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Coronavirus disease-2019 (COVID-19) causes severe pneumonia and acute respiratory distress syndrome. According to the current consensus, immunosuppressants, such as dexamethasone and anti-interleukin-6 receptor monoclonal antibodies, are therapeutic medications in the early stages of infection. However, in critically ill patients, viral, fungal, and bacterial coinfection results in higher mortality. We conducted a single-center, retrospective analysis of 29 mechanically ventilated patients with artificial airways. Patients were adults with confirmed COVID-19 infection and severe pneumonia. Acute respiratory distress syndrome was diagnosed according to the Kigali modification of the Berlin definition. Six patients had invasive pulmonary aspergillosis coinfection based on elevated serum galactomannan levels and/or bronchoalveolar lavage fluid. We present two cases with brief histories and available clinical data. We also conducted a literature review to determine whether immunosuppressants, such as tocilizumab, increase infection risk or invasive aspergillosis in patients with COVID-19. There is no conclusive evidence to suggest that tocilizumab increases coinfection risk. However, further studies are needed to determine the optimal dose, between-dose interval, and timing of tocilizumab administration in patients with COVID-19. [ABSTRACT FROM AUTHOR]

Doping sorted graphene quantum dots (GQDs) with heteroatoms and functionalizing them with amino acid could improve their radiative recombination and two-photon properties—including their excitation-wavelength-independent photoluminescence from the ultraviolet to the near-infrared-I (NIR-I) region, absorption, quantum yield, absolute cross section, lifetime, and radiative-to-nonradiative decay ratio—under two-photon excitation (TPE) at a low excitation energy and short photoexcitation duration, as determined using a self-made optical microscopy system with a femtosecond Ti–sapphire laser. Four types of sorted GQDs were investigated: undoped GQDs, nitrogen-doped GQDs (N-GQDs), amino-functionalized GQDs (amino-GQDs), and N-doped and amino-functionalized GQDs (amino-N-GQDs). Among them, the sorted amino-N-GQDs are effective as a two-photon photosensitizer and generate the highest quantity of reactive oxygen species for the elimination of multidrug-resistant cancer cells through two-photon photodynamic therapy (PDT). Larger amino-N-GQDs result in a greater number of C–N and N–functionalities, leading to a superior photochemical effect and more favorable intrinsic luminescence properties, making the dots effective contrast agents for tracking and localizing cancer cells during in-depth bioimaging in a three-dimensional biological environment under TPE in the NIR-II region. Overall, this study highlights the potential of large amino-N-GQDs as a material for future application to dual-modality two-photon PDT and biomedical imaging. • Highly efficient self-made femtosecond Ti-sapphire laser optical system. • Excitation and emission wavelengths in the NIR-I/II regions for efficient detection. • Size-selective sieving fabricates materials with tunable photochemical properties. • Excitation-wavelength-independent two-photon luminescence emission for bioimaging. • N-functionalities in tunable dual-modality NIR-I/II two-photon PDT and illumination. [ABSTRACT FROM AUTHOR]

• This quadrivalent influenza vaccine was given to subjects 3 to 17 years of age. • Immunogenicity was determined by high seroconversion and seroconversion rates. • This vaccine is well tolerated with a favorable safety profile. • A quadrivalent vaccine may overcome the mismatches with influenza B strains. Quadrivalent influenza vaccines are particularly valuable during seasons in which a mismatch occurs between the predicted influenza B lineage for the trivalent influenza vaccine and the circulating strain. This study evaluated the immunogenicity and safety of a quadrivalent inactivated influenza vaccine AdimFlu-S manufactured in Taiwan for the 2016–2017 influenza season in healthy children. A total of 174 healthy children aged 3 to 17 years old were separated into 3 groups (Group A: 3–8 years old, vaccine naïve; Group B: 3–8 years old, vaccine non-naïve; Group C: 9–17 years old, any vaccine status). Sera was collected pre and post vaccination for each participant. A hemagglutination inhibition (HAI) assay was utilized to calculate geometric mean titer (GMT), seroprotection rate, and seroconversion rate. All enrolled participants completed the study. For the four vaccine strains four weeks after the last vaccination, geometric mean titer ratios (GMTRs) were between 2.9 and 20.9, seroconversion rates were between 42.9% and 90.9%, and seroprotection rates were all above 96.4%. This achieved all immunogenicity endpoints and fulfilled the criteria of the European Medical Agency's Committee for Medicinal Products for Human Use (CHMP). No serious adverse events (AEs) were reported during the follow-up period of 6 months. This quadrivalent influenza vaccine is demonstrated to be well tolerated and displays robust immunogenicity for each influenza strain. This could potentially improve protection against the antigenically distinct B/Yamagata and B/Victoria lineages. [ABSTRACT FROM AUTHOR]

