tenorio, Alfonso; Monroy-Muñoz, Irma Eloísa; Angeles-Martínez, Javier; Santos Coy-Arechavaleta, Andrea; Santacruz-Tinoco, Clara Esperanza; González-Ibarra, Joaquín; Anguiano-Hernández, Yu-Mei; González-Bonilla, César Raúl; Ramón-Gallegos, Eva; Díaz-Quiñonez, José Alberto
2015-01-01
The unpredictable, evolutionary nature of the influenza A virus (IAV) is the primary problem when generating a vaccine and when designing diagnostic strategies; thus, it is necessary to determine the constant regions in viral proteins. In this study, we completed an in silico analysis of the reported epitopes of the 4 IAV proteins that are antigenically most significant (HA, NA, NP, and M2) in the 3 strains with the greatest world circulation in the last century (H1N1, H2N2, and H3N2) and in one of the main aviary subtypes responsible for zoonosis (H5N1). For this purpose, the HMMER program was used to align 3,016 epitopes reported in the Immune Epitope Database and Analysis Resource (IEDB) and distributed in 34,294 stored sequences in the Pfam database. Eighteen epitopes were identified: 8 in HA, 5 in NA, 3 in NP, and 2 in M2. These epitopes have remained constant since they were first identified (~91 years) and are present in strains that have circulated on 5 continents. These sites could be targets for vaccination design strategies based on epitopes and/or as markers in the implementation of diagnostic techniques. PMID:26346523
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O'Donnell, Christopher D.; Wright, Amber; Vogel, Leatrice; Boonnak, Kobporn; Treanor, John J.
2014-01-01
The hypothesis of original antigenic sin (OAS) states that the imprint established by an individual's first influenza virus infection governs the antibody response thereafter. Subsequent influenza virus infection results in an antibody response against the original infecting virus and an impaired immune response against the newer influenza virus. The purpose of our study was to seek evidence of OAS after infection or vaccination with the 2009 pandemic H1N1 (2009 pH1N1) virus in ferrets and humans previously infected with H1N1 viruses with various antigenic distances from the 2009 pH1N1 virus, including viruses from 1935 through 1999. In ferrets, seasonal H1N1 priming did not diminish the antibody response to infection or vaccination with the 2009 pH1N1 virus, nor did it diminish the T-cell response, indicating the absence of OAS in seasonal H1N1 virus-primed ferrets. Analysis of paired samples of human serum taken before and after vaccination with a monovalent inactivated 2009 pH1N1 vaccine showed a significantly greater-fold rise in the titer of antibody against the 2009 pH1N1 virus than against H1N1 viruses that circulated during the childhood of each subject. Thus, prior experience with H1N1 viruses did not result in an impairment of the antibody response against the 2009 pH1N1 vaccine. Our data from ferrets and humans suggest that prior exposure to H1N1 viruses did not impair the immune response against the 2009 pH1N1 virus. PMID:24648486
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O'Donnell, Christopher D; Wright, Amber; Vogel, Leatrice; Boonnak, Kobporn; Treanor, John J; Subbarao, Kanta
2014-05-01
The hypothesis of original antigenic sin (OAS) states that the imprint established by an individual's first influenza virus infection governs the antibody response thereafter. Subsequent influenza virus infection results in an antibody response against the original infecting virus and an impaired immune response against the newer influenza virus. The purpose of our study was to seek evidence of OAS after infection or vaccination with the 2009 pandemic H1N1 (2009 pH1N1) virus in ferrets and humans previously infected with H1N1 viruses with various antigenic distances from the 2009 pH1N1 virus, including viruses from 1935 through 1999. In ferrets, seasonal H1N1 priming did not diminish the antibody response to infection or vaccination with the 2009 pH1N1 virus, nor did it diminish the T-cell response, indicating the absence of OAS in seasonal H1N1 virus-primed ferrets. Analysis of paired samples of human serum taken before and after vaccination with a monovalent inactivated 2009 pH1N1 vaccine showed a significantly greater-fold rise in the titer of antibody against the 2009 pH1N1 virus than against H1N1 viruses that circulated during the childhood of each subject. Thus, prior experience with H1N1 viruses did not result in an impairment of the antibody response against the 2009 pH1N1 vaccine. Our data from ferrets and humans suggest that prior exposure to H1N1 viruses did not impair the immune response against the 2009 pH1N1 virus.
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Synthesis, characterization, and pharmacological studies of ferrocene-1H-1,2,3-triazole hybrids
NASA Astrophysics Data System (ADS)
Haque, Ashanul; Hsieh, Ming-Fa; Hassan, Syed Imran; Haque Faizi, Md. Serajul; Saha, Anannya; Dege, Necmi; Rather, Jahangir Ahmad; Khan, Muhammad S.
2017-10-01
A series of ferrocene-1H-1,2,3-triazole hybrids namely 1-(4-nitrophenyl)-4-ferrocenyl-1H-1,2,3-triazole (1), 1-(4,4‧-dinitro-2-biphenyl)-4-ferrocenyl-1H-1,2,3-triazole (2), 1-(3-chloro-4-fluorophenyl)-4-ferrocenyl-1H-1,2,3-triazole (3), 1-(4-bromophenyl)-4-ferrocenyl-1H-1,2,3-triazole (4) and 1-(2-nitrophenyl)-4-ferrocenyl-1H-1,2,3-triazole (5) were designed and synthesized by copper-catalyzed azide alkyne cycloaddition (CuAAC) reaction. All the new hybrids were characterized by microanalyses, NMR (1H and 13C), UV-vis, IR, ESI-MS and electrochemical techniques. Crystal structure of the compound (3) was solved by single crystal X-ray diffraction method. The structural (single crystal) and spectroscopic (UV-Vis. and IR) properties of the compound 3 have been analyzed and compared by complementary quantum modeling. Hybrids 1-5 exhibited low toxicity and demonstrated neuroprotective effect.
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Huang, Qiu Ying; Zhao, Yang; Meng, Xiang Ru
2017-08-01
Careful choice of the organic ligands is one of the most important parameters in the rational design and synthesis of coordination polymers. Aromatic polycarboxylates have been widely used in the preparation of metal-organic polymers since they can utilize various coordination modes to form diverse structures and can act as hydrogen-bond acceptors and donors in the assembly of supramolecular structures. Nitrogen-heterocyclic organic compounds have also been used extensively as ligands for the construction of polymers with interesting structures. In the polymers catena-poly[[[diaquabis{2-[(1H-imidazol-1-yl)methyl]-6-methyl-1H-benzimidazole-κN 3 }cobalt(II)]-μ 2 -benzene-1,4-dicarboxylato-κ 2 O 1 :O 4 ] dihydrate], {[Co(C 8 H 4 O 4 )(C 12 H 11 N 4 ) 2 (H 2 O) 2 ]·2H 2 O} n , (I), and catena-poly[[[diaquabis{2-[(1H-imidazol-1-yl)methyl]-6-methyl-1H-benzimidazole-κN 3 }nickel(II)]-μ 2 -benzene-1,4-dicarboxylato-κ 2 O 1 :O 4 ] dihydrate], {[Ni(C 8 H 4 O 4 )(C 12 H 11 N 4 ) 2 (H 2 O) 2 ]·2H 2 O} n , (II), the Co II or Ni II ion lies on an inversion centre and exhibits a slightly distorted octahedral coordination geometry, coordinated by two N atoms from two imidazole rings and four O atoms from two monodentate carboxylate groups and two water molecules. The dicarboxylate ligands bridge metal ions forming a polymeric chain. The 2-[(1H-imidazol-1-yl)methyl]-6-methyl-1H-benzimidazole ligands coordinate to the Co II or Ni II centres in monodentate modes through an imidazole N atom and are pendant on opposite sides of the main chain. The two structures are isomorphous. In the crystal, the one-dimensional chains are further connected through O-H...O, O-H...N and N-H...O hydrogen bonds, leading to a three-dimensional supramolecular architecture. In addition, the IR spectroscopic properties, PXRD patterns, thermogravimetric behaviours and fluorescence properties of both polymers have been investigated.
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Rate and Regulation of Copper Transport by Human Copper Transporter 1 (hCTR1)*
Maryon, Edward B.; Molloy, Shannon A.; Ivy, Kristin; Yu, Huijun; Kaplan, Jack H.
2013-01-01
Human copper transporter 1 (hCTR1) is a homotrimer of a 190-amino acid monomer having three transmembrane domains believed to form a pore for copper permeation through the plasma membrane. The hCTR1-mediated copper transport mechanism is not well understood, nor has any measurement been made of the rate at which copper ions are transported by hCTR1. In this study, we estimated the rate of copper transport by the hCTR1 trimer in cultured cells using 64Cu uptake assays and quantification of plasma membrane hCTR1. For endogenous hCTR1, we estimated a turnover number of about 10 ions/trimer/s. When overexpressed in HEK293 cells, a second transmembrane domain mutant of hCTR1 (H139R) had a 3-fold higher Km value and a 4-fold higher turnover number than WT. Truncations of the intracellular C-terminal tail and an AAA substitution of the putative metal-binding HCH C-terminal tripeptide (thought to be required for transport) also exhibited elevated transport rates and Km values when compared with WT hCTR1. Unlike WT hCTR1, H139R and the C-terminal mutants did not undergo regulatory endocytosis in elevated copper. hCTR1 mutants combining methionine substitutions that block transport (M150L,M154L) on the extracellular side of the pore and the high transport H139R or AAA intracellular side mutations exhibited the blocked transport of M150L,M154L, confirming that Cu+ first interacts with the methionines during permeation. Our results show that hCTR1 elements on the intracellular side of the hCTR1 pore, including the carboxyl tail, are not essential for permeation, but serve to regulate the rate of copper entry. PMID:23658018
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Serological Evidence of Pandemic H1N1 Influenza Virus Infections in Greek Swine.
Kyriakis, C S; Papatsiros, V G; Athanasiou, L V; Valiakos, G; Brown, I H; Simon, G; Van Reeth, K; Tsiodras, S; Spyrou, V; Billinis, C
2016-08-01
The introduction of the 2009 pandemic H1N1 (pH1N1) influenza virus in pigs changed the epidemiology of influenza A viruses (IAVs) in swine in Europe and the rest of the world. Previously, three IAV subtypes were found in the European pig population: an avian-like H1N1 and two reassortant H1N2 and H3N2 viruses with human-origin haemagglutinin (HA) and neuraminidase proteins and internal genes of avian decent. These viruses pose antigenically distinct HAs, which allow the retrospective diagnosis of infection in serological investigations. However, cross-reactions between the HA of pH1N1 and the HAs of the other circulating H1 IAVs complicate serological diagnosis. The prevalence of IAVs in Greek swine has been poorly investigated. In this study, we examined and compared haemagglutination inhibition (HI) antibody titres against previously established IAVs and pH1N1 in 908 swine sera from 88 herds, collected before and after the 2009 pandemic. While we confirmed the historic presence of the three IAVs established in European swine, we also found that 4% of the pig sera examined after 2009 had HI antibodies only against the pH1N1 virus. Our results indicate that pH1N1 is circulating in Greek pigs and stress out the importance of a vigorous virological surveillance programme. © 2015 Blackwell Verlag GmbH.
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Antigenic Patterns and Evolution of the Human Influenza A (H1N1) Virus.
Liu, Mi; Zhao, Xiang; Hua, Sha; Du, Xiangjun; Peng, Yousong; Li, Xiyan; Lan, Yu; Wang, Dayan; Wu, Aiping; Shu, Yuelong; Jiang, Taijiao
2015-09-28
The influenza A (H1N1) virus causes seasonal epidemics that result in severe illnesses and deaths almost every year. A deep understanding of the antigenic patterns and evolution of human influenza A (H1N1) virus is extremely important for its effective surveillance and prevention. Through development of antigenicity inference method for human influenza A (H1N1), named PREDAC-H1, we systematically mapped the antigenic patterns and evolution of the human influenza A (H1N1) virus. Eight dominant antigenic clusters have been inferred for seasonal H1N1 viruses since 1977, which demonstrated sequential replacements over time with a similar pattern in Asia, Europe and North America. Among them, six clusters emerged first in Asia. As for China, three of the eight antigenic clusters were detected in South China earlier than in North China, indicating the leading role of South China in H1N1 transmission. The comprehensive view of the antigenic evolution of human influenza A (H1N1) virus can help formulate better strategy for its prevention and control.
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Plasma metabolomics for the diagnosis and prognosis of H1N1 influenza pneumonia.
Banoei, Mohammad M; Vogel, Hans J; Weljie, Aalim M; Kumar, Anand; Yende, Sachin; Angus, Derek C; Winston, Brent W
2017-04-19
Metabolomics is a tool that has been used for the diagnosis and prognosis of specific diseases. The purpose of this study was to examine if metabolomics could be used as a potential diagnostic and prognostic tool for H1N1 pneumonia. Our hypothesis was that metabolomics can potentially be used early for the diagnosis and prognosis of H1N1 influenza pneumonia. 1 H nuclear magnetic resonance spectroscopy and gas chromatography-mass spectrometry were used to profile the metabolome in 42 patients with H1N1 pneumonia, 31 ventilated control subjects in the intensive care unit (ICU), and 30 culture-positive plasma samples from patients with bacterial community-acquired pneumonia drawn within the first 24 h of hospital admission for diagnosis and prognosis of disease. We found that plasma-based metabolomics from samples taken within 24 h of hospital admission can be used to discriminate H1N1 pneumonia from bacterial pneumonia and nonsurvivors from survivors of H1N1 pneumonia. Moreover, metabolomics is a highly sensitive and specific tool for the 90-day prognosis of mortality in H1N1 pneumonia. This study demonstrates that H1N1 pneumonia can create a quite different plasma metabolic profile from bacterial culture-positive pneumonia and ventilated control subjects in the ICU on the basis of plasma samples taken within 24 h of hospital/ICU admission, early in the course of disease.
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NASA Astrophysics Data System (ADS)
Xie, Yahong; Zhou, Xiaofeng; Mi, Hongyu; Ma, Junhong; Yang, Jianya; Cheng, Jian
2018-03-01
Charge recombination at the ZnO photoanode/electrolyte interface is one of the major limitations for high performance dye-sensitized solar cells (DSSCs) toward their theoretical power conversion efficiency (PCE). Here, we proposed an efficient approach for reducing this interfacial losses and consequently facilitating charge transfer by decorating a hydrophobic thin-film on the surface of the dye-coated zinc oxide photoanode via 1H,1H,2H,2H-perfluorodecyltriethoxysilane (PFDTES) hexane solution immersing. As a result, a high PCE of 8.22% was obtained, which far exceeded the efficiency of 5.40% in a conventional DSSC without PFDTES treatment. Furthermore, PFDTES treatment also largely elongated the lifetime of photogenerated electrons, and maintained a good photo-response at the photoelectrode. This work provides a comprehensive explanation of electron injection, transfer and recombination at the ZnO photoanode/electrolyte interface, and a promising strategy to explore high efficiency ZnO-based DSSCs.
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Kumaki, Yohichi; Day, Craig W.; Smee, Donald F.; Morrey, John D.; Barnard, Dale L.
2011-01-01
Various fluorodeoxyribonucleosides were evaluated for their antiviral activities against influenza virus infections in vitro and in vivo. Among the most potent inhibitors was 2'-deoxy-2'-fluorocytidine (2'-FdC). It inhibited various strains of low and highly pathogenic avian influenza H5N1 viruses, pandemic H1N1 viruses, an oseltamivir-resistant pandemic H1N1 virus, and seasonal influenza viruses (H3N2, H1N1, influenza B) in MDCK cells, with the 90% inhibitory concentrations ranging from 0.13 µM to 4.6 µM, as determined by a virus yield reduction assay. 2'-FdC was then tested for efficacy in BALB/c mice infected with a lethal dose of highly pathogenic influenza A/Vietnam/1203/2004 H5N1 virus. 2’FdC (60 mg/kg/d) administered intraperitoneally (i.p.) twice a day beginning 24 h after virus exposure significantly promoted survival (80% survival) of infected mice (p=0.0001). Equally efficacious were the treatment regimens in which mice were treated with 2'-FdC at 30 or 60 mg/kg/day (bid × 8) beginning 24 h before virus exposure. At these doses, 70–80% of the mice were protected from death due to virus infection (p=0.0005, p=0.0001; respectively). The lungs harvested from treated mice at day four of the infection displayed little surface pathology or histopathology, lung weights were lower, and the 60 mg/kg dose reduced lung virus titers, although not significantly compared to the placebo controls. All doses were well tolerated in uninfected mice. 2'-FdC could also be administered as late as 72 h post virus exposure and still significantly protect 60% mice from the lethal effects of the H5N1 virus infection (p=0.019). Other fluorodeoxyribonucleosides tested in the H5N1 mouse model, 2’-deoxy-5-fluorocytidine and 2'-deoxy-2', 2'-difluorocytidine, were very toxic at higher doses and not inhibitory at lower doses. Finally, 2'-FdC, which was active in the H5N1 mouse model, was also active in a pandemic H1N1 influenza A infection model in mice. When given at 30 mg
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Miller, Paula E; Rambachan, Aksharananda; Hubbard, Roderick J; Li, Jiabai; Meyer, Alison E; Stephens, Peter; Mounts, Anthony W; Rolfes, Melissa A; Penn, Charles R
2013-09-01
When the influenza A (H1N1) pandemic spread across the globe from April 2009 to August 2010, many WHO Member States used antiviral drugs, specifically neuraminidase inhibitors (NAIs) oseltamivir and zanamivir, to treat influenza patients in critical condition. Antivirals have been found to be effective in reducing severity and duration of influenza illness, and likely reduce morbidity; however, it is unclear whether NAIs used during the pandemic reduced H1N1 mortality. To assess the association between antivirals and influenza mortality, at an ecologic level, country-level data on supply of oseltamivir and zanamivir were compared to laboratory-confirmed H1N1 deaths (per 100 000 people) from July 2009 to August 2010 in 42 WHO Member States. From this analysis, it was found that each 10% increase in kilograms of oseltamivir, per 100 000 people, was associated with a 1·6% reduction in H1N1 mortality over the pandemic period [relative rate (RR) = 0·84 per log increase in oseltamivir supply]. Each 10% increase in kilogram of active zanamivir, per 100 000, was associated with a 0·3% reduction in H1N1 mortality (RR = 0·97 per log increase). While limitations exist in the inference that can be drawn from an ecologic evaluation, this analysis offers evidence of a protective relationship between antiviral drug supply and influenza mortality and supports a role for influenza antiviral use in future pandemics. This article summarises the original study described previously, which can be accessed through the following citation: Miller PE, Rambachan A, Hubbard RJ, Li J, Meyer AE, et al. (2012) Supply of Neuraminidase Inhibitors Related to Reduced Influenza A (H1N1) Mortality during the 2009-2010 H1N1 Pandemic: An Ecological Study. PLoS ONE 7(9): e43491. © 2013 Blackwell Publishing Ltd.
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H1 antihistamines and driving.
Popescu, Florin Dan
2008-01-01
Driving performances depend on cognitive, psychomotor and perception functions. The CNS adverse effects of some H1 antihistamines can alter the patient ability to drive. Data from studies using standardized objective cognitive and psychomotor tests (Choice Reaction Time, Critical Flicker Fusion. Digital Symbol Substitution Test), functional brain imaging (Positron Emission Tomography, functional Magnetic Resonance Imaging), neurophysiological studies (Multiple Sleep Latency Test, auditory and visual evoked potentials), experimental simulated driving (driving simulators) and real driving studies (the Highway Driving Test, with the evaluation of the Standard Deviation Lateral Position, and the Car Following Test, with the measurement of the Brake Reaction Time) must be discussed in order to classify a H1 antihistamine as a true non-sedating one.
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26 CFR 1.168(h)-1 - Like-kind exchanges involving tax-exempt use property.
Code of Federal Regulations, 2010 CFR
2010-04-01
... property. 1.168(h)-1 Section 1.168(h)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... and Corporations § 1.168(h)-1 Like-kind exchanges involving tax-exempt use property. (a) Scope. (1... property (as defined in section 168(h)) at the time of the transfer; and (ii) Property that does not become...
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Rith, Sareth; Chin, Savuth; Sar, Borann; Y, Phalla; Horm, Srey Viseth; Ly, Sovann; Buchy, Philippe; Dussart, Philippe; Horwood, Paul F
2015-12-01
Despite annual co-circulation of different subtypes of seasonal influenza, co-infections between different viruses are rarely detected. These co-infections can result in the emergence of reassortant progeny. We document the detection of an influenza co-infection, between influenza A/H3N2 with A/H1N1pdm09 viruses, which occurred in a 3 year old male in Cambodia during April 2014. Both viruses were detected in the patient at relatively high viral loads (as determined by real-time RT-PCR CT values), which is unusual for influenza co-infections. As reassortment can occur between co-infected influenza A strains we isolated plaque purified clonal viral populations from the clinical material of the patient infected with A/H3N2 and A/H1N1pdm09. Complete genome sequences were completed for 7 clonal viruses to determine if any reassorted viruses were generated during the influenza virus co-infection. Although most of the viral sequences were consistent with wild-type A/H3N2 or A/H1N1pdm09, one reassortant A/H3N2 virus was isolated which contained an A/H1N1pdm09 NS1 gene fragment. The reassortant virus was viable and able to infect cells, as judged by successful passage in MDCK cells, achieving a TCID50 of 10(4)/ml at passage number two. There is no evidence that the reassortant virus was transmitted further. The co-infection occurred during a period when co-circulation of A/H3N2 and A/H1N1pdm09 was detected in Cambodia. It is unclear how often influenza co-infections occur, but laboratories should consider influenza co-infections during routine surveillance activities. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.
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An improved technique for the 2H/1H analysis of urines from diabetic volunteers
Coplen, T.B.; Harper, I.T.
1994-01-01
The H2-H2O ambient-temperature equilibration technique for the determination of 2H/1H ratios in urinary waters from diabetic subjects provides improved accuracy over the conventional Zn reduction technique. The standard deviation, ~ 1-2???, is at least a factor of three better than that of the Zn reduction technique on urinary waters from diabetic volunteers. Experiments with pure water and solutions containing glucose, urea and albumen indicate that there is no measurable bias in the hydrogen equilibration technique.The H2-H2O ambient-temperature equilibration technique for the determination of 2H/1H ratios in urinary waters from diabetic subjects provides improved accuracy over the conventional Zn reduction technique. The standard deviation, approximately 1-2%, is at least a factor of three better than that of the Zn reduction technique on urinary waters from diabetic volunteers. Experiments with pure water and solutions containing glucose, urea and albumen indicate that there is no measurable bias in the hydrogen equilibration technique.
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26 CFR 1.1402(h)-1 - Members of certain religious groups opposed to insurance.
Code of Federal Regulations, 2010 CFR
2010-04-01
... insurance. 1.1402(h)-1 Section 1.1402(h)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Tax on Self-Employment Income § 1.1402(h)-1... 1402(h) and this section refer does not include liability insurance of a kind that provides only for...
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Li, Hongyan; Weng, Heng; Lan, Changqing; Zhang, Hongying; Wang, Xinhang; Pan, Jianguang; Chen, Lulu; Huang, Jinbao
2018-03-01
The aim of this study was to compare the clinical features of patients with avian influenza A (H7N9) and influenza A (H1N1) complicated by acute respiratory distress syndrome (ARDS).The clinical data of 18 cases of H7N9 and 26 cases of H1N1 with ARDS were collected and compared in the respiratory intensive care unit (RICU) of Fuzhou Pulmonary Hospital of Fujian from March 2014 to December 2016.Patients with H7N9 had a higher acute physiology and chronic health evaluation-II score (P < .05) and lung injury score (P < .05). The rates of coexisting diabetes mellitus, hyperpyrexia, and bloody sputum production were significantly higher in the H7N9 group than in the H1N1 group (P < .05). The H7N9 group had a longer duration of viral shedding from the onset of illness (P < .05) and from the initiation of antiviral therapy (P < .05) to a negative viral test result than the H1N1 group. Patients with H7N9 had higher rates of invasive mechanical ventilation; serious complications, including alimentary tract hemorrhage, pneumothorax or septum emphysema, hospital-acquired pneumonia (HAP) and multiple organ dysfunction syndrome (MODS); and hospital mortality (P < .05). At the 6th month of follow-up, the rates of bronchiectasia, reticular opacities, fibrous stripes, and patchy opacities on chest computed tomography (CT) were significantly higher in the H7N9 group than in the H1N1 group (P < .05). Based on multiple logistic regression analysis, H7N9 influenza viral infection was associated with a higher risk of the presence of severe ARDS than H1N1 influenza viral infection (odds ratio 8.29, 95% confidence interval [CI] 1.53-44.94; P < .05).Compared to patients with H1N1, patients with H7N9 complicated by ARDS had much more severe disease. During long-term follow-up, more changes in pulmonary fibrosis were observed in patients with H7N9 than in patients with H1N1 during the convalescent stage.
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Adult Influenza A (H1N1) Related Encephalitis: A Case Report.
Midha, Devinder; Kumar, Arun; Vasudev, Pratibha; Iqbal, Zafar Ahmad; Mandal, Amit Kumar
2018-05-01
The year 2009-2010 saw H1N1 influenza outbreaks occurring in almost all countries of the world, causing the WHO to declare it a pandemic of an alert level of 6. In India, H1N1 influenza outbreaks were again reported in late 2014 and early 2015. Since then, sporadic cases of H1N1 influenza have been reported. H1N1 influenza usually presents itself with respiratory tract symptoms. In a minority of patients, abdominal symptoms may occur as well. Acute influenza-associated encephalopathy/encephalitis mostly occurs in the pediatric population, whereas in adults, it is a rare complication. The incidence of neurological complications appears to have increased after the 2009 H1N1 influenza A virus pandemic. We would like to draw attention to an adult patient case who initially presented with respiratory symptoms but then deteriorated and developed encephalitis, which is rarely reported. As per literature reviewed by Victoria Bangualid and Judith Berger on PubMed, only 21 cases of neurological complications were found in adult influenza A patients, out of whom 8 had encephalopathy.
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Al Faress, Shaker; Cartet, Gaëlle; Ferraris, Olivier; Norder, Helene; Valette, Martine; Lina, Bruno
2005-07-01
Influenza A viruses are divided into subtypes based on their hemagglutinin (H1 to H15) and neuraminidase (N1 to N9) glycoproteins. Of these, three A subtypes H1N1, H3N2 and H1N2 circulate in the human population. Influenza A viruses display a high antigenic variability called "antigenic drift" which allows the virus to escape antibody neutralization. Evaluate the mutations apparition that might predict a divergent antigenic evolution of hemagglutinin in influenza A H1N1 and A H1N2 viruses. During the three winters of 2001-2002 to 2003-2004, 58 A H1N1 and 23 A H1N2 subtypes have been isolated from patients with influenza-like illness in the south of France. The HA1 region was analyzed by RT-PCR and subsequently sequenced to compare the HA1 genetic evolution of influenza A H1N1 and A H1N2 subtypes. Our results showed that 28 amino acid substitutions have accumulated in the HA1 region since the circulation of A/New Caledonia/20/99-like viruses in France. Of these, fifteen were located in four antigenic sites (B, C, D and E). Six of them were observed only in the A H1N2 isolates, six only in the A H1N1 isolates and three in both subtypes. Furthermore, nine of twenty two A H1N2 isolates from the winter of 2002-2003 shared a T90A amino acid change which has not been observed in any A H1N1 isolate; resulting in the introduction of a new glycosylation site close to the antigenic site E. This might mask some antigenic E determinants and therefore, modify the A H1N2 antigenicity. The divergent genetic evolution of hemagglutinin may ultimately lead to a significant different antigenicity between A H1N1 and A H1N2 subtypes that would require the introduction of a new subtype in the vaccine batches.
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2013-01-01
Background Influenza virus undergoes constant antigenic evolution, and therefore influenza vaccines must be reformulated each year. Time is necessary to produce a vaccine that is antigenically matched to a pandemic strain. A goal of many research works is to produce universal vaccines that can induce protective immunity to influenza A viruses of various subtypes. Despite intensive studies, the precise mechanisms of heterosubtypic immunity (HSI) remain ambiguous. Method In this study, mice were vaccinated with recombinant virus vaccine (rL H5), in which the hemagglutinin (HA) gene of influenza A/H5N1 virus was inserted into the LaSota Newcastle disease virus (NDV) vaccine strain. Following a challenge with influenza A/H1N1 virus, survival rates and lung index of mice were observed. The antibodies to influenza virus were detected using hemagglutination inhibition (HI). The lung viral loads, lung cytokine levels and the percentages of both IFN-γ+CD4+ and IFN-γ+CD8+ T cells in spleen were detected using real-time RT-PCR, ELISA and flow cytometry respectively. Results In comparison with the group of mice given phosphate-buffered saline (PBS), the mice vaccinated with rL H5 showed reductions in lung index and viral replication in the lungs after a challenge with influenza A/H1N1 virus. The antibody titer in group 3 (H1N1-H1N1) was significantly higher than that in other groups which only low levels of antibody were detected. IFN-γ levels increased in both group 1 (rL H5-H1N1) and group 2 (rL H5 + IL-2-H1N1). And the IFN-γ level of group 2 was significantly higher than that of group 1. The percentages of both IFN-γ+CD4+ and IFN-γ+CD8+ T cells in group 1 (rL H5-H1N1) and group 2 (rL H5 + IL-2-H1N1) increased significantly, as measured by flow cytometry. Conclusion After the mice were vaccinated with rL H5, cross-protective immune response was induced, which was against heterosubtypic influenza A/H1N1 virus. To some extent, cross-protective immune response can
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Practical Methylation Procedure for (1H)-1,2,4-Triazole (Postprint)
2007-09-01
Francis Group, LLC. 14. ABSTRACT Conversion of (1H)-1,2,4-triazole to its sodium salt with methanolic sodium methoxide is followed by reaction ...From - To) 04-06-2007 Journal Article 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Practical Methylation Procedure for (1H)-1,2,4-Triazole (Postprint...continuous extraction (chloroform/water) with a final short-path distillation under a controlled vacuum to obtain spectroscopically pure 1- methyl -1,2,4
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26 CFR 1.430(h)(3)-1 - Mortality tables used to determine present value.
Code of Federal Regulations, 2010 CFR
2010-04-01
.... 1.430(h)(3)-1 Section 1.430(h)(3)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Certain Stock Options § 1.430(h)(3)-1 Mortality... forth in this section pursuant to section 430(h)(3)(A). In lieu of using the mortality tables provided...
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Clinical course of asthma patients with H1N1 influenza infection and oseltamivir.
Kim, Min-Hye; Song, Woo-Jung; Yang, Min-Suk; Lee, So-Hee; Kwon, Jae-Woo; Kim, Sae-Hoon; Kang, Hye-Ryun; Park, Heung-Woo; Cho, Young-Joo; Cho, Sang-Heon; Min, Kyung-Up; Kim, You-Young; Chang, Yoon-Seok
2018-02-01
H1N1 influenza virus prevailed throughout the world in 2009. However, there are few reports on the clinical features of H1N1 influenza infection in adult asthma patients. We evaluated the clinical features in asthma patients with H1N1 influenza infection who took oseltamivir and compared them to those with other upper respiratory infections. We reviewed asthma patients over 15 years of age who had visited Seoul National University Hospital and Seoul National University Bundang Hospital for suspected H1N1 influenza infection from August 2009 to March 2010. Various clinical features such as hospital admission days, respiratory symptoms, basal lung function, and past history was compared between H1N1 influenza PCR positive and negative groups. A total of 111 asthmatics were enrolled. All patients took oseltamivir. H1N1 RT-PCR was positive in 62 patients (55.9%), negative in 49 patients (44.1%). Wheezing developed more frequently in the H1N1 positive group. (43.5 vs. 16.7%, P=0.044). The rate of acute asthma exacerbations and pneumonia development were higher in the H1N1 positive group (59.7 vs. 51%, P=0.015, 25.0% vs. 0%, P<0.001). The rates for emergency room visit, hospital admissions, intensive care unit admissions, hospital days were not different between the groups. Underlying medical conditions were accompanied more frequently in the H1N1 negative patients (21.6% vs. 30.6%, P=0.002), especially cardiac disease (7.2% vs. 15.3%, P=0.011). H1N1 influenza infection may affect the clinical course of asthma combined with more severe manifestations; however, Oseltamivir could have affected the clinical course of H1N1 infected patients and made it milder than expected.
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Influenza Virus Vaccines: Lessons from the 2009 H1N1 pandemic
Broadbent, Andrew J.; Subbarao, Kanta
2011-01-01
Reflecting on the 2009 H1N1 pandemic, we summarize lessons regarding influenza vaccines that can be applied in the future. The two major challenges to vaccination during the 2009 H1N1 pandemic were timing and availability of vaccine. Vaccines were, however, well-tolerated and immunogenic, with inactivated vaccines containing 15μg of HA generally inducing antibody titers ≥1:40 in adults within 2 weeks of the administration of a single dose. Moreover, the use of oil-in-water adjuvants in Europe permitted dose- reduction, with vaccines containing as little as 3.75 or 7.5μg HA being immunogenic. Case-control studies demonstrated that monovalent 2009 H1N1 vaccines were effective in preventing infection with the 2009 H1N1 virus, but preliminary data suggests that it is important for individuals to be re-immunized annually. PMID:22125588
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Antigenic Patterns and Evolution of the Human Influenza A (H1N1) Virus
Liu, Mi; Zhao, Xiang; Hua, Sha; Du, Xiangjun; Peng, Yousong; Li, Xiyan; Lan, Yu; Wang, Dayan; Wu, Aiping; Shu, Yuelong; Jiang, Taijiao
2015-01-01
The influenza A (H1N1) virus causes seasonal epidemics that result in severe illnesses and deaths almost every year. A deep understanding of the antigenic patterns and evolution of human influenza A (H1N1) virus is extremely important for its effective surveillance and prevention. Through development of antigenicity inference method for human influenza A (H1N1), named PREDAC-H1, we systematically mapped the antigenic patterns and evolution of the human influenza A (H1N1) virus. Eight dominant antigenic clusters have been inferred for seasonal H1N1 viruses since 1977, which demonstrated sequential replacements over time with a similar pattern in Asia, Europe and North America. Among them, six clusters emerged first in Asia. As for China, three of the eight antigenic clusters were detected in South China earlier than in North China, indicating the leading role of South China in H1N1 transmission. The comprehensive view of the antigenic evolution of human influenza A (H1N1) virus can help formulate better strategy for its prevention and control. PMID:26412348
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Carter, Donald M; Darby, Christopher A; Johnson, Scott K; Carlock, Michael A; Kirchenbaum, Greg A; Allen, James D; Vogel, Thorsten U; Delagrave, Simon; DiNapoli, Joshua; Kleanthous, Harold; Ross, Ted M
2017-12-15
Most preclinical animal studies test influenza vaccines in immunologically naive animal models, even though the results of vaccination may not accurately reflect the effectiveness of vaccine candidates in humans that have preexisting immunity to influenza. In this study, novel, broadly reactive influenza vaccine candidates were assessed in preimmune ferrets. These animals were infected with different H1N1 isolates before being vaccinated or infected with another influenza virus. Previously, our group has described the design and characterization of computationally optimized broadly reactive hemagglutinin (HA) antigens (COBRA) for H1N1 isolates. Vaccinating ferrets with virus-like particle (VLP) vaccines expressing COBRA HA proteins elicited antibodies with hemagglutination inhibition (HAI) activity against more H1N1 viruses in the panel than VLP vaccines expressing wild-type HA proteins. Specifically, ferrets infected with the 1986 virus and vaccinated with a single dose of the COBRA HA VLP vaccines elicited antibodies with HAI activity against 11 to 14 of the 15 H1N1 viruses isolated between 1934 and 2013. A subset of ferrets was infected with influenza viruses expressing the COBRA HA antigens. These COBRA preimmune ferrets had superior breadth of HAI activity after vaccination with COBRA HA VLP vaccines than COBRA preimmune ferrets vaccinated with VLP vaccines expressing wild-type HA proteins. Overall, priming naive ferrets with COBRA HA based viruses or using COBRA HA based vaccines to boost preexisting antibodies induced by wild-type H1N1 viruses, COBRA HA antigens elicited sera with the broadest HAI reactivity against multiple antigenic H1N1 viral variants. This is the first report demonstrating the effectiveness of a broadly reactive or universal influenza vaccine in a preimmune ferret model. IMPORTANCE Currently, many groups are testing influenza vaccine candidates to meet the challenge of developing a vaccine that elicits broadly reactive and long
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Carter, Donald M.; Darby, Christopher A.; Johnson, Scott K.; Carlock, Michael A.; Kirchenbaum, Greg A.; Allen, James D.; Vogel, Thorsten U.; Delagrave, Simon; DiNapoli, Joshua; Kleanthous, Harold
2017-01-01
ABSTRACT Most preclinical animal studies test influenza vaccines in immunologically naive animal models, even though the results of vaccination may not accurately reflect the effectiveness of vaccine candidates in humans that have preexisting immunity to influenza. In this study, novel, broadly reactive influenza vaccine candidates were assessed in preimmune ferrets. These animals were infected with different H1N1 isolates before being vaccinated or infected with another influenza virus. Previously, our group has described the design and characterization of computationally optimized broadly reactive hemagglutinin (HA) antigens (COBRA) for H1N1 isolates. Vaccinating ferrets with virus-like particle (VLP) vaccines expressing COBRA HA proteins elicited antibodies with hemagglutination inhibition (HAI) activity against more H1N1 viruses in the panel than VLP vaccines expressing wild-type HA proteins. Specifically, ferrets infected with the 1986 virus and vaccinated with a single dose of the COBRA HA VLP vaccines elicited antibodies with HAI activity against 11 to 14 of the 15 H1N1 viruses isolated between 1934 and 2013. A subset of ferrets was infected with influenza viruses expressing the COBRA HA antigens. These COBRA preimmune ferrets had superior breadth of HAI activity after vaccination with COBRA HA VLP vaccines than COBRA preimmune ferrets vaccinated with VLP vaccines expressing wild-type HA proteins. Overall, priming naive ferrets with COBRA HA based viruses or using COBRA HA based vaccines to boost preexisting antibodies induced by wild-type H1N1 viruses, COBRA HA antigens elicited sera with the broadest HAI reactivity against multiple antigenic H1N1 viral variants. This is the first report demonstrating the effectiveness of a broadly reactive or universal influenza vaccine in a preimmune ferret model. IMPORTANCE Currently, many groups are testing influenza vaccine candidates to meet the challenge of developing a vaccine that elicits broadly reactive and long
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Structural insights into the histone H1-nucleosome complex
Zhou, Bing-Rui; Feng, Hanqiao; Kato, Hidenori; Dai, Liang; Yang, Yuedong; Zhou, Yaoqi; Bai, Yawen
2013-01-01
Linker H1 histones facilitate formation of higher-order chromatin structures and play important roles in various cell functions. Despite several decades of effort, the structural basis of how H1 interacts with the nucleosome remains elusive. Here, we investigated Drosophila H1 in complex with the nucleosome, using solution nuclear magnetic resonance spectroscopy and other biophysical methods. We found that the globular domain of H1 bridges the nucleosome core and one 10-base pair linker DNA asymmetrically, with its α3 helix facing the nucleosomal DNA near the dyad axis. Two short regions in the C-terminal tail of H1 and the C-terminal tail of one of the two H2A histones are also involved in the formation of the H1–nucleosome complex. Our results lead to a residue-specific structural model for the globular domain of the Drosophila H1 in complex with the nucleosome, which is different from all previous experiment-based models and has implications for chromatin dynamics in vivo. PMID:24218562
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Jones, Frank R.; Gabitzsch, Elizabeth S.; Xu, Younong; Balint, Joseph P.; Borisevich, Viktoriya; Smith, Jennifer; Smith, Jeanon; Peng, Bi-Hung; Walker, Aida; Salazar, Magda; Paessler, Slobodan
2013-01-01
Vaccines against emerging pathogens such as the 2009 H1N1 pandemic virus can benefit from current technologies such as rapid genomic sequencing to construct the most biologically relevant vaccine. A novel platform (Ad5 [E1-, E2b-]) has been utilized to induce immune responses to various antigenic targets. We employed this vector platform to express hemagglutinin (HA) and neuraminidase (NA) genes from 2009 H1N1 pandemic viruses. Inserts were consensuses sequences designed from viral isolate sequences and the vaccine was rapidly constructed and produced. Vaccination induced H1N1 immune responses in mice, which afforded protection from lethal virus challenge. In ferrets, vaccination protected from disease development and significantly reduced viral titers in nasal washes. H1N1 cell mediated immunity as well as antibody induction correlated with the prevention of disease symptoms and reduction of virus replication. The Ad5 [E1-, E2b-] should be evaluated for the rapid development of effective vaccines against infectious diseases. PMID:21821082
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Xia, Guoyao; Benmohamed, Radhia; Morimoto, Richard I; Kirsch, Donald R; Silverman, Richard B
2014-11-01
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons, leading to muscle weakness, paralysis, and death, most often from respiratory failure. Over 200 pyrimidine-2,4,6-trione (PYT) small molecules, which prevent aggregation and reduce the associated toxicity of mutant superoxide dismutase 1 (SOD1) found in patients with familial ALS, have been synthesized and tested. One of the compounds (1,3-bis(2-phenylethyl)pyrimidine-2,4,6(1H,3H,5H)-trione, (1) was previously found to have an excellent combination of potency efficacy, and some desirable pharmacokinetic properties. To improve the solubility and metabolic stability properties of this compound, deuterium and fluorine were introduced into 1. New analogs with better solubility, plasma stability, and human microsome stability were identified. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Contextual view showing H1 on left and H270 in background; ...
Contextual view showing H1 on left and H270 in background; camera facing north. - Mare Island Naval Shipyard, Hospital Headquarters, Johnson Lane, west side at intersection of Johnson Lane & Cossey Street, Vallejo, Solano County, CA
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1-(2-Cyanoethyl)-2-(2-pyridyl)-1H,3H-benzimidazol-3-ium perchlorate
Li, Yan; Tang, Xiaoliang; Chen, Jiayu; Wu, Daxiang; Liu, Weisheng
2010-01-01
The title compound, C15H13N4 +·ClO4 −, comprises a nonplanar 1-(2-cyanoethyl)-2-(2-pyridyl)-1H,3H-benzimidazol-3-ium cation [dihedral angle between the imidazole and pyridine rings = 22.5 (8)°] and a perchlorate anion. The cation is formed by protonation of the N atom of the benzimidazole ring. A charged N—H⋯O hydrogen bond connects the anion and cation, and intermolecular C—H⋯O and C—H⋯N interactions contribute to the crystal packing. PMID:21579831
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Eshuis, Nan; Aspers, Ruud L E G; van Weerdenburg, Bram J A; Feiters, Martin C; Rutjes, Floris P J T; Wijmenga, Sybren S; Tessari, Marco
2016-04-01
SABRE (Signal Amplification By Reversible Exchange) nuclear spin hyperpolarization method can provide strongly enhanced NMR signals as a result of the reversible association of small molecules with para-hydrogen (p-H2) at an iridium metal complex. The conversion of p-H2 singlet order to enhanced substrate proton magnetization within such complex is driven by the scalar coupling interactions between the p-H2 derived hydrides and substrate nuclear spins. In the present study these long-range homonuclear couplings are experimentally determined for several SABRE substrates using an NMR pulse sequence for coherent hyperpolarization transfer at high magnetic field. Pyridine and pyrazine derivatives appear to have a similar ∼1.2 Hz (4)J coupling to p-H2 derived hydrides for their ortho protons, and a much lower (5)J coupling for their meta protons. Interestingly, the (4)J hydride-substrate coupling for five-membered N-heterocyclic substrates is well below 1 Hz. Copyright © 2016 Elsevier Inc. All rights reserved.
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NASA Astrophysics Data System (ADS)
Eshuis, Nan; Aspers, Ruud L. E. G.; van Weerdenburg, Bram J. A.; Feiters, Martin C.; Rutjes, Floris P. J. T.; Wijmenga, Sybren S.; Tessari, Marco
2016-04-01
SABRE (Signal Amplification By Reversible Exchange) nuclear spin hyperpolarization method can provide strongly enhanced NMR signals as a result of the reversible association of small molecules with para-hydrogen (p-H2) at an iridium metal complex. The conversion of p-H2 singlet order to enhanced substrate proton magnetization within such complex is driven by the scalar coupling interactions between the p-H2 derived hydrides and substrate nuclear spins. In the present study these long-range homonuclear couplings are experimentally determined for several SABRE substrates using an NMR pulse sequence for coherent hyperpolarization transfer at high magnetic field. Pyridine and pyrazine derivatives appear to have a similar ∼1.2 Hz 4J coupling to p-H2 derived hydrides for their ortho protons, and a much lower 5J coupling for their meta protons. Interestingly, the 4J hydride-substrate coupling for five-membered N-heterocyclic substrates is well below 1 Hz.
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Harris, J R; Scheffler, D; Gebauer, W; Lehnert, R; Markl, J
2000-12-01
The multimeric/higher oligomeric states of the two isoforms of Haliotis tuberculata hemocyanin (HtH1 and HtH2) have been assessed by transmission electron microscopy (TEM) of negatively stained specimens, for comparison with previously published structural data from keyhole limpet hemocyanin (KLH1 and KLH2) [see Harris, J.R., Gebauer, W., Guderian, F.U., Markl, J., 1997a. Keyhole limpet hemocyanin (KLH), I: Reassociation from Immucothel followed by separation of KLH1 and KLH2. Micron, 28, 31-41; Harris, J.R., Gebauer, W., Söhngen, S.M., Nermut, M.V., Markl, J., 1997b. Keyhole limpet hemocyanin (KLH). II: Characteristic reassociation properties of purified KLH1 and KLH2. Micron, 28, 43-56; Harris, J.R., Gebauer, W., Adrian, M., Markl, J., 1998. Keyhole limpet hemocyanin (KLH): Slow in vitro reassociation of KLH1 and KLH2 from Immucothel. Micron, 29, 329-339]. In purified samples of both HtH isoforms, the hollow cylindrical ca 8MDa didecamer predominates together with a small number of decamers, but tri- and longer multidecamers are detectable only in the HtH2. The stability of the two HtH isoforms under varying ionic conditions have been monitored, thereby enabling conditions for the production of stable decamers to be established. The ability of these decamers to reform multimers in the presence of 10 and 100mM concentrations of calcium and magnesium ions in Tris-HCl buffer (pH 7.4), and also of individual HtH1 and HtH2 subunits (produced by pH 9.6 dissociation in glycine-NaOH buffer), to reassociate in the presence of calcium and magnesium ions, has been assessed. For the HtH1 decamers, the predominant multimeric product is the didecamer at 10 and 100mM calcium and magnesium concentrations, whereas for the HtH2 decamers, large numbers of multidecamers are produced, with the reaction proceeding more completely at the higher calcium and magnesium concentration. With the HtH1 subunit, reassociation in the presence of 10 and 100mM calcium and magnesium ions yielded
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Walker, Lawrence R.; Hoyt, David W.; Walker, S. Michael
We present a novel approach to improve accuracy of metabolite identification by combining direct infusion ESI MS1 with 1D 1H NMR spectroscopy. The new approach first applies standard 1D 1H NMR metabolite identification protocol by matching the chemical shift, J-coupling and intensity information of experimental NMR signals against the NMR signals of standard metabolites in metabolomics library. This generates a list of candidate metabolites. The list contains false positive and ambiguous identifications. Next, we constrained the list with the chemical formulas derived from high-resolution direct infusion ESI MS1 spectrum of the same sample. Detection of the signals of a metabolitemore » both in NMR and MS significantly improves the confidence of identification and eliminates false positive identification. 1D 1H NMR and direct infusion ESI MS1 spectra of a sample can be acquired in parallel in several minutes. This is highly beneficial for rapid and accurate screening of hundreds of samples in high-throughput metabolomics studies. In order to make this approach practical, we developed a software tool, which is integrated to Chenomx NMR Suite. The approach is demonstrated on a model mixture, tomato and Arabidopsis thaliana metabolite extracts, and human urine.« less
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Florin-Dan, Popescu
2008-01-01
Driving performances depend on cognitive, psychomotor and perception functions. The CNS adverse effects of some H1 antihistamines can alter the patient ability to drive. Data from studies using standardized objective cognitive and psychomotor tests (Choice Reaction Time, Critical Flicker Fusion, Digital Symbol Substitution Test), functional brain imaging (Positron Emission Tomography, functional Magnetic Resonance Imaging), neurophysiological studies (Multiple Sleep Latency Test, auditory and visual evoked potentials), experimental simulated driving (driving simulators) and real driving studies (the Highway Driving Test, with the evaluation of the Standard Deviation Lateral Position, and the Car Following Test, with the measurement of the Brake Reaction Time) must be discussed in order to classify a H1 antihistamine as a true non-sedating one. PMID:20108503
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Thromboembolic events in patients with severe pandemic influenza A/H1N1.
Avnon, Lone Sølling; Munteanu, Daniela; Smoliakov, Alexander; Jotkowitz, Alan; Barski, Leonid
2015-10-01
The 2009 pandemic influenza A/H1N1 developed as a novel swine influenza which caused more diseases among younger age groups than in the elderly. Severe hypoxemic respiratory failure from A/H1N1 pneumonia resulted in an increased need for ICU beds. Several risk groups were identified that were at a higher risk for adverse outcomes. Pregnant women were a particularly vulnerable group of patients The CDC reported on the first ten patients with severe illness and acute hypoxemic respiratory failure associated with A/H1N1 infection, none of whom were pregnant, but they noticed that half of the patients had a pulmonary embolism. During a four-month period from September to December 2009, 252 patients were admitted to our hospital with confirmed pandemic influenza H1N1 by real-time reverse transcriptase-polymerase chain reaction test (rRT-PCR). We cared for twenty patients (7.9%) admitted to MICU with severe A/H1N1. Results on Thrombotic events were identified in five (25%) of our critically ill patients. We recommend that patients with severe influenza A/H1N1 pneumonitis and respiratory failure be administered DVT prophylaxis in particular if there are additional risk factors for TVE. Further prospective studies on the relationship of influenza A/H1N1 and VTE are needed. Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
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Contextualizing ethics: ventilators, H1N1 and marginalized populations.
Silva, Diego S; Nie, Jason X; Rossiter, Kate; Sahni, Sachin; Upshur, Ross E G
2010-01-01
If the H1N1 pandemic worsens, there may not be enough ventilated beds to care for all persons with respiratory failure. To date, researchers who explicitly discuss the ethics of intensive care unit admission and the allocation of ventilators during an influenza pandemic have based criteria predominantly on the principles of utility and efficiency, that is, promoting actions that maximize the greatest good for the greatest number of people. However, haphazardly applying utility and efficiency potentially disadvantages marginalized populations who might be at increased risk of severe reactions to H1N1. In Canada, Aboriginals represent 3% of Canadians, yet 11% of H1N1 cases requiring hospitalization involve Aboriginal persons. Aboriginal persons suffer from high rates of obesity due to socio-economic inequalities. Obesity is also a risk factor for severe H1N1 reactions. Yet, since obesity is found to increase the duration of stay in ventilated beds and a long stay is not considered an optimal use of ventilators, applying the principles of utility and efficiency may magnify existing social inequalities. Although promoting utility and efficiency is important, other ethical principles, such as equity and need, require thoughtful consideration and implementation. Furthermore, since public resources are being used to address a public health hazard, the viewpoints of the public, and specifically stakeholders who will be disproportionately affected, should inform decision-makers. Finally, giving attention to the needs and rights of marginalized populations means that ventilators should not be allocated based on criteria that exacerbate the social injustices faced by these groups of people.
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Germline-specific H1 variants: the "sexy" linker histones.
Pérez-Montero, Salvador; Carbonell, Albert; Azorín, Fernando
2016-03-01
The eukaryotic genome is packed into chromatin, a nucleoprotein complex mainly formed by the interaction of DNA with the abundant basic histone proteins. The fundamental structural and functional subunit of chromatin is the nucleosome core particle, which is composed by 146 bp of DNA wrapped around an octameric protein complex formed by two copies of each core histone H2A, H2B, H3, and H4. In addition, although not an intrinsic component of the nucleosome core particle, linker histone H1 directly interacts with it in a monomeric form. Histone H1 binds nucleosomes near the exit/entry sites of linker DNA, determines nucleosome repeat length and stabilizes higher-order organization of nucleosomes into the ∼30 nm chromatin fiber. In comparison to core histones, histone H1 is less well conserved through evolution. Furthermore, histone H1 composition in metazoans is generally complex with most species containing multiple variants that play redundant as well as specific functions. In this regard, a characteristic feature is the presence of specific H1 variants that replace somatic H1s in the germline and during early embryogenesis. In this review, we summarize our current knowledge about their structural and functional properties.
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Qiao, Chuanling; Liu, Liping; Yang, Huanliang; Chen, Yan; Xu, Huiyang; Chen, Hualan
2014-12-01
The pandemic A/H1N1 influenza viruses emerged in both Mexico and the United States in March 2009, and were transmitted efficiently in the human population. Transmissions of the pandemic 2009/H1N1 virus from humans to poultry and other species of mammals were reported from several continents during the course of the 2009 H1N1 pandemic. Reassortant H1N1, H1N2, and H3N2 viruses containing genes of the pandemic 2009/H1N1 viruses appeared in pigs in some countries. In winter of 2012, a total of 2600 nasal swabs were collected from healthy pigs in slaughterhouses located throughout 10 provinces in China. The isolated viruses were subjected to genetic and antigenic analysis. Two novel triple-reassortant H1N2 influenza viruses were isolated from swine in China in 2012, with the HA gene derived from Eurasian avian-like swine H1N1, the NA gene from North American swine H1N2, and the six internal genes from the pandemic 2009/H1N1 viruses. The two viruses had similar antigenic features and some significant changes in antigenic characteristics emerged when compared to the previously identified isolates. We inferred that the novel reassortant viruses in China may have arisen from the accumulation of the three types of influenza viruses, which further indicates that swine herds serve as "mixing vessels" for influenza viruses. Influenza virus reassortment is an ongoing process, and our findings highlight the urgent need for continued influenza surveillance among swine herds. Copyright © 2014 Elsevier B.V. All rights reserved.
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Yang, Chung-Ling; Lin, Cheng-Hung; Luo, Wen-I; Lee, Tsu-Lin; Ramu, Ravirala; Ng, Kok Yaoh; Tsai, Yi-Fang; Wei, Guor-Tzo; Yu, Steve S-F
2017-02-21
Engineered bacterial cytochrome P450s are noted for their ability in the oxidation of inert small alkanes. Cytochrome P450 BM3 L188P A328F (BM3 PF) and A74E L188P A328F (BM3 EPF) variants are able to efficiently oxidize n-butane to 2-butanol. Esterification of the 2-butanol derived from this reaction mediated by the aforementioned two mutants gives diastereomeric excesses (de) of -56±1 and -52±1 %, respectively, with the preference for the oxidation occurring at the C-H S bond. When tailored (2R,3R)- and (2S,3S)-[2- 2 H 1 ,3- 2 H 1 ]butane probes are employed as substrates for both variants, the obtained de values from (2R,3R)-[2- 2 H 1 ,3- 2 H 1 ]butane are -93 and -92 % for BM3 PF and EPF, respectively; whereas the obtained de values from (2S,3S)-[2- 2 H 1 ,3- 2 H 1 ]butane are 52 and 56 % in the BM3 PF and EPF systems, respectively. The kinetic isotope effects (KIEs) for the oxidation of (2R,3R)-[2- 2 H 1 ,3- 2 H 1 ]butane are 7.3 and 7.8 in BM3 PF and EPF, respectively; whereas KIEs for (2S,3S)-[2- 2 H 1 ,3- 2 H 1 ]butanes are 18 and 25 in BM3 PF and EPF, respectively. The discrepancy in KIEs obtained from the two substrates supports the two-state reactivity (TSR) that is proposed for alkane oxidation in cytochrome P450 systems. Moreover, for the first time, experimental evidence for tunneling in the oxidation mediated by P450 is given through the oxidation of the C-H R bond in (2S,3S)-[2- 2 H 1 ,3- 2 H 1 ]butane. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
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A monoclonal antibody-based ELISA for differential diagnosis of 2009 pandemic H1N1
USDA-ARS?s Scientific Manuscript database
The swine-origin 2009 pandemic H1N1 virus (pdmH1N1) is genetically related to North American swine H1 influenza viruses and unrelated to human seasonal H1 viruses. Currently, specific diagnosis of pdmH1N1 relies on RT-PCR. In order to develop an assay that does not rely in amplification of the viral...
