Real-time synthesis of a humanlike agent in response to the user's moving image

This paper describes a parallel computing system and a software algorithm for real-time interaction between a human user and a synthesized, humanlike, moving image. The realistic humanlike agent on a monitor can recognize the palm position and finger motion (finger sign) of the user. She/he then tracks and gazes at the hand position to change her/his facial expression in response to the finger sign in real time. This visual software agent (VSA) is expected to play an important role in building an advanced human interface. We regard this type of interactive agent as avisual software robot. To achieve real-time image recognition and image synthesis, we have developed a parallel visual computer system the transputer network with visual interface to transputers (TN-VIT). The imagesynthesis speed of the TN-VIT is about 24 frames/s, including finger-sign recognition. Some samples of synthesized images and experimental results are shown.     

More Prominent Inflammatory Response to Pachyman than to Whole-Glucan Particle and Oat-β-Glucans in Dextran Sulfate-Induced Mucositis Mice and Mouse Injection through Proinflammatory Macrophages

(1→3)-β-D-glucans (BG) (the glucose polymers) are recognized as pathogen motifs, and different forms of BGs are reported to have various effects. Here, different BGs, including Pachyman (BG with very few (1→6)-linkages), whole-glucan particles (BG with many (1→6)-glycosidic bonds), and Oat-BG (BG with (1→4)-linkages), were tested. In comparison with dextran sulfate solution (DSS) alone in mice, DSS with each of these BGs did not alter the weight loss, stool consistency, colon injury (histology and cytokines), endotoxemia, serum BG, and fecal microbiome but Pachyman–DSS-treated mice demonstrated the highest serum cytokine elicitation (TNF-α and IL-6). Likewise, a tail vein injection of Pachyman together with intraperitoneal lipopolysaccharide (LPS) induced the highest levels of these cytokines at 3 h post-injection than LPS alone or LPS with other BGs. With bone marrow-derived macrophages, BG induced only TNF-α (most prominent with Pachyman), while LPS with BG additively increased several cytokines (TNF-α, IL-6, and IL-10); inflammatory genes (iNOS, IL-1β, Syk, and NF-κB); and cell energy alterations (extracellular flux analysis). In conclusion, Pachyman induced the highest LPS proinflammatory synergistic effect on macrophages, followed by WGP, possibly through Syk-associated interactions between the Dectin-1 and TLR-4 signal transduction pathways. Selection of the proper form of BGs for specific clinical conditions might be beneficial.     

Uremia-Induced Gut Barrier Defect in 5/6 Nephrectomized Mice Is Worsened by Candida Administration through a Synergy of Uremic Toxin,Lipopolysaccharide, and (1➔3)-β-D-Glucan,but Is Attenuated by Lacticaseibacillus rhamnosus L34

A chronic kidney disease (CKD) causes uremic toxin accumulation and gut dysbiosis, which further induces gut leakage and worsening CKD. Lipopolysaccharide (LPS) of Gram-negative bacteria and (1➔3)-β-D-glucan (BG) of fungi are the two most abundant gut microbial molecules. Due to limited data on the impact of intestinal fungi in CKD mouse models, the influences of gut fungi and Lacticaseibacillus rhamnosus L34 (L34) on CKD were investigated using oral C. albicans-administered 5/6 nephrectomy (5/6Nx) mice. At 16 weeks post-5/6Nx, Candida-5/6Nx mice demonstrated an increase in proteinuria, serum BG, serum cytokines (tumor necrotic factor-α; TNF-α and interleukin-6), alanine transaminase (ALT), and level of fecal dysbiosis (Proteobacteria on fecal microbiome) when compared to non-Candida-5/6Nx. However, serum creatinine, renal fibrosis, or gut barrier defect (FITC-dextran assay and endotoxemia) remained comparable between Candida- versus non-Candida-5/6Nx. The probiotics L34 attenuated several parameters in Candida-5/6Nx mice, including fecal dysbiosis (Proteobacteria and Bacteroides), gut leakage (fluorescein isothiocyanate (FITC)-dextran), gut-derived uremic toxin (trimethylamine-N-oxide; TMAO) and indoxyl sulfate; IS), cytokines, and ALT. In vitro, IS combined with LPS with or without BG enhanced the injury on Caco-2 enterocytes (transepithelial electrical resistance and FITC-dextran permeability) and bone marrow-derived macrophages (supernatant cytokines (TNF-α and interleukin-1 β; IL-1β) and inflammatory genes (TNF-α, IL-1β, aryl hydrocarbon receptor, and nuclear factor-κB)), compared with non-IS activation. These injuries were attenuated by the probiotics condition media. In conclusion, Candida administration worsens kidney damage in 5/6Nx mice through systemic inflammation, partly from gut dysbiosis-induced uremic toxins, which were attenuated by the probiotics. The additive effects on cell injury from uremic toxin (IS) and microbial molecules (LPS and BG) on enterocytes and macrophages might be an important underlying mechanism.     

