Multiple Envelope Research Articles

Series–Parallel-Form Switch-Linear Hybrid Envelope-Tracking Power Supply to Achieve High Efficiency

Envelope tracking (ET) techniques have been used to improve the efficiency of power amplifiers in wireless communication systems. The switch-linear hybrid (SLH) ET power supply, which features both wide tracking bandwidth and high efficiency, has received a great deal of attention. In both series- and parallel-form SLH ET power supply, the power loss of the linear amplifier is relatively high. This paper proposes a series–parallel form for the SLH ET power supply, which includes two switched-mode converters and one linear amplifier, to reduce both the output voltage swing and output current of the linear amplifier, thus reducing the power loss of the linear amplifier. A current prediction control scheme is proposed to remove the current sensor in the switched-mode converter, achieving accurate control for high-frequency current. A prototype is built for 5 MHz wideband code division multiple access envelope signal tracking and 40 W peak output power. The tested efficiency of the proposed configuration is 80.4%, which is much higher than that of the series-form SLH ET power supply.

Improvement in measurements of hydroxyapatite layers by hybrid high dynamic range image processing in white-light interferometry

Hydroxyapatite (HA) is one of the most common natural biomaterials widely used in medical applications. Full-field optical coherence tomography can be used to characterise the internal structures of this material by detection of multiple fringe envelope signals. However, the semi-translucent nature of HA and complex spongy aspect is a challenge. We propose here the “IMPROVE-Protocol”, combining a hybrid high dynamic range technique, image averaging and dark and flat corrections to study HA. The resulting increase in the SNR and improvement in the power of detection of the system allows normally unmeasured features to be observed, down to sub-µm in size.

Genomic Instability Is Induced by Persistent Proliferation of Cells Undergoing Epithelial-to-Mesenchymal Transition

TGF-β secreted by tumor stroma induces epithelial-to-mesenchymal transition (EMT) in cancer cells, a reversible phenotype linked to cancer progression and drug resistance. However, exposure to stromal signals may also lead to heritable changes in cancer cells, which are poorly understood. We show that epithelial cells failing to undergo proliferation arrest during TGF-β-induced EMT sustain mitotic abnormalities due to failed cytokinesis, resulting in aneuploidy. This genomic instability is associated with the suppression of multiple nuclear envelope proteins implicated in mitotic regulation and is phenocopied by modulating the expression of LaminB1. While TGF-β-induced mitotic defects in proliferating cells are reversible upon its withdrawal, the acquired genomic abnormalities persist, leading to increased tumorigenic phenotypes. In metastatic breast cancer patients, increased mesenchymal marker expression within single circulating tumor cells is correlated with genomic instability. These observations identify a mechanism whereby microenvironment-derived signals trigger heritable genetic changes within cancer cells, contributing to tumor evolution.

Short Communication: Small-Molecule CD4 Mimetics Sensitize HIV-1-Infected Cells to Antibody-Dependent Cellular Cytotoxicity by Antibodies Elicited by Multiple Envelope Glycoprotein Immunogens in Nonhuman Primates.

Recent studies have linked antibody Fc-mediated effector functions with control of human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus infections. Interestingly, the presence of antibodies with potent antibody-dependent cellular cytotoxicity (ADCC) activity in RV144 vaccine trial participants correlated inversely with HIV-1 acquisition risk. These antibodies were recently found to recognize epitopes on the HIV-1 envelope (Env) glycoprotein exposed upon Env-CD4 binding. Accordingly, small-molecule CD4 mimetics (CD4mc) that induce Env to sample the CD4-bound conformation were shown to sensitize HIV-1-infected cells to ADCC mediated by sera from HIV-1-infected individuals. However, it remains unknown whether antibodies elicited through immunization can also mediate CD4mc-induced ADCC. In this study, we tested the capacity of CD4mc to sensitize HIV-1-infected cells to ADCC by sera from Env-vaccinated nonhuman primates using a FACS-based ADCC assay. In parallel, we evaluated the ability of CD4mc to sensitize HIV-1 viral particles to neutralization by sera from these immunized animals. We found that the vaccine-induced antibodies were able to mediate ADCC and viral neutralization in the presence, but not the absence, of CD4mc. Thus, CD4mc are capable of sensitizing HIV-1-infected cells to ADCC and infectious viral particles to neutralization by easy-to-elicit antibodies that are otherwise unable to mediate these activities.

