Direct Signal Separation Via Extraction of Local Frequencies with Adaptive Time-Varying Parameters

In nature, real-world phenomena that can be formulated as signals (or in terms of time series) are often affected by a number of factors and appear as multi-component modes. The natural approach to understand and process such phenomena is to decompose, or even better, to separate the multi-component signals to their basic building blocks (called sub-signals or time-series components, or fundamental modes). Recently the synchro-squeezing transform (SST) and its variants have been developed for nonstationary signal separation. More recently, a direct method of the time-frequency approach, called signal separation operation (SSO), was introduced for multi-component signal separation. While both SST and SSO are mathematically rigorous on the instantaneous frequency (IF) estimation, SSO avoids the second step of the two-step SST method in signal separation, which depends heavily on the accuracy of the estimated IFs. In the present paper, we solve the signal separation problem by constructing an adaptive signal separation operator (ASSO) for more effective separation of the blind-source multi-component signal, via introducing a time-varying parameter that adapts to local IFs. A recovery scheme is also proposed to extract the signal components one by one, and the time-varying parameter is updated for each component. The proposed method is suitable for engineering implementation, being capable of separating complicated signals into their sub-signals and reconstructing the signal trend directly. Numerical experiments on synthetic and real-world signals are presented to demonstrate our improvement over the previous attempts

Mutations in hepatitis C virus E2 located outside the CD81 binding sites lead to escape from broadly neutralizing antibodies but compromise virus infectivity.

Broadly neutralizing antibodies are commonly present in the sera of patients with chronic hepatitis C virus (HCV) infection. To elucidate possible mechanisms of virus escape from these antibodies, retrovirus particles pseudotyped with HCV glycoproteins (HCVpp) isolated from sequential samples collected over a 26-year period from a chronically infected patient, H, were used to characterize the neutralization potential and binding affinity of a panel of anti-HCV E2 human monoclonal antibodies (HMAbs). Moreover, AP33, a neutralizing murine monoclonal antibody (MAb) to a linear epitope in E2, was also tested against selected variants. The HMAbs used were previously shown to broadly neutralize HCV and to recognize a cluster of highly immunogenic overlapping epitopes, designated domain B, containing residues that are also critical for binding of viral E2 glycoprotein to CD81, a receptor essential for virus entry. Escape variants were observed at different time points with some of the HMAbs. Other HMAbs neutralized all variants except for the isolate 02.E10, obtained in 2002, which was also resistant to MAb AP33. The 02.E10 HCVpp that have reduced binding affinities for all antibodies and for CD81 also showed reduced infectivity. Comparison of the 02.E10 nucleotide sequence with that of the strain H-derived consensus variant, H77c, revealed the former to have two mutations in E2, S501N and V506A, located outside the known CD81 binding sites. Substitution A506V in 02.E10 HCVpp restored binding to CD81, but its antibody neutralization sensitivity was only partially restored. Double substitutions comprising N501S and A506V synergistically restored 02.E10 HCVpp infectivity. Other mutations that are not part of the antibody binding epitope in the context of N501S and A506V were able to completely restore neutralization sensitivity. These findings showed that some nonlinear overlapping epitopes are more essential than others for viral fitness and consequently are more invariant during earlier years of chronic infection. Further, the ability of the 02.E10 consensus variant to escape neutralization by the tested antibodies could be a new mechanism of virus escape from immune containment. Mutations that are outside receptor binding sites resulted in structural changes leading to complete escape from domain B neutralizing antibodies, while simultaneously compromising viral fitness by reducing binding to CD81

A General Framework of Multivariate Wavelets with Duals

AbstractA comprehensive development of multivariate wavelets along with their duals is presented in this paper. The basic ingredients, such as duality relations, reconstruction and decomposition formulas, and the notion of infinite direct sums, are formulated and established in the general nonorthogonal and multivariate setting. Special emphases include duality criteria and stability conditions. As an application, new results are contributed, particularly in dual wavelets, to the existing literature on low-dimensional wavelets. In addition, the special case when the dilation matrix has determinant 2 is studied in some detail

Benchmarking of 3D space charge codes using direct phase space measurements from photoemission high voltage DC gun

We present a comparison between space charge calculations and direct measurements of the transverse phase space for space charge dominated electron bunches after a high voltage photoemission DC gun followed by an emittance compensation solenoid magnet. The measurements were performed using a double-slit setup for a set of parameters such as charge per bunch and the solenoid current. The data is compared with detailed simulations using 3D space charge codes GPT and Parmela3D with initial particle distributions created from the measured transverse and temporal laser profiles. Beam brightness as a function of beam fraction is calculated for the measured phase space maps and found to approach the theoretical maximum set by the thermal energy and accelerating field at the photocathode.Comment: 11 pages, 23 figures. submitted to Phys Rev ST-A

A synthetic human Agouti-related protein-(83–132)-NH2 fragment is a potent inhibitor of melanocortin receptor function

AbstractChemical synthesis of Agouti proteins – Agouti and Agouti-related proteins – is complicated by their large size and by multiple cysteine residues located in the carboxyl terminal regions. Three human Agouti-related protein (AGRP) fragments, two of which correspond to a proposed endoprotease cleavage site between amino acids 82 and 83, were synthesized and tested for anti-melanotropic activity using Xenopus laevis dermal melanophores. Amino-terminal fragments AGRP(25–51) and (54–82) were devoid of significant antagonist activity, whereas the amidated carboxyl-terminal AGRP fragment (83–132)-NH2 was potently active with an inhibitory equilibrium dissociation constant (Ki) of 0.7 nM. The ability to synthesize functionally active AGRP should help unravel its role in the central nervous system and its unusual properties with respect to interaction with the melanocortin family of G-protein coupled receptors