Accumulating evidence suggests AKT1 and DRD2-AKT-GSK3 signaling involvement in schizophrenia. AKT1 activity is also required for lithium, a GSK3 inhibitor, to modulate mood-related behaviors. Notably, GSK3 inhibitor significantly alleviates behavioral deficits in Akt1−/− female mice, whereas typical/atypical antipsychotics have no effect. In agreement with adjunctive therapy with lithium in treating schizophrenia, our data mining indicated that the average utilization rates of lithium in the Taiwan National Health Insurance Research Database from 2002 to 2013 are 10.9% and 6.63% in inpatients and outpatients with schizophrenia, respectively. Given that lithium is commonly used in clinical practice, it is of great interest to evaluate the effect of lithium on alleviating Akt1-related deficits. Taking advantage of Akt1+/− mice to mimic genetic deficiency in patients, behavioral impairments were replicated in female Akt1+/− mice but were alleviated by subchronic lithium treatment for 13 days. Lithium also effectively alleviated the observed reduction in phosphorylated GSK3α/β expression in the brains of Akt1+/− mice. Furthermore, inhibition of Akt expression using an Akt1/2 inhibitor significantly reduced neurite length in P19 cells and primary hippocampal cell cultures, which was also ameliorated by lithium. Collectively, our findings implied the therapeutic potential of lithium and the importance of the AKT1-GSK3 signaling pathway. [ABSTRACT FROM AUTHOR]

This paper presents both an observer/Kalman filter identification (OKID) method-based linear quadratic digital tracker (LQDT) and a new functional observer-based discrete equivalent input disturbance (EID) estimator, for unknown square/non-square singular sampled-data systems with unknown input and output disturbances. Initially, it is shown that even if the solution of the impulsive mode-free singular linear quadratic tracker problem exists, under some quite general conditions the tracker-based generalised algebraic Riccati equation (GARE) might have no solution. To overcome this issue, an innovative methodology that involves an introduced reduced-order equivalent proper regular model (EPRM) of the singular system is presented, to make the tracker-based GARE solvable for a wide class of servo control problems for a singular system. Furthermore, a new functional observer-based design methodology for the discrete EID estimator of the discrete EPRM is proposed in this paper, for a proper sampled-data system with unknown matched/mismatched input and output disturbances. Finally, a discrete-time EPRM of the unknown singular sampled-data system is constructed using the off-line OKID method and the robust prediction-based state-estimate optimal LQDT, associated with the (plug-in) discrete EID estimator, is developed for the singular sampled-data system. [ABSTRACT FROM AUTHOR]

A laboratory study was conducted to determine the effects of membrane filtration treatment on the performance of recirculating aquaponic system and the production of tilapia ( Oreochromis niloticus ♂ × Oreochromis mossambicus ♀) and water spinach ( Ipomoea aquatica ). The recirculation system consisted of a fish tank, a sludge tank with membrane filtration treatment, and a hydroponic tank. The control had the same experimental arrangement excluding the membrane. The experiment was continued for 12 weeks. Final weight gain and specific growth rate of tilapia, and total yield of plants in the membrane filtration system were 69%, 54%, and 34% higher than that of the control, respectively. Furthermore, the membrane treatment effectively retained the microbes and solids in the sludge tank that consequently increased the nitrification process and also showed higher levels of biological oxygen demand (BOD), bacteria, turbidity, and suspended solids than the control. Therefore, the average NH 4 + - N , NO 2 − - N , BOD, chemical oxygen demand (COD), total bacterial count, and turbidity in the fish tank and the plant tank of the membrane filtration system were significantly lower than that in the control. [ABSTRACT FROM AUTHOR]

This letter proposes an algorithm that selects a small number of test patterns for small delay defects from a large N-detect test set. This algorithm uses static upper and lower bound analysis to quickly estimate the sensitized path length so that the central processing unit (CPU) time can be reduced. By ignoring easy faults, only a partial fault dictionary, instead of a complete fault dictionary, is built for test pattern selection. Experimental results on large International Test Conference benchmark circuits show that, with very similar quality, the selected test set is 46% smaller and the CPU time is 42% faster than that of timing-aware automated test pattern generation (ATPG). With the proposed selection algorithm, small delay defect test sets are no longer very expensive to apply. [ABSTRACT FROM PUBLISHER]

Abstract: In this study, several anti-fouling approaches including coagulation conditions (FeCl3 dosage and feed pH), air-enhanced backwash (AEB) conditions (backwash interval and AEB duration) and chemical cleaning conditions (reagents, soak time and temperature) were evaluated to enhance the feasibility of a commercial ultrafiltration (UF) membrane as a pretreatment of RO seawater desalination. A tubular commercial ceramic UF membrane with a surface layer of zirconium dioxide (ZrO2) and a supporting layer of α-alumina oxide (α-Al2O3) was employed in this study. The results showed that ferric coagulation was functional to enhance the performance of ceramic UF for seawater treatment, especially on COD removal. The trial of cleaning demonstrated that the performance of NaClO was much better than that of HNO3 under various evaluated pH values. The relevant additional experiments showed that the cleaning efficiency increased with NaClO concentration, soak time and soak temperature but decreases when soak temperature was up to 60°C. An important finding of this study is that the fouled membrane from coagulation-filtration trial can be easily and quickly recovered by acid cleaning regents followed by NaClO solution. Furthermore, short backwash interval performed more efficiently. However, it is certain that both backwash interval and AEB duration enhanced less than other approaches on the permeate quality. This study finally summarized the operating condition of each anti-fouling approach for the further potential application of UF ceramic membrane as a pretreatment of RO seawater desalination. [Copyright &y& Elsevier]

