Experimental investigation on the enhancement of plenum window noise reduction using solid scatterers

The sound transmission across plenum windows installed with rigid non-resonant cylindrical scatterer arrays was investigated in detail using scale-down model measurements carried out inside a fully anechoic chamber. The arrays have manifested to some extent the acoustical behaviors of virtual sonic crystals. The maximum cross section blockage ratio was 0.6. The effects of plenum window gap, array configuration, and scatterer diameter on the sound transmission characteristics were also examined. Results indicate that the window cavity longitudinal modes and the gap modes control the sound transmission characteristics at low frequencies. The upper bound of this frequency range increases with decreasing gap width. Within this frequency range, the scatterers have negligible effect on the sound transmission. At higher frequencies, the array configurations with scatterer(s) attached to the window walls result in stronger sound reduction. There are relatively higher sound transmission loss improvements around the frequencies where a full bandgap is observed. There are wide bandgaps in various lattice directions, and the present results suggest that they play a role in the broadband improvement of sound reduction

Targeting Tumor-Associated Exosomes with Integrin-Binding Peptides

All cells expel a variety of nanosized extracellular vesicles (EVs), including exosomes, with composition reflecting the cells' biological state. Cancer pathology is dramatically mediated by EV trafficking via key proteins, lipids, metabolites, and microRNAs. Recent proteomics evidence suggests that tumor-associated exosomes exhibit distinct expression of certain membrane proteins, rendering those proteins as attractive targets for diagnostic or therapeutic application, yet it is not currently feasible to distinguish circulating EVs in complex biofluids according to their tissue of origin or state of disease. Here, peptide binding to tumor-associated EVs via overexpressed membrane protein is demonstrated. It is found that SKOV-3 ovarian tumor cells and their released EVs express alpha(3)beta(1) integrin, which can be targeted by the in-house cyclic nonapeptide, LXY30. After measuring bulk SKOV-3 EV association with LXY30 by flow cytometry, Raman spectral analysis of laser-trapped single exosomes with LXY30-dialkyne conjugate enables the differentiation of cancer-associated exosomes from noncancer exosomes. Furthermore, the foundation for a highly specific detection platform for tumor-EVs in solution with biosensor surface-immobilized LXY30 is introduced. LXY30 not only exhibits high specificity and affinity to alpha(3)beta(1) integrin-expressing EVs, but also reduces EV uptake into SKOV-3 parent cells, demonstrating the possibility for therapeutic application.Peer reviewe

A directionally tunable but frequency-invariant beamformer on an acoustic velocity-sensor triad to enhance speech perception

Herein investigated are computationally simple microphone-array beamformers that are independent of the frequency-spectra of all signals, all interference, and all noises. These beamformers allow the listener to tune the desired azimuth-elevation “look direction.” No prior information is needed of the interference. These beamformers deploy a physically compact triad of three collocated but orthogonally oriented velocity sensors. These proposed schemes’ efficacy is verified by a jury test, using simulated data constructed with Mandarin Chinese (a.k.a. Putonghua) speech samples. For example, a desired speech signal, originally at a very adverse signal-to-interference-and-noise power ratio (SINR) of -30 dB, may be processed to become fully intelligible to the jury

Depression literacy among Australians of Chinese-speaking background in Melbourne, Australia

<p>Abstract</p> <p>Background</p> <p>This study investigated the knowledge of depression and preference for professional help, medications and treatment methods among Australians of Chinese-speaking background, and the perceptions of this population of the causes of mental illness.</p> <p>Methods</p> <p>Adopting a cluster convenience sampling method, the study recruited 200 Chinese-speaking subjects from four major areas in metropolitan Melbourne where many Chinese live. The respondents were presented with a vignette describing an individual with depression and then asked questions to assess their understanding of depression and preference for professional help, medications and treatment methods. A comparative approach was used to compare the findings with those of a previous study of the mental health literacy of Australian and Japanese adults.</p> <p>Results</p> <p>Compared to the Australian and Japanese samples, a much lower percentage of Chinese-speaking Australians (14%) could correctly identify major depression described in the vignette, and a higher percentage believed that counseling professionals could be helpful. Higher percentages of those who believed that close family members could be helpful were found in the Chinese-speaking Australian and Japanese samples, and these two groups also expressed more uncertainty about the usefulness or harmfulness of certain medications compared to the Australian sample. Higher percentages of respondents in both the Chinese-speaking Australian and the Australian sample considered "lifestyle changes" to be helpful compared to the Japanese sample. In the Chinese-speaking sample, 30%, 17.4%, 33% and 27% of the respondents rated "traditional Chinese medicine doctors," "Chinese herbal medications," "taking Chinese nutritional foods/supplements" and "<it>qiqong</it>" as helpful. Many perceived "changing <it>fungshui</it>" and "traditional Chinese worship" to be harmful. Regarding the perception of causes of mental illness, items related to psychosocial perspectives including "life stress" and "interpersonal conflict" were rated highly by the respondents, whereas traditional beliefs including "punishment for misdeeds conducted by ancestors" and "demon possession" had the lowest ratings.</p> <p>Conclusions</p> <p>Campaigns to increase the mental health literacy of Chinese-speaking Australians are needed. The abovementioned socially and culturally driven beliefs need to be taken into consideration in the development of culturally relevant education programs.</p

