Stable, chronic in-vivo recordings from a fully wireless subdural-contained 65,536-electrode brain-computer interface device.

Minimally invasive, high-bandwidth brain-computer-interface (BCI) devices can revolutionize human applications. With orders-of-magnitude improvements in volumetric efficiency over other BCI technologies, we developed a 50-µm-thick, mechanically flexible micro-electrocorticography (µECoG) BCI, integrating 256×256 electrodes, signal processing, data telemetry, and wireless powering on a single complementary metal-oxide-semiconductor (CMOS) substrate containing 65,536 recording and 16,384 stimulation channels, from which we can simultaneously record up to 1024 channels at a given time. Fully implanted below the dura, our chip is wirelessly powered, communicating bi-directionally with an external relay station outside the body. We demonstrated chronic, reliable recordings for up to two weeks in pigs and up to two months in behaving non-human primates from somatosensory, motor, and visual cortices, decoding brain signals at high spatiotemporal resolution.

A Wireless, Mechanically Flexible, 25µm-Thick, 65,536-Channel Subdural Surface Recording and Stimulating Microelectrode Array with Integrated Antennas.

This paper presents a fully wireless microelectrode array (MEA) system-on-chip (SoC) with 65,536 electrodes for non-penetrative cortical recording and stimulation, featuring a total sensing area of 6.8mm×7.4mm with a 26.5µm×29µm electrode pitch. Sensing, data telemetry, and powering are monolithically integrated on a single chip, which is made mechanically flexible to conform to the surface of the brain by substrate removal to a total thickness of 25µm allowing it to be contained entirely in the subdural space under the skull.

Post-Synthesis Functionalization Enables Fine-Tuning the Molecular-Sieving Properties of Zeolites for Light Olefin/Paraffin Separations.

Zeolite molecular sieves are widely used in gas separation and shape-selective catalysis, but these applications often require discriminating differences as little as 0.1 Å. Molecular sieving with such size selectivity demands zeolites with highly tunable pore diameters and adsorption properties, which are technically challenging to prepare. Nevertheless, it is shown that a wide range of organic functional groups can be covalently functionalized onto the interior pore walls of the zeolites, MOR, LTL, FAU, and MFI, to systematically "tune" their effective pore diameters with respect to the size of organic groups. For organic functionalization, small and aggressive organic electrophiles are used (e.g., organo-halide and -diazonium) as grafting agents, which are accessible to the intracrystalline void space, forming a C-Ozeolite bond in a reaction with a bridging oxygen as proved by multiple analysis data. It is demonstrated that the post-functionalization can be used to tailor the molecular sieving action of a parent zeolite to give size-selective adsorbents for light olefin/paraffin separations. 4-Methoxybenzene-functionalized MOR separates ethylene from ethane with an ideal-adsorbed-solution-theory selectivity of ≈5873, whereas toluene-grafted MOR completely separates propylene/propane mixtures. Therefore, tailoring the molecular-sieving properties of zeolites by organic functionalization broadens their applications to challenging separations.

Effects of Angelica gigas Nakai as an Anti-Inflammatory Agent in In Vitro and In Vivo Atopic Dermatitis Models.

We investigated the cellular and molecular mechanisms mediating the effects of Angelica gigas Nakai extract (AGNE) through the mitogen-activated protein kinases (MAPKs)/NF-κB pathway using in vitro and in vivo atopic dermatitis (AD) models. We examined the effects of AGNE on the expression of proinflammatory cytokines and chemokines in human mast cell line-1 (HMC-1) cells. Compound 48/80-induced pruritus and 2,4-dinitrochlorobenzene- (DNCB-) induced AD-like skin lesion mouse models were also used to investigate the antiallergic effects of AGNE. AGNE reduced histamine secretion, production of proinflammatory cytokines including interleukin- (IL-) 1ß, IL-4, IL-6, IL-8, and IL-10, and expression of cyclooxygenase- (COX-) 2 in HMC-1 cells. Scratching behavior and DNCB-induced AD-like skin lesions were also attenuated by AGNE administration through the reduction of serum IgE, histamine, tumor necrosis factor-α (TNF-α), IL-6 levels, and COX-2 expression in skin tissue from mouse models. Furthermore, these inhibitory effects were mediated by the blockade of the MAPKs and NF-κB pathway. The findings of this study proved that AGNE improves the scratching behavior and atopy symptoms and reduces the activity of various atopy-related mediators in HMC-1 cells and mice model. These results suggest the AGNE has a therapeutic potential in anti-AD.

