Origin, diversity and maturation of human antiviral antibodies analyzed by high-throughput sequencing

Directory of Open Access Journals (Sweden)

Ponraj ePrabakaran

2012-08-01

Full Text Available Our understanding of how antibodies are generated and function could help develop effective vaccines and antibody-based therapeutics against viruses such as HIV-1, SARS Coronavirus (CoV, and Hendra and Nipah viruses (henipaviruses. Although broadly neutralizing antibodies (bnAbs against the HIV-1 were observed in patients, elicitation of such bnAbs remains a major challenge when compared to other viral targets. We previously hypothesized that HIV-1 could have evolved a strategy to evade the immune system due to absent or very weak binding of germline antibodies to the conserved epitopes that may not be sufficient to initiate and/or maintain an effective immune response. To further explore our hypothesis, we used the 454 sequence analysis of a large naïve library of human IgM antibodies which had been used for selecting antibodies against SARS Coronavirus (CoV receptor-binding domain (RBD, and soluble G proteins (sG of Hendra and Nipah viruses (henipaviruses. We found that the human IgM repertoires from the 454 sequencing have diverse germline usages, recombination patterns, junction diversity and a lower extent of somatic mutation. In this study, we identified germline intermediates of antibodies specific to HIV-1 and other viruses as observed in normal individuals, and compared their genetic diversity and somatic mutation level along with available structural and functional data. Further computational analysis will provide framework for understanding the underlying genetic and molecular determinants related to maturation pathways of antiviral bnAbs that could be useful for applying novel approaches to the design of effective vaccine immunogens and antibody-based therapeutics.

Srv mediated dispersal of streptococcal biofilms through SpeB is observed in CovRS+ strains.

Directory of Open Access Journals (Sweden)

Kristie L Connolly

Full Text Available Group A Streptococcus (GAS is a human specific pathogen capable of causing both mild infections and severe invasive disease. We and others have shown that GAS is able to form biofilms during infection. That is to say, they form a three-dimensional, surface attached structure consisting of bacteria and a multi-component extracellular matrix. The mechanisms involved in regulation and dispersal of these GAS structures are still unclear. Recently we have reported that in the absence of the transcriptional regulator Srv in the MGAS5005 background, the cysteine protease SpeB is constitutively produced, leading to increased tissue damage and decreased biofilm formation during a subcutaneous infection in a mouse model. This was interesting because MGAS5005 has a naturally occurring mutation that inactivates the sensor kinase domain of the two component regulatory system CovRS. Others have previously shown that strains lacking covS are associated with decreased SpeB production due to CovR repression of speB expression. Thus, our results suggest the inactivation of srv can bypass CovR repression and lead to constitutive SpeB production. We hypothesized that Srv control of SpeB production may be a mechanism to regulate biofilm dispersal and provide a mechanism by which mild infection can transition to severe disease through biofilm dispersal. The question remained however, is this mechanism conserved among GAS strains or restricted to the unique genetic makeup of MGAS5005. Here we show that Srv mediated control of SpeB and biofilm dispersal is conserved in the invasive clinical isolates RGAS053 (serotype M1 and MGAS315 (serotype M3, both of which have covS intact. This work provides additional evidence that Srv regulated control of SpeB may mediate biofilm formation and dispersal in diverse strain backgrounds.

Discovery of novel bat coronaviruses in south China that use the same receptor as MERS coronavirus.

Science.gov (United States)

Luo, Chu-Ming; Wang, Ning; Yang, Xing-Lou; Liu, Hai-Zhou; Zhang, Wei; Li, Bei; Hu, Ben; Peng, Cheng; Geng, Qi-Bin; Zhu, Guang-Jian; Li, Fang; Shi, Zheng-Li

2018-04-18

Middle East respiratory syndrome coronavirus (MERS-CoV) has represented a human health threat since 2012. Although several MERS-related CoVs, which belong to the same species as MERS-CoV, have been identified from bats, they do not use the MERS-CoV receptor, dipeptidyl peptidase 4 (DPP4). Here, we screened 1059 bat samples from at least 30 bat species collected in different regions in south China and identified 89 strains of lineage C betacoronaviruses, including Tylonycteris pachypus HKU4 , Pipistrellus pipistrellus HKU5, and MERS-related CoVs. We sequenced the full-length genomes of two positive samples collected from the great evening bat, Ia io , from Guangdong Province. The two genomes were highly similar and exhibited genomic structures identical to those of other lineage C betacoronaviruses. While they exhibited genome-wide nucleotide identities of only 75.3 to 81.2% with other MERS-related CoVs, their gene-coding regions were highly similar to their counterparts, except in the case of the spike proteins. Further protein--protein interaction assays demonstrated that the spike proteins of these MERS-related CoVs bind to the receptor DPP4. Recombination analysis suggested that the newly discovered MERS-related CoVs might have acquired their spike genes from a DPP4-recognizing bat HKU4. Our study provides further evidence that bats represent the evolutionary origins of MERS-CoV. IMPORTANCE Previous studies suggested that the Middle East respiratory syndrome coronavirus (MERS-CoV) may have originated in bats. However, its evolutionary path from bats to humans remains unclear. In this study, we discovered 89 novel lineage C betacoronaviruses (BetaCoVs) in eight bat species. We provide the evidence of a MERS-related CoV derived from the great evening bat that uses the same host receptor as human MERS-CoV. This virus also provides evidence for a natural recombination event between the bat MERS-related CoV and another bat coronavirus HKU4. Our study expands the host

Pains and Gains from China's Experiences with Emerging Epidemics: From SARS to H7N9

OpenAIRE

Wei, Pengfei; Cai, Zelang; Hua, Jinwen; Yu, Weijia; Chen, Jiajie; Kang, Kang; Qiu, Congling; Ye, Lanlan; Hu, Jiayun; Ji, Kunmei

2016-01-01

Over the recent decades, China experienced several emerging virus outbreaks including those caused by the severe acute respiratory syndrome- (SARS-) coronavirus (Cov), H5N1 virus, and H7N9 virus. The SARS tragedy revealed faults in China’s infectious disease prevention system, propelling the Chinese government to enact reforms that enabled better combating of the subsequent H1N1 and H7N9 avian flu epidemics. The system is buttressed by three fundamental, mutually reinforcing components: (1) e...

Differential sensitivity of bat cells to infection by enveloped RNA viruses: coronaviruses, paramyxoviruses, filoviruses, and influenza viruses.

Directory of Open Access Journals (Sweden)

Markus Hoffmann

Full Text Available Bats (Chiroptera host major human pathogenic viruses including corona-, paramyxo, rhabdo- and filoviruses. We analyzed six different cell lines from either Yinpterochiroptera (including African flying foxes and a rhinolophid bat or Yangochiroptera (genera Carollia and Tadarida for susceptibility to infection by different enveloped RNA viruses. None of the cells were sensitive to infection by transmissible gastroenteritis virus (TGEV, a porcine coronavirus, or to infection mediated by the Spike (S protein of SARS-coronavirus (SARS-CoV incorporated into pseudotypes based on vesicular stomatitis virus (VSV. The resistance to infection was overcome if cells were transfected to express the respective cellular receptor, porcine aminopeptidase N for TGEV or angiotensin-converting enzyme 2 for SARS-CoV. VSV pseudotypes containing the S proteins of two bat SARS-related CoV (Bg08 and Rp3 were unable to infect any of the six tested bat cell lines. By contrast, viral pseudotypes containing the surface protein GP of Marburg virus from the family Filoviridae infected all six cell lines though at different efficiency. Notably, all cells were sensitive to infection by two paramyxoviruses (Sendai virus and bovine respiratory syncytial virus and three influenza viruses from different subtypes. These results indicate that bat cells are more resistant to infection by coronaviruses than to infection by paramyxoviruses, filoviruses and influenza viruses. Furthermore, these results show a receptor-dependent restriction of the infection of bat cells by CoV. The implications for the isolation of coronaviruses from bats are discussed.

Human monoclonal antibody as prophylaxis for SARS coronavirus infection in ferrets

NARCIS (Netherlands)

ter Meulen, Jan; Bakker, Alexander B. H.; van den Brink, Edward N.; Weverling, Gerrit J.; Martina, Byron E. E.; Haagmans, Bart L.; Kuiken, Thijs; de Kruif, John; Preiser, Wolfgang; Spaan, Willy; Gelderblom, Hans R.; Goudsmit, Jaap; Osterhaus, Albert D. M. E.

2004-01-01

SARS coronavirus continues to cause sporadic cases of severe acute respiratory syndrome (SARS) in China. No active or passive immunoprophylaxis for disease induced by SARS coronavirus is available. We investigated prophylaxis of SARS coronavirus infection with a neutralising human monoclonal

The integration of Human Factors (HF) in the SAR process training course text

International Nuclear Information System (INIS)

Ryan, T.G.

1995-03-01

This text provides the technical basis for a two-day course on human factors (HF), as applied to the Safety Analysis Report (SAR) process. The overall objective of this text and course is to: provide the participant with a working knowledge of human factors-related requirements, suggestions for doing a human safety analysis applying a graded approach, and an ability to demonstrate using the results of the human safety analysis, that human factors elements as defined by DOE (human factors engineering, procedures, training, oversight, staffing, qualifications), can support wherever necessary, nuclear safety commitments in the SAR. More specifically, the objectives of the text and course are: (1) To provide the SAR preparer with general guidelines for doing HE within the context of a graded approach for the SAR; (2) To sensitize DOE facility managers and staff, safety analysts and SAR preparers, independent reviewers, and DOE reviewers and regulators, to DOE Order 5480.23 requirements for HE in the SAR; (3) To provide managers, analysts, reviewers and regulators with a working knowledge of HE concepts and techniques within the context of a graded approach for the SAR, and (4) To provide SAR managers and DOE reviewers and regulators with general guidelines for monitoring and coordinating the work of preparers of HE inputs throughout the SAR process, and for making decisions regarding the safety relevance of HE inputs to the SAR. As a ready reference for implementing the human factors requirements of DOE Order 5480.22 and DOE Standard 3009-94, this course text and accompanying two-day course are intended for all persons who are involved in the SAR

The integration of Human Factors (HF) in the SAR process training course text

Energy Technology Data Exchange (ETDEWEB)

Ryan, T.G.

1995-03-01

This text provides the technical basis for a two-day course on human factors (HF), as applied to the Safety Analysis Report (SAR) process. The overall objective of this text and course is to: provide the participant with a working knowledge of human factors-related requirements, suggestions for doing a human safety analysis applying a graded approach, and an ability to demonstrate using the results of the human safety analysis, that human factors elements as defined by DOE (human factors engineering, procedures, training, oversight, staffing, qualifications), can support wherever necessary, nuclear safety commitments in the SAR. More specifically, the objectives of the text and course are: (1) To provide the SAR preparer with general guidelines for doing HE within the context of a graded approach for the SAR; (2) To sensitize DOE facility managers and staff, safety analysts and SAR preparers, independent reviewers, and DOE reviewers and regulators, to DOE Order 5480.23 requirements for HE in the SAR; (3) To provide managers, analysts, reviewers and regulators with a working knowledge of HE concepts and techniques within the context of a graded approach for the SAR, and (4) To provide SAR managers and DOE reviewers and regulators with general guidelines for monitoring and coordinating the work of preparers of HE inputs throughout the SAR process, and for making decisions regarding the safety relevance of HE inputs to the SAR. As a ready reference for implementing the human factors requirements of DOE Order 5480.22 and DOE Standard 3009-94, this course text and accompanying two-day course are intended for all persons who are involved in the SAR.

Application of postured human model for SAR measurements

Science.gov (United States)

Vuchkovikj, M.; Munteanu, I.; Weiland, T.

2013-07-01

In the last two decades, the increasing number of electronic devices used in day-to-day life led to a growing interest in the study of the electromagnetic field interaction with biological tissues. The design of medical devices and wireless communication devices such as mobile phones benefits a lot from the bio-electromagnetic simulations in which digital human models are used. The digital human models currently available have an upright position which limits the research activities in realistic scenarios, where postured human bodies must be considered. For this reason, a software application called "BodyFlex for CST STUDIO SUITE" was developed. In its current version, this application can deform the voxel-based human model named HUGO (Dipp GmbH, 2010) to allow the generation of common postures that people use in normal life, ensuring the continuity of tissues and conserving the mass to an acceptable level. This paper describes the enhancement of the "BodyFlex" application, which is related to the movements of the forearm and the wrist of a digital human model. One of the electromagnetic applications in which the forearm and the wrist movement of a voxel based human model has a significant meaning is the measurement of the specific absorption rate (SAR) when a model is exposed to a radio frequency electromagnetic field produced by a mobile phone. Current SAR measurements of the exposure from mobile phones are performed with the SAM (Specific Anthropomorphic Mannequin) phantom which is filled with a dispersive but homogeneous material. We are interested what happens with the SAR values if a realistic inhomogeneous human model is used. To this aim, two human models, a homogeneous and an inhomogeneous one, in two simulation scenarios are used, in order to examine and observe the differences in the results for the SAR values.

Dendritic cell targeted chitosan nanoparticles for nasal DNA immunization against SARS CoV nucleocapsid protein.

Science.gov (United States)

Raghuwanshi, Dharmendra; Mishra, Vivek; Das, Dipankar; Kaur, Kamaljit; Suresh, Mavanur R

2012-04-02

This work investigates the formulation and in vivo efficacy of dendritic cell (DC) targeted plasmid DNA loaded biotinylated chitosan nanoparticles for nasal immunization against nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) as antigen. The induction of antigen-specific mucosal and systemic immune response at the site of virus entry is a major challenge for vaccine design. Here, we designed a strategy for noninvasive receptor mediated gene delivery to nasal resident DCs. The pDNA loaded biotinylated chitosan nanoparticles were prepared using a complex coacervation process and characterized for size, shape, surface charge, plasmid DNA loading and protection against nuclease digestion. The pDNA loaded biotinylated chitosan nanoparticles were targeted with bifunctional fusion protein (bfFp) vector for achieving DC selective targeting. The bfFp is a recombinant fusion protein consisting of truncated core-streptavidin fused with anti-DEC-205 single chain antibody (scFv). The core-streptavidin arm of fusion protein binds with biotinylated nanoparticles, while anti-DEC-205 scFv imparts targeting specificity to DC DEC-205 receptor. We demonstrate that intranasal administration of bfFp targeted formulations along with anti-CD40 DC maturation stimuli enhanced magnitude of mucosal IgA as well as systemic IgG against N protein. The strategy led to the detection of augmented levels of N protein specific systemic IgG and nasal IgA antibodies. However, following intranasal delivery of naked pDNA no mucosal and systemic immune responses were detected. A parallel comparison of targeted formulations using intramuscular and intranasal routes showed that the intramuscular route is superior for induction of systemic IgG responses compared with the intranasal route. Our results suggest that targeted pDNA delivery through a noninvasive intranasal route can be a strategy for designing low-dose vaccines.

Residue analysis of a CTL epitope of SARS-CoV spike protein by IFN-gamma production and bioinformatics prediction

Directory of Open Access Journals (Sweden)

Huang Jun

2012-09-01

Full Text Available Abstract Background Severe acute respiratory syndrome (SARS is an emerging infectious disease caused by the novel coronavirus SARS-CoV. The T cell epitopes of the SARS CoV spike protein are well known, but no systematic evaluation of the functional and structural roles of each residue has been reported for these antigenic epitopes. Analysis of the functional importance of side-chains by mutational study may exaggerate the effect by imposing a structural disturbance or an unusual steric, electrostatic or hydrophobic interaction. Results We demonstrated that N50 could induce significant IFN-gamma response from SARS-CoV S DNA immunized mice splenocytes by the means of ELISA, ELISPOT and FACS. Moreover, S366-374 was predicted to be an optimal epitope by bioinformatics tools: ANN, SMM, ARB and BIMAS, and confirmed by IFN-gamma response induced by a series of S358-374-derived peptides. Furthermore, each of S366-374 was replaced by alanine (A, lysine (K or aspartic acid (D, respectively. ANN was used to estimate the binding affinity of single S366-374 mutants to H-2 Kd. Y367 and L374 were predicated to possess the most important role in peptide binding. Additionally, these one residue mutated peptides were synthesized, and IFN-gamma production induced by G368, V369, A371, T372 and K373 mutated S366-374 were decreased obviously. Conclusions We demonstrated that S366-374 is an optimal H-2 Kd CTL epitope in the SARS CoV S protein. Moreover, Y367, S370, and L374 are anchors in the epitope, while C366, G368, V369, A371, T372, and K373 may directly interact with TCR on the surface of CD8-T cells.

Mechanisms of Host Receptor Adaptation by Severe Acute Respiratory Syndrome Coronavirus

Energy Technology Data Exchange (ETDEWEB)

Wu, Kailang; Peng, Guiqing; Wilken, Matthew; Geraghty, Robert J.; Li, Fang (UMMC)

2012-12-10

The severe acute respiratory syndrome coronavirus (SARS-CoV) from palm civets has twice evolved the capacity to infect humans by gaining binding affinity for human receptor angiotensin-converting enzyme 2 (ACE2). Numerous mutations have been identified in the receptor-binding domain (RBD) of different SARS-CoV strains isolated from humans or civets. Why these mutations were naturally selected or how SARS-CoV evolved to adapt to different host receptors has been poorly understood, presenting evolutionary and epidemic conundrums. In this study, we investigated the impact of these mutations on receptor recognition, an important determinant of SARS-CoV infection and pathogenesis. Using a combination of biochemical, functional, and crystallographic approaches, we elucidated the molecular and structural mechanisms of each of these naturally selected RBD mutations. These mutations either strengthen favorable interactions or reduce unfavorable interactions with two virus-binding hot spots on ACE2, and by doing so, they enhance viral interactions with either human (hACE2) or civet (cACE2) ACE2. Therefore, these mutations were viral adaptations to either hACE2 or cACE2. To corroborate the above analysis, we designed and characterized two optimized RBDs. The human-optimized RBD contains all of the hACE2-adapted residues (Phe-442, Phe-472, Asn-479, Asp-480, and Thr-487) and possesses exceptionally high affinity for hACE2 but relative low affinity for cACE2. The civet-optimized RBD contains all of the cACE2-adapted residues (Tyr-442, Pro-472, Arg-479, Gly-480, and Thr-487) and possesses exceptionally high affinity for cACE2 and also substantial affinity for hACE2. These results not only illustrate the detailed mechanisms of host receptor adaptation by SARS-CoV but also provide a molecular and structural basis for tracking future SARS-CoV evolution in animals.

Quantitative structure-activity relationships of selective antagonists of glucagon receptor using QuaSAR descriptors.

Science.gov (United States)

Manoj Kumar, Palanivelu; Karthikeyan, Chandrabose; Hari Narayana Moorthy, Narayana Subbiah; Trivedi, Piyush

2006-11-01

In the present paper, quantitative structure activity relationship (QSAR) approach was applied to understand the affinity and selectivity of a novel series of triaryl imidazole derivatives towards glucagon receptor. Statistically significant and highly predictive QSARs were derived for glucagon receptor inhibition by triaryl imidazoles using QuaSAR descriptors of molecular operating environment (MOE) employing computer-assisted multiple regression procedure. The generated QSAR models revealed that factors related to hydrophobicity, molecular shape and geometry predominantly influences glucagon receptor binding affinity of the triaryl imidazoles indicating the relevance of shape specific steric interactions between the molecule and the receptor. Further, QSAR models formulated for selective inhibition of glucagon receptor over p38 mitogen activated protein (MAP) kinase of the compounds in the series highlights that the same structural features, which influence the glucagon receptor affinity, also contribute to their selective inhibition.

Ribonucleocapsid Formation of SARS-COV Through Molecular Action of the N-Terminal Domain of N Protein

Energy Technology Data Exchange (ETDEWEB)

Saikatendu, K.S.; Joseph, J.S.; Subramanian, V.; Neuman, B.W.; Buchmeier, M.J.; Stevens, R.C.; Kuhn, P.; /Scripps Res. Inst.

2007-07-12

Conserved amongst all coronaviruses are four structural proteins, the matrix (M), small envelope (E) and spike (S) that are embedded in the viral membrane and the nucleocapsid phosphoprotein (N), which exists in a ribonucleoprotein complex in their lumen. The N terminal domain of coronaviral N proteins (N-NTD) provides a scaffold for RNA binding while the C-terminal domain (N-CTD) mainly acts as oligomerization modules during assembly. The C-terminus of N protein anchors it to the viral membrane by associating with M protein. We characterized the structures of N-NTD from severe acute respiratory syndrome coronavirus (SARS-CoV) in two crystal forms, at 1.17A (monoclinic) and 1.85 A (cubic) respectively, solved by molecular replacement using the homologous avian infectious bronchitis virus (IBV) structure. Flexible loops in the solution structure of SARS-CoV N-NTD are now shown to be well ordered around the beta-sheet core. The functionally important positively charged beta-hairpin protrudes out of the core and is oriented similar to that in the IBV N-NTD and is involved in crystal packing in the monoclinic form. In the cubic form, the monomers form trimeric units that stack in a helical array. Comparison of crystal packing of SARS-CoV and IBV N-NTDs suggest a common mode of RNA recognition, but probably associate differently in vivo during the formation of the ribonucleoprotein complex. Electrostatic potential distribution on the surface of homology models of related coronaviral N-NTDs hints that they employ different modes of both RNA recognition as well as oligomeric assembly, perhaps explaining why their nucleocapsids have different morphologies.

Molecular dynamics of Middle East Respiratory Syndrome Coronavirus (MERS CoV) fusion heptad repeat trimers

KAUST Repository

Kandeel, Mahmoud; Al-Taher, Abdulla; Li, Huifang; Schwingenschlö gl, Udo; Alnazawi, Mohamed

2018-01-01

Structural studies related to Middle East Respiratory Syndrome Coronavirus (MERS CoV) infection process are so limited. In this study, molecular dynamics (MD) simulation was carried out to unravel changes in the MERS CoV heptad repeat domains (HRs

Human factors engineering checklists for application in the SAR process

International Nuclear Information System (INIS)

Overlin, T.K.; Romero, H.A.; Ryan, T.G.

1995-03-01

This technical report was produced to assist the preparers and reviewers of the human factors portions of the SAR in completing their assigned tasks regarding analysis and/or review of completed analyses. The checklists, which are the main body of the report, and the subsequent tables, were developed to assist analysts in generating the needed analysis data to complete the human engineering analysis for the SAR. The technical report provides a series of 19 human factors engineering (HFE) checklists which support the safety analyses of the US Department of Energy's (DOE) reactor and nonreactor facilities and activities. The results generated using these checklists and in the preparation of the concluding analyses provide the technical basis for preparing the human factors chapter, and subsequent inputs to other chapters, required by DOE as a part of the safety analysis reports (SARs). This document is divided into four main sections. The first part explains the origin of the checklists, the sources utilized, and other information pertaining to the purpose and scope of the report. The second part, subdivided into 19 sections, is the checklists themselves. The third section is the glossary which defines terms that could either be unfamiliar or have specific meanings within the context of these checklists. The final section is the subject index in which the glossary terms are referenced back to the specific checklist and page the term is encountered

Evaluation of serologic and antigenic relationships between middle eastern respiratory syndrome coronavirus and other coronaviruses to develop vaccine platforms for the rapid response to emerging coronaviruses.

Science.gov (United States)

Agnihothram, Sudhakar; Gopal, Robin; Yount, Boyd L; Donaldson, Eric F; Menachery, Vineet D; Graham, Rachel L; Scobey, Trevor D; Gralinski, Lisa E; Denison, Mark R; Zambon, Maria; Baric, Ralph S

2014-04-01

Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012, causing severe acute respiratory disease and pneumonia, with 44% mortality among 136 cases to date. Design of vaccines to limit the virus spread or diagnostic tests to track newly emerging strains requires knowledge of antigenic and serologic relationships between MERS-CoV and other CoVs.  Using synthetic genomics and Venezuelan equine encephalitis virus replicons (VRPs) expressing spike and nucleocapsid proteins from MERS-CoV and other human and bat CoVs, we characterize the antigenic responses (using Western blot and enzyme-linked immunosorbent assay) and serologic responses (using neutralization assays) against 2 MERS-CoV isolates in comparison with those of other human and bat CoVs.  Serologic and neutralization responses against the spike glycoprotein were primarily strain specific, with a very low level of cross-reactivity within or across subgroups. CoV N proteins within but not across subgroups share cross-reactive epitopes with MERS-CoV isolates. Our findings were validated using a convalescent-phase serum specimen from a patient infected with MERS-CoV (NA 01) and human antiserum against SARS-CoV, human CoV NL63, and human CoV OC43.  Vaccine design for emerging CoVs should involve chimeric spike protein containing neutralizing epitopes from multiple virus strains across subgroups to reduce immune pathology, and a diagnostic platform should include a panel of nucleocapsid and spike proteins from phylogenetically distinct CoVs.

Human factors engineering checklists for application in the SAR process

Energy Technology Data Exchange (ETDEWEB)

Overlin, T.K.; Romero, H.A.; Ryan, T.G.

1995-03-01

This technical report was produced to assist the preparers and reviewers of the human factors portions of the SAR in completing their assigned tasks regarding analysis and/or review of completed analyses. The checklists, which are the main body of the report, and the subsequent tables, were developed to assist analysts in generating the needed analysis data to complete the human engineering analysis for the SAR. The technical report provides a series of 19 human factors engineering (HFE) checklists which support the safety analyses of the US Department of Energy`s (DOE) reactor and nonreactor facilities and activities. The results generated using these checklists and in the preparation of the concluding analyses provide the technical basis for preparing the human factors chapter, and subsequent inputs to other chapters, required by DOE as a part of the safety analysis reports (SARs). This document is divided into four main sections. The first part explains the origin of the checklists, the sources utilized, and other information pertaining to the purpose and scope of the report. The second part, subdivided into 19 sections, is the checklists themselves. The third section is the glossary which defines terms that could either be unfamiliar or have specific meanings within the context of these checklists. The final section is the subject index in which the glossary terms are referenced back to the specific checklist and page the term is encountered.

SAR in human head model due to resonant wireless power transfer system.

Science.gov (United States)

Zhang, Chao; Liu, Guoqiang; Li, Yanhong; Song, Xianjin

2016-04-29

Efficient mid-range wireless power transfer between transmitter and the receiver has been achieved based on the magnetic resonant coupling method. The influence of electromagnetic field on the human body due to resonant wireless power transfer system (RWPT) should be taken into account during the design process of the system. To analyze the transfer performance of the RWPT system and the change rules of the specific absorption rate (SAR) in the human head model due to the RWPT system. The circuit-field coupling method for a RWPT system with consideration of the displacement current was presented. The relationship between the spiral coil parameters and transfer performance was studied. The SAR in the human head model was calculated under two different exposure conditions. A system with output power higher than 10 W at 0.2 m distance operating at a frequency of approximately 1 MHz was designed. The FEM simulation results show the peak SAR value is below the safety limit which appeared when the human head model is in front of the transmitter. The simulation results agreed well with the experimental results, which verified the validity of the analysis and design.

Mobile phone types and SAR characteristics of the human brain

Science.gov (United States)

Lee, Ae-Kyoung; Hong, Seon-Eui; Kwon, Jong-Hwa; Choi, Hyung-Do; Cardis, Elisabeth

2017-04-01

Mobile phones differ in terms of their operating frequency, outer shape, and form and location of the antennae, all of which affect the spatial distributions of their electromagnetic field and the level of electromagnetic absorption in the human head or brain. For this paper, the specific absorption rate (SAR) was calculated for four anatomical head models at different ages using 11 numerical phone models of different shapes and antenna configurations. The 11 models represent phone types accounting for around 86% of the approximately 1400 commercial phone models released into the Korean market since 2002. Seven of the phone models selected have an internal dual-band antenna, and the remaining four possess an external antenna. Each model was intended to generate an average absorption level equivalent to that of the same type of commercial phone model operating at the maximum available output power. The 1 g peak spatial SAR and ipsilateral and contralateral brain-averaged SARs were reported for all 11 phone models. The effects of the phone type, phone position, operating frequency, and age of head models on the brain SAR were comprehensively determined.

Structural Analysis of Major Species Barriers between Humans and Palm Civets for Severe Acute Respiratory Syndrome Coronavirus Infections

Energy Technology Data Exchange (ETDEWEB)

Li, Fang (UMM)

2008-09-23

It is believed that a novel coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV), was passed from palm civets to humans and caused the epidemic of SARS in 2002 to 2003. The major species barriers between humans and civets for SARS-CoV infections are the specific interactions between a defined receptor-binding domain (RBD) on a viral spike protein and its host receptor, angiotensin-converting enzyme 2 (ACE2). In this study a chimeric ACE2 bearing the critical N-terminal helix from civet and the remaining peptidase domain from human was constructed, and it was shown that this construct has the same receptor activity as civet ACE2. In addition, crystal structures of the chimeric ACE2 complexed with RBDs from various human and civet SARS-CoV strains were determined. These structures, combined with a previously determined structure of human ACE2 complexed with the RBD from a human SARS-CoV strain, have revealed a structural basis for understanding the major species barriers between humans and civets for SARS-CoV infections. They show that the major species barriers are determined by interactions between four ACE2 residues (residues 31, 35, 38, and 353) and two RBD residues (residues 479 and 487), that early civet SARS-CoV isolates were prevented from infecting human cells due to imbalanced salt bridges at the hydrophobic virus/receptor interface, and that SARS-CoV has evolved to gain sustained infectivity for human cells by eliminating unfavorable free charges at the interface through stepwise mutations at positions 479 and 487. These results enhance our understanding of host adaptations and cross-species infections of SARS-CoV and other emerging animal viruses.

A study on antigenicity and receptor-binding ability of fragment 450-650 of the spike protein of SARS coronavirus

International Nuclear Information System (INIS)

Zhao Jincun; Wang Wei; Yuan Zhihong; Jia Rujing; Zhao Zhendong; Xu Xiaojun; Lv Ping; Zhang Yan; Jiang Chengyu; Gao Xiaoming

2007-01-01

The spike (S) protein of SARS coronavirus (SARS-CoV) is responsible for viral binding with ACE2 molecules. Its receptor-binding motif (S-RBM) is located between residues 424 and 494, which folds into 2 anti-parallel β-sheets, β5 and β6. We have previously demonstrated that fragment 450-650 of the S protein (S450-650) is predominantly recognized by convalescent sera of SARS patients. The N-terminal 60 residues (450-510) of the S450-650 fragment covers the entire β6 strand of S-RBM. In the present study, we demonstrate that patient sera predominantly recognized 2 linear epitopes outside the β6 fragment, while the mouse antisera, induced by immunization of BALB/c mice with recombinant S450-650, mainly recognized the β6 strand-containing region. Unlike patient sera, however, the mouse antisera were unable to inhibit the infectivity of S protein-expressing (SARS-CoV-S) pseudovirus. Fusion protein between green fluorescence protein (GFP) and S450-650 (S450-650-GFP) was able to stain Vero E6 cells and deletion of the β6 fragment rendered the fusion product (S511-650-GFP) unable to do so. Similarly, recombinant S450-650, but not S511-650, was able to block the infection of Vero E6 cells by the SARS-CoV-S pseudovirus. Co-precipitation experiments confirmed that S450-650 was able to specifically bind with ACE2 molecules in lysate of Vero E6 cells. However, the ability of S450-510, either alone or in fusion with GFP, to bind with ACE2 was significantly poorer compared with S450-650. Our data suggest a possibility that, although the β6 strand alone is able to bind with ACE2 with relatively high affinity, residues outside the S-RBM could also assist the receptor binding of SARS-CoV-S protein

Comparative analysis of chest radiological findings between avian human influenza and SARS

International Nuclear Information System (INIS)

Cai Mingjin; Mai Weiwen; Xian Jianxing; Zhang Jiayun; Lin Wenjian; Wei Liping; Chen Jincheng

2008-01-01

Objective: To study the chest radiological findings of a mortal avian human influenza case. Methods: One patient in our hospital was proved to be infected avian human influenza in Guangdong province on March 1, 2006. The Clinical appearances and chest radiological findings of this case were retrospectively analyzed and compared with that of 3 mortal SARS cases out of 16 cases in 2003. Results: Large consolidated areas in left lower lobe was showed in pulmonary radiological findings of this patient and soon developed into ARDS (adult respiratory distress syndrome). However, the pulmonary radiological findings had no characteristic. Characteristics of soaring size and number during short term appeared in SARS instead of avian human influenza. Final diagnosis was up to the etiology and serology examination. Conclusion: Bronchial dissemination was not observed in this avian human influenza case. Pay attention to the avian human influenza in spite of no history of contract with sick or dead poultry in large city. (authors)

Síntese de látices com baixa concentração de compostos orgânicos voláteis (COVs: efeito das técnicas de redução dos COVs nas propriedades dos látexes e das tintas

Directory of Open Access Journals (Sweden)

Maurício Pinheiro de Oliveira

2014-08-01

Full Text Available A redução dos compostos orgânicos voláteis (COVs nos látices produzidos via polimerização em emulsão é uma opção viável, mas em algumas situações pode comprometer a qualidade do látex. Diferentes técnicas de redução da concentração dos monômeros e dos COVs foram estudadas com o objetivo de entender o efeito destas técnicas e da concentração dos COVs nas propriedades de aplicação dos látices e das tintas. Os látices de estireno com acrilato de 2-etil hexila funcionalizados com ácido acrílico e acrilamida foram produzidos via polimerização em emulsão, seguido por remoção química, física e a combinação de ambas as técnicas de redução dos monômeros e dos COVs. Os parâmetros relacionados à técnica de redução dos COVs, ao tipo de iniciador, ao agente de redução e à introdução de nitrogênio saturado com vapor de água foram estudados e correlacionados com as propriedades de aplicação das tintas. A combinação da técnica química com a técnica física foi mais eficiente na redução dos monômeros e dos COVs nos látices. As técnicas utilizadas na redução dos COVs tiveram influência negativa nas propriedades de aplicação dos látices. A resistência à abrasão dos filmes de tinta foi dependente da técnica empregada e da concentração dos COVs.

Generation of human antibody fragments recognizing distinct epitopes of the nucleocapsid (N SARS-CoV protein using a phage display approach

Directory of Open Access Journals (Sweden)

Grasso Felicia

2005-09-01

Full Text Available Abstract Background Severe acute respiratory syndrome (SARS-CoV is a newly emerging virus that causes SARS with high mortality rate in infected people. Successful control of the global SARS epidemic will require rapid and sensitive diagnostic tests to monitor its spread, as well as, the development of vaccines and new antiviral compounds including neutralizing antibodies that effectively prevent or treat this disease. Methods The human synthetic single-chain fragment variable (scFv ETH-2 phage antibody library was used for the isolation of scFvs against the nucleocapsid (N protein of SARS-CoV using a bio panning-based strategy. The selected scFvs were characterized under genetics-molecular aspects and for SARS-CoV N protein detection in ELISA, western blotting and immunocytochemistry. Results Human scFv antibodies to N protein of SARS-CoV can be easily isolated by selecting the ETH-2 phage library on immunotubes coated with antigen. These in vitro selected human scFvs specifically recognize in ELISA and western blotting studies distinct epitopes in N protein domains and detect in immunohistochemistry investigations SARS-CoV particles in infected Vero cells. Conclusion The human scFv antibodies isolated and described in this study represent useful reagents for rapid detection of N SARS-CoV protein and SARS virus particles in infected target cells.

Middle East respiratory syndrome coronavirus (MERS Cov outbreak so far exempted Sub Saharan Africa; is it good news or call for action?

Directory of Open Access Journals (Sweden)

Ballah Akawu Denue

2015-01-01

Full Text Available The reported cases of MERS Cov in Arabian Peninsula and sporadic cases elsewhere except in sub Saharan Africa at present is disquieting considering its initial clinical feature that mimic flu like symptoms caused by other viruses. However MERS Cov is associated with organ dysfunction and high mortality. Although the mode of transmission is still unclear, it is postulated that it spreads through close contact, possibly via respiratory route. High similarities of MERS CoV carried by humans and camels may suggest that the diseases are zoonotic. Furthermore, airborne nosocomial transmission can occur in the room shared by the patients in the hospitals. There is still the confusion of transmission through body fluids or clinical samples, including stools and a cross transmission with medical devices or hands. Currently, all known cases can be directly or indirectly linked to Middle East from where it derives its name. Cases reported outside the Middle East first developed infection in the Middle East and then were exported outside the region. Several hospital-acquired outbreaks that resulted in upsurge of MERS Cov cases in Jeddah revealed lack of systematic implementation of infection prevention and control measures to effectively control emerging infectious diseases. The causative agent is detected and identified using Enzyme Linked Immuunosorbent Assay (ELISA and real-time polymerase chain reaction (RT-PCR that is expensive and not readily available in hospitals located in resource poor settings such as sub Saharan Africa. Although, so far no case of MERS Cov has been reported from sub Saharan Africa, the devastating consequences of MERS epidemic will be more catastrophic if it emerges in developing nations especially in sub Saharan Africa where there are no up to date facilities for investigations and management of such cases. Against this backdrop, we review this hazardous and incurable disease believing that it would create the necessary

Structural bases of coronavirus attachment to host aminopeptidase N and its inhibition by neutralizing antibodies.

Directory of Open Access Journals (Sweden)

Juan Reguera

Full Text Available The coronaviruses (CoVs are enveloped viruses of animals and humans associated mostly with enteric and respiratory diseases, such as the severe acute respiratory syndrome and 10-20% of all common colds. A subset of CoVs uses the cell surface aminopeptidase N (APN, a membrane-bound metalloprotease, as a cell entry receptor. In these viruses, the envelope spike glycoprotein (S mediates the attachment of the virus particles to APN and subsequent cell entry, which can be blocked by neutralizing antibodies. Here we describe the crystal structures of the receptor-binding domains (RBDs of two closely related CoV strains, transmissible gastroenteritis virus (TGEV and porcine respiratory CoV (PRCV, in complex with their receptor, porcine APN (pAPN, or with a neutralizing antibody. The data provide detailed information on the architecture of the dimeric pAPN ectodomain and its interaction with the CoV S. We show that a protruding receptor-binding edge in the S determines virus-binding specificity for recessed glycan-containing surfaces in the membrane-distal region of the pAPN ectodomain. Comparison of the RBDs of TGEV and PRCV to those of other related CoVs, suggests that the conformation of the S receptor-binding region determines cell entry receptor specificity. Moreover, the receptor-binding edge is a major antigenic determinant in the TGEV envelope S that is targeted by neutralizing antibodies. Our results provide a compelling view on CoV cell entry and immune neutralization, and may aid the design of antivirals or CoV vaccines. APN is also considered a target for cancer therapy and its structure, reported here, could facilitate the development of anti-cancer drugs.

Molecular characterization of the receptor binding structure-activity relationships of influenza B virus hemagglutinin.

Science.gov (United States)

Carbone, V; Kim, H; Huang, J X; Baker, M A; Ong, C; Cooper, M A; Li, J; Rockman, S; Velkov, T

2013-01-01

Selectivity of α2,6-linked human-like receptors by B hemagglutinin (HA) is yet to be fully understood. This study integrates binding data with structure-recognition models to examine the impact of regional-specific sequence variations within the receptor-binding pocket on selectivity and structure activity relationships (SAR). The receptor-binding selectivity of influenza B HAs corresponding to either B/Victoria/2/1987 or the B/Yamagata/16/88 lineages was examined using surface plasmon resonance, solid-phase ELISA and gel-capture assays. Our SAR data showed that the presence of asialyl sugar units is the main determinant of receptor preference of α2,6 versus α2,3 receptor binding. Changes to the type of sialyl-glycan linkage present on receptors exhibit only a minor effect upon binding affinity. Homology-based structural models revealed that structural properties within the HA pocket, such as a glyco-conjugate at Asn194 on the 190-helix, sterically interfere with binding to avian receptor analogs by blocking the exit path of the asialyl sugars. Similarly, naturally occurring substitutions in the C-terminal region of the 190-helix and near the N-terminal end of the 140-loop narrows the horizontal borders of the binding pocket, which restricts access of the avian receptor analog LSTa. This study helps bridge the gap between ligand structure and receptor recognition for influenza B HA; and provides a consensus SAR model for the binding of human and avian receptor analogs to influenza B HA.

Superior Cycle Stability Performance of Quasi-Cuboidal CoV2O6 Microstructures as Electrode Material for Supercapacitors.

Science.gov (United States)

Wang, Yucheng; Chai, Hui; Dong, Hong; Xu, Jiayu; Jia, Dianzeng; Zhou, Wanyong

2016-10-12

In this study, a rapid, facile, and environment-friendly microwave-assisted method followed by annealing for synthesizing the quasi-cuboidal CoV 2 O 6 is developed. The as-prepared samples manifest high supercapacitor properties with a specific capacitance of 223 F g -1 , good rate capability, and superior cycle stability, retaining 123.3% capacitance when the number of cycles reaches 15,000 after determined by electrochemical tests. More importantly, the quasi-cuboidal CoV 2 O 6 for the first time is introduced into the supercapacitor as a kind of electrode material. The superior electrochemical performance of the quasi-cuboidal CoV 2 O 6 will render the metal vanadium oxides as new and attractive active material for promising application in supercapacitors.

SAR distribution in human beings when using body-worn RF transmitters

International Nuclear Information System (INIS)

Christ, A.; Samaras, T.; Neufeld, E.; Klingenboeck, A.; Kuster, N.

2007-01-01

This study analyzes the exposure of the human torso to electromagnetic fields caused by wireless body-mounted or hand-held devices. Because of the frequency and distance ranges from 30-5800 MHz and 10 to 200 mm, respectively, both near-field and far-field effects are considered. A generic body model and simulations of anatomical models are used to evaluate the worst case tissue composition with respect to the absorption of electromagnetic energy. Both standing wave effects and enhanced coupling of reactive near-field components can lead to a specific absorption rate (SAR) increase in comparison to homogeneous tissue. In addition, the exposure and temperature increase of different inner organs is assessed. With respect to compliance testing, the observed SAR enhancement may require the introduction of a multiplication factor for the spatial peak SAR measured in the liquid-filled phantom in order to obtain a conservative exposure assessment. The observed tissue heating at the body surface under adiabatic conditions can be significant, whereas the temperature increase in the inner organs turned out to be negligible for the cases investigated. (authors)

Les composés organiques volatils réduction des émissions de COV dans l'industrie

CERN Document Server

2013-01-01

Cet ouvrage propose des solutions techniques et une méthodologie pour réduire les émissions de composés organiques volatils (COV) dans l’atmosphère. Il permet : • de connaître l’impact des COV sur l’environnement et sur la santé, ainsi que les réglementations applicables en France et en Europe ; • de choisir les solutions d’amélioration disponibles (prévention, réduction à la source par secteur industriel, technologies de traitement et méthodes de mesure) ; • d’obtenir les clés pour mett re en place une démarche de réduction des émissions de COV (les étapes et les accompagnements possibles) ; • d’observer des exemples réussis d’investissement dans l’industrie. Cet ouvrage est un outil de travail indispensable pour les entreprises concernées par cett e problématique. Il donne les éléments essentiels pour aborder sereinement une démarche de réduction des émissions de COV. Points forts : • Des données rassemblées par un réseau d’experts spécialisés dans...

Chimeric exchange of coronavirus nsp5 proteases (3CLpro) identifies common and divergent regulatory determinants of protease activity.

Science.gov (United States)

Stobart, Christopher C; Sexton, Nicole R; Munjal, Havisha; Lu, Xiaotao; Molland, Katrina L; Tomar, Sakshi; Mesecar, Andrew D; Denison, Mark R

2013-12-01

Human coronaviruses (CoVs) such as severe acute respiratory syndrome CoV (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV) cause epidemics of severe human respiratory disease. A conserved step of CoV replication is the translation and processing of replicase polyproteins containing 16 nonstructural protein domains (nsp's 1 to 16). The CoV nsp5 protease (3CLpro; Mpro) processes nsp's at 11 cleavage sites and is essential for virus replication. CoV nsp5 has a conserved 3-domain structure and catalytic residues. However, the intra- and intermolecular determinants of nsp5 activity and their conservation across divergent CoVs are unknown, in part due to challenges in cultivating many human and zoonotic CoVs. To test for conservation of nsp5 structure-function determinants, we engineered chimeric betacoronavirus murine hepatitis virus (MHV) genomes encoding nsp5 proteases of human and bat alphacoronaviruses and betacoronaviruses. Exchange of nsp5 proteases from HCoV-HKU1 and HCoV-OC43, which share the same genogroup, genogroup 2a, with MHV, allowed for immediate viral recovery with efficient replication albeit with impaired fitness in direct competition with wild-type MHV. Introduction of MHV nsp5 temperature-sensitive mutations into chimeric HKU1 and OC43 nsp5 proteases resulted in clear differences in viability and temperature-sensitive phenotypes compared with MHV nsp5. These data indicate tight genetic linkage and coevolution between nsp5 protease and the genomic background and identify differences in intramolecular networks regulating nsp5 function. Our results also provide evidence that chimeric viruses within coronavirus genogroups can be used to test nsp5 determinants of function and inhibition in common isogenic backgrounds and cell types.

A Study Of EMR And SAR Distribution In Human Head Phantom ...

African Journals Online (AJOL)

power of 0.32W for both simulations were well below the limit of 1.6 W/kg of ICNIRP standard and FCC/IEEE standard of 2W/kg. Keywords: Electromagnetic radiation (EMR), Specific Absorption Rate (SAR), Electromagnetic simulation software (FEKO emss), Radio frequency field, human head, mobile phone, mobile phone ...

Palmitoylation of SARS-CoV S protein is necessary for partitioning into detergent-resistant membranes and cell-cell fusion but not interaction with M protein

International Nuclear Information System (INIS)

McBride, Corrin E.; Machamer, Carolyn E.

2010-01-01

Coronaviruses are enveloped RNA viruses that generally cause mild disease in humans. However, the recently emerged coronavirus that caused severe acute respiratory syndrome (SARS-CoV) is the most pathogenic human coronavirus discovered to date. The SARS-CoV spike (S) protein mediates virus entry by binding cellular receptors and inducing fusion between the viral envelope and the host cell membrane. Coronavirus S proteins are palmitoylated, which may affect function. Here, we created a non-palmitoylated SARS-CoV S protein by mutating all nine cytoplasmic cysteine residues. Palmitoylation of SARS-CoV S was required for partitioning into detergent-resistant membranes and for cell-cell fusion. Surprisingly, however, palmitoylation of S was not required for interaction with SARS-CoV M protein. This contrasts with the requirement for palmitoylation of mouse hepatitis virus S protein for interaction with M protein and may point to important differences in assembly and infectivity of these two coronaviruses.

Molecular dynamics of Middle East Respiratory Syndrome Coronavirus (MERS CoV) fusion heptad repeat trimers

KAUST Repository

Kandeel, Mahmoud

2018-05-17

Structural studies related to Middle East Respiratory Syndrome Coronavirus (MERS CoV) infection process are so limited. In this study, molecular dynamics (MD) simulation was carried out to unravel changes in the MERS CoV heptad repeat domains (HRs) and factors affecting fusion state HR stability. Results indicated that HR trimer is more rapidly stabilized, having stable system energy and lowest root mean square deviations (RMSDs). While trimers were the predominant active form of CoVs HR, monomers were also discovered in both of viral and cellular membranes. In order to find the differences between S2 monomer and trimer molecular dynamics, S2 monomer were modelled and subjected to MD simulation. In contrast to S2 trimer, S2 monomer was unstable, having high RMSDs with major drifts above 8 Å. Fluctuation of HR residue positions revealed major changes in the C-terminal of HR2 and the linker coil between HR1 and HR2 in both monomer and trimer. Hydrophobic residues at the “a” and “d” positions of HR helices stabilize the whole system, having minimal changes in RMSD. The global distance test and contact area difference scores support instability of MERS CoV S2 monomer. Analysis of HR1-HR2 inter-residue contacts and interaction energy revealed three different energy scales along HR helices. Two strong interaction energies were identified at the start of the HR2 helix and at the C-terminal of HR2. The identified critical residues by MD simulation and residues at a and d position of HR helix were strong stabilizers of HRs recognition.

Analysis of SAR distribution in human head of antenna used in wireless power transform based on magnetic resonance.

Science.gov (United States)

Gong, Feixiang; Wei, Zhiqiang; Cong, Yanping; Chi, Haokun; Yin, Bo; Sun, Mingui

2017-07-20

In this paper, a novel wireless power transfer antenna system was designed for human head implantable devices. The antenna system used the structure of three plates and four coils and operated at low frequencies to transfer power via near field. In order to verify the electromagnetic radiation safety on the human head, the electromagnetic intensity and specific absorption rate (SAR) were studied by finite-difference-time-domain (FDTD) method. A three-layer model of human head including skin, bone and brain tissues was constructed. The transmitting and receiving antenna were set outside and inside the model. The local and average SAR were simulated at the resonance frequency of 18.67 MHz in two situations, in one scenario both transmitting and receiving coil worked, while in the other scenario only the transmitting coil worked. The results showed that the maximum of 10 g SAR average value of human thoracic were 0.142 W/kg and 0.148 W/kg, respectively, both were lower than the international safety standards for human body of the ICNIRP and FCC, which verified the safety of the human body in wireless power transmission based on magnetic coupling resonance.

Pains and Gains from China’s Experiences with Emerging Epidemics: From SARS to H7N9

Directory of Open Access Journals (Sweden)

Pengfei Wei

2016-01-01

Full Text Available Over the recent decades, China experienced several emerging virus outbreaks including those caused by the severe acute respiratory syndrome- (SARS- coronavirus (Cov, H5N1 virus, and H7N9 virus. The SARS tragedy revealed faults in China’s infectious disease prevention system, propelling the Chinese government to enact reforms that enabled better combating of the subsequent H1N1 and H7N9 avian flu epidemics. The system is buttressed by three fundamental, mutually reinforcing components: (1 enduring government administration reforms, including legislation establishing a unified public health emergency management system; (2 prioritized funding for biotechnology and biomedicine industrialization, especially in the areas of pathogen identification, drug production, and the development of vaccines and diagnostics; and (3 increasing investment for public health and establishment of a rapid-response infectious diseases prevention and control system. China is now using its hard-gained experience to support the fight against Ebola in Africa and the Middle East Respiratory Syndrome in its own country.

C-band Joint Active/Passive Dual Polarization Sea Ice Detection

Science.gov (United States)

Keller, M. R.; Gifford, C. M.; Winstead, N. S.; Walton, W. C.; Dietz, J. E.

2017-12-01

A technique for synergistically-combining high-resolution SAR returns with like-frequency passive microwave emissions to detect thin (Radar (SAR) is high resolution (5-100m) but because of cross section ambiguities automated algorithms have had difficulty separating thin ice types from water. The radiometric emissivity of thin ice versus water at microwave frequencies is generally unambiguous in the early stages of ice growth. The method, developed using RADARSAT-2 and AMSR-E data, uses higher-ordered statistics. For the SAR, the COV (coefficient of variation, ratio of standard deviation to mean) has fewer ambiguities between ice and water than cross sections, but breaking waves still produce ice-like signatures for both polarizations. For the radiometer, the PRIC (polarization ratio ice concentration) identifies areas that are unambiguously water. Applying cumulative statistics to co-located COV levels adaptively determines an ice/water threshold. Outcomes from extensive testing with Sentinel and AMSR-2 data are shown in the results. The detection algorithm was applied to the freeze-up in the Beaufort, Chukchi, Barents, and East Siberian Seas in 2015 and 2016, spanning mid-September to early November of both years. At the end of the melt, 6 GHz PRIC values are 5-10% greater than those reported by radiometric algorithms at 19 and 37 GHz. During freeze-up, COV separates grease ice (cross-pol/co-pol SAR ratio corrects for COV deficiencies. In general, the dual-sensor detection algorithm reports 10-15% higher total ice concentrations than operational scatterometer or radiometer algorithms, mostly from ice edge and coastal areas. In conclusion, the algorithm presented combines high-resolution SAR returns with passive microwave emissions for automated ice detection at SAR resolutions.

The nucleocapsid proteins of mouse hepatitis virus and severe acute respiratory syndrome coronavirus share the same IFN-β antagonizing mechanism: attenuation of PACT-mediated RIG-I/ MDA5 activation.

Science.gov (United States)

Ding, Zhen; Fang, Liurong; Yuan, Shuangling; Zhao, Ling; Wang, Xunlei; Long, Siwen; Wang, Mohan; Wang, Dang; Foda, Mohamed Frahat; Xiao, Shaobo

2017-07-25

Coronaviruses (CoVs) are a huge threat to both humans and animals and have evolved elaborate mechanisms to antagonize interferons (IFNs). Nucleocapsid (N) protein is the most abundant viral protein in CoV-infected cells, and has been identified as an innate immunity antagonist in several CoVs, including mouse hepatitis virus (MHV) and severe acute respiratory syndrome (SARS)-CoV. However, the underlying molecular mechanism(s) remain unclear. In this study, we found that MHV N protein inhibited Sendai virus and poly(I:C)-induced IFN-β production by targeting a molecule upstream of retinoic acid-induced gene I (RIG-I) and melanoma differentiation gene 5 (MDA5). Further studies showed that both MHV and SARS-CoV N proteins directly interacted with protein activator of protein kinase R (PACT), a cellular dsRNA-binding protein that can bind to RIG-I and MDA5 to activate IFN production. The N-PACT interaction sequestered the association of PACT and RIG-I/MDA5, which in turn inhibited IFN-β production. However, the N proteins from porcine epidemic diarrhea virus (PEDV) and porcine reproductive and respiratory syndrome virus (PRRSV), which are also classified in the order Nidovirales, did not interact and counteract with PACT. Taken together, our present study confirms that both MHV and SARS-CoV N proteins can perturb the function of cellular PACT to circumvent the innate antiviral response. However, this strategy does not appear to be used by all CoVs N proteins.

SAR calculation using FDTD simulations

OpenAIRE

Ferro, Francisco Nabais; Pinto, Guilherme Taveira; Pinho, Pedro

2009-01-01

The main intend of this work, is to determinate the Specific Absorption Rate (SAR) on human head tissues exposed to radiation caused by sources of 900 and 1800MHz, since those are the typical frequencies for mobile communications systems nowadays. In order to determinate the SAR, has been used the FDTD (Finite Difference Time Domain), which is a numeric method in time domain, obtained from the Maxwell equations in differential mode. In order to do this, a computational model from the human he...

Structures of Two Coronavirus Main Proteases: Implications for Substrate Binding and Antiviral Drug Design

Energy Technology Data Exchange (ETDEWEB)

Xue, Xiaoyu; Yu, Hongwei; Yang, Haitao; Xue, Fei; Wu, Zhixin; Shen, Wei; Li, Jun; Zhou, Zhe; Ding, Yi; Zhao, Qi; Zhang, Xuejun C.; Liao, Ming; Bartlam, Mark; Rao, Zihe (SCAU); (Tsinghua); (Chinese Aca. Sci.)

2008-07-21

Coronaviruses (CoVs) can infect humans and multiple species of animals, causing a wide spectrum of diseases. The coronavirus main protease (M{sup pro}), which plays a pivotal role in viral gene expression and replication through the proteolytic processing of replicase polyproteins, is an attractive target for anti-CoV drug design. In this study, the crystal structures of infectious bronchitis virus (IBV) MP{sup pro} and a severe acute respiratory syndrome CoV (SARS-CoV) M{sup pro} mutant (H41A), in complex with an N-terminal autocleavage substrate, were individually determined to elucidate the structural flexibility and substrate binding of M{sup pro}. A monomeric form of IBV M{sup pro} was identified for the first time in CoV M{sup pro} structures. A comparison of these two structures to other available M{sup pro} structures provides new insights for the design of substrate-based inhibitors targeting CoV M{sup pro}s. Furthermore, a Michael acceptor inhibitor (named N3) was cocrystallized with IBV M{sup pro} and was found to demonstrate in vitro inactivation of IBV M{sup pro} and potent antiviral activity against IBV in chicken embryos. This provides a feasible animal model for designing wide-spectrum inhibitors against CoV-associated diseases. The structure-based optimization of N3 has yielded two more efficacious lead compounds, N27 and H16, with potent inhibition against SARS-CoV M{sup pro}.

A patient with asymptomatic severe acute respiratory syndrome (SARS) and antigenemia from the 2003-2004 community outbreak of SARS in Guangzhou, China.

Science.gov (United States)

Che, Xiao-yan; Di, Biao; Zhao, Guo-ping; Wang, Ya-di; Qiu, Li-wen; Hao, Wei; Wang, Ming; Qin, Peng-zhe; Liu, Yu-fei; Chan, Kwok-hong; Cheng, Vincent C C; Yuen, Kwok-yung

2006-07-01

An asymptomatic case of severe acute respiratory syndrome (SARS) occurred early in 2004, during a community outbreak of SARS in Guangzhou, China. This was the first time that a case of asymptomatic SARS was noted in an individual with antigenemia and seroconversion. The asymptomatic case patient and the second index case patient with SARS in the 2003-2004 outbreak both worked in the same restaurant, where they served palm civets, which were found to carry SARS-associated coronaviruses. Epidemiological information and laboratory findings suggested that the findings for the patient with asymptomatic infection, together with the findings from previously reported serological analyses of handlers of wild animals and the 4 index case patients from the 2004 community outbreak, reflected a likely intermediate phase of animal-to-human transmission of infection, rather than a case of human-to-human transmission. This intermediate phase may be a critical stage for virus evolution and disease prevention.

Combinatorial synthetic peptide vaccine strategy protects against hypervirulent CovR/S mutant streptococci

DEFF Research Database (Denmark)

Pandey, Manisha; Mortensen, Rasmus; Calcutt, Ainslie

2016-01-01

-mediated killing and enabling ingress of bacteria from a superficial wound to deep tissue.We previously showed that a combination vaccine incorporating J8-DT (conserved peptide vaccine from theM protein) and a recombinant SpyCEP fragment protects against CovR/S mutants. To enhance the vaccine's safety profile, we......), and it would be to the organism's advantage if the host did not induce a strong Ab response against it. However, S2 conjugated to diphtheria toxoid is highly immunogenic and induces Abs that recognize and neutralize SpyCEP. Hence, we describe a two-component peptide vaccine that induces Abs (anti-S2....... This protection correlated with a significant influx of neutrophils to the infection site. The data strongly suggest that the lack of natural immunity to hypervirulent GAS strains in humans could be rectified by this combination vaccine....

Statistical multi-path exposure method for assessing the whole-body SAR in a heterogeneous human body model in a realistic environment.

Science.gov (United States)

Vermeeren, Günter; Joseph, Wout; Martens, Luc

2013-04-01

Assessing the whole-body absorption in a human in a realistic environment requires a statistical approach covering all possible exposure situations. This article describes the development of a statistical multi-path exposure method for heterogeneous realistic human body models. The method is applied for the 6-year-old Virtual Family boy (VFB) exposed to the GSM downlink at 950 MHz. It is shown that the whole-body SAR does not differ significantly over the different environments at an operating frequency of 950 MHz. Furthermore, the whole-body SAR in the VFB for multi-path exposure exceeds the whole-body SAR for worst-case single-incident plane wave exposure by 3.6%. Moreover, the ICNIRP reference levels are not conservative with the basic restrictions in 0.3% of the exposure samples for the VFB at the GSM downlink of 950 MHz. The homogeneous spheroid with the dielectric properties of the head suggested by the IEC underestimates the absorption compared to realistic human body models. Moreover, the variation in the whole-body SAR for realistic human body models is larger than for homogeneous spheroid models. This is mainly due to the heterogeneity of the tissues and the irregular shape of the realistic human body model compared to homogeneous spheroid human body models. Copyright © 2012 Wiley Periodicals, Inc.