KSHV Entry and Trafficking in Target Cells-Hijacking of Cell Signal Pathways, Actin and Membrane Dynamics.

Kaposi’s sarcoma associated herpesvirus (KSHV) is etiologically associated with human endothelial cell hyperplastic Kaposi’s sarcoma and B-cell primary effusion lymphoma. KSHV infection of adherent endothelial and fibroblast cells are used as in vitro models for infection and KSHV enters these cells by host membrane bleb and actin mediated macropinocytosis or clathrin endocytosis pathways, respectively. Infection in endothelial and fibroblast cells is initiated by the interactions between multiple viral envelope glycoproteins and cell surface associated heparan sulfate (HS), integrins (α3β1, αVβ3 and αVβ5), and EphA2 receptor tyrosine kinase (EphA2R). This review summarizes the accumulated studies demonstrating that KSHV manipulates the host signal pathways to enter and traffic in the cytoplasm of the target cells, to deliver the viral genome into the nucleus, and initiate viral gene expression. KSHV interactions with the cell surface receptors is the key platform for the manipulations of host signal pathways which results in the simultaneous induction of FAK, Src, PI3-K, Rho-GTPase, ROS, Dia-2, PKC ζ, c-Cbl, CIB1, Crk, p130Cas and GEF-C3G signal and adaptor molecules that play critical roles in the modulation of membrane and actin dynamics, and in the various steps of the early stages of infection such as entry and trafficking towards the nucleus. The Endosomal Sorting Complexes Required for Transport (ESCRT) proteins are also recruited to assist in viral entry and trafficking. In addition, KSHV interactions with the cell surface receptors also induces the host transcription factors NF-κB, ERK1/2, and Nrf2 early during infection to initiate and modulate viral and host gene expression. Nuclear delivery of the viral dsDNA genome is immediately followed by the host innate responses such as the DNA damage response (DDR), inflammasome and interferon responses. Overall, these studies form the initial framework for further studies of simultaneous targeting of KSHV glycoproteins, host receptor, signal molecules and trafficking machinery that would lead into novel therapeutic methods to prevent KSHV infection of target cells and consequently the associated malignancies.

Reaction-diffusion basis of retroviral infectivity.

Retrovirus particle (virion) infectivity requires diffusion and clustering of multiple transmembrane envelope proteins (Env3) on the virion exterior, yet is triggered by protease-dependent degradation of a partially occluding, membrane-bound Gag polyprotein lattice on the virion interior. The physical mechanism underlying such coupling is unclear and only indirectly accessible via experiment. Modelling stands to provide insight but the required spatio-temporal range far exceeds current accessibility by all-atom or even coarse-grained molecular dynamics simulations. Nor do such approaches account for chemical reactions, while conversely, reaction kinetics approaches handle neither diffusion nor clustering. Here, a recently developed multiscale approach is considered that applies an ultra-coarse-graining scheme to treat entire proteins at near-single particle resolution, but which also couples chemical reactions with diffusion and interactions. A model is developed of Env3 molecules embedded in a truncated Gag lattice composed of membrane-bound matrix proteins linked to capsid subunits, with freely diffusing protease molecules. Simulations suggest that in the presence of Gag but in the absence of lateral lattice-forming interactions, Env3 diffuses comparably to Gag-absent Env3 Initial immobility of Env3 is conferred through lateral caging by matrix trimers vertically coupled to the underlying hexameric capsid layer. Gag cleavage by protease vertically decouples the matrix and capsid layers, induces both matrix and Env3 diffusion, and permits Env3 clustering. Spreading across the entire membrane surface reduces crowding, in turn, enhancing the effect and promoting infectivity.This article is part of the themed issue 'Multiscale modelling at the physics-chemistry-biology interface'.