Enhanced Bacteremia in Dextran Sulfate-Induced Colitis in Splenectomy Mice Correlates with Gut Dysbiosis and LPS Tolerance

Because both endotoxemia and gut dysbiosis post-splenectomy might be associated with systemic infection, the susceptibility against infection was tested by dextran sulfate solution (DSS)-induced colitis and lipopolysaccharide (LPS) injection models in splenectomy mice with macrophage experiments. Here, splenectomy induced a gut barrier defect (FITC-dextran assay, endotoxemia, bacteria in mesenteric lymph nodes, and the loss of enterocyte tight junction) and gut dysbiosis (increased Proteobacteria by fecal microbiome analysis) without systemic inflammation (serum IL-6). In parallel, DSS induced more severe mucositis in splenectomy mice than sham-DSS mice, as indicated by mortality, stool consistency, gut barrier defect, serum cytokines, and blood bacterial burdens. The presence of green fluorescent-producing (GFP) E. coli in the spleen of sham-DSS mice after an oral gavage supported a crucial role of the spleen in the control of bacteria from gut translocation. Additionally, LPS administration in splenectomy mice induced lower serum cytokines (TNF-α and IL-6) than LPS-administered sham mice, perhaps due to LPS tolerance from pre-existing post-splenectomy endotoxemia. In macrophages, LPS tolerance (sequential LPS stimulation) demonstrated lower cell activities than the single LPS stimulation, as indicated by the reduction in supernatant cytokines, pro-inflammatory genes (iNOS and IL-1β), cell energy status (extracellular flux analysis), and enzymes of the glycolysis pathway (proteomic analysis). In conclusion, a gut barrier defect after splenectomy was vulnerable to enterocyte injury (such as DSS), which caused severe bacteremia due to defects in microbial control (asplenia) and endotoxemia-induced LPS tolerance. Hence, gut dysbiosis and gut bacterial translocation in patients with a splenectomy might be associated with systemic infection, and gut-barrier monitoring or intestinal tight-junction strengthening may be useful.     

Amphotericin B-loaded solid lipid nanoparticles (SLNs) and nanostructured lipid carrier (NLCs): effect of drug loading and biopharmaceutical characterizations

The aim of this study was to further investigate the effect of drug loading, drug entrapment efficiency, the drug release profiles and biopharmaceutical point of views of amphotericin B (AmB) lipid formulations, that is, degree of aggregation by UV-spectroscopy, in vitro hemolytic and antifungal activities. The optimum drug loading was 2.5% by weight corresponded to lipid fraction in formulation. Increasing of the drug entrapment was achieved by blending small amount of phospholipid in solid lipid nanoparticle (SLN) dispersions. All AmB lipid dispersions were less aggregated species and hemolytic response than Fungizone^® indicating that lipid nanoparticles could reduce its toxicity. The sustained release profiles of AmB formulations depended on its aggregated form and entrapment efficiency. Too high AmB loaded (5% w/w) showed a biphasic drug release profile probably due to some amounts of drug deposited on the nanosphere surface including in continuous phase which promptly released. For in vitro antifungal testing, all AmB lipid formulations were equal and more effective than both AmB itself and Fungizone^®. These observations suggested that AmB loaded SLNs, nanostructured lipid carriers and modified SLNs by blending lecithin could enhance AmB solubility, prolong release characteristics, reduce toxicity and improve antifungal activity.     

Deproteinised natural rubber used as a controlling layer membrane in reservoir-type nicotine transdermal patches

Reservoir-type nicotine transdermal patches (NTPs), composed of a concentrated nicotine solution embedded between a backing layer and a controlling layer membrane, were constructed by a heat-sealing technique. The aim of this research was the preparation of a novel controlling layer membrane from deproteinised natural rubber latex (DNRL). The ultimate tensile strength and percentage of elongation at breakage of the DNRL membrane were 0.23 ± 0.04 MPa and 604.46 ± 95.38%, respectively. The DNRL membrane existed as an amorphous phase and was poorly hygroscopic and dense. FT-IR and DSC analysis demonstrated that the membrane consisted almost entirely of isoprene functional groups with a T_g of −64.79 °C. The effects of the DNRL membrane thickness (100–300 μm) and different nicotine concentrations in the reservoir (1.75–4.25 mg/cm²) on the nicotine release rate and nicotine permeation through a pig skin membrane were studied in vitro. The in vitro nicotine release rate and skin permeation rate increased with decreasing membrane thickness and increasing nicotine content in the reservoir. The release and permeation profiles followed first- and zero-order kinetics, respectively. The release and permeation performance was similar to a commercially available Nicotinell TTS-20 patch. The newly developed NTPs were stable under storage in a tightly sealed container at 4 °C or at ambient temperature for up to 3 months. Thus, DNRL is suitable for use as a controlling layer membrane in NTPs in transdermal drug delivery systems.     

Nano-FTIR Absorption Spectroscopy of Molecular Fingerprints at 20 nm Spatial Resolution

We demonstrate Fourier transform infrared nanospectroscopy (nano-FTIR) based on a scattering-type scanning near-field optical microscope (s-SNOM) equipped with a coherent-continuum infrared light source. We show that the method can straightforwardly determine the infrared absorption spectrum of organic samples with a spatial resolution of 20 nm, corresponding to a probed volume as small as 10 zeptoliter (10(-20) L). Corroborated by theory, the nano-FTIR absorption spectra correlate well with conventional FTIR absorption spectra, as experimentally demonstrated with poly(methyl methacrylate) (PMMA) samples. Nano-FTIR can thus make use of standard infrared databases of molecular vibrations to identify organic materials in ultrasmall quantities and at ultrahigh spatial resolution. As an application example we demonstrate the identification of a nanoscale PDMS contamination on a PMMA sample.