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IL-1β and IL-6 Upregulation in Children with H1N1 Influenza Virus Infection
Chiaretti, Antonio; Pulitanò, Silvia; Barone, Giovanni; Ferrara, Pietro; Capozzi, Domenico; Riccardi, Riccardo
2013-01-01
The role of cytokines in relation to clinical manifestations, disease severity, and outcome of children with H1N1 virus infection remains thus far unclear. The aim of this study was to evaluate interleukin IL-1β and IL-6 plasma expressions and their association with clinical findings, disease severity, and outcome of children with H1N1 infection. We prospectively evaluated 15 children with H1N1 virus infection and 15 controls with lower respiratory tract infections (LRTI). Interleukin plasma levels were measured using immunoenzymatic assays. Significantly higher levels of IL-1β and IL-6 were detected in all patients with H1N1 virus infection compared to controls. It is noteworthy to mention that in H1N1 patients with more severe clinical manifestations of disease IL-1β and IL-6 expressions were significantly upregulated compared to H1N1 patients with mild clinical manifestations. In particular, IL-6 was significantly correlated with specific clinical findings, such as severity of respiratory compromise and fever. No correlation was found between interleukin expression and final outcome. In conclusion, H1N1 virus infection induces an early and significant upregulation of both interleukins IL1β and IL-6 plasma expressions. The upregulation of these cytokines is likely to play a proinflammatory role in H1N1 virus infection and may contribute to airway inflammation and bronchial hyperreactivity in these patients. PMID:23737648
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Gagnon, Alain; Acosta, Enrique; Hallman, Stacey; Bourbeau, Robert; Dillon, Lisa Y; Ouellette, Nadine; Earn, David J D; Herring, D Ann; Inwood, Kris; Madrenas, Joaquin; Miller, Matthew S
2018-01-16
Recent outbreaks of H5, H7, and H9 influenza A viruses in humans have served as a vivid reminder of the potentially devastating effects that a novel pandemic could exert on the modern world. Those who have survived infections with influenza viruses in the past have been protected from subsequent antigenically similar pandemics through adaptive immunity. For example, during the 2009 H1N1 "swine flu" pandemic, those exposed to H1N1 viruses that circulated between 1918 and the 1940s were at a decreased risk for mortality as a result of their previous immunity. It is also generally thought that past exposures to antigenically dissimilar strains of influenza virus may also be beneficial due to cross-reactive cellular immunity. However, cohorts born during prior heterosubtypic pandemics have previously experienced elevated risk of death relative to surrounding cohorts of the same population. Indeed, individuals born during the 1890 H3Nx pandemic experienced the highest levels of excess mortality during the 1918 "Spanish flu." Applying Serfling models to monthly mortality and influenza circulation data between October 1997 and July 2014 in the United States and Mexico, we show corresponding peaks in excess mortality during the 2009 H1N1 "swine flu" pandemic and during the resurgent 2013-2014 H1N1 outbreak for those born at the time of the 1957 H2N2 "Asian flu" pandemic. We suggest that the phenomenon observed in 1918 is not unique and points to exposure to pandemic influenza early in life as a risk factor for mortality during subsequent heterosubtypic pandemics. IMPORTANCE The relatively low mortality experienced by older individuals during the 2009 H1N1 influenza virus pandemic has been well documented. However, reported situations in which previous influenza virus exposures have enhanced susceptibility are rare and poorly understood. One such instance occurred in 1918-when those born during the heterosubtypic 1890 H3Nx influenza virus pandemic experienced the highest
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Hurt, A. C.; Hardie, K.; Wilson, N. J.; Deng, Y. M.; Osbourn, M.; Leang, S. K.; Lee, R. T. C.; Iannello, P.; Gehrig, N.; Shaw, R.; Wark, P.; Caldwell, N.; Givney, R. C.; Xue, L.; Maurer-Stroh, S.; Dwyer, D. E.; Wang, B.; Smith, D. W.; Levy, A.; Booy, R.; Dixit, R.; Merritt, T.; Kelso, A.; Dalton, C.; Durrheim, D.; Barr, I. G.
2012-01-01
Background. Oseltamivir resistance in A(H1N1)pdm09 influenza is rare, particularly in untreated community cases. Sustained community transmission has not previously been reported. Methods. Influenza specimens from the Asia–Pacific region were collected through sentinel surveillance, hospital, and general practitioner networks. Clinical and epidemiological information was collected on patients infected with oseltamivir-resistant viruses. Results. Twenty-nine (15%) of 191 A(H1N1)pdm09 viruses collected between May and September 2011 from Hunter New England (HNE), Australia, contained the H275Y neuraminidase substitution responsible for oseltamivir resistance. Only 1 patient had received oseltamivir before specimen collection. The resistant strains were genetically very closely related, suggesting the spread of a single variant. Ninety percent of cases lived within 50 kilometers. Three genetically similar oseltamivir-resistant variants were detected outside of HNE, including 1 strain from Perth, approximately 4000 kilometers away. Computational analysis predicted that neuraminidase substitutions V241I, N369K, and N386S in these viruses may offset the destabilizing effect of the H275Y substitution. Conclusions This cluster represents the first widespread community transmission of H275Y oseltamivir-resistant A(H1N1)pdm09 influenza. These cases and data on potential permissive mutations suggest that currently circulating A(H1N1)pdm09 viruses retain viral fitness in the presence of the H275Y mutation and that widespread emergence of oseltamivir-resistant strains may now be more likely. PMID:22561367
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The Continuing Evolution of H5N1 and H9N2 Influenza Viruses in Bangladesh
Marinova-Petkova, Atanaska; Shanmuganatham, Karthik; Feeroz, Mohammed M.; Jones-Engel, Lisa; Hassan, M. Kamrul; Akhtar, Sharmin; Turner, Jasmine; Walker, David; Seiler, Patrick; Franks, John; McKenzie, Pamela; Krauss, Scott; Webby, Richard J.; Webster, Robert G.
2017-01-01
Summary In 2011, avian influenza surveillance at the Bangladesh live bird markets (LBMs) showed complete replacement of the highly pathogenic avian influenza (HPAI) H5N1 virus of clade 2.2.2 (Qinghai-like H5N1 lineage) by the HPAI H5N1 clade 2.3.2.1. This clade, which continues to circulate in Bangladesh and neighboring countries, is an intra- and inter-clade reassortant; its HA, PB1, PA and NS genes come from subclade 2.3.2.1a; PB2 from subclade 2.3.2.1c; and NA, NP, and M from clade 2.3.4.2. The H9N2 influenza viruses co-circulating in the Bangladesh LBMs are also reassortants, possessing five genes (NS, M, NP, PA, and PB1) from a HPAI H7N3 virus previously isolated in Pakistan. Despite frequent co-infection of chickens and ducks, reassortment between these H5N1 and H9N2 viruses has been rare. However, all such reassortants detected in 2011 through 2013 have carried 7 genes from HPAI H5N1 clade 2.3.2.1a and the PB1 gene from the Bangladeshi H9N2 clade G1 Mideast, itself derived from HPAI H7N3 virus. Although, the live birds which we sampled in Bangladesh showed no clinical signs of morbidity, the emergence of this reassortant HPAI H5N1 lineage further complicates endemic circulation of H5N1 viruses in Bangladesh, posing a threat to both poultry and humans. PMID:27309046
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Dimovasili, Christina; Aschner, Michael; Plaitakis, Andreas; Zaganas, Ioannis
2015-09-01
Manganese (Mn) is an essential trace element that serves as co-factor for many important mammalian enzymes. In humans, the importance of this cation is highlighted by the fact that low levels of Mn cause developmental and metabolic abnormalities and, on the other hand, chronic exposure to excessive amounts of Mn is characterized by neurotoxicity, possibly mediated by perturbation of astrocytic mitochondrial energy metabolism. Here we sought to study the effect of Mn on the two human glutamate dehydrogenases (hGDH1 and hGDH2, respectively), key mitochondrial enzymes involved in numerous cellular processes, including mitochondrial metabolism, glutamate homeostasis and neurotransmission, and cell signaling. Our studies showed that, compared to magnesium (Mg) and calcium (Ca), Mn exerted a significant inhibitory effect on both human isoenzymes with hGDH2 being more sensitive than hGDH1, especially under conditions of low ADP levels. Specifically, in the presence of 0.25 mM ADP, the Mn IC50 was 1.14 ± 0.02 mM and 1.54 ± 0.08 mM for hGDH2 and for hGDH1, respectively (p = 0.0001). Increasing Mn levels potentiated this differential effect, with 3 mM Mn inhibiting hGDH2 by 96.5% and hGDH1 by 70.2%. At 1 mM ADP, the Mn IC50 was 1.84 ± 0.02 mM and 2.04 ± 0.07 mM (p = 0.01) for hGDH2 and hGDH1, respectively, with 3 mM Mn inhibiting hGDH2 by 93.6% and hGDH1 by 70.9%. These results were due to the sigmoidal inhibitory curve of Mn that was more pronounced for hGDH2 than for hGDH1. Indeed, at 0.25 mM, the Hill coefficient value was higher for hGDH2 (3.42 ± 0.20) than for hGDH1 (1.94 ± 0.25; p = 0.0002) indicating that interaction of Mn with hGDH2 was substantially more co-operative than for hGDH1. These findings, showing an enhanced sensitivity of the hGDH2 isoenzyme to Mn, especially at low ADP levels, might be of pathophysiological relevance under conditions of Mn neurotoxicity. Copyright © 2015 Elsevier Ltd. All
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Castrucci, Maria R; Facchini, Marzia; Di Mario, Giuseppina; Garulli, Bruno; Sciaraffia, Ester; Meola, Monica; Fabiani, Concetta; De Marco, Maria A; Cordioli, Paolo; Siccardi, Antonio; Kawaoka, Yoshihiro; Donatelli, Isabella
2014-05-01
To examine cross-reactivity between hemagglutinin (HA) derived from A/California/7/09 (CA/09) virus and that derived from representative Eurasian "avian-like" (EA) H1N1 swine viruses isolated in Italy between 1999 and 2008 during virological surveillance in pigs. Modified vaccinia virus Ankara (MVA) expressing the HA gene of CA/09 virus (MVA-HA-CA/09) was used as a vaccine to investigate cross-protective immunity against H1N1 swine viruses in mice. Two classical swine H1N1 (CS) viruses and four representative EA-like H1N1 swine viruses previously isolated during outbreaks of respiratory disease in pigs on farms in Northern Italy were used in this study. Female C57BL/6 mice were vaccinated with MVA/HA/CA/09 and then challenged intranasally with H1N1 swine viruses. Cross-reactive antibody responses were determined by hemagglutination- inhibition (HI) and virus microneutralizing (MN) assays of sera from MVA-vaccinated mice. The extent of protective immunity against infection with H1N1 swine viruses was determined by measuring lung viral load on days 2 and 4 post-challenge. Systemic immunization of mice with CA/09-derived HA, vectored by MVA, elicited cross-protective immunity against recent EA-like swine viruses. This immune protection was related to the levels of cross-reactive HI antibodies in the sera of the immunized mice and was dependent on the similarity of the antigenic site Sa of H1 HAs. Our findings suggest that the herd immunity elicited in humans by the pandemic (H1N1) 2009 virus could limit the transmission of recent EA-like swine HA genes into the influenza A virus gene pool in humans. © 2013 The Authors Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.
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Monegan, Jessie D; Bunge, Scott D
2009-04-06
The synthesis and structural characterization of several 1,1,3,3-tetramethylguanidine (H-TMG) solvated magnesium aryloxide complexes are reported. Bu(2)Mg was successfully reacted with H-TMG, HOC(6)H(3)(CMe(3))(2)-2,6 (H-DBP), and either ethanol, a carboxylic acid, or diphenyl phosphate in a 1:1 ratio to yield the corresponding [Mg(mu-L)(DBP)(H-TMG)](2) where L = OCH(2)CH(3) (OEt, 1), O(2)CC(CH(3))(3) (OBc, 2), O(2)C(C(6)H(2)-2,4,6-(CH(3))(3)) (TMBA, 3), or O(2)P(OC(6)H(5))(2) (DPP, 4). Bu(2)Mg was also reacted with two equivalents of H-TMG and HOC(6)H(3)(CMe(3))-2-(CH(3))-6 (BMP) or HO-2,6-Ph(2)C(6)H(3) to yield [Mg(BMP)(2)(H-TMG)(2)] (5) and [Mg(O-2,6-Ph(2)C(6)H(3))(2)(H-TMG)(2)] (6). Compounds 1-6 were characterized by single-crystal X-ray diffraction. Polymerization of l- and rac-lactide with 1 was found to generate polylactide (PLA). A discussion concerning the relevance of compounds 2 - 4 to the structure of Mg-activated phosphatase enzymes is also provided. The bulk powders for all complexes were found to be in agreement with the crystal structures based on elemental analyses, FT-IR spectroscopy, and (1)H, (13)C and (31)P NMR studies.
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Detection of influenza A(H1N1)v virus by real-time RT-PCR.
Panning, M; Eickmann, M; Landt, O; Monazahian, M; Olschläger, S; Baumgarte, S; Reischl, U; Wenzel, J J; Niller, H H; Günther, S; Hollmann, B; Huzly, D; Drexler, J F; Helmer, A; Becker, S; Matz, B; Eis-Hübinger, Am; Drosten, C
2009-09-10
Influenza A(H1N1)v virus was first identified in April 2009. A novel real-time RT-PCR for influenza A(H1N1)v virus was set up ad hoc and validated following industry-standard criteria. The lower limit of detection of the assay was 384 copies of viral RNA per ml of viral transport medium (95% confidence interval: 273-876 RNA copies/ml). Specificity was 100% as assessed on a panel of reference samples including seasonal human influenza A virus H1N1 and H3N2, highly pathogenic avian influenza A virus H5N1 and porcine influenza A virus H1N1, H1N2 and H3N2 samples. The real-time RT-PCR assay for the influenza A matrix gene recommended in 2007 by the World Health Organization was modified to work under the same reaction conditions as the influenza A(H1N1)v virus-specific test. Both assays were equally sensitive. Clinical applicability of both assays was demonstrated by screening of almost 2,000 suspected influenza (H1N1)v specimens, which included samples from the first cases of pandemic H1N1 influenza imported to Germany. Measuring influenza A(H1N1)v virus concentrations in 144 laboratory-confirmed samples yielded a median of 4.6 log RNA copies/ml. The new methodology proved its principle and might assist public health laboratories in the upcoming influenza pandemic.
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Clark, Amelia M; Nogales, Aitor; Martinez-Sobrido, Luis; Topham, David J; DeDiego, Marta L
2017-09-01
In 2009, a novel H1N1 influenza virus emerged in humans, causing a global pandemic. It was previously shown that the NS1 protein from this human 2009 pandemic H1N1 (pH1N1) virus was an effective interferon (IFN) antagonist but could not inhibit general host gene expression, unlike other NS1 proteins from seasonal human H1N1 and H3N2 viruses. Here we show that the NS1 protein from currently circulating pH1N1 viruses has evolved to encode 6 amino acid changes (E55K, L90I, I123V, E125D, K131E, and N205S) with respect to the original protein. Notably, these 6 residue changes restore the ability of pH1N1 NS1 to inhibit general host gene expression, mainly by their ability to restore binding to the cellular factor CPSF30. This is the first report describing the ability of the pH1N1 NS1 protein to naturally acquire mutations that restore this function. Importantly, a recombinant pH1N1 virus containing these 6 amino acid changes in the NS1 protein (pH1N1/NSs-6mut) inhibited host IFN and proinflammatory responses to a greater extent than that with the parental virus (pH1N1/NS1-wt), yet virus titers were not significantly increased in cell cultures or in mouse lungs, and the disease was partially attenuated. The pH1N1/NSs-6mut virus grew similarly to pH1N1/NSs-wt in mouse lungs, but infection with pH1N1/NSs-6mut induced lower levels of proinflammatory cytokines, likely due to a general inhibition of gene expression mediated by the mutated NS1 protein. This lower level of inflammation induced by the pH1N1/NSs-6mut virus likely accounts for the attenuated disease phenotype and may represent a host-virus adaptation affecting influenza virus pathogenesis. IMPORTANCE Seasonal influenza A viruses (IAVs) are among the most common causes of respiratory infections in humans. In addition, occasional pandemics are caused when IAVs circulating in other species emerge in the human population. In 2009, a swine-origin H1N1 IAV (pH1N1) was transmitted to humans, infecting people then and up
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Clark, Amelia M.; Nogales, Aitor; Martinez-Sobrido, Luis
2017-01-01
ABSTRACT In 2009, a novel H1N1 influenza virus emerged in humans, causing a global pandemic. It was previously shown that the NS1 protein from this human 2009 pandemic H1N1 (pH1N1) virus was an effective interferon (IFN) antagonist but could not inhibit general host gene expression, unlike other NS1 proteins from seasonal human H1N1 and H3N2 viruses. Here we show that the NS1 protein from currently circulating pH1N1 viruses has evolved to encode 6 amino acid changes (E55K, L90I, I123V, E125D, K131E, and N205S) with respect to the original protein. Notably, these 6 residue changes restore the ability of pH1N1 NS1 to inhibit general host gene expression, mainly by their ability to restore binding to the cellular factor CPSF30. This is the first report describing the ability of the pH1N1 NS1 protein to naturally acquire mutations that restore this function. Importantly, a recombinant pH1N1 virus containing these 6 amino acid changes in the NS1 protein (pH1N1/NSs-6mut) inhibited host IFN and proinflammatory responses to a greater extent than that with the parental virus (pH1N1/NS1-wt), yet virus titers were not significantly increased in cell cultures or in mouse lungs, and the disease was partially attenuated. The pH1N1/NSs-6mut virus grew similarly to pH1N1/NSs-wt in mouse lungs, but infection with pH1N1/NSs-6mut induced lower levels of proinflammatory cytokines, likely due to a general inhibition of gene expression mediated by the mutated NS1 protein. This lower level of inflammation induced by the pH1N1/NSs-6mut virus likely accounts for the attenuated disease phenotype and may represent a host-virus adaptation affecting influenza virus pathogenesis. IMPORTANCE Seasonal influenza A viruses (IAVs) are among the most common causes of respiratory infections in humans. In addition, occasional pandemics are caused when IAVs circulating in other species emerge in the human population. In 2009, a swine-origin H1N1 IAV (pH1N1) was transmitted to humans, infecting people
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Shawali, Ahmad S; Sherif, Sherif M; Darwish, Manal A A; El-merzabani, Mahmoud M
2010-01-01
A new series of 3-(1,3-disubstituted-1H-pyrazole-4-carbonyl)-1,7-diphenyl-[1,2,4]triazolo[4,3-a]pyrimidin-5(1H)-ones 4 was prepared by reaction of the enaminone 2 with hydrazonoyl halides 3. The preliminary screening for antitumor activity of the synthesized compounds was carried out against Ehrlich Ascites Carcinoma tumor cells. The results revealed that the studied compounds 4 have low or no antitumor activity towards EAC tumor cells.
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Computing at h1 - Experience and Future
NASA Astrophysics Data System (ADS)
Eckerlin, G.; Gerhards, R.; Kleinwort, C.; KrÜNer-Marquis, U.; Egli, S.; Niebergall, F.
The H1 experiment has now been successfully operating at the electron proton collider HERA at DESY for three years. During this time the computing environment has gradually shifted from a mainframe oriented environment to the distributed server/client Unix world. This transition is now almost complete. Computing needs are largely determined by the present amount of 1.5 TB of reconstructed data per year (1994), corresponding to 1.2 × 107 accepted events. All data are centrally available at DESY. In addition to data analysis, which is done in all collaborating institutes, most of the centrally organized Monte Carlo production is performed outside of DESY. New software tools to cope with offline computing needs include CENTIPEDE, a tool for the use of distributed batch and interactive resources for Monte Carlo production, and H1 UNIX, a software package for automatic updates of H1 software on all UNIX platforms.
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Mutations in DYNC1H1 cause severe intellectual disability with neuronal migration defects.
Willemsen, Marjolein H; Vissers, Lisenka E L; Willemsen, Michèl A A P; van Bon, Bregje W M; Kroes, Thessa; de Ligt, Joep; de Vries, Bert B; Schoots, Jeroen; Lugtenberg, Dorien; Hamel, Ben C J; van Bokhoven, Hans; Brunner, Han G; Veltman, Joris A; Kleefstra, Tjitske
2012-03-01
DYNC1H1 encodes the heavy chain protein of the cytoplasmic dynein 1 motor protein complex that plays a key role in retrograde axonal transport in neurons. Furthermore, it interacts with the LIS1 gene of which haploinsufficiency causes a severe neuronal migration disorder in humans, known as classical lissencephaly or Miller-Dieker syndrome. To describe the clinical spectrum and molecular characteristics of DYNC1H1 mutations. A family based exome sequencing approach was used to identify de novo mutations in patients with severe intellectual disability. In this report the identification of two de novo missense mutations in DYNC1H1 (p.Glu1518Lys and p.His3822Pro) in two patients with severe intellectual disability and variable neuronal migration defects is described. Since an autosomal dominant mutation in DYNC1H1 was previously identified in a family with the axonal (type 2) form of Charcot- Marie-Tooth (CMT2) disease and mutations in Dync1h1 in mice also cause impaired neuronal migration in addition to neuropathy, these data together suggest that mutations in DYNC1H1 can lead to a broad phenotypic spectrum and confirm the importance of DYNC1H1 in both central and peripheral neuronal functions.
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The Influenza Virus and the 2009 H1N1 Outbreak
2016-04-08
Envelope L’ol • Sequencing Figure 1 Influenza Virus Anatomy -Neuramlnldase (Sialldase) ’ Hemagglutlnln 9 Key laboratory techniques...discover the 2009 H1 N1 influenza virus Phylogenetic Tree Out of the over 400 human H1 ’s USAFSAM sequenced this season no specimen has had less than a...surveillance/vaccine contents • Shot Versus Flu Mist • How does Tamiflu work • Sequencing HA - Culture, HAI, PCR, Serology ••• • t.tt
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H1N1 Swine Influenza Viruses Differ from Avian Precursors by a Higher pH Optimum of Membrane Fusion.
Baumann, Jan; Kouassi, Nancy Mounogou; Foni, Emanuela; Klenk, Hans-Dieter; Matrosovich, Mikhail
2016-02-01
The H1N1 Eurasian avian-like swine (EAsw) influenza viruses originated from an avian H1N1 virus. To characterize potential changes in the membrane fusion activity of the hemagglutinin (HA) during avian-to-swine adaptation of the virus, we studied EAsw viruses isolated in the first years of their circulation in pigs and closely related contemporary H1N1 viruses of wild aquatic birds. Compared to the avian viruses, the swine viruses were less sensitive to neutralization by lysosomotropic agent NH4Cl in MDCK cells, had a higher pH optimum of hemolytic activity, and were less stable at acidic pH. Eight amino acid substitutions in the HA were found to separate the EAsw viruses from their putative avian precursor; four substitutions-T492S, N722D, R752K, and S1132F-were located in the structural regions of the HA2 subunit known to play a role in acid-induced conformational transition of the HA. We also studied low-pH-induced syncytium formation by cell-expressed HA proteins and found that the HAs of the 1918, 1957, 1968, and 2009 pandemic viruses required a lower pH for fusion induction than did the HA of a representative EAsw virus. Our data show that transmission of an avian H1N1 virus to pigs was accompanied by changes in conformational stability and fusion promotion activity of the HA. We conclude that distinctive host-determined fusion characteristics of the HA may represent a barrier for avian-to-swine and swine-to-human transmission of influenza viruses. Continuing cases of human infections with zoonotic influenza viruses highlight the necessity to understand which viral properties contribute to interspecies transmission. Efficient binding of the HA to cellular receptors in a new host species is known to be essential for the transmission. Less is known about required adaptive changes in the membrane fusion activity of the HA. Here we show that adaptation of an avian influenza virus to pigs in Europe in 1980s was accompanied by mutations in the HA, which decreased
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H1N1 Swine Influenza Viruses Differ from Avian Precursors by a Higher pH Optimum of Membrane Fusion
Baumann, Jan; Kouassi, Nancy Mounogou; Foni, Emanuela; Klenk, Hans-Dieter
2015-01-01
ABSTRACT The H1N1 Eurasian avian-like swine (EAsw) influenza viruses originated from an avian H1N1 virus. To characterize potential changes in the membrane fusion activity of the hemagglutinin (HA) during avian-to-swine adaptation of the virus, we studied EAsw viruses isolated in the first years of their circulation in pigs and closely related contemporary H1N1 viruses of wild aquatic birds. Compared to the avian viruses, the swine viruses were less sensitive to neutralization by lysosomotropic agent NH4Cl in MDCK cells, had a higher pH optimum of hemolytic activity, and were less stable at acidic pH. Eight amino acid substitutions in the HA were found to separate the EAsw viruses from their putative avian precursor; four substitutions—T492S, N722D, R752K, and S1132F—were located in the structural regions of the HA2 subunit known to play a role in acid-induced conformational transition of the HA. We also studied low-pH-induced syncytium formation by cell-expressed HA proteins and found that the HAs of the 1918, 1957, 1968, and 2009 pandemic viruses required a lower pH for fusion induction than did the HA of a representative EAsw virus. Our data show that transmission of an avian H1N1 virus to pigs was accompanied by changes in conformational stability and fusion promotion activity of the HA. We conclude that distinctive host-determined fusion characteristics of the HA may represent a barrier for avian-to-swine and swine-to-human transmission of influenza viruses. IMPORTANCE Continuing cases of human infections with zoonotic influenza viruses highlight the necessity to understand which viral properties contribute to interspecies transmission. Efficient binding of the HA to cellular receptors in a new host species is known to be essential for the transmission. Less is known about required adaptive changes in the membrane fusion activity of the HA. Here we show that adaptation of an avian influenza virus to pigs in Europe in 1980s was accompanied by mutations in
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NASA Astrophysics Data System (ADS)
Kumbar, Mahadev N.; Kamble, Ravindra R.; Dasappa, Jagadeesh Prasad; Bayannavar, Praveen K.; Khamees, Hussien Ahmed; Mahendra, M.; Joshi, Shrinivas D.; Dodamani, Suneel; Rasal, V. P.; Jalalpure, Sunil
2018-05-01
A series of novel 5-(1-aryl-3-(thiophen-2-yl)-1H-pyrazol-4-yl)-1H-tetrazoles 7(h-s) were designed and synthesized. Structural characterization was done by spectral and single crystal X-ray studies. The intermolecular interactions of compound 7n were quantified and visualized using Hirshfeld surface analysis. Structures of newly synthesized compounds were docked into active site of COX-2 enzyme PDB:
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40 CFR 721.9078 - 6-Methoxy-1H-benz[de]isoquinoline-2 [3H]-dione derivative (generic).
Code of Federal Regulations, 2010 CFR
2010-07-01
... 40 Protection of Environment 30 2010-07-01 2010-07-01 false 6-Methoxy-1H-benz[de]isoquinoline-2... Significant New Uses for Specific Chemical Substances § 721.9078 6-Methoxy-1H-benz[de]isoquinoline-2 [3H...) The chemical substance identified generically as 6-methoxy-1H-benz[de]isoquinoline-2 [3H]-dione...
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40 CFR 721.9078 - 6-Methoxy-1H-benz[de]isoquinoline-2 [3H]-dione derivative (generic).
Code of Federal Regulations, 2011 CFR
2011-07-01
... 40 Protection of Environment 31 2011-07-01 2011-07-01 false 6-Methoxy-1H-benz[de]isoquinoline-2... Significant New Uses for Specific Chemical Substances § 721.9078 6-Methoxy-1H-benz[de]isoquinoline-2 [3H...) The chemical substance identified generically as 6-methoxy-1H-benz[de]isoquinoline-2 [3H]-dione...
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Fitness of Pandemic H1N1 and Seasonal influenza A viruses during Co-infection
Perez, Daniel Roberto; Sorrell, Erin; Angel, Matthew; Ye, Jianqiang; Hickman, Danielle; Pena, Lindomar; Ramirez-Nieto, Gloria; Kimble, Brian; Araya, Yonas
2009-01-01
On June 11, 2009 the World Health Organization (WHO) declared a new H1N1 influenza pandemic. This pandemic strain is as transmissible as seasonal H1N1 and H3N2 influenza A viruses. Major concerns facing this pandemic are whether the new virus will replace, co-circulate and/or reassort with seasonal H1N1 and/or H3N2 human strains. Using the ferret model, we investigated which of these three possibilities were most likely favored. Our studies showed that the current pandemic virus is more transmissible than, and has a biological advantage over, prototypical seasonal H1 or H3 strains. PMID:20029606
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26 CFR 1.167(h)-1 - Life tenants and beneficiaries of trusts and estates.
Code of Federal Regulations, 2010 CFR
2010-04-01
... 26 Internal Revenue 2 2010-04-01 2010-04-01 false Life tenants and beneficiaries of trusts and estates. 1.167(h)-1 Section 1.167(h)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... and Corporations § 1.167(h)-1 Life tenants and beneficiaries of trusts and estates. (a) Life tenants...
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Peng, Xiuming; Wu, Haibo; Xu, Lihua; Peng, Xiaorong; Cheng, Linfang; Jin, Changzhong; Xie, Tiansheng; Lu, Xiangyun; Wu, Nanping
2016-06-01
Pandemic outbreaks of H1N1 swine influenza virus have been reported since 2009. Reassortant H1N2 viruses that contain genes from the pandemic H1N1 virus have been isolated in Italy and the United States. However, there is limited information regarding the molecular characteristics of reassortant H1N2 swine influenza viruses in eastern China. Active influenza surveillance programs in Zhejiang Province identified a novel H1N2 influenza virus isolated from pigs displaying clinical signs of influenza virus infection. Whole-genome sequencing was performed and this strain was compared with other influenza viruses available in GenBank. Phylogenetic analysis suggested that the novel strain contained genes from the 2009 pandemic human H1N1 and swine H3N2 viruses. BALB/c mice were infected with the isolated virus to assess its virulence in mice. While the novel H1N2 isolate replicated well in mice, it was found to be less virulent. These results provide additional evidence that swine serve as intermediate hosts or 'mixing vessels' for novel influenza viruses. They also emphasize the importance of surveillance in the swine population for use as an early warning system for influenza outbreaks in swine and human populations.
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Khurana, Surender; Sasono, Pretty; Fox, Annette; Nguyen, Van Kinh; Le, Quynh Mai; Pham, Quang Thai; Nguyen, Tran Hien; Nguyen, Thanh Liem; Horby, Peter; Golding, Hana
2011-12-01
Continuing evolution of highly pathogenic (HP) H5N1 influenza viruses in wild birds with transmission to domestic poultry and humans poses a pandemic threat. There is an urgent need for a simple and rapid serological diagnostic assay which can differentiate between antibodies to seasonal and H5N1 strains and that could provide surveillance tools not dependent on virus isolation and nucleic acid technologies. Here we describe the establishment of H5N1 SeroDetect enzyme-linked immunosorbent assay (ELISA) and rapid test assays based on three peptides in HA2 (488-516), PB1-F2 (2-75), and M2e (2-24) that are highly conserved within H5N1 strains. These peptides were identified by antibody repertoire analyses of H5N1 influenza survivors in Vietnam using whole-genome-fragment phage display libraries (GFPDLs). To date, both platforms have demonstrated high levels of sensitivity and specificity in detecting H5N1 infections (clade 1 and clade 2.3.4) in Vietnamese patients as early as 7 days and up to several years postinfection. H5N1 virus-uninfected individuals in Vietnam and the United States, including subjects vaccinated with seasonal influenza vaccines or with confirmed seasonal virus infections, did not react in the H5N1-SeroDetect assays. Moreover, sera from individuals vaccinated with H5N1 subunit vaccine with moderate anti-H5N1 neutralizing antibody titers did not react positively in the H5N1-SeroDetect ELISA or rapid test assays. The simple H5N1-SeroDetect ELISA and rapid tests could provide an important tool for large-scale surveillance for potential exposure to HP H5N1 strains in both humans and birds.
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Sheridan, Helen; Walsh, John J; Cogan, Carina; Jordan, Michael; McCabe, Tom; Passante, Egle; Frankish, Neil H
2009-10-15
The synthesis and biological activity of the novel diastereoisomers of 2-benzyl-2,3-dihydro-2-(1H-inden-2-yl)-1H-inden-1-ol is reported. The 2,2-coupled indane dimers were synthesised by coupling of the silyl enol ether of 1-indanone with the dimethyl ketal of 2-indanone. The coupled product was directly alkylated to give the racemic ketone which was reduced to the diastereoisomeric alcohols. The alcohols were separated and their relative stereochemistry was established by X-ray crystallography. These molecules demonstrate significant anti-inflammatory activity in vivo and in vitro and may represent a new class of anti-inflammatory agent.
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Zagórska, Agnieszka; Bucki, Adam; Kołaczkowski, Marcin; Siwek, Agata; Głuch-Lutwin, Monika; Starowicz, Gabriela; Kazek, Grzegorz; Partyka, Anna; Wesołowska, Anna; Słoczyńska, Karolina; Pękala, Elżbieta; Pawłowski, Maciej
2016-01-01
A series of 2-fluoro and 3-trifluoromethylphenylpiperazinylalkyl derivatives of 1H-imidazo[2,1-f]purine-2,4(3H,8H)-dione (4-21) were synthesized and evaluated for their serotonin (5-HT 1A /5-HT 7 ) receptor affinity and phosphodiesterase (PDE4B and PDE10A) inhibitor activity. The study enabled the identification of potent 5-HT 1A , 5-HT 7 and mixed 5-HT 1A /5-HT 7 receptor ligands with weak inhibitory potencies for PDE4B and PDE10A. The tests have been completed with the determination of lipophilicity and metabolic stability using micellar electrokinetic chromatography (MEKC) system and human liver microsomes (HLM) model. In preliminary pharmacological in vivo studies, selected compound 8-(5-(4-(2-fluorophenyl)piperazin-1-yl)pentyl)-1,3,7-trimethyl-1H-imidazo[2,1-f]purine-2,4(3H,8H)-dione (9) behaved as a potential antidepressant in forced swim test (FST) in mice. Moreover, potency of antianxiety effects evoked by 9 (2.5 mg/kg) is greater than that of the reference anxiolytic drug, diazepam. Molecular modeling revealed that fluorinated arylpiperazinylalkyl derivatives of 1H-imidazo[2,1-f]purine-2,4(3H,8H)-dione have major significance for the provision of lead compounds for antidepressant and/or anxiolytic application.
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Influenza A (H1N1) virus pneumonia in intensive care unit.
Adıgüzel, Nalan; Karakurt, Zuhal; Kalamanoğlu Balcı, Merih; Acartürk, Eylem; Güngör, Gökay; Yazıcıoğlu Moçin, Ozlem; Batı Kutlu, Semra; Yılmaz, Adnan
2010-01-01
Patients with influenza A (H1N1) virus infection have been admitted to intensive care units (ICU) due to development of severe respiratory failure. We described the clinical and epidemiologic characteristics of the 19 patients admitted to ICU due to influenza A (H1N1) virus infection. Study design is a descriptive case series in a third level-20 bed respiratory ICU at training hospital in Istanbul/Turkey. Influenza A (H1N1) virus infection was laboratory confirmed in specimens using real-time reverse transcriptase-polymerase-chain-reaction (RT-PCR). We collected data concerning demographic, epidemiologic and clinical characteristics of the patients, treatment mortality and outcome. From November 10 to December 31 2009, a total of 19 patients; 7 laboratory confirmed, 12 with high clinical suspicion were treated at ICU. Among 12 patients with high clinical suspicion; 3 patients had negative RT-PCR testing for influenza A (H1N1) virus, 9 patients had no tests. Mean age was 41.6 ± 11.9 (range 21 to 61). Median number of lung zone involvement was 4 (IQR= 3-4). Median PaO2/FiO2 was 105 (IQR= 85-165). Mean severity (APACHE II) and organ failure score (SOFA) were 13 ± 4 and 4.0 ± 1.3 respectively. Non-invasive mechanical ventilation (68.4%, n= 13), invasive mechanical ventilation (21.1%, n= 4) and nasal cannula oxygen (31.5%, n= 6) were implicated. The median length of ICU stay was 6 (IQR= 4-8). Oseltamivir therapy was given as 75 mg bid to 12 patients and 150 mg bid to 7 obese patients. ICU mortality rate was 21.1%. Presenting patients with pneumonia and acute respiratory failure due to influenza A (H1N1) virus infection were treated predominantly and successfully with non invasive mechanical ventilation. Clinicians should be aware of pulmonary complications of influenza A (H1N1) virus infection and that patients can be treated with non invasive mechanical ventilation paying attention to protective measures for health care providers.
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A masked NES in INI1/hSNF5 mediates hCRM1-dependent nuclear export: implications for tumorigenesis
Craig, Errol; Zhang, Zhi-Kai; Davies, Kelvin P.; Kalpana, Ganjam V.
2002-01-01
INI1 (integrase interactor 1)/hSNF5 is a component of the mammalian SWI/SNF complex and a tumor suppressor mutated in malignant rhabdoid tumors (MRT). We have identified a nuclear export signal (NES) in the highly conserved repeat 2 domain of INI1 that is unmasked upon deletion of a downstream sequence. Mutation of conserved hydrophobic residues within the NES, as well as leptomycin B treatment abrogated the nuclear export. Full-length INI1 specifically associated with hCRM1/exportin1 in vivo and in vitro. A mutant INI1 [INI1(1–319) delG950] found in MRT lacking the 66 C-terminal amino acids mislocalized to the cytoplasm. Full-length INI1 but not the INI1(1–319 delG950) mutant caused flat cell formation and cell cycle arrest in cell lines derived from MRT. Disruption of the NES in the delG950 mutant caused nuclear localization of the protein and restored its ability to cause cell cycle arrest. These observations demonstrate that INI1 has a masked NES that mediates regulated hCRM1/exportin1-dependent nuclear export and we propose that mutations that cause deregulated nuclear export of the protein could lead to tumorigenesis. PMID:11782423
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Sun, Yipeng; Qin, Kun; Wang, Jingjing; Pu, Juan; Tang, Qingdong; Hu, Yanxin; Bi, Yuhai; Zhao, Xueli; Yang, Hanchun; Shu, Yuelong; Liu, Jinhua
2011-01-01
H9N2 influenza viruses have been circulating worldwide in multiple avian species and repeatedly infecting mammals, including pigs and humans, posing a significant threat to public health. The coexistence of H9N2 and pandemic influenza H1N1/2009 viruses in pigs and humans provides an opportunity for these viruses to reassort. To evaluate the potential public risk of the reassortant viruses derived from these viruses, we used reverse genetics to generate 127 H9 reassortants derived from an avian H9N2 and a pandemic H1N1 virus, and evaluated their compatibility, replication ability, and virulence in mice. These hybrid viruses showed high genetic compatibility and more than half replicated to a high titer in vitro. In vivo studies of 73 of 127 reassortants revealed that all viruses were able to infect mice without prior adaptation and 8 reassortants exhibited higher pathogenicity than both parental viruses. All reassortants with higher virulence than parental viruses contained the PA gene from the 2009 pandemic virus, revealing the important role of the PA gene from the H1N1/2009 virus in generating a reassortant virus with high public health risk. Analyses of the polymerase activity of the 16 ribonucleoprotein combinations in vitro suggested that the PA of H1N1/2009 origin also enhanced polymerase activity. Our results indicate that some avian H9-pandemic reassortants could emerge with a potentially higher threat for humans and also highlight the importance of monitoring the H9-pandemic reassortant viruses that may arise, especially those that possess the PA gene of H1N1/2009 origin. PMID:21368167
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Rej, Supriya; Pramanik, Suman; Tsurugi, Hayato; Mashima, Kazushi
2017-12-07
We report a transition metal-free dehalogenation of vicinal dihalo compounds by 1,1'-bis(trimethylsilyl)-1H,1'H-4,4'-bipyridinylidene (1) under mild conditions, in which trimethylsilyl halide and 4,4'-bipyridine were generated as byproducts. The synthetic protocol for this dehalogenation reaction was effective for a wide scope of dibromo compounds as substrates while keeping the various functional groups intact. Furthermore, the reduction of vicinal dichloro alkanes and vicinal dibromo alkenes also proceeded in a salt-free manner to afford the corresponding alkenes and alkynes.
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Diaquabis{5-carboxy-2-[(1H-1,2,4-triazol-1-yl)methyl]-1H-imidazole-4-carboxylato}manganese(II)
Ding, De-Gang; Tong, Yan
2010-01-01
In the title compound, [Mn(C8H6N5O4)2(H2O)2], the MnII ion is situated on an inversion center and is six-coordinated by two N and two O atoms from two L ligands (HL = 2-[(1H-1,2,4-triazol-1-yl)methyl]-1H-imidazole-4,5-dicarboxylic acid) and two water molecules in a distorted octahedral geometry. In ligand L, the imidazole and triazole rings form a dihedral angle of 74.25 (8)°. Molecules are assembled into a three-dimensional structure via intermolecular O—H⋯O, O—H⋯N and N—H⋯N hydrogen-bonds, and π–π interactions with a short distance of 3.665 (2) Å between the centroids of the imidazole and triazole rings of neighbouring molecules. PMID:21579014
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Epidemiology of pandemic influenza A/H1N1 virus during 2009-2010 in Taiwan.
Lan, Yu-Ching; Su, Mei-Chi; Chen, Chao-Hsien; Huang, Su-Hua; Chen, Wan-Li; Tien, Ni; Lin, Cheng-Wen
2013-10-01
Outbreak of swine-origin influenza A/H1N1 virus (pdmH1N1) occurred in 2009. Taiwanese authorities implemented nationwide vaccinations with pdmH1N1-specific inactivated vaccine as of November 2009. This study evaluates prevalence, HA phylogenetic relationship, and transmission dynamic of influenza A and B viruses in Taiwan in 2009-2010. Respiratory tract specimens were analyzed for influenza A and B viruses. The pdmH1N1 peaked in November 2009, was predominant from August 2009 to January 2010, then sharply dropped in February 2010. Significant prevalence peaks of influenza B in April-June of 2010 and H3N2 virus in July and August were observed. Highest percentage of pdmH1N1- and H3N2-positive cases appeared among 11-15-year-olds; influenza B-positive cases were dominant among those 6-10 years old. Maximum likelihood phylogenetic trees showed 11 unique clusters of pdmH1N1, seasonal H3N2 influenza A and B viruses, as well as transmission clusters and mixed infections of influenza strains in Taiwan. The 2009 pdmH1N1 virus was predominant in Taiwan from August 2009 to January 2010; seasonal H3N2 influenza A and B viruses exhibited small prevalence peaks after nationwide vaccinations. Phylogenetic evidence indicated transmission clusters and multiple independent clades of co-circulating influenza A and B strains in Taiwan. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.
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Congdon, Lauren M; Sims, Jennifer K; Tuzon, Creighton T; Rice, Judd C
2014-04-01
PR-Set7/Set8/KMT5a is the sole histone H4 lysine 20 monomethyltransferase (H4K20me1) in metazoans and is essential for proper cell division and genomic stability. We unexpectedly discovered that normal cellular levels of monomethylated histone H3 lysine 9 (H3K9me1) were also dependent on PR-Set7, but independent of its catalytic activity. This observation suggested that PR-Set7 interacts with an H3K9 monomethyltransferase to establish the previously reported H4K20me1-H3K9me1 trans-tail 'histone code'. Here we show that PR-Set7 specifically and directly binds the C-terminus of the Riz1/PRDM2/KMT8 tumor suppressor and demonstrate that the N-terminal PR/SET domain of Riz1 preferentially monomethylates H3K9. The PR-Set7 binding domain was required for Riz1 nuclear localization and maintenance of the H4K20me1-H3K9me1 trans-tail 'histone code'. Although Riz1 can function as a repressor, Riz1/H3K9me1 was dispensable for the repression of genes regulated by PR-Set7/H4K20me1. Frameshift mutations resulting in a truncated Riz1 incapable of binding PR-Set7 occur frequently in various aggressive cancers. In these cancer cells, expression of wild-type Riz1 restored tumor suppression by decreasing proliferation and increasing apoptosis. These phenotypes were not observed in cells expressing either the Riz1 PR/SET domain or PR-Set7 binding domain indicating that Riz1 methyltransferase activity and PR-Set7 binding domain are both essential for Riz1 tumor suppressor function.
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Yang, Ji-Rong; Chen, Chih-Yuan; Kuo, Chuan-Yi; Cheng, Chieh-Yu; Lee, Min-Shiuh; Cheng, Ming-Chu; Yang, Yu-Chih; Wu, Chia-Ying; Wu, Ho-Sheng; Liu, Ming-Tsan; Hsiao, Pei-Wen
2016-02-01
Avian influenza A(H6N1) virus is one of the most common viruses isolated from migrating birds and domestic poultry in many countries. The first and only known case of human infection by H6N1 virus in the world was reported in Taiwan in 2013. This led to concern that H6N1 virus may cause a threat to public health. In this study, we engineered a recombinant H6N1 virus-like particle (VLP) and investigated its vaccine effectiveness compared to the traditional egg-based whole inactivated virus (WIV) vaccine. The H6N1-VLPs exhibited similar morphology and functional characteristics to influenza viruses. Prime-boost intramuscular immunization in mice with unadjuvanted H6N1-VLPs were highly immunogenic and induced long-lasting antibody immunity. The functional activity of the VLP-elicited IgG antibodies was proved by in vitro seroprotective hemagglutination inhibition and microneutralization titers against the homologous human H6N1 virus, as well as in vivo viral challenge analyses which showed H6N1-VLP immunization significantly reduced viral load in the lung, and protected against human H6N1 virus infection. Of particular note, the H6N1-VLPs but not the H6N1-WIVs were able to confer cross-reactive humoral immunity; antibodies induced by H6N1-VLP vaccine robustly inhibited the hemagglutination activities and in vitro replication of distantly-related heterologous avian H6N1 viruses. Furthermore, the H6N1-VLPs were found to elicit significantly greater anti-HA2 antibody responses in immunized mice than H6N1-WIVs. Collectively, we demonstrated for the first time a novel H6N1-VLP vaccine that effectively provides broadly protective immunity against both human and avian H6N1 viruses. These results, which uncover the underlying mechanisms for induction of wide-range immunity against influenza viruses, may be useful for future influenza vaccine development. Copyright © 2015 Elsevier B.V. All rights reserved.
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Saito, Naoki; Kitamaki, Yuko; Otsuka, Satoko; Yamanaka, Noriko; Nishizaki, Yuzo; Sugimoto, Naoki; Imura, Hisanori; Ihara, Toshihide
2018-07-01
We devised a novel extended internal standard method of quantitative 1 H NMR (qNMR) assisted by chromatography (EIC) that accurately quantifies 1 H signal areas of analytes, even when the chemical shifts of the impurity and analyte signals overlap completely. When impurity and analyte signals overlap in the 1 H NMR spectrum but can be separated in a chromatogram, the response ratio of the impurity and an internal standard (IS) can be obtained from the chromatogram. If the response ratio can be converted into the 1 H signal area ratio of the impurity and the IS, the 1 H signal area of the analyte can be evaluated accurately by mathematically correcting the contributions of the 1 H signal area of the impurity overlapping the analyte in the 1 H NMR spectrum. In this study, gas chromatography and liquid chromatography were used. We used 2-chlorophenol and 4-chlorophenol containing phenol as an impurity as examples in which impurity and analyte signals overlap to validate and demonstrate the EIC, respectively. Because the 1 H signals of 2-chlorophenol and phenol can be separated in specific alkaline solutions, 2-chlorophenol is suitable to validate the EIC by comparing analytical value obtained by the EIC with that by only qNMR under the alkaline condition. By the EIC, the purity of 2-chlorophenol was obtained with a relative expanded uncertainty (k = 2) of 0.24%. The purity matched that obtained under the alkaline condition. Furthermore, the EIC was also validated by evaluating the phenol content with the absolute calibration curve method by gas chromatography. Finally, we demonstrated that the EIC was possible to evaluate the purity of 4-chlorophenol, with a relative expanded uncertainty (k = 2) of 0.22%, which was not able to be separated from the 1 H signal of phenol under any condition. Copyright © 2018 Elsevier B.V. All rights reserved.
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Influenza A H5N1 and H7N9 in China: A spatial risk analysis
Gardner, Lauren; MacIntyre, Raina; Sarkar, Sahotra
2017-01-01
Background Zoonotic avian influenza poses a major risk to China, and other parts of the world. H5N1 has remained endemic in China and globally for nearly two decades, and in 2013, a novel zoonotic influenza A subtype H7N9 emerged in China. This study aimed to improve upon our current understanding of the spreading mechanisms of H7N9 and H5N1 by generating spatial risk profiles for each of the two virus subtypes across mainland China. Methods and findings In this study, we (i) developed a refined data set of H5N1 and H7N9 locations with consideration of animal/animal environment case data, as well as spatial accuracy and precision; (ii) used this data set along with environmental variables to build species distribution models (SDMs) for each virus subtype in high resolution spatial units of 1km2 cells using Maxent; (iii) developed a risk modelling framework which integrated the results from the SDMs with human and chicken population variables, which was done to quantify the risk of zoonotic transmission; and (iv) identified areas at high risk of H5N1 and H7N9 transmission. We produced high performing SDMs (6 of 8 models with AUC > 0.9) for both H5N1 and H7N9. In all our SDMs, H7N9 consistently showed higher AUC results compared to H5N1, suggesting H7N9 suitability could be better explained by environmental variables. For both subtypes, high risk areas were primarily located in south-eastern China, with H5N1 distributions found to be more diffuse and extending more inland compared to H7N9. Conclusions We provide projections of our risk models to public health policy makers so that specific high risk areas can be targeted for control measures. We recommend comparing H5N1 and H7N9 prevalence rates and survivability in the natural environment to better understand the role of animal and environmental transmission in human infections. PMID:28376125
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New H1/H3 antagonists for treating allergic rhinitis: WO2010094643.
Norman, Peter
2011-03-01
This application claims dual receptor specificity antihistamines, active as H(1) and H(3) antagonists, which additionally have a long duration of action that renders them suitable for once daily administration via inhalation for the treatment of allergic rhinitis. The compounds lack CNS penetration and have a high affinity for both histamine receptors.
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Uwai, Yuichi; Taniguchi, Risa; Motohashi, Hideyuki; Saito, Hideyuki; Okuda, Masahiro; Inui, Ken-ichi
2004-10-01
Human organic anion transporters hOAT1 (SLC22A6) and hOAT3 (SLC22A8) are responsible for renal tubular secretion of an antifolic acid methotrexate, and are considered to be involved in drug interaction of methotrexate with nonsteroidal anti-inflammatory drugs (NSAIDs). In our hospital, a delay of methotrexate elimination was experienced in a patient with Hodgkin's disease, who took loxoprofen, a commonly used NSAID in Japan, which suggested a cause. In this study, we examined the drug interaction via hOAT1 and hOAT3, using Xenopus laevis oocytes. hOAT1 and hOAT3 mediated the methotrexate transport with low affinity (K(m) of 724.0 muM) and high affinity (K(m) of 17.2 muM), respectively. Loxoprofen and its trans-OH metabolite, an active major metabolite, markedly inhibited the methotrexate transport by both transporters. Their inhibition concentrations (IC(50)) were in the range of the therapeutic levels. These findings suggest that loxoprofen retards the elimination of methotrexate, at least in part, by inhibiting hOAT1 and hOAT3.
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Kilany, Walid H.; Safwat, Marwa; Mohammed, Samy M.; Salim, Abdullah; Fasina, Folorunso Oludayo; Fasanmi, Olubunmi G.; Shalaby, Azhar G.; Dauphin, Gwenaelle; Hassan, Mohammed K.; Lubroth, Juan; Jobre, Yilma M.
2016-01-01
In Egypt, ducks kept for commercial purposes constitute the second highest poultry population, at 150 million ducks/year. Hence, ducks play an important role in the introduction and transmission of avian influenza (AI) in the Egyptian poultry population. Attempts to control outbreaks include the use of vaccines, which have varying levels of efficacy and failure. To date, the effects of vaccine efficacy has rarely been determined in ducks. In this study, we evaluated the protective efficacy of a live recombinant vector vaccine based on a turkey Herpes Virus (HVT) expressing the H5 gene from a clade 2.2 H5N1 HPAIV strain (A/Swan/Hungary/499/2006) (rHVT-H5) and a bivalent inactivated H5N1 vaccine prepared from clade 2.2.1 and 2.2.1.1 H5N1 seeds in Mulard ducks. A 0.3ml/dose subcutaneous injection of rHVT-H5 vaccine was administered to one-day-old ducklings (D1) and another 0.5ml/dose subcutaneous injection of the inactivated MEFLUVAC was administered at 7 days (D7). Four separate challenge experiments were conducted at Days 21, 28, 35 and 42, in which all the vaccinated ducks were challenged with 106EID50/duck of H5N1 HPAI virus (A/chicken/Egypt/128s/2012(H5N1) (clade 2.2.1) via intranasal inoculation. Maternal-derived antibody regression and post-vaccination antibody immune responses were monitored weekly. Ducks vaccinated at 21, 28, 35 and 42 days with the rHVT-H5 and MEFLUVAC vaccines were protected against mortality (80%, 80%, 90% and 90%) and (50%, 70%, 80% and 90%) respectively, against challenges with the H5N1 HPAI virus. The amount of viral shedding and shedding rates were lower in the rHVT-H5 vaccine groups than in the MEFLUVAC groups only in the first two challenge experiments. However, the non-vaccinated groups shed significantly more of the virus than the vaccinated groups. Both rHVT-H5 and MEFLUVAC provide early protection, and rHVT-H5 vaccine in particular provides protection against HPAI challenge. PMID:27304069
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Kilany, Walid H; Safwat, Marwa; Mohammed, Samy M; Salim, Abdullah; Fasina, Folorunso Oludayo; Fasanmi, Olubunmi G; Shalaby, Azhar G; Dauphin, Gwenaelle; Hassan, Mohammed K; Lubroth, Juan; Jobre, Yilma M
2016-01-01
In Egypt, ducks kept for commercial purposes constitute the second highest poultry population, at 150 million ducks/year. Hence, ducks play an important role in the introduction and transmission of avian influenza (AI) in the Egyptian poultry population. Attempts to control outbreaks include the use of vaccines, which have varying levels of efficacy and failure. To date, the effects of vaccine efficacy has rarely been determined in ducks. In this study, we evaluated the protective efficacy of a live recombinant vector vaccine based on a turkey Herpes Virus (HVT) expressing the H5 gene from a clade 2.2 H5N1 HPAIV strain (A/Swan/Hungary/499/2006) (rHVT-H5) and a bivalent inactivated H5N1 vaccine prepared from clade 2.2.1 and 2.2.1.1 H5N1 seeds in Mulard ducks. A 0.3ml/dose subcutaneous injection of rHVT-H5 vaccine was administered to one-day-old ducklings (D1) and another 0.5ml/dose subcutaneous injection of the inactivated MEFLUVAC was administered at 7 days (D7). Four separate challenge experiments were conducted at Days 21, 28, 35 and 42, in which all the vaccinated ducks were challenged with 106EID50/duck of H5N1 HPAI virus (A/chicken/Egypt/128s/2012(H5N1) (clade 2.2.1) via intranasal inoculation. Maternal-derived antibody regression and post-vaccination antibody immune responses were monitored weekly. Ducks vaccinated at 21, 28, 35 and 42 days with the rHVT-H5 and MEFLUVAC vaccines were protected against mortality (80%, 80%, 90% and 90%) and (50%, 70%, 80% and 90%) respectively, against challenges with the H5N1 HPAI virus. The amount of viral shedding and shedding rates were lower in the rHVT-H5 vaccine groups than in the MEFLUVAC groups only in the first two challenge experiments. However, the non-vaccinated groups shed significantly more of the virus than the vaccinated groups. Both rHVT-H5 and MEFLUVAC provide early protection, and rHVT-H5 vaccine in particular provides protection against HPAI challenge.
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Neurologic complications of influenza A(H1N1)pdm09
Khandaker, Gulam; Zurynski, Yvonne; Buttery, Jim; Marshall, Helen; Richmond, Peter C.; Dale, Russell C.; Royle, Jenny; Gold, Michael; Snelling, Tom; Whitehead, Bruce; Jones, Cheryl; Heron, Leon; McCaskill, Mary; Macartney, Kristine; Elliott, Elizabeth J.
2012-01-01
Objective: We sought to determine the range and extent of neurologic complications due to pandemic influenza A (H1N1) 2009 infection (pH1N1′09) in children hospitalized with influenza. Methods: Active hospital-based surveillance in 6 Australian tertiary pediatric referral centers between June 1 and September 30, 2009, for children aged <15 years with laboratory-confirmed pH1N1′09. Results: A total of 506 children with pH1N1′09 were hospitalized, of whom 49 (9.7%) had neurologic complications; median age 4.8 years (range 0.5–12.6 years) compared with 3.7 years (0.01–14.9 years) in those without complications. Approximately one-half (55.1%) of the children with neurologic complications had preexisting medical conditions, and 42.8% had preexisting neurologic conditions. On presentation, only 36.7% had the triad of cough, fever, and coryza/runny nose, whereas 38.7% had only 1 or no respiratory symptoms. Seizure was the most common neurologic complication (7.5%). Others included encephalitis/encephalopathy (1.4%), confusion/disorientation (1.0%), loss of consciousness (1.0%), and paralysis/Guillain-Barré syndrome (0.4%). A total of 30.6% needed intensive care unit (ICU) admission, 24.5% required mechanical ventilation, and 2 (4.1%) died. The mean length of stay in hospital was 6.5 days (median 3 days) and mean ICU stay was 4.4 days (median 1.5 days). Conclusions: Neurologic complications are relatively common among children admitted with influenza, and can be life-threatening. The lack of specific treatment for influenza-related neurologic complications underlines the importance of early diagnosis, use of antivirals, and universal influenza vaccination in children. Clinicians should consider influenza in children with neurologic symptoms even with a paucity of respiratory symptoms. PMID:22993280
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Pandemic (H1N1) 2009 and Hajj Pilgrims Who Received Predeparture Vaccination, Egypt
Kandeel, Amr; Abdel Kereem, Eman; El-Refay, Samir; Afifi, Salma; Abukela, Mohammed; Earhart, Kenneth; El-Sayed, Nasr; El-Gabaly, Hatem
2011-01-01
In Egypt, vaccination against pandemic (H1N1) 2009 virus was required of pilgrims departing for the 2009 Hajj. A survey of 551 pilgrims as they returned to Egypt found 542 (98.1% [weighted]) reported receiving the vaccine; 6 (1.0% [weighted]) were infected with influenza virus A (H3N2) but none with pandemic (H1N1) 2009 virus. PMID:21762583
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Determination of the delta(2H/1H)of Water: RSIL Lab Code 1574
Revesz, Kinga; Coplen, Tyler B.
2008-01-01
Reston Stable Isotope Laboratory (RSIL) lab code 1574 describes a method used to determine the relative hydrogen isotope-ratio delta(2H,1H), abbreviated hereafter as d2H of water. The d2H measurement of water also is a component of the National Water Quality Laboratory (NWQL) schedules 1142 and 1172. The water is collected unfiltered in a 60-mL glass bottle and capped with a Polyseal cap. In the laboratory, the water sample is equilibrated with gaseous hydrogen using a platinum catalyst (Horita, 1988; Horita and others, 1989; Coplen and others, 1991). The reaction for the exchange of one hydrogen atom is shown in equation 1.