Highly selective adsorption of CO over CO2 in a Cu(I)-chelated porous organic polymer.

Cu(I) species were successfully chelated to nitrogen atoms in a nitrogen-rich porous organic polymer (SNW-1) by mixing with a CuCl solution (Scheme 1). Although pristine SNW-1 adsorbs CO2 better than CO, Cu(I)-incorporated SNW-1 (nCu(I)@SNW-1) shows selective CO adsorption over CO2 because of the π-complexation of CO with Cu(I). To the best of our knowledge, this is the first CO/CO2 selectivity observed for POP-based materials. 1.3Cu(I)@SNW-1 exhibits high CO/CO2 selectivity (23) at 1bar and a large CO working capacity (0.6mmol/g) at 0.1-1bar. Moreover, the breakthrough and thermogravimetric experiments show that 1.3Cu(I)@SNW-1 can effectively separate CO from CO2 under dynamic mixture conditions and can be easily regenerated under mild regeneration conditions without heating the column. Furthermore, 1.3Cu(I)@SNW-1 exhibited a good stability under exposure to atmospheric air for 3h or 9h. These results suggest that chelating Cu(I) species to a nitrogen-rich porous organic polymer can be an efficient strategy to separate and recover CO from CO/CO2 mixtures.

Synthesis of CuCl/Boehmite adsorbents that exhibit high CO selectivity in CO/CO2 separation.

We developed nanoporous adsorbent exhibiting unprecedented performance in separation of toxic carbon monoxide (CO). The adsorbent was prepared by dispersing CuCl on mesoporous boehmite via thermal monolayer dispersion route. A key point of the present synthesis is dispersing optimized amount of CuCl on the boehmite at a moderate temperature to maintain the characteristics of the boehmite. We performed a systematic study to reveal that a CuCl/boehmite composite (30wt% CuCl in total) thermally treated at 573K was the best optimized sample for CO separation. The CuCl/boehmite had a high capacity of CO adsorption (1.56mmolg-1) and an exceedingly low capacity of CO2 adsorption (0.13mmolg-1) under 100kPa of each gas at 293K. The CO/CO2 separation factor was 12.4. To the best of our knowledge, this value is the best on record. The achievement of this work is attributed to finding a new type of suitable supporting material: boehmite. The boehmite has a high affinity to CuCl, exhibits excellent dispersion of the CuCl, and achieves a superior CO adsorption capacity. However, it has a weak interaction with CO2. The CuCl/boehmite composite is a promising adsorbent for selective separation of CO from combustion exhaust and industrial off-gas streams.

Power partial-discard strategy to obtain improved performance for simulated moving bed chromatography.

A novel power partial-discard (PPD) strategy was developed as a variant of the partial-discard (PD) operation to further improve the separation performance of the simulated moving bed (SMB) process. The PPD operation varied the flow rates of discard streams by introducing a new variable, the discard amount (DA) as well as varying the reported variable, discard length (DL), while the conventional PD used fixed discard flow rates. The PPD operations showed significantly improved purities in spite of losses in recoveries. Remarkably, the PPD operation could provide more enhanced purity for a given recovery or more enhanced recovery for a given purity than the PD operation. The two variables, DA and DL, in the PPD operation played a key role in achieving the desired purity and recovery. The PPD operations will be useful for attaining high-purity products with reasonable recoveries.

Protective effect of decursin and decursinol angelate-rich Angelica gigas Nakai extract on dextran sulfate sodium-induced murine ulcerative colitis.