Beyond the single species climate envelope: a multifaceted approach to mapping climate change vulnerability

AbstractFederal land management agencies and conservation organizations have begun incorporating climate change vulnerability assessments (CCVAs) as an important component in the management and conservation of landscapes. It is often a challenge to translate that knowledge into management plans and actions, even when research infers species risk. Predictive maps can improve current CCVAs and assist in quantifying and visualizing species climate change vulnerability across large areas. We assessed the climate change risk for Greater Sage‐Grouse (Centrocercus urophasianus; sage‐grouse) habitat at two spatial scales in Utah and Nevada. At the local scale, multiple species climate envelopes were evaluated with additional stressors (fire, conifer encroachment, invasive grass, and human impact) to create risk maps for mesic (Strawberry) and xeric (Sheeprock) sage‐grouse landscapes in Utah. Both landscapes were predicted to be at risk, but Sheeprock was found to be at higher risk due to future climate change implications coupled with additional habitat‐degrading stressors. By using models, we are able to integrate complex interactions, and visualize the distribution of risk across broad spatial scales, providing land managers and researchers a valuable tool for CCVA and action plans.

Broadly neutralizing antibody specificities detected in the genital tract of HIV-1 infected women.

Broadly neutralizing antibodies (bNAbs) targeting conserved epitopes on the HIV envelope glycoprotein have been identified in blood from HIV-1 infected women. We investigated whether antibodies in the genital tract from these women share similar epitope specificities and functional profiles as those in blood. Immunoglobulin (Ig)G and IgA antibodies were isolated from cervicovaginal lavages or Softcups from 13 HIV-infected women in the CAPRISA cohort using Protein G and Peptide M, respectively. Binding antibodies to envelope antigens were quantified by ELISA and binding antibody multiplex assay. Neutralizing antibody titers and epitope targets were measured using the TZM-bl assay with Env-pseudotyped wild-type and mutated viruses. HIV-specific IgG, but not IgA, was detected in genital secretions and the ratio of total IgG to HIV-specific IgG was similar to plasma. HIV-specific IgG reacted with multiple envelope antigens, including V1V2, gp120, gp140 and gp41. Two women had high plasma titers of HIV-specific IgG3 which was also detected in their genital tract samples. IgG from the genital tract had neutralizing activity against both Tier 1 and Tier 2 primary HIV-isolates. Antibodies targeting well known glycan epitopes and the membrane proximal region of gp41 were detected in genital secretions, and matched specificities in plasma. Women with plasma bNAbs have overlapping specificities in their genital secretions, indicating that these predominantly IgG isotype antibodies may transudate from blood to the genital tract. These data provide evidence that induction of systemic HIV-specific bNAbs can lead to antiviral immunity at the portal of entry.

Ferrite toroidal core with a trifilar wound RF broadband transformer design for tracking generators in wideband code division multiple access envelope tracking RFPA systems

In this paper, the design of an RF broadband transformer for wideband code division multiple access (WCDMA) tracking generators to be used in envelope tracking RF power amplifiers systems is presented. A ferrite toroidal core with a trifilar wound RF broadband transformer has been chosen to satisfy the (WCDMA) bandwidth requirement and also the power amplifier performance criteria that include the efficiency, electrical isolation, size and power consumption. The design components investigated comprises ferrite materials, number of turns on core windings and size.

Antibodies Elicited by Multiple Envelope Glycoprotein Immunogens in Primates Neutralize Primary Human Immunodeficiency Viruses (HIV-1) Sensitized by CD4-Mimetic Compounds.