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Adaptation of Pandemic H1N1 Influenza Viruses in Mice▿
Ilyushina, Natalia A.; Khalenkov, Alexey M.; Seiler, Jon P.; Forrest, Heather L.; Bovin, Nicolai V.; Marjuki, Henju; Barman, Subrata; Webster, Robert G.; Webby, Richard J.
2010-01-01
The molecular mechanism by which pandemic 2009 influenza A viruses were able to sufficiently adapt to humans is largely unknown. Subsequent human infections with novel H1N1 influenza viruses prompted an investigation of the molecular determinants of the host range and pathogenicity of pandemic influenza viruses in mammals. To address this problem, we assessed the genetic basis for increased virulence of A/CA/04/09 (H1N1) and A/TN/1-560/09 (H1N1) isolates, which are not lethal for mice, in a new mammalian host by promoting their mouse adaptation. The resulting mouse lung-adapted variants showed significantly enhanced growth characteristics in eggs, extended extrapulmonary tissue tropism, and pathogenicity in mice. All mouse-adapted viruses except A/TN/1-560/09-MA2 grew faster and to higher titers in cells than the original strains. We found that 10 amino acid changes in the ribonucleoprotein (RNP) complex (PB2 E158G/A, PA L295P, NP D101G, and NP H289Y) and hemagglutinin (HA) glycoprotein (K119N, G155E, S183P, R221K, and D222G) controlled enhanced mouse virulence of pandemic isolates. HA mutations acquired during adaptation affected viral receptor specificity by enhancing binding to α2,3 together with decreasing binding to α2,6 sialyl receptors. PB2 E158G/A and PA L295P amino acid substitutions were responsible for the significant enhancement of transcription and replication activity of the mouse-adapted H1N1 variants. Taken together, our findings suggest that changes optimizing receptor specificity and interaction of viral polymerase components with host cellular factors are the major mechanisms that contribute to the optimal competitive advantage of pandemic influenza viruses in mice. These modulators of virulence, therefore, may have been the driving components of early evolution, which paved the way for novel 2009 viruses in mammals. PMID:20592084
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Preparation and characterization of 3,5-dinitro-1H-1,2,4-triazole.
Haiges, R; Bélanger-Chabot, G; Kaplan, S M; Christe, K O
2015-04-28
Neat 3,5-dinitro-1H-1,2,4-triazole was obtained in quantitative yield from potassium 3,5-dinitro-1,2,4-triazolate and sulfuric acid. The compound was purified by sublimation in vacuo at 110 °C. Pure HDNT is a hygroscopic white solid that is impact and friction sensitive and decomposes explosively upon heating to 170 °C. However, the presence of impurities might lower the decomposition temperature and increase the sensitivity of the material. Potassium 3,5-dinitro-1,2,4-triazolate was prepared from commercially available 3,5-diamino-4H-1,2,4-triazole with sodium nitrite and sulfuric acid. The synthesis of HDNT from 2-cyanoguanidine and hydrazine hydrate without isolation and purification of the 3,5-diamino-4H-1,2,4-triazole intermediate can result in the formation of azidotriazole impurities. A triclinic and a monoclinic polymorph of 3,5-dinitro-1H-1,2,4-triazole were found by X-ray structure determination. In addition, the crystal structure of the hydrate (HDNT)3·4H2O, as well as those of several HDNT impurities and decomposition products were obtained.
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NASA Astrophysics Data System (ADS)
Mindarava, Y. L.; Shundalau, M. B.; Al-Wahaibi, L. H.; El-Emam, A. A.; Matsukovich, A. S.; Gaponenko, S. V.
2018-05-01
Vibrational IR (3200-650 cm-1) and Raman spectra (3200-150 cm-1) of adamantane-containing 3-(adamantan-1-yl)-4-ethyl-1-[(4-phenylpiperazin-1-yl)methyl]-1H-1,2,4-triazole-5(4H)-thione, which is promising for drug design, were examined. The UV/Vis spectrum (450-200 nm) of the compound in EtOH was measured. Full geometry optimization using density functional theory (DFT) in the B3LYP/cc-pVDZ approximation allowed the equilibrium configuration of the molecule to be determined and IR and Raman spectra to be calculated. Based on these, the experimental vibrational IR and Raman spectra were interpreted and the biological activity indices were predicted. The UV/Vis spectrum of the title compound was simulated at the time-dependent DFT/CAM-B3LYP/cc-pVDZ level with and without solvent effects and at the ab initio multi-reference perturbation theory XMCQDPT2 level. The UV/Vis spectrum that was simulated using the multi-reference XMCQDPT2 approximation agreed very successfully with the experimental data, in contrast to the single-reference DFT method. This was probably a consequence of intramolecular charge transfer.
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NASA Astrophysics Data System (ADS)
Mindarava, Y. L.; Shundalau, M. B.; Al-Wahaibi, L. H.; El-Emam, A. A.; Matsukovich, A. S.; Gaponenko, S. V.
2018-05-01
Vibrational IR (3200-650 cm-1) and Raman spectra (3200-150 cm-1) of adamantane-containing 3-(adamantan-1-yl)-4-ethyl-1-[(4-phenylpiperazin-1-yl)methyl]-1H-1,2,4-triazole-5(4H)-thione, which is promising for drug design, were examined. The UV/Vis spectrum (450-200 nm) of the compound in EtOH was measured. Full geometry optimization using density functional theory (DFT) in the B3LYP/cc-pVDZ approximation allowed the equilibrium configuration of the molecule to be determined and IR and Raman spectra to be calculated. Based on these, the experimental vibrational IR and Raman spectra were interpreted and the biological activity indices were predicted. The UV/Vis spectrum of the title compound was simulated at the time-dependent DFT/CAM-B3LYP/cc-pVDZ level with and without solvent effects and at the ab initio multi-reference perturbation theory XMCQDPT2 level. The UV/Vis spectrum that was simulated using the multi-reference XMCQDPT2 approximation agreed very successfully with the experimental data, in contrast to the single-reference DFT method. This was probably a consequence of intramolecular charge transfer.
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Katzir, Z; Nardi, N; Geffen, I; Fuhrer, C; Henis, Y I
1994-08-26
Lateral mobility studies comparing native and mutated membrane proteins, combined with treatments that alter clathrin lattice structure, can measure membrane protein-coated pit interactions in intact cells (Fire, E., Zwart, D., Roth, M. G., and Henis, Y. I. (1991) J. Cell Biol. 115, 1585-1594). We applied this approach to study the interactions of the H1 and H2 human asialoglycoprotein receptor subunits with coated pits. The lateral mobilities of singly expressed and coexpressed H1 and H2B (the H2 species that reaches the cell surface) were measured by fluorescence photobleaching recovery. They were compared with mutant proteins, H1(5A) (Tyr-5 replaced by Ala) and H2(5A) (Phe-5 replaced by Ala). While the mobile fractions of H1, H2B, and their mutants were similar, the lateral diffusion rate (measured by D, the lateral diffusion coefficient) was significantly slower for H1, whether expressed alone or with H2B. Coexpression with H1 reduced D of H2B to that of H1. Disruption of the clathrin lattices by hypertonic medium elevated D of H1, H1(5A), H2B, and H2(5A) to the same final level, without affecting their mobile fractions. Cytosol acidification, which retains altered clathrin lattices attached to the membrane and prevents coated vesicle formation, immobilized part of the H1 molecules, reflecting stable entrapment in "frozen" coated pits. H1(5A), H2B, and H2(5A) were not affected; however, coexpression of H2B with H1 conferred the sensitivity to cytosol acidification on H2B. Our results suggest that H1 lateral mobility is inhibited by dynamic interactions with coated pits in which Tyr-5 is involved. H2B resembles H1(5A) rather than H1, and its interactions with coated pits are weaker; efficient interaction of H2B with coated pits depends on complex formation with H1.
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Cunha, Burke A; Syed, Uzma; Mickail, Nardeen
2010-01-01
The swine influenza (H1N1) pandemic began in Mexico and rapidly spread worldwide. As is the case with pandemic influenza A, the majority of early deaths have been in young healthy adults. The complications of pandemic H1N1 have been reported from several centers. Noteworthy has been the relative rarity of bacterial coinfection in bacterial pneumonia in hospitalized adults with H1N1 pneumonia. Simultaneous bacterial community-acquired pneumonia due to methicillin-sensitive Staphylococcus aureus or community-acquired methicillin resistant S. aureus and subsequent bacterial community-acquired pneumonia due to S. pneumoniae or Haemophilus influenzae have been reportedly rare (0.4%-4% of well-documented cases). Cardiac complications of H1N1 infection have been uncommon. Young healthy adults without a cardiac history who have H1N1 and chest pain usually have either acute myocardial infarction or acute myocarditis. Cardiac symptomatology with H1N1 often overshadows pulmonary manifestations, that is, influenza pneumonia. With H1N1 pneumonia, clinicians should be alert for otherwise unexplained tachycardia or chest pain that may represent acute myocardial infarction or myocarditis. We present a case of rapidly fatal H1N1 in a young adult treated with oseltamivir and peramivir. He was initially tachycardic, thought to represent myocarditis. He subsequently became hypotensive and expired. At autopsy there was cardiomegaly present but there were no signs of acute myocardial infarction or myocarditis. Pathologically, he died of severe H1N1 pneumonia and not bacterial pneumonia. Copyright © 2010 Elsevier Inc. All rights reserved.
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Measurement of Swine H1N1 Hemagglutinin Peptide binding with Piezoresistive Microcantilever Arrays
Bajwa, Navdeep K; Maldonado, Carlos J.; Thundat, Thomas George; ...
2014-03-24
The effective detection of Swine H1N1 Hemagglutinin peptide is crucial as it could be used as a positive control to screen for highly infectious flu strains such as Swine-Origin Influenza A (H1N1). Piezoresistive microcantilever arrays present a pathway towards highly sensitive and label-free detection of biomolecules by transducing the antigen-antibody binding into change in resistivity via induced surface stress variation. We also demonstrate a mechanical transduction of Swine H1N1 Hemagglutinin peptide binding and suggest the employed technique may offer a potential platform for detection of the H1N1 virus, which could be clinically used to diagnose and provide subsequent relief.
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MSX1 cooperates with histone H1b for inhibition of transcription and myogenesis.
Lee, Hansol; Habas, Raymond; Abate-Shen, Cory
2004-06-11
During embryogenesis, differentiation of skeletal muscle is regulated by transcription factors that include members of the Msx homeoprotein family. By investigating Msx1 function in repression of myogenic gene expression, we identified a physical interaction between Msx1 and H1b, a specific isoform of mouse histone H1. We found that Msx1 and H1b bind to a key regulatory element of MyoD, a central regulator of skeletal muscle differentiation, where they induce repressed chromatin. Moreover, Msx1 and H1b cooperate to inhibit muscle differentiation in cell culture and in Xenopus animal caps. Our findings define a previously unknown function for "linker" histones in gene-specific transcriptional regulation.
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Piezoresistive measurement of Swine H1N1 Hemagglutinin peptide binding with microcantilever arrays
NASA Astrophysics Data System (ADS)
Bajwa, N.; Maldonado, C. J.; Thundat, T.; Passian, A.
2014-03-01
Effective detection of Swine H1N1 Hemagglutinin peptide is crucial as it could be used as a positive control to screen for highly infectious flu strains such as Swine-Origin Influenza A (H1N1). Piezoresistive microcantilever arrays present a pathway towards highly sensitive and label-free detection of biomolecules by transducing the antigen-antibody binding into change in resistivity via induced surface stress variation. We demonstrate a mechanical transduction of Swine H1N1 Hemagglutinin peptide binding and suggest the employed technique may offer a potential platform for detection of the H1N1 virus, which could be clinically used to diagnose and provide subsequent relief.
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Measurement of Swine H1N1 Hemagglutinin Peptide binding with Piezoresistive Microcantilever Arrays
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bajwa, Navdeep K; Maldonado, Carlos J.; Thundat, Thomas George
The effective detection of Swine H1N1 Hemagglutinin peptide is crucial as it could be used as a positive control to screen for highly infectious flu strains such as Swine-Origin Influenza A (H1N1). Piezoresistive microcantilever arrays present a pathway towards highly sensitive and label-free detection of biomolecules by transducing the antigen-antibody binding into change in resistivity via induced surface stress variation. We also demonstrate a mechanical transduction of Swine H1N1 Hemagglutinin peptide binding and suggest the employed technique may offer a potential platform for detection of the H1N1 virus, which could be clinically used to diagnose and provide subsequent relief.
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Hippocampal 1H-MRSI in ecstasy users.
Obergriesser, T; Ende, G; Braus, D F; Henn, F A
2001-06-01
In recent years the illicit drug ecstasy (MDMA, 3,4-methylenedioxymethamphetamine) has come into widespread use among young people. Despite clear evidence for the neurotoxic potential of MDMA in animals, corresponding evidence in humans is limited to indirect findings. In an exploratory study we compared the hippocampal 1H-MRSI (magnetic resonance spectroscopic imaging) spectra of five MDMA users with those of controls with no history of substance abuse. Although 1H
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Wang, Jiajia; Xu, Hua; Yang, Xinjing; Zhao, Daguo; Liu, Shenglan; Sun, Xue; Huang, Jian-An; Guo, Qiang
The clinical presentations and disease courses of patients hospitalized with either influenza A virus subtype H7N9 (H7N9) or 2009 pandemic H1N1 influenza virus were compared in a recent report, but associated cardiac complications remain unclear. The present retrospective study investigated whether cardiac complications in critically ill patients with H7N9 infections differed from those infected with the pandemic H1N1 influenza virus strain. Suspect cases were confirmed by reverse transcription polymerase chain reaction assays with specific confirmation of the pandemic H1N1 strain at the Centers for Disease Control and Prevention. Comparisons were conducted at the individual-level data of critically ill patients hospitalized with H7N9 (n=24) or pandemic H1N1 influenza virus (n=22) infections in Suzhou, China. Changes in cardiac biochemical markers, echocardiography, and electrocardiography during hospitalization in the intensive care unit were considered signs of cardiac complications. The following findings were more common among the H7N9 group relative to the pandemic H1N1 influenza virus group: greater tricuspid regurgitation pressure gradient, sinus tachycardia (heartbeat≥130bpm), ST segment depression, right ventricular dysfunction, and elevated cardiac biochemical markers. Pericardial effusion was more often found among pandemic H1N1 influenza virus patients than in the H7N9 group. In both groups, most of the cardiac complications were detected from day 6 to 14 after the onset of influenza symptoms. Those who developed cardiac complications were especially vulnerable during the first four days after initiation of mechanical ventilation. Cardiac complications were reversible in the vast majority of discharged H7N9 patients. Critically ill hospitalized H7N9 patients experienced a higher rate of cardiac complications than did patients with 2009 pandemic H1N1 influenza virus infections, with the exception of pericardial effusion. This study may help in the
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Miyaki, Koichi; Sakurazawa, Hirofumi; Mikurube, Hajime; Nishizaka, Mika; Ando, Hidehiko; Song, Yixuan; Shimbo, Takuro
2011-01-01
To evaluate the effectiveness of a non-vaccine quarantine measure against pandemic influenza A H1N1 in workplaces. Design was quasi-cluster randomized controlled trial in two sibling companies (Cohort 1 n=6,634, Cohort 2 n=8,500). The follow-up period was from July 1st, 2009 to February 19th, 2010 (233 days). Intervention was voluntary waiting at home on full pay if the family became Influenza like Illness (ILI). The incidences of influenza A H1N1 and those of the subgroups whose families got ILI in both cohorts were compared by a Cox regression model and log-rank test. There were 189 and 270 workers who got H1N1 infection during the follow-up period in each cohort. In this period 317 workers in Cohort 1 were asked to wait at home for several days (100% obeyed). The intervention group (Cohort 1) showed a statistically significant lower risk (p for log-rank test=0.033) compared with the control (Cohort 2), and the hazard ratio of the intervention was 0.799 [0.658-0.970] after adjusting for age, sex, BMI and smoking status. The workers who were asked to wait at home showed H1N1 infection more frequently (49 out of 317) compared with the workers whose family got ILI but were not asked to wait and work regularly (77 out of 990, RR=2.17 [1.48-3.18]). The waiting on full pay policy in the workplace reduced the overall risk of influenza A H1N1 by about 20% in one flu season in Japan. This kind of non-vaccine measure will be a promising option in workplaces to control the next flu pandemic.
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Pandemic (H1N1) 2009 virus infection during pregnancy in South India.
Pramanick, Angsumita; Rathore, Swati; Peter, John V; Moorthy, Mahesh; Lionel, Jessie
2011-04-01
To assess the clinical profile of pregnant/puerperal women from a semi-urban Indian population who were infected with pandemic (H1N1) 2009 virus (P[H1N1]2009v) and to evaluate their outcome. In a cross-sectional study, 566 women (79 pregnant/puerperal, 487 nonpregnant) who presented to a tertiary care hospital with influenza-like illness were tested for P(H1N1)2009v by real-time reverse transcriptase polymerase chain reaction. Outcomes measures were the maternal mortality and the perinatal mortality rate (PMR). Twenty (25%) pregnant/puerperal and 144 (30%) nonpregnant women tested positive for P(H1N1)2009v, with 5 pregnant and 3 postpartum women requiring admission to the intensive care unit (ICU). P(H1N1)2009v-related mortality was higher in pregnant than nonpregnant women (25% versus 8%; P=0.04). In the pregnant/puerperal cohort, factors associated with death included delayed presentation (median 6days versus 1.5days in survivors; P=0.007), need for ICU admission (P=0.004), need for ventilation (P=0.001), and renal failure (P=0.001). The PMR was 55.5/1000 births compared with 33.5/1000 births in the hospital overall during the study period. In a low-income country, P(H1N1)2009v infection in pregnancy is associated with considerable mortality. Delayed presentation to a tertiary care center, lack of awareness, and restricted access to treatment might have contributed to the high mortality. Copyright © 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Zhang, Rongchun; Ramamoorthy, Ayyalusamy, E-mail: ramamoor@umich.edu; Nishiyama, Yusuke
2015-10-28
A proton-detected 3D {sup 1}H/{sup 13}C/{sup 1}H chemical shift correlation experiment is proposed for the assignment of chemical shift resonances, identification of {sup 13}C-{sup 1}H connectivities, and proximities of {sup 13}C-{sup 1}H and {sup 1}H-{sup 1}H nuclei under ultrafast magic-angle-spinning (ultrafast-MAS) conditions. Ultrafast-MAS is used to suppress all anisotropic interactions including {sup 1}H-{sup 1}H dipolar couplings, while the finite-pulse radio frequency driven dipolar recoupling (fp-RFDR) pulse sequence is used to recouple dipolar couplings among protons and the insensitive nuclei enhanced by polarization transfer technique is used to transfer magnetization between heteronuclear spins. The 3D experiment eliminates signals from non-carbon-bonded protonsmore » and non-proton-bonded carbons to enhance spectral resolution. The 2D (F1/F3) {sup 1}H/{sup 1}H and 2D {sup 13}C/{sup 1}H (F2/F3) chemical shift correlation spectra extracted from the 3D spectrum enable the identification of {sup 1}H-{sup 1}H proximity and {sup 13}C-{sup 1}H connectivity. In addition, the 2D (F1/F2) {sup 1}H/{sup 13}C chemical shift correlation spectrum, incorporated with proton magnetization exchange via the fp-RFDR recoupling of {sup 1}H-{sup 1}H dipolar couplings, enables the measurement of proximities between {sup 13}C and even the remote non-carbon-bonded protons. The 3D experiment also gives three-spin proximities of {sup 1}H-{sup 1}H-{sup 13}C chains. Experimental results obtained from powder samples of L-alanine and L-histidine ⋅ H{sub 2}O ⋅ HCl demonstrate the efficiency of the 3D experiment.« less
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MacroH2A1.1 regulates mitochondrial respiration by limiting nuclear NAD+ consumption.
Posavec Marjanović, Melanija; Hurtado-Bagès, Sarah; Lassi, Maximilian; Valero, Vanesa; Malinverni, Roberto; Delage, Hélène; Navarro, Miriam; Corujo, David; Guberovic, Iva; Douet, Julien; Gama-Perez, Pau; Garcia-Roves, Pablo M; Ahel, Ivan; Ladurner, Andreas G; Yanes, Oscar; Bouvet, Philippe; Suelves, Mònica; Teperino, Raffaele; Pospisilik, J Andrew; Buschbeck, Marcus
2017-11-01
Histone variants are structural components of eukaryotic chromatin that can replace replication-coupled histones in the nucleosome. The histone variant macroH2A1.1 contains a macrodomain capable of binding NAD + -derived metabolites. Here we report that macroH2A1.1 is rapidly induced during myogenic differentiation through a switch in alternative splicing, and that myotubes that lack macroH2A1.1 have a defect in mitochondrial respiratory capacity. We found that the metabolite-binding macrodomain was essential for sustained optimal mitochondrial function but dispensable for gene regulation. Through direct binding, macroH2A1.1 inhibits basal poly-ADP ribose polymerase 1 (PARP-1) activity and thus reduces nuclear NAD + consumption. The resultant accumulation of the NAD + precursor NMN allows for maintenance of mitochondrial NAD + pools that are critical for respiration. Our data indicate that macroH2A1.1-containing chromatin regulates mitochondrial respiration by limiting nuclear NAD + consumption and establishing a buffer of NAD + precursors in differentiated cells.
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Sternfeld, F; Guiblin, A R; Jelley, R A; Matassa, V G; Reeve, A J; Hunt, P A; Beer, M S; Heald, A; Stanton, J A; Sohal, B; Watt, A P; Street, L J
1999-02-25
The design, synthesis, and biological evaluation of a novel series of 3-[2-(pyrrolidin-1-yl)ethyl]indoles with excellent selectivity for h5-HT1D (formerly 5-HT1Dalpha) receptors over h5-HT1B (formerly 5-HT1Dbeta) receptors are described. Clinically effective antimigraine drugs such as Sumatriptan show little selectivity between h5-HT1D and h5-HT1B receptors. The differential expression of h5-HT1D and h5-HT1B receptors in neural and vascular tissue prompted an investigation of whether a compound selective for the h5-HT1D subtype would have the same clinical efficacy but with reduced side effects. The pyrrolidine 3b was initially identified as having 9-fold selectivity for h5-HT1D over h5-HT1B receptors. Substitution of the pyrrolidine ring of 3b with methylbenzylamine groups gave compounds with nanomolar affinity for the h5-HT1D receptor and 100-fold selectivity with respect to h5-HT1B receptors. Modification of the indole 5-substituent led to the oxazolidinones 24a,b with up to 163-fold selectivity for the h5-HT1D subtype and improved selectivity over other serotonin receptors. The compounds were shown to be full agonists by measurement of agonist-induced [35S]GTPgammaS binding in CHO cells expressed with h5-HT receptors. This study suggests that the h5-HT1D and h5-HT1B receptors can be differentiated by appropriate substitution of the ligand in the region which binds to the aspartate residue and reveals a large binding pocket in the h5-HT1D receptor domain which is absent for the h5-HT1B receptor. The compounds described herein will be important tools to delineate the role of h5-HT1D receptors in migraine.
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López-Vallejo, Fabian; Fragoso-Serrano, Mabel; Suárez-Ortiz, Gloria Alejandra; Hernández-Rojas, Adriana C; Cerda-García-Rojas, Carlos M; Pereda-Miranda, Rogelio
2011-08-05
A protocol for stereochemical analysis, based on the systematic comparison between theoretical and experimental vicinal (1)H-(1)H NMR coupling constants, was developed and applied to a series of flexible compounds (1-8) derived from the 6-heptenyl-5,6-dihydro-2H-pyran-2-one framework. The method included a broad conformational search, followed by geometry optimization at the DFT B3LYP/DGDZVP level, calculation of the vibrational frequencies, thermochemical parameters, magnetic shielding tensors, and the total NMR spin-spin coupling constants. Three scaling factors, depending on the carbon atom hybridizations, were found for the (1)H-C-C-(1)H vicinal coupling constants: f((sp3)-(sp3)) = 0.910, f((sp3)-(sp2)) = 0.929, and f((sp2)-(sp2))= 0.977. A remarkable correlation between the theoretical (J(pre)) and experimental (1)H-(1)H NMR (J(exp)) coupling constants for spicigerolide (1), a cytotoxic natural product, and some of its synthetic stereoisomers (2-4) demonstrated the predictive value of this approach for the stereochemical assignment of highly flexible compounds containing multiple chiral centers. The stereochemistry of two natural 6-heptenyl-5,6-dihydro-2H-pyran-2-ones (14 and 15) containing diverse functional groups in the heptenyl side chain was also analyzed by application of this combined theoretical and experimental approach, confirming its reliability. Additionally, a geometrical analysis for the conformations of 1-8 revealed that weak hydrogen bonds substantially guide the conformational behavior of the tetraacyloxy-6-heptenyl-2H-pyran-2-ones.
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Regulation of intracellular pH in LLC-PK1 cells by Na+/H+ exchange.
Montrose, M H; Murer, H
1986-01-01
Suspensions of LLC-PK1 cells (a continuous epitheliod cell line with renal characteristics) are examined for mechanisms of intracellular pH regulation using the fluorescent probe BCECF. Initial experiments determine suitable calibration procedures for use of the BCECF fluorescent signal. They also determine that the cell suspension contains cells which (after 4 hr in suspension) have Na+ and K+ gradients comparable to those of cells in monolayer culture. The steady-state intracellular pH (7.05 +/- 0.01, n = 5) of cells which have recovered in (pH 7.4) Na+-containing medium is not affected over several minutes by addition of 100 microM amiloride or removal of extracellular Na+ (Na+o less than 1 mM). In contrast, when the cells recover from an acid load (caused by NH4 preincubation and removal), the recovery is largely Na+ dependent and is sensitive to 100 microM amiloride. These results suggest that with resting pH near neutrality, both Na+o/H+i and Na+i/H+o exchange reactions are functionally inactive (compared to cellular buffering capacity). In contrast, Na+o/H+i exchange is activated by an increased cellular acid load. This activation may be observed directly either as a stimulation of net H+ efflux or net Na+ influx with decreasing intracellular pH. The extrapolation of this latter data suggests a "set point" of Na+/H+ exchange of approximately pH 7.0, consistent with the observed resting intracellular pH of approximately 7.05.
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Parella, Teodor; Espinosa, Juan Félix
2008-05-01
An out-and-stay 2D proton-proton NMR correlation experiment is proposed to detect long-range proton-proton connectivities up to six and seven bonds away. The magnetization flow pathway is based on a consecutive, dual-step J(CH)-transfer mechanism and it allows one to trace out (1)H-(1)H connectivities between protons belonging to different spin systems. This novel experimental scheme will be particularly useful in cases when carbon resonances overlap, providing connectivity information that could not be obtained in a HMBC experiment. The success of the experiment is demonstrated in the structural studies of a wide variety of chemical compounds. 2008 John Wiley & Sons, Ltd.
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NMR resonance splitting of urea in stretched hydrogels: proton exchange and (1)H/(2)H isotopologues.
Kuchel, Philip W; Naumann, Christoph; Chapman, Bogdan E; Shishmarev, Dmitry; Håkansson, Pär; Bacskay, George; Hush, Noel S
2014-10-01
Urea at ∼12 M in concentrated gelatin gel, that was stretched, gave (1)H and (2)H NMR spectral splitting patterns that varied in a predictable way with changes in the relative proportions of (1)H2O and (2)H2O in the medium. This required consideration of the combinatorics of the two amide groups in urea that have a total of four protonation/deuteration sites giving rise to 16 different isotopologues, if all the atoms were separately identifiable. The rate constant that characterized the exchange of the protons with water was estimated by back-transformation analysis of 2D-EXSY spectra. There was no (1)H NMR spectral evidence that the chiral gelatin medium had caused in-equivalence in the protons bonded to each amide nitrogen atom. The spectral splitting patterns in (1)H and (2)H NMR spectra were accounted for by intra-molecular scalar and dipolar interactions, and quadrupolar interactions with the electric field gradients of the gelatin matrix, respectively. Copyright © 2014 Elsevier Inc. All rights reserved.
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Dileep, C S; Abdoh, M M M; Chakravarthy, M P; Mohana, K N; Sridhar, M A
2012-11-01
In the title compound, C(9)H(7)NO, the benzene ring forms a dihedral angle of 3.98 (12)° with the pyrrole ring. In the crystal, N-H⋯O hydrogen bonds links the mol-ecules into chains which run parallel to [02-1].
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Chen, Huazhong; Liu, Shelan; Liu, Jun; Chai, Chengliang; Mao, Haiyan; Yu, Zhao; Tang, Yuming; Zhu, Geqin; Chen, Haixiao X.; Zhu, Chengchu; Shao, Hui; Tan, Shuguang; Wang, Qianli; Bi, Yuhai; Zou, Zhen; Liu, Guang; Jin, Tao; Jiang, Chengyu; Gao, George F.; Peiris, Malik
2016-01-01
A nosocomial cluster induced by co-infections with avian influenza A(H7N9) and A(H1N1)pdm09 (pH1N1) viruses occurred in 2 patients at a hospital in Zhejiang Province, China, in January 2014. The index case-patient was a 57-year-old man with chronic lymphocytic leukemia who had been occupationally exposed to poultry. He had co-infection with H7N9 and pH1N1 viruses. A 71-year-old man with polycythemia vera who was in the same ward as the index case-patient for 6 days acquired infection with H7N9 and pH1N1 viruses. The incubation period for the second case-patient was estimated to be <4 days. Both case-patients died of multiple organ failure. Virus genetic sequences from the 2 case-patients were identical. Of 103 close contacts, none had acute respiratory symptoms; all were negative for H7N9 virus. Serum samples from both case-patients demonstrated strong proinflammatory cytokine secretion but incompetent protective immune responses. These findings strongly suggest limited nosocomial co-transmission of H7N9 and pH1N1 viruses from 1 immunocompromised patient to another. PMID:26982379
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Code of Federal Regulations, 2012 CFR
2012-07-01
... 1H-ben-zo-tri-a-zole, 5-(pen-tyl-oxy)-, sodium and potassium salts. 721.1750 Section 721.1750... 1H-Benzotriazole, 5-(pen-tyl-oxy)- and 1H-ben-zo-tri-a-zole, 5-(pen-tyl-oxy)-, sodium and potassium...-tyl-oxy)-, sodium salt (PMN P-92-35), and 1H-benzotriazole, 5-(pentyloxy)- , potassium salt (PMN P-92...
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Code of Federal Regulations, 2014 CFR
2014-07-01
... 1H-ben-zo-tri-a-zole, 5-(pen-tyl-oxy)-, sodium and potassium salts. 721.1750 Section 721.1750... 1H-Benzotriazole, 5-(pen-tyl-oxy)- and 1H-ben-zo-tri-a-zole, 5-(pen-tyl-oxy)-, sodium and potassium...-tyl-oxy)-, sodium salt (PMN P-92-35), and 1H-benzotriazole, 5-(pentyloxy)- , potassium salt (PMN P-92...
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Code of Federal Regulations, 2013 CFR
2013-07-01
... 1H-ben-zo-tri-a-zole, 5-(pen-tyl-oxy)-, sodium and potassium salts. 721.1750 Section 721.1750... 1H-Benzotriazole, 5-(pen-tyl-oxy)- and 1H-ben-zo-tri-a-zole, 5-(pen-tyl-oxy)-, sodium and potassium...-tyl-oxy)-, sodium salt (PMN P-92-35), and 1H-benzotriazole, 5-(pentyloxy)- , potassium salt (PMN P-92...
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Code of Federal Regulations, 2011 CFR
2011-07-01
... 1H-ben-zo-tri-a-zole, 5-(pen-tyl-oxy)-, sodium and potassium salts. 721.1750 Section 721.1750... 1H-Benzotriazole, 5-(pen-tyl-oxy)- and 1H-ben-zo-tri-a-zole, 5-(pen-tyl-oxy)-, sodium and potassium...-tyl-oxy)-, sodium salt (PMN P-92-35), and 1H-benzotriazole, 5-(pentyloxy)- , potassium salt (PMN P-92...
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Histidine168 is crucial for ΔpH-dependent gating of the human voltage-gated proton channel, hHV1.
Cherny, Vladimir V; Morgan, Deri; Thomas, Sarah; Smith, Susan M E; DeCoursey, Thomas E
2018-05-09
We recently identified a voltage-gated proton channel gene in the snail Helisoma trivolvis , HtH V 1, and determined its electrophysiological properties. Consistent with early studies of proton currents in snail neurons, HtH V 1 opens rapidly, but it unexpectedly exhibits uniquely defective sensitivity to intracellular pH (pH i ). The H + conductance ( g H )- V relationship in the voltage-gated proton channel (H V 1) from other species shifts 40 mV when either pH i or pH o (extracellular pH) is changed by 1 unit. This property, called ΔpH-dependent gating, is crucial to the functions of H V 1 in many species and in numerous human tissues. The HtH V 1 channel exhibits normal pH o dependence but anomalously weak pH i dependence. In this study, we show that a single point mutation in human hH V 1-changing His 168 to Gln 168 , the corresponding residue in HtH V 1-compromises the pH i dependence of gating in the human channel so that it recapitulates the HtH V 1 response. This location was previously identified as a contributor to the rapid gating kinetics of H V 1 in Strongylocentrotus purpuratus His 168 mutation in human H V 1 accelerates activation but accounts for only a fraction of the species difference. H168Q, H168S, or H168T mutants exhibit normal pH o dependence, but changing pH i shifts the g H - V relationship on average by <20 mV/unit. Thus, His 168 is critical to pH i sensing in hH V 1. His 168 , located at the inner end of the pore on the S3 transmembrane helix, is the first residue identified in H V 1 that significantly impairs pH sensing when mutated. Because pH o dependence remains intact, the selective erosion of pH i dependence supports the idea that there are distinct internal and external pH sensors. Although His 168 may itself be a pH i sensor, the converse mutation, Q229H, does not normalize the pH i sensitivity of the HtH V 1 channel. We hypothesize that the imidazole group of His 168 interacts with nearby Phe 165 or other parts of hH V 1 to
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de Jong, Menno D; Hien, Tran Tinh
2006-01-01
Since their reemergence in 2003, highly pathogenic avian influenza A (H5N1) viruses have reached endemic levels among poultry in several southeast Asian countries and have caused a still increasing number of more than 100 reported human infections with high mortality. These developments have ignited global fears of an imminent influenza pandemic. The current knowledge of the virology, clinical spectrum, diagnosis and treatment of human influenza H5N1 virus infections is reviewed herein.
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Interleukin-6 Is a Potential Biomarker for Severe Pandemic H1N1 Influenza A Infection
Paquette, Stéphane G.; Banner, David; Zhao, Zhen; Fang, Yuan; Huang, Stephen S. H.; Leόn, Alberto J.; Ng, Derek C. K.; Almansa, Raquel; Martin-Loeches, Ignacio; Ramirez, Paula; Socias, Lorenzo; Loza, Ana; Blanco, Jesus; Sansonetti, Paola; Rello, Jordi; Andaluz, David; Shum, Bianche; Rubino, Salvatore; de Lejarazu, Raul Ortiz; Tran, Dat; Delogu, Giovanni; Fadda, Giovanni; Krajden, Sigmund; Rubin, Barry B.; Bermejo-Martin, Jesús F.; Kelvin, Alyson A.; Kelvin, David J.
2012-01-01
Pandemic H1N1 influenza A (H1N1pdm) is currently a dominant circulating influenza strain worldwide. Severe cases of H1N1pdm infection are characterized by prolonged activation of the immune response, yet the specific role of inflammatory mediators in disease is poorly understood. The inflammatory cytokine IL-6 has been implicated in both seasonal and severe pandemic H1N1 influenza A (H1N1pdm) infection. Here, we investigated the role of IL-6 in severe H1N1pdm infection. We found IL-6 to be an important feature of the host response in both humans and mice infected with H1N1pdm. Elevated levels of IL-6 were associated with severe disease in patients hospitalized with H1N1pdm infection. Notably, serum IL-6 levels associated strongly with the requirement of critical care admission and were predictive of fatal outcome. In C57BL/6J, BALB/cJ, and B6129SF2/J mice, infection with A/Mexico/4108/2009 (H1N1pdm) consistently triggered severe disease and increased IL-6 levels in both lung and serum. Furthermore, in our lethal C57BL/6J mouse model of H1N1pdm infection, global gene expression analysis indicated a pronounced IL-6 associated inflammatory response. Subsequently, we examined disease and outcome in IL-6 deficient mice infected with H1N1pdm. No significant differences in survival, weight loss, viral load, or pathology were observed between IL-6 deficient and wild-type mice following infection. Taken together, our findings suggest IL-6 may be a potential disease severity biomarker, but may not be a suitable therapeutic target in cases of severe H1N1pdm infection due to our mouse data. PMID:22679491
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Wen, Feng; Yu, Hai; Yang, Fu-Ru; Huang, Meng; Yang, Sheng; Zhou, Yan-Jun; Li, Ze-Jun; Tong, Guang-Zhi
2014-11-01
Swine influenza (SI) is an acute, highly contagious respiratory disease caused by swine influenza A viruses (SwIVs), and it poses a potential global threat to human health. Classical H1N1 (cH1N1) SwIVs are still circulating and remain the predominant subtype in the swine population in China. In this study, a high-growth reassortant virus (GD/PR8) harboring the hemagglutinin (HA) and neuraminidase (NA) genes from a novel cH1N1 isolate in China, A/Swine/Guangdong/1/2011 (GD/11) and six internal genes from the high-growth A/Puerto Rico/8/34(PR8) virus was generated by plasmid-based reverse genetics and tested as a candidate seed virus for the preparation of an inactivated vaccine. The protective efficacy of this vaccine was evaluated in mice and pigs challenged with GD/11 virus. Prime and boost inoculation of GD/PR8 vaccine yielded high-titer serum hemagglutination inhibiting (HI) antibodies and IgG antibodies for GD/11 in both mice and pigs. Complete protection of mice and pigs against cH1N1 SIV challenge was observed, with significantly fewer lung lesions and reduced viral shedding in vaccine-inoculated animals compared with unvaccinated control animals. Our data demonstrated that the GD/PR8 may serve as the seed virus for a promising SwIVs vaccine to protect the swine population.
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Outbreak of H3N2 influenza at a US military base in Djibouti during the H1N1 pandemic of 2009.
Cosby, Michael T; Pimentel, Guillermo; Nevin, Remington L; Fouad Ahmed, Salwa; Klena, John D; Amir, Ehab; Younan, Mary; Browning, Robert; Sebeny, Peter J
2013-01-01
Influenza pandemics have significant operational impact on deployed military personnel working in areas throughout the world. The US Department of Defense global influenza-like illness (ILI) surveillance network serves an important role in establishing baseline trends and can be leveraged to respond to outbreaks of respiratory illness. We identified and characterized an operationally unique outbreak of H3N2 influenza at Camp Lemonnier, Djibouti occurring simultaneously with the H1N1 pandemic of 2009 [A(H1N1)pdm09]. Enhanced surveillance for ILI was conducted at Camp Lemonnier in response to local reports of a possible outbreak during the A(H1N1)pdm09 pandemic. Samples were collected from consenting patients presenting with ILI (utilizing a modified case definition) and who completed a case report form. Samples were cultured and analyzed using standard real-time reverse transcriptase PCR (rt-RT-PCR) methodology and sequenced genetic material was phylogenetically compared to other published strains. rt-RT-PCR and DNA sequencing revealed that 25 (78%) of the 32 clinical samples collected were seasonal H3N2 and only 2 (6%) were A(H1N1)pdm09 influenza. The highest incidence of H3N2 occurred during the month of May and 80% of these were active duty military personnel. Phylogenetic analysis revealed that sequenced H3N2 strains were genetically similar to 2009 strains from the United States of America, Australia, and South east Asia. This outbreak highlights challenges in the investigation of influenza among deployed military populations and corroborates the public health importance of maintaining surveillance systems for ILI that can be enhanced locally when needed.
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Dileep, C. S.; Abdoh, M. M. M.; Chakravarthy, M. P.; Mohana, K. N.; Sridhar, M. A.
2012-01-01
In the title compound, C9H7NO, the benzene ring forms a dihedral angle of 3.98 (12)° with the pyrrole ring. In the crystal, N–H⋯O hydrogen bonds links the molecules into chains which run parallel to [02-1]. PMID:23284457
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Liu, Yun; Li, Hongtao; Xue, Yujia; Zhao, Shuang; Li, Chenxi; Qu, Liandong; Zhang, Yun; Liu, Ming
2017-08-08
H1N1 swine influenza viruses (SIV) are prevalent in pigs globally, and occasionally emerge in humans, which raises concern about their pandemic threats. To stimulate hemagglutination (HA) of A/Swine/Guangdong/LM/2004 (H1N1) (SW/GD/04) antibody response, eukaryotic expression plasmid pCI-neo-HA was constructed and used as an immunogen to prepare monoclonal antibodies (mAbs). Five mAbs (designed 8C4, 8C6, 9D6, 8A4, and 8B1) against HA protein were obtained and characterized. Western blot showed that the 70 kDa HA protein could be detected by all mAbs in MDCK cells infected with SW/GD/04. Three mAbs-8C4, 8C6, and 9D6-have hemagglutination inhibition (HI) and neutralization test (NT) activities, and 8C6 induces the highest HI and NT titers. The protection efficacy of 8C6 was investigated in BALB/c mice challenged with homologous or heterologous strains of the H1 subtype SIV. The results indicate that mAb 8C6 protected the mice from viral infections, especially the homologous strain, which was clearly demonstrated by the body weight changes and reduction of viral load. Thus, our findings document for the first time that mAb 8C6 might be of potential therapeutic value for H1 subtype SIV infection.
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Mancera Gracia, José Carlos; Van den Hoecke, Silvie; Richt, Juergen A; Ma, Wenjun; Saelens, Xavier; Van Reeth, Kristien
2017-05-02
Avian H9N2 and 2009 pandemic H1N1 (pH1N1) influenza viruses can infect pigs and humans, raising the concern that H9N2:pH1N1 reassortant viruses could emerge. Such reassortants demonstrated increased replication and transmissibility in pig, but were still inefficient when compared to pH1N1. Here, we evaluated if a reassortant virus containing the hemagglutinin and neuraminidase of A/quail/Hong Kong/G1/1997 (H9N2) in the A/California/04/2009 (pH1N1) backbone could become better adapted to pigs by serial passaging. The tropism of the original H9N2:pH1N1 (P0) virus was restricted to the nasal mucosa, with no virus detected in the trachea or lungs. Nevertheless, after seven passages the H9N2:pH1N1 (P7) virus replicated in the entire respiratory tract. We also compared the transmissibility of H9N2:pH1N1 (P0), H9N2:pH1N1 (P7) and pH1N1. While only 2/6 direct-contact pigs showed nasal virus excretion of H9N2:pH1N1 (P0) ≥five days, 4/6 direct-contact animals shed the H9N2:pH1N1 (P7). Interestingly, those four animals shed virus with titers similar to those of the pH1N1, which readily transmitted to all six contact animals. The broader tissue tropism and the increased post-transmission replication after seven passages were associated with the HA-D225G substitution. Our data demonstrate that the pH1N1 internal-protein genes together with the serial passages favour H9N2 virus adaptation to pigs.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
T. J. Rodovsky
2006-12-06
This report presents the final hazard categorization (FHC) for the remediation of the 118-D-1, 118-D-2, and 118-D-3 Burial Grounds located within the 100-D/DR Area of the Hanford Site and the 118-H-1, 118-H-2, and 118-H-3 Burial Grounds located within the 100-H Area of the Hanford Site.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
T. J. Rodovsky
2007-04-12
This report presents the final hazard categorization (FHC) for the remediation of the 118-D-1, 118-D-2, and 118-D-3 Burial Grounds located within the 100-D/DR Area of the Hanford Site and the 118-H-1, 118-H-2, and 118-H-3 Burial Grounds located within the 100-H Area of the Hanford Site.
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2013-01-01
Background Influenza virus has antigen drift and antigen shift effect, vaccination with some influenza vaccine might not induce sufficient immunity for host to the threat of other influenza virus strains. S-OIV H1N1 and H5N1 influenza vaccines in single-dose immunization were evaluated in mice for cross protection to the challenge of A/California/7/2009 H1N1 or NIBRG-14 H5N1 virus. Results Both H1N1 and H5N1 induced significant homologous IgG, HAI, and microneutralization antibody responses in the mice, while only vaccines plus adjuvant produced significant heterogeneous IgG and HAI antibody responses. Both alum and MPLA adjuvants significantly reduced the S-OIV H1N1 vaccine dose required to elicit protective HAI antibody titers from 0.05 μg to 0.001 μg. Vaccines alone did not protect mice from challenge with heterogeneous influenza virus, while H5N1 vaccine plus alum and MPLA adjuvants did. Mouse body weight loss was also less significant in the presence of adjuvant than in the vaccine without adjuvant. Furthermore, both H1N1 and H5N1 lung viral titers of immunized mice were significantly reduced post challenge with homologous viruses. Conclusion Only in the presence of MPLA adjuvant could the H5N1 vaccine significantly reduce mouse lung viral titers post H1N1 virus challenge, and not vice versa. MPLA adjuvant induced cross protection with a single dose vaccination to the challenge of heterogeneous influenza virus in mice. Lung viral titer seemed to be a better indicator compared to IgG, neutralization antibody, and HAI titer to predict survival of mice infected with influenza virus. PMID:23517052
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USDA-ARS?s Scientific Manuscript database
This study investigated the pathogenicity and transmissibility of a reverse-genetics derived highly pathogenic avian influenza (HPAI) H5N1 influenza A virus (IAV), A/Iraq/775/06, and a reassortant virus comprised of the HA and NA from A/Iraq/775/06 and the internal genes of a 2009 pandemic H1N1, A/N...
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26 CFR 1.642(h)-1 - Unused loss carryovers on termination of an estate or trust.
Code of Federal Regulations, 2010 CFR
2010-04-01
... estate or trust. 1.642(h)-1 Section 1.642(h)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF....642(h)-1 Unused loss carryovers on termination of an estate or trust. (a) If, on the final termination...(h)(1) to the beneficiaries succeeding to the property of the estate or trust. See § 1.641(b)-3 for...
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The H1N1 pandemic: media frames, stigmatization and coping
2013-01-01
Background Throughout history, people have soothed their fear of disease outbreaks by searching for someone to blame. Such was the case with the April 2009 H1N1 flu outbreak. Mexicans and other Latinos living in the US were quickly stigmatized by non-Latinos as carriers of the virus, partly because of news reports on the outbreak’s alleged origin in Mexican pig farms. Methods In this exploratory study we examined the psychological processes of cue convergence and associative priming, through which many people likely conflated news of the H1N1 outbreak with pre-existing cognitive scripts that blamed Latino immigrants for a variety of social problems. We also used a transactional model of stress and coping to analyze the transcripts from five focus groups, in order to examine the ways in which a diverse collection of New England residents appraised the threat of H1N1, processed information about stereotypes and stigmas, and devised personal strategies to cope with these stressors. Results Twelve themes emerged in the final wave of coding, with most of them appearing at distinctive points in the stress and coping trajectories of focus group participants. Primary and secondary appraisals were mostly stressful or negative, with participants born in the USA reporting more stressful responses than those who were not. Latino participants reported no stressful primary appraisals, but spoke much more often than Whites or Non-Hispanic Blacks about negative secondary appraisals. When interactions between participants dealt with stigmas regarding Latinos and H1N1, Latinos in our focus groups reported using far more negative coping strategies than Whites or Non-Hispanic Blacks. When discussions did not focus on stereotypes or stigmas, Latino participants spoke much more often about positive coping strategies compared to members of these same groups. Conclusions Participants in all five focus groups went through a similar process of stress and coping in response to the threat
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The H1N1 pandemic: media frames, stigmatization and coping.
McCauley, Michael; Minsky, Sara; Viswanath, Kasisomayajula
2013-12-03
Throughout history, people have soothed their fear of disease outbreaks by searching for someone to blame. Such was the case with the April 2009 H1N1 flu outbreak. Mexicans and other Latinos living in the US were quickly stigmatized by non-Latinos as carriers of the virus, partly because of news reports on the outbreak's alleged origin in Mexican pig farms. In this exploratory study we examined the psychological processes of cue convergence and associative priming, through which many people likely conflated news of the H1N1 outbreak with pre-existing cognitive scripts that blamed Latino immigrants for a variety of social problems. We also used a transactional model of stress and coping to analyze the transcripts from five focus groups, in order to examine the ways in which a diverse collection of New England residents appraised the threat of H1N1, processed information about stereotypes and stigmas, and devised personal strategies to cope with these stressors. Twelve themes emerged in the final wave of coding, with most of them appearing at distinctive points in the stress and coping trajectories of focus group participants. Primary and secondary appraisals were mostly stressful or negative, with participants born in the USA reporting more stressful responses than those who were not. Latino participants reported no stressful primary appraisals, but spoke much more often than Whites or Non-Hispanic Blacks about negative secondary appraisals. When interactions between participants dealt with stigmas regarding Latinos and H1N1, Latinos in our focus groups reported using far more negative coping strategies than Whites or Non-Hispanic Blacks. When discussions did not focus on stereotypes or stigmas, Latino participants spoke much more often about positive coping strategies compared to members of these same groups. Participants in all five focus groups went through a similar process of stress and coping in response to the threat of H1N1, though individual responses
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Häring, Marleen; Rodríguez-López, Julio; Grijalvo, Santiago; Tautz, Markus; Eritja, Ramón; Martín, Víctor S; Díaz Díaz, David
2018-02-20
In this work, we demonstrated that the simple substitution of the 1,2,4-triazole moiety in 5-(4H-1,2,4-triazol-4-yl)isophthalic acid (5-TIA) by the 1H-1,2,3-triazol-5-yl unit enables the preparation of a hydrogelator (click-TIA). In sharp contrast to 5-TIA, its isostere click-TIA undergoes self-assembly in water upon sonication, leading to the formation of stable supramolecular viscoelastic hydrogels with a critical gelation concentration of 6 g/L. Hydrogels made of click-TIA as well as hybrid hydrogels made of the mixture click-TIA + 5-TIA (molar ratio 1:0.2) were used to compare different properties of the materials (i.e., rheological properties, thermal properties, mechanical stability, morphology). In terms of toxicity, neither click-TIA nor 5-TIA showed cytotoxic effects on cellular viability of HeLa cells up to 2.3 × 10 -3 g/L when compared to untreated cells incubated with DMSO. Furthermore, the hydrogels were used for the encapsulation and in vitro controlled release of oxytetracycline that followed first-order kinetics. For the hydrogel made of click-TIA, a maximum drug release of ∼60% was reached after ∼8 h within a pH range between 6.5 and 10. However, the release rate was reduced to approximately half of its value at pH values between 1.2 and 5.0, whereas the use of hybrid hydrogels made of click-TIA + 5-TIA allowed to reduce the original rate at pH ≤ 6.5.
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Safety of pandemic H1N1 vaccines in children and adolescents.
Wijnans, Leonoor; de Bie, Sandra; Dieleman, Jeanne; Bonhoeffer, Jan; Sturkenboom, Miriam
2011-10-06
During the 2009 influenza A (H1N1) pandemic several pandemic H1N1 vaccines were licensed using fast track procedures, with relatively limited data on the safety in children and adolescents. Different extensive safety monitoring efforts were put in place to ensure timely detection of adverse events following immunization. These combined efforts have generated large amounts of data on the safety of the different pandemic H1N1 vaccines, also in children and adolescents. In this overview we shortly summarize the safety experience with seasonal influenza vaccines as a background and focus on the clinical and post marketing safety data of the pandemic H1N1 vaccines in children. We identified 25 different clinical studies including 10,505 children and adolescents, both healthy and with underlying medical conditions, between the ages of 6 months and 23 years. In addition, large monitoring efforts have resulted in large amounts of data, with almost 13,000 individual case reports in children and adolescents to the WHO. However, the diversity in methods and data presentation in clinical study publications and publications of spontaneous reports hampered the analysis of safety of the different vaccines. As a result, relatively little has been learned on the comparative safety of these pandemic H1N1 vaccines - particularly in children. It should be a collective effort to give added value to the enormous work going into the individual studies by adhering to available guidelines for the collection, analysis, and presentation of vaccine safety data in clinical studies and to guidance for the clinical investigation of medicinal products in the pediatric population. Importantly the pandemic has brought us the beginning of an infrastructure for collaborative vaccine safety studies in the EU, USA and globally. Copyright © 2011 Elsevier Ltd. All rights reserved.
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Academics and competing interests in H1N1 influenza media reporting.
Mandeville, Kate L; O'Neill, Sam; Brighouse, Andrew; Walker, Alice; Yarrow, Kielan; Chan, Kenneth
2014-03-01
Concerns have been raised over competing interests (CoI) among academics during the 2009 to 2010 A/H1N1 pandemic. Media reporting can influence public anxiety and demand for pharmaceutical products. We assessed CoI of academics providing media commentary during the early stages of the pandemic. We performed a retrospective content analysis of UK newspaper articles on A/H1N1 influenza, examining quoted sources. We noted when academics made a risk assessment of the pandemic and compared this with official estimations. We also looked for promotion or rejection of the use of neuraminidase inhibitors or H1N1-specific vaccine. We independently searched for CoI for each academic. Academics were the second most frequently quoted source after Ministers of Health. Where both academics and official agencies estimated the risk of H1N1, one in two academics assessed the risk as higher than official predictions. For academics with CoI, the odds of a higher risk assessment were 5.8 times greater than those made by academics without CoI (Wald p value=0.009). One in two academics commenting on the use of neuraminidase inhibitors or vaccine had CoI. The odds of CoI in academics promoting the use of neuraminidase inhibitors were 8.4 times greater than for academics not commenting on their use (Fisher's exact p=0.005). There is evidence of CoI among academics providing media commentary during the early H1N1 pandemic. Heightened risk assessments, combined with advocacy for pharmaceutical products to counter this risk, may lead to increased public anxiety and demand. Academics should declare, and journalists report, relevant CoI for media interviews.
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[Pulmonary pathology in fatal human influenza A (H1N1) infection].
Duan, Xue-jing; Li, Yong; Gong, En-cong; Wang, Jue; Lü, Fu-dong; Zhang, He-qiu; Sun, Lin; Yue, Zhu-jun; Song, Chen-chao; Zhang, Shi-Jie; Li, Ning; Dai, Jie
2011-12-01
To study the pulmonary pathology in patients died of fatal human influenza A(H1N1) infection. Eight cases of fatal human influenza A (H1N1) infection, including 2 autopsy cases and 6 paramortem needle puncture biopsies, were enrolled into the study. Histologic examination, immunohistochemitry, flow cytometry and Western blotting were carried out. The major pathologic changes included necrotizing bronchiolitis with surrounding inflammation, diffuse alveolar damage and pulmonary hemorrhage. Influenza viral antigen expression was detected in the lung tissue by Western blotting. Immunohistochemical study demonstrated the presence of nuclear protein and hemagglutinin virus antigens in parts of trachea, bronchial epithelium and glands, alveolar epithelium, macrophages and endothelium. Flow cytometry showed that the apoptotic rate of type II pneumocytes (32.15%, 78.15%) was significantly higher than that of the controls (1.93%, 3.77%). Necrotizing bronchiolitis, diffuse alveolar damage and pulmonary hemorrhage followed by pulmonary fibrosis in late stage are the major pathologic changes in fatal human influenza A (H1N1) infection.
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The safety of the H1N1 influenza A vaccine in egg allergic individuals.
Greenhawt, Matthew J; Chernin, Anna S; Howe, Laura; Li, James T; Sanders, Georgiana
2010-11-01
The safety of H1N1 vaccine is unknown in egg allergic (EA) recipients. To establish the safety of administering H1N1 vaccine and to evaluate the predictability of H1N1 skin testing in EA patients. In a controlled, prospective trial, H1N1 skin testing and vaccination was compared between EA patients (n = 105) and non-EA controls (n = 19). Those with negative H1N1 skin test results received a full H1N1 dose; those with a positive skin test result received a graded challenge (10%, 90%). Booster vaccine, if required, was given as a single dose from a different lot without prior testing. Prick and intradermal test results were positive in 3 (2.4%) of 124 and 41 (33.1%) of 124 study participants, respectively. Forty-one individuals received a 2-step graded vaccine challenge, including 13 of 25 with a history of egg anaphylaxis. No significant allergic reactions resulted from either method of vaccination or from subsequent booster doses. All study participants received the H1N1 vaccine without significant allergic reactions. Skin testing is unnecessary and does not predict vaccine tolerance. All study participants who received a graded challenge tolerated a single dose booster from a different, untested lot, including 7 individuals with a history of egg-induced anaphylaxis. We recommend administration of H1N1 vaccine to EA children without prior skin testing or graded challenge dosing. Copyright © 2010 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
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The hemagglutinin structure of an avian H1N1 influenza A virus
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lin, Tianwei; Wang, Gengyan; Li, Anzhang
2009-09-15
The interaction between hemagglutinin (HA) and receptors is a kernel in the study of evolution and host adaptation of H1N1 influenza A viruses. The notion that the avian HA is associated with preferential specificity for receptors with Sia{alpha}2,3Gal glycosidic linkage over those with Sia{alpha}2,6Gal linkage is not all consistent with the available data on H1N1 viruses. By x-ray crystallography, the HA structure of an avian H1N1 influenza A virus, as well as its complexes with the receptor analogs, was determined. The structures revealed no preferential binding of avian receptor analogs over that of the human analog, suggesting that the HA/receptormore » binding might not be as stringent as is commonly believed in determining the host receptor preference for some subtypes of influenza viruses, such as the H1N1 viruses. The structure also showed difference in glycosylation despite the preservation of related sequences, which may partly contribute to the difference between structures of human and avian origin.« less
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40 CFR 721.8965 - 1H-Pyrole-2, 5-dione, 1-(2,4,6-tribromophenyl)-.