Local SAR in High Pass Birdcage and TEM Body Coils for Multiple Human Body Models in Clinical Landmark Positions at 3T

Science.gov (United States)

Yeo, Desmond TB; Wang, Zhangwei; Loew, Wolfgang; Vogel, Mika W; Hancu, Ileana

2011-01-01

Purpose To use EM simulations to study the effects of body type, landmark position, and RF body coil type on peak local SAR in 3T MRI. Materials and Methods Numerically computed peak local SAR for four human body models (HBMs) in three landmark positions (head, heart, pelvic) were compared for a high-pass birdcage and a transverse electromagnetic 3T body coil. Local SAR values were normalized to the IEC whole-body average SAR limit of 2.0 W/kg for normal scan mode. Results Local SAR distributions were highly variable. Consistent with previous reports, the peak local SAR values generally occurred in the neck-shoulder area, near rungs, or between tissues of greatly differing electrical properties. The HBM type significantly influenced the peak local SAR, with stockier HBMs, extending extremities towards rungs, displaying the highest SAR. There was also a trend for higher peak SAR in the head-centric and heart-centric positions. The impact of the coil-types studied was not statistically significant. Conclusion The large variability in peak local SAR indicates the need to include more than one HBM or landmark position when evaluating safety of body coils. It is recommended that a HBM with arms near the rungs be included, to create physically realizable high-SAR scenarios. PMID:21509880

Localization and characterization of angiotensin II receptor binding and angiotensin converting enzyme in the human medulla oblongata.

Science.gov (United States)

Allen, A M; Chai, S Y; Clevers, J; McKinley, M J; Paxinos, G; Mendelsohn, F A

1988-03-08

Angiotensin II receptor and angiotensin converting enzyme distributions in the human medulla oblongata were localised by quantitative in vitro autoradiography. Angiotensin II receptors were labelled with the antagonist analogue 125I-[Sar1, Ile8] AII while angiotensin converting enzyme was labelled with 125I-351A, a derivative of the specific converting enzyme inhibitor, lisinopril. Angiotensin II receptor binding and angiotensin converting enzyme are present in high concentrations in the nucleus of the solitary tract, the dorsal motor nucleus of vagus, the rostral and caudal ventrolateral reticular nucleus, and in a band connecting the dorsal and ventral regions. In the rostral and caudal ventrolateral reticular nucleus, angiotensin II receptors are distributed in a punctate pattern that registers with neuronal cell bodies. The distribution and density of these cell bodies closely resemble those of catecholamine-containing neurones mapped by others. In view of the known interactions of angiotensin II with both central and peripheral catecholamine-containing neurons of laboratory animals, the current anatomical findings suggest similar interactions between these neuroactive compounds in the human central nervous system. The presence of angiotensin II receptors and angiotensin converting enzyme in the nucleus of the solitary tract, dorsal motor nucleus of vagus, and rostral and caudal ventrolateral reticular nucleus demonstrates sites for central angiotensin II to exert its known actions on vasopressin release and autonomic functions including blood pressure control. These data also suggest a possible interaction between angiotensin II and central catecholeminergic systems.

Synthesis and SAR studies of novel 2-(6-aminomethylaryl-2-aryl-4-oxo-quinazolin-3(4H)-yl)acetamide vasopressin V1b receptor antagonists.

Science.gov (United States)

Napier, Susan E; Letourneau, Jeffrey J; Ansari, Nasrin; Auld, Douglas S; Baker, James; Best, Stuart; Campbell-Wan, Leigh; Chan, Ray; Craighead, Mark; Desai, Hema; Ho, Koc-Kan; MacSweeney, Cliona; Milne, Rachel; Richard Morphy, J; Neagu, Irina; Ohlmeyer, Michael H J; Pick, Jack; Presland, Jeremy; Riviello, Chris; Zanetakos, Heather A; Zhao, Jiuqiao; Webb, Maria L

2011-06-15

Synthesis and structure-activity relationships (SAR) of a novel series of vasopressin V(1b) antagonists are described. 2-(6-Aminomethylaryl-2-aryl-4-oxo-quinazolin-3(4H)-yl)acetamide have been identified with low nanomolar affinity for the V(1b) receptor and good selectivity with respect to related receptors V(1a), V(2) and OT. Optimised compound 16 shows a good pharmacokinetic profile and activity in a mechanistic model of HPA dysfunction. Copyright © 2011 Elsevier Ltd. All rights reserved.

Human dopamine receptor and its uses

Energy Technology Data Exchange (ETDEWEB)

Civelli, Olivier (Portland, OR); Van Tol, Hubert Henri-Marie (Toronto, CA)

1999-01-01

The present invention is directed toward the isolation, characterization and pharmacological use of the human D4 dopamine receptor. The nucleotide sequence of the gene corresponding to this receptor and alleleic variant thereof are provided by the invention. The invention also includes recombinant eukaryotic expression constructs capable of expressing the human D4 dopamine receptor in cultures of transformed eukaryotic cells. The invention provides cultures of transformed eukaryotic cells which synthesize the human D4 dopamine receptor, and methods for characterizing novel psychotropic compounds using such cultures.

An Opportunistic Pathogen Afforded Ample Opportunities: Middle East Respiratory Syndrome Coronavirus

Directory of Open Access Journals (Sweden)

Ian M. Mackay

2017-12-01

Full Text Available The human coronaviruses (CoV include HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1, some of which have been known for decades. The severe acute respiratory syndrome (SARS CoV briefly emerged into the human population but was controlled. In 2012, another novel severely human pathogenic CoV—the Middle East Respiratory Syndrome (MERS-CoV—was identified in the Kingdom of Saudi Arabia; 80% of over 2000 human cases have been recorded over five years. Targeted research remains key to developing control strategies for MERS-CoV, a cause of mild illness in its camel reservoir. A new therapeutic toolbox being developed in response to MERS is also teaching us more about how CoVs cause disease. Travel-related cases continue to challenge the world’s surveillance and response capabilities, and more data are needed to understand unexplained primary transmission. Signs of genetic change have been recorded, but it remains unclear whether there is any impact on clinical disease. How camels came to carry the virus remains academic to the control of MERS. To date, human-to-human transmission has been inefficient, but virus surveillance, characterisation, and reporting are key to responding to any future change. MERS-CoV is not currently a pandemic threat; it is spread mainly with the aid of human habit and error.

Development of an injectable formulation for the preparation of radiopharmaceutical 68Ga-DOTA-Sar gastrin

International Nuclear Information System (INIS)

Castillo P, M.

2015-01-01

The CCK2 receptor (cholecystokinin) is located in areas of the central and peripheral nervous system and is over expressed in several types of human cancer, as medullar thyroid, lung and ovarian carcinomas. One of the endogenous ligands for the CCK2 receptor is the gastrin, so that radiolabeled peptides analogues to gastrin as Sar gastrin (Gln-Gly-Pro-Trp-Leu-Glu-Glu-Glu-Glu-Glu-Ala-Tyr-Gly-Trp-Nle-Asp-Phe-NH 2 ) have been proposed as potential diagnostic radiopharmaceuticals for obtaining tumors images with CCK2 receptors over expressed. The 68 Ga is an ideal candidate for the peptides radiolabelled and has favorable characteristics to be used for diagnostic purposes by imaging with Positron emission tomography (PET). This work aimed to verify the technical documentation of the production process of radiopharmaceutical 68 Ga-DOTA-Sar gastrin for its sanitary registration before the Comision Federal contra Riesgos Sanitarios (COFEPRIS) in Mexico. For optimization of the production process was assessed a factorial design of two variables with mixed levels (27 combinations), where the dependent variable was the radiochemical purity. The analytical method used for evaluating the content of Sar gastrin peptide in the injectable formulation was also validated by High-performance liquid chromatography. Subsequently the validation of the production process was carried out by manufacturing of lots in single-dose of the optimized injectable formulation of the radiopharmaceutical 68 Ga-DOTA-Sar gastrin and the stability study was conducted at different times to determine the useful life time. The following was established as the optimal pharmaceutical formulation: 185 MBq of 68 Ga, 50 μg de DOTA-Sar gastrin, 14 mg of sodium acetate and 0.5 m L of buffer acetates, 1.0 M, ph 4.22 in 2.5 m L of the vehicle. The analytical method used to determine the radiochemical purity of the formulation satisfied the requirements for the intended analytical application. The lots in

Three-Dimensional Human Bronchial-Tracheal Epithelial Tissue-Like Assemblies (TLAs) as Hosts for Severe Acute Respiratory Syndrome (SARS)-CoV Infection

Science.gov (United States)

Suderman, M. T.; McCarthy, M.; Mossell, E.; Watts, D. M.; Peters, C. J.; Shope, R.; Goodwin, T. J.

2006-01-01

A three-dimensional (3-D) tissue-like assembly (TLA) of human bronchial-tracheal mesenchymal (HBTC) cells with an overlay of human bronchial epithelial (BEAS-2B) cells was constructed using a NASA Bioreactor to survey the infectivity of SARS-CoV. This TLA was inoculated with a low passage number Urbani strain of SARS-CoV. At selected intervals over a 10-day period, media and cell aliquots of the 3-D TLA were harvested for viral titer assay and for light and electron microscopy examination. All viral titer assays were negative in both BEAS-2B two-dimensional monolayer and TLA. Light microscopy immunohistochemistry demonstrated antigen-antibody reactivity with anti-SARS-CoV polyclonal antibody to spike and nuclear proteins on cell membranes and cytoplasm. Coronavirus Group 2 cross-reactivity was demonstrated by positive reaction to anti-FIPV 1 and anti-FIPV 1 and 2 antibodies. TLA examination by transmission electron microscopy indicated increasing cytoplasmic vacuolation with numerous electron-dense bodies measuring 45 to 270 nm from days 4 through 10. There was no evidence of membrane blebbing, membrane duplication, or fragmentation of organelles in the TLAs. However, progressive disruption of endoplasmic reticulum was observed throughout the cells. Antibody response to SARS-CoV specific spike and nucleocapsid glycoproteins, cross-reactivity with FIPV antibodies, and the cytoplasmic pathology suggests this HBTE TLA model is permissive to SARS-CoV infection.

Design, synthesis, and in vivo SAR of a novel series of pyrazolines as potent selective androgen receptor modulators.

Science.gov (United States)

Zhang, Xuqing; Li, Xiaojie; Allan, George F; Sbriscia, Tifanie; Linton, Olivia; Lundeen, Scott G; Sui, Zhihua

2007-08-09

A novel series of pyrazolines 2 have been designed, synthesized, and evaluated by in vivo screening as tissue-selective androgen receptor modulators (SARMs). Structure-activity relationships (SAR) were investigated at the R1 to R6 positions as well as the core pyrazoline ring and the anilide linker. Overall, strong electron-withdrawing groups at the R1 and R2 positions and a small group at the R5 and R6 position are optimal for AR agonist activity. The (S)-isomer of 7c exhibits more potent AR agonist activity than the corresponding (R)-isomer. (S)-7c exhibited an overall partial androgenic effect but full anabolic effect via oral administration in castrated rats. It demonstrated a noticeable antiandrogenic effect on prostate in intact rats with endogenous testosterone. Thus, (S)-7c is a tissue-selective nonsteroidal androgen receptor modulator with agonist activity on muscle and mixed agonist and antagonist activity on prostate.

Acetylcholine receptors in the human retina

International Nuclear Information System (INIS)

Hutchins, J.B.; Hollyfield, J.G.

1985-01-01

Evidence for a population of acetylcholine (ACh) receptors in the human retina is presented. The authors have used the irreversible ligand 3 H-propylbenzilylcholine mustard ( 3 H-PrBCM) to label muscarinic receptors. 3 H- or 125 I-alpha-bungarotoxin (alpha-BTx) was used to label putative nicotinic receptors. Muscarinic receptors are apparently present in the inner plexiform layer of the retina. Autoradiographic grain densities are reduced in the presence of saturating concentrations of atropine, quinuclidinyl benzilate or scopolamine; this indicates that 3 H-PrBCM binding is specific for a population of muscarinic receptors in the human retina. Binding sites for radiolabeled alpha-BTx are found predominantly in the inner plexiform layer of the retina. Grain densities are reduced in the presence of d-tubocurarine, indicating that alpha-BTx may bind to a pharmacologically relevant nicotinic ACh receptor. This study provides evidence for cholinergic neurotransmission in the human retina

Reverse genetics of SARS-related coronavirus using vaccinia virus-based recombination.

Directory of Open Access Journals (Sweden)

Sjoerd H E van den Worm

Full Text Available Severe acute respiratory syndrome (SARS is a zoonotic disease caused by SARS-related coronavirus (SARS-CoV that emerged in 2002 to become a global health concern. Although the original outbreak was controlled by classical public health measures, there is a real risk that another SARS-CoV could re-emerge from its natural reservoir, either in its original form or as a more virulent or pathogenic strain; in which case, the virus would be difficult to control in the absence of any effective antiviral drugs or vaccines. Using the well-studied SARS-CoV isolate HKU-39849, we developed a vaccinia virus-based SARS-CoV reverse genetic system that is both robust and biosafe. The SARS-CoV genome was cloned in separate vaccinia virus vectors, (vSARS-CoV-5prime and vSARS-CoV-3prime as two cDNAs that were subsequently ligated to create a genome-length SARS-CoV cDNA template for in vitro transcription of SARS-CoV infectious RNA transcripts. Transfection of the RNA transcripts into permissive cells led to the recovery of infectious virus (recSARS-CoV. Characterization of the plaques produced by recSARS-CoV showed that they were similar in size to the parental SARS-CoV isolate HKU-39849 but smaller than the SARS-CoV isolate Frankfurt-1. Comparative analysis of replication kinetics showed that the kinetics of recSARS-CoV replication are similar to those of SARS-CoV Frankfurt-1, although the titers of virus released into the culture supernatant are approximately 10-fold less. The reverse genetic system was finally used to generate a recSARS-CoV reporter virus expressing Renilla luciferase in order to facilitate the analysis of SARS-CoV gene expression in human dendritic cells (hDCs. In parallel, a Renilla luciferase gene was also inserted into the genome of human coronavirus 229E (HCoV-229E. Using this approach, we demonstrate that, in contrast to HCoV-229E, SARS-CoV is not able to mediate efficient heterologous gene expression in hDCs.

Biodistribution and Radiation Dosimetry of the Integrin Marker 64Cu-BaBaSar-RGD2 Determined from Whole-Body PET/CT in a Non-Human Primate

Science.gov (United States)

Liu, Shuanglong; Vorobyova, Ivetta; Park, Ryan; Conti, Peter S.

2017-10-01

Introduction: 64Cu-BaBaSar-RGD2 is a positron emission radiotracer taken up by integrin αvβ3, which is overexpressed in many malignancies. The aim of this study was to evaluate the biodistribution of 64Cu-BaBaSar-RGD2 in a non-human primate with positron emission tomography and to estimate the absorbed doses in major organs for human. Materials and methods: Whole-body PET imaging was done in a Siemens Biograph scanner in a male macaque monkey. After an i.v. injection of 13.1–19.7 MBq/kg of 64Cu-BaBaSar-RGD2, whole body scan was collected for a total duration of 180 min. Attenuation and scatter corrections were applied to reconstruction of the whole-body emission scan. After image reconstruction, three-dimensional volumes of interest (VOI) were hand-drawn on the PET transaxial or coronal slices of the frame where the organ was most conspicuous. Time-activity curves for each VOI were obtained, and residence time of each organ was calculated by integration of the time-activity curves. Human absorbed doses were estimated using the standard human model in OLINDA/EXM software. Results: Injection of 64Cu-BaBaSar-RGD2 was well tolerated in the macaque monkey, with no serious tracer-related adverse events observed. 64Cu-BaBaSar-RGD2 was cleared rapidly from the blood pool, with a 12.1-min biological half-time. Increased 64Cu-BaBaSar-RGD2 uptake was observed in the kidneys, and bladder, with mean percentage injected dose (ID%) values at 1 h after injection approximately 35.50 ± 6.47 and 36.89 ± 5.48, respectively. The calculated effective dose was 15.30 ± 2.21 µSv/MBq, and the kidneys had the highest absorbed dose at 108.43 ± 16.41 µGy/MBq using the non-voiding model. For an injected activity of 925 MBq 64Cu for human, the effective dose would be 14.2 ± 2.1 mSv. Discussion: Due to the limitation of the monkey number, we evaluated 64Cu-BaBaSar-RGD2 in the same monkey of three imaging sessions. Measured absorbed doses and effective doses of 64Cu-BaBaSar-RGD2 are

Combined DEM Extration Method from StereoSAR and InSAR

Science.gov (United States)

Zhao, Z.; Zhang, J. X.; Duan, M. Y.; Huang, G. M.; Yang, S. C.

2015-06-01

A pair of SAR images acquired from different positions can be used to generate digital elevation model (DEM). Two techniques exploiting this characteristic have been introduced: stereo SAR and interferometric SAR. They permit to recover the third dimension (topography) and, at the same time, to identify the absolute position (geolocation) of pixels included in the imaged area, thus allowing the generation of DEMs. In this paper, StereoSAR and InSAR combined adjustment model are constructed, and unify DEM extraction from InSAR and StereoSAR into the same coordinate system, and then improve three dimensional positioning accuracy of the target. We assume that there are four images 1, 2, 3 and 4. One pair of SAR images 1,2 meet the required conditions for InSAR technology, while the other pair of SAR images 3,4 can form stereo image pairs. The phase model is based on InSAR rigorous imaging geometric model. The master image 1 and the slave image 2 will be used in InSAR processing, but the slave image 2 is only used in the course of establishment, and the pixels of the slave image 2 are relevant to the corresponding pixels of the master image 1 through image coregistration coefficient, and it calculates the corresponding phase. It doesn't require the slave image in the construction of the phase model. In Range-Doppler (RD) model, the range equation and Doppler equation are a function of target geolocation, while in the phase equation, the phase is also a function of target geolocation. We exploit combined adjustment model to deviation of target geolocation, thus the problem of target solution is changed to solve three unkonwns through seven equations. The model was tested for DEM extraction under spaceborne InSAR and StereoSAR data and compared with InSAR and StereoSAR methods respectively. The results showed that the model delivered a better performance on experimental imagery and can be used for DEM extraction applications.

Data Analytics for SAR

Energy Technology Data Exchange (ETDEWEB)

Murphy, David Patrick [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Calef, Matthew Thomas [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

2017-10-02

We assess the ability of variants of anomalous change detection (ACD) to identify human activity associated with large outdoor music festivals as they are seen from synthetic aperture radar (SAR) imagery collected by the Sentinel-1 satellite constellation. We found that, with appropriate feature vectors, ACD using random-forest machine learning was most effective at identifying changes associated with the human activity.

Upscaling the impact of convective overshooting (COV) through BRAMS: a continental and wet-season scale study of the water vapour (WV) budget in the tropical tropopause layer (TTL).

Science.gov (United States)

Behera, Abhinna; Rivière, Emmanuel; Marécal, Virginie; Rysman, Jean-François; Claud, Chantal; Burgalat, Jérémie

2017-04-01

The stratospheric water vapour (WV) has a conceding impact on the radiative and chemical budget of Earth's atmosphere. The convective overshooting (COV) at the tropics is well admitted for playing a role in transporting directly WV to the stratosphere. Nonetheless, its impact on the lower stratosphere is yet to be determined at global scale, as the satellite and other air-borne measurements are not of having fine enough resolution to quantify this impact at large scale. Therefore, efforts have been made to quantify the influence of COV over the WV budget in the tropical tropopause layer (TTL) through modelling. Our approach is to build two synthetic tropical wet-seasons; where one would be having only deep convection (DC) but no COV at all, and the second one would be having the COV, and in both cases the WV budget in the TTL would be estimated. Before that, a French-Brazilian TRO-pico campaign was carried out at Bauru, Brazil in order to understand the influence of COV on the WV budget in the TTL. The radio-sounding, and the small balloon-borne WV measurements from the campaign are being utilized to validate the model simulation. Brazilian version of Regional Atmospheric Modeling System (BRAMS) is used with a single grid system to simulate a WV variability in a wet-season. Grell's convective parameterization with ensemble closure, microphysics with double moment scheme and 7 types of hydrometeors are incorporated to simulate the WV variability for a wet-season at the tropics. The grid size of simulation is chosen to be 20 km x 20 km horizontally and from surface to 30 km altitude, so that there cannot be COV at all, only DC due to such a relatively coarse resolution. The European Centre for Medium-range Weather Forecasts (ECMWF) operational analyses data are used every 6 hours for grid initialization and boundary conditions, and grid center nudging. The simulation is carried out for a full wet-season (Nov 2012 - Mar 2013) at Brazilian scale, so that it would

Analysis of the local worst-case SAR exposure caused by an MRI multi-transmit body coil in anatomical models of the human body

International Nuclear Information System (INIS)

Neufeld, Esra; Gosselin, Marie-Christine; Murbach, Manuel; Christ, Andreas; Cabot, Eugenia; Kuster, Niels

2011-01-01

Multi-transmit coils are increasingly being employed in high-field magnetic resonance imaging, along with a growing interest in multi-transmit body coils. However, they can lead to an increase in whole-body and local specific absorption rate (SAR) compared to conventional body coils excited in circular polarization for the same total incident input power. In this study, the maximum increase of SAR for three significantly different human anatomies is investigated for a large 3 T (128 MHz) multi-transmit body coil using numerical simulations and a (generalized) eigenvalue-based approach. The results demonstrate that the increase of SAR strongly depends on the anatomy. For the three models and normalization to the sum of the rung currents squared, the whole-body averaged SAR increases by up to a factor of 1.6 compared to conventional excitation and the peak spatial SAR (averaged over any 10 cm 3 of tissue) by up to 13.4. For some locations the local averaged SAR goes up as much as 800 times (130 when looking only at regions where it is above 1% of the peak spatial SAR). The ratio of the peak spatial SAR to the whole-body SAR increases by a factor of up to 47 and can reach values above 800. Due to the potentially much larger power deposition, additional, preferably patient-specific, considerations are necessary to avoid injuries by such systems.

Novel kinin B1 receptor agonists with improved pharmacological profiles.

Science.gov (United States)

Côté, Jérôme; Savard, Martin; Bovenzi, Veronica; Bélanger, Simon; Morin, Josée; Neugebauer, Witold; Larouche, Annie; Dubuc, Céléna; Gobeil, Fernand

2009-04-01

There is some evidence to suggest that inducible kinin B1 receptors (B1R) may play beneficial and protecting roles in cardiovascular-related pathologies such as hypertension, diabetes, and ischemic organ diseases. Peptide B1R agonists bearing optimized pharmacological features (high potency, selectivity and stability toward proteolysis) hold promise as valuable therapeutic agents in the treatment of these diseases. In the present study, we used solid-phase methodology to synthesize a series of novel peptide analogues based on the sequence of Sar[dPhe(8)]desArg(9)-bradykinin, a relatively stable peptide agonist with moderate affinity for the human B1R. We evaluated the pharmacological properties of these peptides using (1) in vitro competitive binding experiments on recombinant human B1R and B2R (for index of selectivity determination) in transiently transfected human embryonic kidney 293 cells (HEK-293T cells), (2) ex vivo vasomotor assays on isolated human umbilical veins expressing endogenous human B1R, and (3) in vivo blood pressure tests using anesthetized lipopolysaccharide-immunostimulated rabbits. Key chemical modifications at the N-terminus, the positions 3 and 5 on Sar[dPhe(8)]desArg(9)-bradykinin led to potent analogues. For example, peptides 18 (SarLys[Hyp(3),Cha(5), dPhe(8)]desArg(9)-bradykinin) and 20 (SarLys[Hyp(3),Igl(5), dPhe(8)]desArg(9)-bradykinin) outperformed the parental molecule in terms of affinity, functional potency and duration of action in vitro and in vivo. These selective agonists should be valuable in future animal and human studies to investigate the potential benefits of B1R activation.

The effect of gaze angle on the evaluations of SAR and temperature rise in human eye under plane-wave exposures from 0.9 to 10 GHz

International Nuclear Information System (INIS)

Diao, Yinliang; Leung, Sai-Wing; Sun, Weinong; Siu, Yun-Ming; Kong, Richard; Hung Chan, Kwok

2016-01-01

This article investigates the effect of gaze angle on the specific absorption rate (SAR) and temperature rise in human eye under electromagnetic exposures from 0.9 to 10 GHz. Eye models in different gaze angles are developed based on bio-metric data. The spatial-average SARs in eyes are investigated using the finite-difference time-domain method, and the corresponding maximum temperature rises in lens are calculated by the finite-difference method. It is found that the changes in the gaze angle produce a maximum variation of 35, 12 and 20 % in the eye-averaged SAR, peak 10 g average SAR and temperature rise, respectively. Results also reveal that the eye-averaged SAR is more sensitive to the changes in the gaze angle than peak 10 g average SAR, especially at higher frequencies. (authors)

Do receptors get pregnant too? Adrenergic receptor alterations in human pregnancy.

Science.gov (United States)

Smiley, R M; Finster, M

1996-01-01

In this review we discuss adrenergic receptor number and function during pregnancy, with emphasis on evidence that pregnancy results in specific receptor alterations from the nonpregnant state. Changes in adrenergic receptor function or distribution in vascular smooth muscle may be in part responsible for the decreased vascular responsiveness seen in human pregnancy, and the lack of the normal alterations may be a part of the syndromes of gestational hypertension, including preeclampsia-eclampsia. The onset of labor may be influenced by adrenergic modulation, and receptor or postreceptor level molecular alterations may trigger or facilitate normal or preterm labor. Human studies are emphasized when possible to assess the role of adrenergic signal transduction regulation in the physiology and pathophysiology of normal and complicated human pregnancy.

Calibration of SAR probes in waveguide at 900 MHz

International Nuclear Information System (INIS)

Jokela, K.; Puranen, L.; Hyysalo, P.

1998-01-01

The radiation safety tests for hand-held mobile phones require precise calibration of the small electric field probes used for the measurement of SAR in phantoms simulating the human body. In this study a calibration based on a rectangular waveguide was developed for SAR calibrations at 900 MHz

Simplified segmented human models for whole body and localised SAR evaluation of 20 MHz to 6 GHz electromagnetic field exposures

International Nuclear Information System (INIS)

Wu, T.; Shao, Q.; Yang, L.

2013-01-01

The digital human model is a key element in evaluating the electromagnetic field (EMF) exposure. This paper proposes the application of simplified segmented human models for EMF exposure compliance evaluation with the whole body and the localised limits. The method is based on the fact that most of the EMF power absorption is concentrated in several major tissues. Two kinds of human models were simply (the proposed method) and precisely segmented from two sets of whole body magnetic resonance imaging (MRI) scanned images. The whole body average-specific absorption rate (WBA-SAR) and the peak localised SAR averaging over 10 g tissues for the two kinds of models are calculated for various exposure configurations. The results confirmed the efficiency and the validity of the proposed method. The application as evaluating the MRI radiofrequency EMF exposure is also discussed in the paper. (authors)

Analysis of the local worst-case SAR exposure caused by an MRI multi-transmit body coil in anatomical models of the human body

Energy Technology Data Exchange (ETDEWEB)

Neufeld, Esra; Gosselin, Marie-Christine; Murbach, Manuel; Christ, Andreas; Cabot, Eugenia; Kuster, Niels, E-mail: neufeld@itis.ethz.ch [Foundation for Research on Information Technologies in Society (IT' IS), Zeughausstr. 43, 8004 Zuerich (Switzerland)

2011-08-07

Multi-transmit coils are increasingly being employed in high-field magnetic resonance imaging, along with a growing interest in multi-transmit body coils. However, they can lead to an increase in whole-body and local specific absorption rate (SAR) compared to conventional body coils excited in circular polarization for the same total incident input power. In this study, the maximum increase of SAR for three significantly different human anatomies is investigated for a large 3 T (128 MHz) multi-transmit body coil using numerical simulations and a (generalized) eigenvalue-based approach. The results demonstrate that the increase of SAR strongly depends on the anatomy. For the three models and normalization to the sum of the rung currents squared, the whole-body averaged SAR increases by up to a factor of 1.6 compared to conventional excitation and the peak spatial SAR (averaged over any 10 cm{sup 3} of tissue) by up to 13.4. For some locations the local averaged SAR goes up as much as 800 times (130 when looking only at regions where it is above 1% of the peak spatial SAR). The ratio of the peak spatial SAR to the whole-body SAR increases by a factor of up to 47 and can reach values above 800. Due to the potentially much larger power deposition, additional, preferably patient-specific, considerations are necessary to avoid injuries by such systems.

Cloning the interleukin 1 receptor from human T cells

International Nuclear Information System (INIS)

Sims, J.E.; Acres, R.B.; Grubin, C.E.; McMahan, C.J.; Wignall, J.M.; March, C.J.; Dower, S.K.

1989-01-01

cDNA clones of the interleukin 1 (IL-1) receptor expressed in a human T-cell clone have been isolated by using a murine IL-1 receptor cDNA as a probe. The human and mouse receptors show a high degree of sequence conservation. Both are integral membrane proteins possessing a single membrane-spanning segment. Similar to the mouse receptor, the human IL-1 receptor contains a large cytoplasmic region and an extracellular, IL-1 binding portion composed of three immunoglobulin-like domains. When transfected into COS cells, the human IL-1 receptor cDNA clone leads to expression of two different affinity classes of receptors, with K a values indistinguishable from those determined for IL-1 receptors in the original T-cell clone. An IL-1 receptor expressed in human dermal fibroblasts has also been cloned and sequenced and found to be identical to the IL-1 receptor expressed in T cells

Tracking Human-Induced Landscape Disturbance at the Nasca Lines UNESCO World Heritage Site in Peru with COSMO-SkyMed InSAR

Directory of Open Access Journals (Sweden)

Francesca Cigna

2018-04-01

Full Text Available The “Lines and Geoglyphs of Nasca and Palpa” in Peru are among the most well-known UNESCO World Heritage Sites globally, and an exemplar of site where heritage assets cannot be separated from their natural and anthropogenic environment. The site is exposed to interactions with natural processes, as well as human presence. In this work, 3-m resolution synthetic aperture radar (SAR StripMap HIMAGE HH-polarised scenes acquired by the X-band COSMO-SkyMed constellation are exploited to track two events of human-induced landscape disturbance that occurred in December 2014 and January 2018. Pre-, cross-, and post-event interferometric SAR (InSAR pairs characterised by small temporal and normal baselines allow the detection of temporal decorrelation associated with the two events, the extent and time reference of which match with online photographic and video evidence, published literature, web news, and press releases by the Ministry of Culture in Peru. Further elements enhancing the understanding of the 2018 event come from 10-m resolution Sentinel-2B satellite data that reveal the occurrence of apparent changes of surface reflectance due to uncovering of the light grey-yellow clay underneath the darker pebble constituting the fragile surface of the Pampa de Jumana. This scientific study confirms that SAR imagery archives, such as those being built by COSMO-SkyMed for Nasca, prove valuable for the retrospective analysis and digital recording of human-induced landscape disturbance events from space. These archives therefore act as essential sources of geospatial information on the conservation history of heritage sites and assets.

Distribution of melatonin receptor in human fetal brain

Institute of Scientific and Technical Information of China (English)

WANG Guo-quan; SHAO Fu-yuan; ZHAO Ying; LIU Zhi-min

2001-01-01

Objective: To study the distribution of 2 kinds of melatonin receptor subtypes (mtl and MT2) in human fetal brain. Methods: The fetal brain tissues were sliced and the distribution ofmelatonin receptors in human fetal brain were detected using immunohistochemistry and in situ hybridization. Results: Melatonin receptor mtl existed in the cerebellun and hypothalamus, melatonin receptor MT2 exists in hypothalamus, occipital and medulla. Conclusion: Two kinds of melatonin receptors, mtl and MT2 exist in the membrane and cytosol of brain cells, indicating that human fetal brain is a target organ of melatonin.

The discovery of tropane-derived CCR5 receptor antagonists.

Science.gov (United States)

Armour, Duncan R; de Groot, Marcel J; Price, David A; Stammen, Blanda L C; Wood, Anthony; Perros, Manos; Burt, Catherine

2006-04-01

The development of compound 1, a piperidine-based CCR5 receptor antagonist with Type I CYP2D6 inhibition, into the tropane-derived analogue 5, is described. This compound, which is devoid of CYP2D6 liabilities, is a highly potent ligand for the CCR5 receptor and has broad-spectrum activity against a range of clinically relevant HIV isolates. The identification of human ether a-go-go-related gene channel inhibition within this series is described and the potential for QTc interval prolongation discussed. Furthermore, structure activity relationship (SAR) around the piperidine moiety is also described.

Structure-activity relationships of strychnine analogues at glycine receptors

DEFF Research Database (Denmark)

Mohsen, A.M.Y.; Heller, Eberhard; Holzgrabe, Ulrike

2014-01-01

Nine strychnine derivatives including neostrychnine, strychnidine, isostrychnine, 21,22-dihydro-21-hydroxy-22-oxo-strychnine, and several hydrogenated analogs were synthesized, and their antagonistic activities at human α1 and α1β glycine receptors were evaluated. Isostrychnine has shown the best...... pharmacological profile exhibiting an IC50 value of 1.6 μM at α1 glycine receptors and 3.7-fold preference towards the α1 subtype. SAR Analysis indicates that the lactam moiety and the C(21)[DOUBLE BOND]C(22) bond in strychnine are essential structural features for its high antagonistic potency at glycine...

SAR and thermal response effects of a two-arm Archimedean spiral coil in a magnetic induction sensor on a human head.

Science.gov (United States)

Zhang, Ziyi; Liu, Peiguo; Zhou, Dongming; Zhang, Liang; Ding, Liang

2015-01-01

This study investigates the radiation safety of a newly designed magnetic induction sensor. This novel magnetic induction sensor uses a two-arm Archimedean spiral coil (TAASC) as the exciter. A human head model with a real anatomical structure was used to calculate the specific absorption rate (SAR) and temperature change. Computer Simulation Technology (CST) was used to determine the values of the peak 10-g SAR under different operating parameters (current, frequency, horizontal distance between the excitation coil and the receiver coil, vertical distance between the top of the head model and the XOY plane, position of excitation coil, and volume of hemorrhage). Then, the highest response for the SAR and temperature rise was determined. The results showed that this new magnetic induction sensor is safe in the initial state; for safety reasons, the TAASC current should not exceed 4 A. The scalp tissue absorbed most of the electromagnetic energy. The TAASC's SAR/thermal performance was close to that of the circular coil.

Radiolabelled GLP-1 receptor antagonist binds to GLP-1 receptor-expressing human tissues

International Nuclear Information System (INIS)

Waser, Beatrice; Reubi, Jean Claude

2014-01-01

Radiolabelled glucagon-like peptide 1 (GLP-1) receptor agonists have recently been shown to successfully image benign insulinomas in patients. For the somatostatin receptor targeting of tumours, however, it was recently reported that antagonist tracers were superior to agonist tracers. The present study therefore evaluated various forms of the 125 iodinated-Bolton-Hunter (BH)-exendin(9-39) antagonist tracer for the in vitro visualization of GLP-1 receptor-expressing tissues in rats and humans and compared it with the agonist tracer 125 I-GLP-1(7-36)amide. Receptor autoradiography studies with 125 I-GLP-1(7-36)amide agonist or 125 I-BH-exendin(9-39) antagonist radioligands were performed in human and rat tissues. The antagonist 125 I-BH-exendin(9-39) labelled at lysine 19 identifies all human and rat GLP-1 target tissues and GLP-1 receptor-expressing tumours. Binding is of high affinity and is comparable in all tested tissues in its binding properties with the agonist tracer 125 I-GLP-1(7-36)amide. For comparison, 125 I-BH-exendin(9-39) with the BH labelled at lysine 4 did identify the GLP-1 receptor in rat tissues but not in human tissues. The GLP-1 receptor antagonist exendin(9-39) labelled with 125 I-BH at lysine 19 is an excellent GLP-1 radioligand that identifies human and rat GLP-1 receptors in normal and tumoural tissues. It may therefore be the molecular basis to develop suitable GLP-1 receptor antagonist radioligands for in vivo imaging of GLP-1 receptor-expressing tissues in patients. (orig.)

Synthesis and structure-activity relationship of the first nonpeptidergic inverse agonists for the human cytomegalovirus encoded chemokine receptor US28.

Science.gov (United States)

Hulshof, Janneke W; Casarosa, Paola; Menge, Wiro M P B; Kuusisto, Leena M S; van der Goot, Henk; Smit, Martine J; de Esch, Iwan J P; Leurs, Rob

2005-10-06

US28 is a human cytomegalovirus (HCMV) encoded G-protein-coupled receptor that signals in a constitutively active manner. Recently, we identified 1 [5-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-2,2-diphenylpentanenitrile] as the first reported nonpeptidergic inverse agonist for a viral-encoded chemokine receptor. Interestingly, this compound is able to partially inhibit the viral entry of HIV-1. In this study we describe the synthesis of 1 and several of its analogues and unique structure-activity relationships for this first class of small-molecule ligands for the chemokine receptor US28. Moreover, the compounds have been pharmacologically characterized as inverse agonists on US28. By modification of lead structure 1, it is shown that a 4-phenylpiperidine moiety is essential for affinity and activity. Other structural features of 1 are shown to be of less importance. These compounds define the first SAR of ligands on a viral GPCR (US28) and may therefore serve as important tools to investigate the significance of US28-mediated constitutive activity during viral infection.

Rapid resensitization of purinergic receptor function in human platelets.

Science.gov (United States)

Mundell, S J; Barton, J F; Mayo-Martin, M B; Hardy, A R; Poole, A W

2008-08-01

Adenosine diphosphate (ADP) is a critical regulator of platelet activation, mediating its actions through two G protein-coupled receptors (GPCRs), the P2Y(1) and P2Y(12) purinergic receptors. Recently, we demonstrated that both receptors desensitize and internalize in human platelets by differential kinase-dependent mechanisms. To demonstrate whether responses to P2Y(1) and P2Y(12) purinergic receptors resensitize in human platelets and determine the role of receptor traffic in this process. These studies were undertaken either in human platelets or in cells stably expressing epitope-tagged P2Y(1) and P2Y(12) purinergic receptor constructs. In this study we show for the first time that responses to both of these receptors can rapidly resensitize following agonist-dependent desensitization in human platelets. Further, we show that in human platelets or in 1321N1 cells stably expressing receptor constructs, the disruption of receptor internalization, dephosphorylation or subsequent receptor recycling is sufficient to block resensitization of purinergic receptor responses. We also show that, in platelets, internalization of both these receptors is dependent upon dynamin, and that this process is required for resensitization of responses. This study is therefore the first to show that both P2Y(1) and P2Y(12) receptor activities are rapidly and reversibly modulated in human platelets, and it reveals that the underlying mechanism requires receptor trafficking as an essential part of this process.

An econometric analysis of SARS and Avian flu on international tourist arrivals to Asia

NARCIS (Netherlands)

M.J. McAleer (Michael); B-W. Huang (Bing-Wen); H-I. Kuo (Hsiao-I); C-C. Chen (Chi-Chung); C-L. Chang (Chia-Lin)

2008-01-01

textabstractThis paper compares the impacts of SARS and human deaths arising from Avian Flu on international tourist arrivals to Asia. The effects of SARS and human deaths from Avian Flu will be compared directly according to human deaths. The nature of the short run and long run relationship is

Crystal Structure of Feline Infectious Peritonitis Virus Main Protease in Complex with Synergetic Dual Inhibitors.

Science.gov (United States)

Wang, Fenghua; Chen, Cheng; Liu, Xuemeng; Yang, Kailin; Xu, Xiaoling; Yang, Haitao

2016-02-15

Coronaviruses (CoVs) can cause highly prevalent diseases in humans and animals. Feline infectious peritonitis virus (FIPV) belongs to the genus Alphacoronavirus, resulting in a lethal systemic granulomatous disease called feline infectious peritonitis (FIP), which is one of the most important fatal infectious diseases of cats worldwide. No specific vaccines or drugs have been approved to treat FIP. CoV main proteases (M(pro)s) play a pivotal role in viral transcription and replication, making them an ideal target for drug development. Here, we report the crystal structure of FIPV M(pro) in complex with dual inhibitors, a zinc ion and a Michael acceptor. The complex structure elaborates a unique mechanism of two distinct inhibitors synergizing to inactivate the protease, providing a structural basis to design novel antivirals and suggesting the potential to take advantage of zinc as an adjunct therapy against CoV-associated diseases. Coronaviruses (CoVs) have the largest genome size among all RNA viruses. CoV infection causes various diseases in humans and animals, including severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). No approved specific drugs or vaccinations are available to treat their infections. Here, we report a novel dual inhibition mechanism targeting CoV main protease (M(pro)) from feline infectious peritonitis virus (FIPV), which leads to lethal systemic granulomatous disease in cats. M(pro), conserved across all CoV genomes, is essential for viral replication and transcription. We demonstrated that zinc ion and a Michael acceptor-based peptidomimetic inhibitor synergistically inactivate FIPV M(pro). We also solved the structure of FIPV M(pro) complexed with two inhibitors, delineating the structural view of a dual inhibition mechanism. Our study provides new insight into the pharmaceutical strategy against CoV M(pro) through using zinc as an adjuvant therapy to enhance the efficacy of an irreversible

Radiolabelled GLP-1 receptor antagonist binds to GLP-1 receptor-expressing human tissues

Energy Technology Data Exchange (ETDEWEB)

Waser, Beatrice; Reubi, Jean Claude [University of Berne, Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, PO Box 62, Berne (Switzerland)

2014-06-15

Radiolabelled glucagon-like peptide 1 (GLP-1) receptor agonists have recently been shown to successfully image benign insulinomas in patients. For the somatostatin receptor targeting of tumours, however, it was recently reported that antagonist tracers were superior to agonist tracers. The present study therefore evaluated various forms of the {sup 125}iodinated-Bolton-Hunter (BH)-exendin(9-39) antagonist tracer for the in vitro visualization of GLP-1 receptor-expressing tissues in rats and humans and compared it with the agonist tracer {sup 125}I-GLP-1(7-36)amide. Receptor autoradiography studies with {sup 125}I-GLP-1(7-36)amide agonist or {sup 125}I-BH-exendin(9-39) antagonist radioligands were performed in human and rat tissues. The antagonist {sup 125}I-BH-exendin(9-39) labelled at lysine 19 identifies all human and rat GLP-1 target tissues and GLP-1 receptor-expressing tumours. Binding is of high affinity and is comparable in all tested tissues in its binding properties with the agonist tracer {sup 125}I-GLP-1(7-36)amide. For comparison, {sup 125}I-BH-exendin(9-39) with the BH labelled at lysine 4 did identify the GLP-1 receptor in rat tissues but not in human tissues. The GLP-1 receptor antagonist exendin(9-39) labelled with {sup 125}I-BH at lysine 19 is an excellent GLP-1 radioligand that identifies human and rat GLP-1 receptors in normal and tumoural tissues. It may therefore be the molecular basis to develop suitable GLP-1 receptor antagonist radioligands for in vivo imaging of GLP-1 receptor-expressing tissues in patients. (orig.)

Acetylene Black Induced Heterogeneous Growth of Macroporous CoV2O6 Nanosheet for High-Rate Pseudocapacitive Lithium-Ion Battery Anode.

Science.gov (United States)

Zhang, Lei; Zhao, Kangning; Luo, Yanzhu; Dong, Yifan; Xu, Wangwang; Yan, Mengyu; Ren, Wenhao; Zhou, Liang; Qu, Longbing; Mai, Liqiang

2016-03-23

Metal vanadates suffer from fast capacity fading in lithium-ion batteries especially at a high rate. Pseudocapacitance, which is associated with surface or near-surface redox reactions, can provide fast charge/discharge capacity free from diffusion-controlled intercalation processes and is able to address the above issue. In this work, we report the synthesis of macroporous CoV2O6 nanosheets through a facile one-pot method via acetylene black induced heterogeneous growth. When applied as lithium-ion battery anode, the macroporous CoV2O6 nanosheets show typical features of pseudocapacitive behavior: (1) currents that are mostly linearly dependent on sweep rate and (2) redox peaks whose potentials do not shift significantly with sweep rate. The macroporous CoV2O6 nanosheets display a high reversible capacity of 702 mAh g(-1) at 200 mA g(-1), excellent cyclability with a capacity retention of 89% (against the second cycle) after 500 cycles at 500 mA g(-1), and high rate capability of 453 mAh g(-1) at 5000 mA g(-1). We believe that the introduction of pseudocapacitive properties in lithium battery is a promising direction for developing electrode materials with high-rate capability.

Deflation-activated receptors, not classical inflation-activated receptors, mediate the Hering-Breuer deflation reflex.

Science.gov (United States)

Yu, Jerry

2016-11-01

Many airway sensory units respond to both lung inflation and deflation. Whether those responses to opposite stimuli come from one sensor (one-sensor theory) or more than one sensor (multiple-sensor theory) is debatable. One-sensor theory is commonly presumed in the literature. This article proposes a multiple-sensor theory in which a sensory unit contains different sensors for sensing different forces. Two major types of mechanical sensors operate in the lung: inflation- and deflation-activated receptors (DARs). Inflation-activated sensors can be further divided into slowly adapting receptors (SARs) and rapidly adapting receptors (RARs). Many SAR and RAR units also respond to lung deflation because they contain DARs. Pure DARs, which respond to lung deflation only, are rare in large animals but are easily identified in small animals. Lung deflation-induced reflex effects previously attributed to RARs should be assigned to DARs (including pure DARs and DARs associated with SARs and RARs) if the multiple-sensor theory is accepted. Thus, based on the information, it is proposed that activation of DARs can attenuate lung deflation, shorten expiratory time, increase respiratory rate, evoke inspiration, and cause airway secretion and dyspnea.

Cleavage of spike protein of SARS coronavirus by protease factor Xa is associated with viral infectivity

International Nuclear Information System (INIS)

Du, Lanying; Kao, Richard Y.; Zhou, Yusen; He, Yuxian; Zhao, Guangyu; Wong, Charlotte; Jiang, Shibo; Yuen, Kwok-Yung; Jin, Dong-Yan; Zheng, Bo-Jian

2007-01-01

The spike (S) protein of SARS coronavirus (SARS-CoV) has been known to recognize and bind to host receptors, whose conformational changes then facilitate fusion between the viral envelope and host cell membrane, leading to viral entry into target cells. However, other functions of SARS-CoV S protein such as proteolytic cleavage and its implications to viral infection are incompletely understood. In this study, we demonstrated that the infection of SARS-CoV and a pseudovirus bearing the S protein of SARS-CoV was inhibited by a protease inhibitor Ben-HCl. Also, the protease Factor Xa, a target of Ben-HCl abundantly expressed in infected cells, was able to cleave the recombinant and pseudoviral S protein into S1 and S2 subunits, and the cleavage was inhibited by Ben-HCl. Furthermore, this cleavage correlated with the infectivity of the pseudovirus. Taken together, our study suggests a plausible mechanism by which SARS-CoV cleaves its S protein to facilitate viral infection

Antenna modeling considerations for accurate SAR calculations in human phantoms in close proximity to GSM cellular base station antennas.

Science.gov (United States)

van Wyk, Marnus J; Bingle, Marianne; Meyer, Frans J C

2005-09-01

International bodies such as International Commission on Non-Ionizing Radiation Protection (ICNIRP) and the Institute for Electrical and Electronic Engineering (IEEE) make provision for human exposure assessment based on SAR calculations (or measurements) and basic restrictions. In the case of base station exposure this is mostly applicable to occupational exposure scenarios in the very near field of these antennas where the conservative reference level criteria could be unnecessarily restrictive. This study presents a variety of critical aspects that need to be considered when calculating SAR in a human body close to a mobile phone base station antenna. A hybrid FEM/MoM technique is proposed as a suitable numerical method to obtain accurate results. The verification of the FEM/MoM implementation has been presented in a previous publication; the focus of this study is an investigation into the detail that must be included in a numerical model of the antenna, to accurately represent the real-world scenario. This is accomplished by comparing numerical results to measurements for a generic GSM base station antenna and appropriate, representative canonical and human phantoms. The results show that it is critical to take the disturbance effect of the human phantom (a large conductive body) on the base station antenna into account when the antenna-phantom spacing is less than 300 mm. For these small spacings, the antenna structure must be modeled in detail. The conclusion is that it is feasible to calculate, using the proposed techniques and methodology, accurate occupational compliance zones around base station antennas based on a SAR profile and basic restriction guidelines. (c) 2005 Wiley-Liss, Inc.

The Danish (Q)SAR Database Update Project

DEFF Research Database (Denmark)

Nikolov, Nikolai Georgiev; Dybdahl, Marianne; Abildgaard Rosenberg, Sine

2013-01-01

The Danish (Q)SAR Database is a collection of predictions from quantitative structure–activity relationship ((Q)SAR) models for over 70 environmental and human health-related endpoints (covering biodegradation, metabolism, allergy, irritation, endocrine disruption, teratogenicity, mutagenicity......, carcinogenicity and others), each of them available for 185,000 organic substances. The database has been available online since 2005 (http://qsar.food.dtu.dk). A major update project for the Danish (Q)SAR database is under way, with a new online release planned in the beginning of 2015. The updated version...... will contain more than 600,000 discrete organic structures and new, more precise predictions for all endpoints, derived by consensus algorithms from a number of state-of-the-art individual predictions. Copyright © 2013 Published by Elsevier Ireland Ltd....

The estimation of 3D SAR distributions in the human head from mobile phone compliance testing data for epidemiological studies

International Nuclear Information System (INIS)

Wake, Kanako; Watanabe, Soichi; Taki, Masao; Varsier, Nadege; Wiart, Joe; Mann, Simon; Deltour, Isabelle; Cardis, Elisabeth

2009-01-01

A worldwide epidemiological study called 'INTERPHONE' has been conducted to estimate the hypothetical relationship between brain tumors and mobile phone use. In this study, we proposed a method to estimate 3D distribution of the specific absorption rate (SAR) in the human head due to mobile phone use to provide the exposure gradient for epidemiological studies. 3D SAR distributions due to exposure to an electromagnetic field from mobile phones are estimated from mobile phone compliance testing data for actual devices. The data for compliance testing are measured only on the surface in the region near the device and in a small 3D region around the maximum on the surface in a homogeneous phantom with a specific shape. The method includes an interpolation/extrapolation and a head shape conversion. With the interpolation/extrapolation, SAR distributions in the whole head are estimated from the limited measured data. 3D SAR distributions in the numerical head models, where the tumor location is identified in the epidemiological studies, are obtained from measured SAR data with the head shape conversion by projection. Validation of the proposed method was performed experimentally and numerically. It was confirmed that the proposed method provided good estimation of 3D SAR distribution in the head, especially in the brain, which is the tissue of major interest in epidemiological studies. We conclude that it is possible to estimate 3D SAR distributions in a realistic head model from the data obtained by compliance testing measurements to provide a measure for the exposure gradient in specific locations of the brain for the purpose of exposure assessment in epidemiological studies. The proposed method has been used in several studies in the INTERPHONE.

The SARS-unique domain (SUD of SARS coronavirus contains two macrodomains that bind G-quadruplexes.

Directory of Open Access Journals (Sweden)

Jinzhi Tan

2009-05-01

Full Text Available Since the outbreak of severe acute respiratory syndrome (SARS in 2003, the three-dimensional structures of several of the replicase/transcriptase components of SARS coronavirus (SARS-CoV, the non-structural proteins (Nsps, have been determined. However, within the large Nsp3 (1922 amino-acid residues, the structure and function of the so-called SARS-unique domain (SUD have remained elusive. SUD occurs only in SARS-CoV and the highly related viruses found in certain bats, but is absent from all other coronaviruses. Therefore, it has been speculated that it may be involved in the extreme pathogenicity of SARS-CoV, compared to other coronaviruses, most of which cause only mild infections in humans. In order to help elucidate the function of the SUD, we have determined crystal structures of fragment 389-652 ("SUD(core" of Nsp3, which comprises 264 of the 338 residues of the domain. Both the monoclinic and triclinic crystal forms (2.2 and 2.8 A resolution, respectively revealed that SUD(core forms a homodimer. Each monomer consists of two subdomains, SUD-N and SUD-M, with a macrodomain fold similar to the SARS-CoV X-domain. However, in contrast to the latter, SUD fails to bind ADP-ribose, as determined by zone-interference gel electrophoresis. Instead, the entire SUD(core as well as its individual subdomains interact with oligonucleotides known to form G-quadruplexes. This includes oligodeoxy- as well as oligoribonucleotides. Mutations of selected lysine residues on the surface of the SUD-N subdomain lead to reduction of G-quadruplex binding, whereas mutations in the SUD-M subdomain abolish it. As there is no evidence for Nsp3 entering the nucleus of the host cell, the SARS-CoV genomic RNA or host-cell mRNA containing long G-stretches may be targets of SUD. The SARS-CoV genome is devoid of G-stretches longer than 5-6 nucleotides, but more extended G-stretches are found in the 3'-nontranslated regions of mRNAs coding for certain host-cell proteins

Distinct patterns of IFITM-mediated restriction of filoviruses, SARS coronavirus, and influenza A virus.

Directory of Open Access Journals (Sweden)

I-Chueh Huang

2011-01-01

Full Text Available Interferon-inducible transmembrane proteins 1, 2, and 3 (IFITM1, 2, and 3 are recently identified viral restriction factors that inhibit infection mediated by the influenza A virus (IAV hemagglutinin (HA protein. Here we show that IFITM proteins restricted infection mediated by the entry glycoproteins (GP(1,2 of Marburg and Ebola filoviruses (MARV, EBOV. Consistent with these observations, interferon-β specifically restricted filovirus and IAV entry processes. IFITM proteins also inhibited replication of infectious MARV and EBOV. We observed distinct patterns of IFITM-mediated restriction: compared with IAV, the entry processes of MARV and EBOV were less restricted by IFITM3, but more restricted by IFITM1. Moreover, murine Ifitm5 and 6 did not restrict IAV, but efficiently inhibited filovirus entry. We further demonstrate that replication of infectious SARS coronavirus (SARS-CoV and entry mediated by the SARS-CoV spike (S protein are restricted by IFITM proteins. The profile of IFITM-mediated restriction of SARS-CoV was more similar to that of filoviruses than to IAV. Trypsin treatment of receptor-associated SARS-CoV pseudovirions, which bypasses their dependence on lysosomal cathepsin L, also bypassed IFITM-mediated restriction. However, IFITM proteins did not reduce cellular cathepsin activity or limit access of virions to acidic intracellular compartments. Our data indicate that IFITM-mediated restriction is localized to a late stage in the endocytic pathway. They further show that IFITM proteins differentially restrict the entry of a broad range of enveloped viruses, and modulate cellular tropism independently of viral receptor expression.

Gene Transfer and Molecular Cloning of the Human NGF Receptor

Science.gov (United States)

Chao, Moses V.; Bothwell, Mark A.; Ross, Alonzo H.; Koprowski, Hilary; Lanahan, Anthony A.; Buck, C. Randall; Sehgal, Amita

1986-04-01

Nerve growth factor (NGF) and its receptor are important in the development of cells derived from the neural crest. Mouse L cell transformants have been generated that stably express the human NGF receptor gene transfer with total human DNA. Affinity cross-linking, metabolic labeling and immunoprecipitation, and equilibrium binding with 125I-labeled NGF revealed that this NGF receptor had the same size and binding characteristics as the receptor from human melanoma cells and rat PC12 cells. The sequences encoding the NGF receptor were molecularly cloned using the human Alu repetitive sequence as a probe. A cosmid clone that contained the human NGF receptor gene allowed efficient transfection and expression of the receptor.

SARS – virus jumps species

Indian Academy of Sciences (India)

SARS – virus jumps species. Coronavirus reshuffles genes; Rotteir et al, Rotterdam showed the virus to jump from cats to mouse cells after single gene mutation ? Human disease due to virus jumping from wild or domestic animals; Present favourite animal - the cat; - edible or domestic.

Discovery of an Oxybenzylglycine Based Peroxisome Proliferator Activated Receptor Alpha Selective

Energy Technology Data Exchange (ETDEWEB)

Li, J.; Kennedy, L; Shi, Y; Tao, S; Ye, X; Chen, S; Wang, Y; Hernandez, A; Wang, W; et al.

2010-01-01

An 1,3-oxybenzylglycine based compound 2 (BMS-687453) was discovered to be a potent and selective peroxisome proliferator activated receptor (PPAR) {alpha} agonist, with an EC{sub 50} of 10 nM for human PPAR{alpha} and {approx}410-fold selectivity vs human PPAR{gamma} in PPAR-GAL4 transactivation assays. Similar potencies and selectivity were also observed in the full length receptor co-transfection assays. Compound 2 has negligible cross-reactivity against a panel of human nuclear hormone receptors including PPAR{delta}. Compound 2 demonstrated an excellent pharmacological and safety profile in preclinical studies and thus was chosen as a development candidate for the treatment of atherosclerosis and dyslipidemia. The X-ray cocrystal structures of the early lead compound 12 and compound 2 in complex with PPAR{alpha} ligand binding domain (LBD) were determined. The role of the crystal structure of compound 12 with PPAR{alpha} in the development of the SAR that ultimately resulted in the discovery of compound 2 is discussed.

Modulators of the human CCR5 receptor. Part 1: Discovery and initial SAR of 1-(3,3-diphenylpropyl)-piperidinyl amides and ureas.

Science.gov (United States)

Burrows, Jeremy N; Cumming, John G; Fillery, Shaun M; Hamlin, Gordon A; Hudson, Julian A; Jackson, Ruth J; McLaughlin, Sharon; Shaw, John S

2005-01-03

Investigation of weak screening hits led to the identification of N-alkyl-N-[1-(3,3-diphenylpropyl)piperidin-4-yl]-2-phenylacetamides and N-alkyl-N-[1-(3,3-diphenylpropyl)piperidin-4-yl]-N'-benzylureas as potent, selective ligands for the human CCR5 chemokine receptor.

TerraSAR-X InSAR multipass analysis on Venice, Italy)

Science.gov (United States)

Nitti, D. O.; Nutricato, R.; Bovenga, F.; Refice, A.; Chiaradia, M. T.; Guerriero, L.

2009-09-01

The TerraSAR-X (copyright) mission, launched in 2007, carries a new X-band Synthetic Aperture Radar (SAR) sensor optimally suited for SAR interferometry (InSAR), thus allowing very promising application of InSAR techniques for the risk assessment on areas with hydrogeological instability and especially for multi-temporal analysis, such as Persistent Scatterer Interferometry (PSI) techniques, originally developed at Politecnico di Milano. The SPINUA (Stable Point INterferometry over Unurbanised Areas) technique is a PSI processing methodology which has originally been developed with the aim of detection and monitoring of coherent PS targets in non or scarcely-urbanized areas. The main goal of the present work is to describe successful applications of the SPINUA PSI technique in processing X-band data. Venice has been selected as test site since it is in favorable settings for PSI investigations (urban area containing many potential coherent targets such as buildings) and in view of the availability of a long temporal series of TerraSAR-X stripmap acquisitions (27 scenes in all). The Venice Lagoon is affected by land sinking phenomena, whose origins are both natural and man-induced. The subsidence of Venice has been intensively studied for decades by determining land displacements through traditional monitoring techniques (leveling and GPS) and, recently, by processing stacks of ERS/ENVISAT SAR data. The present work is focused on an independent assessment of application of PSI techniques to TerraSAR-X stripmap data for monitoring the stability of the Venice area. Thanks to its orbital repeat cycle of only 11 days, less than a third of ERS/ENVISAT C-band missions, the maximum displacement rate that can be unambiguously detected along the Line-of-Sight (LOS) with TerraSAR-X SAR data through PSI techniques is expected to be about twice the corresponding value of ESA C-band missions, being directly proportional to the sensor wavelength and inversely proportional to the

FMRFamide receptors of Helix aspersa

International Nuclear Information System (INIS)

Payza, K.

1988-01-01

A receptor binding assay and an isolated heart bioassay were used to identify and characterize the FMRFamide receptors in Helix. In the heart bioassay, FMRFamide increased myocardial contraction force. A potent FMRFamide analog, desaminoTyr-Phe-norLeu-arg-Phe-amide (daYFnLRFamide), was used as a radioiodinated receptor ligand. The high affinity binding of 125 I-daYFnLRFamide at 0 degree C to Helix brain membranes was reversible, saturable, pH-dependent and specific, with a K D of 13-14 nM. A lower affinity (245 nM) site was also observed. Radioligand binding sites were also identified in the heart, male reproductive organs and digestive organs. The structure-activity relations (SAR) of cardiostimulation correlated with the specificity of 125 I-daYFnLRFamide binding to brain and heart receptors. The SAR were similar to those of other molluscan FMRFamide bioassays, except that they showed a marked preference for some analogs with blocked amino-terminals

Severe acute respiratory syndrome vaccine efficacy in ferrets: whole killed virus and adenovirus-vectored vaccines.

