305 research outputs found

    Identification of a protein encoded in the EB-viral open reading frame BMRF2

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    Using monospecific rabbit sera against a peptide derived from a potential antigenic region of the Epstein-Barr viral amino acid sequence encoded in the open reading frame BMRF2 we could identify a protein-complex of 53/55 kDa in chemically induced B95-8, P3HR1 and Raji cell lines. This protein could be shown to be membrane-associated, as predicted by previous computer analysis of the secondary structure and hydrophilicity pattern, and may be a member of EBV-induced membrane proteins in lytically infected cells

    Cellulose acetate phthalate, a common pharmaceutical excipient, inactivates HIV-1 and blocks the coreceptor binding site on the virus envelope glycoprotein gp120

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    BACKGROUND: Cellulose acetate phthalate (CAP), a pharmaceutical excipient used for enteric film coating of capsules and tablets, was shown to inhibit infection by the human immunodeficiency virus type 1 (HIV-1) and several herpesviruses. CAP formulations inactivated HIV-1, herpesvirus types 1 (HSV-1) and 2 (HSV-2) and the major nonviral sexually transmitted disease (STD) pathogens and were effective in animal models for vaginal infection by HSV-2 and simian immunodeficiency virus. METHODS: Enzyme-linked immunoassays and flow cytometry were used to demonstrate CAP binding to HIV-1 and to define the binding site on the virus envelope. RESULTS: 1) CAP binds to HIV-1 virus particles and to the envelope glycoprotein gp120; 2) this leads to blockade of the gp120 V3 loop and other gp120 sites resulting in diminished reactivity with HIV-1 coreceptors CXCR4 and CCR5; 3) CAP binding to HIV-1 virions impairs their infectivity; 4) these findings apply to both HIV-1 IIIB, an X4 virus, and HIV-1 BaL, an R5 virus. CONCLUSIONS: These results provide support for consideration of CAP as a topical microbicide of choice for prevention of STDs, including HIV-1 infection

    Measurement of the ultrasound attenuation and dispersion in 3D-printed photopolymer materials from 1 to 3.5 MHz

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    Over the past decade, the range of applications in biomedical ultrasound exploiting 3D printing has rapidly expanded. For wavefront shaping specifically, 3D printing has enabled a diverse range of new, low-cost approaches for controlling acoustic fields. These methods rely on accurate knowledge of the bulk acoustic properties of the materials; however, to date, robust knowledge of these parameters is lacking for many materials that are commonly used. In this work, the acoustic properties of eight 3D-printed photopolymer materials were characterised over a frequency range from 1 to 3.5 MHz. The properties measured were the frequency-dependent phase velocity and attenuation, group velocity, signal velocity, and mass density. The materials were fabricated using two separate techniques [PolyJet and stereolithograph (SLA)], and included Agilus30, FLXA9960, FLXA9995, Formlabs Clear, RGDA8625, RGDA8630, VeroClear, and VeroWhite. The range of measured density values across all eight materials was 1120–1180 kg · m−3, while the sound speed values were between 2020 to 2630 m · s−1, and attenuation values typically in the range 3–9 dB · MHz−1· cm−1

    Fractional Stars

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    This study examines the possibility of starting the process of collapsing and forming stars from a fractional molecular cloud. Although the Verlinde\u27s approach is employed to derive the corresponding gravitational potential, the results are easily generalizable to other gravitational potential proposals for fractional systems. It is due to the fact that the different methods, despite the difference in the details of results, all obtain power forms for the potential in terms of radius. An essential result of this analysis is the derivation of the corresponding Jeans mass limit, which is a crucial parameter in understanding the formation of stars. The study shows that the Jeans mass of a cloud in fractional gravity is much smaller than the traditional value. In addition, the study also determines the burning temperature of the resulting star using the Gamow theory. This calculation provides insight into the complex processes that govern the evolution of these celestial bodies. Finally, the study briefly discusses the investigation of hydrostatic equilibrium, a crucial condition that ensures the stability of these fractional stars. It also addresses the corresponding Lane--Emden equation, which is pivotal in understanding this equilibrium.29 pages, 3 figures, to appear in Astrophysics and Space Scienc