Code of Federal Regulations, 2010 CFR
2010-07-01
... 40 Protection of Environment 30 2010-07-01 2010-07-01 false 1H-Pyrole-2, 5-dione, 1-(2,4,6... Specific Chemical Substances § 721.8965 1H-Pyrole-2, 5-dione, 1-(2,4,6-tribromophenyl)-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as 1H-pyrole...
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Choi, Eun-hye; Song, Min-Suk; Park, Su-Jin; Pascua, Philippe Noriel Q; Baek, Yun Hee; Kwon, Hyeok-il; Kim, Eun-Ha; Kim, Semi; Jang, Hyung-Kwan; Poo, Haryoung; Kim, Chul-Joong; Choi, Young Ki
2015-07-01
An increasing number of outbreaks of avian influenza H5N1 and H9N2 viruses in poultry have caused serious economic losses and raised concerns for human health due to the risk of zoonotic transmission. However, licensed H5N1 and H9N2 vaccines for animals and humans have not been developed. Thus, to develop a dual H5N1 and H9N2 live-attenuated influenza vaccine (LAIV), the HA and NA genes from a virulent mouse-adapted avian H5N2 (A/WB/Korea/ma81/06) virus and a recently isolated chicken H9N2 (A/CK/Korea/116/06) virus, respectively, were introduced into the A/Puerto Rico/8/34 backbone expressing truncated NS1 proteins (NS1-73, NS1-86, NS1-101, NS1-122) but still possessing a full-length NS gene. Two H5N2/NS1-LAIV viruses (H5N2/NS1-86 and H5N2/NS1-101) were highly attenuated compared with the full-length and remaining H5N2/NS-LAIV viruses in a mouse model. Furthermore, viruses containing NS1 modifications were found to induce more IFN-β activation than viruses with full-length NS1 proteins and were correspondingly attenuated in mice. Intranasal vaccination with a single dose (10(4.0) PFU/ml) of these viruses completely protected mice from a lethal challenge with the homologous A/WB/Korea/ma81/06 (H5N2), heterologous highly pathogenic A/EM/Korea/W149/06 (H5N1), and heterosubtypic highly virulent mouse-adapted H9N2 viruses. This study clearly demonstrates that the modified H5N2/NS1-LAIV viruses attenuated through the introduction of mutations in the NS1 coding region display characteristics that are desirable for live attenuated vaccines and hold potential as vaccine candidates for mammalian hosts.
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Ichikawa, T; Kitazaki, T; Matsushita, Y; Yamada, M; Hayashi, R; Yamaguchi, M; Kiyota, Y; Okonogi, K; Itoh, K
2001-09-01
1-[(1R,2R)-2-(2,4-Difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-[4-(1H-1-tetrazolyl)phenyl]-2-imidazolidinone (1: TAK-456) was selected as a candidate for clinical trials, but since its water-solubility was insufficient for an injectable formulation, the quaternary triazolium salts 2 were designed as water-soluble prodrugs. Among the prodrugs prepared, 4-acetoxymethyl-1-[(2R,3R)-2-(2,4-difluorophenyl)-2-hydroxy-3-[2-oxo-3-[4-(1H-1-terazolyl)phenyl]-1-imidazolidinyl]butyl]-1H-1,2,4-triazolium chloride (2a: TAK-457) was selected as an injectable candidate for clinical trials based on the results of evaluations on solubility, stability, hemolytic effect and in vivo antifungal activities.
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H1N1 vaccination in pediatric renal transplant patients.
Kelen, K; Ferenczi, D; Jankovics, I; Varga, M; Molnar, M Z; Sallay, P; Reusz, G; Langer, R M; Pasti, K; Gerlei, Z; Szabo, A J
2011-05-01
Solid organ transplant recipients undergoing immunosuppressive therapy are considered to be at high risk of serious infectious complications. In 2009, a new influenza pandemic caused serious infections and deaths, especially among children and immunocompromised patients. Herein we have reported the safety and efficacy of a single-shot monovalent whole-virus vaccine against H1N1 infection in the pediatric renal transplant population. In November and December 2009, we vaccinated 37 renal transplant children and adolescents and measured their antibody responses. Seroprotection, seroconversion, and seroconversion factors were analyzed at 21 days after vaccination. None of the vaccinated patients experienced vaccine-related side effects. None of the patients had an H1N1 influenza infection after vaccination. All of the patients showed elevations in antibody titer at 21 days after vaccination. In contrast, only 29.72% of the patients achieved a safe seroprotection level and only 18.75% a safe seroconversion rate. More intense immunosuppressive treatment displayed negative effect on seroprotection and seroconversion, and antibody production significantly increased with age. No other factor was observed to influence seroprotection. We recommend vaccination of children and adolescent renal transplant recipients against H1N1 virus. However, a single shot of vaccine may not be sufficient; to achieve seroprotection, a booster vaccination and measurement of the antibody response are needed to assure protection of our patients. Copyright © 2011 Elsevier Inc. All rights reserved.
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Pala, Nicolino; Esposito, Francesca; Rogolino, Dominga; Carcelli, Mauro; Sanna, Vanna; Palomba, Michele; Naesens, Lieve; Corona, Angela; Grandi, Nicole; Tramontano, Enzo; Sechi, Mario
2016-01-01
The HIV-1 ribonuclease H (RNase H) function of the reverse transcriptase (RT) enzyme catalyzes the selective hydrolysis of the RNA strand of the RNA:DNA heteroduplex replication intermediate, and represents a suitable target for drug development. A particularly attractive approach is constituted by the interference with the RNase H metal-dependent catalytic activity, which resides in the active site located at the C-terminus p66 subunit of RT. Herein, we report results of an in-house screening campaign that allowed us to identify 4-[4-(aryl)-1H-1,2,3-triazol-1-yl]benzenesulfonamides, prepared by the “click chemistry” approach, as novel potential HIV-1 RNase H inhibitors. Three compounds (9d, 10c, and 10d) demonstrated a selective inhibitory activity against the HIV-1 RNase H enzyme at micromolar concentrations. Drug-likeness, predicted by the calculation of a panel of physicochemical and ADME properties, putative binding modes for the active compounds, assessed by computational molecular docking, as well as a mechanistic hypothesis for this novel chemotype are reported. PMID:27556447
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Outbreak of H3N2 Influenza at a US Military Base in Djibouti during the H1N1 Pandemic of 2009
Cosby, Michael T.; Pimentel, Guillermo; Nevin, Remington L.; Fouad Ahmed, Salwa; Klena, John D.; Amir, Ehab; Younan, Mary; Browning, Robert; Sebeny, Peter J.
2013-01-01
Background Influenza pandemics have significant operational impact on deployed military personnel working in areas throughout the world. The US Department of Defense global influenza-like illness (ILI) surveillance network serves an important role in establishing baseline trends and can be leveraged to respond to outbreaks of respiratory illness. Objective We identified and characterized an operationally unique outbreak of H3N2 influenza at Camp Lemonnier, Djibouti occurring simultaneously with the H1N1 pandemic of 2009 [A(H1N1)pdm09]. Methods Enhanced surveillance for ILI was conducted at Camp Lemonnier in response to local reports of a possible outbreak during the A(H1N1)pdm09 pandemic. Samples were collected from consenting patients presenting with ILI (utilizing a modified case definition) and who completed a case report form. Samples were cultured and analyzed using standard real-time reverse transcriptase PCR (rt-RT-PCR) methodology and sequenced genetic material was phylogenetically compared to other published strains. Results rt-RT-PCR and DNA sequencing revealed that 25 (78%) of the 32 clinical samples collected were seasonal H3N2 and only 2 (6%) were A(H1N1)pdm09 influenza. The highest incidence of H3N2 occurred during the month of May and 80% of these were active duty military personnel. Phylogenetic analysis revealed that sequenced H3N2 strains were genetically similar to 2009 strains from the United States of America, Australia, and South east Asia. Conclusions This outbreak highlights challenges in the investigation of influenza among deployed military populations and corroborates the public health importance of maintaining surveillance systems for ILI that can be enhanced locally when needed. PMID:24339995
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A Historical Perspective of Influenza A(H1N2) Virus
McVernon, Jodie; Hall, Robert; Leder, Karin
2014-01-01
The emergence and transition to pandemic status of the influenza A(H1N1)A(H1N1)pdm09) virus in 2009 illustrated the potential for previously circulating human viruses to re-emerge in humans and cause a pandemic after decades of circulating among animals. Within a short time of the initial emergence of A(H1N1)pdm09 virus, novel reassortants were isolated from swine. In late 2011, a variant (v) H3N2 subtype was isolated from humans, and by 2012, the number of persons infected began to increase with limited person-to-person transmission. During 2012 in the United States, an A(H1N2)v virus was transmitted to humans from swine. During the same year, Australia recorded its first H1N2 subtype infection among swine. The A(H3N2)v and A(H1N2)v viruses contained the matrix protein from the A(H1N1)pdm09 virus, raising the possibility of increased transmissibility among humans and underscoring the potential for influenza pandemics of novel swine-origin viruses. We report on the differing histories of A(H1N2) viruses among humans and animals. PMID:24377419
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A historical perspective of influenza A(H1N2) virus.
Komadina, Naomi; McVernon, Jodie; Hall, Robert; Leder, Karin
2014-01-01
The emergence and transition to pandemic status of the influenza A(H1N1)A(H1N1)pdm09) virus in 2009 illustrated the potential for previously circulating human viruses to re-emerge in humans and cause a pandemic after decades of circulating among animals. Within a short time of the initial emergence of A(H1N1)pdm09 virus, novel reassortants were isolated from swine. In late 2011, a variant (v) H3N2 subtype was isolated from humans, and by 2012, the number of persons infected began to increase with limited person-to-person transmission. During 2012 in the United States, an A(H1N2)v virus was transmitted to humans from swine. During the same year, Australia recorded its first H1N2 subtype infection among swine. The A(H3N2)v and A(H1N2)v viruses contained the matrix protein from the A(H1N1)pdm09 virus, raising the possibility of increased transmissibility among humans and underscoring the potential for influenza pandemics of novel swine-origin viruses. We report on the differing histories of A(H1N2) viruses among humans and animals.
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Weeks, David E; Niday, Thomas A; Yang, Sang H
2006-10-28
Inelastic scattering matrix elements for the nonadiabatic collision B(2P1/2)+H2(1Sigmag+,j)<-->B(2P3/2)+H2(1Sigmag+,j') are calculated using the time dependent channel packet method (CPM). The calculation employs 1 2A', 2 2A', and 1 2A" adiabatic electronic potential energy surfaces determined by numerical computation at the multireference configuration-interaction level [M. H. Alexander, J. Chem. Phys. 99, 6041 (1993)]. The 1 2A' and 2 2A', adiabatic electronic potential energy surfaces are transformed to yield diabatic electronic potential energy surfaces that, when combined with the total B+H2 rotational kinetic energy, yield a set of effective potential energy surfaces [M. H. Alexander et al., J. Chem. Phys. 103, 7956 (1995)]. Within the framework of the CPM, the number of effective potential energy surfaces used for the scattering matrix calculation is then determined by the size of the angular momentum basis used as a representation. Twenty basis vectors are employed for these calculations, and the corresponding effective potential energy surfaces are identified in the asymptotic limit by the H2 rotor quantum numbers j=0, 2, 4, 6 and B electronic states 2Pja, ja=1/2, 3/2. Scattering matrix elements are obtained from the Fourier transform of the correlation function between channel packets evolving in time on these effective potential energy surfaces. For these calculations the H2 bond length is constrained to a constant value of req=1.402 a.u. and state to state scattering matrix elements corresponding to a total angular momentum of J=1/2 are discussed for j=0<-->j'=0,2,4 and 2P1/2<-->2P1/2, 2P3/2 over a range of total energy between 0.0 and 0.01 a.u.
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Khaliq, Zeeshan; Leijon, Mikael; Belák, Sándor; Komorowski, Jan
2016-07-29
The underlying strategies used by influenza A viruses (IAVs) to adapt to new hosts while crossing the species barrier are complex and yet to be understood completely. Several studies have been published identifying singular genomic signatures that indicate such a host switch. The complexity of the problem suggested that in addition to the singular signatures, there might be a combinatorial use of such genomic features, in nature, defining adaptation to hosts. We used computational rule-based modeling to identify combinatorial sets of interacting amino acid (aa) residues in 12 proteins of IAVs of H1N1 and H3N2 subtypes. We built highly accurate rule-based models for each protein that could differentiate between viral aa sequences coming from avian and human hosts. We found 68 host-specific combinations of aa residues, potentially associated to host adaptation on HA, M1, M2, NP, NS1, NEP, PA, PA-X, PB1 and PB2 proteins of the H1N1 subtype and 24 on M1, M2, NEP, PB1 and PB2 proteins of the H3N2 subtypes. In addition to these combinations, we found 132 novel singular aa signatures distributed among all proteins, including the newly discovered PA-X protein, of both subtypes. We showed that HA, NA, NP, NS1, NEP, PA-X and PA proteins of the H1N1 subtype carry H1N1-specific and HA, NA, PA-X, PA, PB1-F2 and PB1 of the H3N2 subtype carry H3N2-specific signatures. M1, M2, PB1-F2, PB1 and PB2 of H1N1 subtype, in addition to H1N1 signatures, also carry H3N2 signatures. Similarly M1, M2, NP, NS1, NEP and PB2 of H3N2 subtype were shown to carry both H3N2 and H1N1 host-specific signatures (HSSs). To sum it up, we computationally constructed simple IF-THEN rule-based models that could distinguish between aa sequences of avian and human IAVs. From the rules we identified HSSs having a potential to affect the adaptation to specific hosts. The identification of combinatorial HSSs suggests that the process of adaptation of IAVs to a new host is more complex than previously suggested
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Late effects of 1H irradiation on hippocampal physiology
NASA Astrophysics Data System (ADS)
Kiffer, Frederico; Howe, Alexis K.; Carr, Hannah; Wang, Jing; Alexander, Tyler; Anderson, Julie E.; Groves, Thomas; Seawright, John W.; Sridharan, Vijayalakshmi; Carter, Gwendolyn; Boerma, Marjan; Allen, Antiño R.
2018-05-01
NASA's Missions to Mars and beyond will expose flight crews to potentially dangerous levels of charged-particle radiation. Of all charged nuclei, 1H is the most abundant charged particle in both the galactic cosmic ray (GCR) and solar particle event (SPE) spectra. There are currently no functional spacecraft shielding materials that are able to mitigate the charged-particle radiation encountered in space. Recent studies have demonstrated cognitive injuries due to high-dose 1H exposures in rodents. Our study investigated the effects of 1H irradiation on neuronal morphology in the hippocampus of adult male mice. 6-month-old mice received whole-body exposure to 1H at 0.5 and 1 Gy (150 MeV/n; 0.35-0.55 Gy/min) at NASA's Space Radiation Laboratory in Upton, NY. At 9-months post-irradiation, we tested each animal's open-field exploratory performance. After sacrifice, we dissected the brains along the midsagittal plane, and then either fixed or dissected further and snap-froze them. Our data showed that exposure to 0.5 Gy or 1 Gy 1H significantly increased animals' anxiety behavior in open-field testing. Our micromorphometric analyses revealed significant decreases in mushroom spine density and dendrite morphology in the Dentate Gyrus, Cornu Ammonis 3 and 1 of the hippocampus, and lowered expression of synaptic markers. Our data suggest 1H radiation significantly increased exploration anxiety and modulated the dendritic spine and dendrite morphology of hippocampal neurons at a dose of 0.5 or 1 Gy.
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2009 H1N1 influenza and experience in three critical care units.
Teke, Turgut; Coskun, Ramazan; Sungur, Murat; Guven, Muhammed; Bekci, Taha T; Maden, Emin; Alp, Emine; Doganay, Mehmet; Erayman, Ibrahim; Uzun, Kursat
2011-04-07
We describe futures of ICU admission, demographic characteristics, treatment and outcome for critically ill patients with laboratory-confirmed and suspected infection with the H1N1 virus admitted to the three different critical care departments in Turkey. Retrospective study of critically ill patients with 2009 influenza A(H1N1) at ICU. Demographic data, symptoms, comorbid conditions, and clinical outcomes were collected using a case report form. Critical illness occurred in 61 patients admitted to an ICU with confirmed (n=45) or probable and suspected 2009 influenza A(H1N1). Patients were young (mean, 41.5 years), were female (54%). Fifty-six patients, required mechanical ventilation (14 invasive, 27 noninvasive, 15 both) during the course of ICU. On admission, mean APACHE II score was 18.7±6.3 and median PaO(2)/FIO(2) was 127.9±70.4. 31 patients (50.8%) was die. There were no significant differences in baseline PaO(2)/FIO(2 )and ventilation strategies between survivors and nonsurvivors. Patients who survived were more likely to have NIMV use at the time of admission to the ICU. Critical illness from 2009 influenza A(H1N1) in ICU predominantly affects young patients with little major comorbidity and had a high case-fatality rate. NIMV could be used in 2009 influenza A (H1N1) infection-related hypoxemic respiratory failure.
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Oseltamivir-Resistant Influenza Virus A (H1N1), Europe, 2007–08 Season
Lackenby, Angie; Hungnes, Olav; Lina, Bruno; van der Werf, Sylvie; Schweiger, Brunhilde; Opp, Matthias; Paget, John; van de Kassteele, Jan; Hay, Alan; Zambon, Maria
2009-01-01
In Europe, the 2007–08 winter season was dominated by influenza virus A (H1N1) circulation through week 7, followed by influenza B virus from week 8 onward. Oseltamivir-resistant influenza viruses A (H1N1) (ORVs) with H275Y mutation in the neuraminidase emerged independently of drug use. By country, the proportion of ORVs ranged from 0% to 68%, with the highest proportion in Norway. The average weighted prevalence of ORVs across Europe increased gradually over time, from near 0 in week 40 of 2007 to 56% in week 19 of 2008 (mean 20%). Neuraminidase genes of ORVs possessing the H275Y substitution formed a homogeneous subgroup closely related to, but distinguishable from, those of oseltamivir-sensitive influenza viruses A (H1N1). Minor variants of ORVs emerged independently, indicating multiclonal ORVs. Overall, the clinical effect of ORVs in Europe, measured by influenza-like illness or acute respiratory infection, was unremarkable and consistent with normal seasonal activity. PMID:19331731
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Pushko, Peter; Tretyakova, Irina; Hidajat, Rachmat; Zsak, Aniko; Chrzastek, Klaudia; Tumpey, Terrence M.; Kapczynski, Darrell R.
2016-01-01
Avian influenza (AI) viruses circulating in wild birds pose a serious threat to public health. Human and veterinary vaccines against AI subtypes are needed. Here we prepared triple-subtype VLPs that co-localized H5, H7 and H9 antigens derived from H5N1, H7N3 and H9N2 viruses. VLPs also contained influenza N1 neuraminidase and retroviral gag protein. The H5/H7/H9/N1/gag VLPs were prepared using baculovirus expression. Biochemical, functional and antigenic characteristics were determined including hemagglutination and neuraminidase enzyme activities. VLPs were further evaluated in a chicken AI challenge model for safety, immunogenicity and protective efficacy against heterologous AI viruses including H5N2, H7N3 and H9N2 subtypes. All vaccinated birds survived challenges with H5N2 and H7N3 highly pathogenic AI (HPAI) viruses, while all controls died. Immune response was also detectable after challenge with low pathogenicity AI (LPAI) H9N2 virus suggesting that H5/H7/H9/N1/gag VLPs represent a promising approach for the development of broadly protective AI vaccine. PMID:27936463
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Federal Register 2010, 2011, 2012, 2013, 2014
2010-03-12
... of Prevailing Wage Determinations for Use in the H-1B, H-1B1 (Chile/Singapore), H-1C, H- 2B, E-3 (Australia), and Permanent Labor Certification Programs; Prevailing Wage Determinations for Use in the... address where prevailing wage determination requests for H-1B, H-1B1 (Chile/Singapore), H-1C, H- 2B, E-3...
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Childhood narcolepsy with cataplexy: comparison between post-H1N1 vaccination and sporadic cases.
Pizza, Fabio; Peltola, Hanna; Sarkanen, Tomi; Moghadam, Keivan K; Plazzi, Giuseppe; Partinen, Markku
2014-02-01
We aimed to compare post-Pandemrix vaccination (postvaccine) childhood narcolepsy with cataplexy (NC) vs. sporadic pre-H1N1 pandemic (pre-H1N1) cases. Clinical, anthropometric, polysomnographic, and cerebrospinal hypocretin 1 (hcrt-1) measurements were collected together with the video recordings of cataplexy in 27 Finnish patients with NC onset after H1N1 Pandemrix vaccination (mean age, 12±4 years; 52% boys) and 42 Italian NC patients with NC onset before the H1N1 pandemic (mean age, 11±3 years; 48% boys). All subjects carried the HLA-DQB1*0602 allele. Postvaccine subjects were older at NC onset (12±3 vs. 9±3 years; P=.008) and displayed a shorter mean sleep latency in multiple sleep latency tests (MSLT) (2.3±2.2 vs. 3.7±2.9 min; P=.026) compared to pre-H1N1 cases. Anthropometric, clinical (core NC symptoms), hcrt-1 deficiency, and polysomnographic data did not differ among groups, but higher disrupted nocturnal sleep was observed in postvaccine subjects. Comparison of cataplexy features at video assessment showed an overlapping picture with the exception for hyperkinetic movements which appeared to be more evident in pre-H1N1 subjects. The clinical picture of childhood NC was similar in postvaccine and pre-H1N1 children. Copyright © 2013 Elsevier B.V. All rights reserved.
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Cost efficacy of routine screening for diabetes in pregnancy: 1-h versus 2-h specimen.
Weiner, C P; Fraser, M M; Burns, J M; Schnoor, D; Herrig, J; Whitaker, L A
1986-01-01
Undetected gestational diabetes mellitus (GDM) is associated with a two- to fivefold increase in perinatal morbidity and mortality. Widespread screening of the obstetric population (resulting in identification and treatment) should reduce these rates. Seven hundred ninety-eight women were examined during a 13-mo period of universal glucose challenge testing (GCT). A total of 2.8% of the population had an abnormal oral glucose tolerance test (OGTT). Thirty percent of those with an abnormal OGTT were less than 25 yr old. The specificity of a 1-h GCT (50-g carbohydrate load) using a threshold of either 140 or 150 mg/dl was compared with that of a 2-h specimen using a threshold of 118 mg/dl to determine whether the cost of screening could be reduced. One- and 2-h specimens were obtained in 347 of these women. A 34% reduction in the number of follow-up OGTTs required would have been achieved if a 2-h specimen had been used as the index instead of a 1-h specimen (P less than .05). As a result, the (direct and indirect) cost per patient identified with GDM would have declined 23.5%--from $866 to $662. No comment concerning the actual false-negative rate of either the 1- or 2-h GCT can be made because only select women underwent an OGTT. To assess the validity of the 2-h threshold, an OGTT was performed in an additional 190 women if either the 1- or 2-h screen was abnormal. The results were confirmatory: the 2-h screen would have reduced the cost per case identified by 32% in this small group. Screening on the basis of past medical history clearly lacked sensitivity and cost efficacy in comparison with the GCT and should be abandoned as a practice.
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Controls on compound specific 2H/1H of leaf waxes along a North American monsoonal transect
NASA Astrophysics Data System (ADS)
Berke, M. A.; Tipple, B. J.; Hambach, B.; Ehleringer, J. R.
2013-12-01
The use of hydrogen isotope ratios of sedimentary n-alkanes from leaf waxes has become an important method for the reconstruction of paleohydrologic conditions. Ideally, the relationship between lipid 2H/1H values and source water is one-to-one. But the extent to which the 2H/1H values are altered between initial source water and lipid 2H/1H values varies by plant type and environment. Additionally, these variables may be confounded by use of varied source waters by plants in the same ecosystem. Here, we use a transect study across the arid southwestern landscape of the United States, which is heavily influenced by the North American Monsoon, to study the variability in 2H/1H values of leaf waxes in co-occurring plants from Tucson, Arizona to Salt Lake City, Utah. Perennials, including rabbit brush (Chrysothamnus nauseosus), sagebrush (Artemisia tridentata), and gambel oak (Quercus gambelii) and an annual plant, sunflower (Helianthus annuus), were chosen for their wide geographic distribution along the entire transect. Our results indicate that n-alkane distribution for each plant was similar and generally showed no relationship to environmental variables (elevation, mean annual precipitation, latitude, and temperature). However, we find evidence of n-alkane 2H/1H value relating to transect latitude, a relationship that is weaker for all samples combined than the strong individual correlation for each plant species. Further, these 2H/1H values suggest that not all plants in the monsoon region utilize monsoon-delivered precipitation. These results imply an adaptation to discontinuous spatial coverage and amount of monsoonal precipitation and suggest care must be taken when assuming consistent source water for different plants, particularly in regions with highly seasonal precipitation delivery.
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Factors Influencing School Closure and Dismissal Decisions: Influenza A (H1N1), Michigan 2009
ERIC Educational Resources Information Center
Dooyema, Carrie A.; Copeland, Daphne; Sinclair, Julie R.; Shi, Jianrong; Wilkins, Melinda; Wells, Eden; Collins, Jim
2014-01-01
Background: In fall 2009, many US communities experienced school closures during the influenza A H1N1 pandemic (pH1N1) and the state of Michigan reported 567 closures. We conducted an investigation in Michigan to describe pH1N1-related school policies, practices, and identify factors related to school closures. Methods: We distributed an online…
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Influenza A(H1N1)v in Germany: the first 10,000 cases.
Gilsdorf, Andreas; Poggensee, Gabriele
2009-08-27
The analysis of the first 10,000 cases of influenza A(H1N1)v in Germany confirms findings from other sources that the virus is currently mainly causing mild diseases, affecting mostly adolescents and young adults. Overall hospitalisation rate for influenza A(H1N1)v was low (7%). Only 3% of the cases had underlying conditions and pneumonia was rare (0.4%). Both reporting and testing requirements have been adapted recently, taking into consideration the additional information available on influenza A(H1N1)v infections.
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40 CFR Table 1 to Subpart H of... - Batch Processes
Code of Federal Regulations, 2010 CFR
2010-07-01
... 40 Protection of Environment 9 2010-07-01 2010-07-01 false Batch Processes 1 Table 1 to Subpart H... Standards for Organic Hazardous Air Pollutants for Equipment Leaks Pt. 63, Subpt. H, Table 1 Table 1 to Subpart H of Part 63—Batch Processes Monitoring Frequency for Equipment Other than Connectors Operating...
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Hoyer-Fender, S; Grossbach, U
1988-09-01
1. Seven subfractions of histone H1 have been isolated and purified from larvae of Chironomus thummi (Diptera). They have been denominated I-1, II-1, II-2, II-3, III-1, III-2, and III-3, according to the order of migration in two steps of preparative electrophoresis. 2. The amino acid compositions are similar to those of other H1 histones. Subfractions I-1 and II-1 were found to contain one methionine and two tyrosine residues, II-2 contained two methionine and three tyrosine residues, and III-1 one methionine and three tyrosine residues. The other subfractions contained one or two methionine and two or three tyrosine residues. For subfractions I-1 and II-1 a chain length of about 252 amino acids was estimated. 3. Peptide pattern analyses after chemical cleavage at the methionine and tyrosine residues, and enzymatic cleavage with thrombin and chymotrypsin, respectively, showed that all subfractions have different individual primary structures. A comparison of peptide sizes and of the positions in the peptide patterns of epitopes recognized by monoclonal antibodies was made to check whether some of the subfractions could arise by proteolytic degradation of others. This possibility can be excluded for five of the subfractions and is very improbable for the two others. Treatment of C. thummi H1 with alkaline phosphatase did not change the pattern of subfractions, while the phosphorylated subfraction of histone H2A disappeared after this treatment. Most and very probably all subfractions are thus H1 sequence variants. 4. Inbred strains and individual larvae of C. thummi were found to comprise all seven variants. The H1 heterogeneity can therefore not be due to allelic polymorphism. Salivary gland nuclei were found to contain variant I-1 and at least some of the other variants. 5. H1 from Drosophila melanogaster and from calf thymus were used as reference molecules in all cleavage experiments and yielded the peptide patterns expected from the sequence. The comparison
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H1N1 Flu & U.S. Schools: Answers to Frequently Asked Questions
ERIC Educational Resources Information Center
US Department of Education, 2009
2009-01-01
A severe form of influenza known as H1N1, commonly being called swine flu, has health officials around the world concerned. In the United States, the outbreak of H1N1 has prompted school closures and cancellation of school-related events. As the flu spreads, the Department of Education encourages school leaders, parents and students to know how to…
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Obstetricians and the 2009-2010 H1N1 vaccination effort: implications for future pandemics.
Clark, Sarah J; Cowan, Anne E; Wortley, Pascale M
2013-09-01
Our objective was to describe the experiences of obstetricians during the 2009-2010 H1N1 vaccination campaign in order to identify possible improvements for future pandemic situations. We conducted a cross-sectional mail survey of a national random sample of 4,000 obstetricians, fielded in Summer 2010. Survey items included availability, recommendation, and patient acceptance of H1N1 vaccine; prioritization of H1N1 vaccine when supply was limited; problems with H1N1 vaccination; and likelihood of providing vaccine during a future influenza pandemic. Response rate was 66 %. Obstetricians strongly recommended H1N1 vaccine during the second (85 %) and third (86 %) trimesters, and less often during the first trimester (71 %) or the immediate postpartum period (76 %); patient preferences followed a similar pattern. H1N1 vaccine was typically available in outpatient obstetrics clinics (80 %). Overall vaccine supply was a major problem for 30 % of obstetricians, but few rated lack of thimerosal-free vaccine as a major problem (12 %). Over half of obstetricians had no major problems with the H1N1 vaccine campaign. Based on this experience, 74 % would be "very likely" and 12 % "likely" to provide vaccine in the event of a future influenza pandemic. Most obstetricians strongly recommended H1N1 vaccine, had few logistical problems beyond limited vaccine supply, and are willing to vaccinate in a future pandemic. Addressing concerns about first-trimester vaccination, developing guidance for prioritization of vaccine in the event of severe supply constraints, and continued facilitation of the logistical aspects of vaccination should be emphasized in future influenza pandemics.
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Proteomic characterization of the nucleolar linker histone H1 interaction network
Szerlong, Heather J.; Herman, Jacob A.; Krause, Christine M.; DeLuca, Jennifer G.; Skoultchi, Arthur; Winger, Quinton A.; Prenni, Jessica E.; Hansen, Jeffrey C.
2015-01-01
To investigate the relationship between linker histone H1 and protein-protein interactions in the nucleolus, biochemical and proteomics approaches were used to characterize nucleoli purified from cultured human and mouse cells. Mass spectrometry identified 175 proteins in human T-cell nucleolar extracts that bound to sepharose-immobilized H1 in vitro. Gene ontology analysis found significant enrichment for H1 binding proteins with functions related to nucleolar chromatin structure and RNA polymerase I transcription regulation, rRNA processing, and mRNA splicing. Consistent with the affinity binding results, H1 existed in large (400 to >650 kDa) macromolecular complexes in human T cell nucleolar extracts. To complement the biochemical experiments, the effects of in vivo H1 depletion on protein content and structural integrity of the nucleolus were investigated using the H1 triple isoform knock out (H1ΔTKO) mouse embryonic stem cell (mESC) model system. Proteomic profiling of purified wild type mESC nucleoli identified a total of 613 proteins, only ~60% of which were detected in the H1 mutant nucleoli. Within the affected group, spectral counting analysis quantitated 135 specific nucleolar proteins whose levels were significantly altered in H1ΔTKO mESC. Importantly, the functions of the affected proteins in mESC closely overlapped with those of the human T cell nucleolar H1 binding proteins. Immunofluorescence microscopy of intact H1ΔTKO mESC demonstrated both a loss of nucleolar RNA content and altered nucleolar morphology resulting from in vivo H1 depletion. We conclude that H1 organizes and maintains an extensive protein-protein interaction network in the nucleolus required for nucleolar structure and integrity. PMID:25584861
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Histamine response and local cooling in the human skin: involvement of H1- and H2-receptors.
Grossmann, M; Jamieson, M J; Kirch, W
1999-08-01
Histamine may contribute locally to cutaneous blood flow control under normal and pathologic conditions. The objective of this study was to observe the influence of skin temperature on histamine vasodilation, and the roles of H1-and H2-receptors using novel noninvasive methods. Eleven healthy subjects received, double-blind, single doses of the H1-receptor antagonist cetirizine (10 mg), cetirizine (10 mg) plus the H2-receptor antagonist cimetidine (400 mg), or placebo on separate occasions. Histamine was dosed cumulatively by iontophoresis to the forearm skin at 34 degrees C and 14 degrees C. Laser-Doppler flux (LDF) was measured at the same sites using customised probeholder/iontophoretic chambers with Peltier cooling elements. Finger mean arterial pressure (MAP) was measured and cutaneous vascular conductance calculated as LDF/MAP. Histamine vasodilation was reduced in cold skin. Cetirizine shifted the histamine dose-response at both temperatures: statistically significantly at 14 degrees C only. Combined H1- and H2-receptor antagonism shifted the response significantly at both temperatures. H1- and H2-receptors mediate histamine-induced skin vasodilation. The sensitivity of these receptors, particularly the H1- receptor, is attenuated at low skin temperature. Whether the reduced effect in cold skin represents specific receptor or postreceptor desensitization, or nonspecific attenuation of cutaneous vasodilation remains to be elucidated.
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26 CFR 1.338(h)(10)-1 - Deemed asset sale and liquidation.
Code of Federal Regulations, 2011 CFR
2011-04-01
....338-3(c)(1)(i), a section 338(h)(10) election may be made for T where P's acquisition of T stock... P of P's recently purchased target stock. See § 1.338-4(c). (iii) T stock sale. Members of the... to P pursuant to an election under section 338(h)(10), and because paragraph (d)(4) of this section...
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26 CFR 1.338(h)(10)-1 - Deemed asset sale and liquidation.
Code of Federal Regulations, 2010 CFR
2010-04-01
....338-3(c)(1)(i), a section 338(h)(10) election may be made for T where P's acquisition of T stock... P of P's recently purchased target stock. See § 1.338-4(c). (iii) T stock sale. Members of the... to P pursuant to an election under section 338(h)(10), and because paragraph (d)(4) of this section...
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Liver Biochemistry During the Course of Influenza A/H1N1 Infection.
Seretis, Charalampos; Lagoudianakis, Emmanuel; Salemis, Nikolaos; Pappas, Apostolos; Gemenetzis, George; Seretis, Fotios; Gourgiotis, Stavros
2013-06-01
Despite the multi-systemic effects of influenza A/H1N1 virus, the occurrence of hepatic injury during the natural course of the infection remains a matter of debate. We performed a review of the published clinical studies which assess the above mentioned relationship, reviewing the studies published in PubMed database (English literature), using the key words "H1N1", "influenza A" and "liver". We excluded case reports and clinical studies that referred to pediatric and transplanted patients, pregnants and patients with known history of chronic liver diseases. From a total of 96 results, a total of 78 papers met one or more of the exclusion criteria set. Evaluating the remaining 18 published papers, 14 more were excluded as they did not provide any sufficient data, relevant to the subject of our review. Although the analysis of the remaining studies revealed the existence of conflicting results concerning the exact degree and the potential mechanisms of liver injury in H1N1 positive patients, it can be assumed that influenza A/H1N1 virus is -or at least could be- a hepatotropic virus.
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Liver Biochemistry During the Course of Influenza A/H1N1 Infection
Seretis, Charalampos; Lagoudianakis, Emmanuel; Salemis, Nikolaos; Pappas, Apostolos; Gemenetzis, George; Seretis, Fotios; Gourgiotis, Stavros
2013-01-01
Despite the multi-systemic effects of influenza A/H1N1 virus, the occurrence of hepatic injury during the natural course of the infection remains a matter of debate. We performed a review of the published clinical studies which assess the above mentioned relationship, reviewing the studies published in PubMed database (English literature), using the key words “H1N1”, “influenza A” and “liver”. We excluded case reports and clinical studies that referred to pediatric and transplanted patients, pregnants and patients with known history of chronic liver diseases. From a total of 96 results, a total of 78 papers met one or more of the exclusion criteria set. Evaluating the remaining 18 published papers, 14 more were excluded as they did not provide any sufficient data, relevant to the subject of our review. Although the analysis of the remaining studies revealed the existence of conflicting results concerning the exact degree and the potential mechanisms of liver injury in H1N1 positive patients, it can be assumed that influenza A/H1N1 virus is -or at least could be- a hepatotropic virus. PMID:27785237
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Pushko, Peter; Tretyakova, Irina; Hidajat, Rachmat; Zsak, Aniko; Chrzastek, Klaudia; Tumpey, Terrence M; Kapczynski, Darrell R
2017-01-15
Avian influenza (AI) viruses circulating in wild birds pose a serious threat to public health. Human and veterinary vaccines against AI subtypes are needed. Here we prepared triple-subtype VLPs that co-localized H5, H7 and H9 antigens derived from H5N1, H7N3 and H9N2 viruses. VLPs also contained influenza N1 neuraminidase and retroviral gag protein. The H5/H7/H9/N1/gag VLPs were prepared using baculovirus expression. Biochemical, functional and antigenic characteristics were determined including hemagglutination and neuraminidase enzyme activities. VLPs were further evaluated in a chicken AI challenge model for safety, immunogenicity and protective efficacy against heterologous AI viruses including H5N2, H7N3 and H9N2 subtypes. All vaccinated birds survived challenges with H5N2 and H7N3 highly pathogenic AI (HPAI) viruses, while all controls died. Immune response was also detectable after challenge with low pathogenicity AI (LPAI) H9N2 virus suggesting that H5/H7/H9/N1/gag VLPs represent a promising approach for the development of broadly protective AI vaccine. Copyright © 2016. Published by Elsevier Inc.
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Luo, Chang; Liu, Jianxin; Qi, Wenbao; Ren, Xujiao; Lu, Rong; Liao, Ming; Ning, Zhangyong
2018-05-01
H5N1 and H9N2 are the most important causes of avian influenza in China. Chemokines and cytokines play important roles in inflammatory response that clearly differ between H5N1 and H9N2 infection. To investigate whether chemokines and cytokines are differentially regulated following H5N1 and H9N2 AIVs infection, dynamic expression of chemokines and cytokines, including IL8L1, IL8L2, CX3CL1, CCL5, CCL20, K203, SCYA4, XLC1, CCLi10, CCL19, IFN-α, IFN-β, IL-1β, IL-6 and TNF-α, were analyzed by real-time quantitative RT-PCR in DF-1 cells. It was found that IL8L1, IL8L2, CX3CL1, CCL5, CCL20, K203, SCYA4, IFN-α, IFN-β, IL-1β, IL-6 and TNF-α increased significantly after induction of H5N1 or H9N2 AIV infection, whereas no expression of XCL1, CCLi10 or CCL19 was detected. H9N2 AIV infection was associated with much stronger chemokine responses than infection with H5N1, whereas the cytokines showed opposite results. It was found that K203 is a constant chemotactic factor independent of subtype of AIVs and infectious dose, CCL20 and IL-1β are constant regardless of the infectious dose but depend on the subtype of AIV, chemotactic factors IL8L1, IL8L2 and CCL5 are dependent both on subtype of AIVs and infectious dose, and K203, CX3CL1, SCYA4, CCL20, IFN-α, IL-1β and TNF-α are specific to responses to H5N1 AIV infection whereas K203, CCL20, IFN-β, IL-1β and IL-6 are specific to H9N2 infection. These results provide basic data for explaining differences in inflammation and phenotypes of histopathological changes caused by H5N1 and H9N2 and add new information on the roles of chemokines and cytokines in virulence of AIVs. © 2018 The Societies and John Wiley & Sons Australia, Ltd.
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Synthesis, characterization and theoretical studies of 5-(benzylthio)-1-cylopentyl-1H-tetrazole
NASA Astrophysics Data System (ADS)
Saglam, S.; Disli, A.; Erdogdu, Y.; Marchewka, M. K.; Kanagathara, N.; Bay, B.; Güllüoğlu, M. T.
2015-01-01
In this study, 5-(benzylthio)-1-cylopentyl-1H-tetrazole (5B1C1HT) have been synthesized. Boiling points of the obtained compound have been determined and it has been characterized by FT-IR, 1H NMR, 13C-APT and LC-MS spectroscopy techniques. The FT-IR, 1H NMR and 13C-APT spectral measurements of the 5B1C1HT compound and complete assignment of the vibrational bands observed in spectra has been discussed. The spectra were interpreted with the aid of normal coordinate analysis following full structure optimization and force field calculations based on Density Functional Theory (DFT) at 6-311++G**, cc-pVDZ and cc-pVTZ basis sets. The optimized geometry with 6-311++G** basis sets were used to determine the total energy distribution, harmonic vibrational frequencies, IR intensities.
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Assessment of H1N1 questions and answers posted on the Web.
Kim, Sujin; Pinkerton, Thomas; Ganesh, Nithya
2012-04-01
A novel strain of human influenza A (H1N1) posed a serious pandemic threat worldwide during 2009. The public's fear of pandemic flu often raises awareness and discussion of such events. The goal of this study was to characterize major topical matters of H1N1 questions and answers raised by the online question and answer community Yahoo! Answers during H1N1 outbreak. The study used Text Mining for SPSS Clementine (v.12; SPSS Inc., Chicago, IL) to extract the major concepts of the collected Yahoo! questions and answers. The original collections were retrieved using "H1N1" in search, keyword and then filtered for only "resolved questions" in the "health" category submitted within the past 2 years. The most frequently formed categories were as follows: general health (health, disease, medicine, investigation, evidence, problem), flu-specific terms (H1N1, swine, shot, fever, cold, infective, throat), and nonmedical issues (feel, North American, people, child, nations, government, states, help, doubt, emotion). The study found that URL data are fairly predictable: those providing answers are divided between ones dedicated to giving trustworthy information-from news organizations and the government, for instance-and those looking to espouse a more biased point of view. Critical evaluation of online sources should be taught to select the quality of information and improve health literacy. The challenges of pandemic prevention and control, therefore, demand both e-surveillance and better informed "Netizens." Copyright © 2012 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.
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GaAs micromachining in the 1 H2SO4:1 H2O2:8 H2O system. From anisotropy to simulation
NASA Astrophysics Data System (ADS)
Tellier, C. R.
2011-02-01
The bulk micromachining on (010), (110) and (111)A GaAs substrates in the 1 H2SO4:1 H2O2:8 H2O system is investigated. Focus is placed on anisotropy of 3D etching shapes with a special emphasis on convex and concave undercuts which are of prime importance in the wet micromachining of mechanical structures. Etched structures exhibit curved contours and more and less rounded sidewalls showing that the anisotropy is of type 2. This anisotropy can be conveniently described by a kinematic and tensorial model. Hence, a database composed of dissolution constants is further determined from experiments. A self-elaborated simulator which works with the proposed database is used to derive theoretical 3D shapes. Simulated shapes agree well with observed shapes of microstructures. The successful simulations open up two important applications for MEMS: CAD of mask patterns and meshing of simulated shapes for FEM simulation tools.
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Novel triple-reassortant H1N1 swine influenza viruses in pigs in Tianjin, Northern China.
Sun, Ying-Feng; Wang, Xiu-Hui; Li, Xiu-Li; Zhang, Li; Li, Hai-Hua; Lu, Chao; Yang, Chun-Lei; Feng, Jing; Han, Wei; Ren, Wei-Ke; Tian, Xiang-Xue; Tong, Guang-Zhi; Wen, Feng; Li, Ze-Jun; Gong, Xiao-Qian; Liu, Xiao-Min; Ruan, Bao-Yang; Yan, Ming-Hua; Yu, Hai
2016-02-01
Pigs are susceptible to both human and avian influenza viruses and therefore have been proposed to be mixing vessels for the generation of pandemic influenza viruses through reassortment. In this study, for the first time, we report the isolation and genetic analyses of three novel triple-reassortant H1N1 swine influenza viruses from pigs in Tianjin, Northern China. Phylogenetic analysis showed that these novel viruses contained genes from the 2009 pandemic H1N1 (PB2, PB1, PA and NP), Eurasian swine (HA, NA and M) and triple-reassortant swine (NS) lineages. This indicated that the reassortment among the 2009 pandemic H1N1, Eurasian swine and triple-reassortant swine influenza viruses had taken place in pigs in Tianjin and resulted in the generation of new viruses. Furthermore, three human-like H1N1, two classical swine H1N1 and two Eurasian swine H1N1 viruses were also isolated during the swine influenza virus surveillance from 2009 to 2013, which indicated that multiple genetic lineages of swine H1N1 viruses were co-circulating in the swine population in Tianjin, China. The emergence of novel triple-reassortant H1N1 swine influenza viruses may be a potential threat to human health and emphasizes the importance of further continuous surveillance. Copyright © 2015 Elsevier B.V. All rights reserved.
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Surveillance for influenza virus subtypes H1, H2 and H3 among wild birds in Ukraine in 2006-2012
USDA-ARS?s Scientific Manuscript database
Background: Influenza is one of the most important and unpredictable diseases of humans, other mammals and birds. Influenza virus of H1, H2, and H3 subtypes circulate in humans and cause seasonal influenza. Similar subtypes are also circulating in the natural reservoir, wild aquatic birds, and und...
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HIST1H1C Regulates Interferon-β and Inhibits Influenza Virus Replication by Interacting with IRF3
Liu, Xiaokun; Yang, Cha; Hu, Yong; Lei, Erming; Lin, Xian; Zhao, Lianzhong; Zou, Zhong; Zhang, Anding; Zhou, Hongbo; Chen, Huanchun; Qian, Ping; Jin, Meilin
2017-01-01
Influenza virus NS2 is well known for its role in viral ribonucleoprotein nuclear export; however, its function has not been fully understood. A recent study showed that NS2 might interact with HIST1H1C (H1C, H1.2). Histones have been found to affect influenza virus replication, such as the H2A, H2B, H3, and H4, but H1 has not been detected. Here, we found that H1C interacts with NS2 via its C-terminal in the nucleus and that H1C affects influenza virus replication. The H1N1 influenza virus replicates better in H1C knockout A549 cells compared to wild-type A549 cells, primarily because of the regulation of H1C on interferon-β (IFN-β). Further studies showed that the H1C phosphorylation mutant (T146A) decreases IFN-β, while H1C methylation mutants (K34A, K187A) increases IFN-β by releasing the nucleosome and promoting IRF3 binding to the IFN-β promoter. Interestingly, NS2 interacts with H1C, which reduces H1C–IRF3 interaction and results in the inhibition of IFN-β enhanced by H1C. In summary, our study reveals a novel function of H1C to regulate IFN-β and uncovers an underlying mechanism, which suggests H1C plays a role in epigenetic regulation. Moreover, our results suggest a novel mechanism for the influenza virus to antagonize the innate immune response by NS2. PMID:28392790
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26 CFR 1.501(h)-2 - Electing the expenditure test.
Code of Federal Regulations, 2010 CFR
2010-04-01
... 26 Internal Revenue 7 2010-04-01 2010-04-01 true Electing the expenditure test. 1.501(h)-2 Section 1.501(h)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Exempt Organizations § 1.501(h)-2 Electing the expenditure...
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Pandemic and post-pandemic Influenza A (H1N1) infection in critically ill patients
2011-01-01
Background There is a vast amount of information published regarding the impact of 2009 pandemic Influenza A (pH1N1) virus infection. However, a comparison of risk factors and outcome during the 2010-2011 post-pandemic period has not been described. Methods A prospective, observational, multi-center study was carried out to evaluate the clinical characteristics and demographics of patients with positive RT-PCR for H1N1 admitted to 148 Spanish intensive care units (ICUs). Data were obtained from the 2009 pandemic and compared to the 2010-2011 post-pandemic period. Results Nine hundred and ninety-seven patients with confirmed An/H1N1 infection were included. Six hundred and forty-eight patients affected by 2009 (pH1N1) virus infection and 349 patients affected by the post-pandemic Influenza (H1N1)v infection period were analyzed. Patients during the post-pandemic period were older, had more chronic comorbid conditions and presented with higher severity scores (Acute Physiology And Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA)) on ICU admission. Patients from the post-pandemic Influenza (H1N1)v infection period received empiric antiviral treatment less frequently and with delayed administration. Mortality was significantly higher in the post-pandemic period. Multivariate analysis confirmed that haematological disease, invasive mechanical ventilation and continuous renal replacement therapy were factors independently associated with worse outcome in the two periods. HIV was the only new variable independently associated with higher ICU mortality during the post-pandemic Influenza (H1N1)v infection period. Conclusion Patients from the post-pandemic Influenza (H1N1)v infection period had an unexpectedly higher mortality rate and showed a trend towards affecting a more vulnerable population, in keeping with more typical seasonal viral infection. PMID:22126648
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Pandemic and post-pandemic influenza A (H1N1) infection in critically ill patients.
Martin-Loeches, Ignacio; Díaz, Emili; Vidaur, Loreto; Torres, Antoni; Laborda, Cesar; Granada, Rosa; Bonastre, Juan; Martín, Mar; Insausti, Josu; Arenzana, Angel; Guerrero, Jose Eugenio; Navarrete, Ines; Bermejo-Martin, Jesus; Suarez, David; Rodriguez, Alejandro
2011-01-01
There is a vast amount of information published regarding the impact of 2009 pandemic Influenza A (pH1N1) virus infection. However, a comparison of risk factors and outcome during the 2010-2011 post-pandemic period has not been described. A prospective, observational, multi-center study was carried out to evaluate the clinical characteristics and demographics of patients with positive RT-PCR for H1N1 admitted to 148 Spanish intensive care units (ICUs). Data were obtained from the 2009 pandemic and compared to the 2010-2011 post-pandemic period. Nine hundred and ninety-seven patients with confirmed An/H1N1 infection were included. Six hundred and forty-eight patients affected by 2009 (pH1N1) virus infection and 349 patients affected by the post-pandemic Influenza (H1N1)v infection period were analyzed. Patients during the post-pandemic period were older, had more chronic comorbid conditions and presented with higher severity scores (Acute Physiology And Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA)) on ICU admission. Patients from the post-pandemic Influenza (H1N1)v infection period received empiric antiviral treatment less frequently and with delayed administration. Mortality was significantly higher in the post-pandemic period. Multivariate analysis confirmed that haematological disease, invasive mechanical ventilation and continuous renal replacement therapy were factors independently associated with worse outcome in the two periods. HIV was the only new variable independently associated with higher ICU mortality during the post-pandemic Influenza (H1N1)v infection period. Patients from the post-pandemic Influenza (H1N1)v infection period had an unexpectedly higher mortality rate and showed a trend towards affecting a more vulnerable population, in keeping with more typical seasonal viral infection.
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Pandemic H1N1 2009 ('swine flu'): diagnostic and other challenges.
Burkardt, Hans-Joachim
2011-01-01
Pandemic H1N1 2009 ('swine flu') virus was 'the virus of the year 2009' because it affected the lives of many people in this year. H1N1 was first described in California in April 2009 and spread very rapidly all over the globe. The fast global penetration of the swine flu caused the WHO in Geneva to call the infection with H1N1 a new pandemic with a rapid escalation of the different pandemic phases that ended on 11 June 2009, with the declaration of phase 6 (full-blown pandemic). This had far-reaching consequences for the local health authorities in the different affected countries and created awareness in the public and fear in the experts and even more so in many lay people. The consequences were: setting up reliable diagnostic tests as soon as possible; enhanced production, distribution and stock creation of the few drugs that were available to treat newly infected persons; and development, production, distribution and stock creation of new and appropriate anti-H1N1 swine flu vaccines. This all resulted in enormous costs in the local healthcare systems and also required smart and diligent logistics, because demand for all this was, in most cases, much higher than availability. Fortunately, the pandemic ended quite quickly (there was no 'second wave' as had been anticipated by some experts) and the death toll was moderate, compared with other influenza pandemic in the past and even to the regular annual appearance of the seasonal flu. This favorable outcome, however, provoked some harsh criticism that the WHO and healthcare systems in general had over-reacted and by doing so, a lot of money was thrown out of the window. This article describes the history of the H1N1 pandemic, the diagnostic challenges and resolutions, touches on treatment and vaccination very briefly and also comments on the criticism and arguments that came up immediately at the end and following the termination of the pandemic situation.
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The Genomic Contributions of Avian H1N1 Influenza A Viruses to the Evolution of Mammalian Strains
Wu, Gang; Zhang, Jinghui; Webster, Robert G.
2015-01-01
Among the influenza A viruses (IAVs) in wild aquatic birds, only H1, H2, and H3 subtypes have caused epidemics in humans. H1N1 viruses of avian origin have also caused 3 of 5 pandemics. To understand the reappearance of H1N1 in the context of pandemic emergence, we investigated whether avian H1N1 IAVs have contributed to the evolution of human, swine, and 2009 pandemic H1N1 IAVs. On the basis of phylogenetic analysis, we concluded that the polymerase gene segments (especially PB2 and PA) circulating in North American avian H1N1 IAVs have been reintroduced to swine multiple times, resulting in different lineages that led to the emergence of the 2009 pandemic H1N1 IAVs. Moreover, the similar topologies of hemagglutinin and nucleoprotein and neuraminidase and matrix gene segments suggest that each surface glycoprotein coevolved with an internal gene segment within the H1N1 subtype. The genotype of avian H1N1 IAVs of Charadriiformes origin isolated in 2009 differs from that of avian H1N1 IAVs of Anseriformes origin. When the antigenic sites in the hemagglutinin of all 31 North American avian H1N1 IAVs were considered, 60%-80% of the amino acids at the antigenic sites were identical to those in 1918 and/or 2009 pandemic H1N1 viruses. Thus, although the pathogenicity of avian H1N1 IAVs could not be inferred from the phylogeny due to the small dataset, the evolutionary process within the H1N1 IAV subtype suggests that the circulation of H1N1 IAVs in wild birds poses a continuous threat for future influenza pandemics in humans. PMID:26208281
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Moreno, Estefanía; Moreno-Delgado, David; Navarro, Gemma; Hoffmann, Hanne M.; Fuentes, Silvia; Rosell-Vilar, Santi; Gasperini, Paola; Rodríguez-Ruiz, Mar; Medrano, Mireia; Mallol, Josefa; Cortés, Antoni; Casadó, Vicent; Lluís, Carme; Ferré, Sergi; Ortiz, Jordi; Canela, Enric
2014-01-01
The general effects of cocaine are not well understood at the molecular level. What is known is that the dopamine D1 receptor plays an important role. Here we show that a key mechanism may be cocaine's blockade of the histamine H3 receptor-mediated inhibition of D1 receptor function. This blockade requires the σ1 receptor and occurs upon cocaine binding to σ1-D1-H3 receptor complexes. The cocaine-mediated disruption leaves an uninhibited D1 receptor that activates Gs, freely recruits β-arrestin, increases p-ERK 1/2 levels, and induces cell death when over activated. Using in vitro assays with transfected cells and in ex vivo experiments using both rats acutely treated or self-administered with cocaine along with mice depleted of σ1 receptor, we show that blockade of σ1 receptor by an antagonist restores the protective H3 receptor-mediated brake on D1 receptor signaling and prevents the cell death from elevated D1 receptor signaling. These findings suggest that a combination therapy of σ1R antagonists with H3 receptor agonists could serve to reduce some effects of cocaine. PMID:24599455
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Li, Zhuo; Mooney, Alaina J.; Gabbard, Jon D.; Gao, Xiudan; Xu, Pei; Place, Ryan J.; Hogan, Robert J.; Tompkins, S. Mark
2013-01-01
A safe and effective vaccine is the best way to prevent large-scale highly pathogenic avian influenza virus (HPAI) H5N1 outbreaks in the human population. The current FDA-approved H5N1 vaccine has serious limitations. A more efficacious H5N1 vaccine is urgently needed. Parainfluenza virus 5 (PIV5), a paramyxovirus, is not known to cause any illness in humans. PIV5 is an attractive vaccine vector. In our studies, a single dose of a live recombinant PIV5 expressing a hemagglutinin (HA) gene of H5N1 (rPIV5-H5) from the H5N1 subtype provided sterilizing immunity against lethal doses of HPAI H5N1 infection in mice. Furthermore, we have examined the effect of insertion of H5N1 HA at different locations within the PIV5 genome on the efficacy of a PIV5-based vaccine. Interestingly, insertion of H5N1 HA between the leader sequence, the de facto promoter of PIV5, and the first viral gene, nucleoprotein (NP), did not lead to a viable virus. Insertion of H5N1 HA between NP and the next gene, V/phosphorprotein (V/P), led to a virus that was defective in growth. We have found that insertion of H5N1 HA at the junction between the small hydrophobic (SH) gene and the hemagglutinin-neuraminidase (HN) gene gave the best immunity against HPAI H5N1 challenge: a dose as low as 1,000 PFU was sufficient to protect against lethal HPAI H5N1 challenge in mice. The work suggests that recombinant PIV5 expressing H5N1 HA has great potential as an HPAI H5N1 vaccine. PMID:23077314
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26 CFR 301.6223(h)-1 - Responsibilities of pass-thru partner.
Code of Federal Regulations, 2010 CFR
2010-04-01
...(h)-1 Section 301.6223(h)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) PROCEDURE AND ADMINISTRATION PROCEDURE AND ADMINISTRATION Assessment In General § 301.6223(h)-1... October 4, 2001. For years beginning prior to October 4, 2001, see § 301.6223(h)-1T contained in 26 CFR...