Science.gov (United States)

See, Raymond H; Petric, Martin; Lawrence, David J; Mok, Catherine P Y; Rowe, Thomas; Zitzow, Lois A; Karunakaran, Karuna P; Voss, Thomas G; Brunham, Robert C; Gauldie, Jack; Finlay, B Brett; Roper, Rachel L

2008-09-01

Although the 2003 severe acute respiratory syndrome (SARS) outbreak was controlled, repeated transmission of SARS coronavirus (CoV) over several years makes the development of a SARS vaccine desirable. We performed a comparative evaluation of two SARS vaccines for their ability to protect against live SARS-CoV intranasal challenge in ferrets. Both the whole killed SARS-CoV vaccine (with and without alum) and adenovirus-based vectors encoding the nucleocapsid (N) and spike (S) protein induced neutralizing antibody responses and reduced viral replication and shedding in the upper respiratory tract and progression of virus to the lower respiratory tract. The vaccines also diminished haemorrhage in the thymus and reduced the severity and extent of pneumonia and damage to lung epithelium. However, despite high neutralizing antibody titres, protection was incomplete for all vaccine preparations and administration routes. Our data suggest that a combination of vaccine strategies may be required for effective protection from this pathogen. The ferret may be a good model for SARS-CoV infection because it is the only model that replicates the fever seen in human patients, as well as replicating other SARS disease features including infection by the respiratory route, clinical signs, viral replication in upper and lower respiratory tract and lung damage.

SAR matrices: automated extraction of information-rich SAR tables from large compound data sets.

Science.gov (United States)

Wassermann, Anne Mai; Haebel, Peter; Weskamp, Nils; Bajorath, Jürgen

2012-07-23

We introduce the SAR matrix data structure that is designed to elucidate SAR patterns produced by groups of structurally related active compounds, which are extracted from large data sets. SAR matrices are systematically generated and sorted on the basis of SAR information content. Matrix generation is computationally efficient and enables processing of large compound sets. The matrix format is reminiscent of SAR tables, and SAR patterns revealed by different categories of matrices are easily interpretable. The structural organization underlying matrix formation is more flexible than standard R-group decomposition schemes. Hence, the resulting matrices capture SAR information in a comprehensive manner.

Detection of macroalgae blooms by complex SAR imagery

International Nuclear Information System (INIS)

Shen, Hui; Perrie, William; Liu, Qingrong; He, Yijun

2014-01-01

Highlights: • Complex SAR imagery enables better recognition of macroalgae patches. • Combination of different information in SAR matrix forms new index factors. • Proposed index factors contribute to unsupervised recognition of macroalgae. -- Abstract: Increased frequency and enhanced damage to the marine environment and to human society caused by green macroalgae blooms demand improved high-resolution early detection methods. Conventional satellite remote sensing methods via spectra radiometers do not work in cloud-covered areas, and therefore cannot meet these demands for operational applications. We present a methodology for green macroalgae bloom detection based on RADARSAT-2 synthetic aperture radar (SAR) images. Green macroalgae patches exhibit different polarimetric characteristics compared to the open ocean surface, in both the amplitude and phase domains of SAR-measured complex radar backscatter returns. In this study, new index factors are defined which have opposite signs in green macroalgae-covered areas, compared to the open water surface. These index factors enable unsupervised detection from SAR images, providing a high-resolution new tool for detection of green macroalgae blooms, which can potentially contribute to a better understanding of the mechanisms related to outbreaks of green macroalgae blooms in coastal areas throughout the world ocean

Genetic variation of the human α-2-Heremans-Schmid glycoprotein (AHSG gene associated with the risk of SARS-CoV infection.

Directory of Open Access Journals (Sweden)

Xiaohui Zhu

Full Text Available Genetic background may play an important role in the process of SARS-CoV infection and SARS development. We found several proteins that could interact with the nucleocapsid protein of the SARS coronavirus (SARS-CoV. α-2-Heremans-Schmid Glycoprotein (AHSG, which is required for macrophage deactivation by endogenous cations, is associated with inflammatory regulation. Cytochrome P450 Family 3A (CYP4F3A is an ω-oxidase that inactivates Leukotriene B4 (LTB4 in human neutrophils and the liver. We investigated the association between the polymorphisms of these two inflammation-associated genes and SARS development. The linkage disequilibrium (LD maps of these two genes were built with Haploview using data on CHB+JPT (version 2 from the HapMap. A total of ten tag SNPs were selected and genotyped. In the Guangzhou cohort study, after adjusting for age and sex, two AHSG SNPs and one CYP4F3 SNP were found to be associated with SARS susceptibility: rs2248690 (adjusted odds ratio [AOR] 2.42; 95% confidence interval [CI] 1.30-4.51; rs4917 (AOR 1.84; 95% CI 1.02-3.34; and rs3794987 (AOR 2.01; 95% CI 1.10-3.68. To further validate the association, the ten tag SNPs were genotyped in the Beijing cohort. After adjusting for age and sex, only rs2248690 (AOR, 1.63; 95% CI, 1.30-2.04 was found to be associated with SARS susceptibility. The combined analysis of the two studies confirmed tag SNP rs2248690 in AHSG as a susceptibility variant (AOR 1.70; 95% CI 1.37-2.09. The statistical analysis of the rs2248690 genotype data among the patients and healthy controls in the HCW cohort, who were all similarly exposed to the SARS virus, also supported the findings. Further, the SNP rs2248690 affected the transcriptional activity of the AHSG promoter and thus regulated the AHSG serum level. Therefore, our study has demonstrated that the AA genotype of rs2268690, which leads to a higher AHSG serum concentration, was significantly associated with protection against SARS

Human eosinophils - potential pharmacological model applied in human histamine H4 receptor research.

Science.gov (United States)

Grosicki, Marek; Kieć-Kononowicz, Katarzyna

2015-01-01

Histamine and histamine receptors are well known for their immunomodulatory role in inflammation. In this review we describe the role of histamine and histamine H4 receptor on human eosinophils. In the first part of article we provide short summary of histamine and histamine receptors role in physiology and histamine related therapeutics used in clinics. We briefly describe the human histamine receptor H4 and its ligands, as well as human eosinophils. In the second part of the review we provide detailed description of known histamine effects on eosinophils including: intracellular calcium concentration flux, actin polymerization, cellular shape change, upregulation of adhesion proteins and cellular chemotaxis. We provide proofs that these effects are mainly connected with the activation of histamine H4 receptor. When examining experimental data we discuss the controversial results and limitations of the studies performed on isolated eosinophils. In conclusion we believe that studies on histamine H4 receptor on human eosinophils can provide interesting new biomarkers that can be used in clinical studies of histamine receptors, that in future might result in the development of new strategies in the treatment of chronic inflammatory conditions like asthma or allergy, in which eosinophils are involved.

7 T body MRI: B1 shimming with simultaneous SAR reduction

International Nuclear Information System (INIS)

Bergen, Bob van den; Berg, Cornelis A T van den; Bartels, Lambertus W; Lagendijk, Jan J W

2007-01-01

The high frequency of the radiofrequency (RF) fields used in high field magnetic resonance imaging (MRI) results in electromagnetic field variations that can cause local regions to have a large specific absorption rate (SAR) and/or a low excitation. In this study, we evaluated the use of a B 1 shimming technique which can simultaneously improve the B + 1 homogeneity and reduce the SAR for whole body imaging at 7 T. Optimizations for four individual anatomies showed a reduction up to 74% of the peak SAR values with respect to a quadrature excitation and a simultaneous improvement of the B + 1 homogeneity varying between 39 and 75% for different optimization parameters. The average SAR was reduced with approximately 50% for all optimizations. The optimized phase and amplitude settings from an elliptical phantom model were applied to four realistic human anatomy models to evaluate whether a generic application without prior knowledge of the detailed human anatomy is possible. This resulted in an average improvement of the B + 1 homogeneity of 37% and an average reduction of the maximum and average SAR of 50 and 55%, respectively. It can be concluded that this generic method can be used as a simple method to improve the prospects of 7 T body imaging

SLOWLY ADAPTING SENSORY UNITS HAVE MORE RECEPTORS IN LARGE AIRWAYS THAN IN SMALL AIRWAYS IN RABBITS

Directory of Open Access Journals (Sweden)

Jun Liu

2016-12-01

Full Text Available Sensory units of pulmonary slowly adapting receptors (SARs are more active in large airways than in small airways. However, there is no explanation for this phenomenon. Although sensory structures in large airways resemble those in small airways, they are bigger and more complex. Possibly, a larger receptor provides greater surface area for depolarization, and thus has a lower activating threshold and/or a higher sensitivity to stretch, leading to more nerve electrical activities. Recently, a single sensory unit has been reported to contain multiple receptors. Therefore, sensory units in large airways may contain more SARs, which may contribute to high activities. To test this hypothesis, we used a double staining technique to identify sensory receptor sizes. We labeled the sensory structure with Na+/K+-ATPase antibodies and the myelin sheath with myelin basic protein (MBP antibodies. A SAR can be defined as the end formation beyond MBP labeling. Thus, we are able to compare sizes of sensory structures and SARs in large (trachea and bronchi vs small (bronchioles 0.05. However, the sensory structure contains more SARs in large airways than in small airways (9.6±0.6 vs 3.6±0.3; P<0.0001. Thus, our data support the hypothesis that greater numbers of SARs in sensory units of large airways may contribute to higher activities.

SARS - Diagnosis

Indian Academy of Sciences (India)

SARS - Diagnosis. Mainly by exclusion of known causes of atypical pneumonia; * X ray Chest; * PCR on body fluids- primers defined by WHO centres available from website.-ve result does not exclude SARS. * Sequencing of amplicons; * Viral Cultures – demanding; * Antibody tests.

Influence of dentures on SAR in the visible Chinese human head voxel phantom exposed to a mobile phone at 900 and 1800 MHz.

Science.gov (United States)

Yu, Dong; Zhang, Ruoyu; Liu, Qian

2012-09-01

To investigate the influence of dentures on electromagnetic energy absorption during the daily use of a mobile phone, a high-resolution head phantom based on the Visible Chinese Human dataset was reconstructed. Simulations on phantoms with various dentures were performed by using the finite-difference time-domain method with a 0.47 wavelength dipole antenna and a mobile phone model as radiation sources at 900 and 1800 MHz. The Specific energy Absorption Rate (SAR) values including 1 and 10 g average SAR values were assessed. When the metallic dental crowns with resonance lengths of approximately one-third to one-half wavelength in the tissue nearby are parallel to the radiation source, up to 121.6% relative enhancement for 1 g average SAR and 17.1% relative enhancement for 10 g average SAR are observed due to the resonance effect in energy absorption. When the radiation sources operate in the normal configuration, the 10 g average SAR values are still in compliance with the basic restrictions established by the Institute of Electrical and Electronic Engineers (IEEE) and the International Commission on Non-Ionizing Radiation Protection (ICNIRP), indicating that the safety limits will not be challenged by the usage of dentures. Copyright © 2012 Wiley Periodicals, Inc.

Bistatic sAR data processing algorithms

CERN Document Server

Qiu, Xiaolan; Hu, Donghui

2013-01-01

Synthetic Aperture Radar (SAR) is critical for remote sensing. It works day and night, in good weather or bad. Bistatic SAR is a new kind of SAR system, where the transmitter and receiver are placed on two separate platforms. Bistatic SAR is one of the most important trends in SAR development, as the technology renders SAR more flexible and safer when used in military environments. Imaging is one of the most difficult and important aspects of bistatic SAR data processing. Although traditional SAR signal processing is fully developed, bistatic SAR has a more complex system structure, so sign

Diindolylmethane Derivatives: Potent Agonists of the Immunostimulatory Orphan G Protein-Coupled Receptor GPR84.

Science.gov (United States)

Pillaiyar, Thanigaimalai; Köse, Meryem; Sylvester, Katharina; Weighardt, Heike; Thimm, Dominik; Borges, Gleice; Förster, Irmgard; von Kügelgen, Ivar; Müller, Christa E

2017-05-11

The G i protein-coupled receptor GPR84, which is activated by (hydroxy)fatty acids, is highly expressed on immune cells. Recently, 3,3'-diindolylmethane was identified as a heterocyclic, nonlipid-like GPR84 agonist. We synthesized a broad range of diindolylmethane derivatives by condensation of indoles with formaldehyde in water under microwave irradiation. The products were evaluated at the human GPR84 in cAMP and β-arrestin assays. Structure-activity relationships (SARs) were steep. 3,3'-Diindolylmethanes bearing small lipophilic residues at the 5- and/or 7-position of the indole rings displayed the highest activity in cAMP assays, the most potent agonists being di(5-fluoro-1H-indole-3-yl)methane (38, PSB-15160, EC 50 80.0 nM) and di(5,7-difluoro-1H-indole-3-yl)methane (57, PSB-16671, EC 50 41.3 nM). In β-arrestin assays, SARs were different, indicating biased agonism. The new compounds were selective versus related fatty acid receptors and the arylhydrocarbon receptor. Selected compounds were further investigated and found to display an ago-allosteric mechanism of action and increased stability in comparison to the lead structure.

Dopamine receptor repertoire of human granulosa cells

Directory of Open Access Journals (Sweden)

Kunz Lars

2007-10-01

Full Text Available Abstract Background High levels of dopamine (DA were described in human ovary and recently evidence for DA receptors in granulosa and luteal cells has been provided, as well. However, neither the full repertoire of ovarian receptors for DA, nor their specific role, is established. Human granulosa cells (GCs derived from women undergoing in vitro fertilization (IVF are an adequate model for endocrine cells of the follicle and the corpus luteum and were therefore employed in an attempt to decipher their DA receptor repertoire and functionality. Methods Cells were obtained from patients undergoing IVF and examined using cDNA-array, RT-PCR, Western blotting and immunocytochemistry. In addition, calcium measurements (with FLUO-4 were employed. Expression of two DA receptors was also examined by in-situ hybridization in rat ovary. Effects of DA on cell viability and cell volume were studied by using an ATP assay and an electronic cell counter system. Results We found members of the two DA receptor families (D1- and D2 -like associated with different signaling pathways in human GCs, namely D1 (as expected and D5 (both are Gs coupled and linked to cAMP increase and D2, D4 (Gi/Gq coupled and linked to IP3/DAG. D3 was not found. The presence of the trophic hormone hCG (10 IU/ml in the culture medium for several days did not alter mRNA (semiquantitative RT-PCR or protein levels (immunocytochemistry/Western blotting of D1,2,4,5 DA receptors. Expression of prototype receptors for the two families, D1 and D2, was furthermore shown in rat granulosa and luteal cells by in situ hybridization. Among the DA receptors found in human GCs, D2 expression was marked both at mRNA and protein levels and it was therefore further studied. Results of additional RT-PCR and Western blots showed two splice variants (D2L, D2S. Irrespective of these variants, D2 proved to be functional, as DA raised intracellular calcium levels. This calcium mobilizing effect of DA was observed

Evidence for Alpha Receptors in the Human Ureter

Science.gov (United States)

Madeb, Ralph; Knopf, Joy; Golijanin, Dragan; Bourne, Patricia; Erturk, Erdal

2007-04-01

An immunohistochemical and western blot expression analysis of human ureters was performed in order to characterize the alpha-1-adrenergic receptor distribution along the length of the human ureteral wall. Mapping the distribution will assist in understanding the potential role alpha -1-adrenergic receptors and their subtype density might have in the pathophysiology of ureteral colic and stone passage. Patients diagnosed with renal cancer or bladder cancer undergoing nephrectomy, nephroureterectomy, or cystectomy had ureteral specimens taken from the proximal, mid, distal and tunneled ureter. Tissues were processed for fresh frozen examination and fixed in formalin. None of the ureteral specimens were involved with cancer. Serial histologic sections and immunohistochemical studies were performed using antibodies specific for alpha-1-adrenergic receptor subtypes (alpha 1a, alpha 1b, alpha 1d). The sections were examined under a light microscope and scored as positive or negative. In order to validate and quantify the alpha receptor subtypes along the human ureter. Western blotting techniques were applied. Human ureter stained positively for alpha -1-adrenergic receptors. Immunostaining appeared red, with intense reaction in the smooth muscle of the ureter and endothelium of the neighboring blood vessels. There was differential expression between all the receptors with the highest staining for alpha-1D subtype. The highest protein expression for all three subtypes was in the renal pelvis and decreased with advancement along the ureter to the distal ureter. At the distal ureter, there was marked increase in expression as one progressed towards the ureteral orifice. The same pattern of protein expression was exhibited for all three alpha -1-adrenergic receptor subtypes. We provide preliminary evidence for the ability to detect and quantify the alpha-1-receptor subtypes along the human ureter which to the best of our knowledge has never been done with

Radiosequence analysis of the human progestin receptor charged with [3H]promegestone. A comparison with the glucocorticoid receptor

International Nuclear Information System (INIS)

Stroemstedt, P.E.B.; Berkenstam, A.; Joernvall, H.G.; Gustafsson, J.A.; Carlstedt-Duke, J.

1990-01-01

Partially purified preparations of the human progestin receptor and the human and rat glucocorticoid receptor proteins were covalently charged with the synthetic progestin, [ 3 H]promegestone, by photoaffinity labeling. After labeling, the denaturated protein was cleaved and the mixture of peptides subjected to radiosequence analysis as previously described for the rat glucocorticoid receptor protein. The radioactivity labels identified, corresponded to Met-759 and Met-909 after photoaffinity labeling of the human progestin receptor, and Met-622 and Cys-754 after labeling of the rat glucocorticoid receptor. The residues labeled in the glucocorticoid receptor are the same as those previously reported to bind triamcinolone actonide. The corresponding residues were also labeled in the human glucocorticoid receptor. Met-759 of the progestin receptor and Met-622 of the rat glucocorticoid receptor are positioned within a segment with an overall high degree of sequence similarity and are equivalent. However, Met-909 (progestin receptor) and Cys-754 (glucocorticoid receptor) do not occur within equivalent segments of the two proteins. Thus, although the two classes of steroid hormone share a common structure within the A-ring, there are subtle differences in their interaction with the two separate receptor proteins

SAR analysis of a needle type applicator made from a shape memory alloy using 3-D anatomical human head model

International Nuclear Information System (INIS)

Kubo, Mitsunori; Mimoto, Naoki; Hirashima, Taku; Morita, Emi; Shindo, Yasuhiro; Kato, Kazuo; Takahashi, Hideaki; Uzuka, Takeo; Fujii, Yukihiko

2009-01-01

This paper describes the possibility of a new heating method with a needle applicator made of a shape memory alloy (SMA) to expand the heating area for interstitial brain tumor hyperthermia treatments. The purpose of the study described here is to show the capability of the method to expand a defined heating region with the developed three-dimensional (3-D) anatomical human head model using the finite element method (FEM). One major disadvantage of radiofrequency (RF) interstitial hyperthermia treatment is that this heating method has a small heating area. To overcome this problem, a new type of needle made of a SMA was developed. The specific absorption rate (SAR) distributions of this proposed method, when applied to the 3-D anatomical human head model reconstructed from two-dimensional (2-D) MRI and X-ray CT images, were calculated with computer simulations. The calculated SAR distributions showed no unexpected hot spots within the model. The heated area was localized around the tumor. These results suggest that the proposed heating method using the SMA needle applicator and the developed method for reconstructing a 3-D anatomical human head model are capable of being used for invasive brain tumor hyperthermia treatments. (author)

Yeast based small molecule screen for inhibitors of SARS-CoV.

Directory of Open Access Journals (Sweden)

Matthew Frieman

Full Text Available Severe acute respiratory coronavirus (SARS-CoV emerged in 2002, resulting in roughly 8000 cases worldwide and 10% mortality. The animal reservoirs for SARS-CoV precursors still exist and the likelihood of future outbreaks in the human population is high. The SARS-CoV papain-like protease (PLP is an attractive target for pharmaceutical development because it is essential for virus replication and is conserved among human coronaviruses. A yeast-based assay was established for PLP activity that relies on the ability of PLP to induce a pronounced slow-growth phenotype when expressed in S. cerevisiae. Induction of the slow-growth phenotype was shown to take place over a 60-hour time course, providing the basis for conducting a screen for small molecules that restore growth by inhibiting the function of PLP. Five chemical suppressors of the slow-growth phenotype were identified from the 2000 member NIH Diversity Set library. One of these, NSC158362, potently inhibited SARS-CoV replication in cell culture without toxic effects on cells, and it specifically inhibited SARS-CoV replication but not influenza virus replication. The effect of NSC158362 on PLP protease, deubiquitinase and anti-interferon activities was investigated but the compound did not alter these activities. Another suppressor, NSC158011, demonstrated the ability to inhibit PLP protease activity in a cell-based assay. The identification of these inhibitors demonstrated a strong functional connection between the PLP-based yeast assay, the inhibitory compounds, and SARS-CoV biology. Furthermore the data with NSC158362 suggest a novel mechanism for inhibition of SARS-CoV replication that may involve an unknown activity of PLP, or alternatively a direct effect on a cellular target that modifies or bypasses PLP function in yeast and mammalian cells.

β-Adrenergic receptor-mediated suppression of interleukin 2 receptors in human lymphocytes

International Nuclear Information System (INIS)

Feldman, R.D.; Hunninghake, G.W.; McArdle, W.L.

1987-01-01

Adrenergic receptor agonists are know to attenuate the proliferative response of human lymphocytes after activation; however, their mechanism of action is unknown. Since expression of interleukin 2 (IL-2) receptors is a prerequisite for proliferation, the effect of β-adrenergic receptor agonists on lymphocyte IL-2 receptors was studied on both mitogen-stimulated lymphocytes and IL-2-dependent T lymphocyte cell lines. In both cell types the β-adrenergic receptor agonist isoproterenol blocked the expression of IL-2 receptors, as determined with the IL-2 receptor anti-TAC antibody. To determine the effect of β-adrenergic agonists on expression of the high affinity IL-2 receptors, [ 125 I]IL-2 binding studies were performed at concentrations selective for high affinity sites. No significant effect of β-adrenergic agonists on high affinity IL-2 receptor sites could be detected. The data demonstrate that β-adrenergic receptor agonists down-regulate IL-2 receptors primarily affecting low affinity sites

Cloning of the human androgen receptor cDNA

International Nuclear Information System (INIS)

Govindan, M.V.; Burelle, M.; Cantin, C.; Kabrie, C.; Labrie, F.; Lachance, Y.; Leblanc, G.; Lefebvre, C.; Patel, P.; Simard, J.

1988-01-01

The authors discuss how in order to define the functional domains of the human androgen receptor, complementary DNA (cDNA) clones encoding the human androgen receptor (hAR) have been isolated from a human testis λgtll cDNA library using synthetic oligonnucleotide probes, homologous to segments of the human glucocorticoid, estradiol and progesterone receptors. The cDNA clones corresponding to the human glucocorticoid, estradiol and progesterone receptors were eliminated after cross-hybridization with their respective cDNA probes and/or after restriction mapping of the cDNA clones. The remaining cDNA clones were classified into different groups after analysis by restriction digestion and cross-hybridization. Two of the largest cDNA clones from each group were inserted into an expression vector in both orientations. The linearized plasmids were used as templates in in vitro transcription with T7 RNA polymerase. Subsequent in vitro translation of the purified transcripts in rabbit reticulocyte lysate followed by sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) permitted the characterization of the encoded polyeptides. The expressed proteins larger than 30,000 Da were analyzed for their ability to bind tritium-labelled dihydrotestosterone ([ 3 H] DHT) with high affinity and specificity

Keynote presentation : SAR systems

NARCIS (Netherlands)

Halsema, D. van; Otten, M.P.G.; Maas, A.P.M.; Bolt, R.J.; Anitori, L.

2011-01-01

Synthetic Aperture Radar (SAR) systems are becoming increasingly important sensors in as well the military environment as in the civilian market. In this keynote presentation an overview will be given over more than 2 decades of SAR system∼ and SAR application development at TNO in the Netherlands.

Characteristics of recombinantly expressed rat and human histamine H3 receptors.

Science.gov (United States)

Wulff, Birgitte S; Hastrup, Sven; Rimvall, Karin

2002-10-18

Human and rat histamine H(3) receptors were recombinantly expressed and characterized using receptor binding and a functional cAMP assay. Seven of nine agonists had similar affinities and potencies at the rat and human histamine H(3) receptor. S-alpha-methylhistamine had a significantly higher affinity and potency at the human than rat receptor, and for 4-[(1R*,2R*)-2-(5,5-dimethyl-1-hexynyl)cyclopropyl]-1H-imidazole (Perceptin) the preference was the reverse. Only two of six antagonists had similar affinities and potencies at the human and the rat histamine H(3) receptor. Ciproxifan, thioperamide and (1R*,2R*)-trans-2-imidazol-4 ylcyclopropyl) (cyclohexylmethoxy) carboxamide (GT2394) had significantly higher affinities and potencies at the rat than at the human histamine H(3) receptor, while for N-(4-chlorobenzyl)-N-(7-pyrrolodin-1-ylheptyl)guanidine (JB98064) the preference was the reverse. All antagonists also showed potent inverse agonism properties. Iodoproxyfan, Perceptin, proxyfan and GR175737, compounds previously described as histamine H(3) receptor antagonists, acted as full or partial agonists at both the rat and the human histamine H(3) receptor. Copyright 2002 Elsevier Science B.V.

Pharmacological characterization of receptor-activity-modifying proteins (RAMPs) and the human calcitonin receptor.

Science.gov (United States)

Armour, S L; Foord, S; Kenakin, T; Chen, W J

1999-12-01

Receptor-activity-modifying proteins (RAMPs) are a family of single transmembrane domain proteins shown to be important for the transport and ligand specificity of the calcitonin gene-related peptide (CGRP) receptor. In this report, we describe the analysis of pharmacological properties of the human calcitonin receptor (hCTR) coexpressed with different RAMPs with the use of the Xenopus laevis melanophore expression system. We show that coexpression of RAMP3 with human calcitonin receptor changed the relative potency of hCTR to human calcitonin (hCAL) and rat amylin. RAMP1 and RAMP2, in contrast, had little effect on the change of hCTR potency to hCAL or rat amylin. When coexpressed with RAMP3, hCTR reversed the relative potency by a 3.5-fold loss in sensitivity to hCAL and a 19-fold increase in sensitivity to rat amylin. AC66, an inverse agonist, produced apparent simple competitive antagonism of hCAL and rat amylin, as indicated by linear Schild regressions. The potency of AC66 was changed in the blockade of rat amylin but not hCAL responses with RAMP3 coexpression. The mean pK(B) for AC66 to hCAL was 9.4 +/- 0.3 without RAMP3 and 9.45 +/- 0.07 with RAMP3. For the antagonism of AC66 to rat amylin, the pK(B) was 9.25 +/- 0.15 without RAMP3 and 8.2 +/- 0.35 with RAMP3. The finding suggests that RAMP3 might modify the active states of calcitonin receptor in such a way as to create a new receptor phenotype that is "amylin-like." Irrespective of the physiological association of the new receptor species, the finding that a coexpressed membrane protein can completely change agonist and antagonist affinities for a receptor raises implications for screening in recombinant receptor systems.

Monitoring of Three Case Studies of Creeping Landslides in Ecuador using L-band SAR Interferometry (InSAR)

Science.gov (United States)

Mayorga Torres, T. M.; Mohseni Aref, M.

2015-12-01

Tannia Mayorga Torres1,21 Universidad Central del Ecuador. Faculty of Geology, Mining, Oil, and Environment 2 Hubert H. Humphrey Fellowship 2015-16 IntroductionLandslides lead to human and economic losses across the country, mainly in the winter season. On the other hand, satellite radar data has cost-effective benefits due to open-source software and free availability of data. With the purpose of establishing an early warning system of landslide-related surface deformation, three case studies were designed in the Coast, Sierra (Andean), and Oriente (jungle) regions. The objective of this work was to assess the capability of L-band InSAR to get phase information. For the calculation of the interferograms in Repeat Orbit Interferometry PACkage, the displacement was detected as the error and was corrected. The coherence images (Figure 1) determined that L-band is suitable for InSAR processing. Under this frame, as a first approach, the stacking DInSAR technique [1] was applied in the case studies [2]; however, due to lush vegetation and steep topography, it is necessary to apply advanced InSAR techniques [3]. The purpose of the research is to determine a pattern of data acquisition and successful results to understand the spatial and temporal ground movements associated with landslides. The further work consists of establishing landslide inventories to combine phases of SAR images to generate maps of surface deformation in Tumba-San Francisco and Guarumales to compare the results with ground-based measurements to determine the maps' accuracy. References[1] Sandwell D., Price E. (1998). Phase gradient approach to stacking interferograms. Journal of Geophysical Research, Vol. 103, N. B12, pp. 30,183-30,204. [2] Mayorga T., Platzeck G. (2014). Using DInSAR as a tool to detect unstable terrain areas in an Andes region in Ecuador. NH3.5-Blue Poster B298, Vol. 16, EGU2014-16203. Austria. [3] Wasowski J., Bovenga F. (2014). Investigating landslides and unstable slopes with

Human macrophage scavenger receptors: Primary structure, expression, and localization in atherosclerotic lesions

International Nuclear Information System (INIS)

Matsumoto, Akiyo; Itakura, Hiroshige; Kodama, Tatsuhiko; Naito, Makoto; Takahashi, Kiyoshi; Ikemoto, Shinji; Asaoka, Hitoshi; Hayakawa, Ikuho; Kanamori, Hiroshi; Takaku, Fumimaro; Aburatani, Hiroyuki; Suzuki, Hiroshi; Kobari, Yukage; Miyai, Tatsuya; Cohen, E.H.; Wydro, R.; Housman, D.E.

1990-01-01

Two types of cDNAs for human macrophage scavenger receptors were cloned from a cDNA library derived from the phorbol ester-treated human monocytic cell line THP-1. The type I and type II human scavenger receptors encoded by these cDNAs are homologous (73% and 71% amino acid identity) to their previously characterized bovine counterparts and consist of six domains: cytoplasmic (I), membrane-spanning (II), spacer (III), α-helical coiled-coil (IV), collagen-like (V), and a type-specific C-terminal (VI). The receptor gene is located on human chromosome 8. The human receptors expressed in CHO-K1 cells mediated endocytosis of modified low density lipoproteins. Two mRNAs, 4.0 and 3.2 kilobases, have been detected in human liver, placenta, and brain. Immunohistochemical studies using an anti-peptide antibody which recognizes human scavenger receptors indicated the presence of the scavenger receptors in the macrophages of lipid-rich atherosclerotic lesions, suggesting the involvement of scavenger receptors in atherogenesis

Bistatic SAR: Proof of Concept.

Energy Technology Data Exchange (ETDEWEB)

Yocky, David A.; Doren, Neall E.; Bacon, Terry A.; Wahl, Daniel E.; Eichel, Paul H.; Jakowatz, Charles V,; Delaplain, Gilbert G.; Dubbert, Dale F.; Tise, Bertice L.; White, Kyle R.

2014-10-01

Typical synthetic aperture RADAR (SAR) imaging employs a co-located RADAR transmitter and receiver. Bistatic SAR imaging separates the transmitter and receiver locations. A bistatic SAR configuration allows for the transmitter and receiver(s) to be in a variety of geometric alignments. Sandia National Laboratories (SNL) / New Mexico proposed the deployment of a ground-based RADAR receiver. This RADAR receiver was coupled with the capability of digitizing and recording the signal collected. SNL proposed the possibility of creating an image of targets the illuminating SAR observes. This document describes the developed hardware, software, bistatic SAR configuration, and its deployment to test the concept of a ground-based bistatic SAR. In the proof-of-concept experiments herein, the RADAR transmitter will be a commercial SAR satellite and the RADAR receiver will be deployed at ground level, observing and capturing RADAR ground/targets illuminated by the satellite system.

B1-based SAR reconstruction using contrast source inversion-electric properties tomography (CSI-EPT)

NARCIS (Netherlands)

Balidemaj, Edmond; van den Berg, Cornelis A T; van Lier, A.L.H.M.W.; Nederveen, Aart J; Stalpers, Lukas J A; Crezee, Hans; Remis, Rob F

Specific absorption rate (SAR) assessment is essential for safety purposes during MR acquisition. Online SAR assessment is not trivial and requires, in addition, knowledge of the electric tissue properties and the electric fields in the human anatomy. In this study, the potential of the recently

B1-based SAR reconstruction using contrast source inversion–electric properties tomography (CSI-EPT)

NARCIS (Netherlands)

Balidemaj, E.; van den Berg, CAT; van Lier, ALHMW; Nederveen, AJ; Stalpers, LJA; Crezee, H; Remis, R.F.

2016-01-01

Specific absorption rate (SAR) assessment is essential for safety purposes during MR acquisition. Online SAR assessment is not trivial and requires, in addition, knowledge of the electric tissue properties and the electric fields in the human anatomy. In this study, the potential of the recently

The Seamless SAR Archive (SSARA) Project and Other SAR Activities at UNAVCO

Science.gov (United States)

Baker, S.; Crosby, C. J.; Meertens, C. M.; Fielding, E. J.; Bryson, G.; Buechler, B.; Nicoll, J.; Baru, C.

2014-12-01

The seamless synthetic aperture radar archive (SSARA) implements a seamless distributed access system for SAR data and derived data products (i.e. interferograms). SSARA provides a unified application programming interface (API) for SAR data search and results at the Alaska Satellite Facility and UNAVCO (WInSAR and EarthScope data archives) through the use of simple web services. A federated query service was developed using the unified APIs, providing users a single search interface for both archives. Interest from the international community has prompted an effort to incorporate ESA's Virtual Archive 4 Geohazard Supersites and Natural Laboratories (GSNL) collections and other archives into the federated query service. SSARA also provides Digital Elevation Model access for topographic correction via a simple web service through OpenTopography and tropospheric correction products through JPL's OSCAR service. Additionally, UNAVCO provides data storage capabilities for WInSAR PIs with approved TerraSAR-X and ALOS-2 proposals which allows easier distribution to US collaborators on associated proposals and facilitates data access through the SSARA web services. Further work is underway to incorporate federated data discovery for GSNL across SAR, GPS, and seismic datasets provided by web services from SSARA, GSAC, and COOPEUS.

Middle East Respiratory Syndrome Coronavirus Nonstructural Protein 16 Is Necessary for Interferon Resistance and Viral Pathogenesis

Energy Technology Data Exchange (ETDEWEB)

Menachery, Vineet D.; Gralinski, Lisa E.; Mitchell, Hugh D.; Dinnon, Kenneth H.; Leist, Sarah R.; Yount, Boyd L.; Graham, Rachel L.; McAnarney, Eileen T.; Stratton, Kelly G.; Cockrell, Adam S.; Debbink, Kari; Sims, Amy C.; Waters, Katrina M.; Baric, Ralph S.; Fernandez-Sesma, Ana

2017-11-15

Coronaviruses (CoVs) encode a mixture of highly conserved and novel genes, as well as genetic elements necessary for infection and pathogenesis, raising the possibility of common targets for attenuation and therapeutic design. In this study, we focused on highly conserved nonstructural protein 16 (NSP16), a viral 2'O-methyltransferase (2'O-MTase) that encodes critical functions in immune modulation and infection. Using reverse genetics, we disrupted a key motif in the conserved KDKE motif of Middle East respiratory syndrome CoV (MERS-CoV) NSP16 (D130A) and evaluated the effect on viral infection and pathogenesis. While the absence of 2'O-MTase activity had only a marginal impact on propagation and replication in Vero cells, dNSP16 mutant MERS-CoV demonstrated significant attenuation relative to the control both in primary human airway cell cultures andin vivo. Further examination indicated that dNSP16 mutant MERS-CoV had a type I interferon (IFN)-based attenuation and was partially restored in the absence of molecules of IFN-induced proteins with tetratricopeptide repeats. Importantly, the robust attenuation permitted the use of dNSP16 mutant MERS-CoV as a live attenuated vaccine platform protecting from a challenge with a mouse-adapted MERS-CoV strain. These studies demonstrate the importance of the conserved 2'O-MTase activity for CoV pathogenesis and highlight NSP16 as a conserved universal target for rapid live attenuated vaccine design in an expanding CoV outbreak setting.

IMPORTANCECoronavirus (CoV) emergence in both humans and livestock represents a significant threat to global public health, as evidenced by the sudden emergence of severe acute respiratory syndrome CoV (SARS-CoV), MERS-CoV, porcine epidemic diarrhea virus, and swine delta CoV in the 21st century. These studies describe an approach that

Characterization of muscarinic receptor subtypes in human tissues

International Nuclear Information System (INIS)

Giraldo, E.; Martos, F.; Gomez, A.; Garcia, A.; Vigano, M.A.; Ladinsky, H.; Sanchez de La Cuesta, F.

1988-01-01

The affinities of selective, pirenzepine and AF-DX 116, and classical, N-methylscopolamine and atropine, muscarinic cholinergic receptor antagonists were investigated in displacement binding experiments with [ 3 H]Pirenzepine and [ 3 H]N-methylscopolamine in membranes from human autoptic tissues (forebrain, cerebellum, atria, ventricle and submaxillary salivary glands). Affinity estimates of N-methylscopolamine and atropine indicated a non-selective profile. Pirenzepine showed differentiation between the M 1 neuronal receptor of the forebrain and the receptors in other tissues while AF-DX 116 clearly discriminated between muscarinic receptors of heart and glands. The results in human tissues confirm the previously described selectivity profiles of pirenzepine and AF-DX 116 in rat tissues. These findings thus reveal the presence also in man of three distinct muscarinic receptor subtypes: the neuronal M 1 , the cardiac M 2 and the glandular M 3

AUTOMATIC INTERPRETATION OF HIGH RESOLUTION SAR IMAGES: FIRST RESULTS OF SAR IMAGE SIMULATION FOR SINGLE BUILDINGS

Directory of Open Access Journals (Sweden)

J. Tao

2012-09-01

Full Text Available Due to the all-weather data acquisition capabilities, high resolution space borne Synthetic Aperture Radar (SAR plays an important role in remote sensing applications like change detection. However, because of the complex geometric mapping of buildings in urban areas, SAR images are often hard to interpret. SAR simulation techniques ease the visual interpretation of SAR images, while fully automatic interpretation is still a challenge. This paper presents a method for supporting the interpretation of high resolution SAR images with simulated radar images using a LiDAR digital surface model (DSM. Line features are extracted from the simulated and real SAR images and used for matching. A single building model is generated from the DSM and used for building recognition in the SAR image. An application for the concept is presented for the city centre of Munich where the comparison of the simulation to the TerraSAR-X data shows a good similarity. Based on the result of simulation and matching, special features (e.g. like double bounce lines, shadow areas etc. can be automatically indicated in SAR image.

Human orexin/hypocretin receptors form constitutive homo- and heteromeric complexes with each other and with human CB1 cannabinoid receptors

International Nuclear Information System (INIS)

Jäntti, Maria H.; Mandrika, Ilona; Kukkonen, Jyrki P.

2014-01-01

Highlights: • OX 1 and OX 2 orexin and CB 1 cannabinoid receptor dimerization was investigated. • Bioluminescence resonance energy transfer method was used. • All receptors readily formed constitutive homo- and heteromeric complexes. - Abstract: Human OX 1 orexin receptors have been shown to homodimerize and they have also been suggested to heterodimerize with CB 1 cannabinoid receptors. The latter has been suggested to be important for orexin receptor responses and trafficking. In this study, we wanted to assess the ability of the other combinations of receptors to also form similar complexes. Vectors for expression of human OX 1 , OX 2 and CB 1 receptors, C-terminally fused with either Renilla luciferase or GFP 2 green fluorescent protein variant, were generated. The constructs were transiently expressed in Chinese hamster ovary cells, and constitutive dimerization between the receptors was assessed by bioluminescence energy transfer (BRET). Orexin receptor subtypes readily formed homo- and hetero(di)mers, as suggested by significant BRET signals. CB 1 receptors formed homodimers, and they also heterodimerized with both orexin receptors. Interestingly, BRET efficiency was higher for homodimers than for almost all heterodimers. This is likely to be due to the geometry of the interaction; the putatively symmetric dimers may place the C-termini in a more suitable orientation in homomers. Fusion of luciferase to an orexin receptor and GFP 2 to CB 1 produced more effective BRET than the opposite fusions, also suggesting differences in geometry. Similar was seen for the OX 1 –OX 2 interaction. In conclusion, orexin receptors have a significant propensity to make homo- and heterodi-/oligomeric complexes. However, it is unclear whether this affects their signaling. As orexin receptors efficiently signal via endocannabinoid production to CB 1 receptors, dimerization could be an effective way of forming signal complexes with optimal cannabinoid concentrations

Unconventional magnetic phase separation in γ -CoV2O6

Science.gov (United States)

Shen, L.; Jellyman, E.; Forgan, E. M.; Blackburn, E.; Laver, M.; Canévet, E.; Schefer, J.; He, Z.; Itoh, M.

2017-08-01

We have explored the magnetism in the nongeometrically frustrated spin-chain system γ -CoV2O6 which possesses a complex magnetic exchange network. Our neutron diffraction patterns at low temperatures (T ≤TN=6.6 K) are best described by a model in which two magnetic phases coexist in a volume ratio 65(1) : 35(1), with each phase consisting of a single spin modulation. This model fits previous studies and our observations better than the model proposed by Lenertz et al. [J. Phys. Chem. C 118, 13981 (2014), 10.1021/jp503389c], which consisted of one phase with two spin modulations. By decreasing the temperature from TN, the minority phase of our model undergoes an incommensurate-commensurate lock-in transition at T*=5.6 K. Based on these results, we propose that phase separation is an alternative approach for degeneracy-lifting in frustrated magnets.

Severe acute respiratory syndrome (SARS)

Science.gov (United States)

SARS; Respiratory failure - SARS ... Complications may include: Respiratory failure Liver failure Heart failure ... 366. McIntosh K, Perlman S. Coronaviruses, including severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). ...

Alphacoronaviruses in New World Bats: Prevalence, Persistence, Phylogeny, and Potential for Interaction with Humans

Science.gov (United States)

Osborne, Christina; Cryan, Paul M.; O'Shea, Thomas J.; Oko, Lauren M.; Ndaluka, Christina; Calisher, Charles H.; Berglund, Andrew D.; Klavetter, Mead L.; Holmes, Kathryn V.; Dominguez, Samuel R.; Montgomery, Joel Mark

2011-01-01

Bats are reservoirs for many different coronaviruses (CoVs) as well as many other important zoonotic viruses. We sampled feces and/or anal swabs of 1,044 insectivorous bats of 2 families and 17 species from 21 different locations within Colorado from 2007 to 2009. We detected alphacoronavirus RNA in bats of 4 species: big brown bats (Eptesicus fuscus), 10% prevalence; long-legged bats (Myotis volans), 8% prevalence; little brown bats (Myotis lucifugus), 3% prevalence; and western long-eared bats (Myotis evotis), 2% prevalence. Overall, juvenile bats were twice as likely to be positive for CoV RNA as adult bats. At two of the rural sampling sites, CoV RNAs were detected in big brown and long-legged bats during the three sequential summers of this study. CoV RNA was detected in big brown bats in all five of the urban maternity roosts sampled throughout each of the periods tested. Individually tagged big brown bats that were positive for CoV RNA and later sampled again all became CoV RNA negative. Nucleotide sequences in the RdRp gene fell into 3 main clusters, all distinct from those of Old World bats. Similar nucleotide sequences were found in amplicons from gene 1b and the spike gene in both a big-brown and a long-legged bat, indicating that a CoV may be capable of infecting bats of different genera. These data suggest that ongoing evolution of CoVs in bats creates the possibility of a continued threat for emergence into hosts of other species. Alphacoronavirus RNA was detected at a high prevalence in big brown bats in roosts in close proximity to human habitations (10%) and known to have direct contact with people (19%), suggesting that significant potential opportunities exist for cross-species transmission of these viruses. Further CoV surveillance studies in bats throughout the Americas are warranted.

Alphacoronaviruses in New World bats: prevalence, persistence, phylogeny, and potential for interaction with humans.

Directory of Open Access Journals (Sweden)

Christina Osborne

2011-05-01

Full Text Available Bats are reservoirs for many different coronaviruses (CoVs as well as many other important zoonotic viruses. We sampled feces and/or anal swabs of 1,044 insectivorous bats of 2 families and 17 species from 21 different locations within Colorado from 2007 to 2009. We detected alphacoronavirus RNA in bats of 4 species: big brown bats (Eptesicus fuscus, 10% prevalence; long-legged bats (Myotis volans, 8% prevalence; little brown bats (Myotis lucifugus, 3% prevalence; and western long-eared bats (Myotis evotis, 2% prevalence. Overall, juvenile bats were twice as likely to be positive for CoV RNA as adult bats. At two of the rural sampling sites, CoV RNAs were detected in big brown and long-legged bats during the three sequential summers of this study. CoV RNA was detected in big brown bats in all five of the urban maternity roosts sampled throughout each of the periods tested. Individually tagged big brown bats that were positive for CoV RNA and later sampled again all became CoV RNA negative. Nucleotide sequences in the RdRp gene fell into 3 main clusters, all distinct from those of Old World bats. Similar nucleotide sequences were found in amplicons from gene 1b and the spike gene in both a big-brown and a long-legged bat, indicating that a CoV may be capable of infecting bats of different genera. These data suggest that ongoing evolution of CoVs in bats creates the possibility of a continued threat for emergence into hosts of other species. Alphacoronavirus RNA was detected at a high prevalence in big brown bats in roosts in close proximity to human habitations (10% and known to have direct contact with people (19%, suggesting that significant potential opportunities exist for cross-species transmission of these viruses. Further CoV surveillance studies in bats throughout the Americas are warranted.

Alphacoronaviruses in new World bats: Prevalence, persistence, phylogeny, and potential for interaction with humans

Science.gov (United States)

Osborne, C.; Cryan, P.M.; O'Shea, T.J.; Oko, L.M.; Ndaluka, C.; Calisher, C.H.; Berglund, A.D.; Klavetter, M.L.; Bowen, R.A.; Holmes, K.V.; Dominguez, S.R.

2011-01-01

Bats are reservoirs for many different coronaviruses (CoVs) as well as many other important zoonotic viruses. We sampled feces and/or anal swabs of 1,044 insectivorous bats of 2 families and 17 species from 21 different locations within Colorado from 2007 to 2009. We detected alphacoronavirus RNA in bats of 4 species: big brown bats (Eptesicus fuscus), 10% prevalence; long-legged bats (Myotis volans), 8% prevalence; little brown bats (Myotis lucifugus), 3% prevalence; and western long-eared bats (Myotis evotis), 2% prevalence. Overall, juvenile bats were twice as likely to be positive for CoV RNA as adult bats. At two of the rural sampling sites, CoV RNAs were detected in big brown and long-legged bats during the three sequential summers of this study. CoV RNA was detected in big brown bats in all five of the urban maternity roosts sampled throughout each of the periods tested. Individually tagged big brown bats that were positive for CoV RNA and later sampled again all became CoV RNA negative. Nucleotide sequences in the RdRp gene fell into 3 main clusters, all distinct from those of Old World bats. Similar nucleotide sequences were found in amplicons from gene 1b and the spike gene in both a big-brown and a long-legged bat, indicating that a CoV may be capable of infecting bats of different genera. These data suggest that ongoing evolution of CoVs in bats creates the possibility of a continued threat for emergence into hosts of other species. Alphacoronavirus RNA was detected at a high prevalence in big brown bats in roosts in close proximity to human habitations (10%) and known to have direct contact with people (19%), suggesting that significant potential opportunities exist for cross-species transmission of these viruses. Further CoV surveillance studies in bats throughout the Americas are warranted.

The aryl hydrocarbon receptor and glucocorticoid receptor interact to activate human metallothionein 2A

Energy Technology Data Exchange (ETDEWEB)

Sato, Shoko, E-mail: satosho@rs.tus.ac.jp [Laboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555 (Japan); Shirakawa, Hitoshi, E-mail: shirakah@m.tohoku.ac.jp [Laboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555 (Japan); Tomita, Shuhei, E-mail: tomita@med.tottori-u.ac.jp [Division of Molecular Pharmacology, Department of Pathophysiological and Therapeutic Science, Yonago 683-8503 (Japan); Tohkin, Masahiro, E-mail: tohkin@phar.nagoya-cu.ac.jp [Department of Medical Safety Science, Graduate School of Pharmaceutical Science, Nagoya City University, Nagoya 267-8603 (Japan); Gonzalez, Frank J., E-mail: gonzalef@mail.nih.gov [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Komai, Michio, E-mail: mkomai@m.tohoku.ac.jp [Laboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555 (Japan)

2013-11-15

Although the aryl hydrocarbon receptor (AHR) and glucocorticoid receptor (GR) play essential roles in mammalian development, stress responses, and other physiological events, crosstalk between these receptors has been the subject of much debate. Metallothioneins are classic glucocorticoid-inducible genes that were reported to increase upon treatment with AHR agonists in rodent tissues and cultured human cells. In this study, the mechanism of human metallothionein 2A (MT2A) gene transcription activation by AHR was investigated. Cotreatment with 3-methylcholanthrene and dexamethasone, agonists of AHR and GR respectively, synergistically increased MT2A mRNA levels in HepG2 cells. MT2A induction was suppressed by RNA interference against AHR or GR. Coimmunoprecipitation experiments revealed a physical interaction between AHR and GR proteins. Moreover, chromatin immunoprecipitation assays indicated that AHR was recruited to the glucocorticoid response element in the MT2A promoter. Thus, we provide a novel mechanism whereby AHR modulates expression of human MT2A via the glucocorticoid response element and protein–protein interactions with GR. - Highlights: • Aryl hydrocarbon receptor forms a complex with glucocorticoid receptor in cells. • Human metallothionein gene is regulated by the AHR and GR interaction. • AHR–GR complex binds to glucocorticoid response element in metallothionein gene. • We demonstrated a novel transcriptional mechanism via AHR and GR interaction.

The aryl hydrocarbon receptor and glucocorticoid receptor interact to activate human metallothionein 2A

International Nuclear Information System (INIS)

Sato, Shoko; Shirakawa, Hitoshi; Tomita, Shuhei; Tohkin, Masahiro; Gonzalez, Frank J.; Komai, Michio

2013-01-01

Although the aryl hydrocarbon receptor (AHR) and glucocorticoid receptor (GR) play essential roles in mammalian development, stress responses, and other physiological events, crosstalk between these receptors has been the subject of much debate. Metallothioneins are classic glucocorticoid-inducible genes that were reported to increase upon treatment with AHR agonists in rodent tissues and cultured human cells. In this study, the mechanism of human metallothionein 2A (MT2A) gene transcription activation by AHR was investigated. Cotreatment with 3-methylcholanthrene and dexamethasone, agonists of AHR and GR respectively, synergistically increased MT2A mRNA levels in HepG2 cells. MT2A induction was suppressed by RNA interference against AHR or GR. Coimmunoprecipitation experiments revealed a physical interaction between AHR and GR proteins. Moreover, chromatin immunoprecipitation assays indicated that AHR was recruited to the glucocorticoid response element in the MT2A promoter. Thus, we provide a novel mechanism whereby AHR modulates expression of human MT2A via the glucocorticoid response element and protein–protein interactions with GR. - Highlights: • Aryl hydrocarbon receptor forms a complex with glucocorticoid receptor in cells. • Human metallothionein gene is regulated by the AHR and GR interaction. • AHR–GR complex binds to glucocorticoid response element in metallothionein gene. • We demonstrated a novel transcriptional mechanism via AHR and GR interaction

A Novel Cellular Handset Design for an Enhanced Antenna Performance and a Reduced SAR in the Human Head

Directory of Open Access Journals (Sweden)

Salah I. Al-Mously

2008-01-01

Full Text Available This paper presents a novel cellular handset design with a bottom-mounted short loaded-whip antenna. This new handset design is modeled and simulated using a finite difference time-domain (FDTD-based platform SEMCAD. The proposed handset is based on a current commercially available bar-phone type with a curvature shape, keypad positioned above the screen, and top-mounted antenna. The specific absorption rates (SARs are determined computationally in the specific anthropomorphic mannequin (SAM and anatomically correct model of a human head when exposed to the EM-field radiation of the proposed cellular handset and the handset with top-mounted antenna. The two cellular handsets are simulated to operate at both GSM standards, 900 MHz as well as 1800 MHz, having different antenna dimensions and intput power of 0.6 W and 0.125 W, respectively. The proposed human hand holding the two handset models is a semirealistic hand model consists of three tissues: skin, muscle, and bone. The simulations are conducted with handset positions based on the IEEE standard 1528-2003. The results show that the proposed handset has a significant improvement of antenna efficiency when it is hand-held close to head, as compared with the handset of top-mounted antenna. Also, the results show that a significant reduction of the induced SAR in the human head-tissues can be achieved with the proposed handset.

Bioelectronic tongue using heterodimeric human taste receptor for the discrimination of sweeteners with human-like performance.

Science.gov (United States)

Song, Hyun Seok; Jin, Hye Jun; Ahn, Sae Ryun; Kim, Daesan; Lee, Sang Hun; Kim, Un-Kyung; Simons, Christopher T; Hong, Seunghun; Park, Tai Hyun

2014-10-28

The sense of taste helps humans to obtain information and form a picture of the world by recognizing chemicals in their environments. Over the past decade, large advances have been made in understanding the mechanisms of taste detection and mimicking its capability using artificial sensor devices. However, the detection capability of previous artificial taste sensors has been far inferior to that of animal tongues, in terms of its sensitivity and selectivity. Herein, we developed a bioelectronic tongue using heterodimeric human sweet taste receptors for the detection and discrimination of sweeteners with human-like performance, where single-walled carbon nanotube field-effect transistors were functionalized with nanovesicles containing human sweet taste receptors and used to detect the binding of sweeteners to the taste receptors. The receptors are heterodimeric G-protein-coupled receptors (GPCRs) composed of human taste receptor type 1 member 2 (hTAS1R2) and human taste receptor type 1 member 3 (hTAS1R3), which have multiple binding sites and allow a human tongue-like broad selectivity for the detection of sweeteners. This nanovesicle-based bioelectronic tongue can be a powerful tool for the detection of sweeteners as an alternative to labor-intensive and time-consuming cell-based assays and the sensory evaluation panels used in the food and beverage industry. Furthermore, this study also allows the artificial sensor to exam the functional activity of dimeric GPCRs.

p53 down-regulates SARS coronavirus replication and is targeted by the SARS-unique domain and PLpro via E3 ubiquitin ligase RCHY1

Science.gov (United States)

Ma-Lauer, Yue; Carbajo-Lozoya, Javier; Müller, Marcel A.; Deng, Wen; Lei, Jian; Meyer, Benjamin; Kusov, Yuri; von Brunn, Brigitte; Bairad, Dev Raj; Hünten, Sabine; Drosten, Christian; Hermeking, Heiko; Leonhardt, Heinrich; Mann, Matthias; Hilgenfeld, Rolf; von Brunn, Albrecht

2016-01-01

Highly pathogenic severe acute respiratory syndrome coronavirus (SARS-CoV) has developed strategies to inhibit host immune recognition. We identify cellular E3 ubiquitin ligase ring-finger and CHY zinc-finger domain-containing 1 (RCHY1) as an interacting partner of the viral SARS-unique domain (SUD) and papain-like protease (PLpro), and, as a consequence, the involvement of cellular p53 as antagonist of coronaviral replication. Residues 95–144 of RCHY1 and 389–652 of SUD (SUD-NM) subdomains are crucial for interaction. Association with SUD increases the stability of RCHY1 and augments RCHY1-mediated ubiquitination as well as degradation of p53. The calcium/calmodulin-dependent protein kinase II delta (CAMK2D), which normally influences RCHY1 stability by phosphorylation, also binds to SUD. In vivo phosphorylation shows that SUD does not regulate phosphorylation of RCHY1 via CAMK2D. Similarly to SUD, the PLpros from SARS-CoV, MERS-CoV, and HCoV-NL63 physically interact with and stabilize RCHY1, and thus trigger degradation of endogenous p53. The SARS-CoV papain-like protease is encoded next to SUD within nonstructural protein 3. A SUD–PLpro fusion interacts with RCHY1 more intensively and causes stronger p53 degradation than SARS-CoV PLpro alone. We show that p53 inhibits replication of infectious SARS-CoV as well as of replicons and human coronavirus NL63. Hence, human coronaviruses antagonize the viral inhibitor p53 via stabilizing RCHY1 and promoting RCHY1-mediated p53 degradation. SUD functions as an enhancer to strengthen interaction between RCHY1 and nonstructural protein 3, leading to a further increase in in p53 degradation. The significance of these findings is that down-regulation of p53 as a major player in antiviral innate immunity provides a long-sought explanation for delayed activities of respective genes. PMID:27519799

SAR Target Recognition via Supervised Discriminative Dictionary Learning and Sparse Representation of the SAR-HOG Feature

Directory of Open Access Journals (Sweden)

Shengli Song

2016-08-01

Full Text Available Automatic target recognition (ATR in synthetic aperture radar (SAR images plays an important role in both national defense and civil applications. Although many methods have been proposed, SAR ATR is still very challenging due to the complex application environment. Feature extraction and classification are key points in SAR ATR. In this paper, we first design a novel feature, which is a histogram of oriented gradients (HOG-like feature for SAR ATR (called SAR-HOG. Then, we propose a supervised discriminative dictionary learning (SDDL method to learn a discriminative dictionary for SAR ATR and propose a strategy to simplify the optimization problem. Finally, we propose a SAR ATR classifier based on SDDL and sparse representation (called SDDLSR, in which both the reconstruction error and the classification error are considered. Extensive experiments are performed on the MSTAR database under standard operating conditions and extended operating conditions. The experimental results show that SAR-HOG can reliably capture the structures of targets in SAR images, and SDDL can further capture subtle differences among the different classes. By virtue of the SAR-HOG feature and SDDLSR, the proposed method achieves the state-of-the-art performance on MSTAR database. Especially for the extended operating conditions (EOC scenario “Training 17 ∘ —Testing 45 ∘ ”, the proposed method improves remarkably with respect to the previous works.

SU-F-I-27: Measurement of SAR and Temperature Elevation During MRI Scans

Energy Technology Data Exchange (ETDEWEB)

Seo, Y [Korea Research Institute of Standards and Science, Daejeon (Korea, Republic of)

2016-06-15

Purpose: The poor reliability and repeatability of the manufacturer-reported SAR values on clinical MRI systems have been acknowledged. The purpose of this study is to not only measure SAR values, but also RF-induced temperature elevation at 1.5 and 3T MRI systems. Methods: SAR measurement experiment was performed at 1.5 and 3T. Three MRI RF sequences (T1w TSE, T1w inversion recovery, and T2w TSE) with imaging parameters were selected. A hydroxyl-ethylcelluose (HEC) gelled saline phantom mimicking human body tissue was made. Human torso phantom were constructed, based on Korean adult standard anthropometric reference data (Fig.1). FDTD method was utilized to calculate the SAR distribution using Sim4Life software. Based on the results of the simulation, 4 electrical field (E-field) sensors were located inside the phantom. 55 Fiber Bragg Grating (FBG) temperature sensors (27 sensors in upper and lower cover lids, and one sensor located in the center as a reference) were located inside the phantom to measure temperature change during MRI scan (Fig.2). Results: Simulation shows that SAR value is 0.4 W/kg in the periphery and 0.001 W/kg in the center (Fig.2). One 1.5T and one of two 3T MRI systems represent that the measured SAR values were lower than MRI scanner-reported SAR values. However, the other 3T MRI scanner shows that the averaged SAR values measured by probe 2, 3, and 4 are 6.83, 7.59, and 6.01 W/kg, compared to MRI scanner-reported whole body SAR value (<1.5 W/kg) for T2w TSE (Table 1). The temperature elevation measured by FBG sensors is 5.2°C in the lateral shoulder, 5.1°C in the underarm, 4.7°C in the anterior axilla, 4.8°C in the posterior axilla, and 4.8°C in the lateral waist for T2w TSE (Fig.3). Conclusion: It is essential to assess the safety of MRI system for patient by measuring accurate SAR deposited in the body during clinical MRI.