    A novel patient engagement platform using accessible text messages and calls (Epharmix): Feasibility study

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    BACKGROUND: Patient noncompliance with therapy, treatments, and appointments represents a significant barrier to improving health care delivery and reducing the cost of care. One method to improve therapeutic adherence is to improve feedback loops in getting clinically acute events and issues to the relevant clinical providers as necessary (ranging from detecting hypoglycemic events for patients with diabetes to notifying the provider when patients are out of medications). Patients often don\u27t know which information should prompt a call to their physician and proactive checks by the clinics themselves can be very resource intensive. We hypothesized that a two-way SMS system combined with a platform web service for providers would enable both high patient engagement but also the ability to detect relevant clinical alerts. OBJECTIVE: The objectives of this study are to develop a feasible two-way automated SMS/phone call + web service platform for patient-provider communication, and then study the feasibility and acceptability of the Epharmix platform. First, we report utilization rates over the course of the first 18 months of operation including total identified clinically significant events, and second, review results of patient user-satisfaction surveys for interventions for patients with diabetes, COPD, congestive heart failure, hypertension, surgical site infections, and breastfeeding difficulties. METHODS: To test this question, we developed a web service + SMS/phone infrastructure ( Epharmix ). Utilization results were measured based on the total number of text messages or calls sent and received, with percentage engagement defined as a patient responding to a text message at least once in a given week, including the number of clinically significant alerts generated. User satisfaction surveys were sent once per month over the 18 months to measure satisfaction with the system, frequency and degree of communication. Descriptive statistics were used to describe the above information. RESULTS: In total, 28,386 text messages and 24,017 calls were sent to 929 patients over 9 months. Patients responded to 80% to 90% of messages allowing the system to detect 1164 clinically significant events. Patients reported increased satisfaction and communication with their provider. Epharmix increased the number of patient-provider interactions to over 10 on average in any given month for patients with diabetes, COPD, congestive heart failure, hypertension, surgical site infections, and breastfeeding difficulties. CONCLUSIONS: Engaging high-risk patients remains a difficult process that may be improved through novel, digital health interventions. The Epharmix platform enables increased patient engagement with very low risk to improve clinical outcomes. We demonstrated that engagement among high-risk populations is possible when health care comes conveniently to where they are

    Fully three-dimensional sound speed-corrected multi-wavelength photoacoustic breast tomography

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    Photoacoustic tomography is a contrast agent-free imaging technique capable of visualizing blood vessels and tumor-associated vascularization in breast tissue. While sophisticated breast imaging systems have been recently developed, there is yet much to be gained in imaging depth, image quality and tissue characterization capability before clinical translation is possible. In response, we have developed a hybrid photoacoustic and ultrasound-transmission tomographic system PAM3. The photoacoustic component has for the first time three-dimensional multi-wavelength imaging capability, and implements substantial technical advancements in critical hardware and software sub-systems. The ultrasound component enables for the first time, a three-dimensional sound speed map of the breast to be incorporated in photoacoustic reconstruction to correct for inhomogeneities, enabling accurate target recovery. The results demonstrate the deepest photoacoustic breast imaging to date namely 48 mm, with a more uniform field of view than hitherto, and an isotropic spatial resolution that rivals that of Magnetic Resonance Imaging. The in vivo performance achieved, and the diagnostic value of interrogating angiogenesis-driven optical contrast as well as tumor mass sound speed contrast, gives confidence in the system's clinical potential

    Fully three-dimensional sound speed-corrected multi-wavelength photoacoustic breast tomography