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Respiratory failure presenting in H1N1 influenza with Legionnaires disease: two case reports
2011-01-01
Introduction Media sensationalism on the H1N1 outbreak may have influenced decisional processes and clinical diagnosis. Case Presentation We report two cases of patients who presented in 2009 with coexisting H1N1 virus and Legionella infections: a 69-year-old Caucasian man and a 71-year-old Caucasian woman. In our cases all the signs and symptoms, including vomiting, progressive respiratory disease leading to respiratory failure, refractory hypoxemia, leukopenia, lymphopenia, thrombocytopenia, and elevated levels of creatine kinase and hepatic aminotransferases, were consistent with critical illness due to 2009 H1N1 virus infection. Other infectious disorders may mimic H1N1 viral infection especially Legionnaires' disease. Because the swine flu H1N1 pandemic occurred in Autumn in Italy, Legionnaires disease was to be highly suspected since the peak incidence usually occurs in early fall. We do think that our immediate suspicion of Legionella infection based on clinical history and X-ray abnormalities was fundamental for a successful resolution. Conclusion Our two case reports suggest that patients with H1N1 should be screened for Legionella, which is not currently common practice. This is particularly important since the signs and symptoms of both infections are similar. PMID:22018019
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Mo, Jiayu; Müller, Thomas; Oliveira, João C A; Ackermann, Lutz
2018-06-25
C-H activation bears great potential for enabling sustainable molecular syntheses in a step- and atom-economical manner, with major advances having been realized with precious 4d and 5d transition metals. In contrast, we employed earth abundant, nontoxic iron catalysts for versatile allene annulations through a unique C-H/N-H/C-O/C-H functionalization sequence. The powerful iron catalysis occurred under external-oxidant-free conditions even at room temperature, while detailed mechanistic studies revealed an unprecedented 1,4-iron migration regime for facile C-H activations. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Histamine and H1-antihistamines: celebrating a century of progress.
Simons, F Estelle R; Simons, Keith J
2011-12-01
In this review we celebrate a century of progress since the initial description of the physiologic and pathologic roles of histamine and 70 years of progress since the introduction of H(1)-antihistamines for clinical use. We discuss histamine and clinically relevant information about the molecular mechanisms of action of H(1)-antihistamines as inverse agonists (not antagonists or blockers) with immunoregulatory effects. Unlike first (old)-generation H(1)-antihistamines introduced from 1942 to the mid-1980s, most of the second (new)-generation H(1)-antihistamines introduced subsequently have been investigated extensively with regard to clinical pharmacology, efficacy, and safety; moreover, they are relatively free from adverse effects and not causally linked with fatalities after overdose. Important advances include improved nasal and ophthalmic H(1)-antihistamines with rapid onset of action (in minutes) for allergic rhinitis and allergic conjunctivitis treatment, respectively, and effective and safe use of high (up to 4-fold) doses of oral second-generation H(1)-antihistamines for chronic urticaria treatment. New H(1)-antihistamines introduced for clinical use include oral formulations (bilastine and rupatadine), and ophthalmic formulations (alcaftadine and bepotastine). Clinical studies of H(3)-antihistamines with enhanced decongestant effects have been conducted in patients with allergic rhinitis. Additional novel compounds being studied include H(4)-antihistamines with anti-inflammatory effects in allergic rhinitis, atopic dermatitis, and other diseases. Antihistamines have a storied past and a promising future. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
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Khanage, Shantaram Gajanan; Mohite, Popat Baban; Pandhare, Ramdas Bhanudas; Raju, S. Appala
2014-01-01
Purpose: An efficient technique has been developed for microwave assisted synthesis of 1-[5-(substituted aryl)-1H-pyrazol-3-yl]-3,5-diphenyl-1H-1,2,4-triazole as antinociceptive and antimicrobial agents. Methods: The desired compounds (S1-S10) were synthesized by the microwave irradiation via cyclization of formerly synthesized chalcones of 3,5-diphenyl-1H-1,2,4-triazole and hydrazine hydrate in mild acidic condition. All newly synthesized compounds were subjected to study their antinociceptive and antimicrobial activity. The analgesic potential of compounds was tested by acetic acid induced writhing response and hot plate method. The MIC values for antimicrobial activity were premeditated by liquid broth method. Results: The compounds S1, S2, S4, S6 and S10 were found to be excellent peripherally acting analgesic agents when tested on mice by acetic acid induced writhing method and compounds S3, S6 and S1 at dose level of 100 mg/kg were exhibited superior centrally acting antinociceptive activity when tested by Eddy’s hot plate method. In antimicrobial activity compound S10 found to be broad spectrum antibacterial agent at MIC value of 15.62 µg/ml and compound S6 was exhibited antifungal potential at 15.62 µg/mL on both fungal strains. Conclusion: Some novel pyrazoles clubbed with 1,2,4-triazole derivatives were synthesized and evaluated as possible antimicrobial, centrally and peripherally acting analgesics. PMID:24511473
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NASA Astrophysics Data System (ADS)
Armstrong, Geoffrey S.; Bendiak, Brad
2006-07-01
Four-dimensional nuclear magnetic resonance spectroscopy of oligosaccharides that correlates 1H-1H ROESY cross peaks to two additional 13C frequency dimensions is reported. The 13C frequencies were introduced by derivatization of all free hydroxyl groups with doubly 13C-labeled acetyl isotags. Pulse sequences were optimized for processing with the filter diagonalization method. The extensive overlap typically observed in 2D ROESY 1H-1H planes was alleviated by resolution of ROESY cross peaks in the two added dimensions associated with the carbon frequencies of the isotags. This enabled the interresidue 1H-1H ROESY cross peaks to be unambiguously assigned hence spatially proximate sugar spin systems across glycosidic bonds could be effectively ascertained. An experiment that selectively amplifies interresidue ROESY 1H-1H cross peaks is also reported. It moves the magnetization of an intraresidue proton normally correlated to a sugar H-1 signal orthogonally along the z axis prior to a Tr-ROESY mixing sequence. This virtually eliminates the incoherent intraresidue ROESY transfer, suppresses coherent TOCSY transfer, and markedly enhances the intensity of interresidue ROESY cross peaks.
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Armstrong, Geoffrey S; Bendiak, Brad
2006-07-01
Four-dimensional nuclear magnetic resonance spectroscopy of oligosaccharides that correlates 1H-1H ROESY cross peaks to two additional 13C frequency dimensions is reported. The 13C frequencies were introduced by derivatization of all free hydroxyl groups with doubly 13C-labeled acetyl isotags. Pulse sequences were optimized for processing with the filter diagonalization method. The extensive overlap typically observed in 2D ROESY 1H-1H planes was alleviated by resolution of ROESY cross peaks in the two added dimensions associated with the carbon frequencies of the isotags. This enabled the interresidue 1H-1H ROESY cross peaks to be unambiguously assigned hence spatially proximate sugar spin systems across glycosidic bonds could be effectively ascertained. An experiment that selectively amplifies interresidue ROESY 1H-1H cross peaks is also reported. It moves the magnetization of an intraresidue proton normally correlated to a sugar H-1 signal orthogonally along the z axis prior to a Tr-ROESY mixing sequence. This virtually eliminates the incoherent intraresidue ROESY transfer, suppresses coherent TOCSY transfer, and markedly enhances the intensity of interresidue ROESY cross peaks.
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Massin, Pascale; Kuntz-Simon, Gaëlle; Barbezange, Cyril; Deblanc, Céline; Oger, Aurélie; Marquet-Blouin, Estelle; Bougeard, Stéphanie; van der Werf, Sylvie; Jestin, Véronique
2010-05-19
Influenza A viruses have been isolated from a wide range of animal species, aquatic birds being the reservoir for their genetic diversity. Avian influenza viruses can be transmitted to humans, directly or indirectly through an intermediate host like pig. This study aimed to define in vitro conditions that could prove useful to evaluate the potential of influenza viruses to adapt to a different host. Growth of H1N1, H1N2 and H3N2 influenza viruses belonging to different lineages isolated from birds or pigs prior to 2005 was tested on MDCK or NPTr cell lines in the presence or absence of exogenous trypsin. Virus multiplication was compared at 33, 37 and 40 degrees C, the infection site temperatures in human, swine and avian hosts, respectively. Temperature sensitivity of PB2-, NP- and M-RNA replication was also tested by quantitative real-time PCR. Multiplication of avian viruses was cold-sensitive, whatever cell type. By contrast, temperature sensitivity of swine viruses was found to depend on the virus and the host cell: for an H1N1 swine isolate from 1982, multiplication was cold-sensitive on NPTr cells and undetectable at 40 degrees C. From genetic analyses, it appears that temperature sensitivity could involve other residues than PB2 residue 627 and could affect other steps of the replication cycle than replication. Copyright 2009 Elsevier B.V. All rights reserved.
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Transport and Metabolism of 3H-Gibberellin A1 in Dioecious Cucumber Seedlings 1
Rudich, Jehoshua; Sell, Harold M.; Baker, Larry R.
1976-01-01
The transport of 3H-GA1 through hypocotyl segments of cucumber (Cucumis sativus L.) was found to be nonpolar. The transport of 3H-GA1 was increased by pretreatment with relatively high concentrations of either IAA or Ethephon (2-chloroethylphosphonic acid). Hypocotyl segments from plants of a gynoecious genotype transported more 3H-GA1 than those of an androecious. The metabolism of 3H-GA1 in hypocotyl segments was neither related to the sex genotype of the cucumber plant nor influenced by pretreatment with Ethephon. The primary metabolite of GA1 was suggested to be GA8. Two other suspected metabolites were not identified. Differences in the endogenous GA of gynoecious and androecious plants could not be accounted for by transport differences. PMID:16659561
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Prokudina, E N; Semenova, N P; Chumakov, V M; Burtseva, E I; Slepushkin, A N
2003-01-01
A comparative analysis of involving the nucleocapsid protein (NP) into shaping-up of SDS-resistant oligomers was carried out presently in circulating epidemic strains of human influenza, viruses A and B. The study results of viral isolates obtained from clinical samples and recent standard strains revealed that the involvement of NP in the SDS-resistant oligomers, which are different in various subtypes of influenza A viruses. According to this sign, the human viruses A(9H3N2) are close to the avian ones, in which, as proved by us previously, virtually the entire NP transforms itself into the oligomers resistant to SDS. About 10-20% of NP are involved in shaping-up the virus influenza A(H1N1) of SDS-resistant oligomers. No SDS-resistant NP-oligomers were detected in influenza of type B. It is suggested that the prevalence of human viruses A(H3N2) in NP-oligomers are the peculiarities of NP structure and of the presence of the PB1 protein from avian influenza virus.
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Synthesis, characterization and theoretical studies of 5-(benzylthio)-1-cylopentyl-1H-tetrazole.
Saglam, S; Disli, A; Erdogdu, Y; Marchewka, M K; Kanagathara, N; Bay, B; Güllüoğlu, M T
2015-01-25
In this study, 5-(benzylthio)-1-cylopentyl-1H-tetrazole (5B1C1HT) have been synthesized. Boiling points of the obtained compound have been determined and it has been characterized by FT-IR, (1)H NMR, (13)C-APT and LC-MS spectroscopy techniques. The FT-IR, (1)H NMR and (13)C-APT spectral measurements of the 5B1C1HT compound and complete assignment of the vibrational bands observed in spectra has been discussed. The spectra were interpreted with the aid of normal coordinate analysis following full structure optimization and force field calculations based on Density Functional Theory (DFT) at 6-311++G(**), cc-pVDZ and cc-pVTZ basis sets. The optimized geometry with 6-311++G(**) basis sets were used to determine the total energy distribution, harmonic vibrational frequencies, IR intensities. Copyright © 2014 Elsevier B.V. All rights reserved.
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26 CFR 25.2523(h)-1 - Denial of double deduction.
Code of Federal Regulations, 2010 CFR
2010-04-01
... 26 Internal Revenue 14 2010-04-01 2010-04-01 false Denial of double deduction. 25.2523(h)-1 Section 25.2523(h)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) ESTATE AND GIFT TAXES GIFT TAX; GIFTS MADE AFTER DECEMBER 31, 1954 Deductions § 25.2523(h)-1 Denial of...
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Pantin-Jackwood, Mary J; Kapczynski, Darrell R; DeJesus, Eric; Costa-Hurtado, Mar; Dauphin, Gwenaelle; Tripodi, Astrid; Dunn, John R; Swayne, David E
2016-03-01
Domestic ducks are the second most abundant poultry species in many Asian countries and have played a critical role in the epizootiology of H5N1 highly pathogenic avian influenza (HPAI).In this study, the protective efficacy of a live recombinant vector vaccine based on a turkey herpesvirus (HVT) expressing the H5 gene from a clade 2.2 H5N1 HPAI strain (A/Swan/Hungary/4999/ 2006) (rHVT-H5/2.2), given at 3 days of age, was examined in Pekin ducks (Anas platyrhynchos domesticus). The vaccine was given alone or in combination with an inactivated H5N1 clade 2.3.2.1 reverse genetic (rgGD/2.3.2.1) vaccine given at 16 days of age, either as a single vaccination or in a prime-boost regime. At 30 days of age, ducks were challenged with one of two H5N1 HPAI viruses: A/duck/Vietnam/NCVD-2721/2013 (clade 1.1.2) or A/duck/Vietnam/NCVD-1584/2012 (clade 2.3.2.1.C). These viruses produced 100% mortality in less than 5 days in nonvaccinated control ducks. Ducks vaccinated with the rgGD/2.3.2.1 vaccine, with or without the rHVT-H5/2.2 vaccine, were 90%-100% protected against mortality after challenge with either of the two H5N1 HPAI viruses. The rHVT-H5/2.2 vaccine alone, however, conferred only 30% protection against mortality after challenge with either H5N1 HPAI virus; the surviving ducks from these groups shed higher amount of virus and for longer than the single-vaccinated rgGD/2.3.2.1 group. Despite low protection, ducks vaccinated with the rHVT-H5/2.2 vaccine and challenged with the clade 1.1.2 Vietnam virus had a longer mean death time than nonvaccinated controls (P = 0.02). A booster effect was found on reduction of virus shedding when using both vaccines, with lower oropharyngeal viral titers at 4 days after challenge with either HPAI virus (P < 0.05). Neither rHVT-H5/2.2 nor standard HVT vaccine could be detected in samples collected from multiple tissues at different time points, indicting minimal levels of viral replication. In conclusion, although a minor effect on
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Potential antimicrobial agents from triazole-functionalized 2H-benzo[b][1,4]oxazin-3(4H)-ones.
Bollu, Rajitha; Banu, Saleha; Bantu, Rajashaker; Reddy, A Gopi; Nagarapu, Lingaiah; Sirisha, K; Kumar, C Ganesh; Gunda, Shravan Kumar; Shaik, Kamal
2017-12-01
A series of substituted triazole functionalized 2H-benzo[b][1,4]oxazin-3(4H)-ones were synthesized by employing click chemistry and further characterized based on 1 H NMR, 13 C NMR, IR and mass spectral studies. All the synthesized derivatives were screened for their in vitro antimicrobial activities. Further, molecular docking studies were accomplished to explore the binding interactions between 1,2,3-triazol-4-yl-2H-benzo[b][1,4]oxazin-3(4H)-one and the active site of Staphylococcus aureus (CrtM) dehydrosqualene synthase (PDB ID: 2ZCS). These docking studies revealed that the synthesized derivatives showed high binding energies and strong H-bond interactions with the dehydrosqualene synthase validating the observed antimicrobial activity data. Based on antimicrobial activity and docking studies, the compounds 9c, 9d and 9e were identified as promising antimicrobial leads. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Imaging photomultiplier array with integrated amplifiers and high-speed USB interfacea)
NASA Astrophysics Data System (ADS)
Blacksell, M.; Wach, J.; Anderson, D.; Howard, J.; Collis, S. M.; Blackwell, B. D.; Andruczyk, D.; James, B. W.
2008-10-01
Multianode photomultiplier tube (PMT) arrays are finding application as convenient high-speed light sensitive devices for plasma imaging. This paper describes the development of a USB-based "plug-n-play" 16-channel PMT camera with 16bits simultaneous acquisition of 16 signal channels at rates up to 2MS/s per channel. The preamplifiers and digital hardware are packaged in a compact housing which incorporates magnetic shielding, on-board generation of the high-voltage PMT bias, an optical filter mount and slits, and F-mount lens adaptor. Triggering, timing, and acquisition are handled by four field-programmable gate arrays (FPGAs) under instruction from a master FPGA controlled by a computer with a LABVIEW interface. We present technical design details and specifications and illustrate performance with high-speed images obtained on the H-1 heliac at the ANU.
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Imaging photomultiplier array with integrated amplifiers and high-speed USB interface.
Blacksell, M; Wach, J; Anderson, D; Howard, J; Collis, S M; Blackwell, B D; Andruczyk, D; James, B W
2008-10-01
Multianode photomultiplier tube (PMT) arrays are finding application as convenient high-speed light sensitive devices for plasma imaging. This paper describes the development of a USB-based "plug-n-play" 16-channel PMT camera with 16 bits simultaneous acquisition of 16 signal channels at rates up to 2 MSs per channel. The preamplifiers and digital hardware are packaged in a compact housing which incorporates magnetic shielding, on-board generation of the high-voltage PMT bias, an optical filter mount and slits, and F-mount lens adaptor. Triggering, timing, and acquisition are handled by four field-programmable gate arrays (FPGAs) under instruction from a master FPGA controlled by a computer with a LABVIEW interface. We present technical design details and specifications and illustrate performance with high-speed images obtained on the H-1 heliac at the ANU.
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Żmudzki, Paweł; Satała, Grzegorz; Chłoń-Rzepa, Grażyna; Bojarski, Andrzej J; Kazek, Grzegorz; Siwek, Agata; Gryboś, Anna; Głuch-Lutwin, Monika; Wesołowska, Anna; Pawłowski, Maciej
2016-10-01
In our previous papers, we have reported that some 8-amino-1,3-dimethyl-1H-purine-2,6(3H,7H)-dione derivatives possessed high affinity and displayed agonistic, partial agonistic, or antagonistic activity for serotonin 5-HT 1A and dopamine D 2 receptors. In order to examine further the influence of the substituent in the position 8 of the purine moiety and the influence of the xanthine core on the affinity for serotonin 5-HT 1A , 5-HT 2A , 5-HT 6 , 5-HT 7 , and dopamine D 2 receptors, two series of 1-arylpiperazynylalkyl derivatives of 8-amino-3,7-dimethyl-1H-purine-2,6(3H,7H)-dione were synthesized. All the final compounds were investigated in in vitro competition binding experiments for the serotonin 5-HT 1A , 5-HT 2A , 5-HT 6 , 5-HT 7 , and dopamine D 2 receptors. The structure-affinity relationships for this group of compounds were discussed. For selected compounds, the functional assays for the 5-HT 1A and D 2 receptors were carried out. The results of the assays indicated that these groups of derivatives possessed antagonistic activity for 5-HT 1A receptors and agonistic, partial agonistic, or antagonistic activity for D 2 receptors. In total, 26 new compounds were synthesized, 20 of which were tested in in vitro binding experiments and 5 were tested in in vitro functional assays. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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2015-01-01
The synthesis of the title compounds was carried out by reacting dicarboxylic acid chlorides with oximes in the presence of excess triethylamine. Disubstituted malonyl chlorides gave 2-alkenyl-4,4-dialkyl-3,5-isoxazolidinediones (8a–f) and 2,2′-ethylidene-bis[4,4-dialkyl-3,5-isoxazolidinedione]s (9a–f). Compounds 9 were formed from 8 and its N-unsubstituted 3,5-isoxazolidinedione decomposition product. Phthaloyl chlorides reacted with acetone oxime to yield 3-(1-methylethenyl)-1H-2,3-benzoxazine-1,4(3H)-diones (16a–e). Products 16 spontaneously decomposed to give N-unsubstituted 1H-2,3-benzoxazine-1,4(3H)-diones (17a–e) at rates that were dependent on temperature and solvent. Kinetic studies showed that two of the compounds decomposed by zero-order kinetics under neutral conditions. Butanedioyl chloride did not produce a cyclic product. PMID:24620711
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Izydore, Robert A; Jones, Joseph T; Mogesa, Benjamin; Swain, Ira N; Davis-Ward, Ronda G; Daniels, Dwayne L; Kpakima, Felicia Frazier; Spaulding-Phifer, Sharnelle T
2014-04-04
The synthesis of the title compounds was carried out by reacting dicarboxylic acid chlorides with oximes in the presence of excess triethylamine. Disubstituted malonyl chlorides gave 2-alkenyl-4,4-dialkyl-3,5-isoxazolidinediones (8a-f) and 2,2'-ethylidene-bis[4,4-dialkyl-3,5-isoxazolidinedione]s (9a-f). Compounds 9 were formed from 8 and its N-unsubstituted 3,5-isoxazolidinedione decomposition product. Phthaloyl chlorides reacted with acetone oxime to yield 3-(1-methylethenyl)-1H-2,3-benzoxazine-1,4(3H)-diones (16a-e). Products 16 spontaneously decomposed to give N-unsubstituted 1H-2,3-benzoxazine-1,4(3H)-diones (17a-e) at rates that were dependent on temperature and solvent. Kinetic studies showed that two of the compounds decomposed by zero-order kinetics under neutral conditions. Butanedioyl chloride did not produce a cyclic product.
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Inactivation of H1N1 viruses exposed to acidic ozone water
NASA Astrophysics Data System (ADS)
Uhm, Han S.; Lee, Kwang H.; Seong, Baik L.
2009-10-01
The inactivation of H1N1 viruses upon exposure to acidic ozone water was investigated using chicken allantoic fluids of different dilutions, pH values, and initial ozone concentrations. The inactivation effect of the acidic ozone water was found to be stronger than the inactivation effect of the ozone water combined with the degree of acidity, indicating a synergic effect of acidity on ozone decay in water. It is also shown that acidic ozone water with a pH value of 4 or less is very effective means of virus inactivation if provided in conjunction with an ozone concentration of 20 mg/l or higher.
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Code of Federal Regulations, 2010 CFR
2010-04-01
... expenditures to influence legislation; introduction. 1.501(h)-1 Section 1.501(h)-1 Internal Revenue INTERNAL...) Exempt Organizations § 1.501(h)-1 Application of the expenditure test to expenditures to influence... attempting to influence legislation, (except as otherwise provided in subsection (h)).” This requirement is...
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Zheng, C; Baum, BJ; Liu, X; Goldsmith, CM; Perez, P; Jang, S-I; Cotrim, AP; McCullagh, L; Ambudkar, IS; Alevizos, I
2017-01-01
In 2012, we reported that 5 out of 11 subjects in a clinical trial (NCT00372320) administering AdhAQP1 to radiation-damaged parotid glands showed increased saliva flow rates and decreased symptoms over the initial 42 days. AdhAQP1 is a first-generation, E1-deleted, replication-defective, serotype 5 adenoviral vector encoding human aquaporin-1 (hAQP1). This vector uses the human cytomegalovirus enhancer/promoter (hCMVp). As subject peak responses were at times much longer (7–42 days) than expected, we hypothesized that the hCMVp may not be methylated in human salivary gland cells to the extent previously observed in rodent salivary gland cells. This hypothesis was supported in human salivary gland primary cultures and human salivary gland cell lines after transduction with AdhAQP1. Importantly, hAQP1 maintained its function in those cells. Conversely, when we transduced mouse and rat cell lines in vitro and submandibular glands in vivo with AdhAQP1, the hCMVp was gradually methylated over time and associated with decreased hAQP1 expression and function in vitro and decreased hAQP1 expression in vivo. These data suggest that the hCMVp in AdhAQP1was probably not methylated in transduced human salivary gland cells of responding subjects, resulting in an unexpectedly longer functional expression of hAQP1. PMID:26177970
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Uwai, Yuichi; Honjo, Hiroaki; Iwamoto, Kikuo
2010-01-01
Nonsteroidal anti-inflammatory drugs (NSAIDs) delay renal excretion of antifolate methotrexate by inhibiting human organic anion transporters hOAT1 (SLC22A6) and hOAT3 (SLC22A8). In this study, we performed uptake experiments using Xenopus laevis oocytes to assess the inhibitory effect of selective cyclooxygenase-2 inhibitors on hOAT1 and hOAT3. The uptake of methotrexate into oocytes was increased by the injection of hOAT1 and hOAT3 cRNA, and transport was strongly inhibited by lumiracoxib. The apparent 50% inhibitory concentrations of lumiracoxib were estimated to be 3.3 µM and 1.9 µM for uptake of p-aminohippurate by hOAT1 and of estrone sulfate by hOAT3, respectively. Eadie-Hofstee plot analysis showed that lumiracoxib inhibited hOAT1 and hOAT3 in a competitive manner. For other cyclooxygenase-2 inhibitors celecoxib, etoricoxib, rofecoxib and valdecoxib, slight to moderate inhibition of hOAT3 only was observed. These findings show that lumiracoxib has inhibitory potential toward hOAT1 and hOAT3, comparable to that of nonselective NSAIDs.
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Population‐based surveillance for 2009 pandemic influenza A (H1N1) virus in Guatemala, 2009
Reyes, Lissette; Arvelo, Wences; Estevez, Alejandra; Gray, Jennifer; Moir, Juan C.; Gordillo, Betty; Frenkel, Gal; Ardón, Francisco; Moscoso, Fabiola; Olsen, Sonja J.; Fry, Alicia M.; Lindstrom, Steve; Lindblade, Kim A.
2010-01-01
Please cite this paper as: Reyes et al. (2010) Population‐based surveillance for 2009 pandemic influenza A (H1N1) virus in Guatemala, 2009. Influenza and Other Respiratory Viruses 4(3), 129–140. Background In April 2009, 2009 pandemic influenza A H1N1 (2009 H1N1) was first identified in Mexico but did not cause widespread transmission in neighboring Guatemala until several weeks later. Methodology and principle findings Using a population‐based surveillance system for hospitalized pneumonia and influenza‐like illness ongoing before the 2009 H1N1 pandemic began, we tracked the onset of 2009 H1N1 infection in Guatemala. We identified 239 individuals infected with influenza A (2009 H1N1) between May and December 2009, of whom 76 were hospitalized with pneumonia and 11 died (case fatality proportion: 4·6%, 95% confidence interval [CI] 2·3–8·1%). The median age of patients infected with 2009 H1N1 was 8·8 years, the median age of those hospitalized with pneumonia was 4·2 years, and five (45·5%) deaths occurred in children <5 years old. Crude rates of hospitalization between May and December 2009 were highest for children <5 years old. Twenty‐one (27·6%) of the patients hospitalized with 2009 H1N1 were admitted to the intensive care unit and eight (10·5%) required mechanical ventilation. Underlying chronic conditions were noted in 14 (18·4%) of patients with pneumonia hospitalized with 2009 H1N1 infection. Conclusions and significance Chronic illnesses may be underdiagnosed in Guatemala, making it difficult to identify this risk group for vaccination. Children 6 months to 5 years old should be among priority groups for vaccination to prevent serious consequences because of 2009 H1N1 infection. PMID:20409209
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Working safely with H5N1 viruses.
García-Sastre, Adolfo
2012-01-01
Research on H5N1 influenza viruses has received much attention recently due to the possible dangers associated with newly developed avian H5N1 viruses that were derived from highly pathogenic avian viruses and are now transmissible among ferrets via respiratory droplets. An appropriate discussion, based on scientific facts about the risks that such viruses pose and on the biocontainment facilities and practices necessary for working safely with these viruses, is needed. Selecting the right level of biocontainment is critical for minimizing the risks associated with H5N1 research while simultaneously allowing an appropriately fast pace of discovery. Rational countermeasures for preventing the spread of influenza can be developed only by gaining a thorough knowledge of the molecular mechanisms at work in host specificity and transmission.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Pushko, Peter, E-mail: ppushko@medigen-usa.com
Avian influenza (AI) viruses circulating in wild birds pose a serious threat to public health. Human and veterinary vaccines against AI subtypes are needed. Here we prepared triple-subtype VLPs that co-localized H5, H7 and H9 antigens derived from H5N1, H7N3 and H9N2 viruses. VLPs also contained influenza N1 neuraminidase and retroviral gag protein. The H5/H7/H9/N1/gag VLPs were prepared using baculovirus expression. Biochemical, functional and antigenic characteristics were determined including hemagglutination and neuraminidase enzyme activities. VLPs were further evaluated in a chicken AI challenge model for safety, immunogenicity and protective efficacy against heterologous AI viruses including H5N2, H7N3 and H9N2 subtypes.more » All vaccinated birds survived challenges with H5N2 and H7N3 highly pathogenic AI (HPAI) viruses, while all controls died. Immune response was also detectable after challenge with low pathogenicity AI (LPAI) H9N2 virus suggesting that H5/H7/H9/N1/gag VLPs represent a promising approach for the development of broadly protective AI vaccine. - Highlights: •VLPs were prepared that co-localized H5, H7 and H9 subtypes in a VLP envelope. •VLPs were characterized including electron microscopy, HA assay and NA enzyme activity. •Experimental VLP vaccine was evaluated in an avian influenza challenge model. •VLPs induced immune responses against heterologous H5, H7 and H9 virus challenges.« less
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Severe H1N1-Associated acute respiratory distress syndrome: A case series.
Lai, Andrew R; Keet, Kevin; Yong, Celina M; Diaz, Janet V
2010-03-01
Acute respiratory distress syndrome resulting from novel influenza A virus (H1N1) infection remains uncommon. We describe the clinical profiles of adult patients with acute respiratory distress syndrome due to microbiologically confirmed H1N1 admitted to a medical intensive care unit in San Francisco, California over a 2-month period. Between June 1 and July 31, 2009, 7 patients (age range: 25-66 years; 4 patients under the age of 40 years; 6 male; 1 pregnant) were diagnosed with H1N1, with 5 of 6 (83%) having initial false-negative rapid testing. All developed respiratory failure complicated by acute respiratory distress syndrome, with 4 additionally developing multiorgan dysfunction. All were managed with a lung protective ventilator strategy (average number of days on the ventilator: 16), and 4 patients also required additional rescue therapies for refractory hypoxemia, including very high positive end-expiratory pressure, inhaled epoprostenol, recruitment maneuvers, and prone positioning. Despite these measures, 3 patients (43%) ultimately died. Clinicians should be vigilant for the potential of H1N1 infection to progress to severe acute respiratory distress syndrome in a variety of patient demographics, including younger patients without baseline cardiopulmonary disease. A high degree of suspicion is critical, especially with the relative insensitivity of rapid testing, and should prompt empiric antiviral therapy. 2010 Elsevier Inc. All rights reserved.
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Acceptance of 2009 H1N1 influenza vaccine among pregnant women in Delaware.
Drees, Marci; Johnson, Oluwakemi; Wong, Esther; Stewart, Ashley; Ferisin, Stephanie; Silverman, Paul R; Ehrenthal, Deborah B
2012-04-01
Due to disproportionately high mortality from 2009 H1N1 influenza, pregnant women were given highest priority for H1N1 vaccination. We surveyed postpartum women to determine vaccine uptake and reasons for lack of vaccination. We performed a cross-sectional survey of postpartum women delivering at our institution from February 1 to April 15, 2010. The 12-question survey ascertained maternal characteristics and vaccination concerns. Among 307 postpartum women, 191 (62%) had received H1N1 vaccination and 98 (32%) had declined. Factors associated with H1N1 vaccination included older age (relative risk [RR] 1.3, 95% confidence interval [CI] 1.1 to 1.5 for age ≥35 years compared with 20 to 34 years), at least college education (RR 1.5, 95% CI 1.3 to 1.8), prior influenza vaccination (RR 1.6, 95% CI 1.3 to 2.0), provider recommendation (RR 3.9, 95% CI 2.1 to 7.4), vaccination of family members (RR 1.6, 95% CI 1.3 to 1.9), and receipt of seasonal influenza vaccination (RR 2.2, 95% CI 1.7 to 2.9). Non-Hispanic black women were less likely to have been vaccinated (RR 0.6, 95% CI 0.5 to 0.8) than non-Hispanic white women. Safety concerns were cited by the majority (66%) of nonvaccinated women. H1N1 vaccine uptake among pregnant women was substantially higher than reported influenza vaccination rates during previous seasons. Safety concerns were the major barrier to vaccination. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
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Structural Basis of Preexisting Immunity to the 2009 H1N1 Pandemic Influenza Virus
DOE Office of Scientific and Technical Information (OSTI.GOV)
Xu, Rui; Ekiert, Damian C.; Krause, Jens C.
The 2009 H1N1 swine flu is the first influenza pandemic in decades. The crystal structure of the hemagglutinin from the A/California/04/2009 H1N1 virus shows that its antigenic structure, particularly within the Sa antigenic site, is extremely similar to those of human H1N1 viruses circulating early in the 20th century. The cocrystal structure of the 1918 hemagglutinin with 2D1, an antibody from a survivor of the 1918 Spanish flu that neutralizes both 1918 and 2009 H1N1 viruses, reveals an epitope that is conserved in both pandemic viruses. Thus, antigenic similarity between the 2009 and 1918-like viruses provides an explanation for themore » age-related immunity to the current influenza pandemic.« less
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Smith, Katherine C; Rimal, Rajiv N; Sandberg, Helena; Storey, John D; Lagasse, Lisa; Maulsby, Catherine; Rhoades, Elizabeth; Barnett, Daniel J; Omer, Saad B; Links, Jonathan M
2013-09-01
During an evolving public health crisis, news organizations disseminate information rapidly, much of which is uncertain, dynamic, and difficult to verify. We examine factors related to international news coverage of H1N1 during the first month after the outbreak in late April 2009 and consider the news media's role as an information source during an emerging pandemic. Data on H1N1 news were compiled in real time from newspaper websites across twelve countries between April 29, 2009 and May 28, 2009. A news sample was purposively constructed to capture variation in countries' prior experience with avian influenza outbreaks and pandemic preparation efforts. We analyzed the association between H1N1 news volume and four predictor variables: geographic region, prior experience of a novel flu strain (H5N1), existence of a national pandemic plan, and existence of a localized H1N1 outbreak. H1N1 news was initially extensive but declined rapidly (OR = 0.85, P < .001). Pandemic planning did not predict newsworthiness. However, countries with prior avian flu experience had higher news volume (OR = 1.411, P < .05), suggesting that H1N1 newsworthiness was bolstered by past experiences. The proportion of H1N1 news was significantly lower in Europe than elsewhere (OR = 0.388, P < 0.05). Finally, coverage of H1N1 increased after a first in-country case (OR = 1.415, P < .01), interrupting the pattern of coverage decline. Findings demonstrate the enhanced newsworthiness of localized threats, even during an emerging pandemic. We discuss implications for news media's role in effective public health communication throughout an epidemic given the demonstrated precipitous decline in news interest. © 2012 John Wiley & Sons Ltd.
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Phylogeography of influenza A H5N1 clade 2.2.1.1 in Egypt
2013-01-01
Background Influenza A H5N1 has killed millions of birds and raises serious public health concern because of its potential to spread to humans and cause a global pandemic. While the early focus was in Asia, recent evidence suggests that Egypt is a new epicenter for the disease. This includes characterization of a variant clade 2.2.1.1, which has been found almost exclusively in Egypt. We analyzed 226 HA and 92 NA sequences with an emphasis on the H5N1 2.2.1.1 strains in Egypt using a Bayesian discrete phylogeography approach. This allowed modeling of virus dispersion between Egyptian governorates including the most likely origin. Results Phylogeography models of hemagglutinin (HA) and neuraminidase (NA) suggest Ash Sharqiyah as the origin of virus spread, however the support is weak based on Kullback–Leibler values of 0.09 for HA and 0.01 for NA. Association Index (AI) values and Parsimony Scores (PS) were significant (p-value < 0.05), indicating that dispersion of H5N1 in Egypt was geographically structured. In addition, the Ash Sharqiyah to Al Gharbiyah and Al Fayyum to Al Qalyubiyah routes had the strongest statistical support. Conclusion We found that the majority of routes with strong statistical support were in the heavily populated Delta region. In particular, the Al Qalyubiyah governorate appears to represent a popular location for virus transition as it represented a large portion of branches in both trees. However, there remains uncertainty about virus dispersion to and from this location and thus more research needs to be conducted in order to examine this. Phylogeography can highlight the drivers of H5N1 emergence and spread. This knowledge can be used to target public health efforts to reduce morbidity and mortality. For Egypt, future work should focus on using data about vaccination and live bird markets in phylogeography models to study their impact on H5N1 diffusion within the country. PMID:24325606
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Desheva, Yulia; Sychev, Ivan; Smolonogina, Tatiana; Rekstin, Andrey; Ilyushina, Natalia; Lugovtsev, Vladimir; Samsonova, Anastasia; Go, Aleksey; Lerner, Anna
2018-01-01
The main objective of the study was to evaluate neuraminidase inhibiting (NI) antibodies against A/H1N1pdm09 influenza viruses in the community as a whole and after infection. We evaluated NI serum antibodies against A/California/07/09(H1N1)pdm and A/South Africa/3626/2013(H1N1)pdm in 134 blood donors of different ages using enzyme-linked lectin assay and in 15 paired sera from convalescents with laboratory confirmed influenza. The neuraminidase (NA) proteins of both A/H1N1pdm09 viruses had minimal genetic divergence, but demonstrated different enzymatic and antigenic properties. 5.2% of individuals had NI antibody titers ≥1:20 against A/South Africa/3626/2013(H1N1)pdm compared to 53% of those who were positive to A/California/07/2009(H1N1)pdm NA. 2% of individuals had detectable NI titers against A/South Africa/3626/13(H1N1)pdm and 47.3% were positive to A/California/07/2009(H1N1)pdm NA among participants negative to hemagglutinin (HA) of A/H1N1pdm09 but positive to seasonal A/H1N1. The lowest NI antibody levels to both A/H1N1pdm09 viruses were detected in individuals born between 1956 and 1968. Our data suggest that NI antibodies against A/South Africa/3626/13 (H1N1)pdm found in the blood donors could have resulted from direct infection with a new antigenic A/H1N1pdm09 variant rather than from cross-reaction as a result of contact with previously circulating seasonal A/H1N1 variants. The immune responses against HA and NA were formed simultaneously right after natural infection with A/H1N1pdm09. NI antibodies correlated with virus-neutralizing antibodies when acquired shortly after influenza infection. A group of middle-aged patients with the lowest level of anti-NA antibodies against A/California/07/2009 (H1N1)pdm was identified, indicating the highest-priority vaccination against A/H1N1pdm09 viruses.
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Sychev, Ivan; Smolonogina, Tatiana; Rekstin, Andrey; Ilyushina, Natalia; Lugovtsev, Vladimir; Samsonova, Anastasia; Go, Aleksey; Lerner, Anna
2018-01-01
The main objective of the study was to evaluate neuraminidase inhibiting (NI) antibodies against A/H1N1pdm09 influenza viruses in the community as a whole and after infection. We evaluated NI serum antibodies against A/California/07/09(H1N1)pdm and A/South Africa/3626/2013(H1N1)pdm in 134 blood donors of different ages using enzyme-linked lectin assay and in 15 paired sera from convalescents with laboratory confirmed influenza. The neuraminidase (NA) proteins of both A/H1N1pdm09 viruses had minimal genetic divergence, but demonstrated different enzymatic and antigenic properties. 5.2% of individuals had NI antibody titers ≥1:20 against A/South Africa/3626/2013(H1N1)pdm compared to 53% of those who were positive to A/California/07/2009(H1N1)pdm NA. 2% of individuals had detectable NI titers against A/South Africa/3626/13(H1N1)pdm and 47.3% were positive to A/California/07/2009(H1N1)pdm NA among participants negative to hemagglutinin (HA) of A/H1N1pdm09 but positive to seasonal A/H1N1. The lowest NI antibody levels to both A/H1N1pdm09 viruses were detected in individuals born between 1956 and 1968. Our data suggest that NI antibodies against A/South Africa/3626/13 (H1N1)pdm found in the blood donors could have resulted from direct infection with a new antigenic A/H1N1pdm09 variant rather than from cross-reaction as a result of contact with previously circulating seasonal A/H1N1 variants. The immune responses against HA and NA were formed simultaneously right after natural infection with A/H1N1pdm09. NI antibodies correlated with virus-neutralizing antibodies when acquired shortly after influenza infection. A group of middle-aged patients with the lowest level of anti-NA antibodies against A/California/07/2009 (H1N1)pdm was identified, indicating the highest-priority vaccination against A/H1N1pdm09 viruses. PMID:29742168
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Igawa, Hideyuki; Takahashi, Masashi; Shirasaki, Mikio; Kakegawa, Keiko; Kina, Asato; Ikoma, Minoru; Aida, Jumpei; Yasuma, Tsuneo; Okuda, Shoki; Kawata, Yayoi; Noguchi, Toshihiro; Yamamoto, Syunsuke; Fujioka, Yasushi; Kundu, Mrinalkanti; Khamrai, Uttam; Nakayama, Masaharu; Nagisa, Yasutaka; Kasai, Shizuo; Maekawa, Tsuyoshi
2016-06-01
Melanin-concentrating hormone (MCH) is an attractive target for antiobesity agents, and numerous drug discovery programs are dedicated to finding small-molecule MCH receptor 1 (MCHR1) antagonists. We recently reported novel pyridine-2(1H)-ones as aliphatic amine-free MCHR1 antagonists that structurally featured an imidazo[1,2-a]pyridine-based bicyclic motif. To investigate imidazopyridine variants with lower basicity and less potential to inhibit cytochrome P450 3A4 (CYP3A4), we designed pyridine-2(1H)-ones bearing various less basic bicyclic motifs. Among these, a lead compound 6a bearing a 1H-benzimidazole motif showed comparable binding affinity to MCHR1 to the corresponding imidazopyridine derivative 1. Optimization of 6a afforded a series of potent thiophene derivatives (6q-u); however, most of these were found to cause time-dependent inhibition (TDI) of CYP3A4. As bioactivation of thiophenes to form sulfoxide or epoxide species was considered to be a major cause of CYP3A4 TDI, we introduced electron withdrawing groups on the thiophene and found that a CF3 group on the ring or a Cl adjacent to the sulfur atom helped prevent CYP3A4 TDI. Consequently, 4-[(5-chlorothiophen-2-yl)methoxy]-1-(2-cyclopropyl-1-methyl-1H-benzimidazol-6-yl)pyridin-2(1H)-one (6s) was identified as a potent MCHR1 antagonist without the risk of CYP3A4 TDI, which exhibited a promising safety profile including low CYP3A4 inhibition and exerted significant antiobesity effects in diet-induced obese F344 rats. Copyright © 2016 Elsevier Ltd. All rights reserved.
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PLC-γ1 is involved in the inflammatory response induced by influenza A virus H1N1 infection.
Zhu, Liqian; Yuan, Chen; Ding, Xiuyan; Xu, Shuai; Yang, Jiayun; Liang, Yuying; Zhu, Qiyun
2016-09-01
We have previously reported that phosphoinositide-specific phospholipase γ1 (PLC-γ1) signaling is activated by influenza virus H1N1 infection and mediates efficient viral entry in human epithelial cells. In this study, we show that H1N1 also activates PLCγ-1 signaling in human promonocytic cell line -derived macrophages. Surprisingly, the activated PLCγ-1 signaling is not important for viral replication in macrophages, but is involved in the virus-induced inflammatory responses. PLC-γ1-specific inhibitor U73122 strongly inhibits the H1N1 virus-induced NF-κB signaling, blocking the up-regulation of TNF-α, IL-6, MIP-1α, and reactive oxidative species. In a positive feedback loop, IL-1β and TNF-α activate the PLCγ-1 signaling in both epithelial and macrophage cell lines. In summary, we have shown for the first time that the PLCγ-1 signaling plays an important role in the H1N1-induced inflammatory responses. Our study suggests that targeting the PLCγ-1 signaling is a potential antiviral therapy against H1N1 by inhibiting both viral replication and excessive inflammation. Copyright © 2016 Elsevier Inc. All rights reserved.
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Reassortant swine influenza viruses isolated in Japan contain genes from pandemic A(H1N1) 2009.
Kanehira, Katsushi; Takemae, Nobuhiro; Uchida, Yuko; Hikono, Hirokazu; Saito, Takehiko
2014-06-01
In 2013, three reassortant swine influenza viruses (SIVs)-two H1N2 and one H3N2-were isolated from symptomatic pigs in Japan; each contained genes from the pandemic A(H1N1) 2009 virus and endemic SIVs. Phylogenetic analysis revealed that the two H1N2 viruses, A/swine/Gunma/1/2013 and A/swine/Ibaraki/1/2013, were reassortants that contain genes from the following three distinct lineages: (i) H1 and nucleoprotein (NP) genes derived from a classical swine H1 HA lineage uniquely circulating among Japanese SIVs; (ii) neuraminidase (NA) genes from human-like H1N2 swine viruses; and (iii) other genes from pandemic A(H1N1) 2009 viruses. The H3N2 virus, A/swine/Miyazaki/2/2013, comprised genes from two sources: (i) hemagglutinin (HA) and NA genes derived from human and human-like H3N2 swine viruses and (ii) other genes from pandemic A(H1N1) 2009 viruses. Phylogenetic analysis also indicated that each of the reassortants may have arisen independently in Japanese pigs. A/swine/Miyazaki/2/2013 were found to have strong antigenic reactivities with antisera generated for some seasonal human-lineage viruses isolated during or before 2003, whereas A/swine/Miyazaki/2/2013 reactivities with antisera against viruses isolated after 2004 were clearly weaker. In addition, antisera against some strains of seasonal human-lineage H1 viruses did not react with either A/swine/Gunma/1/2013 or A/swine/Ibaraki/1/2013. These findings indicate that emergence and spread of these reassortant SIVs is a potential public health risk. © 2014 The Societies and Wiley Publishing Asia Pty Ltd.
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Ujike, Makoto; Ejima, Miho; Anraku, Akane; Shimabukuro, Kozue; Obuchi, Masatsugu; Kishida, Noriko; Hong, Xu; Takashita, Emi; Fujisaki, Seiichiro; Yamashita, Kazuyo; Horikawa, Hiroshi; Kato, Yumiko; Oguchi, Akio; Fujita, Nobuyuki; Tashiro, Masato
2011-01-01
To monitor and characterize oseltamivir-resistant (OR) pandemic (H1N1) 2009 virus with the H275Y mutation, we analyzed 4,307 clinical specimens from Japan by neuraminidase (NA) sequencing or inhibition assay; 61 OR pandemic (H1N1) 2009 viruses were detected. NA inhibition assay and M2 sequencing indicated that OR pandemic (H1N1) 2009 virus was resistant to M2 inhibitors, but sensitive to zanamivir. Full-genome sequencing showed OR and oseltamivir-sensitive (OS) viruses had high sequence similarity, indicating that domestic OR virus was derived from OS pandemic (H1N1) 2009 virus. Hemagglutination inhibition test demonstrated that OR and OS pandemic (H1N1) 2009 viruses were antigenically similar to the A/California/7/2009 vaccine strain. Of 61 case-patients with OR viruses, 45 received oseltamivir as treatment, and 10 received it as prophylaxis, which suggests that most cases emerged sporadically from OS pandemic (H1N1) 2009, due to selective pressure. No evidence of sustained spread of OR pandemic (H1N1) 2009 was found in Japan; however, 2 suspected incidents of human-to-human transmission were reported. PMID:21392439
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Domestic Ducks and H5N1 Influenza Epidemic, Thailand
Songserm, Thaweesak; Jam-on, Rungroj; Sae-Heng, Numdee; Meemak, Noppadol; Hulse-Post, Diane J.; Sturm-Ramirez, Katharine M.
2006-01-01
In addition to causing 12 human deaths and 17 cases of human infection, the 2004 outbreak of H5N1 influenza virus in Thailand resulted in the death or slaughter of 60 million domestic fowl and the disruption of poultry production and trade. After domestic ducks were recognized as silent carriers of H5N1 influenza virus, government teams went into every village to cull flocks in which virus was detected; these team efforts markedly reduced H5N1 infection. Here we examine the pathobiology and epidemiology of H5N1 influenza virus in the 4 systems of duck raising used in Thailand in 2004. No influenza viruses were detected in ducks raised in "closed" houses with high biosecurity. However, H5N1 influenza virus was prevalent among ducks raised in "open" houses, free-ranging (grazing) ducks, and backyard ducks. PMID:16704804
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Siu, Chi-Kit; Liu, Zhi-Feng; Tse, John S
2002-09-11
We report computational studies on Al(+)(H(2)O)(n), and HAlOH(+)(H(2)O)(n-1), n = 6-14, by the density functional theory based ab initio molecular dynamics method, employing a planewave basis set with pseudopotentials, and also by conventional methods with Gaussian basis sets. The mechanism for the intracluster H(2) elimination reaction is explored. First, a new size-dependent insertion reaction for the transformation of Al(+)(H(2)O)(n), into HAlOH(+)(H(2)O)(n-1) is discovered for n > or = 8. This is because of the presence of a fairly stable six-water-ring structure in Al(+)(H(2)O)(n) with 12 members, including the Al(+). This structure promotes acidic dissociation and, for n > or = 8, leads to the insertion reaction. Gaussian based BPW91 and MP2 calculations with 6-31G* and 6-31G** basis sets confirmed the existence of such structures and located the transition structures for the insertion reaction. The calculated transition barrier is 10.0 kcal/mol for n = 9 and 7.1 kcal/mol for n = 8 at the MP2/6-31G** level, with zero-point energy corrections. Second, the experimentally observed size-dependent H(2) elimination reaction is related to the conformation of HAlOH(+)(H(2)O)(n-1), instead of Al(+)(H(2)O)(n). As n increases from 6 to 14, the structure of the HAlOH(+)(H(2)O)(n-1) cluster changes into a caged structure, with the Al-H bond buried inside, and protons produced in acidic dissociation could then travel through the H(2)O network to the vicinity of the Al-H bond and react with the hydride H to produce H(2). The structural transformation is completed at n = 13, coincident approximately with the onset of the H(2) elimination reaction. From constrained ab initio MD simulations, we estimated the free energy barrier for the H(2) elimination reaction to be 0.7 eV (16 kcal/mol) at n = 13, 1.5 eV (35 kcal/mol) at n = 12, and 4.5 eV (100 kcal/mol) at n = 8. The existence of transition structures for the H(2) elimination has also been verified by ab initio calculations
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Santini, Daniele; Vincenzi, Bruno; Fratto, Maria Elisabetta; Perrone, Giuseppe; Lai, Raymond; Catalano, Vincenzo; Cass, Carol; Ruffini, Pier Adelchi; Spoto, Chiara; Muretto, Pietro; Rizzo, Sergio; Muda, Andrea Onetti; Mackey, John R; Russo, Antonio; Tonini, Giuseppe; Graziano, Francesco
2010-05-01
Nucleoside transporter proteins are specialized proteins that mediate the transport of nucleosides and nucleoside analog drugs across the plasma membrane. The human equilibrative nucleoside transporter 1 (hENT1) is a member of these proteins and mediates cellular entry of gemcitabine, cytarabine, and fludarabine. The hENT1 expression has been demonstrated to be related with prognosis and activity of gemcitabine-based therapy in breast, ampullary, lung, and pancreatic cancer. We investigated the immunohistochemical expression of hENT in tumor samples from 111 patients with resected gastric adenocarcinoma, correlating these data with clinical parameters and disease outcomes. None of the patients received chemotherapy or radiation therapy before or after surgery as a part of an adjuvant or neoadjuvant program. On univariate survival analysis, the hENT1 expression was associated with overall survival (OS) and disease free survival (DFS). Specifically, those patients with overexpression of hENT1 showed a shorter OS (P = 0.021) and a shorter DFS (P = 0.033). Considering only the node positive patients, higher hENT levels were associated with significantly shorter median DFS (21.7 months; 95% CI 11.1-32.4) compared with patients with low expression of hENT1. The hENT1 expression was defined, in the lymph-node positive patients, as an independent prognostic factor (P = 0.019). Furthermore, considering only patients with diffuse or mixed tumors and lymph-node positive, the expression of hENT1 was strongly related with DFS and OS. Immunohistochemistry for the hENT1 protein carries prognostic information in patients with resected gastric cancer and holds promise as a predictive factor in chemotherapy decisions.
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Evidence for the η(b)(2S) and observation of h(b)(1P)→η(b)(1S)γ and h(b)(2P)→η(b)(1S)γ.
Mizuk, R; Asner, D M; Bondar, A; Pedlar, T K; Adachi, I; Aihara, H; Arinstein, K; Aulchenko, V; Aushev, T; Aziz, T; Bakich, A M; Bay, A; Belous, K; Bhardwaj, V; Bhuyan, B; Bischofberger, M; Bonvicini, G; Bozek, A; Bračko, M; Brodzicka, J; Browder, T E; Chekelian, V; Chen, A; Chen, P; Cheon, B G; Chilikin, K; Chistov, R; Cho, I-S; Cho, K; Choi, S-K; Choi, Y; Dalseno, J; Danilov, M; Doležal, Z; Drásal, Z; Drutskoy, A; Eidelman, S; Epifanov, D; Fast, J E; Gaur, V; Gabyshev, N; Garmash, A; Golob, B; Haba, J; Hara, T; Hayasaka, K; Hayashii, H; Horii, Y; Hoshi, Y; Hou, W-S; Hsiung, Y B; Hyun, H J; Iijima, T; Ishikawa, A; Itoh, R; Iwabuchi, M; Iwasaki, Y; Iwashita, T; Jaegle, I; Julius, T; Kang, J H; Kapusta, P; Kawasaki, T; Kim, H J; Kim, H O; Kim, J H; Kim, K T; Kim, M J; Kim, Y J; Kinoshita, K; Ko, B R; Koblitz, S; Kodyš, P; Korpar, S; Kouzes, R T; Križan, P; Krokovny, P; Kuhr, T; Kumita, T; Kuzmin, A; Kwon, Y-J; Lange, J S; Lee, S-H; Li, J; Libby, J; Liu, C; Liu, Y; Liu, Z Q; Liventsev, D; Louvot, R; Matvienko, D; McOnie, S; Miyabayashi, K; Miyata, H; Mohanty, G B; Mohapatra, D; Moll, A; Muramatsu, N; Mussa, R; Nakao, M; Natkaniec, Z; Ng, C; Nishida, S; Nishimura, K; Nitoh, O; Nozaki, T; Ohshima, T; Okuno, S; Olsen, S L; Onuki, Y; Pakhlov, P; Pakhlova, G; Park, C W; Park, H; Pestotnik, R; Petrič, M; Piilonen, L E; Poluektov, A; Röhrken, M; Sakai, Y; Sandilya, S; Santel, D; Sanuki, T; Sato, Y; Schneider, O; Schwanda, C; Senyo, K; Seon, O; Sevior, M E; Shapkin, M; Shen, C P; Shibata, T-A; Shiu, J-G; Shwartz, B; Sibidanov, A; Simon, F; Smerkol, P; Sohn, Y-S; Sokolov, A; Solovieva, E; Stanič, S; Starič, M; Sumihama, M; Sumiyoshi, T; Tanida, K; Tatishvili, G; Teramoto, Y; Tikhomirov, I; Trabelsi, K; Tsuboyama, T; Uchida, M; Uehara, S; Uglov, T; Unno, Y; Uno, S; Vanhoefer, P; Varner, G; Varvell, K E; Vinokurova, A; Vorobyev, V; Wang, C H; Wang, M-Z; Wang, P; Wang, X L; Watanabe, M; Watanabe, Y; Williams, K M; Won, E; Yabsley, B D; Yamaoka, J; Yamashita, Y; Yuan, C Z; Zhang, Z P; Zhilich, V
2012-12-07
We report the first evidence for the η(b)(2S) using the h(b)(2P)→η(b)(2S)γ transition and the first observation of the h(b)(1P)→η(b)(1S)γ and h(b)(2P)→η(b)(1S)γ transitions. The mass and width of the η(b)(1S) and η(b)(2S) are measured to be m(η(b)(1S))=(9402.4±1.5±1.8) MeV/c(2), m(η(b)(2S))=(9999.0±3.5(-1.9)(+2.8)) MeV/c(2), and Γ(η(b)(1S))=(10.8(-3.7-2.0)(+4.0+4.5)) MeV. We also update the h(b)(1P) and h(b)(2P) mass measurements. We use a 133.4 fb(-1) data sample collected at energies near the Υ(5S) resonance with the Belle detector at the KEKB asymmetric-energy e(+)e(-) collider.
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NASA Astrophysics Data System (ADS)
Yuan, Meiling; Li, Wentao; Yuan, Jiuchuang
2018-05-01
A new global potential energy surface (PES) of the NaH2+ system is constructed by fitting 27,621 ab initio energy points with the neural network method. The root mean square error of the new PES is only 4.1609 × 10-4 eV. Based on the new PES, dynamical calculations have been performed using the time-dependent quantum wave packet method. These results are then compared with the H(2S) + LiH+(X2Σ+) → Li+(1S) + H2(X1Σg+) reaction. The direct abstract mechanism is found to play an important role in the reaction because only forward scattering signals on the differential cross section results for all calculated collision energies.
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Trust During the Early Stages of the 2009 H1N1 Pandemic
FREIMUTH, VICKI S.; MUSA, DON; HILYARD, KAREN; QUINN, SANDRA CROUSE; KIM, KEVIN
2013-01-01
Distrust of the government often stands in the way of cooperation with public health recommendations in a crisis. The purpose of this paper is to describe the public’s trust in government recommendations during the early stages of the H1N1 pandemic and identify factors that might account for these trust levels. We surveyed 1543 respondents about their experiences and attitudes related to H1N1 influenza between June 3, 2009 and July 6, 2009, during the first wave of the pandemic using the Knowledge Networks (KN) online panel. This panel is representative of the US population, and uses a combination of random-digit dial and address-based probability sampling frames covering 99% of the US household population to recruit participants. To ensure participation of low-income individuals and those without Internet access, KN provides hardware and access to the Internet if needed. Measures included standard demographics, a trust scale, trust ratings for individual spokespersons, involvement with H1N1, experience with H1N1, and past discrimination in health care. We found that trust of government was low (2.3 out of 4) and varied across demographic groups. Blacks and Hispanics reported higher trust in government than did Whites. Of the spokespersons included, personal health professionals received the highest trust ratings and religious leaders the lowest. Attitudinal and experience variables predicted trust better than demographic characteristics. Closely following the news about the flu virus, having some self-reported knowledge about H1N1, self-reporting of local cases and previously experiencing discrimination were the significant attitudinal and experience predictors of trust. Using a second longitudinal survey, trust in the early stages of the pandemic did predict vaccine acceptance later but only for white, non-Hispanic individuals. PMID:24117390
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Novel reassortant of swine influenza H1N2 virus in Germany.
