Identification of a Highly Conserved H1 Subtype-Specific Epitope with Diagnostic Potential in the Hemagglutinin Protein of Influenza A Virus

Subtype specificity of influenza A virus (IAV) is determined by its two surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA). For HA, 16 distinct subtypes (H1–H16) exist, while nine exist for NA. The epidemic strains of H1N1 IAV change frequently and cause annual seasonal epidemics as well as occasional pandemics, such as the notorious 1918 influenza pandemic. The recent introduction of pandemic A/H1N1 IAV (H1N1pdm virus) into humans re-emphasizes the public health concern about H1N1 IAV. Several studies have identified conserved epitopes within specific HA subtypes that can be used for diagnostics. However, immune specific epitopes in H1N1 IAV have not been completely assessed. In this study, linear epitopes on the H1N1pdm viral HA protein were identified by peptide scanning using libraries of overlapping peptides against convalescent sera from H1N1pdm patients. One epitope, P5 (aa 58–72) was found to be immunodominant in patients and to evoke high titer antibodies in mice. Multiple sequence alignments and in silico coverage analysis showed that this epitope is highly conserved in influenza H1 HA [with a coverage of 91.6% (9,860/10,767)] and almost completely absent in other subtypes [with a coverage of 3.3% (792/23,895)]. This previously unidentified linear epitope is located outside the five well-recognized antigenic sites in HA. A peptide ELISA method based on this epitope was developed and showed high correlation (χ2 = 51.81, P<0.01, Pearson correlation coefficient R = 0.741) with a hemagglutination inhibition test. The highly conserved H1 subtype-specific immunodominant epitope may form the basis for developing novel assays for sero-diagnosis and active surveillance against H1N1 IAVs

Identification of a Highly Conserved H1 Subtype-Specific Epitope with Diagnostic Potential in the Hemagglutinin Protein of Influenza A Virus

Subtype specificity of influenza A virus (IAV) is determined by its two surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA). For HA, 16 distinct subtypes (H1–H16) exist, while nine exist for NA. The epidemic strains of H1N1 IAV change frequently and cause annual seasonal epidemics as well as occasional pandemics, such as the notorious 1918 influenza pandemic. The recent introduction of pandemic A/H1N1 IAV (H1N1pdm virus) into humans re-emphasizes the public health concern about H1N1 IAV. Several studies have identified conserved epitopes within specific HA subtypes that can be used for diagnostics. However, immune specific epitopes in H1N1 IAV have not been completely assessed. In this study, linear epitopes on the H1N1pdm viral HA protein were identified by peptide scanning using libraries of overlapping peptides against convalescent sera from H1N1pdm patients. One epitope, P5 (aa 58–72) was found to be immunodominant in patients and to evoke high titer antibodies in mice. Multiple sequence alignments and in silico coverage analysis showed that this epitope is highly conserved in influenza H1 HA [with a coverage of 91.6% (9,860/10,767)] and almost completely absent in other subtypes [with a coverage of 3.3% (792/23,895)]. This previously unidentified linear epitope is located outside the five well-recognized antigenic sites in HA. A peptide ELISA method based on this epitope was developed and showed high correlation (χ2 = 51.81, P<0.01, Pearson correlation coefficient R = 0.741) with a hemagglutination inhibition test. The highly conserved H1 subtype-specific immunodominant epitope may form the basis for developing novel assays for sero-diagnosis and active surveillance against H1N1 IAVs

Data-driven calibration for cup anemometer at different measurement locations around buildings using transfer learning based on domain adaptation

In recent years, high-precision sensors, e.g., ultrasonic anemometers, have been widely used for wind measurement. However, conventional sensors, e.g., cup anemometers, are yet to be replaced owing to their low-cost advantages and high robustness in an uncertain environment. Considering that data-driven calibration methods are used to improve the measurement accuracy of cup anemometers, this study proposed a transfer learning method based on domain adaptation, so that existing measurement data can be used for model training in new measurement scenarios, thus reducing the cost of secondary data collection. In summary, at the corner and side of a building in a new measurement site considered for experiments, the results of the proposed method indicated that the relative errors of pulsation parameters, e.g., the standard deviation wind speed, turbulence intensity, and gust factor, more significantly reduced compared to the conventional machine learning method

Control of Respiratory Motion by Hypnosis Intervention during Radiotherapy of Lung Cancer I