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    Photoacoustic tomography is a contrast agent-free imaging technique capable of visualizing blood vessels and tumor-associated vascularization in breast tissue. While sophisticated breast imaging systems have been recently developed, there is yet much to be gained in imaging depth, image quality and tissue characterization capability before clinical translation is possible. In response, we have developed a hybrid photoacoustic and ultrasound-transmission tomographic system PAM3. The photoacoustic component has for the first time three-dimensional multi-wavelength imaging capability, and implements substantial technical advancements in critical hardware and software sub-systems. The ultrasound component enables for the first time, a three-dimensional sound speed map of the breast to be incorporated in photoacoustic reconstruction to correct for inhomogeneities, enabling accurate target recovery. The results demonstrate the deepest photoacoustic breast imaging to date namely 48 mm, with a more uniform field of view than hitherto, and an isotropic spatial resolution that rivals that of Magnetic Resonance Imaging. The in vivo performance achieved, and the diagnostic value of interrogating angiogenesis-driven optical contrast as well as tumor mass sound speed contrast, gives confidence in the system's clinical potential.Comment: 33 pages Main Body, 9 pages Supplementary Materia

    Heterologous Epitope-Scaffold Prime∶Boosting Immuno-Focuses B Cell Responses to the HIV-1 gp41 2F5 Neutralization Determinant

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    The HIV-1 envelope glycoproteins (Env) gp120 and gp41 mediate entry and are the targets for neutralizing antibodies. Within gp41, a continuous epitope defined by the broadly neutralizing antibody 2F5, is one of the few conserved sites accessible to antibodies on the functional HIV Env spike. Recently, as an initial attempt at structure-guided design, we transplanted the 2F5 epitope onto several non-HIV acceptor scaffold proteins that we termed epitope scaffolds (ES). As immunogens, these ES proteins elicited antibodies with exquisite binding specificity matching that of the 2F5 antibody. These novel 2F5 epitope scaffolds presented us with the opportunity to test heterologous prime∶boost immunization strategies to selectively boost antibody responses against the engrafted gp41 2F5 epitope. Such strategies might be employed to target conserved but poorly immunogenic sites on the HIV-1 Env, and, more generally, other structurally defined pathogen targets. Here, we assessed ES prime∶boosting by measuring epitope specific serum antibody titers by ELISA and B cell responses by ELISpot analysis using both free 2F5 peptide and an unrelated ES protein as probes. We found that the heterologous ES prime∶boosting immunization regimen elicits cross-reactive humoral responses to the structurally constrained 2F5 epitope target, and that incorporating a promiscuous T cell helper epitope in the immunogens resulted in higher antibody titers against the 2F5 graft, but did not result in virus neutralization. Interestingly, two epitope scaffolds (ES1 and ES2), which did not elicit a detectable 2F5 epitope-specific response on their own, boosted such responses when primed with the ES5. Together, these results indicate that heterologous ES prime∶boost immunization regimens effectively focus the humoral immune response on the structurally defined and immunogen-conserved HIV-1 2F5 epitope

    Fully three-dimensional sound speed-corrected multi-wavelength photoacoustic breast tomography

    Get PDF
    Photoacoustic tomography is a contrast agent-free imaging technique capable of visualizing blood vessels and tumor-associated vascularization in breast tissue. While sophisticated breast imaging systems have been recently developed, there is yet much to be gained in imaging depth, image quality and tissue characterization capability before clinical translation is possible. In response, we have developed a hybrid photoacoustic and ultrasound-transmission tomographic system PAM3. The photoacoustic component has for the first time three-dimensional multi-wavelength imaging capability, and implements substantial technical advancements in critical hardware and software sub-systems. The ultrasound component enables for the first time, a three-dimensional sound speed map of the breast to be incorporated in photoacoustic reconstruction to correct for inhomogeneities, enabling accurate target recovery. The results demonstrate the deepest photoacoustic breast imaging to date namely 48 mm, with a more uniform field of view than hitherto, and an isotropic spatial resolution that rivals that of Magnetic Resonance Imaging. The in vivo performance achieved, and the diagnostic value of interrogating angiogenesis-driven optical contrast as well as tumor mass sound speed contrast, gives confidence in the system\'s clinical potential
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