OBJECTIVE: To investigate the anti-inflammatory effects of decursin and decursinol angelate-rich Angelica gigas Nakai (AGNE) on dextran sulfate sodium (DSS)-induced murine ulcerative colitis (UC). METHODS: The therapeutic effect of an AGNE was analyzed in a mouse model of UC induced by DSS. Disease activity index values were measured by clinical signs such as a weight loss, stool consistency, rectal bleeding and colon length. A histological analysis was performed using hematoxylin and eosin staining. Key inflammatory cytokines and mediators including IL-6, TNF-α, PGE2, COX-2 and HIF-1α were assayed by enzyme-linked immunosorbent assay or western blotting. RESULTS: Treatment with the AGNE at 10, 20, and 40 mg/kg alleviated weight loss, decreased disease activity index scores, and reduced colon shortening in mice with DSS-induced UC. AGNE inhibited the production of IL-6 and TNF-α in serum and colon tissue. Moreover, AGNE suppressed the increased expression of COX-2 and HIF-1α and the increased production of PGE2 in colon tissue were observed in mice with DSS-induced UC. Additionally, histological damage was also alleviated by AGNE treatment. CONCLUSIONS: The findings of this study verified that AGNE significantly improves clinical symptoms and reduces the activity of various inflammatory mediators. These results indicate the AGNE has the therapeutic potential in mice with DSS-induced UC.

Angelica gigas Ameliorates Hyperglycemia and Hepatic Steatosis in C57BL/KsJ-db/db Mice via Activation of AMP-Activated Protein Kinase Signaling Pathway.

The prevention and management of type 2 diabetes mellitus has become a major global public health challenge. Decursin, an active compound of Angelica gigas Nakai roots, was recently reported to have a glucose-lowering activity. However, the antidiabetic effect of Angelica gigas Nakai extract (AGNE) has not yet been investigated. We evaluated the effects of AGNE on glucose homeostasis in type 2 diabetic mice and investigated the underlying mechanism by which AGNE acts. Male C57BL/KsJ-db/db mice were treated with either AGNE (10 mg/kg, 20 mg/kg, and 40 mg/kg) or metformin (100 mg/kg) for 8 weeks. AGNE supplementation (20 and 40 mg/kg) significantly decreased fasting glucose and insulin levels, decreased the areas under the curve of glucose in oral glucose tolerance and insulin tolerance tests, and improved homeostatic model assessment-insulin resistant (HOMA-IR) scores. AGNE also ameliorated hepatic steatosis, hyperlipidemia, and hypercholesterolemia. Mechanistic studies suggested that the glucose-lowering effect of AGNE was mediated by the activation of AMP activated protein kinase, Akt, and glycogen synthase kinase-3[Formula: see text]. AGNE can potentially improve hyperglycemia and hepatic steatosis in patients with type 2 diabetes.

A 72 × 60 Angle-Sensitive SPAD Imaging Array for Lens-less FLIM.

We present a 72 × 60, angle-sensitive single photon avalanche diode (A-SPAD) array for lens-less 3D fluorescence lifetime imaging. An A-SPAD pixel consists of (1) a SPAD to provide precise photon arrival time where a time-resolved operation is utilized to avoid stimulus-induced saturation, and (2) integrated diffraction gratings on top of the SPAD to extract incident angles of the incoming light. The combination enables mapping of fluorescent sources with different lifetimes in 3D space down to micrometer scale. Futhermore, the chip presented herein integrates pixel-level counters to reduce output data-rate and to enable a precise timing control. The array is implemented in standard 180 nm complementary metal-oxide-semiconductor (CMOS) technology and characterized without any post-processing.

Exciton Recombination, Energy-, and Charge Transfer in Single- and Multilayer Quantum-Dot Films on Silver Plasmonic Resonators.