Human myometrial adrenergic receptors: identification of the beta-adrenergic receptor by [3H]dihydroalprenolol binding

International Nuclear Information System (INIS)

Hayashida, D.N.; Leung, R.; Goldfien, A.; Roberts, J.M.

1982-01-01

The radioactive beta-adrenergic antagonist [ 3 H] dihydroalprenolol (DHA) binds to particulate preparations of human myometrium in a manner compatible with binding to the beta-adrenergic receptor. The binding of DHA is rapid (attaining equilibrium in 12 minutes), readily reversible (half time = 16 minutes), high affinity (K/sub D/ = 0.50 nM), low capacity (Bmax = 70 fmoles/mg of protein), and stereoselective ([-]-propranolol is 100 times as potent as [+] -propranolol in inhibiting DHA binding). Adrenergic agonists competed for DHA binding sites in a manner compatible with beta-adrenergic interactions and mirrored β 2 pharmacologic potencies: isoproterenol > epinephrine >> norepinephrine. Studies in which zinterol, a β 2 -adrenergic agonist, competed for DHA binding sites in human myometrial particulate indicated that at least 87% of the beta-adrenergic receptors present are β 2 -adrenergic receptors. Binding of DHA to human myometrial beta-adrenergic receptors provides a tool which may be used in the examination of gonadal hormonal modification of adrenergic response in human uterus as well as in the analysis of beta-adrenergic agents as potentially useful tocolytic agents

Phase I dose-escalation study of the c-Met tyrosine kinase inhibitor SAR125844 in Asian patients with advanced solid tumors, including patients with MET-amplified gastric cancer

OpenAIRE

Shitara, Kohei; Kim, Tae Min; Yokota, Tomoya; Goto, Masahiro; Satoh, Taroh; Ahn, Jin-Hee; Kim, Hyo Song; Assadourian, Sylvie; Gomez, Corinne; Harnois, Marzia; Hamauchi, Satoshi; Kudo, Toshihiro; Doi, Toshihido; Bang, Yung-Jue

2017-01-01

SAR125844 is a potent and selective inhibitor of the c-Met kinase receptor. This was an open-label, phase I, multicenter, dose-escalation, and dose-expansion trial of SAR125844 in Asian patients with solid tumors, a subgroup of whom had gastric cancer and MET amplification (NCT01657214). SAR125844 was administered by intravenous infusion (260–570 mg/m2) on days 1, 8, 15, and 22 of each 28-day cycle. Objectives were to determine the maximum tolerated dose (MTD) and to evaluate SAR125844 safety...

Sigma and opioid receptors in human brain tumors

International Nuclear Information System (INIS)

Thomas, G.E.; Szuecs, M.; Mamone, J.Y.; Bem, W.T.; Rush, M.D.; Johnson, F.E.; Coscia, C.J.

1990-01-01

Human brain tumors and nude mouse-borne human neuroblastomas and gliomas were analyzed for sigma and opioid receptor content. Sigma binding was assessed using [ 3 H] 1, 3-di-o-tolylguanidine (DTG), whereas opioid receptor subtypes were measured with tritiated forms of the following: μ, [D-ala 2 , mePhe 4 , gly-ol 5 ] enkephalin (DAMGE); κ, ethylketocyclazocine (EKC) or U69,593; δ, [D-pen 2 , D-pen 5 ] enkephalin (DPDPE) or [D-ala 2 , D-leu 5 ] enkephalin (DADLE) with μ suppressor present. Binding parameters were estimated by homologous displacement assays followed by analysis using the LIGAND program. Sigma binding was detected in 15 of 16 tumors examined with very high levels found in a brain metastasis from an adenocarcinoma of lung and a human neuroblastoma (SK-N-MC) passaged in nude mice. κ opioid receptor binding was detected in 4 of 4 glioblastoma multiforme specimens and 2 of 2 human astrocytoma cell lines tested but not in the other brain tumors analyzed

Magnetic moment distribution in Co-V alloys

International Nuclear Information System (INIS)

Cable, J.W.

1982-01-01

Magnetization and neutron scattering measurements were made on Co-V alloys containing 10, 15, and 20 at.% V to determine the local environment effects on the magnetic moment distribution in this system. The magnetization data agree with earlier results and suggest the presence of some hcp phase in the 10% sample. This was confirmed by the neutron data which showed both fcc and hcp phases in an approximate 4:1 volume ratio for this alloy. The other two samples were single phase fcc but the 15% alloy was disordered while the 20% alloy was ordered in the Cu 3 Au-type structure with the maximum order consistent with the concentration. In this ordered alloy, the excess Co occupies the V sites. These ''wrong sited'' Co atoms have 12 Co nearest neighbors and larger magnetic moments than the ''properly sited'' Co atoms which have an average of 8.8 Co nearest neighbors. The average moments associated with these two types of sites were determined from flipping-ratio measurements on the superlattice and fundamental reflections. The values obtained are 0.28 μ/sub B//Co for the proper-site atoms and 1.3 μ/sub B//Co for the wrong-site atoms. Average moments at the Co and V sites were determined from the diffuse scattering for the 10% and 15% alloys. The results are 1.38 μ/sub B//Co and -0.26 μ/sub B//V for the 10% sample and 1.05 μ/sub B//Co and -0.11 μ/sub B//V for the 15% sample

Simultaneous Observation Data of GB-SAR/PiSAR to Detect Flooding in an Urban Area

Directory of Open Access Journals (Sweden)

Manabu Watanabe

2010-01-01

Full Text Available We analyzed simultaneous observation data with ground-based synthetic aperture radar (GB-SAR and airborne SAR (PiSAR over a flood test site at which a simple house was constructed in a field. The PiSAR σ∘ under flood condition was 0.9 to 3.4 dB higher than that under nonflood condition. GB-SAR gives high spatial resolution as we could identify a single scattering component and a double bounce component from the house. GB-SAR showed that the σ∘ difference between the flooding and nonflooding conditions came from the double bounce scattering. We also confirm that the entropy is a sensitive parameter in the eigenvalue decomposition parameters, if the scattering process is dominated by the double bounce scattering. We conclude that σ∘ and entropy are a good parameter to be used to detect flooding, not only in agricultural and forest regions, but also in urban areas. We also conclude that GB-SAR is a powerful tool to supplement satellite and airborne observation, which has a relatively low spatial resolution.

Simultaneous Observation Data of GB-SAR/PiSAR to Detect Flooding in an Urban Area

Directory of Open Access Journals (Sweden)

Shimada Masanobu

2010-01-01

Full Text Available Abstract We analyzed simultaneous observation data with ground-based synthetic aperture radar (GB-SAR and airborne SAR (PiSAR over a flood test site at which a simple house was constructed in a field. The PiSAR under flood condition was 0.9 to 3.4 dB higher than that under nonflood condition. GB-SAR gives high spatial resolution as we could identify a single scattering component and a double bounce component from the house. GB-SAR showed that the difference between the flooding and nonflooding conditions came from the double bounce scattering. We also confirm that the entropy is a sensitive parameter in the eigenvalue decomposition parameters, if the scattering process is dominated by the double bounce scattering. We conclude that and entropy are a good parameter to be used to detect flooding, not only in agricultural and forest regions, but also in urban areas. We also conclude that GB-SAR is a powerful tool to supplement satellite and airborne observation, which has a relatively low spatial resolution.

Detection of melatonin receptor mRNA in human muscle

International Nuclear Information System (INIS)

Li Lei

2004-01-01

To verify the expression of melatonin receptor mRNA in human, muscle, muscle beside vertebrae was collected to obtain total RNA and the mRNA of melatonin receptor was detected by RT-PCR method. The electrophoretic results of RT-PCR products by mt 1 and MT 2 primer were all positive and the sequence is corresponding with human melatonin receptor cDNA. It suggests that melatonin may act on the muscle beside vertebrae directly and regulate its growth and development. (authors)

Characterization of receptors for recombinant human tumor necrosis factor-alpha from human placental membranes

International Nuclear Information System (INIS)

Aiyer, R.A.; Aggarwal, B.B.

1990-01-01

High affinity receptors for recombinant human tumor necrosis factor-alpha (rhTNF-alpha) were identified on membranes prepared from full term human placenta. Highly purified rhTNF-alpha iodinated by the iodogen method was found to bind placental membranes in a displaceable manner with an approximate dissociation constant (KD) of 1.9 nM. The membrane bound TNF-alpha receptor could be solubilized by several detergents with optimum extraction being obtained with 1% Triton X-100. The binding of 125I-rhTNF-alpha to the solubilized receptor was found to be time and temperature dependent, yielding maximum binding within 1 h, 24 h and 48 h at 37 degrees C, 24 degrees C and 4 degrees C, respectively. However, the maximum binding obtainable at 4 degrees C was only 40% of that at 37 degrees C. The binding 125I-rhTNF-alpha to solubilized placental membrane extracts was displaceable by unlabeled rhTNF-alpha, but not by a related protein recombinant human tumor necrosis factor-beta (rhTNF-beta; previously called lymphotoxin). This is similar to the behavior of TNF-alpha receptors derived from detergent-solubilized cell extracts, although on intact cells, both rhTNF-alpha and rhTNF-beta bind with equal affinity to TNF receptors. The Scatchard analysis of the binding data of the solubilized receptor revealed high affinity binding sites with a KD of approximately 0.5 nM and a receptor concentration of about 1 pmole/mg protein. Gel filtration of the solubilized receptor-ligand complexes on Sephacryl S-300 revealed two different peaks of radioactivity at approximate molecular masses of 50,000 Da and 400,000 Da. The 400,000 dalton peak corresponded to the receptor-ligand complex. Overall, our results suggest that high affinity receptors for TNF-alpha are present on human placental membranes and provide evidence that these receptors may be different from that of rhTNF-beta

SAR: Stroke Authorship Recognition

KAUST Repository

Shaheen, Sara

2015-10-15

Are simple strokes unique to the artist or designer who renders them? If so, can this idea be used to identify authorship or to classify artistic drawings? Also, could training methods be devised to develop particular styles? To answer these questions, we propose the Stroke Authorship Recognition (SAR) approach, a novel method that distinguishes the authorship of 2D digitized drawings. SAR converts a drawing into a histogram of stroke attributes that is discriminative of authorship. We provide extensive classification experiments on a large variety of data sets, which validate SAR\\'s ability to distinguish unique authorship of artists and designers. We also demonstrate the usefulness of SAR in several applications including the detection of fraudulent sketches, the training and monitoring of artists in learning a particular new style and the first quantitative way to measure the quality of automatic sketch synthesis tools. © 2015 The Eurographics Association and John Wiley & Sons Ltd.

Bistatic SAR: Imagery & Image Products.

Energy Technology Data Exchange (ETDEWEB)

Yocky, David A.; Wahl, Daniel E.; Jakowatz, Charles V,

2014-10-01

While typical SAR imaging employs a co-located (monostatic) RADAR transmitter and receiver, bistatic SAR imaging separates the transmitter and receiver locations. The transmitter and receiver geometry determines if the scattered signal is back scatter, forward scatter, or side scatter. The monostatic SAR image is backscatter. Therefore, depending on the transmitter/receiver collection geometry, the captured imagery may be quite different that that sensed at the monostatic SAR. This document presents imagery and image products formed from captured signals during the validation stage of the bistatic SAR research. Image quality and image characteristics are discussed first. Then image products such as two-color multi-view (2CMV) and coherent change detection (CCD) are presented.

Modeling Human Body Using Four-Pole Debye Model in Piecewise Linear Recursive Convolution FDTD Method for the SAR Calculation in the Case of Vehicular Antenna

Directory of Open Access Journals (Sweden)

Ammar Guellab

2018-01-01

Full Text Available We propose an efficient finite difference time domain (FDTD method based on the piecewise linear recursive convolution (PLRC technique to evaluate the human body exposure to electromagnetic (EM radiation. The source of radiation considered in this study is a high-power antenna, mounted on a military vehicle, covering a broad band of frequency (100 MHz–3 GHz. The simulation is carried out using a nonhomogeneous human body model which takes into consideration most of the internal body tissues. The human tissues are modeled by a four-pole Debye model which is derived from experimental data by using particle swarm optimization (PSO. The human exposure to EM radiation is evaluated by computing the local and whole-body average specific absorption rate (SAR for each occupant. The higher in-tissue electric field intensity points are localized, and the SAR values are compared with the crew safety standard recommendations. The accuracy of the proposed PLRC-FDTD approach and the matching of the Debye model with the experimental data are verified in this study.

Crop Classification by Polarimetric SAR

DEFF Research Database (Denmark)

Skriver, Henning; Svendsen, Morten Thougaard; Nielsen, Flemming

1999-01-01

Polarimetric SAR-data of agricultural fields have been acquired by the Danish polarimetric L- and C-band SAR (EMISAR) during a number of missions at the Danish agricultural test site Foulum during 1995. The data are used to study the classification potential of polarimetric SAR data using...

Maintenance of prolactin receptors in human breast cancer

International Nuclear Information System (INIS)

Ben-David, M.; Dror, Y.; Biran, S.

1981-01-01

Breast tissue specimens of 110 women with various stages of breast cancer were tested in vitro to determine their specific binding sites for human prolactin. In contrast to the case of steroid receptors, binding sites for prolactin were found in the vast majority of breast cancer tissue. Distribution profiles giving amount of prolactin receptor and their affinity coefficients were found to be similar in the tissues of women whose ages, hormonal status, or stage of breast cancer varied. These findings show that in contrast to steroid receptors, human breast cancer tissue maintains binding sites for prolactin. The findings also indicate that there may be a higher dependency of breast cancer on prolactin than on steroids. Clinical trials must be carried out to determine the role of ''positive'' prolactin receptors in prognosis and prediction of response to future hormone therapy. (author)

A mouse-adapted SARS-coronavirus causes disease and mortality in BALB/c mice.

Directory of Open Access Journals (Sweden)

Anjeanette Roberts

2007-01-01

Full Text Available No single animal model for severe acute respiratory syndrome (SARS reproduces all aspects of the human disease. Young inbred mice support SARS-coronavirus (SARS-CoV replication in the respiratory tract and are available in sufficient numbers for statistical evaluation. They are relatively inexpensive and easily accessible, but their use in SARS research is limited because they do not develop illness following infection. Older (12- to 14-mo-old BALB/c mice develop clinical illness and pneumonitis, but they can be hard to procure, and immune senescence complicates pathogenesis studies. We adapted the SARS-CoV (Urbani strain by serial passage in the respiratory tract of young BALB/c mice. Fifteen passages resulted in a virus (MA15 that is lethal for mice following intranasal inoculation. Lethality is preceded by rapid and high titer viral replication in lungs, viremia, and dissemination of virus to extrapulmonary sites accompanied by lymphopenia, neutrophilia, and pathological changes in the lungs. Abundant viral antigen is extensively distributed in bronchial epithelial cells and alveolar pneumocytes, and necrotic cellular debris is present in airways and alveoli, with only mild and focal pneumonitis. These observations suggest that mice infected with MA15 die from an overwhelming viral infection with extensive, virally mediated destruction of pneumocytes and ciliated epithelial cells. The MA15 virus has six coding mutations associated with adaptation and increased virulence; when introduced into a recombinant SARS-CoV, these mutations result in a highly virulent and lethal virus (rMA15, duplicating the phenotype of the biologically derived MA15 virus. Intranasal inoculation with MA15 reproduces many aspects of disease seen in severe human cases of SARS. The availability of the MA15 virus will enhance the use of the mouse model for SARS because infection with MA15 causes morbidity, mortality, and pulmonary pathology. This virus will be of value as

Polarimetric scattering and SAR information retrieval

CERN Document Server

Jin, Ya-Qiu

2013-01-01

Taking an innovative look at Synthetic Aperture Radar (SAR), this practical reference fully covers new developments in SAR and its various methodologies and enables readers to interpret SAR imagery An essential reference on polarimetric Synthetic Aperture Radar (SAR), this book uses scattering theory and radiative transfer theory as a basis for its treatment of topics. It is organized to include theoretical scattering models and SAR data analysis techniques, and presents cutting-edge research on theoretical modelling of terrain surface. The book includes quantitative app

Platelet-derived growth factor receptors in the human central nervous system : autoradiographic distribution and receptor densities in multiple sclerosis

NARCIS (Netherlands)

De Keyser, J; Wilczak, N

1997-01-01

Platelet derived growth factor (PDGF) receptors were studied in postmortem adult human brain and cervical spinal cord using autoradiography with human recombinant I-125-PDGF-BB. PDGF-BB binds to the three different dimers of PDGF receptors (alpha alpha, alpha beta and beta beta) PDGF receptors were

Dopamine receptors in human gastrointestinal mucosa

International Nuclear Information System (INIS)

Hernandez, D.E.; Mason, G.A.; Walker, C.H.; Valenzuela, J.E.

1987-01-01

Dopamine is a putative enteric neurotransmitter that has been implicated in exocrine secretory and motility functions of the gastrointestinal tract of several mammalian species including man. This study was designed to determine the presence of dopamine binding sites in human gastric and duodenal mucosa and to describe certain biochemical characteristics of these enteric receptor sites. The binding assay was performed in triplicate with tissue homogenates obtained from healthy volunteers of both sexes using 3 H-dopamine as a ligand. The extent of nonspecific binding was determined in the presence of a 100-fold excess of unlabeled dopamine. Scatchard analysis performed with increasing concentrations of 3 H-dopamine (20-500 nM) revealed a single class of saturable dopamine binding sites in gastric and duodenal mucosa. The results of this report demonstrate the presence of specific dopamine receptors in human gastric and duodenal mucosa. These biochemical data suggest that molecular abnormalities of these receptor sites may be operative in the pathogenesis of important gastrointestinal disorders. 33 references, 2 figures

Cellular receptors for human enterovirus species A

Directory of Open Access Journals (Sweden)

Yorihiro eNishimura

2012-03-01

Full Text Available Human enterovirus species A (HEV-A is one of the four species of HEV in the genus Enterovirus in the family Picornaviridae. Among HEV-A, coxsackievirus A16 (CVA16 and enterovirus 71 (EV71 are the major causative agents of hand, foot, and mouth disease (HFMD. Some other types of HEV-A are commonly associated with herpangina. Although HFMD and herpangina due to HEV-A are common febrile diseases among infants and children, EV71 can cause various neurological diseases, such as aseptic meningitis and fatal encephalitis.Recently, two human transmembrane proteins, P-selectin glycoprotein ligand-1 (PSGL-1 and scavenger receptor class B, member 2 (SCARB2, were identified as functional receptors for EV71 and CVA16. In in vitro infection experiments using the prototype HEV-A strains, PSGL-1 and SCARB2 could be responsible for the specific receptors for EV71 and CVA16. However, the involvement of both receptors in the in vitro and in vivo infections of clinical isolates of HEV-A has not been clarified yet. To elucidate a diverse array of the clinical outcome of HEV-A-associated diseases, the identification and characterization of HEV-A receptors may provide useful information in understanding the HEV-A pathogenesis at a molecular level.

Pattern of hormone receptors and human epidermal growth factor ...

African Journals Online (AJOL)

Introduction: Breast cancer is the most common cancer among women globally. With immunohistochemistry (IHC), breast cancer is classified into four groups based on IHC profile of estrogen receptor (ER)/progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2/neu) expression, positive (+) and/or ...

Design and realization of an active SAR calibrator for TerraSAR-X

Science.gov (United States)

Dummer, Georg; Lenz, Rainer; Lutz, Benjamin; Kühl, Markus; Müller-Glaser, Klaus D.; Wiesbeck, Werner

2005-10-01

TerraSAR-X is a new earth observing satellite which will be launched in spring 2006. It carries a high resolution X-band SAR sensor. For high image data quality, accurate ground calibration targets are necessary. This paper describes a novel system concept for an active and highly integrated, digitally controlled SAR system calibrator. A total of 16 active transponder and receiver systems and 17 receiver only systems will be fabricated for a calibration campaign. The calibration units serve for absolute radiometric calibration of the SAR image data. Additionally, they are equipped with an extra receiver path for two dimensional satellite antenna pattern recognition. The calibrator is controlled by a dedicated digital Electronic Control Unit (ECU). The different voltages needed by the calibrator and the ECU are provided by the third main unit called Power Management Unit (PMU).

Identification of agonists for a group of human odorant receptors

Directory of Open Access Journals (Sweden)

Daniela eGonzalez-Kristeller

2015-03-01

Full Text Available Olfaction plays a critical role in several aspects of the human life. Odorants are detected by hundreds of odorant receptors (ORs which belong to the superfamily of G protein-coupled receptors. These receptors are expressed in the olfactory sensory neurons of the nose. The information provided by the activation of different combinations of ORs in the nose is transmitted to the brain, leading to odorant perception and emotional and behavioral responses. There are ~400 intact human ORs, and to date only a small percentage of these receptors (~10% have known agonists. The determination of the specificity of the human ORs will contribute to a better understanding of how odorants are discriminated by the olfactory system. In this work, we aimed to identify human specific ORs, that is, ORs that are present in humans but absent from other species, and their corresponding agonists. To do this, we first selected 22 OR gene sequences from the human genome with no counterparts in the mouse, rat or dog genomes. Then we used a heterologous expression system to screen a subset of these human ORs against a panel of odorants of biological relevance, including foodborne aroma volatiles. We found that different types of odorants are able to activate some of these previously uncharacterized human ORs.

A molecular arms race between host innate antiviral response and emerging human coronaviruses.

Science.gov (United States)

Wong, Lok-Yin Roy; Lui, Pak-Yin; Jin, Dong-Yan

2016-02-01

Coronaviruses have been closely related with mankind for thousands of years. Community-acquired human coronaviruses have long been recognized to cause common cold. However, zoonotic coronaviruses are now becoming more a global concern with the discovery of highly pathogenic severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses causing severe respiratory diseases. Infections by these emerging human coronaviruses are characterized by less robust interferon production. Treatment of patients with recombinant interferon regimen promises beneficial outcomes, suggesting that compromised interferon expression might contribute at least partially to the severity of disease. The mechanisms by which coronaviruses evade host innate antiviral response are under intense investigations. This review focuses on the fierce arms race between host innate antiviral immunity and emerging human coronaviruses. Particularly, the host pathogen recognition receptors and the signal transduction pathways to mount an effective antiviral response against SARS and MERS coronavirus infection are discussed. On the other hand, the counter-measures evolved by SARS and MERS coronaviruses to circumvent host defense are also dissected. With a better understanding of the dynamic interaction between host and coronaviruses, it is hoped that insights on the pathogenesis of newly-identified highly pathogenic human coronaviruses and new strategies in antiviral development can be derived.

Sigma and opioid receptors in human brain tumors

Energy Technology Data Exchange (ETDEWEB)

Thomas, G.E.; Szuecs, M.; Mamone, J.Y.; Bem, W.T.; Rush, M.D.; Johnson, F.E.; Coscia, C.J. (St. Louis Univ. School of Medicine, MO (USA))

1990-01-01

Human brain tumors and nude mouse-borne human neuroblastomas and gliomas were analyzed for sigma and opioid receptor content. Sigma binding was assessed using ({sup 3}H) 1, 3-di-o-tolylguanidine (DTG), whereas opioid receptor subtypes were measured with tritiated forms of the following: {mu}, (D-ala{sup 2}, mePhe{sup 4}, gly-ol{sup 5}) enkephalin (DAMGE); {kappa}, ethylketocyclazocine (EKC) or U69,593; {delta}, (D-pen{sup 2}, D-pen{sup 5}) enkephalin (DPDPE) or (D-ala{sup 2}, D-leu{sup 5}) enkephalin (DADLE) with {mu} suppressor present. Binding parameters were estimated by homologous displacement assays followed by analysis using the LIGAND program. Sigma binding was detected in 15 of 16 tumors examined with very high levels found in a brain metastasis from an adenocarcinoma of lung and a human neuroblastoma (SK-N-MC) passaged in nude mice. {kappa} opioid receptor binding was detected in 4 of 4 glioblastoma multiforme specimens and 2 of 2 human astrocytoma cell lines tested but not in the other brain tumors analyzed.

Blockade of human P2X7 receptor function with a monoclonal antibody.

Science.gov (United States)

Buell, G; Chessell, I P; Michel, A D; Collo, G; Salazzo, M; Herren, S; Gretener, D; Grahames, C; Kaur, R; Kosco-Vilbois, M H; Humphrey, P P

1998-11-15

A monoclonal antibody (MoAb) specific for the human P2X7 receptor was generated in mice. As assessed by flow cytometry, the MoAb labeled human blood-derived macrophage cells natively expressing P2X7 receptors and cells transfected with human P2X7 but not other P2X receptor types. The MoAb was used to immunoprecipitate the human P2X7 receptor protein, and in immunohistochemical studies on human lymphoid tissue, P2X7 receptor labeling was observed within discrete areas of the marginal zone of human tonsil sections. The antibody also acted as a selective antagonist of human P2X7 receptors in several functional studies. Thus, whole cell currents, elicited by the brief application of 2',3'-(4-benzoyl)-benzoyl-ATP in cells expressing human P2X7, were reduced in amplitude by the presence of the MoAb. Furthermore, preincubation of human monocytic THP-1 cells with the MoAb antagonized the ability of P2X7 agonists to induce the release of interleukin-1beta.

Human orexin/hypocretin receptors form constitutive homo- and heteromeric complexes with each other and with human CB{sub 1} cannabinoid receptors

Energy Technology Data Exchange (ETDEWEB)

Jäntti, Maria H., E-mail: maria.jantti@helsinki.fi [Department of Veterinary Biosciences, POB 66, FIN-00014 University of Helsinki (Finland); Mandrika, Ilona, E-mail: ilona@biomed.lu.lv [Latvian Biomedical Research and Study Centre, Ratsupites Str. 1, Riga LV 1067 (Latvia); Kukkonen, Jyrki P., E-mail: jyrki.kukkonen@helsinki.fi [Department of Veterinary Biosciences, POB 66, FIN-00014 University of Helsinki (Finland)

2014-03-07

Highlights: • OX{sub 1} and OX{sub 2} orexin and CB{sub 1} cannabinoid receptor dimerization was investigated. • Bioluminescence resonance energy transfer method was used. • All receptors readily formed constitutive homo- and heteromeric complexes. - Abstract: Human OX{sub 1} orexin receptors have been shown to homodimerize and they have also been suggested to heterodimerize with CB{sub 1} cannabinoid receptors. The latter has been suggested to be important for orexin receptor responses and trafficking. In this study, we wanted to assess the ability of the other combinations of receptors to also form similar complexes. Vectors for expression of human OX{sub 1}, OX{sub 2} and CB{sub 1} receptors, C-terminally fused with either Renilla luciferase or GFP{sup 2} green fluorescent protein variant, were generated. The constructs were transiently expressed in Chinese hamster ovary cells, and constitutive dimerization between the receptors was assessed by bioluminescence energy transfer (BRET). Orexin receptor subtypes readily formed homo- and hetero(di)mers, as suggested by significant BRET signals. CB{sub 1} receptors formed homodimers, and they also heterodimerized with both orexin receptors. Interestingly, BRET efficiency was higher for homodimers than for almost all heterodimers. This is likely to be due to the geometry of the interaction; the putatively symmetric dimers may place the C-termini in a more suitable orientation in homomers. Fusion of luciferase to an orexin receptor and GFP{sup 2} to CB{sub 1} produced more effective BRET than the opposite fusions, also suggesting differences in geometry. Similar was seen for the OX{sub 1}–OX{sub 2} interaction. In conclusion, orexin receptors have a significant propensity to make homo- and heterodi-/oligomeric complexes. However, it is unclear whether this affects their signaling. As orexin receptors efficiently signal via endocannabinoid production to CB{sub 1} receptors, dimerization could be an effective way

Characterization of serotonergic receptors in rabbit, porcine and human conjunctivae.

Science.gov (United States)

Turner, Helen C; Alvarez, Lawrence J; Candia, Oscar A; Bernstein, Audrey M

2003-10-01

To characterize the serotonin (5-HT) receptors linked to the modulation of adenylyl cyclase activity in rabbit, porcine and human conjunctivae. Serotonin receptor-subtype expression was examined using reverse transcription-polymerase chain reaction (RT-PCR) and receptor subtype-specific polyclonal antibodies for the immunofluorescent labeling of conjunctival cryosections. In addition, measurements of the effects of serotonergics on the short-circuit current (I(sc)) across rabbit and porcine conjunctivae were contrasted. RT-PCR assays indicated the expression of 5-HT(1B ) and 5-HT(1D) receptors, subtypes negatively coupled to adenylyl cyclase, in the rabbit conjunctiva. This approach also suggested the co-expression of 5-HT(1B), 5-HT(1D), 5-HT(1F), 5-HT(4) and 5-HT(7) mRNA's in the porcine conjunctiva, and 5-HT( 1D), 5-HT(1F) and 5-HT(7) in the human conjunctiva. Since the 5-HT(4) and 5-HT(7) receptors are positively linked to adenylyl cyclase, these results implied that the porcine and human tissues exhibited subtypes both positively and negatively linked to the enzyme. However, immunohistochemical observations, using currently available antibodies solely localized the 5-HT(7) moiety in the porcine and human epithelia, suggested that the 1B/1D forms may be minor elements. Consistent with this prospect, 5-HT was a stimulant of the transepithelial I(sc) across the porcine conjunctiva, an opposite response from earlier findings that demonstrated inhibitory effects by 5-HT on the rabbit I(sc), which are now explained by the localization of the 1B/1D receptors in the rabbit stratified epithelium. The 5-HT receptors expressed by mammalian conjunctivae are not identical. In terms of 5-HT receptor expression, the porcine tissue may be a more appropriate model for human, than is the rabbit, in that 5-HT may serve as a secretagogue in the human epithelium.

Human myometrial adrenergic receptors during pregnancy: identification of the alpha-adrenergic receptor by [3H] dihydroergocryptine binding

International Nuclear Information System (INIS)

Jacobs, M.M.; Hayashida, D.; Roberts, J.M.

1985-01-01

The radioactive alpha-adrenergic antagonist [ 3 H] dihydroergocryptine binds to particulate preparations of term pregnant human myometrium in a manner compatible with binding to the alpha-adrenergic receptor (alpha-receptor). [ 3 H] Dihydroergocryptine binds with high affinity (KD = 2 nmol/L and low capacity (receptor concentration = 100 fmol/mg of protein). Adrenergic agonists compete for [ 3 H] dihydroergocryptine binding sites stereo-selectively ([-]-norepinephrine is 100 times as potent as [+]-norepinephrine) and in a manner compatible with alpha-adrenergic potencies (epinephrine approximately equal to norepinephrine much greater than isoproterenol). Studies in which prazosin, an alpha 1-antagonist, and yohimbine, and alpha 2-antagonist, competed for [ 3 H] dihydroergocryptine binding sites in human myometrium indicated that approximately 70% are alpha 2-receptors and that 30% are alpha 1-receptors. [ 3 H] dihydroergocryptine binding to human myometrial membrane particulate provides an important tool with which to study the molecular mechanisms of uterine alpha-adrenergic response

Frizzled Receptors as Potential Therapeutic Targets in Human Cancers

Directory of Open Access Journals (Sweden)

Chui-Mian Zeng

2018-05-01

Full Text Available Frizzled receptors (FZDs are a family of seven-span transmembrane receptors with hallmarks of G protein-coupled receptors (GPCRs that serve as receptors for secreted Wingless-type (WNT ligands in the WNT signaling pathway. Functionally, FZDs play crucial roles in regulating cell polarity, embryonic development, cell proliferation, formation of neural synapses, and many other processes in developing and adult organisms. In this review, we will introduce the basic structural features and review the biological function and mechanism of FZDs in the progression of human cancers, followed by an analysis of clinical relevance and therapeutic potential of FZDs. We will focus on the development of antibody-based and small molecule inhibitor-based therapeutic strategies by targeting FZDs for human cancers.

Identification of two critical amino acid residues of the severe acute respiratory syndrome coronavirus spike protein for its variation in zoonotic tropism transition via a double substitution strategy.

Science.gov (United States)

Qu, Xiu-Xia; Hao, Pei; Song, Xi-Jun; Jiang, Si-Ming; Liu, Yan-Xia; Wang, Pei-Gang; Rao, Xi; Song, Huai-Dong; Wang, Sheng-Yue; Zuo, Yu; Zheng, Ai-Hua; Luo, Min; Wang, Hua-Lin; Deng, Fei; Wang, Han-Zhong; Hu, Zhi-Hong; Ding, Ming-Xiao; Zhao, Guo-Ping; Deng, Hong-Kui

2005-08-19

Severe acute respiratory syndrome coronavirus (SARS-CoV) is a recently identified human coronavirus. The extremely high homology of the viral genomic sequences between the viruses isolated from human (huSARS-CoV) and those of palm civet origin (pcSARS-CoV) suggested possible palm civet-to-human transmission. Genetic analysis revealed that the spike (S) protein of pcSARS-CoV and huSARS-CoV was subjected to the strongest positive selection pressure during transmission, and there were six amino acid residues within the receptor-binding domain of the S protein being potentially important for SARS progression and tropism. Using the single-round infection assay, we found that a two-amino acid substitution (N479K/T487S) of a huSARS-CoV for those of pcSARS-CoV almost abolished its infection of human cells expressing the SARS-CoV receptor ACE2 but no effect upon the infection of mouse ACE2 cells. Although single substitution of these two residues had no effects on the infectivity of huSARS-CoV, these recombinant S proteins bound to human ACE2 with different levels of reduced affinity, and the two-amino acid-substituted S protein showed extremely low affinity. On the contrary, substitution of these two amino acid residues of pcSARS-CoV for those of huSRAS-CoV made pcSARS-CoV capable of infecting human ACE2-expressing cells. These results suggest that amino acid residues at position 479 and 487 of the S protein are important determinants for SARS-CoV tropism and animal-to-human transmission.

Impact of the Regulators SigB, Rot, SarA and sarS on the Toxic Shock Tst Promoter and TSST-1 Expression in Staphylococcus aureus.

Directory of Open Access Journals (Sweden)

Diego O Andrey

Full Text Available Staphylococcus aureus is an important pathogen manifesting virulence through diverse disease forms, ranging from acute skin infections to life-threatening bacteremia or systemic toxic shock syndromes. In the latter case, the prototypical superantigen is TSST-1 (Toxic Shock Syndrome Toxin 1, encoded by tst(H, and carried on a mobile genetic element that is not present in all S. aureus strains. Transcriptional regulation of tst is only partially understood. In this study, we dissected the role of sarA, sarS (sarH1, RNAIII, rot, and the alternative stress sigma factor sigB (σB. By examining tst promoter regulation predominantly in the context of its native sequence within the SaPI1 pathogenicity island of strain RN4282, we discovered that σB emerged as a particularly important tst regulator. We did not detect a consensus σB site within the tst promoter, and thus the effect of σB is likely indirect. We found that σB strongly repressed the expression of the toxin via at least two distinct regulatory pathways dependent upon sarA and agr. Furthermore rot, a member of SarA family, was shown to repress tst expression when overexpressed, although its deletion had no consistent measurable effect. We could not find any detectable effect of sarS, either by deletion or overexpression, suggesting that this regulator plays a minimal role in TSST-1 expression except when combined with disruption of sarA. Collectively, our results extend our understanding of complex multifactorial regulation of tst, revealing several layers of negative regulation. In addition to environmental stimuli thought to impact TSST-1 production, these findings support a model whereby sporadic mutation in a few key negative regulators can profoundly affect and enhance TSST-1 expression.

Broadening of neutralization activity to directly block a dominant antibody-driven SARS-coronavirus evolution pathway.

Directory of Open Access Journals (Sweden)

Jianhua Sui

2008-11-01

Full Text Available Phylogenetic analyses have provided strong evidence that amino acid changes in spike (S protein of animal and human SARS coronaviruses (SARS-CoVs during and between two zoonotic transfers (2002/03 and 2003/04 are the result of positive selection. While several studies support that some amino acid changes between animal and human viruses are the result of inter-species adaptation, the role of neutralizing antibodies (nAbs in driving SARS-CoV evolution, particularly during intra-species transmission, is unknown. A detailed examination of SARS-CoV infected animal and human convalescent sera could provide evidence of nAb pressure which, if found, may lead to strategies to effectively block virus evolution pathways by broadening the activity of nAbs. Here we show, by focusing on a dominant neutralization epitope, that contemporaneous- and cross-strain nAb responses against SARS-CoV spike protein exist during natural infection. In vitro immune pressure on this epitope using 2002/03 strain-specific nAb 80R recapitulated a dominant escape mutation that was present in all 2003/04 animal and human viruses. Strategies to block this nAb escape/naturally occurring evolution pathway by generating broad nAbs (BnAbs with activity against 80R escape mutants and both 2002/03 and 2003/04 strains were explored. Structure-based amino acid changes in an activation-induced cytidine deaminase (AID "hot spot" in a light chain CDR (complementarity determining region alone, introduced through shuffling of naturally occurring non-immune human VL chain repertoire or by targeted mutagenesis, were successful in generating these BnAbs. These results demonstrate that nAb-mediated immune pressure is likely a driving force for positive selection during intra-species transmission of SARS-CoV. Somatic hypermutation (SHM of a single VL CDR can markedly broaden the activity of a strain-specific nAb. The strategies investigated in this study, in particular the use of structural

FDTD calculation of whole-body average SAR in adult and child models for frequencies from 30 MHz to 3 GHz

International Nuclear Information System (INIS)

Wang Jianqing; Fujiwara, Osamu; Kodera, Sachiko; Watanabe, Soichi

2006-01-01

Due to the difficulty of the specific absorption rate (SAR) measurement in an actual human body for electromagnetic radio-frequency (RF) exposure, in various compliance assessment procedures the incident electric field or power density is being used as a reference level, which should never yield a larger whole-body average SAR than the basic safety limit. The relationship between the reference level and the whole-body average SAR, however, was established mainly based on numerical calculations for highly simplified human modelling dozens of years ago. Its validity is being questioned by the latest calculation results. In verifying the validity of the reference level with respect to the basic SAR limit for RF exposure, it is essential to have a high accuracy of human modelling and numerical code. In this study, we made a detailed error analysis in the whole-body average SAR calculation for the finite-difference time-domain (FDTD) method in conjunction with the perfectly matched layer (PML) absorbing boundaries. We derived a basic rule for the PML employment based on a dielectric sphere and the Mie theory solution. We then attempted to clarify to what extent the whole-body average SAR may reach using an anatomically based Japanese adult model and a scaled child model. The results show that the whole-body average SAR under the ICNIRP reference level exceeds the basic safety limit nearly 30% for the child model both in the resonance frequency and 2 GHz band

FDTD calculation of whole-body average SAR in adult and child models for frequencies from 30 MHz to 3 GHz

Energy Technology Data Exchange (ETDEWEB)

Wang Jianqing [Graduate School of Engineering, Nagoya Institute of Technology, Gokiso-cho, Showa-ku, Nagoya 466-8555 (Japan); Fujiwara, Osamu [Graduate School of Engineering, Nagoya Institute of Technology, Gokiso-cho, Showa-ku, Nagoya 466-8555 (Japan); Kodera, Sachiko [Graduate School of Engineering, Nagoya Institute of Technology, Gokiso-cho, Showa-ku, Nagoya 466-8555 (Japan); Watanabe, Soichi [National Institute of Information and Communications Technology, Nukui-kitamachi, Koganei, Tokyo 184-8795 (Japan)

2006-09-07

Due to the difficulty of the specific absorption rate (SAR) measurement in an actual human body for electromagnetic radio-frequency (RF) exposure, in various compliance assessment procedures the incident electric field or power density is being used as a reference level, which should never yield a larger whole-body average SAR than the basic safety limit. The relationship between the reference level and the whole-body average SAR, however, was established mainly based on numerical calculations for highly simplified human modelling dozens of years ago. Its validity is being questioned by the latest calculation results. In verifying the validity of the reference level with respect to the basic SAR limit for RF exposure, it is essential to have a high accuracy of human modelling and numerical code. In this study, we made a detailed error analysis in the whole-body average SAR calculation for the finite-difference time-domain (FDTD) method in conjunction with the perfectly matched layer (PML) absorbing boundaries. We derived a basic rule for the PML employment based on a dielectric sphere and the Mie theory solution. We then attempted to clarify to what extent the whole-body average SAR may reach using an anatomically based Japanese adult model and a scaled child model. The results show that the whole-body average SAR under the ICNIRP reference level exceeds the basic safety limit nearly 30% for the child model both in the resonance frequency and 2 GHz band.

Characterizing and estimating noise in InSAR and InSAR time series with MODIS

Science.gov (United States)

Barnhart, William D.; Lohman, Rowena B.

2013-01-01

InSAR time series analysis is increasingly used to image subcentimeter displacement rates of the ground surface. The precision of InSAR observations is often affected by several noise sources, including spatially correlated noise from the turbulent atmosphere. Under ideal scenarios, InSAR time series techniques can substantially mitigate these effects; however, in practice the temporal distribution of InSAR acquisitions over much of the world exhibit seasonal biases, long temporal gaps, and insufficient acquisitions to confidently obtain the precisions desired for tectonic research. Here, we introduce a technique for constraining the magnitude of errors expected from atmospheric phase delays on the ground displacement rates inferred from an InSAR time series using independent observations of precipitable water vapor from MODIS. We implement a Monte Carlo error estimation technique based on multiple (100+) MODIS-based time series that sample date ranges close to the acquisitions times of the available SAR imagery. This stochastic approach allows evaluation of the significance of signals present in the final time series product, in particular their correlation with topography and seasonality. We find that topographically correlated noise in individual interferograms is not spatially stationary, even over short-spatial scales (<10 km). Overall, MODIS-inferred displacements and velocities exhibit errors of similar magnitude to the variability within an InSAR time series. We examine the MODIS-based confidence bounds in regions with a range of inferred displacement rates, and find we are capable of resolving velocities as low as 1.5 mm/yr with uncertainties increasing to ∼6 mm/yr in regions with higher topographic relief.

The immunohistochemical expression of calcitonin receptor-like receptor (CRLR) in human gliomas.

Science.gov (United States)

Benes, L; Kappus, C; McGregor, G P; Bertalanffy, H; Mennel, H D; Hagner, S

2004-02-01

Gliomas are the most common primary tumours of the central nervous system and exhibit rapid growth that is associated with neovascularisation. Adrenomedullin is an important tumour survival factor in human carcinogenesis. It has growth promoting effects on gliomas, and blockade of its actions has been experimentally shown to reduce the growth of glioma tissues and cell lines. There is some evidence that the calcitonin receptor-like receptor (CRLR) mediates the tumorigenic actions of adrenomedullin. To determine whether CRLR is expressed in human gliomas and the probable cellular targets of adrenomedullin. Biopsies from 95 human gliomas of varying grade were processed for immunohistochemical analysis using a previously developed and characterised antibody to CRLR. All tumour specimens were positive for CRLR. As previously found in normal peripheral tissues, CRLR immunostaining was particularly intense in the endothelial cells. This was evident in all the various vascular conformations that were observed, and which are typical of gliomas. In addition, clear immunostaining of tumour cells with astrocyte morphology was observed. These were preferentially localised around vessels. This study has shown for the first time that the CRLR protein is present in human glioma tissue. The expression of the receptor in endothelial cells and in astrocytic tumour cells is consistent with the evidence that its endogenous ligand, adrenomedullin, may influence glioma growth by means of both direct mitogenic and indirect angiogenic effects. CRLR may be a valuable target for effective therapeutic intervention in these malignant tumours.

Assessing ScanSAR Interferometry for Deformation Studies

Science.gov (United States)

Buckley, S. M.; Gudipati, K.

2007-12-01

There is a trend in civil satellite SAR mission design to implement an imaging strategy that incorporates both stripmap mode and ScanSAR imaging. This represents a compromise between high resolution data collection and a desire for greater spatial coverage and more frequent revisit times. However, mixed mode imaging can greatly reduce the number of stripmap images available for measuring subtle ground deformation. Although ScanSAR-ScanSAR and ScanSAR-stripmap repeat-pass interferometry have been demonstrated, these approaches are infrequently used for single interferogram formation and nonexistent for InSAR time series analysis. For future mission design, e.g., a dedicated US InSAR mission, the effect of various ScanSAR system parameter choices on InSAR time series analysis also remains unexplored. Our objective is to determine the utility of ScanSAR differential interferometry. We will demonstrate the use of ScanSAR interferograms for several previous deformation studies: localized and broad-scale urban land subsidence, tunneling, volcanic surface movements and several examples associated with the seismic cycle. We also investigate the effect of various ScanSAR burst synchronization levels on our ability to detect and make quality measurements of deformation. To avoid the issues associated with Envisat ScanSAR burst alignment and to exploit a decade of InSAR measurements, we simulate ScanSAR data by bursting (throwing away range lines of) ERS-1/2 data. All the burst mode datasets are processed using a Modified SPECAN algorithm. To investigate the effects of burst misalignment, a number of cases with varying degrees of burst overlap are considered. In particular, we look at phase decorrelation as a function of percentage of burst overlap. Coherence clearly reduces as the percentage of overlap decreases and we find a useful threshold of 40-70% burst overlap depending on the study site. In order to get a more generalized understanding for different surface conditions

Autoradiographic visualization of muscarinic receptor subtypes in human and guinea pig lung

International Nuclear Information System (INIS)

Mak, J.C.; Barnes, P.J.

1990-01-01

Muscarinic receptor subtypes have been localized in human and guinea pig lung sections by an autoradiographic technique, using [3H](-)quinuclidinyl benzilate [( 3H]QNB) and selective muscarinic antagonists. [3H]QNB was incubated with tissue sections for 90 min at 25 degrees C, and nonspecific binding was determined by incubating adjacent serial sections in the presence of 1 microM atropine. Binding to lung sections had the characterization expected for muscarinic receptors. Autoradiography revealed that muscarinic receptors were widely distributed in human lung, with dense labeling over submucosal glands and airway ganglia, and moderate labeling over nerves in intrapulmonary bronchi and of airway smooth muscle of large and small airways. In addition, alveolar walls were uniformly labeled. In guinea pig lung, labeling of airway smooth muscle was similar, but in contrast to human airways, epithelium was labeled but alveolar walls were not. The muscarinic receptors of human airway smooth muscle from large to small airways were entirely of the M3-subtype, whereas in guinea pig airway smooth muscle, the majority were the M3-subtype with a very small population of the M2-subtype present. In human bronchial submucosal glands, M1- and M3-subtypes appeared to coexist in the proportions of 36 and 64%, respectively. In human alveolar walls the muscarinic receptors were entirely of the M1-subtype, which is absent from the guinea pig lung. No M2-receptors were demonstrated in human lung. The localization of M1-receptors was confirmed by direct labeling with [3H]pirenzepine. With the exception of the alveolar walls in human lung, the localization of muscarinic receptor subtypes on structures in the lung is consistent with known functional studies

Mu opioid receptor binding sites in human brain

International Nuclear Information System (INIS)

Pilapil, C.; Welner, S.; Magnan, J.; Zamir, N.; Quirion, R.

1986-01-01

Our experiments focused on the examination of the distribution of mu opioid receptor binding sites in normal human brain using the highly selective ligand [ 3 H]DAGO, in both membrane binding assay and in vitro receptor autoradiography. Mu opioid binding sites are very discretely distributed in human brain with high densities of sites found in the posterior amygdala, caudate, putamen, hypothalamus and certain cortical areas. Moreover the autoradiographic distribution of [ 3 H]DAGO binding sites clearly reveals the discrete lamination (layers I and III-IV) of mu sites in cortical areas

Adrenergic receptors in frontal cortex in human brain.

Science.gov (United States)

Cash, R; Raisman, R; Ruberg, M; Agid, Y

1985-02-05

The binding of three adrenergic ligands ([3H]prazosin, [3H]clonidine, [3H]dihydroalprenolol) was studied in the frontal cortex of human brain. alpha 1-Receptors, labeled by [3H]prazosin, predominated. [3H]Clonidine bound to two classes of sites, one of high affinity and one of low affinity. Guanosine triphosphate appeared to lower the affinity of [3H]clonidine for its receptor. [3H]Dihydroalprenolol bound to three classes of sites: the beta 1-receptor, the beta 2-receptor and a receptor with low affinity which represented about 40% of the total binding, but which was probably a non-specific site; the beta 1/beta 2 ratio was 1/2.

Staphylococcus aureus sarA regulates inflammation and colonization during central nervous system biofilm formation.

Directory of Open Access Journals (Sweden)

Jessica N Snowden

Full Text Available Infection is a frequent and serious complication following the treatment of hydrocephalus with CSF shunts, with limited therapeutic options because of biofilm formation along the catheter surface. Here we evaluated the possibility that the sarA regulatory locus engenders S. aureus more resistant to immune recognition in the central nervous system (CNS based on its reported ability to regulate biofilm formation. We utilized our established model of CNS catheter-associated infection, similar to CSF shunt infections seen in humans, to compare the kinetics of bacterial titers, cytokine production and inflammatory cell influx elicited by wild type S. aureus versus an isogenic sarA mutant. The sarA mutant was more rapidly cleared from infected catheters compared to its isogenic wild type strain. Consistent with this finding, several pro-inflammatory cytokines and chemokines, including IL-17, CXCL1, and IL-1β were significantly increased in the brain following infection with the sarA mutant versus wild type S. aureus, in agreement with the fact that the sarA mutant displayed impaired biofilm growth and favored a planktonic state. Neutrophil influx into the infected hemisphere was also increased in the animals infected with the sarA mutant compared to wild type bacteria. These changes were not attributable to extracellular protease activity, which is increased in the context of SarA mutation, since similar responses were observed between sarA and a sarA/protease mutant. Overall, these results demonstrate that sarA plays an important role in attenuating the inflammatory response during staphylococcal biofilm infection in the CNS via a mechanism that remains to be determined.

Structural Insights into Immune Recognition of the Severe Acute Respiratory Syndrome Coronavirus S Protein Receptor Binding Domain

Energy Technology Data Exchange (ETDEWEB)

Pak, J.; Sharon, C; Satkunarajah, M; Thierry, C; Cameron, C; Kelvin, D; Seetharaman, J; Cochrane, A; Plummer, F; et. al.

2009-01-01

The spike (S) protein of the severe acute respiratory syndrome coronavirus (SARS-CoV) is responsible for host cell attachment and fusion of the viral and host cell membranes. Within S the receptor binding domain (RBD) mediates the interaction with angiotensin-converting enzyme 2 (ACE2), the SARS-CoV host cell receptor. Both S and the RBD are highly immunogenic and both have been found to elicit neutralizing antibodies. Reported here is the X-ray crystal structure of the RBD in complex with the Fab of a neutralizing mouse monoclonal antibody, F26G19, elicited by immunization with chemically inactivated SARS-CoV. The RBD-F26G19 Fab complex represents the first example of the structural characterization of an antibody elicited by an immune response to SARS-CoV or any fragment of it. The structure reveals that the RBD surface recognized by F26G19 overlaps significantly with the surface recognized by ACE2 and, as such, suggests that F26G19 likely neutralizes SARS-CoV by blocking the virus-host cell interaction.

Human corpus luteum: presence of epidermal growth factor receptors and binding characteristics

International Nuclear Information System (INIS)

Ayyagari, R.R.; Khan-Dawood, F.S.

1987-01-01

Epidermal growth factor receptors are present in many reproductive tissues but have not been demonstrated in the human corpus luteum. To determine the presence of epidermal growth factor receptors and its binding characteristics, we carried out studies on the plasma cell membrane fraction of seven human corpora lutea (days 16 to 25) of the menstrual cycle. Specific epidermal growth factor receptors were present in human corpus luteum. Insulin, nerve growth factor, and human chorionic gonadotropin did not competitively displace epidermal growth factor binding. The optimal conditions for corpus luteum-epidermal growth factor receptor binding were found to be incubation for 2 hours at 4 degrees C with 500 micrograms plasma membrane protein and 140 femtomol 125 I-epidermal growth factor per incubate. The number (mean +/- SEM) of epidermal growth factor binding sites was 12.34 +/- 2.99 X 10(-19) mol/micrograms protein; the dissociation constant was 2.26 +/- 0.56 X 10(-9) mol/L; the association constant was 0.59 +/- 0.12 X 10(9) L/mol. In two regressing corpora lutea obtained on days 2 and 3 of the menstrual cycle, there was no detectable specific epidermal growth factor receptor binding activity. Similarly no epidermal growth factor receptor binding activity could be detected in ovarian stromal tissue. Our findings demonstrate that specific receptors for epidermal growth factor are present in the human corpus luteum. The physiologic significance of epidermal growth factor receptors in human corpus luteum is unknown, but epidermal growth factor may be involved in intragonadal regulation of luteal function

Rapid detection of MERS coronavirus-like viruses in bats: pote1ntial for tracking MERS coronavirus transmission and animal origin.

Science.gov (United States)

Woo, Patrick C Y; Lau, Susanna K P; Chen, Yixin; Wong, Emily Y M; Chan, Kwok-Hung; Chen, Honglin; Zhang, Libiao; Xia, Ningshao; Yuen, Kwok-Yung

2018-03-07

Recently, we developed a monoclonal antibody-based rapid nucleocapsid protein detection assay for diagnosis of MERS coronavirus (MERS-CoV) in humans and dromedary camels. In this study, we examined the usefulness of this assay to detect other lineage C betacoronaviruses closely related to MERS-CoV in bats. The rapid MERS-CoV nucleocapsid protein detection assay was tested positive in 24 (88.9%) of 27 Tylonycteris bat CoV HKU4 (Ty-BatCoV-HKU4) RNA-positive alimentary samples of Tylonycteris pachypus and 4 (19.0%) of 21 Pipistrellus bat CoV HKU5 (Pi-BatCoV-HKU5) RNA-positive alimentary samples of Pipistrellus abramus. There was significantly more Ty-BatCoV-HKU4 RNA-positive alimentary samples than Pi-BatCoV-HKU5 RNA-positive alimentary samples that were tested positive by the rapid MERS-CoV nucleocapsid protein detection assay (P < 0.001 by Chi-square test). The rapid assay was tested negative in all 51 alimentary samples RNA-positive for alphacoronaviruses (Rhinolophus bat CoV HKU2, Myotis bat CoV HKU6, Miniopterus bat CoV HKU8 and Hipposideros batCoV HKU10) and 32 alimentary samples positive for lineage B (SARS-related Rhinolophus bat CoV HKU3) and lineage D (Rousettus bat CoV HKU9) betacoronaviruses. No significant difference was observed between the viral loads of Ty-BatCoV-HKU4/Pi-BatCoV-HKU5 RNA-positive alimentary samples that were tested positive and negative by the rapid test (Mann-Witney U test). The rapid MERS-CoV nucleocapsid protein detection assay is able to rapidly detect lineage C betacoronaviruses in bats. It detected significantly more Ty-BatCoV-HKU4 than Pi-BatCoV-HKU5 because MERS-CoV is more closely related to Ty-BatCoV-HKU4 than Pi-BatCoV-HKU5. This assay will facilitate rapid on-site mass screening of animal samples for ancestors of MERS-CoV and tracking transmission in the related bat species.

Neurotensin receptors in human neoplasms: high incidence in Ewing's sarcomas.

Science.gov (United States)

Reubi, J C; Waser, B; Schaer, J C; Laissue, J A

1999-07-19

Receptors for regulatory peptides, such as somatostatin or vasoactive intestinal peptide (VIP), expressed at high density by neoplastic cells, can be instrumental for tumor diagnosis and therapy. Little is known about the expression of neurotensin receptors in human tumors. In the present study, 464 human neoplasms of various types were investigated for their neurotensin receptor content by in vitro receptor autoradiography on tissue sections using 125I-[Tyr3]-neurotensin as radioligand. Neurotensin receptors were identified and localized in tumor cells of 11/17 Ewing's sarcomas, 21/40 meningiomas, 10/23 astrocytomas, 5/13 medulloblastomas, 7/24 medullary thyroid cancers and 2/8 small cell lung cancers. They were rarely found in non-small cell lung cancers and breast carcinomas; they were absent in prostate, ovarian, renal cell and hepatocellular carcinomas, neuroendocrine gut tumors, pituitary adenomas, schwannomas, neuroblastomas and lymphomas. When present, the receptors bound with nanomolar affinity neurotensin and acetyl-neurotensin-(8-13), with lower affinity neuromedin N, diethylenetriamine penta-acetic acidneurotensin-(8-13) and SR 48692, but not neurotensin-(1-11). They were all of the NT1 type, without high affinity for levocabastine. Further, in 2 receptor-positive Ewing's sarcomas, neurotensin mRNA was detected by in situ hybridization techniques. Since neurotensin is known to stimulate cell proliferation, the presence of neurotensin receptors in human neoplasia may be of biological relevance, possibly as an integrative part of an autocrine feedback mechanism of tumor growth stimulation.

Identification of a second putative receptor of platelet activating factor on human polymorphonuclear leukocytes

International Nuclear Information System (INIS)

Hwang, S.B.

1987-01-01

Due to multiple molecular species of platelet activating factor (PAF) and the existence of high affinity binding sites in a variety of cells and tissues, possible existence of PAF receptor subtypes has been suggested. This report shows differences between specific PAF receptors on human leukocytes and platelets. Human PMN leukocyte membranes showed high affinity binding sites for PAF with an equilibrium dissociation constant (Kd) of 4.7 (+/- 1.4) x 10 -10 M. The maximal number (B/sub max/) of receptor sites was estimated to be 3.13 (+/- 1.4) x 10 -13 mol/mg protein. They compared the relative potencies of several PAF agonists and receptor antagonists between human platelet and human leukocyte membranes. One antagonist (Ono-6240) was found to be 8 times less potent at inhibiting the [ 3 H]PAF specific receptor binding to human leukocytes than to human platelets. Mg 2+ , Ca 2+ and K + ions potentiated the [ 3 H]PAF specific binding in both systems. Na + ions inhibited the [ 3 H]PAF specific binding to human platelets but showed no effects in human leukocytes. K + ions decreased the Mg 2+ -potentiated [ 3 H]PAF binding in human leukocytes but showed no effects in human platelets. These results suggest that the PAF specific receptors in human leukocytes are different structurally and possibly functionally from the receptors identified in human platelets

Cardiac glycoside activities link Na(+)/K(+) ATPase ion-transport to breast cancer cell migration via correlative SAR.

Science.gov (United States)

Magpusao, Anniefer N; Omolloh, George; Johnson, Joshua; Gascón, José; Peczuh, Mark W; Fenteany, Gabriel

2015-02-20

The cardiac glycosides ouabain and digitoxin, established Na(+)/K(+) ATPase inhibitors, were found to inhibit MDA-MB-231 breast cancer cell migration through an unbiased chemical genetics screen for cell motility. The Na(+)/K(+) ATPase acts both as an ion-transporter and as a receptor for cardiac glycosides. To delineate which function is related to breast cancer cell migration, structure-activity relationship (SAR) profiles of cardiac glycosides were established at the cellular (cell migration inhibition), molecular (Na(+)/K(+) ATPase inhibition), and atomic (computational docking) levels. The SAR of cardiac glycosides and their analogs revealed a similar profile, a decrease in potency when the parent cardiac glycoside structure was modified, for each activity investigated. Since assays were done at the cellular, molecular, and atomic levels, correlation of SAR profiles across these multiple assays established links between cellular activity and specific protein-small molecule interactions. The observed antimigratory effects in breast cancer cells are directly related to the inhibition of Na(+)/K(+) transport. Specifically, the orientation of cardiac glycosides at the putative cation permeation path formed by transmembrane helices αM1-M6 correlates with the Na(+) pump activity and cell migration. Other Na(+)/K(+) ATPase inhibitors that are structurally distinct from cardiac glycosides also exhibit antimigratory activity, corroborating the conclusion that the antiport function of Na(+)/K(+) ATPase and not the receptor function is important for supporting the motility of MDA-MB-231 breast cancer cells. Correlative SAR can establish new relationships between specific biochemical functions and higher-level cellular processes, particularly for proteins with multiple functions and small molecules with unknown or various modes of action.