Preventable hospital admissions among the homeless in California: A retrospective analysis of care for ambulatory care sensitive conditions

Background Limited research exists that investigates hospital admissions for ambulatory care sensitive conditions (ACSCs) among the homeless, who frequently lack a usual source of care. This study profiled ACSC admissions for homeless patients. Methods Bivariate analyses and logistic regression were completed to investigate ACSC and non-ACSC admissions among homeless patients using the 2010 California State Inpatient Database. Results Homeless patients admitted for an ACSC were mostly male, non-Hispanic white, and on average 49.9 years old. In the predictive model, the odds of an ACSC admission among homeless patients increased when they were black, admitted to the emergency department or transferred from another health facility. Having Medicare was associated with a decreased odds of an ACSC admission. Conclusions Specific characteristics are associated with a greater likelihood of an ACSC admission. Research should examine how these characteristics contribute to ACSC hospitalizations and findings should be linked to programs designed to serve as a safety-net for homeless patients to reduce hospitalizations

Disarmed anthrax toxin delivers antisense oligonucleotides and siRNA with high efficiency and low toxicity

Inefficient cytosolic delivery and vector toxicity contribute to the limited use of antisense oligonucleotides (ASOs) and siRNA as therapeutics. As anthrax toxin (Atx) accesses the cytosol, the purpose of this study was to evaluate the potential of disarmed Atx to deliver either ASOs or siRNA. We hypothesized that this delivery strategy would facilitate improved transfection efficiency while eliminating the toxicity seen for many vectors due to membrane destabilization. Atx complex formation with ASOs or siRNA was achieved via the in-frame fusion of either Saccharomyces cerevisiae GAL4 or Homo sapien sapien PKR (respectively) to a truncation of Atx lethal factor (LFn), which were used with Atx protective antigen (PA). Western immunoblotting confirmed the production of: LFN-GAL4, LFn-PKR and PA which were detected at ~ 45.9 kDa, ~ 37 kDa, and ~ 83 kDa respectively and small angle neutron scattering confirmed the ability of PA to form an annular structure with a radius of gyration of 7.0 ± 1.0 nm when placed in serum. In order to form a complex with LFn-GAL4, ASOs were engineered to contain a double-stranded region, and a cell free in vitro translation assay demonstrated that no loss of antisense activity above 30 pmol ASO was evident. The in vitro toxicity of both PA:LFn-GAL4:ASO and PA:LFn-PKR:siRNA complexes was low (IC50 > 100 μg/mL in HeLa and Vero cells) and subcellular fractionation in conjunction with microscopy confirmed the detection of LFn-GAL4 or LFn-PKR in the cytosol. Syntaxin5 (Synt5) was used as a model target gene to determine pharmacological activity. The PA:LFn-GAL4:ASO complexes had transfection efficiency approximately equivalent to Nucleofection® over a variety of ASO concentrations (24 h post-transfection) and during a 72 h time course. In HeLa cells, at 200 pmol ASO (with PA:LFN-GAL4), 5.4 ± 2.0% Synt5 expression was evident relative to an untreated control after 24 h. Using 200 pmol ASOs, Nucleofection® reduced Synt5 expression to 8.1 ± 2.1% after 24 h. PA:LFn-GAL4:ASO transfection of non- or terminally-differentiated THP-1 cells and Vero cells resulted in 35.2 ± 19.1%, 36.4 ± 1.8% and 22.9 ± 6.9% (respectively) Synt5 expression after treatment with 200 pmol of ASO and demonstrated versatility. Nucleofection® with Stealth RNAi™ siRNA reduced HeLa Synt5 levels to 4.6 ± 6.1% whereas treatment with the PA:LFn-PKR:siRNA resulted in 8.5 ± 3.4% Synt5 expression after 24 h (HeLa cells). These studies report for the first time an ASO and RNAi delivery system based upon protein toxin architecture that is devoid of polycations. This system may utilize regulated membrane back-fusion for the cytosolic delivery of ASOs and siRNA, which would account for the lack of toxicity observed. High delivery efficiency suggests further in vivo evaluation is warranted