We examine exciton recombination, energy-, and charge transfer in multilayer CdS/ZnS quantum dots (QDs) on silver plasmonic resonators using photoluminescence (PL) and excitation spectroscopy along with kinetic modeling and simulations. The exciton dynamics including all the processes are strongly affected by the separation distance between QDs and silver resonators, excitation wavelength, and QD film thickness. For a direct contact or very small distance, interfacial charge transfer and tunneling dominate over intrinsic radiative recombination and exciton energy transfer to surface plasmons (SPs), resulting in PL suppression. With increasing distance, however, tunneling diminishes dramatically, while long-range exciton-SP coupling takes place much faster (>6.5 ns) than intrinsic recombination (~200 ns) causing considerable PL enhancement. The exciton-SP coupling strength shows a strong dependence on excitation wavelengths, suggesting the state-specific dynamics of excitons and the down-conversion of surface plasmons involved. The overlayers as well as the bottom monolayer of QD multilayers exhibit significant PL enhancement mainly through long-range exciton-SP coupling. The overall emission behaviors from single- and multilayer QD films on silver resonators are described quantitatively by a photophysical kinetic model and simulations. The present experimental and simulation results provide important and useful design rules for QD-based light harvesting applications using the exciton-surface plasmon coupling.

Magnetic nanoparticle based purification and enzyme-linked immunosorbent assay using monoclonal antibody against enrofloxacin.

Monoclonal anti-enrofloxacin antibody was prepared for a direct competitive enzyme-linked immunosorbent assay (ELISA) and purification system using monoclonal antibody (mAb) coupled magnetic nanoparticles (MNPs). The IC50 values of the developed mAb for enrofloxacin (ENR), ciprofloxacin, difloxacin, sarafloxacin, pefloxacin, and norfloxacin were 5.0, 8.3, 9.7, 21.7, 36.0, and 63.7 ng/mL, respectively. The lowest detectable level of ENR was 0.7 ng/mL in the prepared ELISA system. To validate the developed ELISA in the food matrix, known amounts of ENR were spiked in meat and egg samples at 10, 20 and 30 ng/mL. Recoveries for ENR ranged from 72.9 to 113.16% with a coefficient of variation (CV) of 2.42 to 10.11%. The applicability of the mAb-MNP system was verified by testing the recoveries for ENR residue in three different matrices. Recoveries for ENR ranged from 75.16 to 86.36%, while the CV ranged from 5.08 to 11.53%. Overall, ENR-specific monoclonal antibody was prepared and developed for use in competitive to ELISAs for the detection of ENR in animal meat samples. Furthermore, we suggest that a purification system for ENR using mAb-coupled MNPs could be useful for determination of ENR residue in food.

Preparation of Tunable (BaSrMg)O for Oxygen Chemisorption: Formation Mechanism and Characterization.

Composition-tunable single-phase three-component alkaline earth oxide of (BaSrMg)O was prepared based on the consecutive precipitation and thermal decomposition of (BaSrMg)CO3. First, the single-phase (BaSrMg)CO3 was coprecipitated via ion self-assembly, phase-transformation, and agglomeration. The element composition of (BaSrMg)CO3 could be simply tuned by the composition of the reactants. Then, (BaSrMg)CO3 was converted to (BaSrMg)O under an H2 atmosphere at 750 °C. This (BaSrMg)O showed fast chemisorption-desorption responses with oxygen chemisorption rate: t80 = 3.9 min and desorption rate: t80 = 14 min and a high thermal stability for the redox reaction of BaO-BaO2. In addition, the chemisorption capacity of (BaSrMg)O (4.39% Sr composition) is ∼1.92 mmol/g, which is much higher than the chemisorption capacity of BaO/MgO at 1.75 mmol/g (Jin et al., Ind. Eng. Chem. Res., 2005, 44, 2942), while the transient oxygen pressure for the redox reaction of (BaSrMg)O (4.39% Sr composition) was significantly enhanced from 76 to 135 mmHg due to the inclusion of Sr in (BaSrMg)O. The transient oxygen pressure could be further improved via adjusting the Sr composition in (BaSrMg)O. Consequently, the tunable (BaSrMg)O has a high potential as a chemisorbent for the industrial application of oxygen separation.

Biology and host response to Cyprinid herpesvirus 3 infection in common carp.