The human immunodeficiency virus (HIV-1) envelope glycoproteins (Env) mediate virus entry through a series of complex conformational changes triggered by binding to the receptors CD4 and CCR5/CXCR4. Broadly neutralizing antibodies that recognize conserved Env epitopes are thought to be an important component of a protective immune response. However, to date, HIV-1 Env immunogens that elicit broadly neutralizing antibodies have not been identified, creating hurdles for vaccine development. Small-molecule CD4-mimetic compounds engage the CD4-binding pocket on the gp120 exterior Env and induce Env conformations that are highly sensitive to neutralization by antibodies, including antibodies directed against the conserved Env region that interacts with CCR5/CXCR4. Here, we show that CD4-mimetic compounds sensitize primary HIV-1 to neutralization by antibodies that can be elicited in monkeys and humans within 6 months by several Env vaccine candidates, including gp120 monomers. Monoclonal antibodies directed against the gp120 V2 and V3 variable regions were isolated from the immunized monkeys and humans; these monoclonal antibodies neutralized a primary HIV-1 only when the virus was sensitized by a CD4-mimetic compound. Thus, in addition to their direct antiviral effect, CD4-mimetic compounds dramatically enhance the HIV-1-neutralizing activity of antibodies that can be elicited with currently available immunogens. Used as components of microbicides, the CD4-mimetic compounds might increase the protective efficacy of HIV-1 vaccines. Preventing HIV-1 transmission is a high priority for global health. Eliciting antibodies that can neutralize transmitted strains of HIV-1 is difficult, creating problems for the development of an effective vaccine. We found that small-molecule CD4-mimetic compounds sensitize HIV-1 to antibodies that can be elicited in vaccinated humans and monkeys. These results suggest an approach to prevent HIV-1 sexual transmission in which a virus-sensitizing microbicide is combined with a vaccine.

New beam-tracking simulation code using bulk-to-point calculation technique for space charge fields

A new two-dimensional beam-tracking simulation code for electron injectors using a bulk-to-point calculation technique for space charge fields was developed. The calculated space charge fields are produced not by a point charge but by a hollow cylinder that has a volume. Each tracked electron is a point charge. This bulk-to-point calculation technique for space charge fields is based on that used in the multiple beam envelope equations, which were developed by the author. The multiple beam envelope equations are a set of differential equations for investigating the beam dynamics of electron injectors and can be used to calculate bunched beam dynamics with high accuracy. However, there is one limitation. The bunched beam is assumed to be an ensemble of several segmentation pieces in both the transverse and longitudinal directions. In this bunch model, each longitudinal segmentation slice in a bunch must not warp; consequently, the accuracy of the calculated emittance is reduced in the case of a highly charged beam for calculations of a typical rf gun injector system. This limitation is related to the calculation model of longitudinal space charge fields. In the newly developed beam-tracking simulation code, the space charge field calculation scheme is upgraded and the limitation has been overcome. Therefore, the applicable range is extended while maintaining the high accuracy of emittance calculations. Simultaneously, the calculation time is markedly shortened because the emittance dependence on the segmentation number is extremely weak. In this paper, several examples of beam dynamics that cannot be calculated accurately using the multiple beam envelope equations are demonstrated using the new beam-tracking simulation code. The accuracy of the calculated emittance is also discussed.

Envelope Interactions in Multi-Channel Amplitude Modulation Frequency Discrimination by Cochlear Implant Users.

RationalePrevious cochlear implant (CI) studies have shown that single-channel amplitude modulation frequency discrimination (AMFD) can be improved when coherent modulation is delivered to additional channels. It is unclear whether the multi-channel advantage is due to increased loudness, multiple envelope representations, or to component channels with better temporal processing. Measuring envelope interference may shed light on how modulated channels can be combined.MethodsIn this study, multi-channel AMFD was measured in CI subjects using a 3-alternative forced-choice, non-adaptive procedure (“which interval is different?”). For the reference stimulus, the reference AM (100 Hz) was delivered to all 3 channels. For the probe stimulus, the target AM (101, 102, 104, 108, 116, 132, 164, 228, or 256 Hz) was delivered to 1 of 3 channels, and the reference AM (100 Hz) delivered to the other 2 channels. The spacing between electrodes was varied to be wide or narrow to test different degrees of channel interaction.ResultsResults showed that CI subjects were highly sensitive to interactions between the reference and target envelopes. However, performance was non-monotonic as a function of target AM frequency. For the wide spacing, there was significantly less envelope interaction when the target AM was delivered to the basal channel. For the narrow spacing, there was no effect of target AM channel. The present data were also compared to a related previous study in which the target AM was delivered to a single channel or to all 3 channels. AMFD was much better with multiple than with single channels whether the target AM was delivered to 1 of 3 or to all 3 channels. For very small differences between the reference and target AM frequencies (2–4 Hz), there was often greater sensitivity when the target AM was delivered to 1 of 3 channels versus all 3 channels, especially for narrowly spaced electrodes.ConclusionsBesides the increased loudness, the present results also suggest that multiple envelope representations may contribute to the multi-channel advantage observed in previous AMFD studies. The different patterns of results for the wide and narrow spacing suggest a peripheral contribution to multi-channel temporal processing. Because the effect of target AM frequency was non-monotonic in this study, adaptive procedures may not be suitable to measure AMFD thresholds with interfering envelopes. Envelope interactions among multiple channels may be quite complex, depending on the envelope information presented to each channel and the relative independence of the stimulated channels.