Embryonic Lethality in Mice Lacking the Nuclear Factor of Activated T Cells 5 Protein Due to Impaired Cardiac Development and Function

Nuclear factor of activated T cells 5 protein (NFAT5) is thought to be important for cellular adaptation to osmotic stress by regulating the transcription of genes responsible for the synthesis or transport of organic osmolytes. It is also thought to play a role in immune function, myogenesis and cancer invasion. To better understand the function of NFAT5, we developed NFAT5 gene knockout mice. Homozygous NFAT5 null (NFAT5−/−) mouse embryos failed to develop normally and died after 14.5 days of embryonic development (E14.5). The embryos showed peripheral edema, and abnormal heart development as indicated by thinner ventricular wall and reduced cell density at the compact and trabecular areas of myocardium. This is associated with reduced level of proliferating cell nuclear antigen and increased caspase-3 in these tissues. Cardiomyocytes from E14.5 NFAT5−/− embryos showed a significant reduction of beating rate and abnormal Ca2+ signaling profile as a consequence of reduced sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) and ryanodine receptor (RyR) expressions. Expression of NFAT5 target genes, such as HSP 70 and SMIT were reduced in NFAT5−/− cardiomyocytes. Our findings demonstrated an essential role of NFAT5 in cardiac development and Ca2+ signaling. Cardiac failure is most likely responsible for the peripheral edema and death of NFAT5−/− embryos at E14.5 days

Small Cationic DDA:TDB Liposomes as Protein Vaccine Adjuvants Obviate the Need for TLR Agonists in Inducing Cellular and Humoral Responses

Most subunit vaccines require adjuvants in order to induce protective immune responses to the targeted pathogen. However, many of the potent immunogenic adjuvants display unacceptable local or systemic reactogenicity. Liposomes are spherical vesicles consisting of single (unilamellar) or multiple (multilamellar) phospholipid bi-layers. The lipid membranes are interleaved with an aqueous buffer, which can be utilised to deliver hydrophilic vaccine components, such as protein antigens or ligands for immune receptors. Liposomes, in particular cationic DDA:TDB vesicles, have been shown in animal models to induce strong humoral responses to the associated antigen without increased reactogenicity, and are currently being tested in Phase I human clinical trials. We explored several modifications of DDA:TDB liposomes - including size, antigen association and addition of TLR agonists – to assess their immunogenic capacity as vaccine adjuvants, using Ovalbumin (OVA) protein as a model protein vaccine. Following triple homologous immunisation, small unilamellar vesicles (SUVs) with no TLR agonists showed a significantly higher capacity for inducing spleen CD8 IFNγ responses against OVA in comparison with the larger multilamellar vesicles (MLVs). Antigen-specific antibody reponses were also higher with SUVs. Addition of the TLR3 and TLR9 agonists significantly increased the adjuvanting capacity of MLVs and OVA-encapsulating dehydration-rehydration vesicles (DRVs), but not of SUVs. Our findings lend further support to the use of liposomes as protein vaccine adjuvants. Importantly, the ability of DDA:TDB SUVs to induce potent CD8 T cell responses without the need for adding immunostimulators would avoid the potential safety risks associated with the clinical use of TLR agonists in vaccines adjuvanted with liposomes

Vaccine delivery by penetratin: mechanism of antigen presentation by dendritic cells

Cell-penetrating peptides (CPP) or membrane-translocating peptides such as penetratin from Antennapedia homeodomain or TAT from human immunodeficiency virus are useful vectors for the delivery of protein antigens or their cytotoxic (Tc) or helper (Th) T cell epitopes to antigen-presenting cells. Mice immunized with CPP containing immunogens elicit antigen-specific Tc and/or Th responses and could be protected from tumor challenges. In the present paper, we investigate the mechanism of class I and class II antigen presentation of ovalbumin covalently linked to penetratin (AntpOVA) by bone marrow-derived dendritic cells with the use of biochemical inhibitors of various pathways of antigen processing and presentation. Results from our study suggested that uptake of AntpOVA is via a combination of energy-independent (membrane fusion) and energy-dependent pathways (endocytosis). Once internalized by either mechanism, multiple tap-dependent or independent antigen presentation pathways are accessed while not completely dependent on proteasomal processing but involving proteolytic trimming in the ER and Golgi compartments. Our study provides an understanding on the mechanism of antigen presentation mediated by CPP and leads to greater insights into future development of vaccine formulations