Viruses from the family Alloherpesviridae form an aquatic clade of herpesviruses infecting fish and amphibia. Diseases caused by these herpesviruses are of increasing importance because of the high morbidity and mortality associated with the infection, and the difficulties in diagnosing latently infected carriers. Cyprinid herpesvirus 3 (CyHV-3) induces a severe disease and mortality in common carp and thus greatly affects carp aquaculture and trade. This review summarises advancements in the understanding of the infection process and the current knowledge on immune responses of carp to CyHV-3. A focus is laid on host genetics and immunity responsible for resistance/survival from the disease and on the viral mechanisms accountable for evasion of carp immune responses. As current knowledge of immune responses to CyHV-3 is still limited, perspectives for future studies are outlined. Analysing CyHV-3 fish-host interactions will be useful and thought-provoking for a basic understanding of fish immune responses.

Comparative genomic characterization of three Streptococcus parauberis strains in fish pathogen, as assessed by wide-genome analyses.

Streptococcus parauberis, which is the main causative agent of streptococcosis among olive flounder (Paralichthys olivaceus) in northeast Asia, can be distinctly divided into two groups (type I and type II) by an agglutination test. Here, the whole genome sequences of two Japanese strains (KRS-02083 and KRS-02109) were determined and compared with the previously determined genome of a Korean strain (KCTC 11537). The genomes of S. parauberis are intermediate in size and have lower GC contents than those of other streptococci. We annotated 2,236 and 2,048 genes in KRS-02083 and KRS-02109, respectively. Our results revealed that the three S. parauberis strains contain different genomic insertions and deletions. In particular, the genomes of Korean and Japanese strains encode different factors for sugar utilization; the former encodes the phosphotransferase system (PTS) for sorbose, whereas the latter encodes proteins for lactose hydrolysis, respectively. And the KRS-02109 strain, specifically, was the type II strain found to be able to resist phage infection through the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system and which might contribute valuably to serologically distribution. Thus, our genome-wide association study shows that polymorphisms can affect pathogen responses, providing insight into biological/biochemical pathways and phylogenetic diversity.

Comparative genome analysis of fish and human isolates of Mycobacterium marinum.

Mycobacterium marinum is a major causative agent of mycobacteriosis in fish that has a broad range of hosts, including in human isolates. So far, genomic analyses have focused on the human isolate. Here, we compared the draft genome sequences of two strains of M. marinum isolated from fish (MB2 and Europe) with the M. marinum M isolated from humans. M. marinum MB2 and Europe have single, circular chromosomes of 6,134,389 and 6,029,340 bp, and average G + C contents of 65.7 and 65.5 %, respectively. A total of 5,464 coding DNA sequences were annotated in both M. marinum MB2 and Europe genome. Dot plot analyses showed that M. marinum MB2 and Europe were closer to M. marinum M when compared to three other Mycobacterium species. The insertion/deletion gene analysis showed that M. marinum MB2 and Europe contained 342 and 487 genes that were not found in M. marinum M, and lacked 625 and 776 genes found in M. marinum M, respectively. Most of the inserted and deleted genes were classified in the fatty acid, lipid, and isoprenoid subsystem and the virulence, disease, and defense subsystem. Therefore, these results provide insights into the genomic diversity associated with variable hosts and pathogens.

wksl3, a New biocontrol agent for Salmonella enterica serovars enteritidis and typhimurium in foods: characterization, application, sequence analysis, and oral acute toxicity study.

Of the Salmonella enterica serovars, S. Enteritidis and S. Typhimurium are responsible for most of the Salmonella outbreaks implicated in the consumption of contaminated foods in the Republic of Korea. Because of the widespread occurrence of antimicrobial-resistant Salmonella in foods and food processing environments, bacteriophages have recently surfaced as an alternative biocontrol tool. In this study, we isolated a virulent bacteriophage (wksl3) that could specifically infect S. Enteritidis, S. Typhimurium, and several additional serovars. Transmission electron microscopy revealed that phage wksl3 belongs to the family Siphoviridae. Complete genome sequence analysis and bioinformatic analysis revealed that the DNA of phage wksl3 is composed of 42,766 bp with 64 open reading frames. Since it does not encode any phage lysogeny factors, toxins, pathogen-related genes, or food-borne allergens, phage wksl3 may be considered a virulent phage with no side effects. Analysis of genetic similarities between phage wksl3 and four of its relatives (SS3e, vB_SenS-Ent1, SE2, and SETP3) allowed wksl3 to be categorized as a SETP3-like phage. A single-dose test of oral toxicity with BALB/c mice resulted in no abnormal clinical observations. Moreover, phage application to chicken skin at 8°C resulted in an about 2.5-log reduction in the number of Salmonella bacteria during the test period. The strong, stable lytic activity, the significant reduction of the number of S. Enteritidis bacteria after application to food, and the lack of clinical symptoms of this phage suggest that wksl3 may be a useful agent for the protection of foods against S. Enteritidis and S. Typhimurium contamination.

