Synthetic studies on indolic enamide natural products: 1. Total syntheses of coscinamide A, concinamide B and igzamide: 2. Synthetic studies towards the synthesis of halocyamine B

The 3-substituded indolic enamide moiety has been found in many marine compounds over the past 20 years. These indolic enamides exhibit various biological properties such as cytotoxic, anthelmintic, antimicrobial and HW-inhibitory activities. Among these indolic enamides, some are (E)-enamides, like coscinamide A and coscinamide B, others are (Z)-configuration in their natural form, like igzamide and halocyamine B. A general method to selectively construct (E)- and (Z)-indolic enamides was devised through an bydroxyl amide formed from amino alcohol followed by a thermally assisted dehydration as the key step. Solvent effects were tested for the dehydration reaction. (Z)-Indolic enamides could be obtained in a moderate yield with xylene as the solvent for the dehydration reaction. (E)-Indolic enamides were the main products with N, N-dimethylformamide as the solvent. Total syntheses of three indolic enamides: coscinamide A, coscinamide B and igzamide have been described. The (E)- or (Z)-isomers of these natural compounds were obtained during the syntheses as well. A synthetic study of halocyamine B is also reported in this thesis

Preparation of (Lu,Y)3(Al,Sc,Cr)2Al3O12 phosphor ceramics with high thermal stability for near-infrared LED/LD

Near-infrared (NIR) phosphor-converted light-emitting diodes/laser diodes (LEDs/LDs) are prospective lighting sources for NIR spectroscopy. However, developing NIR phosphor materials with desired thermal robustness and high photoelectric efficiency is a crucial challenge for their applications. In this work, based on the cationic radius matching effect, a series of (Lu,Y)3(Al,Sc,Cr)2Al3O12 NIR phosphor ceramics (LuYScCr NIR-PCs) were fabricated by vacuum sintering. Excellent thermal stability (95%@150 ℃) was obtained in the prepared NIR-PCs, owing to their weak electron–phonon coupling effect (small Huang–Rhys factor). Being excited at 460 nm, NIR-PCs realized a broadband emission (650–850 nm) with internal quantum efficiency (IQE) of 60.68%. Combining NIR-PCs with LED/LD chips, the maximum output power of the encapsulated LED prototype was 447 mW@300 mA with photoelectric efficiency of as high as 18.6 %@180 mA, and the maximum output power of the LD prototype was 814 [email protected] A. The working temperatures of NIR-PCs were 70.8 ℃@300 mA (LED) and 102.8 ℃@3 A (LD). Finally, the prepared NIR-PCs applied in food detection were verified in this study, demonstrating their anticipated application prospects in the future

Adaption of Seasonal H1N1 Influenza Virus in Mice

The experimental infection of a mouse lung with influenza A virus has proven to be an invaluable model for studying the mechanisms of viral adaptation and virulence. The mouse adaption of human influenza A virus can result in mutations in the HA and other proteins, which is associated with increased virulence in mouse lungs. In this study, a mouse-adapted seasonal H1N1 virus was obtained through serial lung-to-lung passages and had significantly increased virulence and pathogenicity in mice. Genetic analysis indicated that the increased virulence of the mouse-adapted virus was attributed to incremental acquisition of three mutations in the HA protein (T89I, N125T, and D221G). However, the mouse adaption of influenza A virus did not change the specificity and affinity of receptor binding and the pH-dependent membrane fusion of HA, as well as the in vitro replication in MDCK cells. Notably, infection with the mouse adapted virus induced severe lymphopenia and modulated cytokine and chemokine responses in mice. Apparently, mouse adaption of human influenza A virus may change the ability to replicate in mouse lungs, which induces strong immune responses and inflammation in mice. Therefore, our findings may provide new insights into understanding the mechanisms underlying the mouse adaption and pathogenicity of highly virulent influenza viruses

Genomic Polymorphism of the Pandemic A (H1N1) Influenza Viruses Correlates with Viral Replication, Virulence, and Pathogenicity In Vitro and In Vivo

The novel pandemic A (H1N1) virus was first identified in Mexico in April 2009 and quickly spread worldwide. Like all influenzas, the H1N1 strain-specific properties of replication, virulence, and pathogenicity are a result of the particular genomic sequence and concerted expression of multiple genes. Thus, specific mutations may support increased virulence and may be useful as biomarkers of potential threat to human health. We performed comparative genomic analysis of ten strains of the 2009 pandemic A (H1N1) influenza viruses to determine whether genotypes associated with clinical phenotypes, which ranged from mild to severe illness and up to lethal. Virus replication capacity was tested for each strain in vitro using cultured epithelial cells, while virulence and pathogenicity were investigated in vivo using the BALB/c mouse model. The results indicated that A/Sichuan/1/2009 strain had significantly higher replication ability and virulence than the other strains, and five unique non-synonymous mutations were identified in important gene-encoding sequences. These mutations led to amino acid substitutions in HA (L32I), PA (A343T), PB1 (K353R and T566A), and PB2 (T471M), and may be critical molecular determinants for replication, virulence, and pathogenicity. Our results suggested that the replication capacity in vitro and virulence in vivo of the 2009 pandemic A (H1N1) viruses were not associated with the clinical phenotypes. This study offers new insights into the transmission and evolution of the 2009 pandemic A (H1N1) virus