Chimeric porcine reproductive and respiratory syndrome virus containing shuffled multiple envelope genes confers cross-protection in pigs

The extensive genetic diversity of porcine reproductive and respiratory syndrome virus (PRRSV) strains is a major obstacle for vaccine development. We previously demonstrated that chimeric PRRSVs in which a single envelope gene (ORF3, ORF4, ORF5 or ORF6) was shuffled via DNA shuffling had an improved heterologous cross-neutralizing ability. In this study, we incorporate all of the individually-shuffled envelope genes together in different combinations into an infectious clone backbone of PRRSV MLV Fostera® PRRS. Five viable progeny chimeric viruses were rescued, and their growth characteristics were characterized in vitro. In a pilot pig study, two chimeric viruses (FV-SPDS-VR2,FV-SPDS-VR5) were found to induce cross-neutralizing antibodies against heterologous strains. A subsequent vaccination/challenge study in 72 pigs revealed that chimeric virus FV-SPDS-VR2 and parental virus conferred partial cross-protection when challenged with heterologous strains NADC20 or MN184B. The results have important implications for future development of an effective PRRSV vaccine that confers heterologous protection.

Moving toward automatic and standalone delineation of seismocardiogram signal.

The purpose of this research is to propose an algorithm that could accomplish automatic delineation of the seismocardiogram (SCG) signal without using a reference electrocardiogram R-wave. As a result, the SCG signal could be used, as a stand-alone solution for many cardiovascular medical applications such as hemorrhage detection, cardiac computed tomographic gating, cardiac resynchronization therapy, hemodynamics estimations and diastolic timed vibration. Multiple envelopes were derived from the seismocardiogram signal by using filtering and triple integration. The first envelope is referred as the heart rate envelope, which has the characteristics of having a period of exactly one cardiac cycle and its purpose is to replace the ECG R-wave as a reference point. Our dataset is based on the lower body negative pressure (LBNP) test that was conducted on 18 individuals, containing 21610 cardiac cycles. For 94% of the LBNP dataset, the aforementioned envelope estimated heart rate within 3 beats per minute. Three different peaks of the SCG signal are of our interest: isovolumic contraction (IM), aortic valve opening (AO) and aortic valve closure (AC). For each of these desired peaks of the SCG signal, a different envelope was designed in a manner that its peak is very close to IM, AO and AC, respectively. For the same lower body negative pressure data set, a mean difference of (9, 9, 6) and standard deviation of (8, 9, 9) millisecond between the peak of envelopes and IM, AO and AC is accomplished. This could be used as a good initial estimation of the annotation points.

DENGUE VIRUS. Cryo-EM structure of an antibody that neutralizes dengue virus type 2 by locking E protein dimers.