Development of an injectable formulation for the preparation of radiopharmaceutical {sup 68}Ga-DOTA-Sar gastrin; Desarrollo de una formulacion inyectable para la preparacion del radiofarmaco {sup 68}Ga-DOTA-Sargastrina

Energy Technology Data Exchange (ETDEWEB)

Castillo P, M.

2015-07-01

The CCK2 receptor (cholecystokinin) is located in areas of the central and peripheral nervous system and is over expressed in several types of human cancer, as medullar thyroid, lung and ovarian carcinomas. One of the endogenous ligands for the CCK2 receptor is the gastrin, so that radiolabeled peptides analogues to gastrin as Sar gastrin (Gln-Gly-Pro-Trp-Leu-Glu-Glu-Glu-Glu-Glu-Ala-Tyr-Gly-Trp-Nle-Asp-Phe-NH{sub 2}) have been proposed as potential diagnostic radiopharmaceuticals for obtaining tumors images with CCK2 receptors over expressed. The {sup 68}Ga is an ideal candidate for the peptides radiolabelled and has favorable characteristics to be used for diagnostic purposes by imaging with Positron emission tomography (PET). This work aimed to verify the technical documentation of the production process of radiopharmaceutical {sup 68}Ga-DOTA-Sar gastrin for its sanitary registration before the Comision Federal contra Riesgos Sanitarios (COFEPRIS) in Mexico. For optimization of the production process was assessed a factorial design of two variables with mixed levels (27 combinations), where the dependent variable was the radiochemical purity. The analytical method used for evaluating the content of Sar gastrin peptide in the injectable formulation was also validated by High-performance liquid chromatography. Subsequently the validation of the production process was carried out by manufacturing of lots in single-dose of the optimized injectable formulation of the radiopharmaceutical {sup 68}Ga-DOTA-Sar gastrin and the stability study was conducted at different times to determine the useful life time. The following was established as the optimal pharmaceutical formulation: 185 MBq of {sup 68}Ga, 50 μg de DOTA-Sar gastrin, 14 mg of sodium acetate and 0.5 m L of buffer acetates, 1.0 M, ph 4.22 in 2.5 m L of the vehicle. The analytical method used to determine the radiochemical purity of the formulation satisfied the requirements for the intended analytical

The effect of inhibition of PP1 and TNFα signaling on pathogenesis of SARS coronavirus

Energy Technology Data Exchange (ETDEWEB)

McDermott, Jason E.; Mitchell, Hugh D.; Gralinski, Lisa E.; Eisfeld, Amie J.; Josset, Laurence; Bankhead, Armand; Neumann, Gabriele; Tilton, Susan C.; Schäfer, Alexandra; Li, Chengjun; Fan, Shufang; McWeeney, Shannon; Baric, Ralph S.; Katze, Michael G.; Waters, Katrina M.

2016-09-23

The complex interplay between viral replication and host immune response during infection remains poorly understood. While many viruses are known to employ antiimmune strategies to facilitate their replication, highly pathogenic virus infections can also cause an excessive immune response that exacerbates, rather than reduces pathogenicity. To investigate this dichotomy in severe acute respiratory syndrome coronavirus (SARS-CoV), we developed a transcriptional network model of SARS-CoV infection in mice and used the model to prioritize candidate regulatory targets for further investigation. We validated our predictions in 18 different knockout (KO) mouse strains, showing that network topology provides significant predictive power to identify genes that are important for viral infection. We identified a novel player in the immune response to virus infection, Kepi, an inhibitory subunit of the protein phosphatase 1 (PP1) complex, which protects against SARS-CoV pathogenesis. We also found that receptors for the proinflammatory cytokine, tumor necrosis factor alpha (TNFα), promote pathogenesis through a parallel feed-forward circuit that promotes inflammation. These results are consistent with previous studies showing the role of over-stimulation of the inflammatory response to SARS-CoV in pathogenesis. We conclude that the critical balance between immune response and inflammation can be manipulated to improve the outcome of the infection. Further, our study provides two potential therapeutic strategies for mitigating the effects of SARS-CoV infection, and may provide insight into treatment strategies for Middle East Respiratory Syndrome Coronavirus (MERS-CoV).

SARS-related perceptions in Hong Kong.

Science.gov (United States)

Lau, Joseph T F; Yang, Xilin; Pang, Ellie; Tsui, H Y; Wong, Eric; Wing, Yun Kwok

2005-03-01

To understand different aspects of community responses related to severe acute respiratory syndrome (SARS), 2 population-based, random telephone surveys were conducted in June 2003 and January 2004 in Hong Kong. More than 70% of respondents would avoid visiting hospitals or mainland China to avoid contracting SARS. Most respondents believed that SARS could be transmitted through droplets, fomites, sewage, and animals. More than 90% believed that public health measures were efficacious means of prevention; 40.4% believed that SARS would resurge in Hong Kong; and approximately equals 70% would then wear masks in public places. High percentages of respondents felt helpless, horrified, and apprehensive because of SARS. Approximately 16% showed signs of posttraumatic symptoms, and approximately equals 40% perceived increased stress in family or work settings. The general public in Hong Kong has been very vigilant about SARS but needs to be more psychologically prepared to face a resurgence of the epidemic.

Comparison of two next-generation sequencing kits for diagnosis of epileptic disorders with a user-friendly tool for displaying gene coverage, DeCovA

Directory of Open Access Journals (Sweden)

Sarra Dimassi

2015-12-01

Full Text Available In recent years, molecular genetics has been playing an increasing role in the diagnostic process of monogenic epilepsies. Knowing the genetic basis of one patient's epilepsy provides accurate genetic counseling and may guide therapeutic options. Genetic diagnosis of epilepsy syndromes has long been based on Sanger sequencing and search for large rearrangements using MLPA or DNA arrays (array-CGH or SNP-array. Recently, next-generation sequencing (NGS was demonstrated to be a powerful approach to overcome the wide clinical and genetic heterogeneity of epileptic disorders. Coverage is critical for assessing the quality and accuracy of results from NGS. However, it is often a difficult parameter to display in practice. The aim of the study was to compare two library-building methods (Haloplex, Agilent and SeqCap EZ, Roche for a targeted panel of 41 genes causing monogenic epileptic disorders. We included 24 patients, 20 of whom had known disease-causing mutations. For each patient both libraries were built in parallel and sequenced on an Ion Torrent Personal Genome Machine (PGM. To compare coverage and depth, we developed a simple homemade tool, named DeCovA (Depth and Coverage Analysis. DeCovA displays the sequencing depth of each base and the coverage of target genes for each genomic position. The fraction of each gene covered at different thresholds could be easily estimated. None of the two methods used, namely NextGene and Ion Reporter, were able to identify all the known mutations/CNVs displayed by the 20 patients. Variant detection rate was globally similar for the two techniques and DeCovA showed that failure to detect a mutation was mainly related to insufficient coverage.

Biotinylated human. beta. -endorphins as probes for the opioid receptor

Energy Technology Data Exchange (ETDEWEB)

Hochhaus, G.; Gibson, B.W.; Sadee, W.

1988-01-05

The reaction of human ..beta..-endorphin and biotinyl N-hydroxysuccinimide with or without spacer arm, afforded a series of products that were separated by high performance liquid chromatography (HPLC). Liquid secondary ion mass spectrometry of the biotinylated products and their tryptic digests produced abundant protonated molecular ions (MH/sup +/), which specified the number and location of biotinylation. Between 1 and 4 biotinyl residues were incorporated per human ..beta..-endorphin molecule, at Lys-9, -19, -24, -28, and -29, but not at the amino-terminal Try-1. Three HPLC fractions were isolated for receptor binding studies monobiotinylation of Lys-9, Lys-19, and a mixture of Lys-24, Lys-28, and Lys-29 derivatives. IC/sub 50/ values for binding to ..mu.. and delta opioid receptor sites were 3-8 times higher for monobiotinylated derivatives than for the parent human ..beta..-endorphin. Association with avidin decreased opioid receptor affinities for the C/sub 6/ spacer derivative biotinylated at position Lys-9, which is close to the (1-5) enkephalin receptor region. In contrast, avidin did not affect or even increased apparent affinities to ..mu.. and delta sites for derivatives biotinylated at the ..cap alpha..-helical part of the molecule (Lys-19, -24, -28, and -29). Biotinylated human ..beta..-endorphins also bound to low affinity nonopioid binding sites on NG-108-15 cells; however, affinities to these sites were considerably reduced when derivatives were bound to avidin. The ability of biotinylated human ..beta..-endorphin to cross-link the ..mu.. and delta opioid receptors to avidin allows application of the biotin-avidin system as a molecular probe of the opioid receptor.

Syncytin-1 and its receptor is present in human gametes

DEFF Research Database (Denmark)

Bjerregaard, B; Lemmen, J G; Petersen, M R

2014-01-01

and around the equatorial segment. The receptor ASCT-2 is expressed in the acrosomal region and in the sperm tail. Moreover, ASCT-2, but not syncytin-1, is expressed in oocytes and the mRNA level increases with increasing maturity of the oocytes. CONCLUSIONS: Syncytin and its receptor are present in human......MAIN PURPOSE AND RESEARCH QUESTION: To determine whether the true fusogen Syncytin-1 and its receptor (ASCT-2) is present in human gametes using qRT-PCR, immunoblotting and immunofluorescence. METHODS: Donated oocytes and spermatozoa, originating from a fertility center in tertiary referral...

SAR: Stroke Authorship Recognition

KAUST Repository

Shaheen, Sara; Rockwood, Alyn; Ghanem, Bernard

2015-01-01

Are simple strokes unique to the artist or designer who renders them? If so, can this idea be used to identify authorship or to classify artistic drawings? Also, could training methods be devised to develop particular styles? To answer these questions, we propose the Stroke Authorship Recognition (SAR) approach, a novel method that distinguishes the authorship of 2D digitized drawings. SAR converts a drawing into a histogram of stroke attributes that is discriminative of authorship. We provide extensive classification experiments on a large variety of data sets, which validate SAR's ability to distinguish unique authorship of artists and designers. We also demonstrate the usefulness of SAR in several applications including the detection of fraudulent sketches, the training and monitoring of artists in learning a particular new style and the first quantitative way to measure the quality of automatic sketch synthesis tools. © 2015 The Eurographics Association and John Wiley & Sons Ltd.

Cloning of human genes encoding novel G protein-coupled receptors

Energy Technology Data Exchange (ETDEWEB)

Marchese, A.; Docherty, J.M.; Heiber, M. [Univ. of Toronto, (Canada)] [and others

1994-10-01

We report the isolation and characterization of several novel human genes encoding G protein-coupled receptors. Each of the receptors contained the familiar seven transmembrane topography and most closely resembled peptide binding receptors. Gene GPR1 encoded a receptor protein that is intronless in the coding region and that shared identity (43% in the transmembrane regions) with the opioid receptors. Northern blot analysis revealed that GPR1 transcripts were expressed in the human hippocampus, and the gene was localized to chromosome 15q21.6. Gene GPR2 encoded a protein that most closely resembled an interleukin-8 receptor (51% in the transmembrane regions), and this gene, not expressed in the six brain regions examined, was localized to chromosome 17q2.1-q21.3. A third gene, GPR3, showed identity (56% in the transmembrane regions) with a previously characterized cDNA clone from rat and was localized to chromosome 1p35-p36.1. 31 refs., 5 figs., 1 tab.

Precision Rectification of Airborne SAR Image

DEFF Research Database (Denmark)

Dall, Jørgen; Liao, M.; Zhang, Zhe

1997-01-01

A simple and direct procedure for the rectification of a certain class of airborne SAR data is presented. The relief displacements of SAR data are effectively removed by means of a digital elevation model and the image is transformed to the ground coordinate system. SAR data from the Danish EMISAR...

IL-21 Receptor Expression in Human Tendinopathy

Directory of Open Access Journals (Sweden)

Abigail L. Campbell

2014-01-01

Full Text Available The pathogenetic mechanisms underlying tendinopathy remain unclear, with much debate as to whether inflammation or degradation has the prominent role. Increasing evidence points toward an early inflammatory infiltrate and associated inflammatory cytokine production in human and animal models of tendon disease. The IL-21/IL-21R axis is a proinflammatory cytokine complex that has been associated with chronic inflammatory diseases including rheumatoid arthritis and inflammatory bowel disease. This project aimed to investigate the role and expression of the cytokine/receptor pair IL-21/IL-21R in human tendinopathy. We found significantly elevated expression of IL-21 receptor message and protein in human tendon samples but found no convincing evidence of the presence of IL-21 at message or protein level. The level of expression of IL-21R message/protein in human tenocytes was significantly upregulated by proinflammatory cytokines (TNFα/IL-1β in vitro. These findings demonstrate that IL-21R is present in early human tendinopathy mainly expressed by tenocytes and macrophages. Despite a lack of IL-21 expression, these data again suggest that early tendinopathy has an inflammatory/cytokine phenotype, which may provide novel translational targets in the treatment of tendinopathy.

Insecticide resistance profile of Anopheles gambiae from a phase II field station in Cové, southern Benin: implications for the evaluation of novel vector control products.

Science.gov (United States)

Ngufor, Corine; N'Guessan, Raphael; Fagbohoun, Josias; Subramaniam, Krishanthi; Odjo, Abibatou; Fongnikin, Augustin; Akogbeto, Martin; Weetman, David; Rowland, Mark

2015-11-18

Novel indoor residual spraying (IRS) and long-lasting insecticidal net (LLIN) products aimed at improving the control of pyrethroid-resistant malaria vectors have to be evaluated in Phase II semi-field experimental studies against highly pyrethroid-resistant mosquitoes. To better understand their performance it is necessary to fully characterize the species composition, resistance status and resistance mechanisms of the vector populations in the experimental hut sites. Bioassays were performed to assess phenotypic insecticide resistance in the malaria vector population at a newly constructed experimental hut site in Cové, a rice growing area in southern Benin, being used for WHOPES Phase II evaluation of newly developed LLIN and IRS products. The efficacy of standard WHOPES-approved pyrethroid LLIN and IRS products was also assessed in the experimental huts. Diagnostic genotyping techniques and microarray studies were performed to investigate the genetic basis of pyrethroid resistance in the Cové Anopheles gambiae population. The vector population at the Cové experimental hut site consisted of a mixture of Anopheles coluzzii and An. gambiae s.s. with the latter occurring at lower frequencies (23 %) and only in samples collected in the dry season. There was a high prevalence of resistance to pyrethroids and DDT (>90 % bioassay survival) with pyrethroid resistance intensity reaching 200-fold compared to the laboratory susceptible An. gambiae Kisumu strain. Standard WHOPES-approved pyrethroid IRS and LLIN products were ineffective in the experimental huts against this vector population (8-29 % mortality). The L1014F allele frequency was 89 %. CYP6P3, a cytochrome P450 validated as an efficient metabolizer of pyrethroids, was over-expressed. Characterizing pyrethroid resistance at Phase II field sites is crucial to the accurate interpretation of the performance of novel vector control products. The strong levels of pyrethroid resistance at the Cové experimental hut

SARS: systematic review of treatment effects.

Directory of Open Access Journals (Sweden)

Lauren J Stockman

2006-09-01

Full Text Available BACKGROUND: The SARS outbreak of 2002-2003 presented clinicians with a new, life-threatening disease for which they had no experience in treating and no research on the effectiveness of treatment options. The World Health Organization (WHO expert panel on SARS treatment requested a systematic review and comprehensive summary of treatments used for SARS-infected patients in order to guide future treatment and identify priorities for research. METHODS AND FINDINGS: In response to the WHO request we conducted a systematic review of the published literature on ribavirin, corticosteroids, lopinavir and ritonavir (LPV/r, type I interferon (IFN, intravenous immunoglobulin (IVIG, and SARS convalescent plasma from both in vitro studies and in SARS patients. We also searched for clinical trial evidence of treatment for acute respiratory distress syndrome. Sources of data were the literature databases MEDLINE, EMBASE, BIOSIS, and the Cochrane Central Register of Controlled Trials (CENTRAL up to February 2005. Data from publications were extracted and evidence within studies was classified using predefined criteria. In total, 54 SARS treatment studies, 15 in vitro studies, and three acute respiratory distress syndrome studies met our inclusion criteria. Within in vitro studies, ribavirin, lopinavir, and type I IFN showed inhibition of SARS-CoV in tissue culture. In SARS-infected patient reports on ribavirin, 26 studies were classified as inconclusive, and four showed possible harm. Seven studies of convalescent plasma or IVIG, three of IFN type I, and two of LPV/r were inconclusive. In 29 studies of steroid use, 25 were inconclusive and four were classified as causing possible harm. CONCLUSIONS: Despite an extensive literature reporting on SARS treatments, it was not possible to determine whether treatments benefited patients during the SARS outbreak. Some may have been harmful. Clinical trials should be designed to validate a standard protocol for dosage

Clinical significance of melatonin receptors in the human myometrium.

Science.gov (United States)

Olcese, James; Beesley, Stephen

2014-08-01

To review and update the research on melatonin receptor expression in the human myometrium, in particular as it pertains to uterine contractility at labor. Summary of previous studies with the addition of new data on the transcriptional regulation of melatonin receptor expression in human myometrial cells. Not applicable. Late-term pregnant volunteers. Biopsy collection for in vitro analyses provided the original data. More recently, uterine contractions in late-term pregnant volunteers were assessed before, during, and after acute white-light exposure. Melatonin receptor signaling in myometrial cells and uterine contractions in late-term pregnant volunteers. Melatonin acts through the MTNR1B melatonin receptor that is expressed in the myometrium at late term to synergistically enhance oxytocin-dependent signaling and contractions. Acute inhibition of endogenous melatonin levels with light reversibly suppresses uterine contractions. These results point to a significant role for circulating melatonin in the timing and degree of uterine contractions in late-term pregnancy. Understanding the regulation of melatonin receptors remains a future objective. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

SARS knowledge, perceptions, and behaviors: a comparison between Finns and the Dutch during the SARS outbreak in 2003

NARCIS (Netherlands)

Vartti, A.M.; Oenema, A.; Schreck, M.; Uutela, A.; Zwart, de O.; Brug, J.; Aro, A.R.

2009-01-01

BACKGROUND: The SARS outbreak served to test both local and international outbreak management and risk communication practices. PURPOSE: The study compares SARS knowledge, perceptions, behaviors, and information between Finns and the Dutch during the SARS outbreak in 2003. METHOD: The participants

Using InSAR to Observe Sinkhole Activity in Central Florida

Science.gov (United States)

Oliver-Cabrera, T.; Wdowinski, S.; Kruse, S.; Kiflu, H. G.

2017-12-01

Sinkhole collapse in Florida is a major geologic hazard, threatening human life and causing substantial damage to property. Detecting sinkhole deformation before a collapse is an important but difficult task; most techniques used to monitor sinkholes are spatially constrained to relatively small areas (tens to hundred meters). To overcome this limitation, we use Interferometric Synthetic Aperture Radar (InSAR), which is a very useful technique for detecting localized deformation while covering vast areas. InSAR results show localized deformation at several houses and commercial buildings in different locations along the study sites. We use a subsurface imaging technique, ground penetrating radar, to verify sinkhole existence beneath the observed deforming areas.

MULTI-TEMPORAL SAR INTERFEROMETRY FOR LANDSLIDE MONITORING

Directory of Open Access Journals (Sweden)

R. Dwivedi

2016-06-01

Full Text Available In the past few years, SAR Interferometry specially InSAR and D-InSAR were extensively used for deformation monitoring related applications. Due to temporal and spatial decorrelation in dense vegetated areas, effectiveness of InSAR and D-InSAR observations were always under scrutiny. Multi-temporal InSAR methods are developed in recent times to retrieve the deformation signal from pixels with different scattering characteristics. Presently, two classes of multi-temporal InSAR algorithms are available- Persistent Scatterer (PS and Small Baseline (SB methods. This paper discusses the Stanford Method for Persistent Scatterer (StaMPS based PS-InSAR and the Small Baselines Subset (SBAS techniques to estimate the surface deformation in Tehri dam reservoir region in Uttarkhand, India. Both PS-InSAR and SBAS approaches used sixteen ENVISAT ASAR C-Band images for generating single master and multiple master interferograms stack respectively and their StaMPS processing resulted in time series 1D-Line of Sight (LOS mean velocity maps which are indicative of deformation in terms of movement towards and away from the satellites. From 1D LOS velocity maps, localization of landslide is evident along the reservoir rim area which was also investigated in the previous studies. Both PS-InSAR and SBAS effectively extract measurement pixels in the study region, and the general results provided by both approaches show a similar deformation pattern along the Tehri reservoir region. Further, we conclude that StaMPS based PS-InSAR method performs better in terms of extracting more number of measurement pixels and in the estimation of mean Line of Sight (LOS velocity as compared to SBAS method. It is also proposed to take up a few major landslides area in Uttarakhand for slope stability assessment.

SARS: Key factors in crisis management.

Science.gov (United States)

Tseng, Hsin-Chao; Chen, Thai-Form; Chou, Shieu-Ming

2005-03-01

This study was conducted at a single hospital selected in Taipei during the SARS (Severe Acute Respiratory Syndrome) outbreak from March to July, 2003 in Taiwan. During this period of time, 104 SARS patients were admitted to the hospital. There were no negative reports related to the selected hospital despite its being located right in the center of an area struck by the epidemic. The purpose of this study was to identify the key factors enabling the hospital to survive SARS unscathed. Data were collected from in-depth interviews with the nursing directors and nursing managers of the SARS units, along with a review of relevant hospital documents. The five key elements identified as survival factors during this SARS crisis are as follows: 1. good control of timing for crisis management, 2. careful decision-making, 3. thorough implementation, 4. effective communication, and 5. trust between management and employees. The results of this study reconfirmed the selected hospital as a model for good crisis management during the SARS epidemic.

UAVSAR and TerraSAR-X Based InSAR Detection of Localized Subsidence in the New Orleans Area

Science.gov (United States)

Blom, R. G.; An, K.; Jones, C. E.; Latini, D.

2014-12-01

Vulnerability of the US Gulf coast to inundation has received increased attention since hurricanes Katrina and Rita. Compounding effects of sea level rise, wetland loss, and regional and local subsidence makes flood protection a difficult challenge, and particularly for the New Orleans area. Key to flood protection is precise knowledge of elevations and elevation changes. Analysis of historical and continuing geodetic measurements show surprising complexity, including locations subsiding more rapidly than considered during planning of hurricane protection and coastal restoration projects. Combining traditional, precise geodetic data with interferometric synthetic aperture radar (InSAR) observations can provide geographically dense constraints on surface deformation. The Gulf Coast environment is challenging for InSAR techniques, especially with systems not designed for interferometry. We use two InSAR capable systems, the L- band (24 cm wavelength) airborne JPL/NASA UAVSAR, and the DLR/EADS Astrium spaceborne TerraSAR X-band (3 cm wavelength), and compare results. First, we are applying pair-wise InSAR to the longer wavelength UAVSAR data to detect localized elevation changes potentially impacting flood protection infrastructure from 2009 - 2014. We focus on areas on and near flood protection infrastructure to identify changes indicative of subsidence, structural deformation, and/or seepage. The Spaceborne TerraSAR X-band SAR system has relatively frequent observations, and dense persistent scatterers in urban areas, enabling measurement of very small displacements. We compare L-band UAVSAR results with permanent scatterer (PS-InSAR) and Short Baseline Subsets (SBAS) interferometric analyses of a stack composed by 28 TerraSAR X-band images acquired over the same period. Thus we can evaluate results from the different radar frequencies and analyses techniques. Preliminary results indicate subsidence features potentially of a variety of causes, including ground water

SAR Raw Data Generation for Complex Airport Scenes

Directory of Open Access Journals (Sweden)

Jia Li

2014-10-01

Full Text Available The method of generating the SAR raw data of complex airport scenes is studied in this paper. A formulation of the SAR raw signal model of airport scenes is given. Via generating the echoes from the background, aircrafts and buildings, respectively, the SAR raw data of the unified SAR imaging geometry is obtained from their vector additions. The multipath scattering and the shadowing between the background and different ground covers of standing airplanes and buildings are analyzed. Based on the scattering characteristics, coupling scattering models and SAR raw data models of different targets are given, respectively. A procedure is given to generate the SAR raw data of airport scenes. The SAR images from the simulated raw data demonstrate the validity of the proposed method.

Space Radar Image of West Texas - SAR scan

Science.gov (United States)

1999-01-01

forthcoming Canadian RADARSAT satellite. Spaceborne Imaging Radar-C and X-band Synthetic Aperture Radar (SIR-C/X-SAR) is part of NASA's Mission to Planet Earth. The radars illuminate Earth with microwaves, allowing detailed observations at any time, regardless of weather or sunlight conditions. SIR-C/X-SAR uses three microwave wavelengths: L-band (24 cm), C-band (6 cm) and X-band (3 cm). The multi-frequency data will be used by the international scientific community to better understand the global environment and how it is changing. The SIR-C/X-SAR data, complemented by aircraft and ground studies, will give scientists clearer insights into those environmental changes which are caused by nature and those changes which are induced by human activity. SIR-C was developed by NASA's Jet Propulsion Laboratory. X-SAR was developed by the Dornier and Alenia Spazio companies for the German space agency, Deutsche Agentur fuer Raumfahrtangelegenheiten (DARA), and the Italian space agency, Agenzia Spaziale Italiana (ASI), with the Deutsche Forschungsanstalt fuer Luft und Raumfahrt e.v.(DLR), the major partner in science, operations, and data processing of X-SAR.

Deep learning for SAR image formation

Science.gov (United States)

Mason, Eric; Yonel, Bariscan; Yazici, Birsen

2017-04-01

The recent success of deep learning has lead to growing interest in applying these methods to signal processing problems. This paper explores the applications of deep learning to synthetic aperture radar (SAR) image formation. We review deep learning from a perspective relevant to SAR image formation. Our objective is to address SAR image formation in the presence of uncertainties in the SAR forward model. We present a recurrent auto-encoder network architecture based on the iterative shrinkage thresholding algorithm (ISTA) that incorporates SAR modeling. We then present an off-line training method using stochastic gradient descent and discuss the challenges and key steps of learning. Lastly, we show experimentally that our method can be used to form focused images in the presence of phase uncertainties. We demonstrate that the resulting algorithm has faster convergence and decreased reconstruction error than that of ISTA.

Spatial averaging of fields from half-wave dipole antennas and corresponding SAR calculations in the NORMAN human voxel model between 65 MHz and 2 GHz.

Science.gov (United States)

Findlay, R P; Dimbylow, P J

2009-04-21

If an antenna is located close to a person, the electric and magnetic fields produced by the antenna will vary in the region occupied by the human body. To obtain a mean value of the field for comparison with reference levels, the Institute of Electrical and Electronic Engineers (IEEE) and International Commission on Non-Ionizing Radiation Protection (ICNIRP) recommend spatially averaging the squares of the field strength over the height the body. This study attempts to assess the validity and accuracy of spatial averaging when used for half-wave dipoles at frequencies between 65 MHz and 2 GHz and distances of lambda/2, lambda/4 and lambda/8 from the body. The differences between mean electric field values calculated using ten field measurements and that of the true averaged value were approximately 15% in the 600 MHz to 2 GHz range. The results presented suggest that the use of modern survey equipment, which takes hundreds rather than tens of measurements, is advisable to arrive at a sufficiently accurate mean field value. Whole-body averaged and peak localized SAR values, normalized to calculated spatially averaged fields, were calculated for the NORMAN voxel phantom. It was found that the reference levels were conservative for all whole-body SAR values, but not for localized SAR, particularly in the 1-2 GHz region when the dipole was positioned very close to the body. However, if the maximum field is used for normalization of calculated SAR as opposed to the lower spatially averaged value, the reference levels provide a conservative estimate of the localized SAR basic restriction for all frequencies studied.

Diagnostic sensitivity of two radio receptor assays (TRAK Assay and TRAK Dyno human) for the detection of TSH receptor antibodies

International Nuclear Information System (INIS)

Paunkovic, N.; Paunkovic, J.

2003-01-01

Radio receptor assays for the detection of TSH receptor antibodies in serum are typically based on binding the competition of TSH-R antibodies and 125I -labelled-TSH for membrane preparation of thyrocytes (TBII tests). The sensitivity of the available tests utilizing porcine cell membranes was found to be around 80%. A new test (TRAK Dyno human, BRAHMS) utilizes human recombinant TSH receptor and human standard material that is supposed to improve the performance of the test. We have compared the results of these two assays. The sensitivity of the TRAK Assay tested in 356 patients with untreated Grave's disease was found to be 85%, and 97.5% for TRAK Dyno human in 111 newly diagnosed patients. Both tests were performed from the same serum specimen for 60 of the investigated patients. The TRAK Assay was positive in 50 patients (83.2%) and TRAK Dyno human in 59 patients (98.3%). The specificity of the new radio receptor assay was also improved. (author)

Interaction of PHM, PHI and 24-glutamine PHI with human VIP receptors from colonic epithelium: comparison with rat intestinal receptors

International Nuclear Information System (INIS)

Laburthe, M.; Couvineau, A.; Rouyer-Fessard, C.; Moroder, L.

1985-01-01

PHM, the human counterpart of porcine Peptide Histidine Isoleucine amide (PHI), is shown to be a VIP agonist with low potency on human VIP receptors located in colonic epithelial cell membranes. Its potency is identical to that of PHI but by 3 orders of magnitude lower than that of VIP itself in inhibiting 125 I-VIP binding and in stimulating adenylate cyclase activity. This contrasts markedly with the behavior of PHI on rat VIP receptors located in intestinal epithelial cell membranes where PHI is a potent agonist with a potency that is 1/5 that of VIP. In another connection, the authors show that 24-glutamine PHI has the same affinity as 24-glutamic acid PHI (the natural peptide) for rat or human VIP receptors. These results indicate that while PHI may exert some physiological function through its interaction with VIP receptors in rodents, its human counterpart PHM is a very poor agonist of VIP in human. Furthermore, they show that the drastic change in position 24 of PHI (neutral versus acid residue) does not affect the activity of PHI, at least on VIP receptors. 21 references, 1 figure

Low-SAR metamaterial-inspired printed monopole antenna

Science.gov (United States)

Hossain, M. I.; Faruque, M. R. I.; Islam, M. T.; Ali, M. T.

2017-01-01

In this paper, a low-SAR metamaterial-embedded planar monopole antenna is introduced for a wireless communication system. A printed monopole antenna is designed for modern mobile, which operates in GSM, UMTS, LTE, WLAN, and Bluetooth frequency bands. A metamaterial structure is designed to use in the mobile handset with a multi-band printed monopole antenna. The finite integration technique of the CST microwave studio is used in this study. The measurement of antenna performances is taken in an anechoic chamber, and the SAR values are measured using COMOSAR system. The results indicate that metamaterial structure leads to reduce SAR without affecting antenna performance significantly. According to the measured results, the metamaterial attachment leads to reduce 87.7% peak SAR, 68.2% 1-g SAR, and 46.78% 10-g SAR compared to antenna without metamaterial.

Cytotoxic Activities, SAR and Anti-Invasion Effects of Butylphthalide Derivatives on Human Hepatocellular Carcinoma SMMC7721 Cells

Directory of Open Access Journals (Sweden)

Yihan Hu

2015-11-01

Full Text Available A series of butylphthalide derivatives (BPDs 1–8 were isolated from the extract of the dried rhizome of Ligusticum chuanxiong Hort. (Umbelliferae. The cytotoxic activities of BPDs 1–8 were evaluated using a panel of human cancer cell lines. In addition, the SAR analysis and potential anti-invasion activities were investigated. The sp2 carbons at C-7 and C-7a appeared to be essential for the cytotoxic activities of BPDs. BPDs 5 and 6 remarkably inhibited the migration and invasion of cancer cells. The anti-invasion activity of dimer 6 was demonstrated to be significantly higher than monomer 5.

Endothelin receptors and activity differ in human, dog, and rabbit lung.

Science.gov (United States)

McKay, K O; Armour, C L; Black, J L

1996-01-01

In this study, we have examined dog and rabbit airways as potential models for human airways in regard to the activity of endothelin. The receptors involved in the response to endothelin-1 (ET-1) in airway tissue from human, rabbit, and dog lung were investigated, as was the mechanism responsible for the contraction to ET-1 in tissue from the three species. By using specific endothelin receptor agonists and antagonists, we have demonstrated that ETB receptors predominate in rabbit and human airways and ETA receptors in dog airways. The contraction to ET-1 is not dependent on cyclooxygenase products of arachidonic acid, as indomethacin had no effect on the response to ET-1. Extracellular calcium influx via voltage-dependent channels is necessary for contraction to ET-1 in rabbit and dog airways. These results are in contrast to our previously reported results in human airways, in which neither removal of extracellular calcium nor verapamil affected the ET-1 response. The sustained phase of the contraction to ET-1 in all three species may be mediated in part by activation of protein kinase C (PKC), as the inhibitor staurosporine significantly altered the time course of the response to endothelin. We therefore conclude that in rabbit airways ET-1 activates ETB receptors, triggers the influx of extracellular calcium through voltage-dependent channels, and induces a contractile response that is, in part, dependent upon stimulation of PKC. The same mechanism is triggered in dog bronchus; however, the receptors involved in this species are of the ETA type. Finally, in human airways, the contractile response to ET-1, while independent of extracellular calcium influx, is dependent upon PKC activation after binding of the peptide to ETB receptors.

A NEW SAR CLASSIFICATION SCHEME FOR SEDIMENTS ON INTERTIDAL FLATS BASED ON MULTI-FREQUENCY POLARIMETRIC SAR IMAGERY

Directory of Open Access Journals (Sweden)

W. Wang

2017-11-01

Full Text Available We present a new classification scheme for muddy and sandy sediments on exposed intertidal flats, which is based on synthetic aperture radar (SAR data, and use ALOS-2 (L-band, Radarsat-2 (C-band and TerraSAR-X (X-band fully polarimetric SAR imagery to demonstrate its effectiveness. Four test sites on the German North Sea coast were chosen, which represent typical surface compositions of different sediments, vegetation, and habitats, and of which a large amount of SAR is used for our analyses. Both Freeman-Durden and Cloude-Pottier polarimetric decomposition are utilized, and an additional descriptor called Double-Bounce Eigenvalue Relative Difference (DERD is introduced into the feature sets instead of the original polarimetric intensity channels. The classification is conducted following Random Forest theory, and the results are verified using ground truth data from field campaigns and an existing classification based on optical imagery. In addition, the use of Kennaugh elements for classification purposes is demonstrated using both fully and dual-polarization multi-frequency and multi-temporal SAR data. Our results show that the proposed classification scheme can be applied for the discrimination of muddy and sandy sediments using L-, C-, and X-band SAR images, while SAR imagery acquired at short wavelengths (C- and X-band can also be used to detect more detailed features such as bivalve beds on intertidal flats.

Comparative distribution of human and avian type sialic acid influenza receptors in the pig

Directory of Open Access Journals (Sweden)

Perez Belinda

2010-01-01

Full Text Available Abstract Background A major determinant of influenza infection is the presence of virus receptors on susceptible host cells to which the viral haemagglutinin is able to bind. Avian viruses preferentially bind to sialic acid α2,3-galactose (SAα2,3-Gal linked receptors, whereas human strains bind to sialic acid α2,6-galactose (SAα2,6-Gal linked receptors. To date, there has been no detailed account published on the distribution of SA receptors in the pig, a model host that is susceptible to avian and human influenza subtypes, thus with potential for virus reassortment. We examined the relative expression and spatial distribution of SAα2,3-GalG(1-3GalNAc and SAα2,6-Gal receptors in the major organs from normal post-weaned pigs by binding with lectins Maackia amurensis agglutinins (MAA II and Sambucus nigra agglutinin (SNA respectively. Results Both SAα2,3-Gal and SAα2,6-Gal receptors were extensively detected in the major porcine organs examined (trachea, lung, liver, kidney, spleen, heart, skeletal muscle, cerebrum, small intestine and colon. Furthermore, distribution of both SA receptors in the pig respiratory tract closely resembled the published data of the human tract. Similar expression patterns of SA receptors between pig and human in other major organs were found, with exception of the intestinal tract. Unlike the limited reports on the scarcity of influenza receptors in human intestines, we found increasing presence of SAα2,3-Gal and SAα2,6-Gal receptors from duodenum to colon in the pig. Conclusions The extensive presence of SAα2,3-Gal and SAα2,6-Gal receptors in the major organs examined suggests that each major organ may be permissive to influenza virus entry or infection. The high similarity of SA expression patterns between pig and human, in particular in the respiratory tract, suggests that pigs are not more likely to be potential hosts for virus reassortment than humans. Our finding of relative abundance of SA receptors

[Ceruloplasmin receptor on human erythrocytes].

Science.gov (United States)

Saenko, E L; Basevich, V V; Iaropolov, A I

1988-08-01

The structural fragments of the human ceruloplasmin (CP) molecule and of erythrocyte receptors which provide for the specific interaction of CP with erythrocytes were identified, and their properties were investigated. The interaction of CP with erythrocytes, both intact and treated with neuroaminidase and proteolytic enzymes (trypsin, chymotrypsin, papaine, pronase E) is described. Experiments with CP reception were performed at 4 degrees C, using [125I]CP and [125I]asialo-CP. The parameters of binding were determined in Scatchard plots. It was demonstrated that the specific binding of CP to erythrocyte receptors is determined by its interaction with two structural sites of the carbohydrate moiety of the CP molecule, i.e., the terminal residues of sialic acids and a site, (formula; see text) located at a large distance from the chain terminus.

Transferrin receptors on human reticulocytes: variation in site number in hematologic disorders

International Nuclear Information System (INIS)

Shumak, K.H.; Rachkewich, R.A.

1984-01-01

Assays of binding of 125iodine-labeled ( 125 I) human transferrin were used to study transferrin receptor sites on reticulocytes from 15 normal subjects and from 66 patients with various hematologic disorders. In normal subjects, few or no transferrin receptors were detected whereas the average number of receptors per reticulocyte varied greatly from patient to patient, ranging from 0 to 67,700 in samples, from 35 patients, on which Scatchard analysis of binding of [ 125 I]-transferrin was done. Marked heterogeneity in the number of reticulocyte transferrin receptors in different hematologic disorders was also found in assays with [ 125 I]-OKT9 (monoclonal antibody to the human transferrin receptor). The number of receptors was not correlated with either the reticulocyte count or the hemoglobin

SAR Image Classification Based on Its Texture Features

Institute of Scientific and Technical Information of China (English)

LI Pingxiang; FANG Shenghui

2003-01-01

SAR images not only have the characteristics of all-ay, all-eather, but also provide object information which is different from visible and infrared sensors. However, SAR images have some faults, such as more speckles and fewer bands. The authors conducted the experiments of texture statistics analysis on SAR image features in order to improve the accuracy of SAR image interpretation.It is found that the texture analysis is an effective method for improving the accuracy of the SAR image interpretation.

Experimental Quasi-Microwave Whole-Body Averaged SAR Estimation Method Using Cylindrical-External Field Scanning

Science.gov (United States)

Kawamura, Yoshifumi; Hikage, Takashi; Nojima, Toshio

The aim of this study is to develop a new whole-body averaged specific absorption rate (SAR) estimation method based on the external-cylindrical field scanning technique. This technique is adopted with the goal of simplifying the dosimetry estimation of human phantoms that have different postures or sizes. An experimental scaled model system is constructed. In order to examine the validity of the proposed method for realistic human models, we discuss the pros and cons of measurements and numerical analyses based on the finite-difference time-domain (FDTD) method. We consider the anatomical European human phantoms and plane-wave in the 2GHz mobile phone frequency band. The measured whole-body averaged SAR results obtained by the proposed method are compared with the results of the FDTD analyses.

Group 2 coronaviruses prevent immediate early interferon induction by protection of viral RNA from host cell recognition

International Nuclear Information System (INIS)

Versteeg, Gijs A.; Bredenbeek, Peter J.; Worm, Sjoerd H.E. van den; Spaan, Willy J.M.

2007-01-01

Many viruses encode antagonists to prevent interferon (IFN) induction. Infection of fibroblasts with the murine hepatitis coronavirus (MHV) and SARS-coronavirus (SARS-CoV) did not result in nuclear translocation of interferon-regulatory factor 3 (IRF3), a key transcription factor involved in IFN induction, and induction of IFN mRNA transcription. Furthermore, MHV and SARS-CoV infection could not prevent IFN induction by poly (I:C) or Sendai virus, suggesting that these CoVs do not inactivate IRF3-mediated transcription regulation, but apparently prevent detection of replicative RNA by cellular sensory molecules. Our data indicate that shielding of viral RNA to host cell sensors might be the main general mechanism for coronaviruses to prevent IFN induction

Advanced InSAR imaging for dune mapping

Science.gov (United States)

Havivi, Shiran; August, Yitzhak; Blumberg, Dan G.; Rotman, Stanley R.

2015-04-01

Aeolian morphologies are formed in the presence of sufficient wind energy and available particles. These processes occur naturally or are further enhanced or reduced by human intervention. The dimensions of change are dependent primarily on the wind energy and surface properties. Since the 1970's, remote sensing imagery both optical and radar, are used for documentation and interpretation of the geomorphologic changes of sand dunes. Remote sensing studies of Aeolian morphologies is mostly useful to document major changes, yet, subtle changes, occurring in a period of days or months in scales of centimeters, are very difficult to detect in imagery. Interferometric Synthetic Aperture Radar (InSAR) is an imaging technique for measuring Earth's surface topography and deformation. InSAR images are produced by measuring the radar phase difference between two separated antennas that view the same surface area. Classical InSAR is based on high coherence between two images or more. The output (interferogram) can show subtle changes with an accuracy of several millimeters to centimeters. Very little work has been done on measuring or identifying the changes in dunes using InSAR. The reason is that dunes tend to be less coherent than firm, stable, surfaces. This research aims to demonstrate how interferometric decorrelation, or, coherence change detection, can be used for identifying dune instability. We hypothesize and demonstrate that the loss of radar coherence over time on dunes can be used as an indication of the dune's instability. When SAR images are acquired at sufficiently close intervals one can measure the time it takes to lose coherence and associate this time with geomorphic stability. To achieve our goals, the Nitzanim coastal dunes along the Mediterranean, 40 km south of Tel-Aviv, Israel, were chosen as a case study. The dunes in this area are of varying levels of stability and vegetation cover and have been monitored meteorologically, geomorphologically and

The SARS Coronavirus 3a protein causes endoplasmic reticulum stress and induces ligand-independent downregulation of the type 1 interferon receptor.

Directory of Open Access Journals (Sweden)

Rinki Minakshi

2009-12-01

Full Text Available The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV is reported to cause apoptosis of infected cells and several of its proteins including the 3a accessory protein, are pro-apoptotic. Since the 3a protein localizes to the endoplasmic reticulum (ER-Golgi compartment, its role in causing ER stress was investigated in transiently transfected cells. Cells expressing the 3a proteins showed ER stress based on activation of genes for the ER chaperones GRP78 and GRP94. Since ER stress can cause differential modulation of the unfolded protein response (UPR, which includes the inositol-requiring enzyme 1 (IRE-1, activating transcription factor 6 (ATF6 and PKR-like ER kinase (PERK pathways, these were individually tested in 3a-expressing cells. Only the PERK pathway was found to be activated in 3a-expressing cells based on (1 increased phosphorylation of eukaryotic initiation factor 2 alpha (eIF2alpha and inhibitory effects of a dominant-negative form of eIF2alpha on GRP78 promoter activity, (2 increased translation of activating transcription factor 4 (ATF4 mRNA, and (3 ATF4-dependent activation of the C/EBP homologous protein (CHOP gene promoter. Activation of PERK affects innate immunity by suppression of type 1 interferon (IFN signaling. The 3a protein was found to induce serine phosphorylation within the IFN alpha-receptor subunit 1 (IFNAR1 degradation motif and to increase IFNAR1 ubiquitination. Confocal microscopic analysis showed increased translocation of IFNAR1 into the lysosomal compartment and flow cytometry showed reduced levels of IFNAR1 in 3a-expressing cells. These results provide further mechanistic details of the pro-apoptotic effects of the SARS-CoV 3a protein, and suggest a potential role for it in attenuating interferon responses and innate immunity.

Cloning of the cDNA and gene for a human D2 dopamine receptor

International Nuclear Information System (INIS)

Grady, D.K.; Makam, H.; Stofko, R.E.; Bunzow, J.R.; Civelli, O.; Marchionni, M.A.; Alfano, M.; Frothingham, L.; Fischer, J.B.; Burke-Howie, K.J.; Server, A.C.

1989-01-01

A clone encoding a human D 2 dopamine receptor was isolated from a pituitary cDNA library and sequenced. The deduced protein sequence is 96% identical with that of the cloned rat receptor with one major difference: the human receptor contains an additional 29 amino acids in its putative third cytoplasmic loop. Southern blotting demonstrated the presence of only one human D 2 receptor gene. Two overlapping phage containing the gene were isolated and characterized. DNA sequence analysis of these clones showed that the coding sequence is interrupted by six introns and that the additional amino acids present in the human pituitary receptor are encoded by a single exon of 87 base pairs. The involvement of this sequence in alternative splicing and its biological significance are discussed

Structure and function of the IFNγ receptor on human mononuclear phagocytes

International Nuclear Information System (INIS)

Schreiber, R.D.; Celada, A.

1986-01-01

Human mononuclear phagocytes bear a receptor that binds 125 I-IFNγ in a saturable, reversible and specific manner. The receptor consists minimally of a 70 kD polypeptide chain and its expression (5000/cell) and binding affinity (Ka=10 9 M -1 ) are unaffected by cellular activation or differentiation. The receptor's biological relevance was validated by correlating receptor occupancy with induction of a cellular response. 50% maximal induction of Fc receptors on U937 was effected by 0.8 nM IFNγ; the same concentration needed to half saturate U937 IFNγ receptors. Ligand-receptor interaction displayed species specificity but not cellular specificity. The receptors on U937 and human fibroblasts displayed identical ligand binding affinities (1.5-1.8 x 10 9 M -1 ). At 37 0 C, IFNγ bound to U937 in a biphasic manner. The high affinity binding component was due to ligand internalization since purified cell membranes and paraformaldehyde fixed cells displayed only the lower Ka and ligand internalization could be directly demonstrated. Using lysosomotropic amines, the internalized IFNγ-IFNγ receptor complex was tracked into an acid compartment where dissociation occurred. Free intracellular IFNγ was then degraded while free receptor entered an intracellular pool and eventually recycled back to the cell surface

The Ecosystems SAR (EcoSAR) an Airborne P-band Polarimetric InSAR for the Measurement of Vegetation Structure, Biomass and Permafrost

Science.gov (United States)

Rincon, Rafael F.; Fatoyinbo, Temilola; Ranson, K. Jon; Osmanoglu, Batuhan; Sun, Guoqing; Deshpande, Manohar D.; Perrine, Martin L.; Du Toit, Cornelis F.; Bonds, Quenton; Beck, Jaclyn;

Three mutations switch H7N9 influenza to human-type receptor specificity

Energy Technology Data Exchange (ETDEWEB)

de Vries, Robert P.; Peng, Wenjie; Grant, Oliver C.; Thompson, Andrew J.; Zhu, Xueyong; Bouwman, Kim M.; de la Pena, Alba T. Torrents; van Breemen, Marielle J.; Ambepitiya Wickramasinghe, Iresha N.; de Haan, Cornelis A. M.; Yu, Wenli; McBride, Ryan; Sanders, Rogier W.; Woods, Robert J.; Verheije, Monique H.; Wilson, Ian A.; Paulson, James C.; Fernandez-Sesma, Ana

2017-06-15

The avian H7N9 influenza outbreak in 2013 resulted from an unprecedented incidence of influenza transmission to humans from infected poultry. The majority of human H7N9 isolates contained a hemagglutinin (HA) mutation (Q226L) that has previously been associated with a switch in receptor specificity from avian-type (NeuAcα2-3Gal) to human-type (NeuAcα2-6Gal), as documented for the avian progenitors of the 1957 (H2N2) and 1968 (H3N2) human influenza pandemic viruses. While this raised concern that the H7N9 virus was adapting to humans, the mutation was not sufficient to switch the receptor specificity of H7N9, and has not resulted in sustained transmission in humans. To determine if the H7 HA was capable of acquiring human-type receptor specificity, we conducted mutation analyses. Remarkably, three amino acid mutations conferred a switch in specificity for human-type receptors that resembled the specificity of the 2009 human H1 pandemic virus, and promoted binding to human trachea epithelial cells.

Three mutations switch H7N9 influenza to human-type receptor specificity.

Directory of Open Access Journals (Sweden)

Robert P de Vries

2017-06-01

Full Text Available The avian H7N9 influenza outbreak in 2013 resulted from an unprecedented incidence of influenza transmission to humans from infected poultry. The majority of human H7N9 isolates contained a hemagglutinin (HA mutation (Q226L that has previously been associated with a switch in receptor specificity from avian-type (NeuAcα2-3Gal to human-type (NeuAcα2-6Gal, as documented for the avian progenitors of the 1957 (H2N2 and 1968 (H3N2 human influenza pandemic viruses. While this raised concern that the H7N9 virus was adapting to humans, the mutation was not sufficient to switch the receptor specificity of H7N9, and has not resulted in sustained transmission in humans. To determine if the H7 HA was capable of acquiring human-type receptor specificity, we conducted mutation analyses. Remarkably, three amino acid mutations conferred a switch in specificity for human-type receptors that resembled the specificity of the 2009 human H1 pandemic virus, and promoted binding to human trachea epithelial cells.

Avian and human influenza A virus receptors in trachea and lung of animals.

Science.gov (United States)

Thongratsakul, Sukanya; Suzuki, Yasuo; Hiramatsu, Hiroaki; Sakpuaram, Thavajchai; Sirinarumitr, Theerapol; Poolkhet, Chaithep; Moonjit, Pattra; Yodsheewan, Rungrueang; Songserm, Thaweesak

2010-12-01

Influenza A viruses are capable of crossing the specific barrier between human beings and animals resulting in interspecies transmission. The important factor of potential infectivity of influenza A viruses is the suitability of the receptor binding site of the host and viruses. The affinities of avian and human influenza virus to bind with the receptors and the distributions of receptors in animals are different. This study aims to investigate the anatomical distribution of avian and human influenza virus receptors using the double staining lectin histochemistry method. Double staining of lectin histochemistry was performed to identify both SA alpha2,3 Gal and SA alpha2,6 Gal receptors in trachea and lung tissue of dogs, cats, tigers, ferret, pigs, ducks and chickens. We have demonstrated that avian and human influenza virus receptors were abundantly present in trachea, bronchus and bronchiole, but in alveoli of dogs, cats and tigers showed SA alpha2,6 Gal only. Furthermore, endothelial cells in lung tissues showed presence of SA alpha2,3 Gal. The positive sites of both receptors in respiratory tract, especially in the trachea, suggest that all mammalian species studied can be infected with avian influenza virus. These findings suggested that dogs and cats in close contact with humans should be of greater concern as an intermediate host for avian influenza A in which there is the potential for viral adaptation and reassortment.

FlexSAR, a high quality, flexible, cost effective, prototype SAR system

Science.gov (United States)

Jensen, Mark; Knight, Chad; Haslem, Brent

2016-05-01

The FlexSAR radar system was designed to be a high quality, low-cost, flexible research prototype instrument. Radar researchers and practitioners often desire the ability to prototype new or advanced configurations, yet the ability to enhance or upgrade existing radar systems can be cost prohibitive. FlexSAR answers the need for a flexible radar system that can be extended easily, with minimal cost and time expenditures. The design approach focuses on reducing the resources required for developing and validating new advanced radar modalities. Such an approach fosters innovation and provides risk reduction since actual radar data can be collected in the appropriate mode, processed, and analyzed early in the development process. This allows for an accurate, detailed understanding of the corresponding trade space. This paper is a follow-on to last years paper and discusses the advancements that have been made to the FlexSAR system. The overall system architecture is discussed and presented along with several examples illustrating the system utility.

Cloning and expression of a human kidney cDNA for an α2-adrenergic receptor subtype

International Nuclear Information System (INIS)

Regan, J.W.; Kobilka, T.S.; Yang-Feng, T.L.; Caron, M.G.; Lefkowitz, R.J.; Kobilka, B.K.

1988-01-01

An α 2 -adrenergic receptor subtype has been cloned from a human kidney cDNA library using the gene for the human platelet α 2 -adrenergic receptor as a probe. The deduced amino acid sequence resembles the human platelet α 2 -adrenergic receptor and is consistent with the structure of other members of he family of guanine nucleotide-binding protein-coupled receptors. The cDNA was expressed in a mammalian cell line (COS-7), and the α 2 -adrenergic ligand [ 3 H]rauwolscine was bound. Competition curve analysis with a variety of adrenergic ligands suggests that this cDNA clone represents the α 2 B-adrenergic receptor. The gene for this receptor is on human chromosome 4, whereas the gene for the human platelet α 2 -adrenergic receptor (α 2 A) lies on chromosome 10. This ability to express the receptor in mammalian cells, free of other adrenergic receptor subtypes, should help in developing more selective α-adrenergic ligands

Convolutional Neural Networks for SAR Image Segmentation

DEFF Research Database (Denmark)

Malmgren-Hansen, David; Nobel-Jørgensen, Morten

2015-01-01

Segmentation of Synthetic Aperture Radar (SAR) images has several uses, but it is a difficult task due to a number of properties related to SAR images. In this article we show how Convolutional Neural Networks (CNNs) can easily be trained for SAR image segmentation with good results. Besides...

PHARUS : PHased ARray Universal SAR

NARCIS (Netherlands)

Paquay, M.H.A.; Vermeulen, B.C.B.; Koomen, P.J.; Hoogeboom, P.; Snoeij, P.; Pouwels, H.

1996-01-01

In the Netherlands, a polarimetric C-band aircraft SAR (Synthetic Aperture Radar) has been developed. The project is called PHARUS, an acronm for PHased ARray Universal SAR. This instrument serves remote sensing applications. The antenna system contains 48 active modules (expandable to 96). A module

Beta adrenergic receptors in human cavernous tissue

Energy Technology Data Exchange (ETDEWEB)

Dhabuwala, C.B.; Ramakrishna, C.V.; Anderson, G.F.

1985-04-01

Beta adrenergic receptor binding was performed with /sup 125/I iodocyanopindolol on human cavernous tissue membrane fractions from normal tissue and transsexual procedures obtained postoperatively, as well as from postmortem sources. Isotherm binding studies on normal fresh tissues indicated that the receptor density was 9.1 fmoles/mg. with a KD of 23 pM. Tissue stored at room temperature for 4 to 6 hours, then at 4C in saline solution for 19 to 20 hours before freezing showed no significant changes in receptor density or affinity, and provided evidence for the stability of postmortem tissue obtained within the same time period. Beta receptor density of 2 cavernous preparations from transsexual procedures was not significantly different from normal control tissues, and showed that high concentrations of estrogen received by these patients had no effect on beta adrenergic receptor density. Displacement of /sup 125/iodocyanopindolol by 5 beta adrenergic agents demonstrated that 1-propranolol had the greatest affinity followed by ICI 118,551, zinterol, metoprolol and practolol. When the results of these displacement studies were subjected to Scatfit, non- linear regression line analysis, a single binding site was described. Based on the relative potency of the selective beta adrenergic agents it appears that these receptors were of the beta 2 subtype.

Spaceborne Polarimetric SAR Interferometry: Performance Analysis and Mission Concepts

Directory of Open Access Journals (Sweden)

Shane R. Cloude

2005-12-01

Full Text Available We investigate multichannel imaging radar systems employing coherent combinations of polarimetry and interferometry (Pol-InSAR. Such systems are well suited for the extraction of bio- and geophysical parameters by evaluating the combined scattering from surfaces and volumes. This combination leads to several important differences between the design of Pol-InSAR sensors and conventional single polarisation SAR interferometers. We first highlight these differences and then investigate the Pol-InSAR performance of two proposed spaceborne SAR systems (ALOS/PalSAR and TerraSAR-L operating in repeat-pass mode. For this, we introduce the novel concept of a phase tube which enables (1 a quantitative assessment of the Pol-InSAR performance, (2 a comparison between different sensor configurations, and (3 an optimization of the instrument settings for different Pol-InSAR applications. The phase tube may hence serve as an interface between system engineers and application-oriented scientists. The performance analysis reveals major limitations for even moderate levels of temporal decorrelation. Such deteriorations may be avoided in single-pass sensor configurations and we demonstrate the potential benefits from the use of future bi- and multistatic SAR interferometers.

SARS-related Perceptions in Hong Kong

OpenAIRE

Lau, Joseph T.F.; Yang, Xilin; Pang, Ellie; Tsui, H.Y.; Wong, Eric; Wing, Yun Kwok

2005-01-01

To understand different aspects of community responses related to severe acute respiratory syndrome (SARS), 2 population-based, random telephone surveys were conducted in June 2003 and January 2004 in Hong Kong. More than 70% of respondents would avoid visiting hospitals or mainland China to avoid contracting SARS. Most respondents believed that SARS could be transmitted through droplets, fomites, sewage, and animals. More than 90% believed that public health measures were efficacious means o...

Genome organization of the SARS-CoV

DEFF Research Database (Denmark)

Xu, Jing; Hu, Jianfei; Wang, Jing

2003-01-01

Annotation of the genome sequence of the SARS-CoV (severe acute respiratory syndrome-associated coronavirus) is indispensable to understand its evolution and pathogenesis. We have performed a full annotation of the SARS-CoV genome sequences by using annotation programs publicly available or devel......Annotation of the genome sequence of the SARS-CoV (severe acute respiratory syndrome-associated coronavirus) is indispensable to understand its evolution and pathogenesis. We have performed a full annotation of the SARS-CoV genome sequences by using annotation programs publicly available...

Human estrogen receptor (ESR) gene locus: PssI dimorphism

Energy Technology Data Exchange (ETDEWEB)

Coleman, R T; Taylor, J E; Frossard, P M [California Biotechnology Inc., Mountain View, CA (USA); Shine, J J [Garvan Institute, Darlinghurst (Australia)

1988-07-25

pESR-2, a 2.1 kb partial cDNA containing the entire translated sequence of the human estrogen receptor mRNA isolated from MCF-7 human breast cancer cells, was subcloned in the Eco RI site of pBR322. PssI (PuGGNCCPy) identifies a single two-allele polymorphism with bands at either 1.7 or 1.4 kb, as well as invariant bands at 12.6, 9.3, 4.1, 3.7, 2.4, 2.2, and 1.2 kb. Its frequency was studied in 77 unrelated North American Caucasians. The human estrogen receptor gene has been localized to 6q24 -- q27 by in situ hybridization. Co-dominant segregation is demonstrated in one family (8 individuals).

How infectious is SARS virus

Indian Academy of Sciences (India)

First page Back Continue Last page Overview Graphics. How infectious is SARS virus. Influenza: 1 patient infects ten people. SARS: 1 patient infects 2-4 people. Incubation period 10 days. Are there `silent´ cases ? Is quarantine enough ? How will it behave if and when it returns ?

Imaging in severe acute respiratory syndrome (SARS)

International Nuclear Information System (INIS)

Antonio, G.E.; Wong, K.T.; Chu, W.C.W.; Hui, D.S.C.; Cheng, F.W.T.; Yuen, E.H.Y.; Chung, S.S.C.; Fok, T.F.; Sung, J.J.Y.; Ahuja, A.T.

2003-01-01

Severe acute respiratory syndrome (SARS) is a highly infectious disease caused by a novel coronavirus, and has become pandemic within a short period of time. Imaging plays an important role in the diagnosis, management and follow-up of patients with SARS. The current status of imaging in SARS is presented in this review

PRF Ambiguity Detrmination for Radarsat ScanSAR System

Science.gov (United States)

Jin, Michael Y.