Comparative sequence analysis of a multidrug-resistant plasmid from Aeromonas hydrophila.

Aeromonas hydrophila is a pathogenic bacterium that has been implicated in fish, animal, and human disease. Recently, a multidrug resistance (MDR) plasmid, pR148, was isolated from A. hydrophila obtained from a tilapia (Oreochromis niloticus) farm in Thailand. pR148 is a 165,906-bp circular plasmid containing 147 coding regions showing highest similarity to pNDM-1_Dok1, an MDR plasmid isolated from a human pathogen. pR148 was also very similar to other IncA/C plasmids isolated from humans, animals, food, and fish. pR148 contains a mercuric resistance operon and encodes the complete set of genes for the type 4 secretion system. pR148 encodes a Tn21 type transposon. This transposon contains the drug resistance genes qacH, bla(OXA-10), aadA1, and sul1 in a class 1 integron; tetA and tetR in transposon Tn1721; and catA2 and a duplicate sul1 in a locus showing 100% similarity to IncU plasmids isolated from fish. The bla(OXA-10) and aadA1 genes showed 100% similarity to those from the Acinetobacter baumannii AYE genome. The similarity of pR148 to a human pathogen-derived plasmid indicates that the plasmids were either transferred between different genera or that they are derived from a common origin. Previous studies have shown that IncA/C plasmids retain a conserved backbone, while the accessory region points to lateral gene transfer. These observations point out the dangers of indiscriminate use of antibiotics in humans and in animals and the necessity of understanding how drug resistance determinants are disseminated and transferred.

Bacterial classification of fish-pathogenic Mycobacterium species by multigene phylogenetic analyses and MALDI Biotyper identification system.

Mycobacterium marinum is difficult to distinguish from other species of Mycobacterium isolated from fish using biochemical methods. Here, we used genetic and proteomic analyses to distinguish three Mycobacterium strains: M. marinum strains MB2 and Europe were isolated from tropical and marine fish in Thailand and Europe, and Mycobacterium sp. 012931 strain was isolated from yellowtail in Japan. In phylogenetic trees based on gyrB, rpoB, and Ag85B genes, Mycobacterium sp. 012931 clustered with M. marinum strains MB2 and Europe, but in trees based on 16S rRNA, hsp65, and Ag85A genes Mycobacterium sp. 012931 did not cluster with the other strains. In proteomic analyses using a Bruker matrix-assisted laser desorption ionization Biotyper, the mass profile of Mycobacterium sp. 012931 differed from the mass profiles of the other two fish M. marinum strains. Therefore, Mycobacterium sp. 012931 is similar to M. marinum but is not the same, suggesting that it could be a subspecies of M. marinum.

Variable domain antibodies specific for viral hemorrhagic septicemia virus (VHSV) selected from a randomized IgNAR phage display library.

Phage display libraries are used to screen for nucleotide sequences that encode immunoglobulin variable (V) regions that are specific for a target antigen. We previously constructed an immunoglobulin new antigen receptor (IgNAR) phage display library. Here we used this library to obtain an IgNAR V region that is specific for viral hemorrhagic septicemia virus (VHSV). A phage clone (clone 653) was found to be specific for VHSV by the biopanning method. The V region of clone 653 was used to construct a 6 × His tagged recombinant IgNAR-653 V protein (rIgNAR-653) using the Escherichia coli pET system. The rIgNAR-653 protein bound specifically to VHSV, confirming its activity.