Generation, Characterization and Epitope Mapping of Two Neutralizing and Protective Human Recombinant Antibodies against Influenza A H5N1 Viruses

The development of new therapeutic targets and strategies to control highly pathogenic avian influenza (HPAI) H5N1 virus infection in humans is urgently needed. Broadly cross-neutralizing recombinant human antibodies obtained from the survivors of H5N1 avian influenza provide an important role in immunotherapy for human H5N1 virus infection and definition of the critical epitopes for vaccine development.We have characterized two recombinant baculovirus-expressed human antibodies (rhAbs), AVFluIgG01 and AVFluIgG03, generated by screening a Fab antibody phage library derived from a patient recovered from infection with a highly pathogenic avian influenza A H5N1 clade 2.3 virus. AVFluIgG01 cross-neutralized the most of clade 0, clade 1, and clade 2 viruses tested, in contrast, AVFluIgG03 only neutralized clade 2 viruses. Passive immunization of mice with either AVFluIgG01 or AVFluIgG03 antibody resulted in protection from a lethal H5N1 clade 2.3 virus infection. Furthermore, through epitope mapping, we identify two distinct epitopes on H5 HA molecule recognized by these rhAbs and demonstrate their potential to protect against a lethal H5N1 virus infection in a mouse model.Importantly, localization of the epitopes recognized by these two neutralizing and protective antibodies has provided, for the first time, insight into the human antibody responses to H5N1 viruses which contribute to the H5 immunity in the recovered patient. These results highlight the potential of a rhAbs treatment strategy for human H5N1 virus infection and provide new insight for the development of effective H5N1 pandemic vaccines

Clinical Characteristics of 26 Human Cases of Highly Pathogenic Avian Influenza A (H5N1) Virus Infection in China

BACKGROUND: While human cases of highly pathogenic avian influenza A (H5N1) virus infection continue to increase globally, available clinical data on H5N1 cases are limited. We conducted a retrospective study of 26 confirmed human H5N1 cases identified through surveillance in China from October 2005 through April 2008. METHODOLOGY/PRINCIPAL FINDINGS: Data were collected from hospital medical records of H5N1 cases and analyzed. The median age was 29 years (range 6-62) and 58% were female. Many H5N1 cases reported fever (92%) and cough (58%) at illness onset, and had lower respiratory findings of tachypnea and dyspnea at admission. All cases progressed rapidly to bilateral pneumonia. Clinical complications included acute respiratory distress syndrome (ARDS, 81%), cardiac failure (50%), elevated aminotransaminases (43%), and renal dysfunction (17%). Fatal cases had a lower median nadir platelet count (64.5 x 10(9) cells/L vs 93.0 x 10(9) cells/L, p = 0.02), higher median peak lactic dehydrogenase (LDH) level (1982.5 U/L vs 1230.0 U/L, p = 0.001), higher percentage of ARDS (94% [n = 16] vs 56% [n = 5], p = 0.034) and more frequent cardiac failure (71% [n = 12] vs 11% [n = 1], p = 0.011) than nonfatal cases. A higher proportion of patients who received antiviral drugs survived compared to untreated (67% [8/12] vs 7% [1/14], p = 0.003). CONCLUSIONS/SIGNIFICANCE: The clinical course of Chinese H5N1 cases is characterized by fever and cough initially, with rapid progression to lower respiratory disease. Decreased platelet count, elevated LDH level, ARDS and cardiac failure were associated with fatal outcomes. Clinical management of H5N1 cases should be standardized in China to include early antiviral treatment for suspected H5N1 cases

Cyclic Redundancy Check for Zigbee-Based Meeting Attendance Registration System

The research accomplished in this dissertation is focused on the design of effective solutions to the problem that error codes occur in the ZigBee-based meeting attendance registration system. In this work, several different check algorithms are compared, and the powerful error-detecting Cyclic Redundancy Check (CRC) algorithm is studied. In view of the features of the meeting attendance registration system, we implement the check module of CRC-8. This work also considers the data reliability. We assume use retransmission mechanism to ensure the validity and completeness of transmission data. Finally, the potential technical improvement and future work are presented