1998-01-01

PRF ambiguity is a potential problem for a spaceborne SAR operated at high frequencies. For a strip mode SAR, there were several approaches to solve this problem. This paper, however, addresses PRF ambiguity determination algorithms suitable for a burst mode SAR system such as the Radarsat ScanSAR. The candidate algorithms include the wavelength diversity algorithm, range look cross correlation algorithm, and multi-PRF algorithm.

Interleukin-6 receptor expression in contracting human skeletal muscle: regulating role of IL-6

DEFF Research Database (Denmark)

Keller, Pernille; Penkowa, Milena; Keller, Charlotte

2005-01-01

Contracting muscle fibers produce and release IL-6, and plasma levels of this cytokine are markedly elevated in response to physical exercise. We recently showed autocrine regulation of IL-6 in human skeletal muscle in vivo and hypothesized that this may involve up-regulation of the IL-6 receptor....... Infusion of rhIL-6 to humans had no effect on the mRNA level of the IL-6 receptor, whereas there was an increase at the protein level. IL-6 receptor mRNA increased similarly in muscle of both IL-6 KO mice and wild-type mice in response to exercise. In conclusion, exercise increases IL-6 receptor production....... Therefore, we investigated IL-6 receptor regulation in response to exercise and IL-6 infusion in humans. Furthermore, using IL-6-deficient mice, we investigated the role of IL-6 in the IL-6 receptor response to exercise. Human skeletal muscle biopsies were obtained in relation to: 3 h of bicycle exercise...

Satellite on-board real-time SAR processor prototype

Science.gov (United States)

Bergeron, Alain; Doucet, Michel; Harnisch, Bernd; Suess, Martin; Marchese, Linda; Bourqui, Pascal; Desnoyers, Nicholas; Legros, Mathieu; Guillot, Ludovic; Mercier, Luc; Châteauneuf, François

2017-11-01

A Compact Real-Time Optronic SAR Processor has been successfully developed and tested up to a Technology Readiness Level of 4 (TRL4), the breadboard validation in a laboratory environment. SAR, or Synthetic Aperture Radar, is an active system allowing day and night imaging independent of the cloud coverage of the planet. The SAR raw data is a set of complex data for range and azimuth, which cannot be compressed. Specifically, for planetary missions and unmanned aerial vehicle (UAV) systems with limited communication data rates this is a clear disadvantage. SAR images are typically processed electronically applying dedicated Fourier transformations. This, however, can also be performed optically in real-time. Originally the first SAR images were optically processed. The optical Fourier processor architecture provides inherent parallel computing capabilities allowing real-time SAR data processing and thus the ability for compression and strongly reduced communication bandwidth requirements for the satellite. SAR signal return data are in general complex data. Both amplitude and phase must be combined optically in the SAR processor for each range and azimuth pixel. Amplitude and phase are generated by dedicated spatial light modulators and superimposed by an optical relay set-up. The spatial light modulators display the full complex raw data information over a two-dimensional format, one for the azimuth and one for the range. Since the entire signal history is displayed at once, the processor operates in parallel yielding real-time performances, i.e. without resulting bottleneck. Processing of both azimuth and range information is performed in a single pass. This paper focuses on the onboard capabilities of the compact optical SAR processor prototype that allows in-orbit processing of SAR images. Examples of processed ENVISAT ASAR images are presented. Various SAR processor parameters such as processing capabilities, image quality (point target analysis), weight and

Cyto- and receptor architecture of area 32 in human and macaque brains.

Science.gov (United States)

Palomero-Gallagher, Nicola; Zilles, Karl; Schleicher, Axel; Vogt, Brent A

2013-10-01

Human area 32 plays crucial roles in emotion and memory consolidation. It has subgenual (s32), pregenual (p32), dorsal, and midcingulate components. We seek to determine whether macaque area 32 has subgenual and pregenual subdivisions and the extent to which they are comparable to those in humans by means of NeuN immunohistochemistry and multireceptor analysis of laminar profiles. The macaque has areas s32 and p32. In s32, layer IIIa/b neurons are larger than those of layer IIIc. This relationship is reversed in p32. Layer Va is thicker and Vb thinner in s32. Area p32 contains higher kainate, benzodiazepine (BZ), and serotonin (5-HT)1A but lower N-methyl-D-aspartate (NMDA) and α2 receptor densities. Most differences were found in layers I, II, and VI. Together, these differences support the dual nature of macaque area 32. Comparative analysis of human and macaque s32 and p32 supports equivalences in cyto- and receptor architecture. Although there are differences in mean areal receptor densities, there are considerable similarities at the layer level. Laminar receptor distribution patterns in each area are comparable in the two species in layers III-Va for kainate, NMDA, γ-aminobutyric acid (GABA)B , BZ, and 5-HT1A receptors. Multivariate statistical analysis of laminar receptor densities revealed that human s32 is more similar to macaque s32 and p32 than to human p32. Thus, macaque 32 is more complex than hitherto known. Our data suggest a homologous neural architecture in anterior cingulate s32 and p32 in human and macaque brains. © 2013 Wiley Periodicals, Inc.

Implementation of integrated circuit and design of SAR ADC for fully implantable hearing aids.

Science.gov (United States)

Kim, Jong Hoon; Lee, Jyung Hyun; Cho, Jin-Ho

2017-07-20

The hearing impaired population has been increasing; many people suffer from hearing problems. To deal with this difficulty, various types of hearing aids are being rapidly developed. In particular, fully implantable hearing aids are being actively studied to improve the performance of existing hearing aids and to reduce the stigma of hearing loss patients. It has to be of small size and low-power consumption for easy implantation and long-term use. The objective of the study was to implement a small size and low-power consumption successive approximation register analog-to-digital converter (SAR ADC) for fully implantable hearing aids. The ADC was selected as the SAR ADC because its analog circuit components are less required by the feedback circuit of the SAR ADC than the sigma-delta ADC which is conventionally used in hearing aids, and it has advantages in the area and power consumption. So, the circuit of SAR ADC is designed considering the speech region of humans because the objective is to deliver the speech signals of humans to hearing loss patients. If the switch of sample and hold works in the on/off positions, the charge injection and clock feedthrough are produced by a parasitic capacitor. These problems affect the linearity of the hold voltage, and as a result, an error of the bit conversion is generated. In order to solve the problem, a CMOS switch that consists of NMOS and PMOS was used, and it reduces the charge injection because the charge carriers in the NMOS and PMOS have inversed polarity. So, 16 bit conversion is performed before the occurrence of the Least Significant Bit (LSB) error. In order to minimize the offset voltage and power consumption of the designed comparator, we designed a preamplifier with current mirror. Therefore, the power consumption was reduced by the power control switch used in the comparator. The layout of the designed SAR ADC was performed by Virtuoso Layout Editor (Cadence, USA). In the layout result, the size of the

Monitoring Building Deformation with InSAR: Experiments and Validation

Science.gov (United States)

Yang, Kui; Yan, Li; Huang, Guoman; Chen, Chu; Wu, Zhengpeng

2016-01-01

Synthetic Aperture Radar Interferometry (InSAR) techniques are increasingly applied for monitoring land subsidence. The advantages of InSAR include high accuracy and the ability to cover large areas; nevertheless, research validating the use of InSAR on building deformation is limited. In this paper, we test the monitoring capability of the InSAR in experiments using two landmark buildings; the Bohai Building and the China Theater, located in Tianjin, China. They were selected as real examples to compare InSAR and leveling approaches for building deformation. Ten TerraSAR-X images spanning half a year were used in Permanent Scatterer InSAR processing. These extracted InSAR results were processed considering the diversity in both direction and spatial distribution, and were compared with true leveling values in both Ordinary Least Squares (OLS) regression and measurement of error analyses. The detailed experimental results for the Bohai Building and the China Theater showed a high correlation between InSAR results and the leveling values. At the same time, the two Root Mean Square Error (RMSE) indexes had values of approximately 1 mm. These analyses show that a millimeter level of accuracy can be achieved by means of InSAR technique when measuring building deformation. We discuss the differences in accuracy between OLS regression and measurement of error analyses, and compare the accuracy index of leveling in order to propose InSAR accuracy levels appropriate for monitoring buildings deformation. After assessing the advantages and limitations of InSAR techniques in monitoring buildings, further applications are evaluated. PMID:27999403

Monitoring Building Deformation with InSAR: Experiments and Validation

Directory of Open Access Journals (Sweden)

Kui Yang

2016-12-01

Full Text Available Synthetic Aperture Radar Interferometry (InSAR techniques are increasingly applied for monitoring land subsidence. The advantages of InSAR include high accuracy and the ability to cover large areas; nevertheless, research validating the use of InSAR on building deformation is limited. In this paper, we test the monitoring capability of the InSAR in experiments using two landmark buildings; the Bohai Building and the China Theater, located in Tianjin, China. They were selected as real examples to compare InSAR and leveling approaches for building deformation. Ten TerraSAR-X images spanning half a year were used in Permanent Scatterer InSAR processing. These extracted InSAR results were processed considering the diversity in both direction and spatial distribution, and were compared with true leveling values in both Ordinary Least Squares (OLS regression and measurement of error analyses. The detailed experimental results for the Bohai Building and the China Theater showed a high correlation between InSAR results and the leveling values. At the same time, the two Root Mean Square Error (RMSE indexes had values of approximately 1 mm. These analyses show that a millimeter level of accuracy can be achieved by means of InSAR technique when measuring building deformation. We discuss the differences in accuracy between OLS regression and measurement of error analyses, and compare the accuracy index of leveling in order to propose InSAR accuracy levels appropriate for monitoring buildings deformation. After assessing the advantages and limitations of InSAR techniques in monitoring buildings, further applications are evaluated.

Tracking Human-Induced Landscape Disturbance at the Nasca Lines UNESCO World Heritage Site in Peru with COSMO-SkyMed InSAR

OpenAIRE

Francesca Cigna; Deodato Tapete

2018-01-01

The “Lines and Geoglyphs of Nasca and Palpa” in Peru are among the most well-known UNESCO World Heritage Sites globally, and an exemplar of site where heritage assets cannot be separated from their natural and anthropogenic environment. The site is exposed to interactions with natural processes, as well as human presence. In this work, 3-m resolution synthetic aperture radar (SAR) StripMap HIMAGE HH-polarised scenes acquired by the X-band COSMO-SkyMed constellation are exploited to track two ...

Molecular mechanisms of severe acute respiratory syndrome (SARS

Directory of Open Access Journals (Sweden)

Zabel Peter

2005-01-01

Full Text Available Abstract Severe acute respiratory syndrome (SARS is a new infectious disease caused by a novel coronavirus that leads to deleterious pulmonary pathological features. Due to its high morbidity and mortality and widespread occurrence, SARS has evolved as an important respiratory disease which may be encountered everywhere in the world. The virus was identified as the causative agent of SARS due to the efforts of a WHO-led laboratory network. The potential mutability of the SARS-CoV genome may lead to new SARS outbreaks and several regions of the viral genomes open reading frames have been identified which may contribute to the severe virulence of the virus. With regard to the pathogenesis of SARS, several mechanisms involving both direct effects on target cells and indirect effects via the immune system may exist. Vaccination would offer the most attractive approach to prevent new epidemics of SARS, but the development of vaccines is difficult due to missing data on the role of immune system-virus interactions and the potential mutability of the virus. Even in a situation of no new infections, SARS remains a major health hazard, as new epidemics may arise. Therefore, further experimental and clinical research is required to control the disease.

Distribution of cellular HSV-1 receptor expression in human brain.

Science.gov (United States)

Lathe, Richard; Haas, Juergen G

2017-06-01

Herpes simplex virus type 1 (HSV-1) is a neurotropic virus linked to a range of acute and chronic neurological disorders affecting distinct regions of the brain. Unusually, HSV-1 entry into cells requires the interaction of viral proteins glycoprotein D (gD) and glycoprotein B (gB) with distinct cellular receptor proteins. Several different gD and gB receptors have been identified, including TNFRSF14/HVEM and PVRL1/nectin 1 as gD receptors and PILRA, MAG, and MYH9 as gB receptors. We investigated the expression of these receptor molecules in different areas of the adult and developing human brain using online transcriptome databases. Whereas all HSV-1 receptors showed distinct expression patterns in different brain areas, the Allan Brain Atlas (ABA) reported increased expression of both gD and gB receptors in the hippocampus. Specifically, for PVRL1, TNFRFS14, and MYH9, the differential z scores for hippocampal expression, a measure of relative levels of increased expression, rose to 2.9, 2.9, and 2.5, respectively, comparable to the z score for the archetypical hippocampus-enriched mineralocorticoid receptor (NR3C2, z = 3.1). These data were confirmed at the Human Brain Transcriptome (HBT) database, but HBT data indicate that MAG expression is also enriched in hippocampus. The HBT database allowed the developmental pattern of expression to be investigated; we report that all HSV1 receptors markedly increase in expression levels between gestation and the postnatal/adult periods. These results suggest that differential receptor expression levels of several HSV-1 gD and gB receptors in the adult hippocampus are likely to underlie the susceptibility of this brain region to HSV-1 infection.

Identification of the proteins responsible for SAR DNA binding in nuclear matrix of ''Cucurbita pepo''

International Nuclear Information System (INIS)

Rzepecki, R.; Markiewicz, E.; Szopa, J.

1995-01-01

The nuclear matrices from White bush (''Cucurbita pepo var. patisonina'') cell nuclei have been isolated using three methods: I, standard procedure involving extraction of cell nuclei with 2 M NaCl and 1% Triton X-100; II, the same with pre-treatment of cell nuclei with 0.5 mM CuSO 4 (stabilisation step); and III, method with extraction by lithium diiodosalicylate (LIS), and compared the polypeptide pattern. The isolated matrices specifically bind SAR DNA derived from human β-interferon gene in the exogenous SAR binding assay and in the gel mobility shift assay. Using IgG against the 32 kDa endonuclease we have found in the DNA-protein blot assay that this protein is one of the proteins binding SAR DNA. We have identified three proteins with molecular mass of 65 kDa, 60 kDa and 32 kDa which are responsible for SAR DNA binding in the gel mobility shift assay experiments. (author). 21 refs, 3 figs

Cloning and expression of a cDNA coding for the human platelet-derived growth factor receptor: Evidence for more than one receptor class

International Nuclear Information System (INIS)

Gronwald, R.G.K.; Grant, F.J.; Haldeman, B.A.; Hart, C.E.; O'Hara, P.J.; Hagen, F.S.; Ross, R.; Bowen-Pope, D.F.; Murray, M.J.

1988-01-01

The complete nucleotide sequence of a cDNA encoding the human platelet-derived growth factor (PDGF) receptor is presented. The cDNA contains an open reading frame that codes for a protein of 1106 amino acids. Comparison to the mouse PDGF receptor reveals an overall amino acid sequence identity of 86%. This sequence identity rises to 98% in the cytoplasmic split tyrosine kinase domain. RNA blot hybridization analysis of poly(A) + RNA from human dermal fibroblasts detects a major and a minor transcript using the cDNA as a probe. Baby hamster kidney cells, transfected with an expression vector containing the receptor cDNA, express an ∼ 190-kDa cell surface protein that is recognized by an anti-human PDGF receptor antibody. The recombinant PDGF receptor is functional in the transfected baby hamster kidney cells as demonstrated by ligand-induced phosphorylation of the receptor. Binding properties of the recombinant PDGF receptor were also assessed with pure preparations of BB and AB isoforms of PDGF. Unlike human dermal fibroblasts, which bind both isoforms with high affinity, the transfected baby hamster kidney cells bind only the BB isoform of PDGF with high affinity. This observation is consistent with the existence of more than one PDGF receptor class

Vaccine efficacy in senescent mice challenged with recombinant SARS-CoV bearing epidemic and zoonotic spike variants.

Directory of Open Access Journals (Sweden)

Damon Deming

2006-12-01

Full Text Available In 2003, severe acute respiratory syndrome coronavirus (SARS-CoV was identified as the etiological agent of severe acute respiratory syndrome, a disease characterized by severe pneumonia that sometimes results in death. SARS-CoV is a zoonotic virus that crossed the species barrier, most likely originating from bats or from other species including civets, raccoon dogs, domestic cats, swine, and rodents. A SARS-CoV vaccine should confer long-term protection, especially in vulnerable senescent populations, against both the 2003 epidemic strains and zoonotic strains that may yet emerge from animal reservoirs. We report the comprehensive investigation of SARS vaccine efficacy in young and senescent mice following homologous and heterologous challenge.Using Venezuelan equine encephalitis virus replicon particles (VRP expressing the 2003 epidemic Urbani SARS-CoV strain spike (S glycoprotein (VRP-S or the nucleocapsid (N protein from the same strain (VRP-N, we demonstrate that VRP-S, but not VRP-N vaccines provide complete short- and long-term protection against homologous strain challenge in young and senescent mice. To test VRP vaccine efficacy against a heterologous SARS-CoV, we used phylogenetic analyses, synthetic biology, and reverse genetics to construct a chimeric virus (icGDO3-S encoding a synthetic S glycoprotein gene of the most genetically divergent human strain, GDO3, which clusters among the zoonotic SARS-CoV. icGD03-S replicated efficiently in human airway epithelial cells and in the lungs of young and senescent mice, and was highly resistant to neutralization with antisera directed against the Urbani strain. Although VRP-S vaccines provided complete short-term protection against heterologous icGD03-S challenge in young mice, only limited protection was seen in vaccinated senescent animals. VRP-N vaccines not only failed to protect from homologous or heterologous challenge, but resulted in enhanced immunopathology with eosinophilic

Detecting Emergence, Growth, and Senescence of Wetland Vegetation with Polarimetric Synthetic Aperture Radar (SAR Data

Directory of Open Access Journals (Sweden)

Alisa L. Gallant

2014-03-01

Full Text Available Wetlands provide ecosystem goods and services vitally important to humans. Land managers and policymakers working to conserve wetlands require regularly updated information on the statuses of wetlands across the landscape. However, wetlands are challenging to map remotely with high accuracy and consistency. We investigated the use of multitemporal polarimetric synthetic aperture radar (SAR data acquired with Canada’s Radarsat-2 system to track within-season changes in wetland vegetation and surface water. We speculated, a priori, how temporal and morphological traits of different types of wetland vegetation should respond over a growing season with respect to four energy-scattering mechanisms. We used ground-based monitoring data and other ancillary information to assess the limits and consistency of the SAR data for tracking seasonal changes in wetlands. We found the traits of different types of vertical emergent wetland vegetation were detected well with the SAR data and corresponded with our anticipated backscatter responses. We also found using data from Landsat’s optical/infrared sensors in conjunction with SAR data helped remove confusion of wetland features with upland grasslands. These results suggest SAR data can provide useful monitoring information on the statuses of wetlands over time.

Detecting emergence, growth, and senescence of wetland vegetation with polarimetric synthetic aperture radar (SAR) data

Science.gov (United States)

Gallant, Alisa L.; Kaya, Shannon G.; White, Lori; Brisco, Brian; Roth, Mark F.; Sadinski, Walter J.; Rover, Jennifer

2014-01-01

Wetlands provide ecosystem goods and services vitally important to humans. Land managers and policymakers working to conserve wetlands require regularly updated information on the statuses of wetlands across the landscape. However, wetlands are challenging to map remotely with high accuracy and consistency. We investigated the use of multitemporal polarimetric synthetic aperture radar (SAR) data acquired with Canada’s Radarsat-2 system to track within-season changes in wetland vegetation and surface water. We speculated, a priori, how temporal and morphological traits of different types of wetland vegetation should respond over a growing season with respect to four energy-scattering mechanisms. We used ground-based monitoring data and other ancillary information to assess the limits and consistency of the SAR data for tracking seasonal changes in wetlands. We found the traits of different types of vertical emergent wetland vegetation were detected well with the SAR data and corresponded with our anticipated backscatter responses. We also found using data from Landsat’s optical/infrared sensors in conjunction with SAR data helped remove confusion of wetland features with upland grasslands. These results suggest SAR data can provide useful monitoring information on the statuses of wetlands over time.

Quantitative relationship between SAR and temperature rise inside eyeball in a realistic human heat model for 1.5 GHz-microwave exposure; 1.5GHz maikuroha wo abita tobu real model ni okeru gankyunai no hikyushuritsu to josho ondo tono teiryo kankei

Energy Technology Data Exchange (ETDEWEB)

Takai, K.; Fujiwara, O. [Nagoya Institute of Technology, Nagoya (Japan)

1997-12-20

For investigating biological effects of a localized SAR (specific absorption rate) deposited in a human body for electromagnetic wave exposure, it is indispensable to graps a temperature-rise inside a human brain including the control center for the body temperature. This paper numerically analyzes a temperature-rise inside an eyeball of our developed realistic head model for 1.5 GHz microwave exposure, using the FD-TD (finite-difference time-domain) method. The computed results are validated in comparison with the data obtained by Taflove and his colleague. In order to examine a quantitative relationship between the localized SAR and temperature-rise, we also obtained a tissue amount over which the localized SAR should be averaged so as to well reflect the temperature-rise distribution inside the eyeball. 15 refs., 9 figs., 3 tabs.

(−) Arctigenin and (+) Pinoresinol Are Antagonists of the Human Thyroid Hormone Receptor β

Science.gov (United States)

2015-01-01

Lignans are important biologically active dietary polyphenolic compounds. Consumption of foods that are rich in lignans is associated with positive health effects. Using modeling tools to probe the ligand-binding pockets of molecular receptors, we found that lignans have high docking affinity for the human thyroid hormone receptor β. Follow-up experimental results show that lignans (−) arctigenin and (+) pinoresinol are antagonists of the human thyroid hormone receptor β. The modeled complexes show key plausible interactions between the two ligands and important amino acid residues of the receptor. PMID:25383984

Inhibition of cytokine gene expression and induction of chemokine genes in non-lymphatic cells infected with SARS coronavirus

Directory of Open Access Journals (Sweden)

Weber Friedemann

2006-03-01

Full Text Available Abstract Background SARS coronavirus (SARS-CoV is the etiologic agent of the severe acute respiratory syndrome. SARS-CoV mainly infects tissues of non-lymphatic origin, and the cytokine profile of those cells can determine the course of disease. Here, we investigated the cytokine response of two human non-lymphatic cell lines, Caco-2 and HEK 293, which are fully permissive for SARS-CoV. Results A comparison with established cytokine-inducing viruses revealed that SARS-CoV only weakly triggered a cytokine response. In particular, SARS-CoV did not activate significant transcription of the interferons IFN-α, IFN-β, IFN-λ1, IFN-λ2/3, as well as of the interferon-induced antiviral genes ISG56 and MxA, the chemokine RANTES and the interleukine IL-6. Interestingly, however, SARS-CoV strongly induced the chemokines IP-10 and IL-8 in the colon carcinoma cell line Caco-2, but not in the embryonic kidney cell line 293. Conclusion Our data indicate that SARS-CoV suppresses the antiviral cytokine system of non-immune cells to a large extent, thus buying time for dissemination in the host. However, synthesis of IP-10 and IL-8, which are established markers for acute-stage SARS, escapes the virus-induced silencing at least in some cell types. Therefore, the progressive infiltration of immune cells into the infected lungs observed in SARS patients could be due to the production of these chemokines by the infected tissue cells.

Unsupervised SBAS-DInSAR Processing of Space-borne SAR data for Earth Surface Displacement Time Series Generation

Science.gov (United States)

Casu, F.; de Luca, C.; Lanari, R.; Manunta, M.; Zinno, I.

2016-12-01

During the last 25 years, the Differential Synthetic Aperture Radar Interferometry (DInSAR) has played an important role for understanding the Earth's surface deformation and its dynamics. In particular, the large collections of SAR data acquired by a number of space-borne missions (ERS, ENVISAT, ALOS, RADARSAT, TerraSAR-X, COSMO-SkyMed) have pushed toward the development of advanced DInSAR techniques for monitoring the temporal evolution of the ground displacements with an high spatial density. Moreover, the advent of the Copernicus Sentinel-1 (S1) constellation is providing a further increase in the SAR data flow available to the Earth science community, due to its characteristics of global coverage strategy and free and open access data policy. Therefore, managing and storing such a huge amount of data, processing it in an effcient way and maximizing the available archives exploitation are becoming high priority issues. In this work we present some recent advances in the DInSAR field for dealing with the effective exploitation of the present and future SAR data archives. In particular, an efficient parallel SBAS implementation (namely P-SBAS) that takes benefit from high performance computing is proposed. Then, the P-SBAS migration to the emerging Cloud Computing paradigm is shown, together with extensive tests carried out in the Amazon's Elastic Cloud Compute (EC2) infrastructure. Finally, the integration of the P-SBAS processing chain within the ESA Geohazards Exploitation Platform (GEP), for setting up operational on-demand and systematic web tools, open to every user, aimed at automatically processing stacks of SAR data for the generation of SBAS displacement time series, is also illustrated. A number of experimental results obtained by using the ERS, ENVISAT and S1 data in areas characterized by volcanic, seismic and anthropogenic phenomena will be shown. This work is partially supported by: the DPC-CNR agreement, the EPOS-IP project and the ESA GEP project.

Expression of prostanoid receptors in human ductus arteriosus

Science.gov (United States)

Leonhardt, Andreas; Glaser, Alexander; Wegmann, Markus; Schranz, Dietmar; Seyberth, Hannsjörg; Nüsing, Rolf

2003-01-01

Prostaglandins play a major role in maintaining ductal patency in utero. Ductal tone is regulated by both locally released and circulating vasodilatory prostaglandins. In infants with ductus arteriosus-dependent congenital heart disease, ductal patency is maintained by intravenous administration of prostaglandin (PG) E1. Little information is available regarding the expression of prostaglandin receptors in man. By means of RT–PCR and immunohistochemistry we studied the expression of the PGI2 receptor (IP), the four different PGE2 receptors (EP1, EP2, EP3 and EP4), and the receptors for thromboxane (Tx) A2 (TP), PGD2 (DP) and PGF2α (FP) in the ductus arteriosus of three newborn infants with ductus arteriosus-dependent congenital heart disease and intravenous infusion of PGE1 and of one 8 month old child with a patent ductus arteriosus. The EP3, EP4, FP, IP and TP receptor were markedly expressed at the mRNA and protein level, whereas the EP2 receptor was weakly expressed and the EP1 receptor was detected in two out of four tissue specimens only. The DP receptor was not detected in any of the samples. The most pronounced expression, which was located in the media of the ductus arteriosus, was observed for the EP4 and TP receptors followed by IP and FP receptor protein. These data indicate that ductal patency during the infusion of PGE1 in infants with ductus arteriosus-dependent congenital heart disease might be mediated by the EP4 and IP receptor. The data further suggest that a heterogeneous population of prostanoid receptors may contribute to the regulation of ductus arteriosus tone in humans. PMID:12598419

Discovery of an Oxybenzylglycine Based Peroxisome Proliferator Activated Receptor [alpha] Selective Agonist 2-((3-((2-(4-Chlorophenyl)-5-methyloxazol-4-yl)methoxy)benzyl)(methoxycarbonyl)amino)acetic Acid (BMS-687453)

Energy Technology Data Exchange (ETDEWEB)

Li, Jun; Kennedy, Lawrence J.; Shi, Yan; Tao, Shiwei; Ye, Xiang-Yang; Chen, Stephanie Y.; Wang, Ying; Hernndez, Andrs S.; Wang, Wei; Devasthale, Pratik V.; Chen, Sean; Lai, Zhi; Zhang, Hao; Wu, Shung; Smirk, Rebecca A.; Bolton, Scott A.; Ryono, Denis E.; Zhang, Huiping; Lim, Ngiap-Kie; Chen, Bang-Chi; Locke, Kenneth T.; O’Malley, Kevin M.; Zhang, Litao; Srivastava, Rai Ajit; Miao, Bowman; Meyers, Daniel S.; Monshizadegan, Hossain; Search, Debra; Grimm, Denise; Zhang, Rongan; Harrity, Thomas; Kunselman, Lori K.; Cap, Michael; Kadiyala, Pathanjali; Hosagrahara, Vinayak; Zhang, Lisa; Xu, Carrie; Li, Yi-Xin; Muckelbauer, Jodi K.; Chang, Chiehying; An, Yongmi; Krystek, Stanley R.; Blanar, Michael A.; Zahler, Robert; Mukherjee, Ranjan; Cheng, Peter T.W.; Tino, Joseph A. (BMS)

2010-04-12

An 1,3-oxybenzylglycine based compound 2 (BMS-687453) was discovered to be a potent and selective peroxisome proliferator activated receptor (PPAR) {alpha} agonist, with an EC{sub 50} of 10 nM for human PPAR{alpha} and 410-fold selectivity vs human PPAR{gamma} in PPAR-GAL4 transactivation assays. Similar potencies and selectivity were also observed in the full length receptor co-transfection assays. Compound 2 has negligible cross-reactivity against a panel of human nuclear hormone receptors including PPAR{delta}. Compound 2 demonstrated an excellent pharmacological and safety profile in preclinical studies and thus was chosen as a development candidate for the treatment of atherosclerosis and dyslipidemia. The X-ray cocrystal structures of the early lead compound 12 and compound 2 in complex with PPAR{alpha} ligand binding domain (LBD) were determined. The role of the crystal structure of compound 12 with PPAR{alpha} in the development of the SAR that ultimately resulted in the discovery of compound 2 is discussed.

β-arrestins negatively control human adrenomedullin type 1-receptor internalization

International Nuclear Information System (INIS)

Kuwasako, Kenji; Kitamura, Kazuo; Nagata, Sayaka; Sekiguchi, Toshio; Danfeng, Jiang; Murakami, Manabu; Hattori, Yuichi; Kato, Johji

2017-01-01

Adrenomedullin (AM) is a potent hypotensive peptide that exerts a powerful variety of protective effects against multiorgan damage through the AM type 1 receptor (AM 1 receptor), which consists of the calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 2 (RAMP2). Two β-arrestin (β-arr) isoforms, β-arr-1 and β-arr-2, play a central role in the agonist-induced internalization of many receptors for receptor resensitization. Notably, β-arr-biased agonists are now being tested in phase II clinical trials, targeting acute pain and acute heart failure. Here, we examined the effects of β-arr-1 and β-arr-2 on human AM 1 receptor internalization. We constructed a V5-tagged chimera in which the cytoplasmic C-terminal tail (C-tail) of CLR was replaced with that of the β 2 -adrenergic receptor (β 2 -AR), and it was transiently transfected into HEK-293 cells that stably expressed RAMP2. The cell-surface expression and internalization of the wild-type or chimeric receptor were quantified by flow cytometric analysis. The [ 125 I]AM binding and the AM-induced cAMP production of these receptors were also determined. Surprisingly, the coexpression of β-arr-1 or -2 resulted in significant decreases in AM 1 receptor internalization without affecting AM binding and signaling prior to receptor internalization. Dominant-negative (DN) β-arr-1 or -2 also significantly decreased AM-induced AM 1 receptor internalization. In contrast, the AM-induced internalization of the chimeric AM 1 receptor was markedly augmented by the cotransfection of β-arr-1 or -2 and significantly reduced by the coexpression of DN-β-arr-1 or -2. These results were consistent with those seen for β 2 -AR. Thus, both β-arrs negatively control AM 1 receptor internalization, which depends on the C-tail of CLR. - Highlights: • We found that β-arrestins 1 and 2 negatively control agonist-induced GPCR internalization. • β-arrestins 1 and 2 significantly inhibits the AM

Dynamic changes of serum SARS-Coronavirus IgG, pulmonary function and radiography in patients recovering from SARS after hospital discharge

Directory of Open Access Journals (Sweden)

Chen Liangan

2005-01-01

Full Text Available Abstract Objective The intent of this study was to examine the recovery of individuals who had been hospitalized for severe acute respiratory syndrome (SARS in the year following their discharge from the hospital. Parameters studied included serum levels of SARS coronavirus (SARS-CoV IgG antibody, tests of lung function, and imaging data to evaluate changes in lung fibrosis. In addition, we explored the incidence of femoral head necrosis in some of the individuals recovering from SARS. Methods The subjects of this study were 383 clinically diagnosed SARS patients in Beijing, China. They were tested regularly for serum levels of SARS-CoV IgG antibody and lung function and were given chest X-rays and/or high resolution computerized tomography (HRCT examinations at the Chinese PLA General Hospital during the 12 months that followed their release from the hospital. Those individuals who were found to have lung diffusion abnormities (transfer coefficient for carbon monoxide [DLCO] Findings Of all the subjects, 81.2% (311 of 383 patients tested positive for serum SARS-CoV IgG. Of those testing positive, 27.3% (85 of 311 patients were suffering from lung diffusion abnormities (DLCO Interpretation The lack of sero-positive SARS-CoV in some individuals suggests that there may have been some misdiagnosed cases among the subjects included in this study. Of those testing positive, the serum levels of SARS-CoV IgG antibody decreased significantly during the 12 months after hospital discharge. Additionally, we found that the individuals who had lung fibrosis showed some spontaneous recovery. Finally, some of the subjects developed femoral head necrosis.

Value of the radiolabelled GLP-1 receptor antagonist exendin(9-39) for targeting of GLP-1 receptor-expressing pancreatic tissues in mice and humans

International Nuclear Information System (INIS)

Waser, Beatrice; Reubi, Jean Claude

2011-01-01

Radiolabelled glucagon-like peptide 1 (GLP-1) receptor agonists have recently been shown to successfully image benign insulinomas in patients. Moreover, it was recently reported that antagonist tracers were superior to agonist tracers for somatostatin and gastrin-releasing peptide receptor targeting of tumours. The present preclinical study determines therefore the value of an established GLP-1 receptor antagonist for the in vitro visualization of GLP-1 receptor-expressing tissues in mice and humans. Receptor autoradiography studies with 125 I-GLP-1(7-36)amide agonist or 125 I-Bolton-Hunter-exendin(9-39) antagonist radioligands were performed in mice pancreas and insulinomas as well as in human insulinomas; competition experiments were performed in the presence of increasing concentration of GLP-1(7-36)amide or exendin(9-39). The antagonist 125 I-Bolton-Hunter-exendin(9-39) labels mouse pancreatic β-cells and mouse insulinomas, but it does not label human pancreatic β-cells and insulinomas. High affinity displacement (IC 50 approximately 2 nM) is observed in mouse β-cells and insulinomas with either the exendin(9-39) antagonist or GLP-1(7-36)amide agonist. For comparison, the agonist 125 I-GLP-1(7-36)amide intensively labels mouse pancreatic β-cells, mouse insulinoma and human insulinomas; high affinity displacement is observed for the GLP-1(7-36)amide in all tissues; however, a 5 and 20 times lower affinity is found for exendin(9-39) in the mouse and human tissues, respectively. This study reports a species-dependent behaviour of the GLP-1 receptor antagonist exendin(9-39) that can optimally target GLP-1 receptors in mice but not in human tissue. Due to its overly low binding affinity, this antagonist is an inadequate targeting agent for human GLP-1 receptor-expressing tissues, as opposed to the GLP-1 receptor agonist, GLP-1(7-36)amide. (orig.)

Nano(Q)SAR: Challenges, pitfalls and perspectives.

Science.gov (United States)

Tantra, Ratna; Oksel, Ceyda; Puzyn, Tomasz; Wang, Jian; Robinson, Kenneth N; Wang, Xue Z; Ma, Cai Y; Wilkins, Terry

2015-01-01

Regulation for nanomaterials is urgently needed, and the drive to adopt an intelligent testing strategy is evident. Such a strategy will not only provide economic benefits but will also reduce moral and ethical concerns arising from animal testing. For regulatory purposes, such an approach is promoted by REACH, particularly the use of quantitative structure-activity relationships [(Q)SAR] as a tool for the categorisation of compounds according to their physicochemical and toxicological properties. In addition to compounds, (Q)SAR has also been applied to nanomaterials in the form of nano(Q)SAR. Although (Q)SAR in chemicals is well established, nano(Q)SAR is still in early stages of development and its successful uptake is far from reality. This article aims to identify some of the pitfalls and challenges associated with nano-(Q)SARs in relation to the categorisation of nanomaterials. Our findings show clear gaps in the research framework that must be addressed if we are to have reliable predictions from such models. Three major barriers were identified: the need to improve quality of experimental data in which the models are developed from, the need to have practical guidelines for the development of the nano(Q)SAR models and the need to standardise and harmonise activities for the purpose of regulation. Of these three, the first, i.e. the need to improve data quality requires immediate attention, as it underpins activities associated with the latter two. It should be noted that the usefulness of data in the context of nano-(Q)SAR modelling is not only about the quantity of data but also about the quality, consistency and accessibility of those data.

Playback system designed for X-Band SAR

International Nuclear Information System (INIS)

Yuquan, Liu; Changyong, Dou

2014-01-01

SAR(Synthetic Aperture Radar) has extensive application because it is daylight and weather independent. In particular, X-Band SAR strip map, designed by Institute of Remote Sensing and Digital Earth, Chinese Academy of Sciences, provides high ground resolution images, at the same time it has a large spatial coverage and a short acquisition time, so it is promising in multi-applications. When sudden disaster comes, the emergency situation acquires radar signal data and image as soon as possible, in order to take action to reduce loss and save lives in the first time. This paper summarizes a type of X-Band SAR playback processing system designed for disaster response and scientific needs. It describes SAR data workflow includes the payload data transmission and reception process. Playback processing system completes signal analysis on the original data, providing SAR level 0 products and quick image. Gigabit network promises radar signal transmission efficiency from recorder to calculation unit. Multi-thread parallel computing and ping pong operation can ensure computation speed. Through gigabit network, multi-thread parallel computing and ping pong operation, high speed data transmission and processing meet the SAR radar data playback real time requirement

Playback system designed for X-Band SAR

Science.gov (United States)

Yuquan, Liu; Changyong, Dou

2014-03-01

SAR(Synthetic Aperture Radar) has extensive application because it is daylight and weather independent. In particular, X-Band SAR strip map, designed by Institute of Remote Sensing and Digital Earth, Chinese Academy of Sciences, provides high ground resolution images, at the same time it has a large spatial coverage and a short acquisition time, so it is promising in multi-applications. When sudden disaster comes, the emergency situation acquires radar signal data and image as soon as possible, in order to take action to reduce loss and save lives in the first time. This paper summarizes a type of X-Band SAR playback processing system designed for disaster response and scientific needs. It describes SAR data workflow includes the payload data transmission and reception process. Playback processing system completes signal analysis on the original data, providing SAR level 0 products and quick image. Gigabit network promises radar signal transmission efficiency from recorder to calculation unit. Multi-thread parallel computing and ping pong operation can ensure computation speed. Through gigabit network, multi-thread parallel computing and ping pong operation, high speed data transmission and processing meet the SAR radar data playback real time requirement.

Structural Probing and Molecular Modeling of the A₃ Adenosine Receptor: A Focus on Agonist Binding.

Science.gov (United States)

Ciancetta, Antonella; Jacobson, Kenneth A

2017-03-11

Adenosine is an endogenous modulator exerting its functions through the activation of four adenosine receptor (AR) subtypes, termed A₁, A 2A , A 2B and A₃, which belong to the G protein-coupled receptor (GPCR) superfamily. The human A₃AR (hA₃AR) subtype is implicated in several cytoprotective functions. Therefore, hA₃AR modulators, and in particular agonists, are sought for their potential application as anti-inflammatory, anticancer, and cardioprotective agents. Structure-based molecular modeling techniques have been applied over the years to rationalize the structure-activity relationships (SARs) of newly emerged A₃AR ligands, guide the subsequent lead optimization, and interpret site-directed mutagenesis (SDM) data from a molecular perspective. In this review, we showcase selected modeling-based and guided strategies that were applied to elucidate the binding of agonists to the A₃AR and discuss the challenges associated with an accurate prediction of the receptor extracellular vestibule through homology modeling from the available X-ray templates.

A third human retinoic acid receptor, hRAR-γ

International Nuclear Information System (INIS)

Krust, A.; Kastner, Ph.; Petkovich, M.; Zelent, A.; Chambon, P.

1989-01-01

Retinoic acid receptors (RARs) are retinoic acid (RA)-inducible enhancer factors belonging to the superfamily of steroid/thyroid nuclear receptors. The authors have previously characterized two human RAR (hRAR-α and hRAR-β) cDNAs and have recently cloned their murine cognates (mRAR-α and mRAR-β) together with a third RAR (mRAR-γ) whose RNA was detected predominantly in skin, a well-known target for RA. mRAR-γ cDNA was used here to clone its human counterpart (hRAR-γ) from a T47D breast cancer cell cDNA library. Using a transient transfection assay in HeLa cells and a reporter gene harboring a synthetic RA responsive element, they demonstrate that hRAR-γ cDNA indeed encodes a RA-inducible transcriptional trans-activator. Interestingly, comparisons of the amino acid sequences of all six human and mouse RARs indicate that the interspecies conservation of a given member of the RAR subfamily (either α, β, or γ) is much higher than the conservation of all three receptors within a given species. These observations indicate that RAR-α, -β, and -γ may perform specific functions. They show also that hRAR-γ RNA is the predominant RAR RNA species in human skin, which suggests that hRAR-γ mediates some of the retinoid effects in this tissue

Evaluation of SAR in a human body model due to wireless power transmission in the 10 MHz band.

Science.gov (United States)

Laakso, Ilkka; Tsuchida, Shogo; Hirata, Akimasa; Kamimura, Yoshitsugu

2012-08-07

This study discusses a computational method for calculating the specific absorption rate (SAR) due to a wireless power transmission system in the 10 MHz frequency band. A two-step quasi-static method comprised of the method of moments and the scalar potential finite-difference method are proposed. The applicability of the quasi-static approximation for localized exposure in this frequency band is discussed by comparing the SAR in a lossy dielectric cylinder computed with a full-wave electromagnetic analysis and the quasi-static approximation. From the computational results, the input impedance of the resonant coils was affected by the existence of the cylinder. On the other hand, the magnetic field distribution in free space and considering the cylinder and an impedance matching circuit were in good agreement; the maximum difference in the amplitude of the magnetic field was 4.8%. For a cylinder-coil distance of 10 mm, the difference between the peak 10 g averaged SAR in the cylinder computed with the full-wave electromagnetic method and our quasi-static method was 7.8%. These results suggest that the quasi-static approach is applicable for conducting the dosimetry of wireless power transmission in the 10 MHz band. With our two-step quasi-static method, the SAR in the anatomically based model was computed for different exposure scenarios. From those computations, the allowable input power satisfying the limit of a peak 10 g averaged SAR of 2.0 W kg(-1) was 830 W in the worst case exposure scenario with a coil positioned at a distance of 30 mm from the chest.

A Constellation of CubeSat InSAR Sensors for Rapid-Revisit Surface Deformation Studies

Science.gov (United States)

Wye, L.; Lee, S.; Yun, S. H.; Zebker, H. A.; Stock, J. D.; Wicks, C. W., Jr.; Doe, R.

2016-12-01

The 2007 NRC Decadal Survey for Earth Sciences highlights three major Earth surface deformation themes: 1) solid-earth hazards and dynamics; 2) human health and security; and 3) land-use change, ecosystem dynamics and biodiversity. Space-based interferometric synthetic aperture radar (InSAR) is a key change detection tool for addressing these themes. Here, we describe the mission and radar payload design for a constellation of S-band InSAR sensors specifically designed to provide the global, high temporal resolution, sub-cm level deformation accuracy needed to address some of the major Earth system goals. InSAR observations with high temporal resolution are needed to properly monitor certain nonlinearly time-varying features (e.g., unstable volcanoes, active fault lines, and heavily-used groundwater or hydrocarbon reservoirs). Good temporal coverage is also needed to reduce atmospheric artifacts by allowing multiple acquisitions to be averaged together, since each individual SAR measurement is corrupted by up to several cm of atmospheric noise. A single InSAR platform is limited in how often it can observe a given scene without sacrificing global spatial coverage. Multiple InSAR platforms provide the spatial-temporal flexibility required to maximize the science return. However, building and launching multiple InSAR platforms is cost-prohibitive for traditional satellites. SRI International (SRI) and our collaborators are working to exploit developments in nanosatellite technology, in particular the emergence of the CubeSat standard, to provide high-cadence InSAR capabilities in an affordable package. The CubeSat Imaging Radar for Earth Science (CIRES) subsystem, a prototype SAR elec­tronics package developed by SRI with support from a 2014 NASA ESTO ACT award, is specifically scaled to be a drop-in radar solution for resource-limited delivery systems like CubeSats and small airborne vehicles. Here, we present our mission concept and flow-down requirements for a

T3 receptors in human pituitary tumors.

Science.gov (United States)

Machiavelli, Gloria A; Pauni, Micaela; Heredia Sereno, Gastón M; Szijan, Irene; Basso, Armando; Burdman, José A

2009-11-01

The purpose of this work was to investigate the synthesis of T3 receptors in human tumors of the anterior pituitary gland, its relationship with the hormone synthesized and/or secreted by the tumor and the post-surgical evolution of the patient. Patients were evaluated clinically and by magnetic nuclear resonance to classify the adenoma according to their size. Hormonal concentrations in sera were determined by radioimmunoassay. Immunohistochemistry of the pituitary hormones was performed in the tumors. Tumors were obtained at surgery and immediately frozen in ice, transported to the laboratory and stored at -70 degrees C. Reverse transcription was performed with purified RNA from the tumors. Out of 33 pituitary tumors, 29 had RNA for T3 receptors synthesis (88%). They were present in different histological specimens, the tumors were grades 1-4 according to their size, and there was no relationship between the size of the tumor and the presence of T3 receptor RNAs. The post-surgical evolution of the patient was mostly dependent on the size and not on the presence of T3 receptors. The presence of thyroid hormone receptors in pituitary tumors is in line with two important characteristics of these tumors: they are histologically benign and well differentiated.

Wave directional spectrum from SAR imagery

Digital Repository Service at National Institute of Oceanography (India)

Fernandes, A.A.; Sarma, Y.V.B.; Menon, H.B.; Vethamony, P.

< 2m and the zero-crossing period during the satellite overpass is small (< 6s, �O�O < 60m). We therefore utilized the visit of one of the authors (Sarma) to the Southampton Oceanographic Centre, U.K., to procure two ERS-1 digital image mode SAR...-dimensional FFT as well as a computer program for downloading SAR data from CCT. Finally we owe a debt of gratitude to J C da Silva, Southampton Oceanographic Centre, U K for sharing some of his SAR data with us. References Allan T. D. (Ed) (1983...

Wave directional spectrum from SAR imagery

Digital Repository Service at National Institute of Oceanography (India)

Fernandes, A.A.; Sarma, Y.V.B.; Menon, H.B.; Vethamony, P.

Gaussian smoothed SAR image spectra have been evaluated from 512 x 512 pixel subscenes of image mode ERS-1 SAR scenes off Goa, Visakhapatnam, Paradeep and Portugal. The two recently acquired scenes off Portugal showed the signature of swell...

Association of acute adverse effects with high local SAR induced in the brain from prolonged RF head and neck hyperthermia

International Nuclear Information System (INIS)

Adibzadeh, F; Verhaart, R F; Rijnen, Z; Franckena, M; Van Rhoon, G C; Paulides, M M; Verduijn, G M; Fortunati, V

2015-01-01

To provide an adequate level of protection for humans from exposure to radio-frequency (RF) electromagnetic fields (EMF) and to assure that any adverse health effects are avoided. The basic restrictions in terms of the specific energy absorption rate (SAR) were prescribed by IEEE and ICNIRP. An example of a therapeutic application of non-ionizing EMF is hyperthermia (HT), in which intense RF energy is focused at a target region. Deep HT in the head and neck (H and N) region involves inducing energy at 434 MHz for 60 min on target. Still, stray exposure of the brain is considerable, but to date only very limited side-effects were observed. The objective of this study is to investigate the stringency of the current basic restrictions by relating the induced EM dose in the brain of patients treated with deep head and neck (H and N) HT to the scored acute health effects. We performed a simulation study to calculate the induced peak 10 g spatial-averaged SAR (psSAR 10g ) in the brains of 16 selected H and N patients who received the highest SAR exposure in the brain, i.e. who had the minimum brain-target distance and received high forwarded power during treatment. The results show that the maximum induced SAR in the brain of the patients can exceed the current basic restrictions (IEEE and ICNIRP) on psSAR 10g for occupational environments by 14 times. Even considering the high local SAR in the brain, evaluation of acute effects by the common toxicity criteria (CTC) scores revealed no indication of a serious acute neurological effect. In addition, this study provides pioneering quantitative human data on the association between maximum brain SAR level and acute adverse effects when brains are exposed to prolonged RF EMF. (paper)

Crystal Structure of an LSD-Bound Human Serotonin Receptor

Energy Technology Data Exchange (ETDEWEB)

Wacker, Daniel; Wang, Sheng; McCorvy, John D.; Betz, Robin M.; Venkatakrishnan, A.J.; Levit, Anat; Lansu, Katherine; Schools, Zachary L.; Che, Tao; Nichols, David E.; Shoichet, Brian K.; Dror, Ron O.; Roth, Bryan L. (UNCSM); (UNC); (Stanford); (Stanford-MED); (UCSF)

2017-01-01

The prototypical hallucinogen LSD acts via serotonin receptors, and here we describe the crystal structure of LSD in complex with the human serotonin receptor 5-HT2B. The complex reveals conformational rearrangements to accommodate LSD, providing a structural explanation for the conformational selectivity of LSD’s key diethylamide moiety. LSD dissociates exceptionally slow from both 5-HT2BR and 5-HT2AR—a major target for its psychoactivity. Molecular dynamics (MD) simulations suggest that LSD’s slow binding kinetics may be due to a “lid” formed by extracellular loop 2 (EL2) at the entrance to the binding pocket. A mutation predicted to increase the mobility of this lid greatly accelerates LSD’s binding kinetics and selectively dampens LSD-mediated β-arrestin2 recruitment. This study thus reveals an unexpected binding mode of LSD; illuminates key features of its kinetics, stereochemistry, and signaling; and provides a molecular explanation for LSD’s actions at human serotonin receptors.

Crystal Structure of an LSD-Bound Human Serotonin Receptor.

Science.gov (United States)

Wacker, Daniel; Wang, Sheng; McCorvy, John D; Betz, Robin M; Venkatakrishnan, A J; Levit, Anat; Lansu, Katherine; Schools, Zachary L; Che, Tao; Nichols, David E; Shoichet, Brian K; Dror, Ron O; Roth, Bryan L

2017-01-26

The prototypical hallucinogen LSD acts via serotonin receptors, and here we describe the crystal structure of LSD in complex with the human serotonin receptor 5-HT 2B . The complex reveals conformational rearrangements to accommodate LSD, providing a structural explanation for the conformational selectivity of LSD's key diethylamide moiety. LSD dissociates exceptionally slow from both 5-HT 2B R and 5-HT 2A R-a major target for its psychoactivity. Molecular dynamics (MD) simulations suggest that LSD's slow binding kinetics may be due to a "lid" formed by extracellular loop 2 (EL2) at the entrance to the binding pocket. A mutation predicted to increase the mobility of this lid greatly accelerates LSD's binding kinetics and selectively dampens LSD-mediated β-arrestin2 recruitment. This study thus reveals an unexpected binding mode of LSD; illuminates key features of its kinetics, stereochemistry, and signaling; and provides a molecular explanation for LSD's actions at human serotonin receptors. PAPERCLIP. Copyright © 2017 Elsevier Inc. All rights reserved.

Avian and human influenza virus compatible sialic acid receptors in little brown bats.

Science.gov (United States)

Chothe, Shubhada K; Bhushan, Gitanjali; Nissly, Ruth H; Yeh, Yin-Ting; Brown, Justin; Turner, Gregory; Fisher, Jenny; Sewall, Brent J; Reeder, DeeAnn M; Terrones, Mauricio; Jayarao, Bhushan M; Kuchipudi, Suresh V

2017-04-06

Influenza A viruses (IAVs) continue to threaten animal and human health globally. Bats are asymptomatic reservoirs for many zoonotic viruses. Recent reports of two novel IAVs in fruit bats and serological evidence of avian influenza virus (AIV) H9 infection in frugivorous bats raise questions about the role of bats in IAV epidemiology. IAVs bind to sialic acid (SA) receptors on host cells, and it is widely believed that hosts expressing both SA α2,3-Gal and SA α2,6-Gal receptors could facilitate genetic reassortment of avian and human IAVs. We found abundant co-expression of both avian (SA α2,3-Gal) and human (SA α2,6-Gal) type SA receptors in little brown bats (LBBs) that were compatible with avian and human IAV binding. This first ever study of IAV receptors in a bat species suggest that LBBs, a widely-distributed bat species in North America, could potentially be co-infected with avian and human IAVs, facilitating the emergence of zoonotic strains.

[Epidemiological perspectives on SARS and avian influenza].

Science.gov (United States)

del Rey Calero, Juan

2004-01-01

SARS is a respiratory infection caused by Coronavirus (Nidoviruses, RNA) from which 3 groups are known. Group 1 affects dogs, cats, pigs, and the human agent is 229 E. Group 2 affects bovines or rodents, and the human agent is OC43. And group 3 corresponds to the avian pathology.... The epidemics emerged on February 2003 in Guangdong, South China, due to consumption of exotic animals (Civeta, etc.), and it spread through interperson contagion to other regions in Asia, America and Europe. Incubation period is about 2-7 days. Transmission Of the virus is person-to person, but also by excretions and residual water. Basic reproductive rate is 2 to 4, and it is considered that 2.7 persons are infected from the initial case. In June 2003, SARS affected over 8,000 people and 774 were killed. Mortality approaches to 10%, and it is higher among older people rising up to 50% in those aged over 65 years. It is important to quickly establish action protocols regarding clinical, epidemiological and prevention aspects. Avian influenza is an infection caused by type A Influenza Orthomixovirus, in which migration birds and wild ducks are the main reservoir. Avian viruses correspond to H5, H7, H9. In 1997 it was observed that type AH5N1 jumped interspecies barrier and affected 18 humans, and 6 of them died. At the end of 2003 and in 2004 this type of poultry flu was described in Asia. FAO has emphasized that sacrifice of chicken in affected farms is the most effective measure to fight against the disease. It has also been established suppression of imports from these countries. There is no evidence on interperson contagion from chicken contagion, nor on food-borne contagion to humans.

Recognition of Human Erythrocyte Receptors by the Tryptophan-Rich Antigens of Monkey Malaria Parasite Plasmodium knowlesi.

Directory of Open Access Journals (Sweden)

Kriti Tyagi

Full Text Available The monkey malaria parasite Plasmodium knowlesi also infect humans. There is a lack of information on the molecular mechanisms that take place between this simian parasite and its heterologous human host erythrocytes leading to this zoonotic disease. Therefore, we investigated here the binding ability of P. knowlesi tryptophan-rich antigens (PkTRAgs to the human erythrocytes and sharing of the erythrocyte receptors between them as well as with other commonly occurring human malaria parasites.Six PkTRAgs were cloned and expressed in E.coli as well as in mammalian CHO-K1 cell to determine their human erythrocyte binding activity by cell-ELISA, and in-vitro rosetting assay, respectively.Three of six PkTRAgs (PkTRAg38.3, PkTRAg40.1, and PkTRAg67.1 showed binding to human erythrocytes. Two of them (PkTRAg40.1 and PkTRAg38.3 showed cross-competition with each other as well as with the previously described P.vivax tryptophan-rich antigens (PvTRAgs for human erythrocyte receptors. However, the third protein (PkTRAg67.1 utilized the additional but different human erythrocyte receptor(s as it did not cross-compete for erythrocyte binding with either of these two PkTRAgs as well as with any of the PvTRAgs. These three PkTRAgs also inhibited the P.falciparum parasite growth in in-vitro culture, further indicating the sharing of human erythrocyte receptors by these parasite species and the biological significance of this receptor-ligand interaction between heterologous host and simian parasite.Recognition and sharing of human erythrocyte receptor(s by PkTRAgs with human parasite ligands could be part of the strategy adopted by the monkey malaria parasite to establish inside the heterologous human host.

Recognition of Human Erythrocyte Receptors by the Tryptophan-Rich Antigens of Monkey Malaria Parasite Plasmodium knowlesi.

Science.gov (United States)

Tyagi, Kriti; Gupta, Deepali; Saini, Ekta; Choudhary, Shilpa; Jamwal, Abhishek; Alam, Mohd Shoeb; Zeeshan, Mohammad; Tyagi, Rupesh K; Sharma, Yagya D

2015-01-01

The monkey malaria parasite Plasmodium knowlesi also infect humans. There is a lack of information on the molecular mechanisms that take place between this simian parasite and its heterologous human host erythrocytes leading to this zoonotic disease. Therefore, we investigated here the binding ability of P. knowlesi tryptophan-rich antigens (PkTRAgs) to the human erythrocytes and sharing of the erythrocyte receptors between them as well as with other commonly occurring human malaria parasites. Six PkTRAgs were cloned and expressed in E.coli as well as in mammalian CHO-K1 cell to determine their human erythrocyte binding activity by cell-ELISA, and in-vitro rosetting assay, respectively. Three of six PkTRAgs (PkTRAg38.3, PkTRAg40.1, and PkTRAg67.1) showed binding to human erythrocytes. Two of them (PkTRAg40.1 and PkTRAg38.3) showed cross-competition with each other as well as with the previously described P.vivax tryptophan-rich antigens (PvTRAgs) for human erythrocyte receptors. However, the third protein (PkTRAg67.1) utilized the additional but different human erythrocyte receptor(s) as it did not cross-compete for erythrocyte binding with either of these two PkTRAgs as well as with any of the PvTRAgs. These three PkTRAgs also inhibited the P.falciparum parasite growth in in-vitro culture, further indicating the sharing of human erythrocyte receptors by these parasite species and the biological significance of this receptor-ligand interaction between heterologous host and simian parasite. Recognition and sharing of human erythrocyte receptor(s) by PkTRAgs with human parasite ligands could be part of the strategy adopted by the monkey malaria parasite to establish inside the heterologous human host.

Nicotinic acid receptor abnormalities in human skin cancer: implications for a role in epidermal differentiation.

Directory of Open Access Journals (Sweden)

Yira Bermudez

Full Text Available Chronic UV skin exposure leads to epidermal differentiation defects in humans that can be largely restored by pharmacological doses of nicotinic acid. Nicotinic acid has been identified as a ligand for the human G-protein-coupled receptors GPR109A and GPR109B that signal through G(i-mediated inhibition of adenylyl cyclase. We have examined the expression, cellular distribution, and functionality of GPR109A/B in human skin and skin derived epidermal cells.Nicotinic acid increases epidermal differentiation in photodamaged human skin as judged by the terminal differentiation markers caspase 14 and filaggrin. Both GPR109A and GPR109B genes are transcribed in human skin and in epidermal keratinocytes, but expression in dermal fibroblasts is below limits of detection. Receptor transcripts are greatly over-expressed in squamous cell cancers. Receptor protein in normal skin is prominent from the basal through granular layers of the epidermis, with cellular localization more dispersive in the basal layer but predominantly localized at the plasma membrane in more differentiated epidermal layers. In normal human primary and immortalized keratinocytes, nicotinic acid receptors show plasma membrane localization and functional G(i-mediated signaling. In contrast, in a squamous cell carcinoma derived cell line, receptor protein shows a more diffuse cellular localization and the receptors are nearly non-functional.The results of these studies justify future genetic and pharmacological intervention studies to define possible specific role(s of nicotinic acid receptors in human skin homeostasis.

C5a binding to human polymorphonuclear leukocyte plasma membrane (PMNLM) receptors

International Nuclear Information System (INIS)

Conway, R.G.; Mollison, K.W.; Carter, G.W.; Lane, B.