There are four closely-related dengue virus (DENV) serotypes. Infection with one serotype generates antibodies that may cross-react and enhance infection with other serotypes in a secondary infection. We demonstrated that DENV serotype 2 (DENV2)-specific human monoclonal antibody (HMAb) 2D22 is therapeutic in a mouse model of antibody-enhanced severe dengue disease. We determined the cryo-electron microscopy (cryo-EM) structures of HMAb 2D22 complexed with two different DENV2 strains. HMAb 2D22 binds across viral envelope (E) proteins in the dimeric structure, which probably blocks the E protein reorganization required for virus fusion. HMAb 2D22 "locks" two-thirds of or all dimers on the virus surface, depending on the strain, but neutralizes these DENV2 strains with equal potency. The epitope defined by HMAb 2D22 is a potential target for vaccines and therapeutics.

An antibody to lock dengue virus out

Dengue Virus Mosquito-borne dengue virus (DENV) is a growing public health threat. Nearly 400 million people are infected annually, and no vaccine is currently available. Fibriansah et al. report that a human antibody (2D22) specific for DENV serotype 2, when given therapeutically, can protect mice from a lethal form of this virus. Structural analysis revealed that 2D22 binds across multiple DENV envelope proteins, which probably blocks the ability of these proteins to assemble into the orientation necessary for viral entry. The epitope where 2D22 binds to the virus may therefore represent a potential vaccine target. Science , this issue p. [88][1] [1]: /lookup/doi/10.1126/science.aaa8651

Modeling a Decision Support Tool for Buildable and Sustainable Building Envelope Designs

Sustainability and buildability requirements in building envelope design have significantly gained more importance nowadays, yet there is a lack of an appropriate decision support system (DSS) that can help a building design team to incorporate these requirements and manage their tradeoffs at once. The main objective of this study is to build such a tool to facilitate a building design team to take into account sustainability and buildability criteria for assessment of building envelopes of high-rise residential buildings in Singapore. Literature reviews were conducted to investigate a comprehensive set of the sustainability and buildability criteria. This also included development of the tool using a Quality Functional Deployment (QFD) approach combined with fuzzy set theory. A building design team was engaged to test the tool with the aim to evaluate usefulness of the tool in managing the tradeoffs among the sustainability and buildability criteria. The results from a qualitative data analysis suggested that the tool allowed the design team to effectively find a balance between the tradeoffs among the criteria when assessing multiple building envelope design alternatives. Main contributions of using this tool are achievement of a more efficient assessment of the building envelopes and more sustainable and buildable building envelope design.

Multiple sclerosis retrovirus-like envelope gene: Role of the chromosome 20 insertion

BackgroundThe genetic basis involved in multiple sclerosis (MS) susceptibility was not completely revealed by genome-wide association studies. Part of it could lie in repetitive sequences, as those corresponding to human Endogenous Retroviruses (HERVs). Retrovirus-like particles were isolated from MS patients and the genome of the MS-associated retrovirus (MSRV) was the founder of the HERV-W family. We aimed to ascertain which chromosomal origin encodes the pathogenic ENV protein by genomic analysis of the HERV-W insertions. Methods/resultsIn silico analyses allowed to uncover putative open reading frames containing the specific sequence previously reported for MSRV-like envelope (env) detection. Out of the 261 genomic insertions of HERV-W env, only 9 copies harbor the specific primers and probe featuring MSRV-like env. The copy from chromosome 20 was further studied considering its size, a truncated homologue of the functional HERV-W env sequence encoding syncytin. High Resolution Melting analysis of this sequence identified two single nucleotide polymorphisms, subsequently genotyped by Taqman chemistry in 668 MS patients and 678 healthy controls. No significant association of these polymorphisms with MS risk was evidenced. Transcriptional activity of this MSRV-like env copy was detected in peripheral blood mononuclear cells from patients and controls. RNA expression levels of chromosome 20-specific MSRV-like env did not show significant differences between MS patients and controls, neither were related to genotypes of the two mentioned polymorphisms. ConclusionsThe lack of association with MS risk of the identified polymorphisms together with the transcription results discard chromosome 20 as genomic origin of MSRV-like env.

Envelope variants circulating as initial neutralization breadth developed in two HIV-infected subjects stimulate multiclade neutralizing antibodies in rabbits.