Zell, Roland; Motzke, Susann; Krumbholz, Andi; Wutzler, Peter; Herwig, Volker; Dürrwald, Ralf
2008-01-01
European porcine H1N2 influenza viruses arose after multiple reassortment steps involving a porcine influenza virus with avian-influenza-like internal segments and human H1N1 and H3N2 viruses in 1994. In Germany, H1N2 swine influenza viruses first appeared in 2000. Two German H1N2 swine influenza virus strains isolated from pigs with clinical symptoms of influenza are described. They were characterized by the neutralization test, haemagglutination inhibition (HI) test and complete sequencing of the viral genomes. The data demonstrate that these viruses represent a novel H1N2 reassortant. The viruses showed limited neutralization by sera raised against heterologous A/sw/Bakum/1,832/00-like H1N2 viruses. Sera pools from recovered pigs showed a considerably lower HI reaction, indicative of diagnostic difficulties in using the HI test to detect these viruses with A/sw/Bakum/1,832/00-like H1N2 antigens. Genome sequencing revealed the novel combination of the human-like HAH1 gene of European porcine H1N2 influenza viruses and the NAN2 gene of European porcine H3N2 viruses.
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Age as Risk Factor for Death from Pandemic (H1N1) 2009, Chile
Dabanch, Jeannette; Nájera, Manuel; González, Claudia; Guerrero, Andrea; Olea, Andrea; Fasce, Rodrigo; Morales, Cecilia; Vega, Jeanette
2011-01-01
Pandemic (H1N1) 2009 affected Chile during the winter of 2009. The hospitalization rate was 0.56% overall and 3.47% for persons >60 years of age at risk for severe disease and death independent of concurrent conditions. Age >60 years was the major risk factor for death from pandemic (H1N1) 2009. PMID:21762580
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Verma, Chandrabhan; Quraishi, M. A.; Kluza, K.; Makowska-Janusik, M.; Olasunkanmi, Lukman O.; Ebenso, Eno E.
2017-01-01
D-glucose derivatives of dihydropyrido-[2,3-d:6,5-d′]-dipyrimidine-2, 4, 6, 8(1H,3H, 5H,7H)-tetraone (GPHs) have been synthesized and investigated as corrosion inhibitors for mild steel in 1M HCl solution using gravimetric, electrochemical, surface, quantum chemical calculations and Monte Carlo simulations methods. The order of inhibition efficiencies is GPH-3 > GPH-2 > GPH-1. The results further showed that the inhibitor molecules with electron releasing (-OH, -OCH3) substituents exhibit higher efficiency than the parent molecule without any substituents. Polarization study suggests that the studied compounds are mixed-type but exhibited predominantly cathodic inhibitive effect. The adsorption of these compounds on mild steel surface obeyed the Langmuir adsorption isotherm. SEM, EDX and AFM analyses were used to confirm the inhibitive actions of the molecules on mild steel surface. Quantum chemical (QC) calculations and Monte Carlo (MC) simulations studies were undertaken to further corroborate the experimental results. PMID:28317849
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Comparative virulence of wild-type H1N1pdm09 influenza A isolates in swine
USDA-ARS?s Scientific Manuscript database
In 2009, a novel swine-origin H1N1 (H1N1pdm09) influenza A virus (IAV) reached pandemic status and was soon after detected in pigs worldwide. The objective of this study was to evaluate whether differences in the HA protein can affect pathogenicity and antigenicity of H1N1pdm09 in swine. We compared...
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Zhou, Yuefen; Wei, Linyi; Brady, Thomas P; Murali Mohan Redddy, P S; Nguyen, Tram; Chen, Jinhua; Au, Qingyan; Yoon, Il Sang; Yip, Gary; Zhang, Bin; Barber, Jack R; Ng, Shi Chung
2009-08-01
Pyrimido[5,4-e][1,2,4]triazine-5,7(1H,6H)-dione derivatives were investigated as novel small molecule amplifiers of heat shock factor 1 transcriptional activity. Lead optimization led to the discovery of compound 4A-13, which displayed potent HSF1 activity under mild heat stress (EC(50)=2.5microM) and significant cytoprotection in both rotenone (EC(50)=0.23microM) and oxygen-glucose deprivation cell toxicity models (80% protection at 2.5microM).
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2.1 Natural History of Highly Pathogenic Avian Influenza H5N1
Sonnberg, Stephanie; Webby, Richard J.; Webster, Robert G.
2013-01-01
The ecology of highly pathogenic avian influenza (HPAI) H5N1 has significantly changed from sporadic outbreaks in terrestrial poultry to persistent circulation in terrestrial and aquatic poultry and potentially in wild waterfowl. A novel genotype of HPAI H5N1 arose in 1996 in southern China and through ongoing mutation, reassortment, and natural selection, has diverged into distinct lineages and expanded into multiple reservoir hosts. The evolution of Goose/Guangdong-lineage highly pathogenic H5N1 viruses is ongoing: while stable interactions exist with some reservoir hosts, these viruses are continuing to evolve and adapt to others, and pose an un-calculable risk to sporadic hosts, including humans. PMID:23735535
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The transmissibility and control of pandemic influenza A (H1N1) virus.
Yang, Yang; Sugimoto, Jonathan D; Halloran, M Elizabeth; Basta, Nicole E; Chao, Dennis L; Matrajt, Laura; Potter, Gail; Kenah, Eben; Longini, Ira M
2009-10-30
Pandemic influenza A (H1N1) 2009 (pandemic H1N1) is spreading throughout the planet. It has become the dominant strain in the Southern Hemisphere, where the influenza season has now ended. Here, on the basis of reported case clusters in the United States, we estimated the household secondary attack rate for pandemic H1N1 to be 27.3% [95% confidence interval (CI) from 12.2% to 50.5%]. From a school outbreak, we estimated that a typical schoolchild infects 2.4 (95% CI from 1.8 to 3.2) other children within the school. We estimated the basic reproductive number, R0, to range from 1.3 to 1.7 and the generation interval to range from 2.6 to 3.2 days. We used a simulation model to evaluate the effectiveness of vaccination strategies in the United States for fall 2009. If a vaccine were available soon enough, vaccination of children, followed by adults, reaching 70% overall coverage, in addition to high-risk and essential workforce groups, could mitigate a severe epidemic.
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Cost-Effectiveness of 2009 Pandemic Influenza A(H1N1) Vaccination in the United States
Prosser, Lisa A.; Lavelle, Tara A.; Fiore, Anthony E.; Bridges, Carolyn B.; Reed, Carrie; Jain, Seema; Dunham, Kelly M.; Meltzer, Martin I.
2011-01-01
Background Pandemic influenza A(H1N1) (pH1N1) was first identified in North America in April 2009. Vaccination against pH1N1 commenced in the U.S. in October 2009 and continued through January 2010. The objective of this study was to evaluate the cost-effectiveness of pH1N1 vaccination. Methodology A computer simulation model was developed to predict costs and health outcomes for a pH1N1 vaccination program using inactivated vaccine compared to no vaccination. Probabilities, costs and quality-of-life weights were derived from emerging primary data on pH1N1 infections in the US, published and unpublished data for seasonal and pH1N1 illnesses, supplemented by expert opinion. The modeled target population included hypothetical cohorts of persons aged 6 months and older stratified by age and risk. The analysis used a one-year time horizon for most endpoints but also includes longer-term costs and consequences of long-term sequelae deaths. A societal perspective was used. Indirect effects (i.e., herd effects) were not included in the primary analysis. The main endpoint was the incremental cost-effectiveness ratio in dollars per quality-adjusted life year (QALY) gained. Sensitivity analyses were conducted. Results For vaccination initiated prior to the outbreak, pH1N1 vaccination was cost-saving for persons 6 months to 64 years under many assumptions. For those without high risk conditions, incremental cost-effectiveness ratios ranged from $8,000–$52,000/QALY depending on age and risk status. Results were sensitive to the number of vaccine doses needed, costs of vaccination, illness rates, and timing of vaccine delivery. Conclusions Vaccination for pH1N1 for children and working-age adults is cost-effective compared to other preventive health interventions under a wide range of scenarios. The economic evidence was consistent with target recommendations that were in place for pH1N1 vaccination. We also found that the delays in vaccine availability had a substantial
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46. OUTLET WORKS: ELECTRICAL SYSTEM NO. 1. Sheet H1, date ...
46. OUTLET WORKS: ELECTRICAL SYSTEM NO. 1. Sheet H-1, date stamped May, 1939. File no. SA 342/9. - Prado Dam, Outlet Works, Santa Ana River near junction of State Highways 71 & 91, Corona, Riverside County, CA
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Characterization of hMTr1, a Human Cap1 2′-O-Ribose Methyltransferase*
Bélanger, François; Stepinski, Janusz; Darzynkiewicz, Edward; Pelletier, Jerry
2010-01-01
Cellular eukaryotic mRNAs are capped at their 5′ ends with a 7-methylguanosine nucleotide, a structural feature that has been shown to be important for conferring mRNA stability, stimulating mRNA biogenesis (splicing, poly(A) addition, nucleocytoplasmic transport), and increasing translational efficiency. Whereas yeast mRNAs have no additional modifications to the cap, called cap0, higher eukaryotes are methylated at the 2′-O-ribose of the first or the first and second transcribed nucleotides, called cap1 and cap2, respectively. In the present study, we identify the methyltransferase responsible for cap1 formation in human cells, which we call hMTr1 (also known as FTSJD2 and ISG95). We show in vitro that hMTr1 catalyzes specific methylation of the 2′-O-ribose of the first nucleotide of a capped RNA transcript. Using siRNA-mediated knockdown of hMTr1 in HeLa cells, we demonstrate that hMTr1 is responsible for cap1 formation in vivo. PMID:20713356
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Bortolot, Carolina S; da S M Forezi, Luana; Marra, Roberta K F; Reis, Marcelo I P; Sa, Barbara V F E; Filho, Ricardo Imbroisi; Ghasemishahrestani, Zeinab; Sola-Penna, Mauro; Zancan, Patricia; Ferreira, Vitor F; de C da Silva, Fernando
2018-05-23
Low molecular weight 1,2,3-triazoles and naphthoquinones are endowed with various types of biological activity, such as against cancer, HIV and bacteria. However, in some cases, the conjugation of these two nuclei considerably increases their biological activities Objective: In this work, we decided to study the synthesis and screening of bis-naphthoquinones and xanthenes tethered to 1,2,3-triazoles against cancer cell lines, specifically the human breast cancer cell line MCF-7. Starting from lawsone and aryl-1H-1,2,3-triazole-4-carbaldehydes (10a-h) several new 7-(1-aryl-1H-1,2,3-triazol-4-yl)-6H-dibenzo[b,h]xanthene-5,6,8,13(7H)-tetraones (12a-h) and 3,3'-((1-aryl-1H-1,2,3-triazol-4-yl)methylene)bis(2-hydroxynaphthalene-1,4-diones) 11a-h were synthesized and evaluated for their cytotoxic activities using the human breast cancer cell line MCF-7 and the non-tumor cell line MCF10A as control. We performed test of cell viability, cell proliferation, intracellular ATP content and cell cytometry to determine reactive oxygen species (ROS) formation. Based on these results, we found that compound 12a promote ROS production, interfering with energy metabolism, cell viability and proliferation, and thus promoting an whole cell damage. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
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Maia, Lucas de Lima; Peterle, Gabriela Tonini; Dos Santos, Marcelo; Trivilin, Leonardo Oliveira; Mendes, Suzanny Oliveira; de Oliveira, Mayara Mota; Dos Santos, Joaquim Gasparini; Stur, Elaine; Agostini, Lidiane Pignaton; Couto, Cinthia Vidal Monteiro da Silva; Dalbó, Juliana; de Assis, Aricia Leone Evangelista Monteiro; Archanjo, Anderson Barros; Mercante, Ana Maria Da Cunha; Lopez, Rossana Veronica Mendoza; Nunes, Fábio Daumas; de Carvalho, Marcos Brasilino; Tajara, Eloiza Helena; Louro, Iúri Drumond; Álvares-da-Silva, Adriana Madeira
2018-01-01
Jumonji Domain-Containing 1A (JMJD1A) protein promotes demethylation of histones, especially at lysin-9 of di-methylated histone H3 (H3K9me2) or mono-methylated (H3K9me1). Increased levels of H3 histone methylation at lysin-9 (H3K9) is related to tumor suppressor gene silencing. JMJD1A gene target Adrenomeduline (ADM) has shown to promote cell growth and tumorigenesis. JMJD1A and ADM expression, as well as H3K9 methylation level have been related with development risk and prognosis of several tumor types. We aimed to evaluate JMJD1A, ADM, H3K9me1 and H3K9me2expression in paraffin-embedded tissue microarrays from 84 oral and oropharyngeal squamous cell carcinoma samples through immunohistochemistry analysis. Our results showed that nuclear JMJD1A expression was related to lymph node metastasis risk. In addition, JMJD1A cytoplasmic expression was an independent risk marker for advanced tumor stages. H3K9me1 cytoplasmic expression was associated with reduced disease-specific death risk. Furthermore, high H3K9me2 nuclear expression was associated with worse specific-disease and disease-free survival. Finally, high ADM cytoplasmic expression was an independent marker of lymph node metastasis risk. JMJD1A, H3K9me1/2 and ADM expression may be predictor markers of progression and prognosis in oral and oropharynx cancer patients, as well as putative therapeutic targets.
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Peterle, Gabriela Tonini; dos Santos, Marcelo; Trivilin, Leonardo Oliveira; Mendes, Suzanny Oliveira; de Oliveira, Mayara Mota; dos Santos, Joaquim Gasparini; Stur, Elaine; Agostini, Lidiane Pignaton; Couto, Cinthia Vidal Monteiro da Silva; Dalbó, Juliana; de Assis, Aricia Leone Evangelista Monteiro; Archanjo, Anderson Barros; Mercante, Ana Maria Da Cunha; Lopez, Rossana Veronica Mendoza; Nunes, Fábio Daumas; de Carvalho, Marcos Brasilino; Tajara, Eloiza Helena; Louro, Iúri Drumond; Álvares-da-Silva, Adriana Madeira
2018-01-01
Aims Jumonji Domain-Containing 1A (JMJD1A) protein promotes demethylation of histones, especially at lysin-9 of di-methylated histone H3 (H3K9me2) or mono-methylated (H3K9me1). Increased levels of H3 histone methylation at lysin-9 (H3K9) is related to tumor suppressor gene silencing. JMJD1A gene target Adrenomeduline (ADM) has shown to promote cell growth and tumorigenesis. JMJD1A and ADM expression, as well as H3K9 methylation level have been related with development risk and prognosis of several tumor types. Methods and results We aimed to evaluate JMJD1A, ADM, H3K9me1 and H3K9me2expression in paraffin-embedded tissue microarrays from 84 oral and oropharyngeal squamous cell carcinoma samples through immunohistochemistry analysis. Our results showed that nuclear JMJD1A expression was related to lymph node metastasis risk. In addition, JMJD1A cytoplasmic expression was an independent risk marker for advanced tumor stages. H3K9me1 cytoplasmic expression was associated with reduced disease-specific death risk. Furthermore, high H3K9me2 nuclear expression was associated with worse specific-disease and disease-free survival. Finally, high ADM cytoplasmic expression was an independent marker of lymph node metastasis risk. Conclusion JMJD1A, H3K9me1/2 and ADM expression may be predictor markers of progression and prognosis in oral and oropharynx cancer patients, as well as putative therapeutic targets. PMID:29590186
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Restored PB1-F2 in the 2009 Pandemic H1N1 Influenza Virus Has Minimal Effects in Swine
Pena, Lindomar; Loving, Crystal L.; Henningson, Jamie N.; Lager, Kelly M.; Lorusso, Alessio
2012-01-01
PB1-F2 is an 87- to 90-amino-acid-long protein expressed by certain influenza A viruses. Previous studies have shown that PB1-F2 contributes to virulence in the mouse model; however, its role in natural hosts—pigs, humans, or birds—remains largely unknown. Outbreaks of domestic pigs infected with the 2009 pandemic H1N1 influenza virus (pH1N1) have been detected worldwide. Unlike previous pandemic strains, pH1N1 viruses do not encode a functional PB1-F2 due to the presence of three stop codons resulting in premature truncation after codon 11. However, pH1N1s have the potential to acquire the full-length form of PB1-F2 through mutation or reassortment. In this study, we assessed whether restoring the full-length PB1-F2 open reading frame (ORF) in the pH1N1 background would have an effect on virus replication and virulence in pigs. Restoring the PB1-F2 ORF resulted in upregulation of viral polymerase activity at early time points in vitro and enhanced virus yields in porcine respiratory explants and in the lungs of infected pigs. There was an increase in the severity of pneumonia in pigs infected with isogenic virus expressing PB1-F2 compared to the wild-type (WT) pH1N1. The extent of microscopic pneumonia correlated with increased pulmonary levels of alpha interferon and interleukin-1β in pigs infected with pH1N1 encoding a functional PB1-F2 but only early in the infection. Together, our results indicate that PB1-F2 in the context of pH1N1 moderately modulates viral replication, lung histopathology, and local cytokine response in pigs. PMID:22379102
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Jiménez, Luisa Fernanda Mancipe; Ramírez Nieto, Gloria; Alfonso, Victor Vera; Correa, Jairo Jaime
2014-08-01
Porcine respiratory disease complex (PRDC) is a serious health problem that mainly affects growing and finishing pigs. PRDC is caused by a combination of viral and bacterial agents, such as porcine reproductive and respiratory syndrome virus (PRRSV), swine influenza virus (SIV), Mycoplasma hyopneumoniae (Myh), Actinobacillus pleuropneumoniae (APP), Pasteurella multocida and Porcine circovirus 2 (PCV2). To characterize the specific role of swine influenza virus in PRDC presentation in Colombia, 11 farms from three major production regions in Colombia were examined in this study. Nasal swabs, bronchial lavage and lung tissue samples were obtained from animals displaying symptoms compatible with SIV. Isolation of SIV was performed in 9-day embryonated chicken eggs or Madin-Darby Canine Kidney (MDCK) cells. Positive isolates, identified via the hemagglutination inhibition test, were further analyzed using PCR. Overall, 7 of the 11 farms were positive for SIV. Notably, sequencing of the gene encoding the hemagglutinin (HA) protein led to grouping of strains into circulating viruses identified during the human outbreak of 2009, classified as pandemic H1N1-2009. Serum samples from 198 gilts and multiparous sows between 2008 and 2009 were obtained to determine antibody presence of APP, Myh, PCV2 and PRRSV in both SIV-H1N1p-negative and -positive farms, but higher levels were recorded for SIV-H1N1p-positive farms. Odds ratio (OR) and P values revealed statistically significant differences (p<0.05) in PRDC presentation in gilts and multiparous sows of farms positive for SIV-H1N1p. Our findings indicate that positive farms have increased risk of PRDC presentation, in particular, PCV2, APP and Myh.
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Electronic properties of in-plane phase engineered 1T'/2H/1T' MoS2
NASA Astrophysics Data System (ADS)
Thakur, Rajesh; Sharma, Munish; Ahluwalia, P. K.; Sharma, Raman
2018-04-01
We present the first principles studies of semi-infinite phase engineered MoS2 along zigzag direction. The semiconducting (2H) and semi-metallic (1T') phases are known to be stable in thin-film MoS2. We described the electronic and structural properties of the infinite array of 1T'/2H/1T'. It has been found that 1T'phase induced semi-metallic character in 2H phase beyond interface but, only Mo atoms in 2H phase domain contribute to the semi-metallic nature and S atoms towards semiconducting state. 1T'/2H/1T' system can act as a typical n-p-n structure. Also high holes concentration at the interface of Mo layer provides further positive potential barriers.
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Frieling, Michelle L; Williams, Angela; Al Shareef, Turki; Kala, Gunjeet; Teh, Jun Chuan; Langlois, Valerie; Allen, Upton D; Hebert, Diane; Robinson, Lisa A
2012-03-01
In 2009, novel influenza A H1N1 caused significant morbidity and mortality worldwide, particularly in children. Because they are immunocompromised, pediatric transplant recipients are presumed to be at high risk. This study assessed epidemiological characteristics, presenting symptoms, and clinical course among pediatric renal transplant recipients with confirmed H1N1 infection. A retrospective review was conducted in renal transplant recipients followed at The Hospital for Sick Children (Toronto) who contracted H1N1 infection between June and November, 2009. Epidemiological, clinical, and laboratory features at presentation, and clinical course were analyzed. Of 59 children, 14 (23.7%) developed H1N1 infection. Children with H1N1 infection had undergone kidney transplantation more recently than their uninfected counterparts. The most common symptoms included fever (92.9%), cough (85.7%), headache (42.9%), and vomiting (42.9%). Fifty percent of patients required hospitalization, of median duration 3.0 (1.0-5.0) days. No child required intensive care treatment. Half the H1N1-infected children had acute renal dysfunction, with serum creatinine elevated >10% above basal values (median increase 21.6 [14.3-46.2]%). In five of the seven children, serum creatinine returned to baseline within two wk. These findings indicate that H1N1 influenza infection in pediatric kidney transplant recipients followed at our center was surprisingly mild, and produced no lasting sequelae. © 2011 John Wiley & Sons A/S.
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Antypenko, Oleksii M.; Kovalenko, Sergiy I.; Zhernova, Galina O.
2016-01-01
Methods of 1-[2-(1H-tetrazol-5-yl)-R1-phenyl]-3-R2-phenyl(ethyl)ureas and R1-tetrazolo[1,5-c]quinazolin-5(6H)-ones synthesis were designed. IR, LC-MS, 1H NMR, and elemental analysis data evaluated the structure and purity of the obtained compounds. Different products, depending on the reaction conditions, were distinguished and discussed. The preliminary hypoglycemic activity of 36 synthesized compounds was revealed. Docking studies to 11β-hydroxysteroid dehydrogenase 1, γ-peroxisome proliferator-activated receptor, and dipeptidyl peptidase-4 were conducted. Eight of these substances were further tested on glucocorticoid-induced insulin resistance models, namely glucose tolerance, oral rapid insulin, and adrenalin tests. One of the most active compounds turned out to be tetrazolo[1,5-c]quinazolin-5(6H)-one 3.1, exceeding the reference drugs Metformin (50 and 200 mg/kg) and Gliclazide (50 mg/kg). PMID:27222601
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Anti-pandemic influenza A (H1N1) virus potential of catechin and gallic acid.
You, Huey-Ling; Huang, Chao-Chun; Chen, Chung-Jen; Chang, Cheng-Chin; Liao, Pei-Lin; Huang, Sheng-Teng
2018-05-01
The pandemic influenza A (H1N1) virus has spread worldwide and infected a large proportion of the human population. Discovery of new and effective drugs for the treatment of influenza is a crucial issue for the global medical community. According to our previous study, TSL-1, a fraction of the aqueous extract from the tender leaf of Toonasinensis, has demonstrated antiviral activities against pandemic influenza A (H1N1) through the down-regulation of adhesion molecules and chemokine to prevent viral attachment. The aim of the present study was to identify the active compounds in TSL-1 which exert anti-influenza A (H1N1) virus effects. XTT assay was used to detect the cell viability. Meanwhile, the inhibitory effect on the pandemic influenza A (H1N1) virus was analyzed by observing plaque formation, qRT-PCR, neuraminidase activity, and immunofluorescence staining of influenza A-specific glycoprotein. Both catechin and gallic acid were found to be potent inhibitors in terms of influenza virus mRNA replication and MDCK plaque formation. Additionally, both compounds inhibited neuraminidase activities and viral glycoprotein. The 50% effective inhibition concentration (EC 50 ) of catechin and gallic acid for the influenza A (H1N1) virus were 18.4 μg/mL and 2.6 μg/mL, respectively; whereas the 50% cytotoxic concentrations (CC 50 ) of catechin and gallic acid were >100 μg/mL and 22.1 μg/mL, respectively. Thus, the selectivity indexes (SI) of catechin and gallic acid were >5.6 and 22.1, respectively. The present study demonstrates that catechin might be a safe reagent for long-term use to prevent influenza A (H1N1) virus infection; whereas gallic acid might be a sensitive reagent to inhibit influenza virus infection. We conclude that these two phyto-chemicals in TSL-1 are responsible for exerting anti-pandemic influenza A (H1N1) virus effects. Copyright © 2017. Published by Elsevier Taiwan LLC.
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Henrich, Natalie; Holmes, Bev
2011-04-18
During the 2009 H1N1 pandemic, a vaccine was made available to all Canadians. Despite efforts to promote vaccination, the public's intent to vaccinate remained low. In order to better understand the public's resistance to getting vaccinated, this study addressed factors that influenced the public's decision making about uptake. To do this, we used a relatively novel source of qualitative data--comments posted on-line in response to news articles on a particular topic. This study analysed 1,796 comments posted in response to 12 articles dealing with H1N1 vaccine on websites of three major Canadian news sources. Articles were selected based on topic and number of comments. A second objective was to assess the extent to which on-line comments can be used as a reliable data source to capture public attitudes during a health crisis. The following seven themes were mentioned in at least 5% of the comments (% indicates the percentage of comments that included the theme): fear of H1N1 (18.8%); responsibility of media (17.8%); government competency (17.7%); government trustworthiness (10.7%); fear of H1N1 vaccine (8.1%); pharmaceutical companies (7.6%); and personal protective measures (5.8%). It is assumed that the more frequently a theme was mentioned, the more that theme influenced decision making about vaccination. These key themes for the public were often not aligned with the issues and information officials perceived, and conveyed, as relevant in the decision making process. The main themes from the comments were consistent with results from surveys and focus groups addressing similar issues, which suggest that on-line comments do provide a reliable source of qualitative data on attitudes and perceptions of issues that emerge in a health crisis. The insights derived from the comments can contribute to improved communication and policy decisions about vaccination in health crises that incorporate the public's views.
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Henrich, Natalie; Holmes, Bev
2011-01-01
During the 2009 H1N1 pandemic, a vaccine was made available to all Canadians. Despite efforts to promote vaccination, the public's intent to vaccinate remained low. In order to better understand the public's resistance to getting vaccinated, this study addressed factors that influenced the public's decision making about uptake. To do this, we used a relatively novel source of qualitative data – comments posted on-line in response to news articles on a particular topic. This study analysed 1,796 comments posted in response to 12 articles dealing with H1N1 vaccine on websites of three major Canadian news sources. Articles were selected based on topic and number of comments. A second objective was to assess the extent to which on-line comments can be used as a reliable data source to capture public attitudes during a health crisis. The following seven themes were mentioned in at least 5% of the comments (% indicates the percentage of comments that included the theme): fear of H1N1 (18.8%); responsibility of media (17.8%); government competency (17.7%); government trustworthiness (10.7%); fear of H1N1 vaccine (8.1%); pharmaceutical companies (7.6%); and personal protective measures (5.8%). It is assumed that the more frequently a theme was mentioned, the more that theme influenced decision making about vaccination. These key themes for the public were often not aligned with the issues and information officials perceived, and conveyed, as relevant in the decision making process. The main themes from the comments were consistent with results from surveys and focus groups addressing similar issues, which suggest that on-line comments do provide a reliable source of qualitative data on attitudes and perceptions of issues that emerge in a health crisis. The insights derived from the comments can contribute to improved communication and policy decisions about vaccination in health crises that incorporate the public's views. PMID:21533161
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BRCA1 regulation on β-hCG: a mechanism for tumorigenicity in BRCA1 defective breast cancer.
Sengodan, S K; Nadhan, R; Nair, R S; Hemalatha, S K; Somasundaram, V; Sushama, R R; Rajan, A; Latha, N R; Varghese, G R; Thankappan, R K; Kumar, J M; Chil, A; Anilkumar, T V; Srinivas, P
2017-09-04
Human chorionic gonadotropin β (β-hCG) has been implicated in breast tumorigenesis. However, the role of this hormone is highly controversial as certain studies suggest it has anti-tumor properties while others have found it to be pro-tumorigenic. To unveil the truth, we have analyzed the expression of β-hCG in breast cancer. We identified for the first time that β-hCG expression is linked to BRCA1 status and its overexpression is seen in BRCA1 mutated breast cancer cells, BRCA1 conditional knockout mouse breast cancer tissues and BRCA1 floxed basal cell carcinoma (BCC) tissues. An analysis of three large, transcriptomic data sets from TCGA (The Cancer Genome Atlas) expression profile confirmed the inverse correlation between BRCA1 and β-hCG in human breast cancer. Using ChIP and luciferase assays, we also demonstrated that the cancer cells with wild-type but not mutant BRCA1 directly repress the expression of β-hCG by binding to its promoter. Further, β-hCG promotes migration and invasion predominantly in BRCA1 mutant breast cancer cells. Interestingly, stable overexpression of β-hCG in BRCA1 mutant but not wild-type breast cancer cells results in the formation of spheres even on monolayer cultures. The cells of these spheres show high expression of both EMT and stem cell markers. Since β-hCG belongs to a cysteine knot family of proteins like TGFβ and TGFβ signaling is deregulated in BRCA1 defective tumors, we checked whether β-hCG can mediate signaling through TGFβRII in BRCA1 mutated cells. We found for the first time that β-hCG can bind and phosphorylate TGFβRII, irrespective of LHCGR status and induce proliferation in BRCA1 defective cells. Our results confirmed that there exists a transcriptional regulation of BRCA1 on β-hCG and BRCA1 mutation promotes β-hCG mediated tumorigenesis through TGFβRII signaling. Thus inhibiting β-hCG-TGFβRII could prove an effective treatment strategy for BRCA1 mutated tumors.
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Distribution of gene segments of the pandemic A(H1N1) 2009 virus lineage in pig populations.
Okuya, K; Matsuu, A; Kawabata, T; Koike, F; Ito, M; Furuya, T; Taneno, A; Akimoto, S; Deguchi, E; Ozawa, M
2018-05-06
Swine influenza viruses (SIVs) are important not only for pig farming, but also for public health. In fact, pandemic A(H1N1) 2009 viruses [A(H1N1)pdm09] were derived from SIVs. Therefore, timely characterization of locally circulating SIVs is necessary for understanding the global status of SIVs. To genetically characterize SIVs circulating in Japanese pig populations, we isolated 24 SIVs of three subtypes (17 H1N1, four H1N2 and three H3N2 strains) from 14 pig farms in Japan from 2013 to 2016. Genetic analyses revealed that the haemagglutinin (HA) and neuraminidase (NA) genes of the 17 H1N1 and the HA gene of one H1N2, A/swine/Aichi/02/2016 (H1N2), SIVs belonged to the A(H1N1)pdm09 lineage. More importantly, all of the remaining six gene segments (i.e., PB1, PB1, PA, NP, M and NS) of the 24 SIVs, regardless of the HA and NA subtype, were also classified as belonging to the A(H1N1)pdm09 lineage. These results indicate that gene segments of A(H1N1)pdm09 lineage are widely distributed in SIVs circulating in Japanese pig populations In addition, the NA gene of A/swine/Aichi/02/2016 (H1N2) shared less than 88.5% nucleotide identity with that of the closest relative A/swine/Miyagi/5/2003 (H1N2), which was isolated in Japan in 2003. These results indicate the sustained circulation of classical H1N2-derived SIVs with remarkable diversity in the NA genes in Japanese pig populations. These findings highlight the necessity of both intensive biosecurity systems and active SIV surveillance in pig populations worldwide for both animal and public health. © 2018 Blackwell Verlag GmbH.
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Asymptomatic ratio for seasonal H1N1 influenza infection among schoolchildren in Taiwan.
Hsieh, Ying-Hen; Tsai, Chen-An; Lin, Chien-Yu; Chen, Jin-Hua; King, Chwan-Chuen; Chao, Day-Yu; Cheng, Kuang-Fu
2014-02-12
Studies indicate that asymptomatic infections do indeed occur frequently for both seasonal and pandemic influenza, accounting for about one-third of influenza infections. Studies carried out during the 2009 pH1N1 pandemic have found significant antibody response against seasonal H1N1 and H3N2 vaccine strains in schoolchildren receiving only pandemic H1N1 monovalent vaccine, yet reported either no symptoms or only mild symptoms. Serum samples of 255 schoolchildren, who had not received vaccination and had pre-season HI Ab serotiters <40, were collected from urban, rural areas and an isolated island in Taiwan during the 2005-2006 influenza season. Their hemagglutination inhibition antibody (HI Ab) serotiters against the 2005 A/New Caledonia/20/99 (H1N1) vaccine strain at pre-season and post-season were measured to determine the symptoms with the highest correlation with infection, as defined by 4-fold rise in HI titer. We estimate the asymptomatic ratio, or the proportion of asymptomatic infections, for schoolchildren during the 2005-6 influenza season when this vaccine strain was found to be antigenically related to the circulating H1N1 strain. Fever has the highest correlation with the 2005-06 seasonal influenza A(H1N1) infection, followed by headache, cough, vomiting, and sore throat. Asymptomatic ratio for the schoolchildren is found to range between 55.6% (95% CI: 44.7-66.4)-77.9% (68.8-87.0) using different sets of predictive symptoms. Moreover, the asymptomatic ratio was 66.9% (56.6-77.2) when using US-CDC criterion of fever + (cough/sore throat), and 73.0 (63.3-82.8) when under Taiwan CDC definition of Fever + (cough or sore throat or nose) + ( headache or pain or fatigue). Asymptomatic ratio for children is found to be substantially higher than that of the general population in literature. In providing reasonable quantification of the asymptomatic infected children spreading pathogens to others in a seasonal epidemic or a pandemic, our estimates
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Urzúa, Alejandro; Echeverría, Javier; Rezende, Marcos C; Wilkens, Marcela
2008-10-01
A re-examination of cuticular components of Heliotropium filifolium allowed the isolation of four new compounds: 3'-hydroxy-2',2',6'-trimethyl-3H-spiro[1-benzo-furan-2,1'-cyclohexane]-5-carboxylic acid(2), methyl 3'-acetyloxy-2',2',6'-trimethyl-3H-spiro[1-benzofuran-2,1'-cyclohexane]-5-carboxylate (3), methyl 3'-isopentanoyloxy-2',2',6'-trimethyl-3H-spiro[1-benzofuran-2,1'-cyclohexane]-5-carboxylate (4) and methyl 3'-benzoyloxy-2',2',6'-trimethyl-3H-spiro[1-benzofuran-2,1'-cyclohexane]-5-carboxylate (5).Compounds 2-5 were identified by their spectroscopic analogies with filifolinol (1), and their structures confirmed by chemical correlation with 1. The antimicrobial properties of the compounds were tested against Gram positive and Gram negative bacteria. Some of them proved to be active against Gram positive, but inactive against Gram negative bacteria. In searching for structure-activity relationships from the obtained MIC values, lipophilicity was shown to be an important variable.
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Illinois department of public health H1N1/A pandemic communications evaluation survey.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Walsh, D.; Decision and Information Sciences
Because of heightened media coverage, a 24-hour news cycle and the potential miscommunication of health messages across all levels of government during the onset of the H1N1 influenza outbreak in spring 2009, the Illinois Department of Public Health (IDPH) decided to evaluate its H1N1 influenza A communications system. IDPH wanted to confirm its disease information and instructions were helping stakeholders prepare for and respond to a novel influenza outbreak. In addition, the time commitment involved in preparing, issuing, monitoring, updating, and responding to H1N1 federal guidelines/updates and media stories became a heavy burden for IDPH staff. The process and resultsmore » of the H1N1 messaging survey represent a best practice that other health departments and emergency management agencies can replicate to improve coordination efforts with stakeholder groups during both emergency preparedness and response phases. Importantly, the H1N1 survey confirmed IDPH's messages were influencing stakeholders decisions to activate their pandemic plans and initiate response operations. While there was some dissatisfaction with IDPH's delivery of information and communication tools, such as the fax system, this report should demonstrate to IDPH that its core partners believe it has the ability and expertise to issue timely and accurate instructions that can help them respond to a large-scale disease outbreak in Illinois. The conclusion will focus on three main areas: (1) the survey development process, (2) survey results: best practices and areas for improvement and (3) recommendations: next steps.« less
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Molecular evolution of H1N1 swine influenza in Guangdong, China, 2016-2017.
Cai, Mengkai; Huang, Junming; Bu, Dexin; Yu, Zhiqing; Fu, Xinliang; Ji, Chihai; Zhou, Pei; Zhang, Guihong
2018-06-01
Swine are the main host of the H1N1 swine influenza virus (SIV), however, H1N1 can also infect humans and occasionally cause serious respiratory disease. To trace the evolution of the SIV in Guangdong, China, we performed an epidemic investigation during the period of 2016-2017. Nine H1N1 influenza viruses were isolated from swine nasal swabs. Antigenic analysis revealed that these viruses belonged to two distinct antigenic groups, represented by A/Swine/Guangdong/101/2016 and A/Swine/Guangdong/52/2017. Additionally, three genotypes, known as GD52/17-like, GD493/17-like and GD101/16-like, were identified by phylogenetic analysis. Importantly, the genotypes including a minimum of 4 pdm/09-origin internal genes have become prevalent in China in recent years. A total of 2966 swine serum samples were used to perform hemagglutination inhibition (HI) tests, and the results showed that the seroprevalence values of SW/GD/101/16 (32.2% in 2016, 32.1% in 2017) were significantly higher than the seroprevalence values of SW/GD/52/17 (18.0% in 2016, 16.7% in 2017). Our study showed that the three reassortant genotypes of H1N1 SIV currently circulating in China are stable, but H1N1pdm09 poses challenges to human health by the introduction of internal genes into these reassortant genotypes. Strengthening SIV surveillance is therefore critical for SIV control and minimizing its potential threat to public health. Copyright © 2018 Elsevier B.V. All rights reserved.
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Possible basis for the emergence of H1N1 viruses with pandemic potential from avian hosts.
Koçer, Zeynep A; Krauss, Scott; Zanin, Mark; Danner, Angela; Gulati, Shelly; Jones, Jeremy C; Friedman, Kimberly; Graham, Allison; Forrest, Heather; Seiler, Jon; Air, Gillian M; Webster, Robert G
2015-07-01
Influenza A viruses of the H1N1 subtype have emerged from the avian influenza gene pool in aquatic birds and caused human pandemics at least twice during the past century. Despite this fact, surprisingly little is known about the H1N1 gene pool in the aquatic bird reservoir. A preliminary study showed that an H1N1 virus from a shorebird of the Charadriiformes order was transmitted between animals through the airborne route of infection, whereas an H1N1 virus from a bird of the Anseriformes order was not. Here we show that two of the three H1N1 viruses isolated from Charadriiformes species in 2009 were transmitted between animals through the airborne route of infection, and five H1N1 isolates from Anseriformes species were not. The one H1N1 virus from a Charadriiformes species that failed to transmit through the airborne route was a reassortant possessing multiple internal gene segments from Anseriformes species. The molecular differences between the airborne-transmissible and non-airborne-transmissible H1N1 viruses were multigenic, involving the selection of virus with human-like receptor-binding specificity (α2-6 sialic acid) and multiple differences in the polymerase complex, mainly in the PB2, PB1-F2, and nonstructural genes.
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Possible basis for the emergence of H1N1 viruses with pandemic potential from avian hosts
Koçer, Zeynep A; Krauss, Scott; Zanin, Mark; Danner, Angela; Gulati, Shelly; Jones, Jeremy C; Friedman, Kimberly; Graham, Allison; Forrest, Heather; Seiler, Jon; Air, Gillian M; Webster, Robert G
2015-01-01
Influenza A viruses of the H1N1 subtype have emerged from the avian influenza gene pool in aquatic birds and caused human pandemics at least twice during the past century. Despite this fact, surprisingly little is known about the H1N1 gene pool in the aquatic bird reservoir. A preliminary study showed that an H1N1 virus from a shorebird of the Charadriiformes order was transmitted between animals through the airborne route of infection, whereas an H1N1 virus from a bird of the Anseriformes order was not. Here we show that two of the three H1N1 viruses isolated from Charadriiformes species in 2009 were transmitted between animals through the airborne route of infection, and five H1N1 isolates from Anseriformes species were not. The one H1N1 virus from a Charadriiformes species that failed to transmit through the airborne route was a reassortant possessing multiple internal gene segments from Anseriformes species. The molecular differences between the airborne-transmissible and non-airborne-transmissible H1N1 viruses were multigenic, involving the selection of virus with human-like receptor-binding specificity (α2-6 sialic acid) and multiple differences in the polymerase complex, mainly in the PB2, PB1-F2, and nonstructural genes. PMID:26251829
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Calculating the potential for within-flight transmission of influenza A (H1N1)
2009-01-01
Background Clearly air travel, by transporting infectious individuals from one geographic location to another, significantly affects the rate of spread of influenza A (H1N1). However, the possibility of within-flight transmission of H1N1 has not been evaluated; although it is known that smallpox, measles, tuberculosis, SARS and seasonal influenza can be transmitted during commercial flights. Here we present the first quantitative risk assessment to assess the potential for within-flight transmission of H1N1. Methods We model airborne transmission of infectious viral particles of H1N1 within a Boeing 747 using methodology from the field of quantitative microbial risk assessment. Results The risk of catching H1N1 will essentially be confined to passengers travelling in the same cabin as the source case. Not surprisingly, we find that the longer the flight the greater the number of infections that can be expected. We calculate that H1N1, even during long flights, poses a low to moderate within-flight transmission risk if the source case travels First Class. Specifically, 0-1 infections could occur during a 5 hour flight, 1-3 during an 11 hour flight and 2-5 during a 17 hour flight. However, within-flight transmission could be significant, particularly during long flights, if the source case travels in Economy Class. Specifically, two to five infections could occur during a 5 hour flight, 5-10 during an 11 hour flight and 7-17 during a 17 hour flight. If the aircraft is only partially loaded, under certain conditions more infections could occur in First Class than in Economy Class. During a 17 hour flight, a greater number of infections would occur in First Class than in Economy if the First Class Cabin is fully occupied, but Economy class is less than 30% full. Conclusions Our results provide insights into the potential utility of air travel restrictions on controlling influenza pandemics in the winter of 2009/2010. They show travel by one infectious individual
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Calculating the potential for within-flight transmission of influenza A (H1N1).
Wagner, Bradley G; Coburn, Brian J; Blower, Sally
2009-12-24
Clearly air travel, by transporting infectious individuals from one geographic location to another, significantly affects the rate of spread of influenza A (H1N1). However, the possibility of within-flight transmission of H1N1 has not been evaluated; although it is known that smallpox, measles, tuberculosis, SARS and seasonal influenza can be transmitted during commercial flights. Here we present the first quantitative risk assessment to assess the potential for within-flight transmission of H1N1. We model airborne transmission of infectious viral particles of H1N1 within a Boeing 747 using methodology from the field of quantitative microbial risk assessment. The risk of catching H1N1 will essentially be confined to passengers travelling in the same cabin as the source case. Not surprisingly, we find that the longer the flight the greater the number of infections that can be expected. We calculate that H1N1, even during long flights, poses a low to moderate within-flight transmission risk if the source case travels First Class. Specifically, 0-1 infections could occur during a 5 hour flight, 1-3 during an 11 hour flight and 2-5 during a 17 hour flight. However, within-flight transmission could be significant, particularly during long flights, if the source case travels in Economy Class. Specifically, two to five infections could occur during a 5 hour flight, 5-10 during an 11 hour flight and 7-17 during a 17 hour flight. If the aircraft is only partially loaded, under certain conditions more infections could occur in First Class than in Economy Class. During a 17 hour flight, a greater number of infections would occur in First Class than in Economy if the First Class Cabin is fully occupied, but Economy class is less than 30% full. Our results provide insights into the potential utility of air travel restrictions on controlling influenza pandemics in the winter of 2009/2010. They show travel by one infectious individual, rather than causing a single outbreak of H1N
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Inactivation and removal of influenza A virus H1N1 during the manufacture of plasma derivatives.
Jeong, Eun Kyo; Sung, Hark Mo; Kim, In Seop
2010-11-01
Although transmission of pandemic influenza A virus H1N1 2009 is still occurring globally, little has been reported about how this outbreak has affected the safety of plasma derivatives. To evaluate the safety of plasma derivatives, dedicated virus clearance processes used during their production were investigated for their effectiveness in eliminating this virus of recent concern. In this study, influenza A virus H1N1 strain A/NWS/33 (H1N1) was chosen as a surrogate. H1N1 was completely inactivated by fraction IV fractionation as well as pasteurization during the manufacture of albumin. H1N1 was also effectively removed into the precipitate by fraction III fractionation and completely inactivated by low pH incubation as well as pasteurization during the manufacture of intravenous immunoglobulin. H1N1 was completely inactivated within 1 min of solvent/detergent treatment using 0.3% tri (n-butyl) phosphate and 1.0% Triton X-100 and also completely inactivated within 10 min of dry-heat treatment at 98 °C during the manufacture of factor VIII. H1N1 was completely removed by virus filtration process using Viresolve NFP filter and also completely inactivated by pasteurization during the manufacture of anti-thrombin III. These results indicate that all the virus clearance processes commonly used have sufficient H1N1 reducing capacity to achieve a high margin of safety. Copyright © 2010 The International Association for Biologicals. Published by Elsevier Ltd. All rights reserved.
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Yao, Hai-Ping; Zhu, Zhi-Xiang; Ji, Ming; Chen, Xiao-Guang; Xu, Bai-Ling
2014-04-01
Poly(ADP-ribose) polymerase-1 (PARP-1) has emerged as a promising anticancer drug target due to its key role in the DNA repair process. It can polymerize ADP-ribose units on its substrate proteins which are involved in the regulation of DNA repair. In this work, a novel series of para-substituted 1-benzyl-quinazoline-2, 4 (1H, 3H)-diones was designed and synthesized, and the inhibitory activities against PARP-1 of compounds 7a-7e, 8a-8f, 9a-9c and 10a-10c were evaluated. Of all the tested compounds, nine compounds displayed inhibitory activities with IC50 values ranging from 4.6 to 39.2 micromol x L(-1). In order to predict the binding modes of the potent molecules, molecular docking was performed using CDOCKER algorithm, and that will facilitate to further develop more potent PARP-1 inhibitors with a quinazolinedione scaffold.
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Twin Peaks: A/H1N1 Pandemic Influenza Virus Infection and Vaccination in Norway, 2009–2010
Van Effelterre, Thierry; Dos Santos, Gaël; Shinde, Vivek
2016-01-01
Background Vaccination campaigns against A/H1N1 2009 pandemic influenza virus (A/H1N1p) began in autumn 2009 in Europe, after the declaration of the pandemic at a global level. This study aimed to estimate the proportion of individuals vaccinated against A/H1N1p in Norway who were already infected (asymptomatically or symptomatically) by A/H1N1p before vaccination, using a mathematical model. Methods A dynamic, mechanistic, mathematical model of A/H1N1p transmission was developed for the Norwegian population. The model parameters were estimated by calibrating the model-projected number of symptomatic A/H1N1p cases to the number of laboratory-confirmed A/H1N1p cases reported to the surveillance system, accounting for potential under-reporting. It was assumed in the base case that the likelihood of vaccination was independent of infection/disease state. A sensitivity analysis explored the effects of four scenarios in which current or previous symptomatic A/H1N1p infection would influence the likelihood of being vaccinated. Results The number of model-projected symptomatic A/H1N1p cases by week during the epidemic, accounting for under-reporting and timing, closely matched that of the laboratory-confirmed A/H1N1p cases reported to the surveillance system. The model-projected incidence of symptomatic A/H1N1p infection was 27% overall, 55% in people <10 years old and 41% in people 10–20 years old. The model-projected percentage of individuals vaccinated against A/H1N1p who were already infected with A/H1N1p before being vaccinated was 56% overall, 62% in people <10 years old and 66% in people 10–20 years old. The results were sensitive to assumptions about the independence of vaccination and infection; however, even when current or previous symptomatic A/H1N1p infection was assumed to reduce the likelihood of vaccination, the estimated percentage of individuals who were infected before vaccination remained at least 32% in all age groups. Conclusion This analysis
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Development of Tricyclic Hydroxy-1H-pyrrolopyridine-trione Containing HIV-1 Integrase Inhibitors
Zhao, Xue Zhi; Maddali, Kasthuraiah; Metifiot, Mathieu; Smith, Steven J.; Vu, B. Christie; Marchand, Christophe; Hughes, Stephen H.; Pommier, Yves; Burke, Terrence R.
2011-01-01
New tricyclic HIV-1 integrase (IN) inhibitors were prepared that combined structural features of bicyclic pyrimidinones with recently disclosed 4,5-dihydroxy-1H-isoindole-1,3(2H)-diones. This combination resulted in the introduction of a nitrogen into the aryl ring and the addition of a fused third ring to our previously described inhibitors. The resulting analogues showed low micromolar inhibitory potency in in vitro HIV-1 integrase assays, with good selectivity for strand transfer relative to 3′-processing. PMID:21493066
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Mo, Phoenix K H; Lau, Joseph T F
2015-12-01
This study examined illness representations of new influenza Human Swine Influenza A (H1N1) and association with H1N1 preventive behaviors among 300 Chinese adults using a population-based randomized telephone survey. Results showed that relatively few participants thought H1N1 would have serious consequences (12%-15.7%) and few showed negative emotional responses toward H1N1 (9%-24.7%). The majority of the participants thought H1N1 could be controlled by treatment (70.4%-72.7%). Multiple logistic regression analyses showed that treatment control (odds ratio = 1.78) and psychological attribution (odds ratio = .75) were associated with intention to take up influenza vaccination. Emotional representations were associated with lower likelihood of wearing face mask (odds ratio = .77) and hand washing (odds ratio = .67). Results confirm that illness representation variables are associated with H1N1 preventive behaviors. © The Author(s) 2014.
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Transcriptional regulation of α1H T-type calcium channel under hypoxia
Sellak, Hassan; Zhou, Chun; Liu, Bainan; Chen, Hairu; Lincoln, Thomas M.
2014-01-01
The low-voltage-activated T-type Ca2+ channels play an important role in mediating the cellular responses to altered oxygen tension. Among three T-type channel isoforms, α1G, α1H, and α1I, only α1H was found to be upregulated under hypoxia. However, mechanisms underlying such hypoxia-dependent isoform-specific gene regulation remain incompletely understood. We, therefore, studied the hypoxia-dependent transcriptional regulation of α1G and α1H gene promoters with the aim to identify the functional hypoxia-response elements (HREs). In rat pulmonary artery smooth muscle cells (PASMCs) and pheochromocytoma (PC12) cells after hypoxia (3% O2) exposure, we observed a prominent increase in α1H mRNA at 12 h along with a significant rise in α1H-mediated T-type current at 24 and 48 h. We then cloned two promoter fragments from the 5′-flanking regions of rat α1G and α1H gene, 2,000 and 3,076 bp, respectively, and inserted these fragments into a luciferase reporter vector. Transient transfection of PASMCs and PC12 cells with these recombinant constructs and subsequent luciferase assay revealed a significant increase in luciferase activity from the reporter containing the α1H, but not α1G, promoter fragment under hypoxia. Using serial deletion and point mutation analysis strategies, we identified a functional HRE at site −1,173cacgc−1,169 within the α1H promoter region. Furthermore, an electrophoretic mobility shift assay using this site as a DNA probe demonstrated an increased binding activity to nuclear protein extracts from the cells after hypoxia exposure. Taken together, these findings indicate that hypoxia-induced α1H upregulation involves binding of hypoxia-inducible factor to an HRE within the α1H promoter region. PMID:25099734
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H1-MAPT and the Risk for Familial Essential Tremor
García-Martín, Elena; Martínez, Carmen; Alonso-Navarro, Hortensia; Benito-León, Julián; Lorenzo-Betancor, Oswaldo; Pastor, Pau; López-Alburquerque, Tomás; Samaranch, Lluis; Lorenzo, Elena; Agúndez, José A. G.; Jiménez-Jiménez, Félix Javier
2012-01-01
The most frequent MAPT H1 haplotype is associated with the risk for developing progressive supranuclear palsy and other neurodegenerative diseases such as Parkinson’s disease. A recent report suggests that the MAPT H1 is associated with the risk for developing essential tremor. We wanted to confirm this association in a different population. We analyzed the distribution of allelic and genotype frequencies of rs1052553, which is an H1/H2 SNP, in 200 subjects with familial ET and 291 healthy controls. rs1052553 genotype and allelic frequencies did not differ significantly between subjects with ET and controls and were unrelated with the age at onset of tremor or gender, and with the presence of head, voice, chin, and tongue tremor. Our study suggests that the MAPT H1 rs1052553 is not associated with the risk for developing familial ET in the Spanish population. PMID:22911817
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Fuchs-Kliewer phonons of H-covered and clean GaN(1 1 bar 00)
NASA Astrophysics Data System (ADS)
Rink, M.; Himmerlich, M.; Krischok, S.; Kröger, J.
2018-01-01
Inelastic electron scattering is used to study surface phonon polaritons on H-covered and clean GaN(1 1 bar 00) surfaces. The Fuchs-Kliewer phonon of GaN(1 1 bar 00) -H gives rise to characteristic signatures of its single and multiple excitation in specular electron energy loss spectra. The loss intensities for multi-phonon scattering processes decrease according to a Poisson distribution. Vibrational spectra of this surface are invariant on the time scale of days reflecting its chemical passivation by the H layer. In contrast, vibrational spectra of pristine GaN(1 1 bar 00) are subject to a pronounced temporal evolution where spectroscopic weight is gradually shifted towards the multiple excitation of the Fuchs-Kliewer phonon. As a consequence, the monotonous decrease of the cross section for multiple quantum excitation as observed for the H-covered surface is not applicable. This remarkable effect is particularly strong in spectra acquired at low primary energies of incident electrons, which hints at processes occurring in the very surface region. Scenarios that may contribute to these observations are discussed.
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Structural Characterization of the 1918 Influenza H1N1 Neuraminidase
DOE Office of Scientific and Technical Information (OSTI.GOV)
Xu, X.; Zhu, X.; Dwek, R.A.
2009-05-28
Influenza virus neuraminidase (NA) plays a crucial role in facilitating the spread of newly synthesized virus in the host and is an important target for controlling disease progression. The NA crystal structure from the 1918 'Spanish flu' (A/Brevig Mission/1/18 H1N1) and that of its complex with zanamivir (Relenza) at 1.65-{angstrom} and 1.45-{angstrom} resolutions, respectively, corroborated the successful expression of correctly folded NA tetramers in a baculovirus expression system. An additional cavity adjacent to the substrate-binding site is observed in N1, compared to N2 and N9 NAs, including H5N1. This cavity arises from an open conformation of the 150 loop (Gly147more » to Asp151) and appears to be conserved among group 1 NAs (N1, N4, N5, and N8). It closes upon zanamivir binding. Three calcium sites were identified, including a novel site that may be conserved in N1 and N4. Thus, these high-resolution structures, combined with our recombinant expression system, provide new opportunities to augment the limited arsenal of therapeutics against influenza.« less
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Dennehey, Briana K.; Noone, Seth; Liu, Wallace H.; Smith, Luke
2013-01-01
The central histone H3/H4 chaperone Asf1 comprises a highly conserved globular core and a divergent C-terminal tail. While the function and structure of the Asf1 core are well known, the function of the tail is less well understood. Here, we have explored the role of the yeast (yAsf1) and human (hAsf1a and hAsf1b) Asf1 tails in Saccharomyces cerevisiae. We show, using a photoreactive, unnatural amino acid, that Asf1 tail residue 210 cross-links to histone H3 in vivo and, further, that loss of C-terminal tail residues 211 to 279 weakens yAsf1-histone binding affinity in vitro nearly 200-fold. Via several yAsf1 C-terminal truncations and yeast-human chimeric proteins, we found that truncations at residue 210 increase transcriptional silencing and that the hAsf1a tail partially substitutes for full-length yAsf1 with respect to silencing but that full-length hAsf1b is a better overall substitute for full-length yAsf1. In addition, we show that the C-terminal tail of Asf1 is phosphorylated at T270 in yeast. Loss of this phosphorylation site does not prevent coimmunoprecipitation of yAsf1 and Rad53 from yeast extracts, whereas amino acid residue substitutions at the Asf1-histone H3/H4 interface do. Finally, we show that residue substitutions in yAsf1 near the CAF-1/HIRA interface also influence yAsf1's function in silencing. PMID:23184661
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Selenolate Complexes of CYP101 and the Heme-bound hHO-1/H25A Proximal Cavity Mutant
Jiang, Yongying; Ortiz de Montellano, Paul R.
2009-01-01
Thiolate and selenolate complexes of CYP101 (P450cam) and the H25A proximal cavity mutant of heme-bound human heme oxygenase-1 (hHO-1) have been examined by UV-visible spectroscopy. Both thiolate and selenolate ligands bound to the heme distal side in CYP101 and gave rise to characteristic hyperporphyrin spectra. Thiolate ligands also bound to the proximal side of the heme in the cavity created by the H25A mutation in hHO-1, giving a Soret absorption similar to that of the H25C hHO-1 mutant. Selenolate ligands also bound to this cavity mutant under anaerobic conditions, but reduced the heme iron to the ferrous state as shown by formation of a ferrous-CO complex. Under aerobic conditions, the selenolate but not thiolate ligand was rapidly oxidized. These results indicate that selenocysteine-coordinated heme proteins will not be stable species in the absence of a redox potential stabilizing effect. PMID:18376820
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Selenolate complexes of CYP101 and the heme-bound hHO-1/H25A proximal cavity mutant.