1986-01-01

Previous investigations of the C5a receptor have been performed using intact human PMNL. To circumvent some of the potential problems with such whole cell assays (e.g. internalization or metabolism of radioligand) the authors have developed a PMNLM binding assay. Human PMNLM were prepared by nitrogen cavitation and Percoll gradient centrifugation. Specific binding of [ 125 I]C5a to PMNLM was: high affinity, K/sub D/ = 0.6 nM; saturable, B/sub max/ = 8.7 pmol/mg protein; and reversible. Kinetic measurements agree with the K/sub D/ value obtained by Scatchard analysis. Furthermore, the binding activity of C5a correlates with biological activity as measured by myeloperoxidase release from human PMNL. Human serum C5a and recombinant C5a bind with similar affinities when measured by competition or direct binding and label the same number of sites in human PMNLM. The nonhydrolyzable GTP analog, GppNHp, induces a low affinity state of the C5a receptor (4-6 fold shift in K/sub D/) with little effect on B/sub max/. In summary, the criteria have been satisfied for identification of a biologically relevant C5a binding site in human PMNLM. Regulation of the C5a receptor and its membrane transduction mechanism(s) appears to involve guanyl nucleotides, as has been found for other chemoattractant receptors

Reproductive physiology of a humanized GnRH receptor mouse model: application in evaluation of human-specific analogs.

Science.gov (United States)

Tello, Javier A; Kohout, Trudy; Pineda, Rafael; Maki, Richard A; Scott Struthers, R; Millar, Robert P

2013-07-01

The human GnRH receptor (GNRHR1) has a specific set of properties with physiological and pharmacological influences not appropriately modeled in laboratory animals or cell-based systems. To address this deficiency, we have generated human GNRHR1 knock-in mice and described their reproductive phenotype. Measurement of pituitary GNRHR1 transcripts from homozygous human GNRHR1 knock-in (ki/ki) mice revealed a severe reduction (7- to 8-fold) compared with the mouse Gnrhr1 in wild-type mice. ¹²⁵I-GnRH binding assays on pituitary membrane fractions corroborated reduced human GNRHR1 protein expression in ki/ki mice, as occurs with transfection of human GNRHR1 in cell lines. Female homozygous knock-in mice displayed normal pubertal onset, indicating that a large reduction in GNRHR1 expression is sufficient for this process. However, ki/ki females exhibited periods of prolonged estrous and/or metestrous and reduced fertility. No impairment was found in reproductive maturity or adult fertility in male ki/ki mice. Interestingly, the serum LH response to GnRH challenge was reduced in both knock-in males and females, indicating a reduced GNRHR1 signaling capacity. Small molecules targeting human GPCRs usually have poor activities at homologous rodent receptors, thus limiting their use in preclinical development. Therefore, we tested a human-specific GnRH1 antagonist, NBI-42902, in our mouse model and demonstrated abrogation of a GnRH1-induced serum LH rise in ki/ki mice and an absence of effect in littermates expressing the wild-type murine receptor. This novel model provides the opportunity to study the human receptor in vivo and for screening the activity of human-specific GnRH analogs.

Immunolocalisation of oestrogen receptor beta in human tissues.

Science.gov (United States)

Taylor, A H; Al-Azzawi, F

2000-02-01

Oestrogens exert their actions via specific nuclear protein receptors that are members of the steroid/thyroid receptor superfamily of transcription factors. Recently, a second oestrogen receptor (ERbeta) has been cloned, and using reverse transcription-PCR and immunohistochemistry it has been shown to have a wide tissue distribution in the rat that is distinct from the classical oestrogen receptor, ERalpha. Using commercial polyclonal antisera against peptides specific to human ERbeta, we have determined the sites of ERbeta expression in archival and formalin-fixed human tissue and compared its expression with that of ERalpha. ERbeta was localised to the cell nuclei of a wide range of normal adult human tissues including ovary, Fallopian tube, uterus, lung, kidney, brain, heart, prostate and testis. In the ovary, ERbeta was present in multiple cell types including granulosa cells in small, medium and large follicles, theca and corpora lutea, whereas ERalpha was weakly expressed in the nuclei of granulosa cells, but not in the theca nor in the copora lutea. In the endometrium, both ERalpha and ERbeta were observed in luminal epithelial cells and in the nuclei of stromal cells but, significantly, ERbeta was weak or absent from endometrial glandular epithelia. Epithelial cells in most male tissues including the prostate, the urothelium and muscle layers of the bladder, and Sertoli cells in the testis, were also immunopositive for ERbeta. Significant ERbeta immunoreactivity was detected in most areas of the brain, with the exception of the hippocampus - a tissue that stained positively for ERalpha. In conclusion, the almost ubiquitous immunohistochemical localisation of ERbeta indicates that ERbeta may play a major role in the mediation of oestrogen action. The differential expression of ERalpha and ERbeta in some of these tissues suggests a more complex control mechanism in oestrogenic potential than originally envisioned.

Immunohistochemical detection of somatostatin receptor subtypes sst1 and sst2A in human somatostatin receptor positive tumors

NARCIS (Netherlands)

L.J. Hofland (Leo); Q. Liu; P.M. van Koetsveld (Peter); J. Zuijderwijk; F. van der Ham (Frieda); R.R. de Krijger (Ronald); A. Schonbrunn; S.W.J. Lamberts (Steven)

1999-01-01

textabstractAlthough in situ hybridization has been used to examine the distribution of messenger RNA for somatostatin receptor subtypes (sst) in human tumors, the cellular localization of sst1 and sst2A receptors has not been reported. In this study, we describe the

A single mutation in Taiwanese H6N1 influenza hemagglutinin switches binding to human-type receptors

Energy Technology Data Exchange (ETDEWEB)

de Vries, Robert P.; Tzarum, Netanel; Peng, Wenjie; Thompson, Andrew J.; Ambepitiya Wickramasinghe, Iresha N.; de la Pena, Alba T. Torrents; van Breemen, Marielle J.; Bouwman, Kim M.; Zhu, Xueyong; McBride, Ryan; Yu, Wenli; Sanders, Rogier W.; Verheije, Monique H.; Wilson, Ian A.; Paulson, James C.

2017-07-10

In June 2013, the first case of human infection with an avian H6N1 virus was reported in a Taiwanese woman. Although this was a single non-fatal case, the virus continues to circulate in Taiwanese poultry. As with any emerging avian virus that infects humans, there is concern that acquisition of human-type receptor specificity could enable transmission in the human population. Despite mutations in the receptor-binding pocket of the human H6N1 isolate, it has retained avian-type (NeuAcα2-3Gal) receptor specificity. However, we show here that a single nucleotide substitution, resulting in a change from Gly to Asp at position 225 (G225D), completely switches specificity to human-type (NeuAcα2-6Gal) receptors. Significantly, G225D H6 loses binding to chicken trachea epithelium and is now able to bind to human tracheal tissue. Structural analysis reveals that Asp225 directly interacts with the penultimate Gal of the human-type receptor, stabilizing human receptor binding.

Image based SAR product simulation for analysis

Science.gov (United States)

Domik, G.; Leberl, F.

1987-01-01

SAR product simulation serves to predict SAR image gray values for various flight paths. Input typically consists of a digital elevation model and backscatter curves. A new method is described of product simulation that employs also a real SAR input image for image simulation. This can be denoted as 'image-based simulation'. Different methods to perform this SAR prediction are presented and advantages and disadvantages discussed. Ascending and descending orbit images from NASA's SIR-B experiment were used for verification of the concept: input images from ascending orbits were converted into images from a descending orbit; the results are compared to the available real imagery to verify that the prediction technique produces meaningful image data.

Spaceborne Differential SAR Interferometry: Data Analysis Tools for Deformation Measurement

Directory of Open Access Journals (Sweden)

Michele Crosetto

2011-02-01

Full Text Available This paper is focused on spaceborne Differential Interferometric SAR (DInSAR for land deformation measurement and monitoring. In the last two decades several DInSAR data analysis procedures have been proposed. The objective of this paper is to describe the DInSAR data processing and analysis tools developed at the Institute of Geomatics in almost ten years of research activities. Four main DInSAR analysis procedures are described, which range from the standard DInSAR analysis based on a single interferogram to more advanced Persistent Scatterer Interferometry (PSI approaches. These different procedures guarantee a sufficient flexibility in DInSAR data processing. In order to provide a technical insight into these analysis procedures, a whole section discusses their main data processing and analysis steps, especially those needed in PSI analyses. A specific section is devoted to the core of our PSI analysis tools: the so-called 2+1D phase unwrapping procedure, which couples a 2D phase unwrapping, performed interferogram-wise, with a kind of 1D phase unwrapping along time, performed pixel-wise. In the last part of the paper, some examples of DInSAR results are discussed, which were derived by standard DInSAR or PSI analyses. Most of these results were derived from X-band SAR data coming from the TerraSAR-X and CosmoSkyMed sensors.

An Adaptive Ship Detection Scheme for Spaceborne SAR Imagery

Directory of Open Access Journals (Sweden)

Xiangguang Leng

2016-08-01

Full Text Available With the rapid development of spaceborne synthetic aperture radar (SAR and the increasing need of ship detection, research on adaptive ship detection in spaceborne SAR imagery is of great importance. Focusing on practical problems of ship detection, this paper presents a highly adaptive ship detection scheme for spaceborne SAR imagery. It is able to process a wide range of sensors, imaging modes and resolutions. Two main stages are identified in this paper, namely: ship candidate detection and ship discrimination. Firstly, this paper proposes an adaptive land masking method using ship size and pixel size. Secondly, taking into account the imaging mode, incidence angle, and polarization channel of SAR imagery, it implements adaptive ship candidate detection in spaceborne SAR imagery by applying different strategies to different resolution SAR images. Finally, aiming at different types of typical false alarms, this paper proposes a comprehensive ship discrimination method in spaceborne SAR imagery based on confidence level and complexity analysis. Experimental results based on RADARSAT-1, RADARSAT-2, TerraSAR-X, RS-1, and RS-3 images demonstrate that the adaptive scheme proposed in this paper is able to detect ship targets in a fast, efficient and robust way.

Long-Term Monitoring of Water Dynamics in the Sahel Region Using the Multi-Sar

Science.gov (United States)

Bertram, A.; Wendleder, A.; Schmitt, A.; Huber, M.

2016-06-01

Fresh water is a scarce resource in the West-African Sahel region, seasonally influenced by droughts and floods. Particularly in terms of climate change, the importance of wetlands increases for flora, fauna, human population, agriculture, livestock and fishery. Hence, access to open water is a key factor. Long-term monitoring of water dynamics is of great importance, especially with regard to the spatio-temporal extend of wetlands and drylands. It can predict future trends and facilitate the development of adequate management strategies. Lake Tabalak, a Ramsar wetland of international importance, is one of the most significant ponds in Niger and a refuge for waterbirds. Nevertheless, human population growth increased the pressure on this ecosystem, which is now degrading for all uses. The main objective of the study is a long-term monitoring of the Lake Tabalak's water dynamics to delineate permanent and seasonal water bodies, using weather- and daytime-independent multi-sensor and multi-temporal Synthetic Aperture Radar (SAR) data available for the study area. Data of the following sensors from 1993 until 2016 are used: Sentinel-1A, TerraSARX, ALOS PALSAR-1/2, Envisat ASAR, RADARSAT-1/2, and ERS-1/2. All SAR data are processed with the Multi-SAR-System, unifying the different characteristics of all above mentioned sensors in terms of geometric, radiometric and polarimetric resolution to a consistent format. The polarimetric representation in Kennaugh elements allows fusing single-polarized data acquired by older sensors with multi-polarized data acquired by current sensors. The TANH-normalization guarantees a consistent and therefore comparable description in a closed data range in terms of radiometry. The geometric aspect is solved by projecting all images to an earth-fixed coordinate system correcting the brightness by the help of the incidence angle. The elevation model used in the geocoding step is the novel global model produced by the TanDEM-X satellite

Enhanced Human-Type Receptor Binding by Ferret-Transmissible H5N1 with a K193T Mutation.

Science.gov (United States)

Peng, Wenjie; Bouwman, Kim M; McBride, Ryan; Grant, Oliver C; Woods, Robert J; Verheije, Monique H; Paulson, James C; de Vries, Robert P

2018-05-15

All human influenza pandemics have originated from avian influenza viruses. Although multiple changes are needed for an avian virus to be able to transmit between humans, binding to human-type receptors is essential. Several research groups have reported mutations in H5N1 viruses that exhibit specificity for human-type receptors and promote respiratory droplet transmission between ferrets. Upon detailed analysis, we have found that these mutants exhibit significant differences in fine receptor specificity compared to human H1N1 and H3N2 and retain avian-type receptor binding. We have recently shown that human influenza viruses preferentially bind to α2-6-sialylated branched N-linked glycans, where the sialic acids on each branch can bind to receptor sites on two protomers of the same hemagglutinin (HA) trimer. In this binding mode, the glycan projects over the 190 helix at the top of the receptor-binding pocket, which in H5N1 would create a stearic clash with lysine at position 193. Thus, we hypothesized that a K193T mutation would improve binding to branched N-linked receptors. Indeed, the addition of the K193T mutation to the H5 HA of a respiratory-droplet-transmissible virus dramatically improves both binding to human trachea epithelial cells and specificity for extended α2-6-sialylated N-linked glycans recognized by human influenza viruses. IMPORTANCE Infections by avian H5N1 viruses are associated with a high mortality rate in several species, including humans. Fortunately, H5N1 viruses do not transmit between humans because they do not bind to human-type receptors. In 2012, three seminal papers have shown how these viruses can be engineered to transmit between ferrets, the human model for influenza virus infection. Receptor binding, among others, was changed, and the viruses now bind to human-type receptors. Receptor specificity was still markedly different compared to that of human influenza viruses. Here we report an additional mutation in ferret

Identification of a new human coronavirus

NARCIS (Netherlands)

van der Hoek, Lia; Pyrc, Krzysztof; Jebbink, Maarten F.; Vermeulen-Oost, Wilma; Berkhout, Ron J. M.; Wolthers, Katja C.; Wertheim-van Dillen, Pauline M. E.; Kaandorp, Jos; Spaargaren, Joke; Berkhout, Ben

2004-01-01

Three human coronaviruses are known to exist: human coronavirus 229E (HCoV-229E), HCoV-OC43 and severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV). Here we report the identification of a fourth human coronavirus, HCoV-NL63, using a new method of virus discovery. The virus was

Evaluation of SAR in a human body model due to wireless power transmission in the 10 MHz band

International Nuclear Information System (INIS)

Laakso, Ilkka; Tsuchida, Shogo; Hirata, Akimasa; Kamimura, Yoshitsugu

2012-01-01

This study discusses a computational method for calculating the specific absorption rate (SAR) due to a wireless power transmission system in the 10 MHz frequency band. A two-step quasi-static method comprised of the method of moments and the scalar potential finite-difference method are proposed. The applicability of the quasi-static approximation for localized exposure in this frequency band is discussed by comparing the SAR in a lossy dielectric cylinder computed with a full-wave electromagnetic analysis and the quasi-static approximation. From the computational results, the input impedance of the resonant coils was affected by the existence of the cylinder. On the other hand, the magnetic field distribution in free space and considering the cylinder and an impedance matching circuit were in good agreement; the maximum difference in the amplitude of the magnetic field was 4.8%. For a cylinder–coil distance of 10 mm, the difference between the peak 10 g averaged SAR in the cylinder computed with the full-wave electromagnetic method and our quasi-static method was 7.8%. These results suggest that the quasi-static approach is applicable for conducting the dosimetry of wireless power transmission in the 10 MHz band. With our two-step quasi-static method, the SAR in the anatomically based model was computed for different exposure scenarios. From those computations, the allowable input power satisfying the limit of a peak 10 g averaged SAR of 2.0 W kg −1 was 830 W in the worst case exposure scenario with a coil positioned at a distance of 30 mm from the chest. (paper)

Pyrimidine and nucleoside gamma-esters of L-Glu-Sar

DEFF Research Database (Denmark)

Eriksson, André H; Elm, Peter L; Begtrup, Mikael

2005-01-01

-tetrahydrofuran-3-yl ester)-Sar (I), l-Glu(thymine-1-yl-methyl ester)-Sar (II) and l-Glu(acyclothymidine)-Sar (III) were synthesised and in vitro stability was studied in various aqueous and biological media. Affinity to and translocation via hPEPT1 was investigated in mature Caco-2 cell monolayers, grown......The aim of the present study was to improve the synthetic pathway of bioreversible dipeptide derivatives as well as evaluate the potential of using l-Glu-Sar as a pro-moiety for delivering three newly synthesised nucleoside and pyrimidine l-Glu-Sar derivatives. l-Glu(trans-2-thymine-1-yl...

Use of SAR data for proliferation monitoring

International Nuclear Information System (INIS)

Lafitte, M.; Robin, J.P.

2013-01-01

Synthetic Aperture Radar (SAR) is an active and coherent system. SAR images are complex data which contain both amplitude and phase information. The analysis of single SAR data required a very good experience and a good understanding of SAR geometry regarding layover, shadowing, texture and speckle. Image analyst can depicts and describes most of the facilities related to nuclear proliferation and weapons of mass destruction (WMD). The Amplitude Change Detection (ACD) technique consists of a combination of two or three SAR amplitude data acquired with similar orbit and frequency parameters on different dates. That technique provides a very good overview of the changes and particularly regarding vehicles activity and constructions ongoing within the area of interest over the monitoring period. One of the particularities of the SAR systems is to be coherent. The phase of a single image is not exploitable. Thus when two or more SAR data have been acquired with identical orbit and frequency parameters, the phases shift are indicators of changes such as structural changes, terrain subsidence or motion. The Multi-Temporal Coherence (MTC) product merged the two type of information previously detailed: the ACD and coherence analysis. It consists of the combination of two amplitude images and the corresponding coherence computed image. The MTC image may highlights changes between two states of a target which on the ACD analysis appeared unchanged. EUSC uses the difference interferometry techniques in order to estimate volumes that have changed between two acquisition dates. The paper is followed by the slides of the presentation. (A.C.)

SAR and LIDAR fusion: experiments and applications

Science.gov (United States)

Edwards, Matthew C.; Zaugg, Evan C.; Bradley, Joshua P.; Bowden, Ryan D.

2013-05-01

In recent years ARTEMIS, Inc. has developed a series of compact, versatile Synthetic Aperture Radar (SAR) systems which have been operated on a variety of small manned and unmanned aircraft. The multi-frequency-band SlimSAR has demonstrated a variety of capabilities including maritime and littoral target detection, ground moving target indication, polarimetry, interferometry, change detection, and foliage penetration. ARTEMIS also continues to build upon the radar's capabilities through fusion with other sensors, such as electro-optical and infrared camera gimbals and light detection and ranging (LIDAR) devices. In this paper we focus on experiments and applications employing SAR and LIDAR fusion. LIDAR is similar to radar in that it transmits a signal which, after being reflected or scattered by a target area, is recorded by the sensor. The differences are that a LIDAR uses a laser as a transmitter and optical sensors as a receiver, and the wavelengths used exhibit a very different scattering phenomenology than the microwaves used in radar, making SAR and LIDAR good complementary technologies. LIDAR is used in many applications including agriculture, archeology, geo-science, and surveying. Some typical data products include digital elevation maps of a target area and features and shapes extracted from the data. A set of experiments conducted to demonstrate the fusion of SAR and LIDAR data include a LIDAR DEM used in accurately processing the SAR data of a high relief area (mountainous, urban). Also, feature extraction is used in improving geolocation accuracy of the SAR and LIDAR data.

Cloaked similarity between HIV-1 and SARS-CoV suggests an anti-SARS strategy

Directory of Open Access Journals (Sweden)

Kliger Yossef

2003-09-01

Full Text Available Abstract Background Severe acute respiratory syndrome (SARS is a febrile respiratory illness. The disease has been etiologically linked to a novel coronavirus that has been named the SARS-associated coronavirus (SARS-CoV, whose genome was recently sequenced. Since it is a member of the Coronaviridae, its spike protein (S2 is believed to play a central role in viral entry by facilitating fusion between the viral and host cell membranes. The protein responsible for viral-induced membrane fusion of HIV-1 (gp41 differs in length, and has no sequence homology with S2. Results Sequence analysis reveals that the two viral proteins share the sequence motifs that construct their active conformation. These include (1 an N-terminal leucine/isoleucine zipper-like sequence, and (2 a C-terminal heptad repeat located upstream of (3 an aromatic residue-rich region juxtaposed to the (4 transmembrane segment. Conclusions This study points to a similar mode of action for the two viral proteins, suggesting that anti-viral strategy that targets the viral-induced membrane fusion step can be adopted from HIV-1 to SARS-CoV. Recently the FDA approved Enfuvirtide, a synthetic peptide corresponding to the C-terminal heptad repeat of HIV-1 gp41, as an anti-AIDS agent. Enfuvirtide and C34, another anti HIV-1 peptide, exert their inhibitory activity by binding to a leucine/isoleucine zipper-like sequence in gp41, thus inhibiting a conformational change of gp41 required for its activation. We suggest that peptides corresponding to the C-terminal heptad repeat of the S2 protein may serve as inhibitors for SARS-CoV entry.

Functional genomics highlights differential induction of antiviral pathways in the lungs of SARS-CoV-infected macaques.

Directory of Open Access Journals (Sweden)

Anna de Lang

2007-08-01

Full Text Available The pathogenesis of severe acute respiratory syndrome coronavirus (SARS-CoV is likely mediated by disproportional immune responses and the ability of the virus to circumvent innate immunity. Using functional genomics, we analyzed early host responses to SARS-CoV infection in the lungs of adolescent cynomolgus macaques (Macaca fascicularis that show lung pathology similar to that observed in human adults with SARS. Analysis of gene signatures revealed induction of a strong innate immune response characterized by the stimulation of various cytokine and chemokine genes, including interleukin (IL-6, IL-8, and IP-10, which corresponds to the host response seen in acute respiratory distress syndrome. As opposed to many in vitro experiments, SARS-CoV induced a wide range of type I interferons (IFNs and nuclear translocation of phosphorylated signal transducer and activator of transcription 1 in the lungs of macaques. Using immunohistochemistry, we revealed that these antiviral signaling pathways were differentially regulated in distinctive subsets of cells. Our studies emphasize that the induction of early IFN signaling may be critical to confer protection against SARS-CoV infection and highlight the strength of combining functional genomics with immunohistochemistry to further unravel the pathogenesis of SARS.

Polarimetric SAR interferometry-based decomposition modelling for reliable scattering retrieval

Science.gov (United States)

Agrawal, Neeraj; Kumar, Shashi; Tolpekin, Valentyn

2016-05-01

Fully Polarimetric SAR (PolSAR) data is used for scattering information retrieval from single SAR resolution cell. Single SAR resolution cell may contain contribution from more than one scattering objects. Hence, single or dual polarized data does not provide all the possible scattering information. So, to overcome this problem fully Polarimetric data is used. It was observed in previous study that fully Polarimetric data of different dates provide different scattering values for same object and coefficient of determination obtained from linear regression between volume scattering and aboveground biomass (AGB) shows different values for the SAR dataset of different dates. Scattering values are important input elements for modelling of forest aboveground biomass. In this research work an approach is proposed to get reliable scattering from interferometric pair of fully Polarimetric RADARSAT-2 data. The field survey for data collection was carried out for Barkot forest during November 10th to December 5th, 2014. Stratified random sampling was used to collect field data for circumference at breast height (CBH) and tree height measurement. Field-measured AGB was compared with the volume scattering elements obtained from decomposition modelling of individual PolSAR images and PolInSAR coherency matrix. Yamaguchi 4-component decomposition was implemented to retrieve scattering elements from SAR data. PolInSAR based decomposition was the great challenge in this work and it was implemented with certain assumptions to create Hermitian coherency matrix with co-registered polarimetric interferometric pair of SAR data. Regression analysis between field-measured AGB and volume scattering element obtained from PolInSAR data showed highest (0.589) coefficient of determination. The same regression with volume scattering elements of individual SAR images showed 0.49 and 0.50 coefficients of determination for master and slave images respectively. This study recommends use of

Federated query services provided by the Seamless SAR Archive project

Science.gov (United States)

Baker, S.; Bryson, G.; Buechler, B.; Meertens, C. M.; Crosby, C. J.; Fielding, E. J.; Nicoll, J.; Youn, C.; Baru, C.

2013-12-01

The NASA Advancing Collaborative Connections for Earth System Science (ACCESS) seamless synthetic aperture radar (SAR) archive (SSARA) project is a 2-year collaboration between UNAVCO, the Alaska Satellite Facility (ASF), the Jet Propulsion Laboratory (JPL), and OpenTopography at the San Diego Supercomputer Center (SDSC) to design and implement a seamless distributed access system for SAR data and derived data products (i.e. interferograms). A major milestone for the first year of the SSARA project was a unified application programming interface (API) for SAR data search and results at ASF and UNAVCO (WInSAR and EarthScope data archives) through the use of simple web services. A federated query service was developed using the unified APIs, providing users a single search interface for both archives (http://www.unavco.org/ws/brokered/ssara/sar/search). A command line client that utilizes this new service is provided as an open source utility for the community on GitHub (https://github.com/bakerunavco/SSARA). Further API development and enhancements added more InSAR specific keywords and quality control parameters (Doppler centroid, faraday rotation, InSAR stack size, and perpendicular baselines). To facilitate InSAR processing, the federated query service incorporated URLs for DEM (from OpenTopography) and tropospheric corrections (from the JPL OSCAR service) in addition to the URLs for SAR data. This federated query service will provide relevant QC metadata for selecting pairs of SAR data for InSAR processing and all the URLs necessary for interferogram generation. Interest from the international community has prompted an effort to incorporate other SAR data archives (the ESA Virtual Archive 4 and the DLR TerraSAR-X_SSC Geohazard Supersites and Natural Laboratories collections) into the federated query service which provide data for researchers outside the US and North America.

Value of the radiolabelled GLP-1 receptor antagonist exendin(9-39) for targeting of GLP-1 receptor-expressing pancreatic tissues in mice and humans

Energy Technology Data Exchange (ETDEWEB)

Waser, Beatrice; Reubi, Jean Claude [University of Berne, Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, P.O. Box 62, Bern (Switzerland)

2011-06-15

Radiolabelled glucagon-like peptide 1 (GLP-1) receptor agonists have recently been shown to successfully image benign insulinomas in patients. Moreover, it was recently reported that antagonist tracers were superior to agonist tracers for somatostatin and gastrin-releasing peptide receptor targeting of tumours. The present preclinical study determines therefore the value of an established GLP-1 receptor antagonist for the in vitro visualization of GLP-1 receptor-expressing tissues in mice and humans. Receptor autoradiography studies with {sup 125}I-GLP-1(7-36)amide agonist or {sup 125}I-Bolton-Hunter-exendin(9-39) antagonist radioligands were performed in mice pancreas and insulinomas as well as in human insulinomas; competition experiments were performed in the presence of increasing concentration of GLP-1(7-36)amide or exendin(9-39). The antagonist {sup 125}I-Bolton-Hunter-exendin(9-39) labels mouse pancreatic {beta}-cells and mouse insulinomas, but it does not label human pancreatic {beta}-cells and insulinomas. High affinity displacement (IC{sub 50} approximately 2 nM) is observed in mouse {beta}-cells and insulinomas with either the exendin(9-39) antagonist or GLP-1(7-36)amide agonist. For comparison, the agonist {sup 125}I-GLP-1(7-36)amide intensively labels mouse pancreatic {beta}-cells, mouse insulinoma and human insulinomas; high affinity displacement is observed for the GLP-1(7-36)amide in all tissues; however, a 5 and 20 times lower affinity is found for exendin(9-39) in the mouse and human tissues, respectively. This study reports a species-dependent behaviour of the GLP-1 receptor antagonist exendin(9-39) that can optimally target GLP-1 receptors in mice but not in human tissue. Due to its overly low binding affinity, this antagonist is an inadequate targeting agent for human GLP-1 receptor-expressing tissues, as opposed to the GLP-1 receptor agonist, GLP-1(7-36)amide. (orig.)

Muscarinic receptor agonists stimulate matrix metalloproteinase 1-dependent invasion of human colon cancer cells

International Nuclear Information System (INIS)

Raufman, Jean-Pierre; Cheng, Kunrong; Saxena, Neeraj; Chahdi, Ahmed; Belo, Angelica; Khurana, Sandeep; Xie, Guofeng

2011-01-01

Highlights: ► Muscarinic receptor agonists stimulated robust human colon cancer cell invasion. ► Anti-matrix metalloproteinase1 antibody pre-treatment blocks cell invasion. ► Bile acids stimulate MMP1 expression, cell migration and MMP1-dependent invasion. -- Abstract: Mammalian matrix metalloproteinases (MMPs) which degrade extracellular matrix facilitate colon cancer cell invasion into the bloodstream and extra-colonic tissues; in particular, MMP1 expression correlates strongly with advanced colon cancer stage, hematogenous metastasis and poor prognosis. Likewise, muscarinic receptor signaling plays an important role in colon cancer; muscarinic receptors are over-expressed in colon cancer compared to normal colon epithelial cells. Muscarinic receptor activation stimulates proliferation, migration and invasion of human colon cancer cells. In mouse intestinal neoplasia models genetic ablation of muscarinic receptors attenuates carcinogenesis. In the present work, we sought to link these observations by showing that MMP1 expression and activation plays a mechanistic role in muscarinic receptor agonist-induced colon cancer cell invasion. We show that acetylcholine, which robustly increases MMP1 expression, stimulates invasion of HT29 and H508 human colon cancer cells into human umbilical vein endothelial cell monolayers – this was abolished by pre-incubation with atropine, a non-selective muscarinic receptor inhibitor, and by pre-incubation with anti-MMP1 neutralizing antibody. Similar results were obtained using a Matrigel chamber assay and deoxycholyltaurine (DCT), an amidated dihydroxy bile acid associated with colon neoplasia in animal models and humans, and previously shown to interact functionally with muscarinic receptors. DCT treatment of human colon cancer cells resulted in time-dependent, 10-fold increased MMP1 expression, and DCT-induced cell invasion was also blocked by pre-treatment with anti-MMP1 antibody. This study contributes to understanding

Muscarinic receptor agonists stimulate matrix metalloproteinase 1-dependent invasion of human colon cancer cells

Energy Technology Data Exchange (ETDEWEB)

Raufman, Jean-Pierre, E-mail: jraufman@medicine.umaryland.edu [Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD (United States); Cheng, Kunrong; Saxena, Neeraj; Chahdi, Ahmed; Belo, Angelica; Khurana, Sandeep; Xie, Guofeng [Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD (United States)

2011-11-18

Highlights: Black-Right-Pointing-Pointer Muscarinic receptor agonists stimulated robust human colon cancer cell invasion. Black-Right-Pointing-Pointer Anti-matrix metalloproteinase1 antibody pre-treatment blocks cell invasion. Black-Right-Pointing-Pointer Bile acids stimulate MMP1 expression, cell migration and MMP1-dependent invasion. -- Abstract: Mammalian matrix metalloproteinases (MMPs) which degrade extracellular matrix facilitate colon cancer cell invasion into the bloodstream and extra-colonic tissues; in particular, MMP1 expression correlates strongly with advanced colon cancer stage, hematogenous metastasis and poor prognosis. Likewise, muscarinic receptor signaling plays an important role in colon cancer; muscarinic receptors are over-expressed in colon cancer compared to normal colon epithelial cells. Muscarinic receptor activation stimulates proliferation, migration and invasion of human colon cancer cells. In mouse intestinal neoplasia models genetic ablation of muscarinic receptors attenuates carcinogenesis. In the present work, we sought to link these observations by showing that MMP1 expression and activation plays a mechanistic role in muscarinic receptor agonist-induced colon cancer cell invasion. We show that acetylcholine, which robustly increases MMP1 expression, stimulates invasion of HT29 and H508 human colon cancer cells into human umbilical vein endothelial cell monolayers - this was abolished by pre-incubation with atropine, a non-selective muscarinic receptor inhibitor, and by pre-incubation with anti-MMP1 neutralizing antibody. Similar results were obtained using a Matrigel chamber assay and deoxycholyltaurine (DCT), an amidated dihydroxy bile acid associated with colon neoplasia in animal models and humans, and previously shown to interact functionally with muscarinic receptors. DCT treatment of human colon cancer cells resulted in time-dependent, 10-fold increased MMP1 expression, and DCT-induced cell invasion was also blocked by pre

Inhibitory effects of two G protein-coupled receptor kinases on the cell surface expression and signaling of the human adrenomedullin receptor

Energy Technology Data Exchange (ETDEWEB)

Kuwasako, Kenji, E-mail: kuwasako@med.miyazaki-u.ac.jp [Frontier Science Research Center, University of Miyazaki, Miyazaki, 889-1692 (Japan); Sekiguchi, Toshio [Noto Marine Laboratory, Division of Marine Environmental Studies, Institute of Nature and Environmental Technology, Kanazawa University, Ishikawa, 927-0553 (Japan); Nagata, Sayaka [Division of Circulatory and Body Fluid Regulation, Faculty of Medicine, University of Miyazaki, Miyazaki, 889-1692 (Japan); Jiang, Danfeng; Hayashi, Hidetaka [Frontier Science Research Center, University of Miyazaki, Miyazaki, 889-1692 (Japan); Murakami, Manabu [Department of Pharmacology, Hirosaki University, Graduate School of Medicine, Hirosaki, 036-8562 (Japan); Hattori, Yuichi [Department of Molecular and Medical Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, 930-0194 (Japan); Kitamura, Kazuo [Division of Circulatory and Body Fluid Regulation, Faculty of Medicine, University of Miyazaki, Miyazaki, 889-1692 (Japan); Kato, Johji [Frontier Science Research Center, University of Miyazaki, Miyazaki, 889-1692 (Japan)

2016-02-19

Receptor activity-modifying protein 2 (RAMP2) enables the calcitonin receptor-like receptor (CLR, a family B GPCR) to form the type 1 adrenomedullin receptor (AM{sub 1} receptor). Here, we investigated the effects of the five non-visual GPCR kinases (GRKs 2 through 6) on the cell surface expression of the human (h)AM{sub 1} receptor by cotransfecting each of these GRKs into HEK-293 cells that stably expressed hRAMP2. Flow cytometric analysis revealed that when coexpressed with GRK4 or GRK5, the cell surface expression of the AM{sub 1} receptor was markedly decreased prior to stimulation with AM, thereby attenuating both the specific [{sup 125}I]AM binding and AM-induced cAMP production. These inhibitory effects of both GRKs were abolished by the replacement of the cytoplasmic C-terminal tail (C-tail) of CLR with that of the calcitonin receptor (a family B GPCR) or β{sub 2}-adrenergic receptor (a family A GPCR). Among the sequentially truncated CLR C-tail mutants, those lacking the five residues 449–453 (Ser-Phe-Ser-Asn-Ser) abolished the inhibition of the cell surface expression of CLR via the overexpression of GRK4 or GRK5. Thus, we provided new insight into the function of GRKs in agonist-unstimulated GPCR trafficking using a recombinant AM{sub 1} receptor and further determined the region of the CLR C-tail responsible for this GRK function. - Highlights: • We discovered a novel function of GRKs in GPCR trafficking using human CLR/RAMP2. • GRKs 4 and 5 markedly inhibited the cell surface expression of human CLR/RAMP2. • Both GRKs exhibited highly significant receptor signaling inhibition. • Five residues of the C-terminal tail of CLR govern this function of GRKs.

Inhibitory effects of two G protein-coupled receptor kinases on the cell surface expression and signaling of the human adrenomedullin receptor

International Nuclear Information System (INIS)

Kuwasako, Kenji; Sekiguchi, Toshio; Nagata, Sayaka; Jiang, Danfeng; Hayashi, Hidetaka; Murakami, Manabu; Hattori, Yuichi; Kitamura, Kazuo; Kato, Johji

2016-01-01

Receptor activity-modifying protein 2 (RAMP2) enables the calcitonin receptor-like receptor (CLR, a family B GPCR) to form the type 1 adrenomedullin receptor (AM_1 receptor). Here, we investigated the effects of the five non-visual GPCR kinases (GRKs 2 through 6) on the cell surface expression of the human (h)AM_1 receptor by cotransfecting each of these GRKs into HEK-293 cells that stably expressed hRAMP2. Flow cytometric analysis revealed that when coexpressed with GRK4 or GRK5, the cell surface expression of the AM_1 receptor was markedly decreased prior to stimulation with AM, thereby attenuating both the specific ["1"2"5I]AM binding and AM-induced cAMP production. These inhibitory effects of both GRKs were abolished by the replacement of the cytoplasmic C-terminal tail (C-tail) of CLR with that of the calcitonin receptor (a family B GPCR) or β_2-adrenergic receptor (a family A GPCR). Among the sequentially truncated CLR C-tail mutants, those lacking the five residues 449–453 (Ser-Phe-Ser-Asn-Ser) abolished the inhibition of the cell surface expression of CLR via the overexpression of GRK4 or GRK5. Thus, we provided new insight into the function of GRKs in agonist-unstimulated GPCR trafficking using a recombinant AM_1 receptor and further determined the region of the CLR C-tail responsible for this GRK function. - Highlights: • We discovered a novel function of GRKs in GPCR trafficking using human CLR/RAMP2. • GRKs 4 and 5 markedly inhibited the cell surface expression of human CLR/RAMP2. • Both GRKs exhibited highly significant receptor signaling inhibition. • Five residues of the C-terminal tail of CLR govern this function of GRKs.

Application of cultured human mast cells (CHMC) for the design and structure-activity relationship of IgE-mediated mast cell activation inhibitors.

Science.gov (United States)

Argade, Ankush; Bhamidipati, Somasekhar; Li, Hui; Carroll, David; Clough, Jeffrey; Keim, Holger; Sylvain, Catherine; Rossi, Alexander B; Coquilla, Christina; Issakani, Sarkiz D; Masuda, Esteban S; Payan, Donald G; Singh, Rajinder

2015-01-01

Here we report the optimization of small molecule inhibitors of human mast cell degranulation via anti-IgE-mediated tryptase release following cross-linking and activation of IgE-loaded FcεR1 receptors. The compounds are selective upstream inhibitors of FcεR1-dependent human mast cell degranulation and proved to be devoid of activity in downstream ionomycin mediated degranulation. Structure-activity relationship (SAR) leading to compound 26 is outlined. Copyright © 2015 Elsevier Ltd. All rights reserved.

Attribute Learning for SAR Image Classification

Directory of Open Access Journals (Sweden)

Chu He

2017-04-01

Full Text Available This paper presents a classification approach based on attribute learning for high spatial resolution Synthetic Aperture Radar (SAR images. To explore the representative and discriminative attributes of SAR images, first, an iterative unsupervised algorithm is designed to cluster in the low-level feature space, where the maximum edge response and the ratio of mean-to-variance are included; a cross-validation step is applied to prevent overfitting. Second, the most discriminative clustering centers are sorted out to construct an attribute dictionary. By resorting to the attribute dictionary, a representation vector describing certain categories in the SAR image can be generated, which in turn is used to perform the classifying task. The experiments conducted on TerraSAR-X images indicate that those learned attributes have strong visual semantics, which are characterized by bright and dark spots, stripes, or their combinations. The classification method based on these learned attributes achieves better results.

SAR system development for UAV multicopter platforms

OpenAIRE

Escartin Martínez, Antonio

2015-01-01

SAR system development for UAV multicopter platforms This thesis describes the optimization of a synthetic aperture radar (SAR) at X-band and its integration into an unmanned aerial vehicle (UAV) of type octocopter. For such optimization the SAR system functionality was extended from singlepol to fulpol and it has been optimized at hardware level in order to improve its quality against noise figure. After its integration into the octocopter platform, its features has been used in order to ...

Novel Polarimetric SAR Interferometry Algorithms, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — Polarimetric radar interferometry (PolInSAR) is a new SAR imaging mode that is rapidly becoming an important technique for bare earth topographic mapping, tree...

Function of the cytoplasmic tail of human calcitonin receptor-like receptor in complex with receptor activity-modifying protein 2

Energy Technology Data Exchange (ETDEWEB)

Kuwasako, Kenji, E-mail: kuwasako@fc.miyazaki-u.ac.jp [Frontier Science Research Center, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692 (Japan); Kitamura, Kazuo; Nagata, Sayaka; Hikosaka, Tomomi [Division of Circulation and Body Fluid Regulation, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692 (Japan); Kato, Johji [Frontier Science Research Center, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692 (Japan)

2010-02-12

Receptor activity-modifying protein 2 (RAMP2) enables calcitonin receptor-like receptor (CRLR) to form an adrenomedullin (AM)-specific receptor. Here we investigated the function of the cytoplasmic C-terminal tail (C-tail) of human (h)CRLR by co-transfecting its C-terminal mutants into HEK-293 cells stably expressing hRAMP2. Deleting the C-tail from CRLR disrupted AM-evoked cAMP production or receptor internalization, but did not affect [{sup 125}I]AM binding. We found that CRLR residues 428-439 are required for AM-evoked cAMP production, though deleting this region had little effect on receptor internalization. Moreover, pretreatment with pertussis toxin (100 ng/mL) led to significant increases in AM-induced cAMP production via wild-type CRLR/RAMP2 complexes. This effect was canceled by deleting CRLR residues 454-457, suggesting Gi couples to this region. Flow cytometric analysis revealed that CRLR truncation mutants lacking residues in the Ser/Thr-rich region extending from Ser{sup 449} to Ser{sup 467} were unable to undergo AM-induced receptor internalization and, in contrast to the effect on wild-type CRLR, overexpression of GPCR kinases-2, -3 and -4 failed to promote internalization of CRLR mutants lacking residues 449-467. Thus, the hCRLR C-tail is crucial for AM-evoked cAMP production and internalization of the CRLR/RAMP2, while the receptor internalization is dependent on the aforementioned GPCR kinases, but not Gs coupling.

The SARVIEWS Project: Automated SAR Processing in Support of Operational Near Real-time Volcano Monitoring

Science.gov (United States)

Meyer, F. J.; Webley, P. W.; Dehn, J.; Arko, S. A.; McAlpin, D. B.; Gong, W.

2016-12-01

Volcanic eruptions are among the most significant hazards to human society, capable of triggering natural disasters on regional to global scales. In the last decade, remote sensing has become established in operational volcano monitoring. Centers like the Alaska Volcano Observatory rely heavily on remote sensing data from optical and thermal sensors to provide time-critical hazard information. Despite this high use of remote sensing data, the presence of clouds and a dependence on solar illumination often limit their impact on decision making. Synthetic Aperture Radar (SAR) systems are widely considered superior to optical sensors in operational monitoring situations, due to their weather and illumination independence. Still, the contribution of SAR to operational volcano monitoring has been limited in the past due to high data costs, long processing times, and low temporal sampling rates of most SAR systems. In this study, we introduce the automatic SAR processing system SARVIEWS, whose advanced data analysis and data integration techniques allow, for the first time, a meaningful integration of SAR into operational monitoring systems. We will introduce the SARVIEWS database interface that allows for automatic, rapid, and seamless access to the data holdings of the Alaska Satellite Facility. We will also present a set of processing techniques designed to automatically generate a set of SAR-based hazard products (e.g. change detection maps, interferograms, geocoded images). The techniques take advantage of modern signal processing and radiometric normalization schemes, enabling the combination of data from different geometries. Finally, we will show how SAR-based hazard information is integrated in existing multi-sensor decision support tools to enable joint hazard analysis with data from optical and thermal sensors. We will showcase the SAR processing system using a set of recent natural disasters (both earthquakes and volcanic eruptions) to demonstrate its

PHARUS: A C-band Airborne SAR

NARCIS (Netherlands)

Hoogeboom, P.; Koomen, P.J.; Pouwels, H.; Snoeij, P.

1990-01-01

In The Netherlands a plan to design aircraft and build a polarimetric C-band SAR system of a novel design, called PHARUS (PHased Array Universal SAR) is carried out by three institutes. These institutes are the Physics and Electronics Laboratory TNO in The Hague (prime contractor and project

Aging Effects of Caenorhabditis elegans Ryanodine Receptor Variants Corresponding to Human Myopathic Mutations

Directory of Open Access Journals (Sweden)

Katie Nicoll Baines

2017-05-01

Full Text Available Delaying the decline in skeletal muscle function will be critical to better maintenance of an active lifestyle in old age. The skeletal muscle ryanodine receptor, the major intracellular membrane channel through which calcium ions pass to elicit muscle contraction, is central to calcium ion balance and is hypothesized to be a significant factor for age-related decline in muscle function. The nematode Caenorhabditis elegans is a key model system for the study of human aging, and strains were generated with modified C. elegans ryanodine receptors corresponding to human myopathic variants linked with malignant hyperthermia and related conditions. The altered response of these strains to pharmacological agents reflected results of human diagnostic tests for individuals with these pathogenic variants. Involvement of nerve cells in the C. elegans responses may relate to rare medical symptoms concerning the central nervous system that have been associated with ryanodine receptor variants. These single amino acid modifications in C. elegans also conferred a reduction in lifespan and an accelerated decline in muscle integrity with age, supporting the significance of ryanodine receptor function for human aging.

G protein-coupled receptor mutations and human genetic disease.

Science.gov (United States)

Thompson, Miles D; Hendy, Geoffrey N; Percy, Maire E; Bichet, Daniel G; Cole, David E C

2014-01-01

Genetic variations in G protein-coupled receptor genes (GPCRs) disrupt GPCR function in a wide variety of human genetic diseases. In vitro strategies and animal models have been used to identify the molecular pathologies underlying naturally occurring GPCR mutations. Inactive, overactive, or constitutively active receptors have been identified that result in pathology. These receptor variants may alter ligand binding, G protein coupling, receptor desensitization and receptor recycling. Receptor systems discussed include rhodopsin, thyrotropin, parathyroid hormone, melanocortin, follicle-stimulating hormone (FSH), luteinizing hormone, gonadotropin-releasing hormone (GNRHR), adrenocorticotropic hormone, vasopressin, endothelin-β, purinergic, and the G protein associated with asthma (GPRA or neuropeptide S receptor 1 (NPSR1)). The role of activating and inactivating calcium-sensing receptor (CaSR) mutations is discussed in detail with respect to familial hypocalciuric hypercalcemia (FHH) and autosomal dominant hypocalemia (ADH). The CASR mutations have been associated with epilepsy. Diseases caused by the genetic disruption of GPCR functions are discussed in the context of their potential to be selectively targeted by drugs that rescue altered receptors. Examples of drugs developed as a result of targeting GPCRs mutated in disease include: calcimimetics and calcilytics, therapeutics targeting melanocortin receptors in obesity, interventions that alter GNRHR loss from the cell surface in idiopathic hypogonadotropic hypogonadism and novel drugs that might rescue the P2RY12 receptor congenital bleeding phenotype. De-orphanization projects have identified novel disease-associated receptors, such as NPSR1 and GPR35. The identification of variants in these receptors provides genetic reagents useful in drug screens. Discussion of the variety of GPCRs that are disrupted in monogenic Mendelian disorders provides the basis for examining the significance of common

Individual Building Extraction from TerraSAR-X Images Based on Ontological Semantic Analysis

Directory of Open Access Journals (Sweden)

Rong Gui

2016-08-01

Full Text Available Accurate building information plays a crucial role for urban planning, human settlements and environmental management. Synthetic aperture radar (SAR images, which deliver images with metric resolution, allow for analyzing and extracting detailed information on urban areas. In this paper, we consider the problem of extracting individual buildings from SAR images based on domain ontology. By analyzing a building scattering model with different orientations and structures, the building ontology model is set up to express multiple characteristics of individual buildings. Under this semantic expression framework, an object-based SAR image segmentation method is adopted to provide homogeneous image objects, and three categories of image object features are extracted. Semantic rules are implemented by organizing image object features, and the individual building objects expression based on an ontological semantic description is formed. Finally, the building primitives are used to detect buildings among the available image objects. Experiments on TerraSAR-X images of Foshan city, China, with a spatial resolution of 1.25 m × 1.25 m, have shown the total extraction rates are above 84%. The results indicate the ontological semantic method can exactly extract flat-roof and gable-roof buildings larger than 250 pixels with different orientations.

Detection and characterization of Ah receptor in tissue and cells from human tonsils

International Nuclear Information System (INIS)

Lorenzen, A.; Okey, A.B.

1991-01-01

Ah receptor was identified and characterized in cytosol and nuclear extracts from human tonsils obtained at surgery from children 2 to 6 years of age. Ah receptor was found in cytosol prepared from whole-tonsil homogenates as well as in cytosol and nuclear fractions prepared from tonsil lymphocytes or tonsil fibroblasts grown in primary culture. Cytosolic Ah receptor was detectable in tonsillar tissue with either halogenated (2,3,7,8-[3H]tetrachlorodibenzo-p-dioxin (TCDD)) or nonhalogenated (3-[3H]methylcholanthrene and [3H]benzo[a]pyrene) aromatic hydrocarbons and sedimented at approximately 9 S after velocity sedimentation on sucrose gradients. The apparent binding affinity (Kd) of [3H]TCDD for Ah receptor ranged from 3 to 12 nM in cytosols from seven different donors. The same analyses indicated a concentration of Ah receptor in human tonsils of approximately 100-300 fmol/mg cytosolic protein. Incubation of either tonsil lymphocytes or tonsil fibroblasts with [3H]TCDD resulted in transformation of cytosolic Ah receptor to a nuclear binding form which could be detected as a specifically labeled peak sedimenting at approximately 6 S on sucrose gradients. These data demonstrate the existence of Ah receptor in human tonsils and suggest that this immune organ may be an appropriate model for further studies on the mechanism and manifestation of aromatic hydrocarbon-induced immunotoxicity in man

Crystal Structure of the Human Laminin Receptor Precursor

Energy Technology Data Exchange (ETDEWEB)

Jamieson,K.; Wu, J.; Hubbard, S.; Meruelo, D.

2008-01-01

The human laminin receptor (LamR) interacts with many ligands, including laminin, prions, Sindbis virus, and the polyphenol (-)-epigallocatechin-3-gallate (EGCG), and has been implicated in a number of diseases. LamR is overexpressed on tumor cells, and targeting LamR elicits anti-cancer effects. Here, we report the crystal structure of human LamR, which provides insights into its function and should facilitate the design of novel therapeutics targeting LamR.

Characterisation of the human NMDA receptor subunit NR3A glycine binding site

DEFF Research Database (Denmark)

Nilsson, A; Duan, J; Mo-Boquist, L-L

2007-01-01

In this study, we characterise the binding site of the human N-methyl-d-aspartate (NMDA) receptor subunit NR3A. Saturation radioligand binding of the NMDA receptor agonists [(3)H]-glycine and [(3)H]-glutamate showed that only glycine binds to human NR3A (hNR3A) with high affinity (K(d)=535nM (277...

Accelerated Scientific InSAR Processing, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — Neva Ridge Technologies proposes to develop a suite of software tools for the analysis of SAR and InSAR data, focused on having a robust and adopted capability well...

An Outbreak of Human Coronavirus OC43 Infection and Serological Cross-Reactivity with SARS Coronavirus

Directory of Open Access Journals (Sweden)

David M Patrick

2006-01-01

Full Text Available BACKGROUND: In summer 2003, a respiratory outbreak was investigated in British Columbia, during which nucleic acid tests and serology unexpectedly indicated reactivity for severe acute respiratory syndrome coronavirus (SARS-CoV.

Polarimetric SAR image classification based on discriminative dictionary learning model

Science.gov (United States)

Sang, Cheng Wei; Sun, Hong

2018-03-01

Polarimetric SAR (PolSAR) image classification is one of the important applications of PolSAR remote sensing. It is a difficult high-dimension nonlinear mapping problem, the sparse representations based on learning overcomplete dictionary have shown great potential to solve such problem. The overcomplete dictionary plays an important role in PolSAR image classification, however for PolSAR image complex scenes, features shared by different classes will weaken the discrimination of learned dictionary, so as to degrade classification performance. In this paper, we propose a novel overcomplete dictionary learning model to enhance the discrimination of dictionary. The learned overcomplete dictionary by the proposed model is more discriminative and very suitable for PolSAR classification.

Expression, purification and crystallization of the SARS-CoV macro domain

International Nuclear Information System (INIS)

Malet, Hélène; Dalle, Karen; Brémond, Nicolas; Tocque, Fabienne; Blangy, Stéphanie; Campanacci, Valérie; Coutard, Bruno; Grisel, Sacha; Lichière, Julie; Lantez, Violaine; Cambillau, Christian; Canard, Bruno; Egloff, Marie-Pierre

2006-01-01

The SARS-CoV macro domain was expressed, purified and crystallized. Selenomethionine-labelled crystals diffracted to 1.8 Å resolution. Macro domains or X domains are found as modules of multidomain proteins, but can also constitute a protein on their own. Recently, biochemical and structural studies of cellular macro domains have been performed, showing that they are active as ADP-ribose-1′′-phosphatases. Macro domains are also present in a number of positive-stranded RNA viruses, but their precise function in viral replication is still unknown. The major human pathogen severe acute respiratory syndrome coronavirus (SARS-CoV) encodes 16 non-structural proteins (nsps), one of which (nsp3) encompasses a macro domain. The SARS-CoV nsp3 gene region corresponding to amino acids 182–355 has been cloned, expressed in Escherichia coli, purified and crystallized. The crystals belong to space group P2 1 , with unit-cell parameters a = 37.5, b = 55.6, c = 108.9 Å, β = 91.4°, and the asymmetric unit contains either two or three molecules. Both native and selenomethionine-labelled crystals diffract to 1.8 Å

Expression, purification and crystallization of the SARS-CoV macro domain

Energy Technology Data Exchange (ETDEWEB)

Malet, Hélène; Dalle, Karen; Brémond, Nicolas; Tocque, Fabienne; Blangy, Stéphanie; Campanacci, Valérie; Coutard, Bruno; Grisel, Sacha; Lichière, Julie; Lantez, Violaine; Cambillau, Christian; Canard, Bruno; Egloff, Marie-Pierre, E-mail: marie-pierre.egloff@afmb.univ-mrs.fr [Centre National de la Recherche Scientifique and Universités d’Aix-Marseille I et II, UMR 6098, Architecture et Fonction des Macromolécules Biologiques, UMR 6098-Case 932, 163 Avenue de Luminy, 13288 Marseille CEDEX 9 (France)

2006-04-01

The SARS-CoV macro domain was expressed, purified and crystallized. Selenomethionine-labelled crystals diffracted to 1.8 Å resolution. Macro domains or X domains are found as modules of multidomain proteins, but can also constitute a protein on their own. Recently, biochemical and structural studies of cellular macro domains have been performed, showing that they are active as ADP-ribose-1′′-phosphatases. Macro domains are also present in a number of positive-stranded RNA viruses, but their precise function in viral replication is still unknown. The major human pathogen severe acute respiratory syndrome coronavirus (SARS-CoV) encodes 16 non-structural proteins (nsps), one of which (nsp3) encompasses a macro domain. The SARS-CoV nsp3 gene region corresponding to amino acids 182–355 has been cloned, expressed in Escherichia coli, purified and crystallized. The crystals belong to space group P2{sub 1}, with unit-cell parameters a = 37.5, b = 55.6, c = 108.9 Å, β = 91.4°, and the asymmetric unit contains either two or three molecules. Both native and selenomethionine-labelled crystals diffract to 1.8 Å.

Characterization of a receptor for human monocyte-derived neutrophil chemotactic factor/interleukin-8

International Nuclear Information System (INIS)

Grob, P.M.; David, E.; Warren, T.C.; DeLeon, R.P.; Farina, P.R.; Homon, C.A.

1990-01-01

Monocyte-derived neutrophil chemotactic factor/interleukin-8 (MDNCF/IL-8) is an 8,000-dalton protein produced by monocytes which exhibits activity as a chemoattractant for neutrophils with maximal activity achieved at a concentration of 50 ng/ml. This polypeptide has been iodinated by chloramine-T methodology (350 Ci/mM), and specific receptors for MDNCF/IL-8 have been detected on human neutrophils, U937 cells, THP-1 cells, and dimethyl sulfoxide-differentiated HL-60 cells. The binding of MDNCF/IL-8 to human neutrophils is not inhibited by interleukin-1 alpha, tumor necrosis factor-alpha, insulin, or epidermal growth factor. In addition, chemoattractants such as C5a, fMet-Leu-Phe, leukotriene B4, and platelet-activating factor fail to inhibit binding, suggesting that MDNCF/IL-8 utilizes a unique receptor. The receptor for MDNCF/IL-8 is apparently glycosylated since ligand binding is inhibited by the presence of wheat germ agglutinin, a lectin with a binding specificity for N-acetylglucosamine and neuraminic acid. Steady state binding experiments indicate Kd values of 4 and 0.5 nM and receptor numbers of 75,000 and 7,400 for human neutrophils and differentiated HL-60 cells, respectively. 125I-MDNCF/IL-8 bound to human neutrophils is rapidly internalized and subsequently released from cells as trichloroacetic acid-soluble radioactivity. Affinity labeling experiments suggest that the human neutrophil MDNCF/IL-8 receptor exhibits a mass of approximately 58,000 daltons

LONG-TERM MONITORING OF WATER DYNAMICS IN THE SAHEL REGION USING THE MULTI-SAR-SYSTEM

Directory of Open Access Journals (Sweden)

A. Bertram

2016-06-01

Full Text Available Fresh water is a scarce resource in the West-African Sahel region, seasonally influenced by droughts and floods. Particularly in terms of climate change, the importance of wetlands increases for flora, fauna, human population, agriculture, livestock and fishery. Hence, access to open water is a key factor. Long-term monitoring of water dynamics is of great importance, especially with regard to the spatio-temporal extend of wetlands and drylands. It can predict future trends and facilitate the development of adequate management strategies. Lake Tabalak, a Ramsar wetland of international importance, is one of the most significant ponds in Niger and a refuge for waterbirds. Nevertheless, human population growth increased the pressure on this ecosystem, which is now degrading for all uses. The main objective of the study is a long-term monitoring of the Lake Tabalak’s water dynamics to delineate permanent and seasonal water bodies, using weather- and daytime-independent multi-sensor and multi-temporal Synthetic Aperture Radar (SAR data available for the study area. Data of the following sensors from 1993 until 2016 are used: Sentinel-1A, TerraSARX, ALOS PALSAR-1/2, Envisat ASAR, RADARSAT-1/2, and ERS-1/2. All SAR data are processed with the Multi-SAR-System, unifying the different characteristics of all above mentioned sensors in terms of geometric, radiometric and polarimetric resolution to a consistent format. The polarimetric representation in Kennaugh elements allows fusing single-polarized data acquired by older sensors with multi-polarized data acquired by current sensors. The TANH-normalization guarantees a consistent and therefore comparable description in a closed data range in terms of radiometry. The geometric aspect is solved by projecting all images to an earth-fixed coordinate system correcting the brightness by the help of the incidence angle. The elevation model used in the geocoding step is the novel global model produced by the

Probenecid inhibits α-adrenergic receptor-mediated vasoconstriction in the human leg vasculature

DEFF Research Database (Denmark)

Nyberg, Michael Permin; Piil, Peter Bergmann; Kiehn, Oliver Thistrup

2018-01-01

to α1- and α2-adrenergic receptor stimulation in the human forearm and leg vasculature of young healthy male subjects (23±3 years). By use of immunolabeling and confocal microscopy, Panx1 channels were found to be expressed in vascular smooth muscle cells of arterioles in human leg skeletal muscle....... Probenecid treatment increased (Padrenergic receptor stimulation) by ≈15%, whereas the response to the α1-agonist phenylephrine was unchanged. Inhibition...

Primary structure and functional characterization of a Drosophila dopamine receptor with high homology to human D1/5 receptors.

Science.gov (United States)

Gotzes, F; Balfanz, S; Baumann, A

1994-01-01

Members of the superfamily of G-protein coupled receptors share significant similarities in sequence and transmembrane architecture. We have isolated a Drosophila homologue of the mammalian dopamine receptor family using a low stringency hybridization approach. The deduced amino acid sequence is approximately 70% homologous to the human D1/D5 receptors. When expressed in HEK 293 cells, the Drosophila receptor stimulates cAMP production in response to dopamine application. This effect was mimicked by SKF 38393, a specific D1 receptor agonist, but inhibited by dopaminergic antagonists such as butaclamol and flupentixol. In situ hybridization revealed that the Drosophila dopamine receptor is highly expressed in the somata of the optic lobes. This suggests that the receptor might be involved in the processing of visual information and/or visual learning in invertebrates.