The uncertain position of lung tumor during radiotherapy compromises the treatment effect. To effectively control respiratory motion during radiotherapy of lung cancer without any side effects, a novel control scheme, hypnosis, has been introduced in lung cancer treatment. In order to verify the suggested method, six volunteers were selected with a wide range of distribution of age, weight, and chest circumference. A set of experiments have been conducted for each volunteer, under the guidance of the professional hypnotist. All the experiments were repeated in the same environmental condition. The amplitude of respiration has been recorded under the normal state and hypnosis, respectively. Experimental results show that the respiration motion of volunteers in hypnosis has smaller and more stable amplitudes than in normal state. That implies that the hypnosis intervention can be an alternative way for respiratory control, which can effectively reduce the respiratory amplitude and increase the stability of respiratory cycle. The proposed method will find useful application in image-guided radiotherapy

Polysaccharides, Saponins, and Water Decoction of Astragalus membranaceus Significantly Enhance the Non-Specific Immune Response of Spotted Maigre (Nibea albiflora)

The effects of polysaccharides, saponins, and water decoction of the Chinese herb Astragalus membranaceus on the immune response of spotted maigre (Nibea albiflora) were investigated. Fish with an average initial weight of 49.6±5.5 g were fed a diet containing 2% extract for four weeks. The lysozyme and phagocytic activities of the fish were determined and compared with those of control fish fed an unsupplemented feed on days 0, 3, 7, 14, 21, and 28. Both activities were significantly higher in groups fed the Astragalus extract than in the control group (p0.05). Most important, the Astragalus-fed groups were significantly protected against Vibrio vulnificus challenge compared to the control group (p<0.01). Our results indicatd that polysaccharides and saponins are main active components of Astragalus extracts and can enhance the non-specific immune response in spotted maigre

Terminal Repeats in Collagen Triple-Helices

Nearly 30% of human proteins have tandem repeating sequences. Structural understanding of the terminal repeats is well-established for many repeat proteins with the common α-helix and β-sheet foldings. By contrast, the sequence-structure interplay of the terminal repeats of the collagen triple-helix remains unexplored to date. As the most abundant human repeat protein and the most prevalent structural component of the extracellular matrix, collagen features a hallmark triple-helix formed by three supercoiled polypeptide chains of long repeating sequences of the Gly-X-Y triplets. Here, with CD characterization of 28 collagen-mimetic peptides (CMPs) featuring various terminal motifs, as well as DSC measurements, crystal structure analysis, and computational simulations, we show that CMPs only differing in terminal repeat may have distinct end structures and stabilities. We reveal that the cross-chain hydrogen bonding mediated by the terminal repeat is key to maintaining the triple-helix’s end structure, and that disruption of it with a single amide to carboxylate substitution can lead to destabilization as drastic as 19 °C. We further demonstrate that the terminal repeat also impacts how strong the CMP strands form hybrid triple-helices with unfolded natural collagen chains in tissue. Our findings provide a fresh spatial profile of hydrogen bonding within the CMP triple-helix, marking a critical guideline for future crystallographic or NMR studies of collagen, and algorithms for predicting triple-helix stability, as well as peptide-based collagen assemblies and materials. This study will also inspire new understandings of the sequence-structure relationship of many other complex structural proteins with repeating sequences

Strongly leakage resilient authenticated key exchange, revisited

Authenticated Key Exchange (AKE) protocols allow two (or multiple) parties to authenticate each other and agree on a common secret key, which is essential for establishing a secure communication channel over a public network. AKE protocols form a central component in many network security standards such as IPSec, TLS/SSL, and SSH. However, it has been demonstrated that many standardized AKE protocols are vulnerable to side-channel and key leakage attacks. In order to defend against such attacks, leakage resilient (LR-) AKE protocols have been proposed in the literature. Nevertheless, most of the existing LR-AKE protocols only focused on the resistance to long-term key leakage, while in reality leakage of ephemeral secret key (or randomness) can also occur due to various reasons such as the use of poor randomness sources or insecure pseudo-random number generators (PRNGs). In this paper, we revisit the strongly leakage resilient AKE protocol (CT-RSA’16) that aimed to resist challenge-dependent leakage on both long-term and ephemeral secret keys. We show that there is a security issue in the design of the protocol and propose an improved version that can fix the problem. In addition, we extend the protocol to a more general framework that can be efficiently instantiated under various assumptions, including hybrid instantiations that can resist key leakage attacks while preserving session key security against future quantum machines