Identifying characteristics of the human immunodeficiency virus type 1 (HIV-1) envelope that are effective in generating broad, protective antibodies remains a hurdle to HIV vaccine design. Emerging evidence of the development of broad and potent neutralizing antibodies in HIV-infected subjects suggests that founder and subsequent progeny viruses may express unique antigenic motifs that contribute to this developmental pathway. We hypothesize that over the course of natural infection, B cells are programmed to develop broad antibodies by exposure to select populations of emerging envelope quasispecies variants. To test this hypothesis, we identified two unrelated subjects whose antibodies demonstrated increasing neutralization breadth against a panel of HIV-1 isolates over time. Full-length functional env genes were cloned longitudinally from these subjects from months after infection through 2.6 to 5.8 years of infection. Motifs associated with the development of breadth in published, cross-sectional studies were found in both subjects. We compared the immunogenicity of envelope vaccines derived from time points obtained during and after broadening of neutralization activity within these subjects. Rabbits were coimmunized four times with selected multiple gp160 DNAs and gp140-trimeric envelope proteins. The affinity of the polyclonal response increased as a function of boosting. The most rapid and persistent neutralization of multiclade tier 1 viruses was elicited by envelopes that were circulating in plasma at time points prior to the development of 50% neutralization breadth in both human subjects. The breadth elicited in rabbits was not improved by exposure to later envelope variants. These data have implications for vaccine development in describing a target time point to identify optimal envelope immunogens. Vaccine protection against viral infections correlates with the presence of neutralizing antibodies; thus, vaccine components capable of generating potent neutralization are likely to be critical constituents in an effective HIV vaccine. However, vaccines tested thus far have elicited only weak antibody responses and very modest, waning protection. We hypothesized that B cells develop broad antibodies by exposure to the evolving viral envelope population and tested this concept using multiple envelopes from two subjects who developed neutralization breadth within a few years of infection. We compared different combinations of envelopes from each subject to identify the most effective immunogens and regimens. In each subject, use of HIV envelopes circulating during the early development and maturation of breadth generated more-potent antibodies that were modestly cross neutralizing. These data suggest a new approach to identifying envelope immunogens that may be more effective in generating protective antibodies in humans.

Envelope-based boundary image matching for smart devices under arbitrary rotations

Recently, a variety of smart devices have been introduced for entertainment or industrial purposes, and there have been a lot of needs for image matching applications exploiting a large number of images stored in those smart devices. Boundary image matching identifies similar boundary images using their corresponding time-series, and supporting the rotation invariance is crucial to provide more intuitive matching results not only in conventional computing devices but also in smart devices such as smartphones, smart pads, and smart cameras. Computing the rotation-invariant distance between image time-series, however, is a very time-consuming process since it requires a lot of Euclidean distance computations for all possible rotations. We here note that, for smart devices, a very efficient mechanism of computing rotation-invariant distances is required. For this purpose, in this paper we use a novel notion of envelope-based lower bound proposed by Keogh et al. (VLDB J 18:611---630, 2009) to reduce the number of distance computations dramatically. With the help of Keogh et al.'s prior work (Keogh in Proceedings of the 28th International Conference on Very Large Data Bases, 406---417, 2002; Keogh et al. in VLDB J 18:611---630, 2009), we first explain how to construct a single envelope from a query sequence and how to obtain a lower bound of the rotation-invariant distance using the envelope. We then explain that the single envelope lower bound can reduce a number of distance computations. This single envelope approach, however, may cause bad performance since it may incur a larger lower bound due to considering all possible rotated sequences in a single envelope. To solve this problem, we present a concept of rotation interval, and using the concept of multiple envelopes proposed by Keogh et al. (VLDB J 18:611---630, 2009) with these rotation intervals, we then generalize the envelope-based lower bound by exploiting multiple envelopes rather than a single envelope. We also propose equi-width and envelope-minimization divisions as the method of determining rotation intervals in the multi-envelope approach. We further present an advanced multi-step matching algorithm that progressively prunes search spaces by dividing the rotation interval in half. Experimental results show that our envelope-based solutions outperform naive solutions by one to three orders of magnitude. We believe that this performance improvement makes our algorithms very suitable for smart devices.