Characterization of human endothelial cell urokinase-type plasminogen activator receptor protein and messenger RNA

DEFF Research Database (Denmark)

Barnathan, E S; Kuo, A; Karikó, K

1990-01-01

Human umbilical vein endothelial cells in culture (HUVEC) express receptors for urokinase-type plasminogen activators (u-PA). The immunochemical nature of this receptor and its relationship to u-PA receptors expressed by other cell types is unknown. Cross-linking active site-blocked u-PA to HUVEC...... an endothelial cell cDNA library using the polymerase chain reaction (PCR) and oligonucleotide primers corresponding to the DNA sequence of the receptor cloned from transformed human fibroblasts (Roldan et al, EMBO J 9:467, 1990). The size of the cDNA (approximately 1,054 base pairs, bp) and the presence...

Identification of functional VEGF receptors on human platelets.

Science.gov (United States)

Selheim, Frode; Holmsen, Holm; Vassbotn, Flemming S

2002-02-13

Platelets secrete platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) upon stimulation. We have demonstrated that platelets have functionally active PDGF alpha-receptors, a transmembrane tyrosine kinase involved in negative feedback regulation. Here we demonstrate the presence of the related VEGF receptors fms-like tyrosine kinase-1 and kinase-insert domain region on human platelets. VEGF itself did not cause platelet aggregation. However, addition of exogenous VEGF to SFRLLN or thrombin-stimulated platelets potentiated platelet aggregation. Moreover, thrombin-induced phosphoinositide 3-kinase and mitogen-activated protein kinase activity were enhanced in the presence of VEGF.

Mapping the calcitonin receptor in human brain stem

DEFF Research Database (Denmark)

Bower, Rebekah L; Eftekhari, Sajedeh; Waldvogel, Henry J

2016-01-01

understanding of these hormone systems by mapping CTR expression in the human brain stem, specifically the medulla oblongata. Widespread CTR-like immunoreactivity was observed throughout the medulla. Dense CTR staining was noted in several discrete nuclei, including the nucleus of the solitary tract...... receptors (AMY) are a heterodimer formed by the coexpression of CTR with receptor activity-modifying proteins (RAMPs). CTR with RAMP1 responds potently to both amylin and CGRP. The brain stem is a major site of action for circulating amylin and is a rich site of CGRP binding. This study aimed to enhance our...

Synthesis and SAR study of a novel series of dopamine receptor agonists

DEFF Research Database (Denmark)

Risgaard, R.; Jensen, M.; Jørgensen, M.

2014-01-01

The synthesis of a novel series of dopamine receptor agonists are described as well as their in vitro potency and efficacy on dopamine D and D receptors. This series was designed from pergolide and (4aR,10aR)-1-propyl-1,2,3,4,4a,5,10,10a-octahydro-benzo[g]quinolin-6-ol (PHBQ) and resulted in the ...... in the synthesis of (2R,4aR,10aR)-2-methylsulfanylmethyl-4-propyl-3,4,4a,5,10,10a-hexahydro-2H-naphtho[2,3-b][1,4]oxazin-9-ol (compound 27), which has a D and D receptor profile similar to that of the most recently approved drug for Parkinson's disease, rotigotine.......The synthesis of a novel series of dopamine receptor agonists are described as well as their in vitro potency and efficacy on dopamine D and D receptors. This series was designed from pergolide and (4aR,10aR)-1-propyl-1,2,3,4,4a,5,10,10a-octahydro-benzo[g]quinolin-6-ol (PHBQ) and resulted...

Satellite SAR interferometric techniques applied to emergency mapping

Science.gov (United States)

Stefanova Vassileva, Magdalena; Riccardi, Paolo; Lecci, Daniele; Giulio Tonolo, Fabio; Boccardo Boccardo, Piero; Chiesa, Giuliana; Angeluccetti, Irene

2017-04-01

This paper aim to investigate the capabilities of the currently available SAR interferometric algorithms in the field of emergency mapping. Several tests have been performed exploiting the Copernicus Sentinel-1 data using the COTS software ENVI/SARscape 5.3. Emergency Mapping can be defined as "creation of maps, geo-information products and spatial analyses dedicated to providing situational awareness emergency management and immediate crisis information for response by means of extraction of reference (pre-event) and crisis (post-event) geographic information/data from satellite or aerial imagery". The conventional differential SAR interferometric technique (DInSAR) and the two currently available multi-temporal SAR interferometric approaches, i.e. Permanent Scatterer Interferometry (PSI) and Small BAseline Subset (SBAS), have been applied to provide crisis information useful for the emergency management activities. Depending on the considered Emergency Management phase, it may be distinguished between rapid mapping, i.e. fast provision of geospatial data regarding the area affected for the immediate emergency response, and monitoring mapping, i.e. detection of phenomena for risk prevention and mitigation activities. In order to evaluate the potential and limitations of the aforementioned SAR interferometric approaches for the specific rapid and monitoring mapping application, five main factors have been taken into account: crisis information extracted, input data required, processing time and expected accuracy. The results highlight that DInSAR has the capacity to delineate areas affected by large and sudden deformations and fulfills most of the immediate response requirements. The main limiting factor of interferometry is the availability of suitable SAR acquisition immediately after the event (e.g. Sentinel-1 mission characterized by 6-day revisiting time may not always satisfy the immediate emergency request). PSI and SBAS techniques are suitable to produce

Forest parameter estimation using polarimetric SAR interferometry techniques at low frequencies

International Nuclear Information System (INIS)

Lee, Seung-Kuk

2013-01-01

Polarimetric Synthetic Aperture Radar Interferometry (Pol-InSAR) is an active radar remote sensing technique based on the coherent combination of both polarimetric and interferometric observables. The Pol-InSAR technique provided a step forward in quantitative forest parameter estimation. In the last decade, airborne SAR experiments evaluated the potential of Pol-InSAR techniques to estimate forest parameters (e.g., the forest height and biomass) with high accuracy over various local forest test sites. This dissertation addresses the actual status, potentials and limitations of Pol-InSAR inversion techniques for 3-D forest parameter estimations on a global scale using lower frequencies such as L- and P-band. The multi-baseline Pol-InSAR inversion technique is applied to optimize the performance with respect to the actual level of the vertical wave number and to mitigate the impact of temporal decorrelation on the Pol-InSAR forest parameter inversion. Temporal decorrelation is a critical issue for successful Pol-InSAR inversion in the case of repeat-pass Pol-InSAR data, as provided by conventional satellites or airborne SAR systems. Despite the limiting impact of temporal decorrelation in Pol-InSAR inversion, it remains a poorly understood factor in forest height inversion. Therefore, the main goal of this dissertation is to provide a quantitative estimation of the temporal decorrelation effects by using multi-baseline Pol-InSAR data. A new approach to quantify the different temporal decorrelation components is proposed and discussed. Temporal decorrelation coefficients are estimated for temporal baselines ranging from 10 minutes to 54 days and are converted to height inversion errors. In addition, the potential of Pol-InSAR forest parameter estimation techniques is addressed and projected onto future spaceborne system configurations and mission scenarios (Tandem-L and BIOMASS satellite missions at L- and P-band). The impact of the system parameters (e.g., bandwidth

NParCov3: A SAS/IML Macro for Nonparametric Randomization-Based Analysis of Covariance

Directory of Open Access Journals (Sweden)

Richard C. Zink

2012-07-01

Full Text Available Analysis of covariance serves two important purposes in a randomized clinical trial. First, there is a reduction of variance for the treatment effect which provides more powerful statistical tests and more precise confidence intervals. Second, it provides estimates of the treatment effect which are adjusted for random imbalances of covariates between the treatment groups. The nonparametric analysis of covariance method of Koch, Tangen, Jung, and Amara (1998 defines a very general methodology using weighted least-squares to generate covariate-adjusted treatment effects with minimal assumptions. This methodology is general in its applicability to a variety of outcomes, whether continuous, binary, ordinal, incidence density or time-to-event. Further, its use has been illustrated in many clinical trial settings, such as multi-center, dose-response and non-inferiority trials.NParCov3 is a SAS/IML macro written to conduct the nonparametric randomization-based covariance analyses of Koch et al. (1998. The software can analyze a variety of outcomes and can account for stratification. Data from multiple clinical trials will be used for illustration.

The binding site for neohesperidin dihydrochalcone at the human sweet taste receptor

Directory of Open Access Journals (Sweden)

Kratochwil Nicole A

2007-10-01

Full Text Available Abstract Background Differences in sweet taste perception among species depend on structural variations of the sweet taste receptor. The commercially used isovanillyl sweetener neohesperidin dihydrochalcone activates the human but not the rat sweet receptor TAS1R2+TAS1R3. Analysis of interspecies combinations and chimeras of rat and human TAS1R2+TAS1R3 suggested that the heptahelical domain of human TAS1R3 is crucial for the activation of the sweet receptor by neohesperidin dihydrochalcone. Results By mutational analysis combined with functional studies and molecular modeling we identified a set of different amino acid residues within the heptahelical domain of human TAS1R3 that forms the neohesperidin dihydrochalcone binding pocket. Sixteen amino acid residues in the transmembrane domains 2 to 7 and one in the extracellular loop 2 of hTAS1R3 influenced the receptor's response to neohesperidin dihydrochalcone. Some of these seventeen residues are also part of the binding sites for the sweetener cyclamate or the sweet taste inhibitor lactisole. In line with this observation, lactisole inhibited activation of the sweet receptor by neohesperidin dihydrochalcone and cyclamate competitively, whereas receptor activation by aspartame, a sweetener known to bind to the N-terminal domain of TAS1R2, was allosterically inhibited. Seven of the amino acid positions crucial for activation of hTAS1R2+hTAS1R3 by neohesperidin dihydrochalcone are thought to play a role in the binding of allosteric modulators of other class C GPCRs, further supporting our model of the neohesperidin dihydrochalcone pharmacophore. Conclusion From our data we conclude that we identified the neohesperidin dihydrochalcone binding site at the human sweet taste receptor, which overlaps with those for the sweetener cyclamate and the sweet taste inhibitor lactisole. This readily delivers a molecular explanation of our finding that lactisole is a competitive inhibitor of the receptor

Activated human mast cells induce LOX-1-specific scavenger receptor expression in human monocyte-derived macrophages.

Directory of Open Access Journals (Sweden)

Mervi Alanne-Kinnunen

Full Text Available Activated mast cells in atherosclerotic lesions degranulate and release bioactive compounds capable of regulating atherogenesis. Here we examined the ability of activated human primary mast cells to regulate the expression of the major scavenger receptors in cultured human primary monocyte-derived macrophages (HMDMs.Components released by immunologically activated human primary mast cells induced a transient expression of lectin-like oxidized LDL receptor (LOX-1 mRNA in HMDMs, while the expression of two other scavenger receptors, MSR1 and CD36, remained unaffected. The LOX-1-inducing secretory components were identified as histamine, tumor necrosis factor alpha (TNF-α, and transforming growth factor beta (TGF-β1, which exhibited a synergistic effect on LOX-1 mRNA expression. Histamine induced a transient expression of LOX-1 protein. Mast cell -induced increase in LOX-1 expression was not associated with increased uptake of oxidized LDL by the macrophages.Mast cell-derived histamine, TNF-α, and TGF-β1 act in concert to induce a transient increase in LOX-1 expression in human primary monocyte-derived macrophages. The LOX-1-inducing activity potentially endows mast cells a hitherto unrecognized role in the regulation of innate immune reactions in atherogenesis.

Infrastructure monitoring with spaceborne SAR sensors

CERN Document Server

ANGHEL, ANDREI; CACOVEANU, REMUS

2017-01-01

This book presents a novel non-intrusive infrastructure monitoring technique based on the detection and tracking of scattering centers in spaceborne SAR images. The methodology essentially consists of refocusing each available SAR image on an imposed 3D point cloud associated to the envisaged infrastructure element and identifying the reliable scatterers to be monitored by means of four dimensional (4D) tomography. The methodology described in this book provides a new perspective on infrastructure monitoring with spaceborne SAR images, is based on a standalone processing chain, and brings innovative technical aspects relative to conventional approaches. The book is intended primarily for professionals and researchers working in the area of critical infrastructure monitoring by radar remote sensing.

Demonstration of specific dopamine receptors on human pituitary adenomas

Energy Technology Data Exchange (ETDEWEB)

Koga, Masafumi; Nakao, Haruyoshi; Arao, Masayo; Sato, Bunzo; Noma, Keizo; Morimoto, Yasuhiko; Kishimoto, Susumu; Mori, Shintaro; Uozumi, Toru

1987-01-01

Dopamine receptors on human pituitary adenoma membranes were characterized using (/sup 3/H)spiperone as the radioligand. The specific (/sup 3/H)spiperone binding sites on prolactin (PRL)-secreting adenoma membranes were recognized as a dopamine receptor, based upon the data showing high affinity binding, saturability, specificity, temperature dependence, and reversibility. All of 14 PRL-secreting adenomas had high affinity dopamine receptors, with a dissociation constant (Kd) of 0.85 +- 0.11 nmol/l (mean+-SEM) and a maximal binding capacity (Bmax) of 428 +- 48.6 fmol/mg protein. Among 14 growth hormone (GH)-secreting adenomas examined, 8 (57%) had dopamine receptors with a Kd of 1.90 +- 0.47 nmol/l and a Bmax of 131 +- 36.9 fmol/mg protein. Furthermore, 15 of 24 (58%) nonsecreting pituitary adenomas also had dopamine receptors with a Kd of 1.86 +- 0.37 nmol/l and a Bmax of 162 +- 26.0 fmol/mg protein. These results indicate that some GH-secreting adenomas as well as some nonsecreting pituitary adenomas contain dopamine receptors. But their affinity and number of binding sites are significantly lower (P<0.05) and fewer (P<0.001) respectively, than those in PRL-secreting adenomas.

Human platelet vasopressin receptor identification by direct ultraviolet photoaffinity labeling

International Nuclear Information System (INIS)

Thibonnier, M.

1987-01-01

Tritiated vasopressin ([ 3 H]AVP) was directly crosslinked to its human platelet receptor by using an ultraviolet irradiation procedure. After preincubation with [ 3 H]AVP, the hydrodynamic parameters of the hormone-receptor complexes solubilized with 3-[(3-cholamidopropyl)dimethylammonio]-1-propane sulfonate were derived from Sephacryl S-300 superfine gel filtration and from sucrose density gradient ultracentrifugation experiments. The following values were obtained: Stoke's radius = 5.48 +/- 0.1 nm, apparent sedimentation coefficient = 5.55 +/- 0.1 S, and calculated molecular weight = 132,000. On sodium dodecyl sulfate-8% polyacrylamide slab gel electrophoresis under reducing conditions, [ 3 H]AVP preferentially and specifically labeled a 125,000-dalton protein. The labeling of this protein was suppressed by addition of excess cold vasopressin, whereas angiotensin II did not inhibit incorporation of tritiated vasopressin in this protein. These results suggest that direct UV-photoaffinity labelling with [ 3 H]AVP is a suitable tool for the purification of the human platelet vasopressin receptor

IGF-II receptors and IGF-II-stimulated glucose transport in human fat cells

International Nuclear Information System (INIS)

Sinha, M.K.; Buchanan, C.; Raineri-Maldonado, C.; Khazanie, P.; Atkinson, S.; DiMarchi, R.; Caro, J.F.

1990-01-01

Insulin-like growth factor II (IGF-II) receptors have been described in rat but not in human adipocytes. In both species, IGF-II has been reported to stimulate glucose transport by interacting with the insulin receptor. In this study, we have unequivocally demonstrated the presence of IGF-II receptors in human adipocytes. 125I-labeled IGF-II specifically binds to intact adipocytes, membranes, and lectin-purified detergent solubilized extracts. Through the use of 0.5 mM disuccinimidyl suberate, 125I-IGF-II is cross-linked to a 260-kDa protein that is identified as the IGF-II receptor by displacement experiments with unlabeled IGF-II, IGF-I, and insulin and either by immunoprecipitation or by Western blot analysis with mannose 6-phosphate receptor antibodies. The concentrations of IGF-II required for half-maximal and maximal stimulation of glucose transport in human adipocytes are 35 and 100 times more than that of insulin. The possibility of IGF-II stimulating glucose transport by interacting predominantly with the insulin receptor is suggested by the following: (1) the concentration of IGF-II that inhibits half of insulin binding is only 20 times more than that of insulin; (2) the lack of an additive effect of IGF-II and insulin for maximal stimulation of glucose transport; (3) the ability of monoclonal insulin receptor antibodies to decrease glucose transport stimulated by submaximal concentrations of both IGF-II and insulin; and (4) the ability of IGF-II to stimulate insulin receptor autophosphorylation albeit at a reduced potency when compared with insulin

Mapping mountain meadow with high resolution and polarimetric SAR data

International Nuclear Information System (INIS)

Tian, Bangsen; Li, Zhen; Xu, Juan; Fu, Sitao; Liu, Jiuli

2014-01-01

This paper presents a method to map the large grassland in the eastern margin of the Tibetan Plateau with the high resolution polarimetric SAR (PolSAR) imagery. When PolSAR imagery is used for land cover classification, the brightness of a SAR image is affected by topography due to varying projection between ground and image coordinates. The objective of this paper is twofold: (1) we first extend the theory of SAR terrain correction to the polarimetric case, to utilize the entire available polarimetric signature, where correction is performed explicitly based on a matrix format like covariance matrix. (2) Next, the orthoectified PolSAR is applied to classify mountain meadow and investigate the potential of PolSAR in mapping grassland. In this paper, the gamma naught radiometric correction estimates the local illuminated area at each grid point in the radar geometry. Then, each element of the coherency matrix is divided by the local area to produce a polarimetric product. Secondly, the impact of radiometric correction upon classification accuracy is investigated. A supervised classification is performed on the orthorectified Radarsat-2 PolSAR to map the spatial distribution of meadow and evaluate monitoring capabilities of mountain meadow

Determining the influence of Korean population variation on whole-body average SAR.

Science.gov (United States)

Lee, Ae-Kyoung; Choi, Hyung-Do

2012-05-07

Compliance of the ICNIRP reference and IEEE action levels with the basic restrictions on whole-body average (WBA) SAR was investigated based on age, physique, and posture under isolated and grounded conditions. First, Korean male models 1, 3, 5, 7, and 20 years of age with body sizes in the 50th percentile were developed and used as the test subjects: 1y(50th), 3y(50th), 5y(50th), 7y(50th), and 20y(50th). The effects of age-dependent dielectric properties due to the water content of the tissue on WBA SAR were analysed, and showed that the changes in WBA SAR are marginal. At the ages of 1, 5, and 20, thin models 1y(10th), 5y(10th), and 20y(10th) with body sizes in the 10th percentile for the horizontal plane were added in order to determine the influence of physical variations of the population. We considered standing postures with arms up and arms down. The WBA SAR for each human model was calculated when exposed to a vertically polarized plane wave in the frequency range of 10 MHz-3 GHz using the finite-difference time-domain method. The evaluated WBA SAR-based safety factor of each model is discussed for exposure to the ICNIRP reference and IEEE action levels. Finally, the lowest external electric field strength required to produce the basic restrictions on the WBA SAR, 0.08 W kg(-1), was obtained. The results showed that the ICNIRP public reference level is not conservative in the frequency range of 20-200 MHz for an arms-up posture, in the range of 40-200 MHz for an arms-down posture, and above 1 GHz for both postures. The IEEE action level is different from the ICNIRP reference level below 30 MHz, where most cases showed a safety factor of less than 50, which is the minimum value compliant with the basic restrictions for exposure to the general public.

Feline aminopeptidase N is not a functional receptor for avian infectious bronchitis virus

Directory of Open Access Journals (Sweden)

Harbison Carole E

2007-02-01

Full Text Available Abstract Background Coronaviruses are an important cause of infectious diseases in humans, including severe acute respiratory syndrome (SARS, and have the continued potential for emergence from animal species. A major factor in the host range of a coronavirus is its receptor utilization on host cells. In many cases, coronavirus-receptor interactions are well understood. However, a notable exception is the receptor utilization by group 3 coronaviruses, including avian infectious bronchitis virus (IBV. Feline aminopeptidase N (fAPN serves as a functional receptor for most group 1 coronaviruses including feline infectious peritonitis virus (FIPV, canine coronavirus, transmissible gastroenteritis virus (TGEV, and human coronavirus 229E (HCoV-229E. A recent report has also suggested a role for fAPN during IBV entry (Miguel B, Pharr GT, Wang C: The role of feline aminopeptidase N as a receptor for infectious bronchitis virus. Brief review. Arch Virol 2002, 147:2047–2056. Results Here we show that, whereas both transient transfection and constitutive expression of fAPN on BHK-21 cells can rescue FIPV and TGEV infection in non-permissive BHK cells, fAPN expression does not rescue infection by the prototype IBV strain Mass41. To account for the previous suggestion that fAPN could serve as an IBV receptor, we show that feline cells can be infected with the prototype strain of IBV (Mass 41, but with low susceptibility compared to primary chick kidney cells. We also show that BHK-21 cells are slightly susceptible to certain IBV strains, including Ark99, Ark_DPI, CA99, and Iowa97 ( Conclusion We conclude that fAPN is not a functional receptor for IBV, the identity of which is currently under investigation.

Follitropin receptors in rat testis. Characterization with enzymatically 125I-labeled human follitropin.

Science.gov (United States)

Ketelslegers, J M; Catt, K J

1978-07-03

The interaction between enzymatically radioiodinated human follitropin and the follitropin receptors in testis homogenate was investigated in immature and adult rats. The 125I-labeled human follitropin exhibited high binding activity with specific binding of up to 17% in the presence of an excess of testis homogenate. Approx. 50% of the bound hormone could be eluted at pH 5, and the receptor purified tracer exhibited a 3.6-fold increase in binding activity when compared with the original tracer preparation. Quantitative analysis of equilibrium binding data was performed with corrections for the measured specific activity and maximum binding activity of the tracer hormone. The equilibrium association constants (Ka) determined 24 degrees C were not significantly different in immature and adult rat testis, and the mean value for Ka was 3.9 . 10(9) M-1. At 37 degrees C, the Ka value obtained using immature rat testis was 1.3 . 10(10) M-1. The association of 125I-labeled human follitropin with immature rat testis homogenate was time and temperature dependent. In the presence of an excess of unlabeled hormone, 30--60% of the preformed hormone . receptor complex was dissociated after 24 h incubation. A specific and sensitive radioligand-receptor assay for follitropin was developed using immature rat testis homogenate. The minimum detectable dose of purified human follitropin was 0.6 ng, and human urinary and pituitary follitropin, ovine follitropin and pregnant mare serum gonadotropin reacted in the assay with equivalent slopes. The potencies of highly purified pregnent mare serum gonadotropin and highly purified human follitropin were similar in the radioligand-receptor assay, consistent with the follitropin bioactivity of the equine gonadotropin.

Geometric calibration of ERS satellite SAR images

DEFF Research Database (Denmark)

Mohr, Johan Jacob; Madsen, Søren Nørvang

2001-01-01

Geometric calibration of the European Remote Sensing (ERS) Satellite synthetic aperture radar (SAR) slant range images is important in relation to mapping areas without ground reference points and also in relation to automated processing. The relevant SAR system parameters are discussed...

Improved delineation of human dopamine receptors using [18F]-N-methylspiroperidol and PET

International Nuclear Information System (INIS)

Arnett, C.D.; Wolf, A.P.; Shiue, C.Y.; Fowler, J.S.; MacGregor, R.R.; Christman, D.R.; Smith, M.R.

1986-01-01

The brain uptake of [18F]-N-methylspiroperidol, a butyrophenone neuroleptic with high selectivity for the dopamine receptor, has been measured in three normal human volunteers using positron emission tomography for times up to 12 hr postinjection. These studies demonstrated two unique findings concerning the in vivo distribution of this neuroleptic: (a) it is tightly bound to dopamine D-2 receptors in the caudate-putamen brain regions, and (b) these regions are the only large brain structures which exhibit appreciable long-term retention. In addition, radioactivity clears rapidly from plasma, and the percentage of unchanged [18F]-N-methylspiroperidol in plasma declines rapidly. These results suggest that this compound binds irreversibly to dopamine D-2 receptors, and that there are few if any dopamine D-2 receptors in the human frontal cortex. These studies emphasize not only the importance of characterizing neurotransmitter receptors in living human brain using a ligand labeled with a positron emitting nuclide of sufficiently long half-life to allow monitoring of brain radioactivity distribution for several hours after the injection of radioligand, but also of accurately determining the amount of unchanged tracer in plasma for tracer kinetic modeling

HLA-A*0201 T-cell epitopes in severe acute respiratory syndrome (SARS) coronavirus nucleocapsid and spike proteins

International Nuclear Information System (INIS)

Tsao, Y.-P.; Lin, J.-Y.; Jan, J.-T.; Leng, C.-H.; Chu, C.-C.; Yang, Y.-C.; Chen, S.-L.

2006-01-01

The immunogenicity of HLA-A*0201-restricted cytotoxic T lymphocyte (CTL) peptide in severe acute respiratory syndrome coronavirus (SARS-CoV) nuclear capsid (N) and spike (S) proteins was determined by testing the proteins' ability to elicit a specific cellular immune response after immunization of HLA-A2.1 transgenic mice and in vitro vaccination of HLA-A2.1 positive human peripheral blood mononuclearcytes (PBMCs). First, we screened SARS N and S amino acid sequences for allele-specific motif matching those in human HLA-A2.1 MHC-I molecules. From HLA peptide binding predictions (http://thr.cit.nih.gov/molbio/hla_bind/), ten each potential N- and S-specific HLA-A2.1-binding peptides were synthesized. The high affinity HLA-A2.1 peptides were validated by T2-cell stabilization assays, with immunogenicity assays revealing peptides N223-231, N227-235, and N317-325 to be First identified HLA-A*0201-restricted CTL epitopes of SARS-CoV N protein. In addition, previous reports identified three HLA-A*0201-restricted CTL epitopes of S protein (S978-986, S1203-1211, and S1167-1175), here we found two novel peptides S787-795 and S1042-1050 as S-specific CTL epitopes. Moreover, our identified N317-325 and S1042-1050 CTL epitopes could induce recall responses when IFN-γ stimulation of blood CD8 + T-cells revealed significant difference between normal healthy donors and SARS-recovered patients after those PBMCs were in vitro vaccinated with their cognate antigen. Our results would provide a new insight into the development of therapeutic vaccine in SARS

Mutation of Asn28 Disrupts the Dimerization and Enzymatic Activity of SARS 3CL

Energy Technology Data Exchange (ETDEWEB)

Barrila, J.; Gabelli, S; Bacha, U; Amzel, M; Freire, E

2010-01-01

Coronaviruses are responsible for a significant proportion of annual respiratory and enteric infections in humans and other mammals. The most prominent of these viruses is the severe acute respiratory syndrome coronavirus (SARS-CoV) which causes acute respiratory and gastrointestinal infection in humans. The coronavirus main protease, 3CL{sup pro}, is a key target for broad-spectrum antiviral development because of its critical role in viral maturation and high degree of structural conservation among coronaviruses. Dimerization is an indispensable requirement for the function of SARS 3CL{sup pro} and is regulated through mechanisms involving both direct and long-range interactions in the enzyme. While many of the binding interactions at the dimerization interface have been extensively studied, those that are important for long-range control are not well-understood. Characterization of these dimerization mechanisms is important for the structure-based design of new treatments targeting coronavirus-based infections. Here we report that Asn28, a residue 11 {angstrom} from the closest residue in the opposing monomer, is essential for the enzymatic activity and dimerization of SARS 3CLpro. Mutation of this residue to alanine almost completely inactivates the enzyme and results in a 19.2-fold decrease in the dimerization K{sub d}. The crystallographic structure of the N28A mutant determined at 2.35 {angstrom} resolution reveals the critical role of Asn28 in maintaining the structural integrity of the active site and in orienting key residues involved in binding at the dimer interface and substrate catalysis. These findings provide deeper insight into complex mechanisms regulating the activity and dimerization of SARS 3CL{sup pro}.

The overexpressed human 46-kDa mannose 6-phosphate receptor mediates endocytosis and sorting of β-glucuronidase

International Nuclear Information System (INIS)

Watanabe, H.; Grubb, J.H.; Sly, W.S.

1990-01-01

The authors studied the function of the human small (46-kDa) mannose 6-phosphate receptor (SMPR) in transfected mouse L cells that do not express the larger insulin-like growth factor II/mannose 6-phosphate receptor. Cells overexpressing human SMPR were studied for enzyme binding to cell surface receptors, for binding to intracellular receptors in permeabilized cells, and for receptor-mediated endocytosis of recombinant human β-glucuronidase. Specific binding to human SMPR in permeabilized cells showed a pH optimum between pH 6.0 and pH 6.5. Binding was significant in the present of EDTA but was enhanced by added divalent cations. Up to 2.3% of the total functional receptor could be detected on the cell surface by enzyme binding. They present experiments showing that at very high levels of overexpression, and at pH 6.5, human SMPR mediated the endocytosis of β-glucuronidase. At pH 7.5, the rate of endocytosis was only 14% the rate seen at pH 6.5. Cells overexpressing human SMPR also showed reduced secretion of newly synthesized β-glucuronidase when compared to cells transfected with vector only, suggesting that overexpressed human SMPR can participate in sorting of newly synthesized β-glucuronidase and partially correct the sorting defect in mouse L cells that do not express the insulin-like growth factor II/mannose 6-phosphate receptor

Genetic Variations in the Human Cannabinoid Receptor Gene Are Associated with Happiness

Science.gov (United States)

Matsunaga, Masahiro; Isowa, Tokiko; Yamakawa, Kaori; Fukuyama, Seisuke; Shinoda, Jun; Yamada, Jitsuhiro; Ohira, Hideki

2014-01-01

Happiness has been viewed as a temporary emotional state (e.g., pleasure) and a relatively stable state of being happy (subjective happiness level). As previous studies demonstrated that individuals with high subjective happiness level rated their current affective states more positively when they experience positive events, these two aspects of happiness are interrelated. According to a recent neuroimaging study, the cytosine to thymine single-nucleotide polymorphism of the human cannabinoid receptor 1 gene is associated with sensitivity to positive emotional stimuli. Thus, we hypothesized that our genetic traits, such as the human cannabinoid receptor 1 genotypes, are closely related to the two aspects of happiness. In Experiment 1, 198 healthy volunteers were used to compare the subjective happiness level between cytosine allele carriers and thymine-thymine carriers of the human cannabinoid receptor 1 gene. In Experiment 2, we used positron emission tomography with 20 healthy participants to compare the brain responses to positive emotional stimuli of cytosine allele carriers to that of thymine-thymine carriers. Compared to thymine-thymine carriers, cytosine allele carriers have a higher subjective happiness level. Regression analysis indicated that the cytosine allele is significantly associated with subjective happiness level. The positive mood after watching a positive film was significantly higher for the cytosine allele carriers compared to the thymine-thymine carriers. Positive emotion-related brain region such as the medial prefrontal cortex was significantly activated when the cytosine allele carriers watched the positive film compared to the thymine-thymine carriers. Thus, the human cannabinoid receptor 1 genotypes are closely related to two aspects of happiness. Compared to thymine-thymine carriers, the cytosine allele carriers of the human cannabinoid receptor 1 gene, who are sensitive to positive emotional stimuli, exhibited greater magnitude

Genetic variations in the human cannabinoid receptor gene are associated with happiness.

Directory of Open Access Journals (Sweden)

Masahiro Matsunaga

Full Text Available Happiness has been viewed as a temporary emotional state (e.g., pleasure and a relatively stable state of being happy (subjective happiness level. As previous studies demonstrated that individuals with high subjective happiness level rated their current affective states more positively when they experience positive events, these two aspects of happiness are interrelated. According to a recent neuroimaging study, the cytosine to thymine single-nucleotide polymorphism of the human cannabinoid receptor 1 gene is associated with sensitivity to positive emotional stimuli. Thus, we hypothesized that our genetic traits, such as the human cannabinoid receptor 1 genotypes, are closely related to the two aspects of happiness. In Experiment 1, 198 healthy volunteers were used to compare the subjective happiness level between cytosine allele carriers and thymine-thymine carriers of the human cannabinoid receptor 1 gene. In Experiment 2, we used positron emission tomography with 20 healthy participants to compare the brain responses to positive emotional stimuli of cytosine allele carriers to that of thymine-thymine carriers. Compared to thymine-thymine carriers, cytosine allele carriers have a higher subjective happiness level. Regression analysis indicated that the cytosine allele is significantly associated with subjective happiness level. The positive mood after watching a positive film was significantly higher for the cytosine allele carriers compared to the thymine-thymine carriers. Positive emotion-related brain region such as the medial prefrontal cortex was significantly activated when the cytosine allele carriers watched the positive film compared to the thymine-thymine carriers. Thus, the human cannabinoid receptor 1 genotypes are closely related to two aspects of happiness. Compared to thymine-thymine carriers, the cytosine allele carriers of the human cannabinoid receptor 1 gene, who are sensitive to positive emotional stimuli, exhibited greater

Genetic variations in the human cannabinoid receptor gene are associated with happiness.

Science.gov (United States)

Matsunaga, Masahiro; Isowa, Tokiko; Yamakawa, Kaori; Fukuyama, Seisuke; Shinoda, Jun; Yamada, Jitsuhiro; Ohira, Hideki

2014-01-01

Happiness has been viewed as a temporary emotional state (e.g., pleasure) and a relatively stable state of being happy (subjective happiness level). As previous studies demonstrated that individuals with high subjective happiness level rated their current affective states more positively when they experience positive events, these two aspects of happiness are interrelated. According to a recent neuroimaging study, the cytosine to thymine single-nucleotide polymorphism of the human cannabinoid receptor 1 gene is associated with sensitivity to positive emotional stimuli. Thus, we hypothesized that our genetic traits, such as the human cannabinoid receptor 1 genotypes, are closely related to the two aspects of happiness. In Experiment 1, 198 healthy volunteers were used to compare the subjective happiness level between cytosine allele carriers and thymine-thymine carriers of the human cannabinoid receptor 1 gene. In Experiment 2, we used positron emission tomography with 20 healthy participants to compare the brain responses to positive emotional stimuli of cytosine allele carriers to that of thymine-thymine carriers. Compared to thymine-thymine carriers, cytosine allele carriers have a higher subjective happiness level. Regression analysis indicated that the cytosine allele is significantly associated with subjective happiness level. The positive mood after watching a positive film was significantly higher for the cytosine allele carriers compared to the thymine-thymine carriers. Positive emotion-related brain region such as the medial prefrontal cortex was significantly activated when the cytosine allele carriers watched the positive film compared to the thymine-thymine carriers. Thus, the human cannabinoid receptor 1 genotypes are closely related to two aspects of happiness. Compared to thymine-thymine carriers, the cytosine allele carriers of the human cannabinoid receptor 1 gene, who are sensitive to positive emotional stimuli, exhibited greater magnitude

Characterisation of the expression of NMDA receptors in human astrocytes.

Directory of Open Access Journals (Sweden)

Ming-Chak Lee

Full Text Available Astrocytes have long been perceived only as structural and supporting cells within the central nervous system (CNS. However, the discovery that these glial cells may potentially express receptors capable of responding to endogenous neurotransmitters has resulted in the need to reassess astrocytic physiology. The aim of the current study was to characterise the expression of NMDA receptors (NMDARs in primary human astrocytes, and investigate their response to physiological and excitotoxic concentrations of the known endogenous NMDAR agonists, glutamate and quinolinic acid (QUIN. Primary cultures of human astrocytes were used to examine expression of these receptors at the mRNA level using RT-PCR and qPCR, and at the protein level using immunocytochemistry. The functionality role of the receptors was assessed using intracellular calcium influx experiments and measuring extracellular lactate dehydrogenase (LDH activity in primary cultures of human astrocytes treated with glutamate and QUIN. We found that all seven currently known NMDAR subunits (NR1, NR2A, NR2B, NR2C, NR2D, NR3A and NR3B are expressed in astrocytes, but at different levels. Calcium influx studies revealed that both glutamate and QUIN could activate astrocytic NMDARs, which stimulates Ca2+ influx into the cell and can result in dysfunction and death of astrocytes. Our data also show that the NMDAR ion channel blockers, MK801, and memantine can attenuate glutamate and QUIN mediated cell excitotoxicity. This suggests that the mechanism of glutamate and QUIN gliotoxicity is at least partially mediated by excessive stimulation of NMDARs. The present study is the first to provide definitive evidence for the existence of functional NMDAR expression in human primary astrocytes. This discovery has significant implications for redefining the cellular interaction between glia and neurons in both physiological processes and pathological conditions.

Improved SAR Image Coregistration Using Pixel-Offset Series

KAUST Repository

Wang, Teng

2014-03-14

Synthetic aperture radar (SAR) image coregistration is a key procedure before interferometric SAR (InSAR) time-series analysis can be started. However, many geophysical data sets suffer from severe decorrelation problems due to a variety of reasons, making precise coregistration a nontrivial task. Here, we present a new strategy that uses a pixel-offset series of detected subimage patches dominated by point-like targets (PTs) to improve SAR image coregistrations. First, all potentially coherent image pairs are coregistered in a conventional way. In this step, we propose a coregistration quality index for each image to rank its relative “significance” within the data set and to select a reference image for the SAR data set. Then, a pixel-offset series of detected PTs is made from amplitude maps to improve the geometrical mapping functions. Finally, all images are resampled depending on the pixel offsets calculated from the updated geometrical mapping functions. We used images from a rural region near the North Anatolian Fault in eastern Turkey to test the proposed method, and clear coregistration improvements were found based on amplitude stability. This enhanced the fact that the coregistration strategy should therefore lead to improved InSAR time-series analysis results.

Improved SAR Image Coregistration Using Pixel-Offset Series

KAUST Repository

Wang, Teng; Jonsson, Sigurjon; Hanssen, Ramon F.

2014-01-01

Synthetic aperture radar (SAR) image coregistration is a key procedure before interferometric SAR (InSAR) time-series analysis can be started. However, many geophysical data sets suffer from severe decorrelation problems due to a variety of reasons, making precise coregistration a nontrivial task. Here, we present a new strategy that uses a pixel-offset series of detected subimage patches dominated by point-like targets (PTs) to improve SAR image coregistrations. First, all potentially coherent image pairs are coregistered in a conventional way. In this step, we propose a coregistration quality index for each image to rank its relative “significance” within the data set and to select a reference image for the SAR data set. Then, a pixel-offset series of detected PTs is made from amplitude maps to improve the geometrical mapping functions. Finally, all images are resampled depending on the pixel offsets calculated from the updated geometrical mapping functions. We used images from a rural region near the North Anatolian Fault in eastern Turkey to test the proposed method, and clear coregistration improvements were found based on amplitude stability. This enhanced the fact that the coregistration strategy should therefore lead to improved InSAR time-series analysis results.

URBAN MODELLING PERFORMANCE OF NEXT GENERATION SAR MISSIONS

Directory of Open Access Journals (Sweden)

U. G. Sefercik

2017-09-01

Full Text Available In synthetic aperture radar (SAR technology, urban mapping and modelling have become possible with revolutionary missions TerraSAR-X (TSX and Cosmo-SkyMed (CSK since 2007. These satellites offer 1m spatial resolution in high-resolution spotlight imaging mode and capable for high quality digital surface model (DSM acquisition for urban areas utilizing interferometric SAR (InSAR technology. With the advantage of independent generation from seasonal weather conditions, TSX and CSK DSMs are much in demand by scientific users. The performance of SAR DSMs is influenced by the distortions such as layover, foreshortening, shadow and double-bounce depend up on imaging geometry. In this study, the potential of DSMs derived from convenient 1m high-resolution spotlight (HS InSAR pairs of CSK and TSX is validated by model-to-model absolute and relative accuracy estimations in an urban area. For the verification, an airborne laser scanning (ALS DSM of the study area was used as the reference model. Results demonstrated that TSX and CSK urban DSMs are compatible in open, built-up and forest land forms with the absolute accuracy of 8–10 m. The relative accuracies based on the coherence of neighbouring pixels are superior to absolute accuracies both for CSK and TSX.

InSAR deformation monitoring of high risk landslides

Science.gov (United States)

Singhroy, V.; Li, J.

2013-05-01

During the past year there were at least twenty five media reports of landslides and seismic activities some fatal, occurring in various areas in Canada. These high risk geohazards sites requires high resolution monitoring both spatially and temporally for mitigation purposes, since they are near populated areas and energy, transportation and communication corridors. High resolution air photos, lidar and satellite images are quite common in areas where the landslides can be fatal. Radar interferometry (InSAR) techniques using images from several radar satellites are increasingly being used in slope stability assessment. This presentation provides examples of using high-resolution (1-3m) frequent revisits InSAR techniques from RADARSAT 2 and TerraSAR X to monitor several types of high-risk landslides affecting transportation and energy corridors and populated areas. We have analyses over 200 high resolution InSAR images over a three year period on geologically different landslides. The high-resolution InSAR images are effective in characterizing differential motion within these low velocity landslides. The low velocity landslides become high risk during the active wet spring periods. The wet soils are poor coherent targets and corner reflectors provide an effective means of InSAR monitoring the slope activities.

Dopamine D2 receptor expression in the corticotroph cells of the human normal pituitary gland.

Science.gov (United States)

Pivonello, Rosario; Waaijers, Marlijn; Kros, Johan M; Pivonello, Claudia; de Angelis, Cristina; Cozzolino, Alessia; Colao, Annamaria; Lamberts, Steven W J; Hofland, Leo J

2017-08-01

The dopamine D 2 receptor is the main dopamine receptor expressed in the human normal pituitary gland. The aim of the current study was to evaluate dopamine D 2 receptor expression in the corticotroph cell populations of the anterior lobe and pars intermedia, as well as posterior lobe of the human normal pituitary gland by immunohistochemistry. Human normal pituitary gland samples obtained from routine autopsies were used for the study. In all cases, histology together with immunostaining for adrenocorticotropic hormone, melanocyte-stimulating hormone, prolactin, and neurofilaments were performed and compared to the immunostaining for D 2 receptor. D 2 receptor was heterogeneously expressed in the majority of the cell populations of the anterior and posterior lobe as well as in the area localized between the anterior and posterior lobe, and arbitrary defined as "intermediate zone". This zone, characterized by the presence of nerve fibers included the residual pars intermedia represented by the colloid-filled cysts lined by the remnant melanotroph cells strongly expressing D 2 receptors, and clusters of corticotroph cells, belonging to the anterior lobe but localized within the cysts and adjacent to the posterior lobe, variably expressing D 2 receptors. D 2 dopamine receptor is expressed in the majority of the cell populations of the human normal pituitary gland, and particularly, in the different corticotroph cell populations localized in the anterior lobe and the intermediate zone of the pituitary gland.

Human neural progenitors express functional lysophospholipid receptors that regulate cell growth and morphology

Directory of Open Access Journals (Sweden)

Callihan Phillip

2008-12-01

Full Text Available Abstract Background Lysophospholipids regulate the morphology and growth of neurons, neural cell lines, and neural progenitors. A stable human neural progenitor cell line is not currently available in which to study the role of lysophospholipids in human neural development. We recently established a stable, adherent human embryonic stem cell-derived neuroepithelial (hES-NEP cell line which recapitulates morphological and phenotypic features of neural progenitor cells isolated from fetal tissue. The goal of this study was to determine if hES-NEP cells express functional lysophospholipid receptors, and if activation of these receptors mediates cellular responses critical for neural development. Results Our results demonstrate that Lysophosphatidic Acid (LPA and Sphingosine-1-phosphate (S1P receptors are functionally expressed in hES-NEP cells and are coupled to multiple cellular signaling pathways. We have shown that transcript levels for S1P1 receptor increased significantly in the transition from embryonic stem cell to hES-NEP. hES-NEP cells express LPA and S1P receptors coupled to Gi/o G-proteins that inhibit adenylyl cyclase and to Gq-like phospholipase C activity. LPA and S1P also induce p44/42 ERK MAP kinase phosphorylation in these cells and stimulate cell proliferation via Gi/o coupled receptors in an Epidermal Growth Factor Receptor (EGFR- and ERK-dependent pathway. In contrast, LPA and S1P stimulate transient cell rounding and aggregation that is independent of EGFR and ERK, but dependent on the Rho effector p160 ROCK. Conclusion Thus, lysophospholipids regulate neural progenitor growth and morphology through distinct mechanisms. These findings establish human ES cell-derived NEP cells as a model system for studying the role of lysophospholipids in neural progenitors.

Indigenous and Medicinal Uses of Plants in Nech Sar National Park, Ethiopia.

OpenAIRE

Alemu, M.; Bhattacharyya, Subhes; Reeves, Andrew; Lemon, Mark

2017-01-01

Open Access Journal For many years humans have used different parts of plants for medicinal purposes, as source of food and feed. Hence the benefits of indigenous knowledge for the development of present day sophisticated medicinal inventions cannot be overlooked. Indigenous people living in and around protected areas are still making use of plants to cure human and animal related diseases. Guji, Kore and Gamo people of Nech Sar National Park are not indifferent to this fact. Primary data ...

Spacial Variation in SAR Images of Different Resolution for Agricultural Fields

DEFF Research Database (Denmark)

Sandholt, Inge; Skriver, Henning

1999-01-01

The spatial variation in two types of Synthetic Aperture Radar (SAR) images covering agricultural fields is analysed. C-band polarimetric SAR data from the Danish airborne SAR, EMISAR, have been compared to space based ERS-1 C-band SAR with respect to scale and effect of polarization. The general...

hPEPT1 Affinity and Translocation of Selected Gln-Sar and Glu-Sar Dipeptide Derivatives

DEFF Research Database (Denmark)

Eriksson, A. H.; Elm, Peter L.; Begtrup, Mikael

2005-01-01

using 14C-labeled Gly-Sar. Translocation was measured as fluorescence ratios induced by the substrates using the fluorescent probe BCECF and an epifluorescence microscope setup. All compounds showed high affinity to hPEPT1, but only the amides l-Gln(N,N-dimethyl)-Sar and l-Gln(N-piperidinyl)-Sar were...... been suggested. However, these are not necessarily predictive of compounds that are actually translocated by hPEPT1. More information on affinity to and translocation via hPEPT1 of side-chain-modified dipeptides may be gained by conducting a study of selected dipeptide derivatives with variety in size...... translocated by hPEPT1. hPEPT1 is very susceptible to modifications of the N-terminal amino acid side chain of dipeptidomimetic substrates, in terms of achieving compounds with high affinity for the transporter. However, as affinity is not predictive of translocation, derivatization in this position must...

Flood extent and water level estimation from SAR using data-model integration

Science.gov (United States)

Ajadi, O. A.; Meyer, F. J.

2017-12-01

Synthetic Aperture Radar (SAR) images have long been recognized as a valuable data source for flood mapping. Compared to other sources, SAR's weather and illumination independence and large area coverage at high spatial resolution supports reliable, frequent, and detailed observations of developing flood events. Accordingly, SAR has the potential to greatly aid in the near real-time monitoring of natural hazards, such as flood detection, if combined with automated image processing. This research works towards increasing the reliability and temporal sampling of SAR-derived flood hazard information by integrating information from multiple SAR sensors and SAR modalities (images and Interferometric SAR (InSAR) coherence) and by combining SAR-derived change detection information with hydrologic and hydraulic flood forecast models. First, the combination of multi-temporal SAR intensity images and coherence information for generating flood extent maps is introduced. The application of least-squares estimation integrates flood information from multiple SAR sensors, thus increasing the temporal sampling. SAR-based flood extent information will be combined with a Digital Elevation Model (DEM) to reduce false alarms and to estimate water depth and flood volume. The SAR-based flood extent map is assimilated into the Hydrologic Engineering Center River Analysis System (Hec-RAS) model to aid in hydraulic model calibration. The developed technology is improving the accuracy of flood information by exploiting information from data and models. It also provides enhanced flood information to decision-makers supporting the response to flood extent and improving emergency relief efforts.

Characterization of solubilized human and rat brain US -endorphin-receptor complex

Energy Technology Data Exchange (ETDEWEB)

Helmeste, D.M.; Li, C.H.

1986-01-01

Opioid receptors have been solubilized from human striatal and rat whole-brain membranes by use of 3-((3-cholamidopropyl)dimethylammonio)-1-propanesulfonate (CHAPS). Tritiated human US -endorphin (TH-US /sub h/-EP) binding revealed high-affinity competition by morphine, naloxone, and various US -EP analogues. Lack of high-affinity competition by (+/-)-3,4-dichloro-N-methyl-N-(2-(1-pyrrolidinyl)cyclohexyl)benzeneacetamide methanesulfonate (U50-488, Upjohn) indicated that k sites were not labeled by TH-US -/sub h/-EP under these conditions. Affinities were similar in both soluble and membrane preparations except for (Met)enkephalin, which appears to be rapidly degraded by the solubilized extract. Size differences between human and rat solubilized TH-US /sub h/-EP-receptor complexes were revealed by exclusion chromatography.

The experience of SARS-related stigma at Amoy Gardens.

Science.gov (United States)

Lee, Sing; Chan, Lydia Y Y; Chau, Annie M Y; Kwok, Kathleen P S; Kleinman, Arthur

2005-11-01

Severe Acute Respiratory Syndrome (SARS) possesses characteristics that render it particularly prone to stigmatization. SARS-related stigma, despite its salience for public health and stigma research, has had little examination. This study combines survey and case study methods to examine subjective stigma among residents of Amoy Gardens (AG), the first officially recognized site of community outbreak of SARS in Hong Kong. A total of 903 residents of AG completed a self-report questionnaire derived from two focus groups conducted toward the end of the 3-month outbreak. Case studies of two residents who lived in Block E, the heart of the SARS epidemic at AG, complement the survey data. Findings show that stigma affected most residents and took various forms of being shunned, insulted, marginalized, and rejected in the domains of work, interpersonal relationships, use of services and schooling. Stigma was also associated with psychosomatic distress. Residents' strategies for diminishing stigma varied with gender, age, education, occupation, and proximity to perceived risk factors for SARS such as residential location, previous SARS infection and the presence of ex-SARS household members. Residents attributed stigma to government mismanagement, contagiousness of the mysterious SARS virus, and alarmist media reporting. Stigma clearly decreased, but never completely disappeared, after the outbreak. The findings confirm and add to existing knowledge on the varied origins, correlates, and impacts of stigma. They also highlight the synergistic roles of inconsistent health policy responses and risk miscommunication by the media in rapidly amplifying stigma toward an unfamiliar illness. While recognizing the intrinsically stigmatizing nature of public health measures to control SARS, we recommend that a consistent inter-sectoral approach is needed to minimize stigma and to make an effective health response to future outbreaks.

Estimating Elevation Angles From SAR Crosstalk

Science.gov (United States)

Freeman, Anthony

1994-01-01

Scheme for processing polarimetric synthetic-aperture-radar (SAR) image data yields estimates of elevation angles along radar beam to target resolution cells. By use of estimated elevation angles, measured distances along radar beam to targets (slant ranges), and measured altitude of aircraft carrying SAR equipment, one can estimate height of target terrain in each resolution cell. Monopulselike scheme yields low-resolution topographical data.

EGF-induced stimualtion of EGF-receptor synthesis in human cytotrophoblasts and A431 cells

International Nuclear Information System (INIS)

DePalo, L.; Basu, A.; Das, M.

1987-01-01

EGF-receptor is a transmembrane glycoprotein whose intracellular degradation is known to be enhanced by EGF. The authors tested whether the receptor is replenished during this process by an enhanced rate of synthesis. Human A431 epidermoid carcinoma cells, and primary cultures of human placental cytotrophoblasts were used in these studies. Cells were labeled with 35 S-methionine, and EGF-receptor biosynthesis was quantitated by immunoprecipitation using a monoclonal anti-EGF-receptor antibody. EGF stimulated receptor biosynthesis at concentrations of 0.1-1 nM. The effect was seen within 2 h of EGF addition. The maximal stimulatory effect was modest in A431 (∼ 2-fold), but marked in the cytotrophoblasts (>5-fold). At EGF concentrations higher than 3 nM, the stimulatory effect was abolished. In contrast, the effect of EGF on receptor degradation is negligible at low subnanomolar concentrations, and is pronounced only at saturating concentrations. These results show that occupation of the cell surface EGF-receptor by its ligand can lead to production of more receptor protein, thus counterbalancing the negative effect on receptor degradation. At low subnanomolar (mitogenic) concentrations of EGF the stimulator effect on receptor synthesis is likely to predominate over the effect on receptor degradation

SAR Study of Mobile Phones as a function of Antenna Q

DEFF Research Database (Denmark)

Bahramzy, Pevand; Svendsen, Simon; Jagielski, Ole

2015-01-01

density associated with high-Q antennas. The higher energy stored in the electric and magnetic near-field components can result in higher SAR. Hence, SAR study of high-Q antennas is necessary which, if not addressed, might not comply with the SAR safety guidelines. In this paper, SAR as a function...

Erythropoietin Receptor in Human Tumor Cells: Expression and Aspects Regarding Functionality

NARCIS (Netherlands)

T.A. Knoch (Tobias); G. Westphal; E. Niederberger; C. Blum; Y. Wollman; W. Rebel; J. Debus; E. Friedrich

2001-01-01

textabstractRecombinant human erythropoietin (Epo)and granu l o cy t e - c o l o ny - s t i mulating factor (G-CSF) are used to stimulate hematopoiesis in patients with malignant dise a s e s . These cytokines transduce their biological signal via the Epo receptor (EpoR) and G-CSF receptor (G-CSF-R)

Muscarinic receptor subtypes in porcine detrusor: comparison with humans and regulation by bladder augmentation

NARCIS (Netherlands)

Goepel, M.; Gronewald, A.; Krege, S.; Michel, M. C.

1998-01-01

The properties of muscarinic acetylcholine receptors of porcine and human bladder detrusor were compared in radioligand binding studies using [3H]quinuclidinylbenzylate as the radioligand. The receptor affinity for the radioligand and the density of muscarinic receptors was similar in male and

Roadmap to developing a recombinant coronavirus S protein receptor-binding domain vaccine for severe acute respiratory syndrome

Science.gov (United States)

Jiang, Shibo; Bottazzi, Maria Elena; Du, Lanying; Lustigman, Sara; Tseng, Chien-Te Kent; Curti, Elena; Jones, Kathryn; Zhan, Bin; Hotez, Peter J

2013-01-01

A subunit vaccine, RBD-S, is under development to prevent severe acute respiratory syndrome (SARS) caused by SARS coronavirus (SARS-CoV), which is classified by the US NIH as a category C pathogen. This vaccine is comprised of a recombinant receptor-binding domain (RBD) of the SARS-CoV spike (S) protein and formulated on alum, together with a synthetic glucopyranosyl lipid A. The vaccine would induce neutralizing antibodies without causing Th2-type immunopathology. Vaccine development is being led by the nonprofit product development partnership; Sabin Vaccine Institute and Texas Children’s Hospital Center for Vaccine Development in collaboration with two academic partners (the New York Blood Center and University of Texas Medical Branch); an industrial partner (Immune Design Corporation); and Walter Reed Army Institute of Research. A roadmap for the product development of the RBD-S SARS vaccine is outlined with a goal to manufacture the vaccine for clinical testing within the next 5 years. PMID:23252385

Crystallization and preliminary X-ray diffraction analysis of Nsp15 from SARS coronavirus

International Nuclear Information System (INIS)

Ricagno, Stéfano; Coutard, Bruno; Grisel, Sacha; Brémond, Nicolas; Dalle, Karen; Tocque, Fabienne; Campanacci, Valérie; Lichière, Julie; Lantez, Violaine; Debarnot, Claire; Cambillau, Christian; Canard, Bruno; Egloff, Marie-Pierre

2006-01-01

Crystals of Nsp15 from the aetiological agent of SARS have been grown at room temperature. Crystals have cubic symmetry and diffract to a maximum resolution of 2.7 Å. The non-structural protein Nsp15 from the aetiological agent of SARS (severe acute respiratory syndrome) has recently been characterized as a uridine-specific endoribonuclease. This enzyme plays an essential role in viral replication and transcription since a mutation in the related H229E human coronavirus nsp15 gene can abolish viral RNA synthesis. SARS full-length Nsp15 (346 amino acids) has been cloned and expressed in Escherichia coli with an N-terminal hexahistidine tag and has been purified to homogeneity. The protein was subsequently crystallized using PEG 8000 or 10 000 as precipitants. Small cubic crystals of the apoenzyme were obtained from 100 nl nanodrops. They belong to space group P4 1 32 or P4 3 32, with unit-cell parameters a = b = c = 166.8 Å. Diffraction data were collected to a maximum resolution of 2.7 Å

Crystallization and preliminary X-ray diffraction analysis of Nsp15 from SARS coronavirus

Energy Technology Data Exchange (ETDEWEB)

Ricagno, Stéfano; Coutard, Bruno; Grisel, Sacha; Brémond, Nicolas; Dalle, Karen; Tocque, Fabienne; Campanacci, Valérie; Lichière, Julie; Lantez, Violaine; Debarnot, Claire; Cambillau, Christian; Canard, Bruno; Egloff, Marie-Pierre, E-mail: marie-pierre.egloff@afmb.univ-mrs.fr [Centre National de la Recherche Scientifique and Universités d’Aix-Marseille I et II, UMR 6098, Architecture et Fonction des Macromolécules Biologiques, Ecole Supérieure d’Ingénieurs de Luminy-Case 925, 163 Avenue de Luminy, 13288 Marseille CEDEX 9 (France)

2006-04-01

Crystals of Nsp15 from the aetiological agent of SARS have been grown at room temperature. Crystals have cubic symmetry and diffract to a maximum resolution of 2.7 Å. The non-structural protein Nsp15 from the aetiological agent of SARS (severe acute respiratory syndrome) has recently been characterized as a uridine-specific endoribonuclease. This enzyme plays an essential role in viral replication and transcription since a mutation in the related H229E human coronavirus nsp15 gene can abolish viral RNA synthesis. SARS full-length Nsp15 (346 amino acids) has been cloned and expressed in Escherichia coli with an N-terminal hexahistidine tag and has been purified to homogeneity. The protein was subsequently crystallized using PEG 8000 or 10 000 as precipitants. Small cubic crystals of the apoenzyme were obtained from 100 nl nanodrops. They belong to space group P4{sub 1}32 or P4{sub 3}32, with unit-cell parameters a = b = c = 166.8 Å. Diffraction data were collected to a maximum resolution of 2.7 Å.

High-Level Performance Modeling of SAR Systems

Science.gov (United States)

Chen, Curtis

2006-01-01

SAUSAGE (Still Another Utility for SAR Analysis that s General and Extensible) is a computer program for modeling (see figure) the performance of synthetic- aperture radar (SAR) or interferometric synthetic-aperture radar (InSAR or IFSAR) systems. The user is assumed to be familiar with the basic principles of SAR imaging and interferometry. Given design parameters (e.g., altitude, power, and bandwidth) that characterize a radar system, the software predicts various performance metrics (e.g., signal-to-noise ratio and resolution). SAUSAGE is intended to be a general software tool for quick, high-level evaluation of radar designs; it is not meant to capture all the subtleties, nuances, and particulars of specific systems. SAUSAGE was written to facilitate the exploration of engineering tradeoffs within the multidimensional space of design parameters. Typically, this space is examined through an iterative process of adjusting the values of the design parameters and examining the effects of the adjustments on the overall performance of the system at each iteration. The software is designed to be modular and extensible to enable consideration of a variety of operating modes and antenna beam patterns, including, for example, strip-map and spotlight SAR acquisitions, polarimetry, burst modes, and squinted geometries.

César Vallejo and the Stones of Darwinian Risk

Directory of Open Access Journals (Sweden)

Christiane von Buelow

1990-01-01

Full Text Available César Vallejo's short story, "Los caynas" (1923, relates a tale of species mutation, of men who become apes. The story, however, is something more than the reflection of the positivist interpretation of Darwinian theory. It can be read as a critique of Positivism's pseudo-scientific ideals or as a version of the Oedipal drama in which the son encounters and rejects his ape father. The ambivalence raises the question of whether Vallejo's Darwinism is to be read literally or ironically as well, as marking an antinomy present throughout his writing between the human subject's immersion in the species and the possibility of a collective human-transformation.