Jiang, Yongying; Ortiz de Montellano, Paul R
2008-05-05
Thiolate and selenolate complexes of CYP101 (P450cam) and the H25A proximal cavity mutant of heme-bound human heme oxygenase-1 (hHO-1) have been examined by UV-vis spectroscopy. Both thiolate and selenolate ligands bound to the heme distal side in CYP101 and gave rise to characteristic hyperporphyrin spectra. Thiolate ligands also bound to the proximal side of the heme in the cavity created by the H25A mutation in hHO-1, giving a Soret absorption similar to that of the H25C hHO-1 mutant. Selenolate ligands also bound to this cavity mutant under anaerobic conditions but reduced the heme iron to the ferrous state, as shown by the formation of a ferrous CO complex. Under aerobic conditions, the selenolate ligand but not the thiolate ligand was rapidly oxidized. These results indicate that selenocysteine-coordinated heme proteins will not be stable species in the absence of a redox potential stabilizing effect.
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Nachbagauer, Raffael; Shore, David; Yang, Hua; Johnson, Scott K; Gabbard, Jon D; Tompkins, S Mark; Wrammert, Jens; Wilson, Patrick C; Stevens, James; Ahmed, Rafi; Krammer, Florian; Ellebedy, Ali H
2018-06-13
Broadly cross-reactive antibodies that recognize conserved epitopes within the influenza virus hemagglutinin (HA) stalk domain are of particular interest for their potential use as therapeutic and prophylactic agents against multiple influenza virus subtypes including zoonotic virus strains. Here, we characterized four human HA stalk-reactive monoclonal antibodies (mAbs) for their binding breadth and affinity, in vitro neutralization capacity, and in vivo protective potential against an highly pathogenic avian influenza virus. The monoclonal antibodies were isolated from individuals shortly following infection with (70-1F02 and 1009-3B05) or vaccination against (05-2G02 and 09-3A01) A(H1N1)pdm09. Three of the mAbs bound HAs from multiple strains of group 1 viruses, and one mAb, 05-2G02, bound to both group 1 and group 2 influenza A HAs. All four antibodies prophylactically protected mice against a lethal challenge with the highly pathogenic A/Vietnam/1203/04 (H5N1) strain. Two mAbs, 70-1F02 and 09-3A01, were further tested for their therapeutic efficacy against the same strain and showed good efficacy in this setting as well. One mAb, 70-1F02, was co-crystallized with H5 HA and showed similar heavy chain only interactions as a the previously described anti-stalk antibody CR6261. Finally, we showed that antibodies that compete with these mAbs are prevalent in serum from an individual recently infected with A(H1N1)pdm09 virus. The antibodies described here can be developed into broad-spectrum antiviral therapeutics that could be used to combat infections with zoonotic or emerging pandemic influenza viruses. IMPORTANCE The rise in zoonotic infections of humans with emerging influenza viruses is a worldwide public health concern. The majority of recent zoonotic human influenza cases were caused by H7N9 and H5Nx viruses and were associated with high morbidity and mortality. In addition, seasonal influenza viruses are estimated to cause up to 650,000 deaths annually
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1H Magnetic Resonance Spectroscopy of live human sperm.
Reynolds, S; Calvert, S J; Paley, M N; Pacey, A A
2017-07-01
Can 1H Magnetic Resonance Spectroscopy (MRS) be used to obtain information about the molecules and metabolites in live human spermatozoa? Percoll-based density gradient centrifugation (DGC) followed by a further two washing steps, yielded enough sperm with minimal contamination (<0.01%) from seminal fluid to permit effective MRS which detected significant differences (P < 0.05) in the choline/glycerophosphocholine (GPC), lipid and lactate regions of the 1H MRS spectrum between sperm in the pellet and those from the 40%/80% interface. Current methods to examine sperm are either limited in their value (e.g. semen analysis) or are destructive (e.g. immunohistochemistry, sperm DNA testing). A few studies have previously used MRS to examine sperm, but these have either looked at seminal plasma from men with different ejaculate qualities or at the molecules present in pooled samples of lyophilized sperm. Sperm suspended in phosphate buffered saline (PBS) at 37°C were examined by 1H MRS scanning using a 1H excitation-sculpting solvent suppression sequence after recovery from fresh ejaculates by one of three different methods: (i) simple centrifugation; (ii) DGC with one wash; or (iii) DGC with two washes. In the case of DGC, sperm were collected both from the pellet ('80%' sperm) and the 40/80 interface ('40%' sperm). Spectrum processing was carried out using custom Matlab scripts to determine; the degree of seminal plasma/Percoll contamination, the minimum sperm concentration for 1H MRS detection and differences between the 1H MRS spectra of '40%' and '80%' sperm. DGC with two washes minimized the 1H MRS peak intensity for both seminal plasma and Percoll/PBS solution contamination while retaining sperm specific peaks. For the MRS scanner used in this study, the minimum sperm concentration required to produce a choline/GPC 1H MRS peak greater than 3:1 signal to noise ratio (SNR) was estimated at ~3 × 106/ml. The choline/GPC and lactate/lipid regions of the 1H spectrum
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The viscosity and temperature dependence of 1H T1-NMRD of the Gd(H 2O) 83+ complex
NASA Astrophysics Data System (ADS)
Zhou, Xiangzhi; Westlund, Per-Olof
2005-11-01
Water proton T1-NMRD profiles of the Gd(H 2O) 83+ complex have been recorded at three temperatures and at four concentrations of glycerol. The analysis is performed using both the generalized Solomon-Bloembergen-Morgan (GSBM) theory [J. Magn. Reson. 167(2004), 147-160], and the stochastic Liouville approach (SLA). The GSBM approach uses a two processes dynamic model of the zero-field splitting (ZFS) correlation function whereas SLA uses a single process model. Both models reproduce the proton T1-NMRD profiles well. However, the model parameters extracted from the two analyses, yield different ESR X-band spectra which moreover do not reproduce the experimental ESR spectra. It is shown that the analyses of the proton T1-NMRD profiles recorded for a solution Gd(H 2O) 83+ ions are relatively insensitive to the slow modulation part of dynamic model of the ZFS interaction correlation function. The description of the electron spin system results in a very small static ZFS, while recent ESR lineshape analysis indicates that the contribution from the static ZFS is important. Analysis of proton T1-NMRD profiles of Gd(H 2O) 83+ complex do result in a description of the electron spin system but these microscopic parameters are uncertain unless they also are tested in a ESR-lineshape analysis.
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Gauger, Phillip C; Vincent, Amy L; Loving, Crystal L; Lager, Kelly M; Janke, Bruce H; Kehrli, Marcus E; Roth, James A
2011-03-24
Influenza is an economically important respiratory disease affecting swine world-wide with potential zoonotic implications. Genetic reassortment and drift has resulted in genetically and antigenically distinct swine influenza viruses (SIVs). Consequently, prevention of SIV infection is challenging due to the increased rate of genetic change and a potential lack of cross-protection between vaccine strains and circulating novel isolates. This report describes a vaccine-heterologous challenge model in which pigs were administered an inactivated H1N2 vaccine with a human-like (δ-cluster) H1 six and three weeks before challenge with H1 homosubtypic, heterologous 2009 pandemic H1N1. At necropsy, macroscopic and microscopic pneumonia scores were significantly higher in the vaccinated and challenged (Vx/Ch) group compared to non-vaccinated and challenged (NVx/Ch) pigs. The Vx/Ch group also demonstrated enhanced clinical disease and a significantly elevated pro-inflammatory cytokine profile in bronchoalveolar lavage fluid compared to the NVx/Ch group. In contrast, viral shedding and replication were significantly higher in NVx/Ch pigs although all challenged pigs, including Vx/Ch pigs, were shedding virus in nasal secretions. Hemagglutination inhibition (HI) and serum neutralizing (SN) antibodies were detected to the priming antigen in the Vx/Ch pigs but no measurable cross-reacting HI or SN antibodies were detected to pandemic H1N1 (pH1N1). Overall, these results suggest that inactivated SIV vaccines may potentiate clinical signs, inflammation and pneumonia following challenge with divergent homosubtypic viruses that do not share cross-reacting HI or SN antibodies. Published by Elsevier Ltd.
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Qiu, Chao; Huang, Yang; Wang, Qian; Tian, Di; Zhang, Wanju; Hu, Yunwen; Yuan, Zhenghong; Zhang, Xiaoyan; Xu, Jianqing
2012-01-01
A mass vaccination has been implemented to prevent the spread of 2009 pandemic influenza virus in China. Highly limited information is available on whether this vaccine induces cross-reactive neutralization antibodies against other subtypes of influenza viruses. We employed pseudovirus-based assays to analyze heterosubtypic neutralization responses in serum samples of 23 recipients of 2009 pandemic influenza vaccine. One dose of pandemic vaccine not only stimulated good neutralization antibodies against cognate influenza virus 2009 influenza A (H1N1), but also raised broad cross-reactive neutralization activities against seasonal H3N2 and highly pathogenic avian influenza virus H5N1 and lesser to H2N2. The cross-reactive neutralization activities were completely abolished after the removal of immunoglobin G (IgG). In contrast, H1N1 vaccination alone in influenza-naive mice elicited only vigorous homologous neutralizing activities but not cross-reactive neutralization activities. Our data suggest that the cross-reactive neutralization epitopes do exist in this vaccine and could elicit significant cross-reactive neutralizing IgG antibodies in the presence of preexisting responses. The exposure to H1N1 vaccine is likely to modify the hierarchical order of preexisting immune responses to influenza viruses. These findings provide insights into the evolution of human immunity to influenza viruses after experiencing multiple influenza virus infections and vaccinations.
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Polesello, Vania; Zupin, Luisa; Di Lenarda, Roberto; Biasotto, Matteo; Pozzato, Gabriele; Ottaviani, Giulia; Gobbo, Margherita; Crovella, Sergio; Segat, Ludovica
2017-01-01
The aetiology of Oral Lichen Planus (OLP), a chronic inflammatory disease of oral mucosa, is not yet well understood. Since innate immunity may be hypothesized as involved in the susceptibility to OLP, we studied human beta defensin 1 (hBD-1) an antimicrobial peptide constitutively expressed in the saliva, looking at functional genetic variants possibly able to diminish hBD-1 production an consequently conferring major susceptibility to OLP. We analysed three DEFB1 polymorphisms at 5' UTR, -52G>A (rs1799946), -44C>G (rs1800972), -20G>A (rs11362) and two DEFB1 polymorphisms at 3'UTR, c*5G>A (rs1047031), c*87A>G (rs1800971), with the aim of correlating these genetic variants and hBD-1 salivary level in a group of OLP patients and in healthy subjects. We also evaluated hBD-1 salivary concentrations, using ELISA, in OLP and healthy controls. We compared hBD-1 concentrations in OLP and healthy subjects: hBD-1 concentration was significantly higher in OLP patients respect to control. When considering the correlation between DEFB1 polymorphisms genotypes and hBD-1 expression levels, significant results were obtained for SNPs -52G>A (p=0.03 both in OLP patients and healthy individuals) and -44C>G (p=0.02 in OLP patients). hBD-1 production was different between OLP and healthy subjects (not age-matched with OLP). DEFB1 gene polymorphisms, -52G>A and -44C>G, correlated with hBD-1 salivary concentrations. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Mammalian-transmissible H5N1 influenza: facts and perspective.
Osterholm, Michael T; Kelley, Nicholas S
2012-01-01
Two recently submitted (but as yet unpublished) studies describe success in creating mutant isolates of H5N1 influenza A virus that can be transmitted via the respiratory route between ferrets; concern has been raised regarding human-to-human transmissibility of these or similar laboratory-generated influenza viruses. Furthermore, the potential release of methods used in these studies has engendered a great deal of controversy around publishing potential dual-use data and also has served as a catalyst for debates around the true case-fatality rate of H5N1 influenza and the capability of influenza vaccines and antivirals to impact any future unintentional or intentional release of H5N1 virus. In this report, we review available seroepidemiology data for H5N1 infection and discuss how case-finding strategies may influence the overall case-fatality rate reported by the WHO. We also provide information supporting the position that if an H5N1 influenza pandemic occurred, available medical countermeasures would have limited impact on the associated morbidity and mortality. Copyright © 2012 Osterholm et al.
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BRCA1 regulation on β-hCG: a mechanism for tumorigenicity in BRCA1 defective breast cancer
Sengodan, S K; Nadhan, R; Nair, R S; Hemalatha, S K; Somasundaram, V; Sushama, R R; Rajan, A; Latha, N R; Varghese, G R; Thankappan, R k; Kumar, J M; Chil, A; Anilkumar, T V; Srinivas, P
2017-01-01
Human chorionic gonadotropin β (β-hCG) has been implicated in breast tumorigenesis. However, the role of this hormone is highly controversial as certain studies suggest it has anti-tumor properties while others have found it to be pro-tumorigenic. To unveil the truth, we have analyzed the expression of β-hCG in breast cancer. We identified for the first time that β-hCG expression is linked to BRCA1 status and its overexpression is seen in BRCA1 mutated breast cancer cells, BRCA1 conditional knockout mouse breast cancer tissues and BRCA1 floxed basal cell carcinoma (BCC) tissues. An analysis of three large, transcriptomic data sets from TCGA (The Cancer Genome Atlas) expression profile confirmed the inverse correlation between BRCA1 and β-hCG in human breast cancer. Using ChIP and luciferase assays, we also demonstrated that the cancer cells with wild-type but not mutant BRCA1 directly repress the expression of β-hCG by binding to its promoter. Further, β-hCG promotes migration and invasion predominantly in BRCA1 mutant breast cancer cells. Interestingly, stable overexpression of β-hCG in BRCA1 mutant but not wild-type breast cancer cells results in the formation of spheres even on monolayer cultures. The cells of these spheres show high expression of both EMT and stem cell markers. Since β-hCG belongs to a cysteine knot family of proteins like TGFβ and TGFβ signaling is deregulated in BRCA1 defective tumors, we checked whether β-hCG can mediate signaling through TGFβRII in BRCA1 mutated cells. We found for the first time that β-hCG can bind and phosphorylate TGFβRII, irrespective of LHCGR status and induce proliferation in BRCA1 defective cells. Our results confirmed that there exists a transcriptional regulation of BRCA1 on β-hCG and BRCA1 mutation promotes β-hCG mediated tumorigenesis through TGFβRII signaling. Thus inhibiting β-hCG-TGFβRII could prove an effective treatment strategy for BRCA1 mutated tumors. PMID:28869585
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NASA Astrophysics Data System (ADS)
Sachs, Julian P.; Maloney, Ashley E.; Gregersen, Joshua
2017-07-01
Continuous cultures of the marine diatom Thalassiosira pseudonana were grown at irradiances between 6 and 47 μmol m-2 s-1 in order to evaluate the effect of light on hydrogen isotope fractionation in lipids. δ2H values increased with irradiance in phytol by 1.1‰ (μmol m-2 s-1)-1 and by 0.3‰ (μmol m-2 s-1)-1 in the C14:0 fatty acid, but decreased by 0.8‰ (μmol m-2 s-1)-1 in the sterol 24-methyl-cholesta-5,24(28)-dien-3β-ol (C28Δ5,24(28)). The anticorrelation between δ2H values in C28Δ5,24(28) and irradiance is attributed to enhanced sterol precursor synthesis via the plastidic methylerythritol phosphate (MEP) pathway at high irradiance, relative to the cytosolic mevalonic acid (MVA) pathway, and the supposition that MEP precursors are 2H-depleted compared to MVA precursors because they incorporate a greater proportion of hydrogen from photosynthetically produced NADPH. Increasing δ2H values of phytol and C14:0 with irradiance is attributed to a greater proportion of pyruvate, the last common precursor to both lipids, being sourced from glycolysis in the mitochondria and cytosol, where enhanced incorporation of metabolic NADPH and further hydrogen exchange with cell water can enrich pyruvate with 2H relative to pyruvate from the chloroplast. Irrespective of the biosynthetic mechanisms responsible for the 2H/1H fractionation response to light, the high sensitivity of lipid δ2H values in T. pseudonana continuous cultures would result in -30‰ to +40‰ variations in δ2H over a 40 μmol m-2 s-1 range in sub-saturating irradiance if expressed in the environment, depending on the lipid.
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Kato, Yukinari; Jin, Genglin; Kuan, Chien-Tsun; McLendon, Roger E; Yan, Hai; Bigner, Darell D
2009-12-18
IDH1 (isocitrate dehydrogenase 1) mutations have been identified as early and frequent genetic alterations in astrocytomas, oligodendrogliomas, and oligoastrocytomas as well as secondary glioblastomas. In contrast, primary glioblastomas very rarely contain IDH1 mutations, although primary and secondary glioblastomas are histologically indistinguishable. The IDH1 mutations are remarkably specific to a single codon in the conserved and functionally important Arg132 in IDH1. In gliomas, the most frequent IDH1 mutations (>90%) were G395A (R132H). In this study, we immunized mice with R132H-containing IDH1 (IDH1(R132H)) peptide. After cell fusion using Sendai virus envelope, the monoclonal antibodies (mAbs), which specifically reacted with IDH1(R132H), were screened in ELISA. One of the mAbs, IMab-1 reacted with the IDH1(R132H) peptide, but not with wild type IDH1 (IDH1(wt)) peptide in ELISA. In Western-blot analysis, IMab-1 reacted with only the IDH1(R132H) protein, not IDH1(wt) protein or the other IDH1 mutants, indicating that IMab-1 is IDH1(R132H)-specific. Furthermore, IMab-1 specifically stained the IDH1(R132H)-expressing cells in astrocytomas in immunohistochemistry, whereas it did not react with IDH1(R132H)-negative primary glioblastoma sections. In conclusion, we established an anti-IDH1(R132H)-specific monoclonal antibody IMab-1, which should be significantly useful for diagnosis and biological evaluation of mutation-bearing gliomas.
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The Potential of Avian H1N1 Influenza A Viruses to Replicate and Cause Disease in Mammalian Models
Koçer, Zeynep A.; Krauss, Scott; Stallknecht, David E.; Rehg, Jerold E.; Webster, Robert G.
2012-01-01
H1N1 viruses in which all gene segments are of avian origin are the most frequent cause of influenza pandemics in humans; therefore, we examined the disease-causing potential of 31 avian H1N1 isolates of American lineage in DBA/2J mice. Thirty of 31 isolates were very virulent, causing respiratory tract infection; 22 of 31 resulted in fecal shedding; and 10 of 31 were as pathogenic as the pandemic 2009 H1N1 viruses. Preliminary studies in BALB/cJ mice and ferrets showed that 1 of 4 isolates tested was more pathogenic than the pandemic 2009 H1N1 viruses in BALB/cJ mice, and 1 of 2 strains transmitted both by direct and respiratory-droplet contact in ferrets. Preliminary studies of other avian subtypes (H2, H3, H4, H6, H10, H12) in DBA/2J mice showed lower pathogenicity than the avian H1N1 viruses. These findings suggest that avian H1N1 influenza viruses are unique among influenza A viruses in their potential to infect mammals. PMID:22848544
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Lu, Jun; Choi, Young Joon; Fang, Zhigang Zak; Sohn, Hong Yong; Rönnebro, Ewa
2009-11-04
Magnesium hydride (MgH(2)) is an attractive candidate for solid-state hydrogen storage applications. To improve the kinetics and thermodynamic properties of MgH(2) during dehydrogenation-rehydrogenation cycles, a nanostructured MgH(2)-0.1TiH(2) material system prepared by ultrahigh-energy-high-pressure mechanical milling was investigated. High-resolution transmission electron microscope (TEM) and scanning TEM analysis showed that the grain size of the milled MgH(2)-0.1TiH(2) powder is approximately 5-10 nm with uniform distributions of TiH(2) among MgH(2) particles. Pressure-composition-temperature (PCT) analysis demonstrated that both the nanosize and the addition of TiH(2) contributed to the significant improvement of the kinetics of dehydrogenation and hydrogenation compared to commercial MgH(2). More importantly, PCT cycle analysis demonstrated that the MgH(2)-0.1TiH(2) material system showed excellent cycle stability. The results also showed that the DeltaH value for the dehydrogenation of nanostructured MgH(2)-0.1TiH(2) is significantly lower than that of commercial MgH(2). However, the DeltaS value of the reaction was also lower, which results in minimum net effects of the nanosize and the addition of TiH(2) on the equilibrium pressure of dehydrogenation reaction of MgH(2).
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26 CFR 31.3402(h)(4)-1 - Other methods.
Code of Federal Regulations, 2013 CFR
2013-04-01
... 26 Internal Revenue 15 2013-04-01 2013-04-01 false Other methods. 31.3402(h)(4)-1 Section 31.3402... Collection of Income Tax at Source § 31.3402(h)(4)-1 Other methods. (a) Maximum permissible deviations. An employer may use any other method of withholding under which the employer will deduct and withhold upon...
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26 CFR 31.3402(h)(4)-1 - Other methods.
Code of Federal Regulations, 2010 CFR
2010-04-01
... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Other methods. 31.3402(h)(4)-1 Section 31.3402... Collection of Income Tax at Source § 31.3402(h)(4)-1 Other methods. (a) Maximum permissible deviations. An employer may use any other method of withholding under which the employer will deduct and withhold upon...
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26 CFR 31.3402(h)(4)-1 - Other methods.
Code of Federal Regulations, 2011 CFR
2011-04-01
... 26 Internal Revenue 15 2011-04-01 2011-04-01 false Other methods. 31.3402(h)(4)-1 Section 31.3402... Collection of Income Tax at Source § 31.3402(h)(4)-1 Other methods. (a) Maximum permissible deviations. An employer may use any other method of withholding under which the employer will deduct and withhold upon...
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26 CFR 31.3402(h)(4)-1 - Other methods.
Code of Federal Regulations, 2012 CFR
2012-04-01
... 26 Internal Revenue 15 2012-04-01 2012-04-01 false Other methods. 31.3402(h)(4)-1 Section 31.3402... Collection of Income Tax at Source § 31.3402(h)(4)-1 Other methods. (a) Maximum permissible deviations. An employer may use any other method of withholding under which the employer will deduct and withhold upon...
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26 CFR 31.3402(h)(4)-1 - Other methods.
Code of Federal Regulations, 2014 CFR
2014-04-01
... 26 Internal Revenue 15 2014-04-01 2014-04-01 false Other methods. 31.3402(h)(4)-1 Section 31.3402... Collection of Income Tax at Source § 31.3402(h)(4)-1 Other methods. (a) Maximum permissible deviations. An employer may use any other method of withholding under which the employer will deduct and withhold upon...
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The Continuing Evolution of H5N1 and H9N2 Influenza Viruses in Bangladesh Between 2013 and 2014.
Marinova-Petkova, Atanaska; Shanmuganatham, Karthik; Feeroz, Mohammed M; Jones-Engel, Lisa; Hasan, M Kamrul; Akhtar, Sharmin; Turner, Jasmine; Walker, David; Seiler, Patrick; Franks, John; McKenzie, Pamela; Krauss, Scott; Webby, Richard J; Webster, Robert G
2016-05-01
In 2011, avian influenza surveillance at the Bangladesh live bird markets (LBMs) showed complete replacement of the highly pathogenic avian influenza (HPAI) H5N1 virus of clade 2.2.2 (Qinghai-like H5N1 lineage) by the HPAI H5N1 clade 2.3.2.1. This clade, which continues to circulate in Bangladesh and neighboring countries, is an intra-and interclade reassortant; its HA, polymerase basic 1 (PB1), polymerase (PA), and nonstructural (NS) genes come from subclade 2.3.2.1a; the polymerase basic 2 (PB2) comes from subclade 2.3.2.1c; and the NA, nucleocapsid protein (NP), and matrix (M) gene from clade 2.3.4.2. The H9N2 influenza viruses cocirculating in the Bangladesh LBMs are also reassortants, possessing five genes (NS, M, NP, PA, and PB1) from an HPAI H7N3 virus previously isolated in Pakistan. Despite frequent coinfection of chickens and ducks, reassortment between these H5N1 and H9N2 viruses has been rare. However, all such reassortants detected in 2011 through 2013 have carried seven genes from the local HPAI H5N1 lineage and the PB1 gene from the Bangladeshi H9N2 clade G1 Mideast, itself derived from HPAI H7N3 virus. Although the live birds we sampled in Bangladesh showed no clinical signs of morbidity, the emergence of this reassortant HPAI H5N1 lineage further complicates endemic circulation of H5N1 viruses in Bangladesh, posing a threat to both poultry and humans.
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26 CFR 48.6416(h)-1 - Accounting procedures for like articles.
Code of Federal Regulations, 2010 CFR
2010-04-01
... 26 Internal Revenue 16 2010-04-01 2010-04-01 true Accounting procedures for like articles. 48.6416(h)-1 Section 48.6416(h)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... Administrative Provisions of Special Application to Retailers and Manufacturers Taxes § 48.6416(h)-1 Accounting...
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Orozco, Fabián; Insuasty, Braulio; Cobo, Justo; Glidewell, Christopher
2009-05-01
The title compound, piperidinium 6-amino-3-methyl-5-nitroso-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-ide 6-amino-3-methyl-5-nitrosopyrimidine-2,4(1H,3H)-dione, C(5)H(12)N(+).C(5)H(5)N(4)O(3)(-).C(5)H(6)N(4)O(3), (I), crystallizes with Z' = 2 in the space group P1. There is an intramolecular N-H...O hydrogen bond in each pyrimidine unit and within the selected asymmetric unit the six independent components are linked by 11 hydrogen bonds, seven of the N-H...O type and four of the N-H...N type. These six-component aggregates are linked into sheets by five further hydrogen bonds, three of the N-H...O type and one each of the N-H...N and C-H...O types.
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Eaton, Abigail; Lewis, Ned; Fireman, Bruce; Hansen, John; Baxter, Roger; Gee, Julianne; Klein, Nicola P
2018-05-03
Following the H1N1 influenza pandemic in 2009, pregnant women were recommended to receive both seasonal (TIV) and H1N1 influenza vaccines. This study presents incidence of adverse birth and pregnancy outcomes among a population of pregnant women immunized with TIV and H1N1 vaccines at Kaiser Permanente Northern California during 2009-2010. We telephone surveyed pregnant Kaiser Permanente Northern California members to assess non-medically-attended reactions following H1N1, TIV or both vaccines during 2009-2010 (n=5365) in a separate study. Here we assessed preterm birth (<37weeks), very preterm birth (<32weeks), low birth weight (<2500 g, LBW), very low birth weight (<1500g), small for gestational age, spontaneous abortions, stillbirths and congenital anomalies among this cohort by comparing incidence and 95% confidence intervals between the following immunization groups: TIV only, H1N1 only, H1N1 prior to TIV immunization, TIV prior to H1N1 and both immunizations given at the same time. Results did not vary significantly between groups. Comparing H1N1 with TIV, incidence were similar for preterm births (6.37vs 6.28/100 births), very preterm births (5.30vs 8.29/1000 births), LBW (4.19vs 2.90/100 births), very LBW (4.54vs 5.52/1000 births), small for gestational age (9.99vs 9.24/1000 births), spontaneous abortion (7.10vs 6.83/1000 pregnancies), stillbirths (7.10vs 4.57/1000 pregnancies), and congenital anomalies (2.66vs 2.43/100 births). Although constrained by small sample size, complex vaccine groups, and differential vaccine availability during 2009-2010, this study found no difference in adverse birth outcomes between H1N1 vaccine and TIV. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Strategy for assessment of the colloidal and biological stability of H1N1 influenza A viruses.
Hämmerling, Frank; Lorenz-Cristea, Oliver; Baumann, Pascal; Hubbuch, Jürgen
2017-01-30
Current influenza vaccines are mostly formulated as liquids which requires a continuous cold chain to maintain the stability of the antigen. For development of vaccines with an increased stability at ambient temperatures, manifold parameters and their influences on the colloidal stability and activity of the antigen have to be understood. This work presents a strategy to examine both, the colloidal stability and the remaining biological activity of H1N1 influenza viruses under various conditions after an incubation of 40 days. H1N1 phase diagrams were generated for several pH values and different initial H1N1 and NaCl concentrations. It was shown that the highest H1N1 recoveries were obtained for pH 6 and that moderate amounts of NaCl are favorable for increased recoveries. In contrast to colloidal stability, the highest remaining HA activity was observed at pH 9. The electrostatic and hydrophobic surface properties of H1N1 were investigated to reveal the mechanisms accounting for the decrease in stability. Secondly, the capability of virus precipitation by polyethylene glycol in combination with determination of surface hydrophobicity was proven to be useful as a predictive tool to rank stability under different conditions. This methodology enables the rapid assessment of aggregation propensity of H1N1 formulations and the influence on the activity of the virus particles and might become a standard tool during the development of vaccine formulations. Copyright © 2016 Elsevier B.V. All rights reserved.
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Campus Response to Novel Influenza H1N1
ERIC Educational Resources Information Center
Journal of American College Health, 2009
2009-01-01
Colleges and universities have been engaged in pandemic planning since 2005 when the threat of H5N1 was brought to the attention of health care providers and organizations by the Centers for Disease Control and Prevention (CDC) and the World Health Organization. Schools developed plans, based on a 1918 scenario, that were centered on evacuation of…
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1H NMR spectra part 31: 1H chemical shifts of amides in DMSO solvent.
Abraham, Raymond J; Griffiths, Lee; Perez, Manuel
2014-07-01
The (1)H chemical shifts of 48 amides in DMSO solvent are assigned and presented. The solvent shifts Δδ (DMSO-CDCl3 ) are large (1-2 ppm) for the NH protons but smaller and negative (-0.1 to -0.2 ppm) for close range protons. A selection of the observed solvent shifts is compared with calculated shifts from the present model and from GIAO calculations. Those for the NH protons agree with both calculations, but other solvent shifts such as Δδ(CHO) are not well reproduced by the GIAO calculations. The (1)H chemical shifts of the amides in DMSO were analysed using a functional approach for near ( ≤ 3 bonds removed) protons and the electric field, magnetic anisotropy and steric effect of the amide group for more distant protons. The chemical shifts of the NH protons of acetanilide and benzamide vary linearly with the π density on the αN and βC atoms, respectively. The C=O anisotropy and steric effect are in general little changed from the values in CDCl3. The effects of substituents F, Cl, Me on the NH proton shifts are reproduced. The electric field coefficient for the protons in DMSO is 90% of that in CDCl3. There is no steric effect of the C=O oxygen on the NH proton in an NH…O=C hydrogen bond. The observed deshielding is due to the electric field effect. The calculated chemical shifts agree well with the observed shifts (RMS error of 0.106 ppm for the data set of 257 entries). Copyright © 2014 John Wiley & Sons, Ltd.
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Swine flu. Mexico's handling of A/H1N1 in comparative perspective.
Ear, Sophal
2012-01-01
Emerging infectious diseases (EIDs) pose international security threats because of their potential to inflict harm upon humans, crops, livestock, health infrastructure, and economies. Despite the scale of this threat, there are inherent limitations in preventing and controlling EIDs, including the scope of current disease surveillance efforts. All of this leads to the following questions in the context of Mexico's recent swine flu experience: What were the cultural, political, and economic challenges to Influenza A/H1N1 virus response in Mexico? By way of comparison, what can we learn from the U.S. experience in 1976 with A/New Jersey/76 (Hsw1N1), later referred to as H1N1? This article explores the comparative political economy of Mexico's handling of influenza virus A/H1N1 outbreak in 2009. Research provides notable observations-based on the strengths and weaknesses of each country's response--that can be used as a starting point of discussion for the design of effective EIDs surveillance programs in developing and middle-income countries. In the U.S., the speed and efficiency of the 1976 U.S. mobilization against H1N1 was laudable. Although the U.S. response to the outbreak is seldom praised, the unity of the scientific and political communities demonstrated the national ability to respond to the situation. Mexico's strongest characteristics were its transparency, as well as the cooperation the country exhibited with other nations, particularly the U.S. and Canada. While Mexico showed savvy in its effective management of public and media relations, as the article details, political, economic, and cultural problems persisted.
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Sarmento, Dmitry José de Santana; Godoy, Gustavo Pina; Miguel, Márcia Cristina da Costa; da Silveira, Éricka Janine Dantas
2016-01-01
Background The studies found in the literature associate the immunoexpression of hMLH1 and hMSH2 proteins with histologic aspects, but do not correlate it with clinical and epidemiological data. Objective To evaluate the immunoexpression of hMLH1 and hMSH2 in actinic cheilitis, correlating it with clinical characteristics. Methods We analyzed 40 cases. Histological and immunohistochemical analyses were performed. The following clinical variables were evaluated: gender, age range, ethnicity, clinical aspect and occupational sunlight exposure. Statistical evaluation included the Student t-test, while the significance level was set at 5%. Results Greater immunoexpression of hMLH1 and hMSH2 was observed in females, individuals aged over 40, and mixed-race/black patients. Furthermore, the immunoexpression of these proteins was greater in actinic cheilitis with a white-colored appearance and in patients without occupational sunlight exposure. No statistical differences were observed for the variables studied. Conclusion This study uncovered variations of hMLH1 and hMSH2 protein expression upon evaluation of clinical aspects in actinic cheilitis. PMID:27579741
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Sarmento, Dmitry José de Santana; Godoy, Gustavo Pina; Miguel, Márcia Cristina da Costa; Silveira, Éricka Janine Dantas da
2016-01-01
The studies found in the literature associate the immunoexpression of hMLH1 and hMSH2 proteins with histologic aspects, but do not correlate it with clinical and epidemiological data. To evaluate the immunoexpression of hMLH1 and hMSH2 in actinic cheilitis, correlating it with clinical characteristics. We analyzed 40 cases. Histological and immunohistochemical analyses were performed. The following clinical variables were evaluated: gender, age range, ethnicity, clinical aspect and occupational sunlight exposure. Statistical evaluation included the Student t-test, while the significance level was set at 5%. Greater immunoexpression of hMLH1 and hMSH2 was observed in females, individuals aged over 40, and mixed-race/black patients. Furthermore, the immunoexpression of these proteins was greater in actinic cheilitis with a white-colored appearance and in patients without occupational sunlight exposure. No statistical differences were observed for the variables studied. This study uncovered variations of hMLH1 and hMSH2 protein expression upon evaluation of clinical aspects in actinic cheilitis.
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In-Flight Transmission of Novel Influenza A (H1N1)
Kim, Joon Hyung; Lee, Dong-Han; Shin, Sang-Sook; Kang, Chun; Kim, Jin Seok; Jun, Byung Yool
2010-01-01
The Korea Centers for Disease Control and Prevention confirmed two patients, who had taken the same plane from Los Angeles to Seoul, with novel influenza A (H1N1). Through contact tracing, we concluded that the second patient was infected during the flight. PMID:21191459
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Expression of the serine/threonine kinase hSGK1 in chronic viral hepatitis.
Fillon, Sophie; Klingel, Karin; Wärntges, Simone; Sauter, Martina; Gabrysch, Sabine; Pestel, Sabine; Tanneur, Valerie; Waldegger, Siegfried; Zipfel, Annette; Viebahn, Richard; Häussinger, Dieter; Bröer, Stefan; Kandolf, Reinhard; Lang, Florian
2002-01-01
The human serine/threonine kinase hSGK1 is expressed ubiquitously with highest transcript levels in pancreas and liver. This study has been performed to determine the hSGK1 distribution in normal liver and its putative role in fibrosing liver disease. HSGK1-localization was determined by in situ hybridization, regulation of hSGK1-transcription by Northern blotting, fibronectin synthesis and hSGK1 phosphorylation by Western blotting. In normal liver hSGK1 was mainly transcribed by Kupffer cells. In liver tissue from patients with chronic viral hepatitis, hSGK1 transcript levels were excessively high in numerous activated Kupffer cells and inflammatory cells localized within fibrous septum formations. HSGK1 transcripts were also detected in activated hepatic stellate cells. Accordingly, Western blotting revealed that tissue from fibrotic liver expresses excessive hSGK1 protein as compared to normal liver. TGF-beta1 (2 ng/ml) increases hSGK1 transcription in both human U937 macro-phages and HepG2 hepatoma cells. H(2)O(2) (0.3 mM) activated hSGK1 and increased fibronectin formation in HepG2 cells overexpressing hSGK1 but not in HepG2 cells expressing the inactive mutant hSGK1(K127R). In conclusion hSGK1 is upregulated by TGF-beta1 during hepatitis and may contribute to enhanced matrix formation during fibrosing liver disease. Copyright 2002 S. Karger AG, Basel
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Gastric pH and residual volume after 1 and 2 h fasting time for clear fluids in children†.
Schmidt, A R; Buehler, P; Seglias, L; Stark, T; Brotschi, B; Renner, T; Sabandal, C; Klaghofer, R; Weiss, M; Schmitz, A
2015-03-01
Current guidelines suggest a fasting time of 2 h for clear fluids, which is often exceeded in clinical practice, leading to discomfort, dehydration and stressful anaesthesia induction to patients, especially in the paediatric population. Shorter fluid fasting might be a strategy to improve patient comfort but has not been investigated yet. This prospective clinical trial compares gastric pH and residual volume after 1 vs 2 h of preoperative clear fluid fasting. Children (1-16 yr, ASA I or II) undergoing elective procedures in general anaesthesia requiring tracheal intubation were randomized into group A with 60 min or B with 120 min preoperative clear fluid fasting. To determine gastric pH and residual volume, the gastric content was sampled in supine, left and right lateral patient position using an oro-gastric tube after intubation. Data are median (interquartile range) for group A or B (P<0.05). In total, 131 children aged 1.01-16.23 yr were included; gastric pH was determined in 120 cases. Patient characteristic data were similar between the two groups, except for gender (46/33 males in group A/B; P=0.02). Despite significantly shorter fasting times for clear fluids in group A compared with group B (76/136 min; P<0.001), no significant difference was observed regarding gastric pH [1.43 (1.30-1.56)/1.44 (1.29-1.68), P=0.66] or residual volume [0.43 (0.21-0.84)/0.46 (0.19-0.78) ml kg(-1), P=0.47]. One hour clear fluid fasting does not alter gastric pH or residual volume significantly compared with 2 h fasting. The study was approved by the local ethics committee (KEK-ZH-Nr. 2011-0034) and registered with ClinicalTrials.gov (NCT01516775). © The Author 2014. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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Ji, Haofeng; Shen, Xiuda; Gao, Feng; Ke, Bibo; Freitas, Maria Cecilia S; Uchida, Yoichiro; Busuttil, Ronald W; Zhai, Yuan; Kupiec-Weglinski, Jerzy W
2010-10-01
Programmed death-1 (PD-1)/B7-H1 costimulation acts as a negative regulator of host alloimmune responses. Although CD4 T cells mediate innate immunity-dominated ischemia and reperfusion injury (IRI) in the liver, the underlying mechanisms remain to be elucidated. This study focused on the role of PD-1/B7-H1 negative signaling in liver IRI. We used an established mouse model of partial liver warm ischemia (90 minutes) followed by reperfusion (6 hours). Although disruption of PD-1 signaling after anti-B7-H1 monoclonal antibody treatment augmented hepatocellular damage, its stimulation following B7-H1 immunoglobulin (B7-H1Ig) fusion protected livers from IRI, as evidenced by low serum alanine aminotransferase levels and well-preserved liver architecture. The therapeutic potential of B7-H1 engagement was evident by diminished intrahepatic T lymphocyte, neutrophil, and macrophage infiltration/activation; reduced cell necrosis/apoptosis but enhanced anti-necrotic/apoptotic Bcl-2/Bcl-xl; and decreased proinflammatory chemokine/cytokine gene expression in parallel with selectively increased interleukin (IL)-10. Neutralization of IL-10 re-created liver IRI and rendered B7-H1Ig-treated hosts susceptible to IRI. These findings were confirmed in T cell-macrophage in vitro coculture in which B7-H1Ig diminished tumor necrosis factor-α/IL-6 levels in an IL-10-dependent manner. Our novel findings document the essential role of the PD-1/B7-H1 pathway in liver IRI. This study is the first to demonstrate that stimulating PD-1 signals ameliorated liver IRI by inhibiting T cell activation and Kupffer cell/macrophage function. Harnessing mechanisms of negative costimulation by PD-1 upon T cell-Kupffer cell cross-talk may be instrumental in the maintenance of hepatic homeostasis by minimizing organ damage and promoting IL-10-dependent cytoprotection.
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NASA Technical Reports Server (NTRS)
Pullockaran, A. J.; Kingston, D. G.; Lewis, N. G.
1989-01-01
[4 beta- 2H1]Desoxypodophyllotoxin [3], [4 alpha- 2H1]desoxypodophyllotoxin [4], and [4, 4- 2 H2]desoxypodophyllotoxin [9] were prepared from podophyllotoxin [1] via its chloride [5]. A complete assignment of the 1H-nmr spectrum of desoxypodophyllotoxin [2] was made on the basis of the spectra of the deuterated compounds [3] and [4].
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Litchfield, Sheila M
2010-01-01
This article addresses the following aspects of a new Occupational Safety and Health Administration (OSHA) directive associated with H1N1 in the workplace: the recordability of H1N1 exposure in the workplace; the need for employers to have a pandemic plan that addresses the identification and management of H1N1 exposure risk to employees; the respiratory protection requirements of an exposure control plan; OSHA workplace inspections in response to exposure complaints or fatalities associated with H1N1; and the availability of OSHA compliance guidance for employers. Copyright 2010, SLACK Incorporated.
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NASA Astrophysics Data System (ADS)
Che, Zhijian; Wang, Shaoxiang; Liu, Shenggui; Li, Guobi; Wu, Qiting; Lin, Chunyu; Kong, Linglang; Wang, Sheng
2015-01-01
A new complex [Zn(bbb)Cl2]·DMF, where bbb is 2-(2-(1H-benzo[d]imidazol-2-yl)benzyl)-1H-benzo[d]imidazole, was synthesized and characterized by element analysis, 1H NMR and X-ray single crystal structure analyses. For complex: crystal system, triclinic, space group, P-1, a = 9.4661(13), b = 10.3534(14), c = 13.0025(18) Å, α = 73.477(2), β = 80.743(2), γ = 88.658(2)°, V = 1205.5(3) Å3, Z = 2. In this complex, the Zn2+ distorted tetrahedron geometry is coordinated by two nitrogen atoms from 2-(2-(1H-benzo[d]imidazol-2-yl)benzyl)-1H-benzo[d]imidazole and two Cl-. The complex emits yellow green luminescence with the maximal emission peak at 550 nm in DMF solution. The complex exhibits inhibition on the growth of Eca109 cancer cell with IC50 value of 8.9 ± 1.1 μM, which was lower than that of cisplatin (14.3 ± 1.4 μM). This complex has potential application in treatment of esophageal cancer.
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Recognizing the Palynological Signal of Heinrich Event H1
NASA Astrophysics Data System (ADS)
Delusina, I.
2017-12-01
One of the most challenging intervals for paleo-vegetation reconstruction of the post-Glacial environment is the transition that occurred at the beginning and the end of Heinrich event H1 and that stretched up to the beginning of the Younger Dryas. The main ambiguity is related to the magnitude and timing of H1 and the non-linear response of the Earth system to the Heinrich event itself in different geographical locations. We consider the H1 event as the entire transition interval since 18 to 14.5 Kya. The main problem that arises is the uncertainty in the interpretation of the pollen assemblages due to their mixed nature, particularly the presence of both "warm" and "cold" pollen. We have compared the pollen signal from the beginning to the end of the H1 event along a tropic to subpolar transect, using data from our own studies and the published literature. We find that despite regional peculiarities, most of the pollen assemblages demonstrate a similar sequence of patterns. One of the most prominent common features, seen at the beginning and the end of H1, is the appearance of saw-tooth like shapes in the variables of the pollen diagram, independent of location, vegetation composition and other factors. The most noticeable "saw-tooth" occurs after H1, between about 14 and 12 Kya, the interval that roughly corresponds to the Bølling/Allerød. The common features of a "saw-tooth" for both the beginning and the end of the H1 event, appear in this order: 1) increase in ferns, usually coinciding with or followed by an increased percentage of conifer pollen. 2) The beginning of dominance of xerophyte assemblages, again as a "saw-tooth" which lasts for about 2 Kya. 3) Each "saw-tooth", no matter where it occurs, terminates with the beginning of an increase in arboreal (or steppe) vegetation. For all of the different sites, the isotopic evidence is that this was a period of warming, but the pollen records tell a more complex story. Despite the local individualities of
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NASA Astrophysics Data System (ADS)
Zhang, Rongchun; Ramamoorthy, Ayyalusamy
2015-05-01
Dynamics plays important roles in determining the physical, chemical, and functional properties of a variety of chemical and biological materials. However, a material (such as a polymer) generally has mobile and rigid regions in order to have high strength and toughness at the same time. Therefore, it is difficult to measure the role of mobile phase without being affected by the rigid components. Herein, we propose a highly sensitive solid-state NMR approach that utilizes a dipolar-coupling based filter (composed of 12 equally spaced 90° RF pulses) to selectively measure the correlation of 1H chemical shifts from the mobile regions of a material. It is interesting to find that the rotor-synchronized dipolar filter strength decreases with increasing inter-pulse delay between the 90° pulses, whereas the dipolar filter strength increases with increasing inter-pulse delay under static conditions. In this study, we also demonstrate the unique advantages of proton-detection under ultrafast magic-angle-spinning conditions to enhance the spectral resolution and sensitivity for studies on small molecules as well as multi-phase polymers. Our results further demonstrate the use of finite-pulse radio-frequency driven recoupling pulse sequence to efficiently recouple weak proton-proton dipolar couplings in the dynamic regions of a molecule and to facilitate the fast acquisition of 1H/1H correlation spectrum compared to the traditional 2D NOESY (Nuclear Overhauser effect spectroscopy) experiment. We believe that the proposed approach is beneficial to study mobile components in multi-phase systems, such as block copolymers, polymer blends, nanocomposites, heterogeneous amyloid mixture of oligomers and fibers, and other materials.
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Ma, Wenjun; Lager, Kelly M; Lekcharoensuk, Porntippa; Ulery, Eva S; Janke, Bruce H; Solórzano, Alicia; Webby, Richard J; García-Sastre, Adolfo; Richt, Jürgen A
2010-09-01
Triple-reassortant swine influenza viruses circulating in North American pigs contain the internal genes derived from swine (matrix, non-structural and nucleoprotein), human [polymerase basic 1 (PB1)] and avian (polymerase acidic and PB2) influenza viruses forming a constellation of genes that is well conserved and is called the triple-reassortant internal gene (TRIG) cassette. In contrast, the external genes [haemagglutinin (HA) and neuraminidase (NA)] are less conserved, reflecting multiple reassortant events that have produced viruses with different combinations of HA and NA genes. This study hypothesized that maintenance of the TRIG cassette confers a selective advantage to the virus. To test this hypothesis, pigs were co-infected with the triple-reassortant H3N2 A/Swine/Texas/4199-2/98 (Tx/98) and the classical H1N1 A/Swine/Iowa/15/1930 viruses and co-housed with a group of sentinel animals. This direct contact group was subsequently moved into contact with a second group of naïve animals. Four different subtypes (H1N1, H1N2, H3N1 and H3N2) of influenza virus were identified in bronchoalveolar lavage fluid collected from the lungs of the experimentally infected pigs, with most of the viruses containing TRIG from the Tx/98 virus. Interestingly, only the intact H3N2 Tx/98 virus was transmitted from the infected pigs to the direct-contact animals and from them to the second contact group of pigs. These results demonstrated that multiple reassortments can occur within a host; however, only specific gene constellations are readily transmissible. It was concluded that certain HA and NA gene pairs, in conjunction with the TRIG cassette, may have a competitive advantage over other combinations for transmission and maintenance in swine.
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Zhu, Wenfei; Zhang, Hong; Xiang, Xingyu; Zhong, Lili; Yang, Lei; Guo, Junfeng; Xie, Yiran; Li, Fangcai; Deng, Zhihong; Feng, Hong; Huang, Yiwei; Hu, Shixiong; Xu, Xin; Zou, Xiaohui; Li, Xiaodan; Bai, Tian; Chen, Yongkun; Li, Zi; Li, Junhua; Shu, Yuelong
2016-11-01
In 2015, a novel influenza A(H1N1) virus was isolated from a boy in China who had severe pneumonia. The virus was a genetic reassortant of Eurasian avian-like influenza A(H1N1) (EA-H1N1) virus. The hemagglutinin, neuraminidase, and matrix genes of the reassortant virus were highly similar to genes in EA-H1N1 swine influenza viruses, the polybasic 1 and 2, polymerase acidic, and nucleoprotein genes originated from influenza A(H1N1)pdm09 virus, and the nonstructural protein gene derived from classical swine influenza A(H1N1) (CS H1N1) virus. In a mouse model, the reassortant virus, termed influenza A/Hunan/42443/2015(H1N1) virus, showed higher infectivity and virulence than another human EA-H1N1 isolate, influenza A/Jiangsu/1/2011(H1N1) virus. In the respiratory tract of mice, virus replication by influenza A/Hunan/42443/2015(H1N1) virus was substantially higher than that by influenza A/Jiangsu/1/2011(H1N1) virus. Human-to-human transmission of influenza A/Hunan/42443/2015(H1N1) virus has not been detected; however, given the circulation of novel EA-H1N1 viruses in pigs, enhanced surveillance should be instituted among swine and humans.
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Zhu, Wenfei; Zhang, Hong; Xiang, Xingyu; Zhong, Lili; Yang, Lei; Guo, Junfeng; Xie, Yiran; Li, Fangcai; Deng, Zhihong; Feng, Hong; Huang, Yiwei; Hu, Shixiong; Xu, Xin; Zou, Xiaohui; Li, Xiaodan; Bai, Tian; Chen, Yongkun; Li, Zi
2016-01-01
In 2015, a novel influenza A(H1N1) virus was isolated from a boy in China who had severe pneumonia. The virus was a genetic reassortant of Eurasian avian-like influenza A(H1N1) (EA-H1N1) virus. The hemagglutinin, neuraminidase, and matrix genes of the reassortant virus were highly similar to genes in EA-H1N1 swine influenza viruses, the polybasic 1 and 2, polymerase acidic, and nucleoprotein genes originated from influenza A(H1N1)pdm09 virus, and the nonstructural protein gene derived from classical swine influenza A(H1N1) (CS H1N1) virus. In a mouse model, the reassortant virus, termed influenza A/Hunan/42443/2015(H1N1) virus, showed higher infectivity and virulence than another human EA-H1N1 isolate, influenza A/Jiangsu/1/2011(H1N1) virus. In the respiratory tract of mice, virus replication by influenza A/Hunan/42443/2015(H1N1) virus was substantially higher than that by influenza A/Jiangsu/1/2011(H1N1) virus. Human-to-human transmission of influenza A/Hunan/42443/2015(H1N1) virus has not been detected; however, given the circulation of novel EA-H1N1 viruses in pigs, enhanced surveillance should be instituted among swine and humans. PMID:27767007
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Reactions of gas phase H atoms with ethylene, acetylene and ethane adsorbed on Ni( 1 1 1 )
NASA Astrophysics Data System (ADS)
Bürgi, T.; Trautman, T. R.; Gostein, M.; Lahr, D. L.; Haug, K. L.; Ceyer, S. T.
2002-03-01
The products of the reaction of the most energetic form of hydrogen, gas phase H atoms, with ethylene, acetylene and ethane adsorbed on a Ni(1 1 1) surface at 60 K are probed. Adsorbed ethylidyne (CCH 3) is identified by high resolution electron energy loss spectroscopy to be the major product (30% yield) in all three cases. Adsorbed acetylene is a minor product (3% yield) and arises as a consequence of a dynamic equilibrium between CCH 3 and C 2H 2 in the presence of gas phase H atoms. The observation of the same product for the reaction of H atoms with all three hydrocarbons implies that CCH 3 is the most stable C 2 species in the presence of coadsorbed hydrogen. The rates of CCH 3 production are measured as a function of the time of exposure of H atoms to each hydrocarbon. A simple kinetic model treating each reaction as a pseudo-first order reaction in the hydrocarbon coverage is fit to these data. A mechanism for the formation of CCH 3 via a CHCH 2 intermediate common to all three reactants is proposed to describe this model. The observed instability of the CH 2CH 3 species relative to C 2H 4 plays a role in the formulation of this mechanism as does the observed stability of CHCH 2 species in the presence of coadsorbed hydrogen. The CH 2CH 3 and the CHCH 2 species are produced by the translational activation of ethane and the dissociative ionization of ethane and ethylene, respectively. In addition, the binding energy and the vibrational spectrum of ethane adsorbed on Ni(1 1 1) are determined and exceptionally high resolution vibrational spectra of adsorbed ethylene and acetylene are presented.
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Viral shedding of 2009 pandemic H1N1 and evaluation of quarantine recommendations.
Chin, Bum Sik; Chae, Yun Tae; Choi, Hee Kyung; Baek, Ji-Hyeon; Jin, Sung Joon; Shin, So Youn; Han, Sang Hoon; Choi, Jun Yong; Kim, Chang Oh; Song, Young Goo; Jeong, Seok Hoon; Kim, June Myung
2012-01-01
Public health authorities recommend that isolation precautions for influenza should be continued for 7 days after illness onset or until 24 h after the resolution of symptoms, whichever event lasts longer. However, little data are available regarding the duration of isolation for patients with 2009 pandemic H1N1 (pH1N1). We recruited patients with confirmed pH1N1 virus infection at a 2,000-bed tertiary care center. Influenza viral loads from oropharyngeal swab specimens were serially determined by reverse transcriptase quantitative polymerase chain reaction every other day, and the risk factors for prolonged viral shedding were investigated. To evaluate the current recommendations for isolation precautions, we measured the intervals between symptom onset and the last viral RNA detection, and that between the last viral RNA detection and the point at which the patient was symptom-free for 24 h. From November 2009 to January 2010, 26 patients were enrolled, and viral RNA was detected in more than half of the eligible patients (10 of 19, 52.6%) for ≥7 days after symptom onset. While evaluating the policy for lifting quarantine, we found that viral RNA was detected in 4 of 15 patients (26.7%) beyond the recommended duration of isolation. In conclusion, viral RNA was detected in a substantial proportion of hospitalized patients even when they fulfilled the recommended conditions for lifting quarantine, and we believe that more prudence is required in this aspect.
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Lundius, Ebba Gregorsson; Sanchez-Alavez, Manuel; Ghochani, Yasmin; Klaus, Joseph; Tabarean, Iustin V.
2010-01-01
The preoptic area/anterior hypothalamus (PO/AH), a region that contains neurons that control thermoregulation, is the main locus at which histamine affects body temperature. Here we report that histamine reduced the spontaneous firing rate of GABAergic preoptic neurons by activating H3 subtype histamine receptors. This effect involved a decrease in the level of phosphorylation of the extracellular signal-regulated kinase (ERK) and was not dependent on synaptic activity. Furthermore, a population of nonGABAergic neurons was depolarized and their firing rate was enhanced by histamine acting at H1 subtype receptors. In our experiments, activation of the H1R receptors was linked to the PLC pathway and Ca2+ release from intracellular stores. This depolarization persisted in TTX or when fast synaptic potentials were blocked indicating that it represents a postsynaptic effect. Single-cell reverse transcription –PCR analysis revealed expression of H3 receptors in a population of GABAergic neurons while H1 receptors were expressed in nonGABAergic cells. Histamine applied in the median preoptic nucleus induced a robust, long lasting hyperthermia effect that was mimicked by either H1 or H3 histamine receptor subtype specific agonists. Our data indicate that histamine modulates the core body temperature by acting at two distinct populations of preoptic neurons which express H1 and H3 receptor subtypes, respectively. PMID:20335473
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Lundius, Ebba Gregorsson; Sanchez-Alavez, Manuel; Ghochani, Yasmin; Klaus, Joseph; Tabarean, Iustin V
2010-03-24
The preoptic area/anterior hypothalamus, a region that contains neurons that control thermoregulation, is the main locus at which histamine affects body temperature. Here we report that histamine reduced the spontaneous firing rate of GABAergic preoptic neurons by activating H3 subtype histamine receptors. This effect involved a decrease in the level of phosphorylation of the extracellular signal-regulated kinase and was not dependent on synaptic activity. Furthermore, a population of non-GABAergic neurons was depolarized, and their firing rate was enhanced by histamine acting at H1 subtype receptors. In our experiments, activation of the H1R receptors was linked to the PLC pathway and Ca(2+) release from intracellular stores. This depolarization persisted in TTX or when fast synaptic potentials were blocked, indicating that it represents a postsynaptic effect. Single-cell reverse transcription-PCR analysis revealed expression of H3 receptors in a population of GABAergic neurons, while H1 receptors were expressed in non-GABAergic cells. Histamine applied in the median preoptic nucleus induced a robust, long-lasting hyperthermia effect that was mimicked by either H1 or H3 histamine receptor subtype-specific agonists. Our data indicate that histamine modulates the core body temperature by acting at two distinct populations of preoptic neurons that express H1 and H3 receptor subtypes, respectively.
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Kim, Hyun Chul; Gu, Ja Min; Huh, Seong; Yo, Chul Hyun; Kim, Youngmee
2015-10-01
Two new one-dimensional Cu(II) coordination polymers (CPs) containing the C2h-symmetric terphenyl-based dicarboxylate linker 1,1':4',1''-terphenyl-3,3'-dicarboxylate (3,3'-TPDC), namely catena-poly[[bis(dimethylamine-κN)copper(II)]-μ-1,1':4',1''-terphenyl-3,3'-dicarboxylato-κ(4)O,O':O'':O'''] monohydrate], {[Cu(C20H12O4)(C2H7N)2]·H2O}n, (I), and catena-poly[[aquabis(dimethylamine-κN)copper(II)]-μ-1,1':4',1''-terphenyl-3,3'-dicarboxylato-κ(2)O(3):O(3')] monohydrate], {[Cu(C20H12O4)(C2H7N)2(H2O)]·H2O}n, (II), were both obtained from two different methods of preparation: one reaction was performed in the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO) as a potential pillar ligand and the other was carried out in the absence of the DABCO pillar. Both reactions afforded crystals of different colours, i.e. violet plates for (I) and blue needles for (II), both of which were analysed by X-ray crystallography. The 3,3'-TPDC bridging ligands coordinate the Cu(II) ions in asymmetric chelating modes in (I) and in monodenate binding modes in (II), forming one-dimensional chains in each case. Both coordination polymers contain two coordinated dimethylamine ligands in mutually trans positions, and there is an additional aqua ligand in (II). The solvent water molecules are involved in hydrogen bonds between the one-dimensional coordination polymer chains, forming a two-dimensional network in (I) and a three-dimensional network in (II).
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Tocco, Graziella; Zedda, Gloria; Casu, Mariano; Simbula, Gabriella; Begala, Michela
2017-10-17
New 1-[1-(1 H -indol-3-yl) alkyl]-1 H -indoles, surprisingly, have been obtained from the addition of indole to a variety of aldehydes under neat conditions. CaO, present in excess, was fundamental for carrying out the reaction with paraformaldehyde. Under the same reaction conditions, aromatic and heteroaromatic aldehydes afforded only classical bis (indolyl) aryl indoles. In this paper, the role of CaO, together with the regiochemistry and the mechanism of the reaction, are discussed in detail. The effect of some selected 3,3'- and 1,3'-diindolyl methane derivatives on cell proliferation of the hepatoma cell line FaO was also evaluated.
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DFT study on bimetallic Pt/Cu(1 1 1) as efficient catalyst for H2 dissociation
NASA Astrophysics Data System (ADS)
Liu, Ji; Fan, Xiaofeng; Sun, Chang Q.; Zhu, Weiguang
2018-05-01
To design a catalyst for the dissociation of H2 with better CO-tolerance performance is very important for proton exchange membrane fuel cells (PEMFCs) towards high efficiency. With slab model, the catalytic properties of overlayer Pt on Cu substrate (Pt/Cu) are analyzed by first-principle calculations. The CO saturation coverage (40%) on Pt2/Cu is found to be lower than that of pure Pt (about 75%). The dissociation barrier from H2 to H is less than 0.4 eV under the saturation coverage of CO. On the basis of kinetics of proton formation, the CO-tolerance ability on double-layer Pt with Cu is found to be greatly improved compared with that on pure Pt. It is expected that Pt overlayer on Cu(1 1 1) is a potential anode material with lower cost for PEMFCs.
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IRD evidence for Heinrich Events H1 and H2 on the NJ Margin
NASA Astrophysics Data System (ADS)
Christensen, B. A.; Calabrese, J.; O'Neill, C.; Goff, J. A.
2011-12-01
Recent seismic reflection studies suggest icebergs grounded on the late Pleistocene New Jersey margin (Goff and Austin, 2009) during Heinrich events H1 (~17 cal Ka), H2 (~23 cal Ka), H3 (~30 cal Ka) and H4 (~37 cal Ka). We tested this hypothesis by analyzing sediments on the upper NJ continental slope, near the area where icebergs were found. Ocean Drilling Program Site 1073A is located at 39°13.5214'N, 72°16.5461'W in 639 m water depth. The greater water depth increases the likelihood of preservation and improves the stratigraphic control. We obtained elemental measurements for Site 1073A Cores 1-6 using the X-ray Fluorescence (XRF) Core Scanner at the MARUM IODP core repository, University of Bremen. Cores were scanned at 10kV and 30kV to obtain a full suite of elements for analysis, with XRF data collected between 1 and 10 cm intervals. The values are reported in areas for the elements and were then converted to elemental ratios (Ca/Sr, Si/Sr, K/Al, and Si/Ti) for analysis. The origin of a Heinrich layer within an IRD belt can be identified by geochemical measures along with magnetic susceptibility and the presence of detrital materials that reflect its provenance (Hemming, 2004). Following analyses for Atlantic Ocean IRD by Hodell et al. (2008), higher Si/Sr values indicate abundant detrital silicates and low biogenic carbonate. Abundant detrital carbonate is identified by higher Ca/Sr values. K/Al may be used as a proxy for weathered matter being deposited and is a good indicator of terrigenous material (Yarincik, 2000). Si/Ti ratios may be used as a proxy for organic and siliceous productivity (Agnihotri, 2008). The elemental analysis was ground-truthed with grain size analysis at 10 cm intervals. Grain size analysis reveals large particles in a finer matrix at 123 cm and 284 cm. We interpret these as IRD. A linear sedimentation age model places the IRD around the time of Heinrich events H1 and H2. Age control is provided for the late Pleistocene
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Privett, Austin J.; Teixeira, Erico S.; Stopera, Christopher; Morales, Jorge A.
2017-01-01
To elucidate microscopic details of proton cancer therapy (PCT), we apply the simplest-level electron nuclear dynamics (SLEND) method to H+ + (H2O)1-6 at ELab = 100 keV. These systems are computationally tractable prototypes to simulate water radiolysis reactions—i.e. the PCT processes that generate the DNA-damaging species against cancerous cells. To capture incipient bulk-water effects, ten (H2O)1-6 isomers are considered, ranging from quasi-planar/multiplanar (H2O)1-6 to “smallest-drop” prism and cage (H2O)6 structures. SLEND is a time-dependent, variational, non-adiabatic and direct method that adopts a nuclear classical-mechanics description and an electronic single-determinantal wavefunction in the Thouless representation. Short-time SLEND/6-31G* (n = 1–6) and /6-31G** (n = 1–5) simulations render cluster-to-projectile 1-electron-transfer (1-ET) total integral cross sections (ICSs) and 1-ET probabilities. In absolute quantitative terms, SLEND/6-31G* 1-ET ICS compares satisfactorily with alternative experimental and theoretical results only available for n = 1 and exhibits almost the same accuracy of the best alternative theoretical result. SLEND/6-31G** overestimates 1-ET ICS for n = 1, but a comparable overestimation is also observed with another theoretical method. An investigation on H+ + H indicates that electron direct ionization (DI) becomes significant with the large virtual-space quasi-continuum in large basis sets; thus, SLEND/6-31G** 1-ET ICS is overestimated by DI contributions. The solution to this problem is discussed. In relative quantitative terms, both SLEND/6-31* and /6-31G** 1-ET ICSs precisely fit into physically justified scaling formulae as a function of the cluster size; this indicates SLEND’s suitability for predicting properties of water clusters with varying size. Long-time SLEND/6-31G* (n = 1–4) simulations predict the formation of the DNA-damaging radicals H, OH, O and H3O. While “smallest-drop” isomers are
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DOE Office of Scientific and Technical Information (OSTI.GOV)
T. J. Rodovsky
2006-03-01
This report presents the initial hazard categorization, final hazard categorization and auditable safety analysis for the remediation of the 118-D-1, 118-D-2, and 118-D-3 Burial Grounds located within the 100-D/DR Area of the Hanford Site and the 118-H-1, 118-H-2, and 118-H-3 Burial Grounds located within the 100-H Area of the Hanford Site.
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Carter, Donald M.; Darby, Christopher A.; Lefoley, Bradford C.; Crevar, Corey J.; Alefantis, Timothy; Oomen, Raymond; Anderson, Stephen F.; Strugnell, Tod; Cortés-Garcia, Guadalupe; Vogel, Thorsten U.; Parrington, Mark; Kleanthous, Harold
2016-01-01
ABSTRACT One of the challenges of developing influenza A vaccines is the diversity of antigenically distinct isolates. Previously, a novel hemagglutinin (HA) for H5N1 influenza was derived from a methodology termed computationally optimized broadly reactive antigen (COBRA). This COBRA HA elicited a broad antibody response against H5N1 isolates from different clades. We now report the development and characterization of a COBRA-based vaccine for both seasonal and pandemic H1N1 influenza virus isolates. Nine prototype H1N1 COBRA HA proteins were developed and tested in mice using a virus-like particle (VLP) format for the elicitation of broadly reactive, functional antibody responses and protection against viral challenge. These candidates were designed to recognize H1N1 viruses isolated within the last 30 years. In addition, several COBRA candidates were designed based on sequences of H1N1 viruses spanning the past 100 years, including modern pandemic H1N1 isolates. Four of the 9 H1N1 COBRA HA proteins (X1, X3, X6, and P1) had the broadest hemagglutination inhibition (HAI) activity against a panel of 17 H1N1 viruses. These vaccines were used in cocktails or prime-boost combinations. The most effective regimens that both elicited the broadest HAI response and protected mice against a pandemic H1N1 challenge were vaccines that contained the P1 COBRA VLP and either the X3 or X6 COBRA VLP vaccine. These mice had little or no detectable viral replication, comparable to that observed with a matched licensed vaccine. This is the first report describing a COBRA-based HA vaccine strategy that elicits a universal, broadly reactive, protective response against seasonal and pandemic H1N1 isolates. IMPORTANCE Universal influenza vaccine approaches have the potential to be paradigm shifting for the influenza vaccine field, with the goal of replacing the current standard of care with broadly cross-protective vaccines. We have used COBRA technology to develop an HA head
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The reaction of O(1 D) with H2O and the reaction of OH with C3H6
NASA Technical Reports Server (NTRS)
Simonaitis, R.; Heicklen, J.
1972-01-01
The N2O was photolyzed at 2139 A to produce O(1 D) atoms in the presence of H2O and CO. The O(1 D) atoms react with H2O to produce HO radicals, as measured by CO2 production from the reaction of OH with CO. The relative rate constant for O(1 D) removal by H2O compared to that by N2O is 2.1. In the presence of C3H6, the OH can be removed by reaction with either CO or C3H6.
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Reassortment process after co-infection of pigs with avian H1N1 and swine H3N2 influenza viruses.
Urbaniak, Kinga; Markowska-Daniel, Iwona; Kowalczyk, Andrzej; Kwit, Krzysztof; Pomorska-Mól, Małgorzata; Frącek, Barbara; Pejsak, Zygmunt
2017-07-08
The influenza A virus is highly variable, which, to some degree, is caused by the reassortment of viral genetic material. This process plays a major role in the generation of novel influenza virus strains that can emerge in a new host population. Due to the susceptibility of pigs to infections with avian, swine and human influenza viruses, they are considered intermediate hosts for the adaptation of the avian influenza virus to humans. In order to test the reassortment process in pigs, they were co-infected with H3N2 A/swine/Gent/172/2008 (Gent/08) and H1N1 A/duck/Italy/1447/2005 (Italy/05) and co-housed with a group of naïve piglets. The Gent/08 strains dominated over Italy/05, but reassortment occurred. The reassortant strains of the H1N1 subtype (12.5%) with one gene (NP or M) of swine-origin were identified in the nasal discharge of the contact-exposed piglets. These results demonstrate that despite their low efficiency, genotypically and phenotypically different influenza A viruses can undergo genetic exchange during co-infection of pigs.
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A Meta-Analysis of the Prevalence of Influenza A H5N1 and H7N9 Infection in Birds.
Bui, C; Rahman, B; Heywood, A E; MacIntyre, C R
2017-06-01
Despite a much higher rate of human influenza A (H7N9) infection compared to influenza A (H5N1), and the assumption that birds are the source of human infection, detection rates of H7N9 in birds are lower than those of H5N1. This raises a question about the role of birds in the spread and transmission of H7N9 to humans. We conducted a meta-analysis of overall prevalence of H5N1 and H7N9 in different bird populations (domestic poultry, wild birds) and different environments (live bird markets, commercial poultry farms, wild habitats). The electronic database, Scopus, was searched for published papers, and Google was searched for country surveillance reports. A random effect meta-analysis model was used to produce pooled estimates of the prevalence of H5N1 and H7N9 for various subcategories. A random effects logistic regression model was used to compare prevalence rates between H5N1 and H7N9. Both viruses have low prevalence across all bird populations. Significant differences in prevalence rates were observed in domestic birds, farm settings, for pathogen and antibody testing, and during routine surveillance. Random effects logistic regression analyses show that among domestic birds, the prevalence of H5N1 is 47.48 (95% CI: 17.15-133.13, P < 0.001) times higher than H7N9. In routine surveillance (where surveillance was not conducted in response to human infections or bird outbreaks), the prevalence of H5N1 is still higher than H7N9 with an OR of 43.02 (95% CI: 16.60-111.53, P < 0.001). H7N9 in humans has occurred at a rate approximately four times higher than H5N1, and for both infections, birds are postulated to be the source. Much lower rates of H7N9 in birds compared to H5N1 raise doubts about birds as the sole source of high rates of human H7N9 infection. Other sources of transmission of H7N9 need to be considered and explored. © 2016 The Authors. Transboundary and Emerging Diseases Published by Blackwell Verlag GmbH.
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Influenza A (H1N1) in Rome, Italy in family: three case reports.
Lisena, Francesco; Bordi, Licia; Carletti, Fabrizio; Castilletti, Concetta; Ferraro, Federica; Lalle, Eleonora; Lanini, Simone; Ruscitti, Luca Enrico; Fusco, Francesco Maria
2009-12-01
A new Influenza A virus H1N1 appeared in March-April 2009, and thousands of cases are being reported worldwide. In the initial months, several imported cases were reported in many European countries, while some countries reported local chains of transmission. We describe the first cluster of in-country transmission of the new Influenza A H1N1 which occurred in Italy, involving 3 patients. Patient 1, a 11-year-old male child developed fever, cough, and general malaise 4 days after returning from a travel to Mexico. Some days later, the 69-year-old grandfather (patient 2), who did not travel to Mexico, and the 33-month-old brother (patient 3) of patient 1 developed mild influenza symptoms. PCR tests resulted positive for Influenza A, and sequence analysis confirmed infection with the Influenza A (H1N1) strain for all three patients. Some problems were experienced in the administration of chemoprophylaxis and therapy in the patient 3. The chemoprophylaxis policies in other family members are described, too. Some interesting facts emerge from the analysis of this cluster. The transmission of Influenza A H1N1 virus seems to be dependent on strict contacts. Patient 2 and patient 3 did not take the chemoprophylaxis properly. The problems in the administration of chemoprophylaxis and therapy to patient 3 suggest that in infants specific individual-based strategies for assuring the correct administration are advisable.
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Improved background suppression in 1H MAS NMR using composite pulses
NASA Astrophysics Data System (ADS)
Odedra, Smita; Wimperis, Stephen
2012-08-01
A well known feature of 1H MAS NMR spectroscopy, particularly of solids where the concentration of 1H nuclei is low, is the presence in the spectrum of a significant broad "background" signal arising from 1H nuclei that are outside the MAS rotor and radiofrequency coil, probably located on the surfaces of the static components of the probehead. A popular method of suppressing this unwanted signal is the "depth pulse" method, consisting of a 90° pulse followed by one or two 180° pulses that are phase cycled according to the "Exorcycle" scheme, which removes signal associated with imperfect 180° pulses. Consequently, only spins in the centre of the radiofrequency coil contribute to the 1H MAS spectrum, while those experiencing a low B1 field outside the coil are suppressed. Although very effective at removing background signal from the spectrum, one drawback with this approach is that significant loss of the desired signal from the sample also occurs. Here we investigate the 1H background suppression problem and, in particular, the use of novel antisymmetric passband composite pulses to replace the simple pulses in a depth pulse experiment. We show that it is possible to improve the intensity of the 1H signals of interest while still maintaining effective background suppression. We expect that these results will be relevant to 1H MAS NMR studies of, for example, nominally perdeuterated biological samples or nominally anhydrous inorganic materials.
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Guo, Chun-yan; Tang, Yi-gui; Qi, Zong-li; Liu, Yang; Zhao, Xiang-rong; Huo, Xue-ping; Li, Yan; Feng, Qing; Zhao, Peng-hua; Wang, Xin; Li, Yuan; Wang, Hai-fang; Hu, Jun; Zhang, Xin-jian
2015-08-01
To characterize the antigenic epitopes of the hemagglutinin (HA) protein of H1N1 influenza virus, a panel consisting of 84 clones of murine monoclonal antibodies (mAbs) were generated using the HA proteins from the 2009 pandemic H1N1 vaccine lysate and the seasonal influenza H1N1(A1) vaccines. Thirty-three (39%) of the 84 mAbs were found to be strain-specific, and 6 (7%) of the 84 mAbs were subtype-specific. Twenty (24%) of the 84 mAbs recognized the common HA epitopes shared by 2009 pandemic H1N1, seasonal A1 (H1N1), and A3 (H3N2) influenza viruses. Twenty-five of the 84 clones recognized the common HA epitopes shared by the 2009 pandemic H1N1, seasonal A1 (H1N1) and A3 (H3N2) human influenza viruses, and H5N1 and H9N2 avian influenza viruses. We found that of the 16 (19%) clones of the 84 mAbs panel that were cross-reactive with human respiratory pathogens, 15 were made using the HA of the seasonal A1 (H1N1) virus and 1 was made using the HA of the 2009 pandemic H1N1 influenza virus. Immunohistochemical analysis of the tissue microarray (TMA) showed that 4 of the 84 mAb clones cross-reacted with human tissue (brain and pancreas). Our results indicated that the influenza virus HA antigenic epitopes not only induce type-, subtype-, and strain-specific monoclonal antibodies against influenza A virus but also cross-reactive monoclonal antibodies against human tissues. Further investigations of these cross-reactive (heterophilic) epitopes may significantly improve our understanding of viral antigenic variation, epidemics, pathophysiologic mechanisms, and adverse effects of influenza vaccines. Copyright © 2015 Elsevier GmbH. All rights reserved.
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1H Magnetic Resonance Spectroscopy of live human sperm
Calvert, S J; Paley, M N; Pacey, A A
2017-01-01
Abstract STUDY QUESTION Can 1H Magnetic Resonance Spectroscopy (MRS) be used to obtain information about the molecules and metabolites in live human spermatozoa? SUMMARY ANSWER Percoll-based density gradient centrifugation (DGC) followed by a further two washing steps, yielded enough sperm with minimal contamination (<0.01%) from seminal fluid to permit effective MRS which detected significant differences (P < 0.05) in the choline/glycerophosphocholine (GPC), lipid and lactate regions of the 1H MRS spectrum between sperm in the pellet and those from the 40%/80% interface. WHAT IS KNOWN ALREADY Current methods to examine sperm are either limited in their value (e.g. semen analysis) or are destructive (e.g. immunohistochemistry, sperm DNA testing). A few studies have previously used MRS to examine sperm, but these have either looked at seminal plasma from men with different ejaculate qualities or at the molecules present in pooled samples of lyophilized sperm. STUDY DESIGN, SAMPLES/MATERIALS, METHODS Sperm suspended in phosphate buffered saline (PBS) at 37°C were examined by 1H MRS scanning using a 1H excitation-sculpting solvent suppression sequence after recovery from fresh ejaculates by one of three different methods: (i) simple centrifugation; (ii) DGC with one wash; or (iii) DGC with two washes. In the case of DGC, sperm were collected both from the pellet (‘80%’ sperm) and the 40/80 interface (‘40%’ sperm). Spectrum processing was carried out using custom Matlab scripts to determine; the degree of seminal plasma/Percoll contamination, the minimum sperm concentration for 1H MRS detection and differences between the 1H MRS spectra of ‘40%’ and ‘80%’ sperm. MAIN RESULTS AND THE ROLE OF CHANCE DGC with two washes minimized the 1H MRS peak intensity for both seminal plasma and Percoll/PBS solution contamination while retaining sperm specific peaks. For the MRS scanner used in this study, the minimum sperm concentration required to produce a choline
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Endothelial necrosis at 1h post-burn predicts progression of tissue injury
Hirth, Douglas; McClain, Steve A.; Singer, Adam J.; Clark, Richard A.F.
2013-01-01
Burn injury progression has not been well characterized at the cellular level. To define burn injury progression in terms of cell death, histopathologic spatiotemporal relationships of cellular necrosis and apoptosis were investigated in a validated porcine model of vertical burn injury progression. Cell necrosis was identified by High Mobility Group Box 1 protein and apoptosis by Caspase 3a staining of tissue samples taken 1h, 24h and 7 days post-burn. Level of endothelial cell necrosis at 1h was predictive of level of apoptosis at 24h (Pearson's r=0.87) and of level of tissue necrosis at 7 days (Pearson's r=0.87). Furthermore, endothelial cell necrosis was deeper than interstitial cell necrosis at 1h (p<0.001). Endothelial cell necrosis at 1h divided the zone of injury progression (Jackson's zone of stasis) into an upper subzone with necrotic endothelial cells and initially viable adnexal and interstitial cells at 1h that progressed to necrosis by 24h, and a lower zone with initially viable endothelial cells at 1h, but necrosis and apoptosis of all cell types by 24h. Importantly, this spatiotemporal series of events and rapid progression resembles myocardial infarction and stroke, and implicates mechanisms of these injuries, ischemia, ischemia reperfusion, and programmed cell death, in burn progression. PMID:23627744
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Development of a real-time RT-PCR assay for a novel influenza A (H1N1) virus.
Jiang, Tao; Kang, Xiaoping; Deng, Yongqiang; Zhao, Hui; Li, Xiaofeng; Yu, Xuedong; Yu, Man; Qin, Ede; Zhu, Qingyu; Yang, Yinhui; Qin, Chengfeng
2010-02-01
A pandemic caused by a novel influenza A virus (H1N1) poses a serious public health threat. In this study, a real-time reverse transcriptase PCR (RT-PCR) assay based on the hemagglutinin gene was developed that discriminates the novel H1N1 from swine influenza virus, seasonal H1N1/H3N2 virus and the highly pathogenic H5N1 avian influenza virus. The sensitivity of this assay was 0.2 50% tissue culture infective dose of virus and 200 copies of in vitro-transcribed target RNA. Three hundred and forty-eight clinical specimens from suspected H1N1 patients were tested using this assay, and forty-two (12.07%) were found to be positive. Tests using the real-time PCR assay recommended by WHO and virus isolation gave identical results. This sensitive and specific real-time RT-PCR assay will contribute to the early diagnosis and control of the emerging H1N1 influenza pandemic. 2009 Elsevier B.V. All rights reserved.
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Schlippenbach, Trixi von; Oefner, Peter J; Gronwald, Wolfram
2018-03-09
Non-uniform sampling (NUS) allows the accelerated acquisition of multidimensional NMR spectra. The aim of this contribution was the systematic evaluation of the impact of various quantitative NUS parameters on the accuracy and precision of 2D NMR measurements of urinary metabolites. Urine aliquots spiked with varying concentrations (15.6-500.0 µM) of tryptophan, tyrosine, glutamine, glutamic acid, lactic acid, and threonine, which can only be resolved fully by 2D NMR, were used to assess the influence of the sampling scheme, reconstruction algorithm, amount of omitted data points, and seed value on the quantitative performance of NUS in 1 H, 1 H-TOCSY and 1 H, 1 H-COSY45 NMR spectroscopy. Sinusoidal Poisson-gap sampling and a compressed sensing approach employing the iterative re-weighted least squares method for spectral reconstruction allowed a 50% reduction in measurement time while maintaining sufficient quantitative accuracy and precision for both types of homonuclear 2D NMR spectroscopy. Together with other advances in instrument design, such as state-of-the-art cryogenic probes, use of 2D NMR spectroscopy in large biomedical cohort studies seems feasible.
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Serial 1H-MRS in GM2 gangliosidoses.
Assadi, Mitra; Baseman, Susan; Janson, Christopher; Wang, Dah-Jyuu; Bilaniuk, Larissa; Leone, Paola
2008-03-01
GM2 gangliosidoses are a group of neuronal storage disorders caused by deficiency in the lysosomal enzyme hexosaminidase A. Clinically, the disease is marked by a relentless encephalopathy. Proton magnetic resonance spectroscopy (1H-MRS) provides in-vivo measurement of various brain metabolites including N-acetyl aspartate+N-acetyl aspartate glutamate (NAA), myo-inositol (mI), choline (Cho) and creatine (Cr). The NAA represents neuronal integrity while elevation in the mI reflects abnormal inflammation and gliosis in the brain tissue. An elevation in the Cho levels suggest cell membrane breakdown and demyelination. We report the clinical and laboratory data in two patients with GM2 gangliosidoses. Serial 1H-MRS evaluations were performed to drive metabolite ratios of NAA/Cr, mI/Cr and Cho/Cr. We acquired the data from four regions of interest (ROI) according to a standard protocol. The results documented a progressive elevation in mI/Cr in all four ROI in patient one and only one ROI (occipital gray matter) in patient 2. We also documented a decline in the NAA/Cr ratios in both cases in most ROI. These results were compared to six age-matched controls and confirmed statistically significant elevation in the mI in our cases. In conclusion, 1H-MRS alterations were suggestive of neuronal loss and inflammation in these patients. 1H-MRS may be a valuable tool in monitoring the disease progress and response to therapy in GM2 gangliosidoses. Elevation in the mI may prove to be more sensitive than the other metabolite alterations.
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Engelhardt, Othmar G.; Wood, John; Heath, Alan; Katz, Jacqueline M.; Peiris, Malik; Hoschler, Katja; Hungnes, Olav; Zhang, Wenqing; Van Kerkhove, Maria D.
2015-01-01
The microneutralization assay is commonly used to detect antibodies to influenza virus, and multiple protocols are used worldwide. These protocols differ in the incubation time of the assay as well as in the order of specific steps, and even within protocols there are often further adjustments in individual laboratories. The impact these protocol variations have on influenza serology data is unclear. Thus, a laboratory comparison of the 2-day enzyme-linked immunosorbent assay (ELISA) and 3-day hemagglutination (HA) microneutralization (MN) protocols, using A(H1N1)pdm09, A(H3N2), and A(H5N1) viruses, was performed by the CONSISE Laboratory Working Group. Individual laboratories performed both assay protocols, on multiple occasions, using different serum panels. Thirteen laboratories from around the world participated. Within each laboratory, serum sample titers for the different assay protocols were compared between assays to determine the sensitivity of each assay and were compared between replicates to assess the reproducibility of each protocol for each laboratory. There was good correlation of the results obtained using the two assay protocols in most laboratories, indicating that these assays may be interchangeable for detecting antibodies to the influenza A viruses included in this study. Importantly, participating laboratories have aligned their methodologies to the CONSISE consensus 2-day ELISA and 3-day HA MN assay protocols to enable better correlation of these assays in the future. PMID:26108286
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Genetic makeup of amantadine-resistant and oseltamivir-resistant human influenza A/H1N1 viruses.
Zaraket, Hassan; Saito, Reiko; Suzuki, Yasushi; Baranovich, Tatiana; Dapat, Clyde; Caperig-Dapat, Isolde; Suzuki, Hiroshi
2010-04-01
The emergence and widespread occurrence of antiviral drug-resistant seasonal human influenza A viruses, especially oseltamivir-resistant A/H1N1 virus, are major concerns. To understand the genetic background of antiviral drug-resistant A/H1N1 viruses, we performed full genome sequencing of prepandemic A/H1N1 strains. Seasonal influenza A/H1N1 viruses, including antiviral-susceptible viruses, amantadine-resistant viruses, and oseltamivir-resistant viruses, obtained from several areas in Japan during the 2007-2008 and 2008-2009 influenza seasons were analyzed. Sequencing of the full genomes of these viruses was performed, and the phylogenetic relationships among the sequences of each individual genome segment were inferred. Reference genome sequences from the Influenza Virus Resource database were included to determine the closest ancestor for each segment. Phylogenetic analysis revealed that the oseltamivir-resistant strain evolved from a reassortant oseltamivir-susceptible strain (clade 2B) which circulated in the 2007-2008 season by acquiring the H275Y resistance-conferring mutation in the NA gene. The oseltamivir-resistant lineage (corresponding to the Northern European resistant lineage) represented 100% of the H1N1 isolates from the 2008-2009 season and further acquired at least one mutation in each of the polymerase basic protein 2 (PB2), polymerase basic protein 1 (PB1), hemagglutinin (HA), and neuraminidase (NA) genes. Therefore, a reassortment event involving two distinct oseltamivir-susceptible lineages, followed by the H275Y substitution in the NA gene and other mutations elsewhere in the genome, contributed to the emergence of the oseltamivir-resistant lineage. In contrast, amantadine-resistant viruses from the 2007-2008 season distinctly clustered in clade 2C and were characterized by extensive amino acid substitutions across their genomes, suggesting that a fitness gap among its genetic components might have driven these mutations to maintain it in the
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Rakheja, Dinesh; Kapur, Payal; Tomlinson, Gail E; Margraf, Linda R
2005-01-01
Alveolar soft part sarcoma and pediatric renal cell carcinoma share a similar chromosomal abnormality, t(X;17)(p11.2;q25). Recently, it has been suggested that the inactivation of DNA mismatch repair genes hMLH1 and hMSH2 may play an additional role in the pathogenesis of alveolar soft part sarcoma. Immunohistochemical expression of the proteins hMLH1 and hMSH2 is indicative of the activation status of the corresponding genes. We performed immunohistochemistry for hMLH1 and hMSH2 in 4 cases of pediatric renal cell carcinomas with Xp11.2 rearrangements. All cases showed nuclear immunoreactivity for both proteins, although the staining was patchy. Our study demonstrates that inactivation of the DNA mismatch repair genes hMLH1 and hMSH2 does not appear to play a role in the tumorigenesis of pediatric renal cell carcinomas with Xp11.2 rearrangements.
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Narcolepsy with cataplexy and hyperthyroidism sudden appeared after H1N1 vaccination
Leiva, Silvia; Madrazo, Jimena; Podesta, Claudio
2018-01-01
Narcolepsy type 1 (NT1) is a chronic sleep disorder, characterized by excessive daytime sleepiness, cataplexy and fragmented nocturnal sleep. It is caused by a hypocretin deficiency due to a significant reduction of the neurons producing it. In the last years, it has been postulated that an autoimmune mechanism would be responsible for the destruction of these neurons in those genetically predisposed patients. The increased incidence of narcolepsy after the pandemic H1N1 influenza vaccination campaign in 2009-2010 is known. We present below the case of an adult patient who, 10 days after receiving H1N1 vaccination, suffers a traffic accident after falling asleep. Subsequent studies revealed hyperthyroidism due to Graves disease. In spite of the treatment, the patient persisted with daily and disabling daytime sleepiness, sleep attacks and episodes of generalized muscle atony with preservation of consciousness. A nocturnal polysomnography and multiple sleep latency test (MSLT) were performed with a diagnosis of NT1. The particularity of this case is the presentation of 2 autoimmune diseases triggered by an H1N1 vaccine without adjuvant, so far there is only evidence of NT1 associated with vaccines with adjuvant and viral infection. The association of both entities has made us reflect on the autoimmune mechanism, reinforcing the theory of its role in the onset of the disease. PMID:29796199
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H1N1 Preventive Health Behaviors in a University Setting
ERIC Educational Resources Information Center
Katz, Rebecca; May, Larissa; Sanza, Megan; Johnston, Lindsay; Petinaux, Bruno
2012-01-01
Background: When H1N1 emerged in 2009, institutions of higher education were immediately faced with questions about how best to protect their community from the virus, yet limited information existed to help predict student preventive behaviors. Methods: The authors surveyed students at a large urban university in November 2009 to better…
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Hillaire, Marine L B; Vogelzang-van Trierum, Stella E; Kreijtz, Joost H C M; de Mutsert, Gerrie; Fouchier, Ron A M; Osterhaus, Albert D M E; Rimmelzwaan, Guus F
2013-03-01
Virus-specific CD8(+) T-cells contribute to protective immunity against influenza A virus (IAV) infections. As the majority of these cells are directed to conserved viral proteins, they may afford protection against IAVs of various subtypes. The present study assessed the cross-reactivity of human CD8(+) T-lymphocytes, induced by infection with seasonal A (H1N1) or A (H3N2) influenza virus, with 2009 pandemic influenza A (H1N1) virus [A(H1N1)pdm09] and swine-origin triple-reassortant A (H3N2) [A(H3N2)v] viruses that are currently causing an increasing number of human cases in the USA. It was demonstrated that CD8(+) T-cells induced after seasonal IAV infections exerted lytic activity and produced gamma interferon upon in vitro restimulation with A(H1N1)pdm09 and A(H3N2)v influenza A viruses. Furthermore, CD8(+) T-cells directed to A(H1N1)pdm09 virus displayed a high degree of cross-reactivity with A(H3N2)v viruses. It was concluded that cross-reacting T-cells had the potential to afford protective immunity against A(H1N1)pdm09 viruses during the pandemic and offer some degree of protection against infection with A(H3N2)v viruses.
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Predictors of fatality in pandemic influenza A (H1N1) virus infection among adults
2014-01-01
Background The fatality attributed to pandemic influenza A H1N1 was not clear in the literature. We described the predictors for fatality related to pandemic influenza A H1N1 infection among hospitalized adult patients. Methods This is a multicenter study performed during the pandemic influenza A H1N1 [A(H1N1)pdm09] outbreak which occurred in 2009 and 2010. Analysis was performed among laboratory confirmed patients. Multivariate analysis was performed for the predictors of fatality. Results In the second wave of the pandemic, 848 adult patients were hospitalized because of suspected influenza, 45 out of 848 (5.3%) died, with 75% of fatalities occurring within the first 2 weeks of hospitalization. Among the 241 laboratory confirmed A(H1N1)pdm09 patients, the case fatality rate was 9%. In a multivariate logistic regression model that was performed for the fatalities within 14 days after admission, early use of neuraminidase inhibitors was found to be protective (Odds ratio: 0.17, confidence interval: 0.03-0.77, p = 0.022), nosocomial infections (OR: 5.7, CI: 1.84-18, p = 0.013), presence of malignant disease (OR: 3.8, CI: 0.66-22.01, p = 0.133) significantly increased the likelihood of fatality. Conclusions Early detection of the infection, allowing opportunity for the early use of neuraminidase inhibitors, was found to be important for prevention of fatality. Nosocomial bacterial infections and underlying malignant diseases increased the rate of fatality. PMID:24916566
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Early Outbreak of 2009 Influenza A (H1N1) in Mexico Prior to Identification of pH1N1 Virus
Hsieh, Ying-Hen; Ma, Stefan; Velasco Hernandez, Jorge X.; Lee, Vernon J.; Lim, Wei Yen
2011-01-01
Background In the aftermath of the global spread of 2009 influenza A (pH1N1) virus, still very little is known of the early stages of the outbreak in Mexico during the early months of the year, before the virus was identified. Methodology/Main Findings We fit a simple mathematical model, the Richards model, to the number of excess laboratory-confirmed influenza cases in Mexico and Mexico City during the first 15 weeks in 2009 over the average influenza case number of the previous five baseline years of 2004-2008 during the same period to ascertain the turning point (or the peak incidence) of a wave of early influenza infections, and to estimate the transmissibility of the virus during these early months in terms of its basic reproduction number. The results indicate that there may have been an early epidemic in Mexico City as well as in all of Mexico during February/March. Based on excess influenza cases, the estimated basic reproduction number R0 for the early outbreak was 1.59 (0.55 to 2.62) for Mexico City during weeks 5–9, and 1.25 (0.76, 1.74) for all of Mexico during weeks 5–14. Conclusions We established the existence of an early epidemic in Mexico City and in all of Mexico during February/March utilizing the routine influenza surveillance data, although the location of seeding is unknown. Moreover, estimates of R0 as well as the time of peak incidence (the turning point) for Mexico City and all of Mexico indicate that the early epidemic in Mexico City in February/March had been more transmissible (larger R0) and peaked earlier than the rest of the country. Our conclusion lends support to the possibility that the virus could have already spread to other continents prior to the identification of the virus and the reporting of lab-confirmed pH1N1 cases in North America in April. PMID:21909366
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Dynamic gene expression analysis in a H1N1 influenza virus mouse pneumonia model.
Bao, Yanyan; Gao, Yingjie; Shi, Yujing; Cui, Xiaolan
2017-06-01
H1N1, a major pathogenic subtype of influenza A virus, causes a respiratory infection in humans and livestock that can range from a mild infection to more severe pneumonia associated with acute respiratory distress syndrome. Understanding the dynamic changes in the genome and the related functional changes induced by H1N1 influenza virus infection is essential to elucidating the pathogenesis of this virus and thereby determining strategies to prevent future outbreaks. In this study, we filtered the significantly expressed genes in mouse pneumonia using mRNA microarray analysis. Using STC analysis, seven significant gene clusters were revealed, and using STC-GO analysis, we explored the significant functions of these seven gene clusters. The results revealed GOs related to H1N1 virus-induced inflammatory and immune functions, including innate immune response, inflammatory response, specific immune response, and cellular response to interferon-beta. Furthermore, the dynamic regulation relationships of the key genes in mouse pneumonia were revealed by dynamic gene network analysis, and the most important genes were filtered, including Dhx58, Cxcl10, Cxcl11, Zbp1, Ifit1, Ifih1, Trim25, Mx2, Oas2, Cd274, Irgm1, and Irf7. These results suggested that during mouse pneumonia, changes in the expression of gene clusters and the complex interactions among genes lead to significant changes in function. Dynamic gene expression analysis revealed key genes that performed important functions. These results are a prelude to advancements in mouse H1N1 influenza virus infection biology, as well as the use of mice as a model organism for human H1N1 influenza virus infection studies.
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Structural and functional analysis of the putative pH sensor in the Kir1.1 (ROMK) potassium channel.
Rapedius, Markus; Haider, Shozeb; Browne, Katharine F; Shang, Lijun; Sansom, Mark S P; Baukrowitz, Thomas; Tucker, Stephen J
2006-06-01
The pH-sensitive renal potassium channel Kir1.1 is important for K+ homeostasis. Disruption of the pH-sensing mechanism causes type II Bartter syndrome. The pH sensor is thought to be an anomalously titrated lysine residue (K80) that interacts with two arginine residues as part of an 'RKR triad'. We show that a Kir1.1 orthologue from Fugu rubripes lacks this lysine and yet is still highly pH sensitive, indicating that K80 is not the H+ sensor. Instead, K80 functionally interacts with A177 on transmembrane domain 2 at the 'helix-bundle crossing' and controls the ability of pH-dependent conformational changes to induce pore closure. Although not required for pH inhibition, K80 is indispensable for the coupling of pH gating to the extracellular K+ concentration, explaining its conservation in most Kir1.1 orthologues. Furthermore, we demonstrate that instead of interacting with K80, the RKR arginine residues form highly conserved inter- and intra-subunit interactions that are important for Kir channel gating and influence pH sensitivity indirectly.
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Su, Yvonne C. F.; Bahl, Justin; Joseph, Udayan; Butt, Ka Man; Peck, Heidi A.; Koay, Evelyn S. C.; Oon, Lynette L. E.; Barr, Ian G.; Vijaykrishna, Dhanasekaran; Smith, Gavin J. D.
2015-01-01
Influenza A H1N1/2009 virus that emerged from swine rapidly replaced the previous seasonal H1N1 virus. Although the early emergence and diversification of H1N1/2009 is well characterized, the ongoing evolutionary and global transmission dynamics of the virus remain poorly investigated. To address this we analyse >3,000 H1N1/2009 genomes, including 214 full genomes generated from our surveillance in Singapore, in conjunction with antigenic data. Here we show that natural selection acting on H1N1/2009 directly after introduction into humans was driven by adaptation to the new host. Since then, selection has been driven by immunological escape, with these changes corresponding to restricted antigenic diversity in the virus population. We also show that H1N1/2009 viruses have been subject to regular seasonal bottlenecks and a global reduction in antigenic and genetic diversity in 2014. PMID:26245473
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Stucchi, R S B; Boin, I F S F; Angerami, R Nogueira; Sinckoc, V; Sa, F Cesar; Seva-Pereira, T; Escanhoela, C A Fazzio
2010-12-01
Influenza is a common cause of respiratory infection in transplant recipients. It is expected that A/H1N1 influenza virus causes more severe disease in solid-organ recipients. Our goal was to describe two A/H1N1 infections that occurred after Orthotopic liver transplantation followed by acute allograft rejection episodes. From March 2009 to March 2010 we observe two liver transplant patients with symptoms suggestive of A/H1N1 infection. The diagnosis was out based on a temperature of 37.8°C (100°F) or higher and the presence of a cough or using materials from anasopharyngeal and oropharyngeal swabs a sore throat. The diagnosis was confirmed by viral RNA detection by real-time reverse-transcriptase-polymerase-chain-reaction assay (RT-PCR) using materials from nasopharyngeal and oropharyngeal swabs. We performed the RT-PCR assay for A/H1N1 detection in a liver biopsy from one patient. Both patients were treated with usual doses of oseltamivir (75 mg twice daily for 5 days). One patient developed acute bacterial sinusitis requiring antibiotic therapy. Thereafter the liver enzymes increased and transplant biopsies showed moderate-to-severe acute cellular rejection. They were treated with corticosteroids. The liver enzymes normalized after 3 months. A/H1N1 influenza can lead to a severe acute cellular rejection episode with corticosteroid resistant treatment in liver transplant patients. Transplant centers should be aware of a possible relationship between A/H1N1 infections and acute allograft rejection episodes. Copyright © 2010 Elsevier Inc. All rights reserved.
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Farrán, M Ángeles; Bonet, M Ángels; Claramunt, Rosa M; Torralba, M Carmen; Alkorta, Ibon; Elguero, José
2018-04-01
J147 [N-(2,4-dimethylphenyl)-2,2,2-trifluoro-N'-(3-methoxybenzylidene)acetohydrazide] has recently been reported as a promising new drug for the treatment of Alzheimer's disease. The X-ray structures of seven new 1,4-diaryl-5-trifluoromethyl-1H-1,2,3-triazoles, namely 1-(3,4-dimethylphenyl)-4-phenyl-5-trifluoromethyl-1H-1,2,3-triazole (C 17 H 14 F 3 N 3 , 1), 1-(3,4-dimethylphenyl)-4-(3-methoxyphenyl)-5-trifluoromethyl-1H-1,2,3-triazole (C 18 H 16 F 3 N 3 O, 2), 1-(3,4-dimethylphenyl)-4-(4-methoxyphenyl)-5-trifluoromethyl-1H-1,2,3-triazole (C 18 H 16 F 3 N 3 O, 3), 1-(2,4-dimethylphenyl)-4-(4-methoxyphenyl)-5-trifluoromethyl-1H-1,2,3-triazole (C 18 H 16 F 3 N 3 O, 4), 1-[2,4-bis(trifluoromethyl)phenyl]-4-(3-methoxyphenyl)-5-trifluoromethyl-1H-1,2,3-triazole (C 18 H 10 F 9 N 3 O, 5), 1-(3,4-dimethoxyphenyl)-4-(3,4-dimethoxyphenyl)-5-trifluoromethyl-1H-1,2,3-triazole (C 19 H 18 F 3 N 3 O 4 , 6) and 3-[4-(3,4-dimethoxyphenyl)-5-(trifluoromethyl)-1H-1,2,3-triazol-1-yl]phenol (C 17 H 14 F 3 N 3 O 3 , 7), have been determined and compared to that of J147. B3LYP/6-311++G(d,p) calculations have been performed to determine the potential surface and molecular electrostatic potential (MEP) of J147, and to examine the correlation between hydrazone J147 and the 1,2,3-triazoles, both bearing a CF 3 substituent. Using MEPs, it was found that the minimum-energy conformation of 4, which is nearly identical to its X-ray structure, is closely related to one of the J147 seven minima.
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Critical illness in children with influenza A/pH1N1 2009 infection in Canada.
Jouvet, Philippe; Hutchison, Jamie; Pinto, Ruxandra; Menon, Kusum; Rodin, Rachel; Choong, Karen; Kesselman, Murray; Veroukis, Stasa; André Dugas, Marc; Santschi, Miriam; Guerguerian, Anne-Marie; Withington, Davinia; Alsaati, Basem; Joffe, Ari R; Drews, Tanya; Skippen, Peter; Rolland, Elizabeth; Kumar, Anand; Fowler, Robert
2010-09-01
To describe characteristics, treatment, and outcomes of critically ill children with influenza A/pandemic influenza A virus (pH1N1) infection in Canada. An observational study of critically ill children with influenza A/pH1N1 infection in pediatric intensive care units (PICUs). Nine Canadian PICUs. A total of 57 patients admitted to PICUs between April 16, 2009 and August 15, 2009. None. Characteristics of critically ill children with influenza A/pH1N1 infection were recorded. Confirmed intensive care unit cases were compared with a national surveillance database containing all hospitalized pediatric patients with influenza A/pH1N1 infection. Risk factors were assessed with a Cox proportional hazard model. The PICU cohort and national surveillance data were compared, using chi-square tests. Fifty-seven children were admitted to the PICU for community-acquired influenza A/pH1N1 infection. One or more chronic comorbid illnesses were observed in 70.2% of patients, and 24.6% of patients were aboriginal. Mechanical ventilation was used in 68% of children, 20 children (35.1%) had acute lung injury on the first day of admission, and the median duration of ventilation was 6 days (range, 0-67 days). The PICU mortality rate was 7% (4 of 57 patients). When compared with nonintensive care unit hospitalized children, PICU children were more likely to have a chronic medical condition (relative risk, 1.73); aboriginal ethnicity was not a risk factor of intensive care unit admission. During the first outbreak of influenza A/pH1N1 infection, when the population was naïve to this novel virus, severe illness was common among children with underlying chronic conditions and aboriginal children. Influenza A/pH1N1-related critical illness in children was associated with severe hypoxemic respiratory failure and prolonged mechanical ventilation. However, this higher rate and severity of respiratory illness did not result in an increased mortality when compared with seasonal influenza.
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Sanz, Ivan; Rojo, Silvia; Tamames, Sonia; Eiros, José María; Ortiz de Lejarazu, Raúl
2017-01-01
Avian influenza viruses are currently one of the main threats to human health in the world. Although there are some screening reports of antibodies against these viruses in humans from Western countries, most of these types of studies are conducted in poultry and market workers of Asian populations. The presence of antibodies against avian influenza viruses was evaluated in an elderly European population. An experimental study was conducted, including pre- and post-vaccine serum samples obtained from 174 elderly people vaccinated with seasonal influenza vaccines of 2006–2007, 2008–2009, 2009–2010, and 2010–2011 Northern Hemisphere vaccine campaigns. The presence of antibodies against A/H5N1, A/H7N3, and A/H9N2 avian influenza viruses were tested by using haemaglutination inhibition assays. Globally, heterotypic antibodies were found before vaccination in 2.9% of individuals against A/H5N1, 1.2% against A/H7N3, and 25.9% against A/H9N2. These pre-vaccination antibodies were present at titers ≥1/40 in 1.1% of individuals against A/H5N1, in 1.1% against H7N3, and in 0.6% against the A/H9N2 subtype. One 76 year-old male showed pre-vaccine antibodies (Abs) against those three avian influenza viruses, and another three individuals presented Abs against two different viruses. Seasonal influenza vaccination induced a significant number of heterotypic seroconversions against A/H5N1 (14.4%) and A/H9N2 (10.9%) viruses, but only one seroconversion was observed against the A/H7N3 subtype. After vaccination, four individuals showed Abs titers ≥1/40 against those three avian viruses, and 55 individuals against both A/H5N1 and A/H9N2. Seasonal vaccination is able to induce some weak heterotypic responses to viruses of avian origin in elderly individuals with no previous exposure to them. However, this response did not accomplish the European Medicament Agency criteria for influenza vaccine efficacy. The results of this study show that seasonal vaccines induce a broad
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Guo, Xinkun; Zhu, Zhaoqin; Zhang, Wanju; Meng, Xiaoxiao; Zhu, Yong; Han, Peng; Zhou, Xiaohui; Hu, Yunwen; Wang, Ruilan
2017-05-24
Infection with the influenza A (H1N1) virus is a major challenge for public health because it can cause severe morbidity and even mortality in humans. The over-secretion of inflammatory cytokines (cytokine storm) is considered to be a key contributor to the severe pneumonia caused by H1N1 infection. It has been reported that hypoxia-inducible factor 1-alpha (HIF-1α) is associated with the production of proinflammatory molecules, but whether HIF-1α participates in the acute inflammatory responses against H1N1 infection is still unclear. To investigate the role of HIF-1α in H1N1 infection, the expression and nuclear translocation of HIF-1α in A549 and THP-1 cell lines infected with H1N1 virus were observed. The results showed that without altering the intracellular mRNA or protein expression of HIF-1α, H1N1 infection only induced nuclear translocation of HIF-1α under normal oxygen concentrations. The use of 2-methoxyestradiol (2ME2), a HIF-1α inhibitor that blocks HIF-1α nuclear accumulation, in H1N1-infected cells decreased the mRNA and protein expression of tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6 and increased the levels of IL-10. In contrast, H1N1-infected cells under hypoxic conditions had increased HIF-1α nuclear accumulation, increased expression of TNF-α and IL-6 and decreased levels of IL-10. In conclusion, our data implied that in vitro H1N1 infection induced nuclear translocation of HIF-1α without altering the expression of HIF-1α, which may promote the secretion of proinflammatory cytokines during H1N1 infection.
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H5N1 influenza viruses: outbreaks and biological properties
Neumann, Gabriele; Chen, Hualan; Gao, George F; Shu, Yuelong; Kawaoka, Yoshihiro
2010-01-01
All known subtypes of influenza A viruses are maintained in wild waterfowl, the natural reservoir of these viruses. Influenza A viruses are isolated from a variety of animal species with varying morbidity and mortality rates. More importantly, influenza A viruses cause respiratory disease in humans with potentially fatal outcome. Local or global outbreaks in humans are typically characterized by excess hospitalizations and deaths. In 1997, highly pathogenic avian influenza viruses of the H5N1 subtype emerged in Hong Kong that transmitted to humans, resulting in the first documented cases of human death by avian influenza virus infection. A new outbreak started in July 2003 in poultry in Vietnam, Indonesia, and Thailand, and highly pathogenic avian H5N1 influenza viruses have since spread throughout Asia and into Europe and Africa. These viruses continue to infect humans with a high mortality rate and cause worldwide concern of a looming pandemic. Moreover, H5N1 virus outbreaks have had devastating effects on the poultry industries throughout Asia. Since H5N1 virus outbreaks appear to originate from Southern China, we here examine H5N1 influenza viruses in China, with an emphasis on their biological properties. PMID:19884910
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2009-08-07
Health • Prevention, Preparation and Mitigation » Seasonal Influenza » Pandemic Influenza 8/7/2009 2 Approved for Public Release, Distribution...health challenges in managing seasonal influenza and pandemics E h i ti l i di id l h lth t t i d l i th t• mp as ze some prac ca n v ua ea s ra...eg es an p ann ng a may protect employees and their families during the fall influenza season and beyond ROE: • Questions at anytime Disclaimers
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Effect of dispersion correction on the Au(1 1 1)-H2O interface: A first-principles study
NASA Astrophysics Data System (ADS)
Nadler, Roger; Sanz, Javier Fdez.
2012-09-01
A theoretical study of the H2O-Au(1 1 1) interface based on first principles density functional theory (DFT) calculations with and without inclusion of dispersion correction is reported. Three different computational approaches are considered. First, the standard generalized gradient approximation (GGA) functional PBE is employed. Second, an additional energy term is further included that adds a semi-empirically derived dispersion correction (PBE-D2), and, finally, a recently proposed functional that includes van der Waals (vdW) interactions directly in its functional form (optB86b-vdW) was used to represent the state-of-the art of DFT functionals. The monomeric water adsorption was first considered in order to explore the dependency of geometry on the details of the model slab used to represent it (size, thickness, coverage). When the dispersion corrections are included the Au-H2O interaction is stronger, as manifested by the smaller dAu-O and stronger adsorption energies. Additionally, the interfacial region between Au(1 1 1) slab surfaces and a liquid water layer was investigated with Born-Oppenheimer molecular dynamics (BOMD) using the same functionals. Two or three interfacial orientations can be determined, depending on the theoretical methodology applied. Closest to the surface, H2O is adsorbed O-down, whereas further away it is oriented with one OH bond pointing to the surface and the molecular plane parallel to the normal direction. For the optB86b-vdW functional a third orientation is found where one H atom points into the bulk water layer and the second OH bond is oriented parallel to the metal surface. As for the water density in the first adsorption layer we find a very small increase of roughly 8%. From the analysis of vibrational spectra a weakening of the H-bond network is observed upon the inclusion of the Au(1 1 1) slab, however, no disruption of H-bonds is observed. While the PBE and PBE-D2 spectra are very similar, the optB86b-vdW spectrum shows
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Cunha, Burke A; Syed, Uzma; Mickail, Nardeen
2011-01-01
We present a young woman with a negative medical history who presented with acute systemic lupus erythematosus (SLE) pneumonitis mimicking swine influenza (H1N1) pneumonia. Because this case occurred during the H1N1 pandemic, the initial diagnostic impression was of H1N1 pneumonia. Although her clinical and laboratory findings were consistent with the diagnosis of H1N1 pneumonia, e.g., fever, sore throat, dry cough, arthralgias, myalgias, thrombocytopenia, relative lymphopenia, and elevated serum transaminases, some findings suggested an alternate diagnosis, e.g., leukopenia, a highly elevated erythrocyte sedimentation rate, highly elevated serum ferritin levels, elevated antinuclear antibody (ANA) levels, and double-stranded (DS) DNA titers. Her chest x-ray showed an accentuation of basilar lung markings, with a small pleural effusion similar to the chest x-ray findings of early H1N1 pneumonia. Initially, her headaches were thought to be related to central nervous system manifestations of H1N1. After laboratory test results demonstrated elevated ANA and anti-DS DNA titers, she was diagnosed with acute SLE pneumonitis. The take-home lesson for clinicians is that other infectious diseases, e.g., human parainfluenza virus or Legionnaires' disease, can mimic H1N1 pneumonia during an influenza pandemic. Excluding asthma, congestive heart failure, exacerbations of acute bronchitis, chronic obstructive pulmonary disorder, and pulmonary interstitial disease, noninfectious mimics of H1N1 are extremely rare. To the best of our knowledge, this is the first reported case of de novo SLE pneumonitis mimicking H1N1 pneumonia during the swine influenza pandemic. Copyright © 2011 Elsevier Inc. All rights reserved.
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Yeast Surface-Displayed H5N1 Avian Influenza Vaccines
Lei, Han; Jin, Sha; Karlsson, Erik; Schultz-Cherry, Stacey
2016-01-01
Highly pathogenic H5N1 avian influenza viruses pose a pandemic threat to human health. A rapid vaccine production against fast outbreak is desired. We report, herein, a paradigm-shift influenza vaccine technology by presenting H5N1 hemagglutinin (HA) to the surface of yeast. We demonstrated, for the first time, that the HA surface-presented yeast can be used as influenza vaccines to elicit both humoral and cell-mediated immunity in mice. The HI titer of antisera reached up to 128 in vaccinated mice. A high level of H5N1 HA-specific IgG1 and IgG2a antibody production was detected after boost immunization. Furthermore, we demonstrated that the yeast surface-displayed HA preserves its antigenic sites. It preferentially binds to both avian- and human-type receptors. In addition, the vaccine exhibited high cross-reactivity to both homologous and heterologous H5N1 viruses. A high level production of anti-HA antibodies was detected in the mice five months after vaccination. Finally, our animal experimental results indicated that the yeast vaccine offered complete protection of mice from lethal H5N1 virus challenge. No severe side effect of yeast vaccines was noted in animal studies. This new technology allows for rapid and large-scale production of influenza vaccines for prepandemic preparation. PMID:28078309
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Virological characterization of influenza H1N1pdm09 in Vietnam, 2010-2013.
Nguyen, Hang K L; Nguyen, Phuong T K; Nguyen, Thach C; Hoang, Phuong V M; Le, Thanh T; Vuong, Cuong D; Nguyen, Anh P; Tran, Loan T T; Nguyen, Binh G; Lê, Mai Q
2015-07-01
Influenza A/H1N1pdm09 virus was first detected in Vietnam on May 31, 2009, and continues to circulate in Vietnam as a seasonal influenza virus. This study has monitored genotypic and phenotypic changes in this group of viruses during 2010-2013 period. We sequenced hemagglutinin (HA) and neuraminidase (NA) genes from representative influenza A/H1N1pdm09 and compared with vaccine strain A/California/07/09 and other contemporary isolates from neighboring countries. Hemagglutination inhibition (HI) and neuraminidase inhibition (NAI) assays also were performed on these isolates. Representative influenza A/H1N1pdm09 isolates (n = 61) from ILI and SARI surveillances in northern Vietnam between 2010 and 2013. The HA and NA phylogenies revealed six and seven groups, respectively. Five isolates (8·2%) had substitutions G155E and N156K in the HA, which were associated with reduced HI titers by antiserum raised against the vaccine virus A/California/07/2009. One isolate from 2011 and one isolate from 2013 had a predicted H275Y substitution in the neuraminidase molecule, which was associated with reduced susceptibility to oseltamivir in a NAI assay. We also identified a D222N change in the HA of a virus isolated from a fatal case in 2013. Significant genotypic and phenotypic changes in A/ H1N1pdm09 influenza viruses were detected by the National Influenza Surveillance System (NISS) in Vietnam between 2010 and 2013 highlighting the value of this system to Vietnam and to the region. Sustained NISS and continued virological monitoring of seasonal influenza viruses are required for vaccine policy development in Vietnam. 3. © 2015 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.
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Final report on COOMET Vickers PTB/VNIIFTRI key comparison (COOMET.M.H-K1.b and COOMET.M.H-K1.c)
NASA Astrophysics Data System (ADS)
Aslanyan, E.; Herrmann, K.
2013-01-01
This report describes a COOMET key comparison on Vickers hardness scales of two National Metrology Institutes—PTB and VNIIFTRI. The pilot laboratory was PTB, which was the linking institute with the key comparison reference values of CCM.H-K1. In the key comparison two sets of hardness reference blocks for the Vickers hardness scales HV1 and HV30, each consisting of three hardness reference blocks with the hardness levels 240 HV, 540 HV and 840 HV, are used. The same hardness reference blocks were used previously in the key comparison CCM.H-K1. The measurement results and uncertainty assessments, announced by VNIIFTRI, are in good agreement with the key comparison reference values of CCM.H-K1. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).