This paper proposes a bit-level parallel ATPG algorithm (SWK) that generates multiple test patterns at a time. This algorithm converts decisions into bitwise logic operation so that W (CPU word size) test patterns are searched independently. Multiple objectives for different quality metrics can therefore be achieved in a single test generation process. Experimental results on ISCAS'89 and IWLS'05 benchmark circuits show that SWK test sets are better in many quality metrics than traditional 50-detect test sets, while the length of the former is shorter. Also, patterns selected from large N-detect pattern pool cannot achieve the same or higher quality than patterns generated by SWK. [ABSTRACT FROM PUBLISHER]

Abstract: The feasibility of treating acrylonitrile–butadiene–styrene (ABS) resin manufacturing wastewater by Fenton oxidation treatment was investigated. The experiments were conducted in six different operating modes. For all tests, total dosage of ferrous (Fe2+) salt and hydrogen peroxide (H2O2) was kept at 2000mg L−1 and 4000mg L−1, respectively and the total reaction time was maintained at 160min. The kinetics of the decomposition of organic matter in terms of dissolved chemical oxygen demand (DCOD) by H2O2 followed the pseudo-first order reaction. For DCOD decomposition, the removal rate constant equation of DCOD, k 1 =2.95×10−6[H2O2]0 0.17[Fe2+]0 1.60 was obtained, where k 1 is the reaction rate coefficient of DOCD decomposition. The consumption rate constant equation of H2O2, k 2 =1.85×10−3[H2O2]0 −1.70[Fe2+]0 2.90 was obtained, where k 2 is the reaction rate coefficient of hydrogen peroxide consumption. Batch and semi-batch studies indicated that oxidation with Fenton''s reagent is feasible for treating ABS wastewater. [Copyright &y& Elsevier]

Abstract: A two-stage aerobic membrane bioreactor (MBR) system for treating acrylonitrile butadiene styrene (ABS) resin wastewater was carried out in this study to evaluate the system performance on nitrification. The results showed that nitrification of the aerobic MBR system was significant and the highest TKN removal of approximately 90% was obtained at hydraulic retention time (HRT) 18h. In addition, the result of nitrogen mass balance revealed that the percentage of TN removal due to denitrification was in the range of 8.7–19.8%. Microbial community analysis based on 16s rDNA molecular approach indicated that the dominant ammonia oxidizing bacteria (AOB) group in the system was a β-class ammonia oxidizer which was identified as uncultured sludge bacterium (AF234732). A heterotrophic aerobic denitrifier identified as Thauera mechernichensis was found in the system. The results indicated that a sole aerobic MBR system for simultaneous removals of carbon and nitrogen can be designed and operated for neglect with an anaerobic unit. [Copyright &y& Elsevier]

Abstract: This study investigated the feasibility and the treatment efficiency of a cyclic anoxic/aerobic two-stage MBR for treating polymeric industrial wastewater. The anoxic/aerobic hybrid MBR was operated without sludge withdrawal except sampling during the study. The results showed that the highest COD organic loading rate of 8.7kg COD/m3 day from bioreactor was obtained at phase 3. The system achieved 97% BOD5 and 89% COD removal. It also revealed that 93% of COD removal was contributed by bioreactor at phase 3 and the similar results happened to phases 1 and 2. The highest TN and TKN removals for each phase were 60, 74, 80% and 61, 74, 81%, respectively and limited by nitritation step. SEM images of nascent and fouled membranes were offered to evaluate the cleaning method. The system was operated for 174days, resulting in high degradation rate, flexibility towards influent fluctuations and limited sludge production. [Copyright &y& Elsevier]

Abstract: Pretreatment to reverse osmosis (RO) seawater desalination historically has been achieved using organic (polymer) ultra- and micro-filter (UF/MF) membranes. Newly developed inorganic (ceramic) membranes offer unique advantages over the currently employed membranes, and were recently introduced for the purpose. In this work, we investigate the performance of a zirconium dioxide ceramic membrane with 0.05μm pore diameter to clarify raw seawater under different operating conditions. The influences of cross-flow velocity (2.7–4.9ms−1), temperature (15–55°C), transmembrane pressure (TMP) 0.1–0.2MPa, and seawater pH (5.5–9.5) on permeate flux and rejection were assessed. The results show that the zirconium dioxide membrane at cross-flow velocity of 3.7–4.2ms−1, TMP of 0.14–0.18MPa, temperature of 25–30°C and seawater pH of 8.0–9.0 exhibited a high flux of 420–450Lm−2 h−1 with turbidity and CODMn rejection of 99.0–99.5% and 32–35%, respectively. This work also introduces a new experimental procedure to determine different filtration resistance (R m, R sads, R pads, R cp, R pb and R cr) components, which helps the analysis of performance characteristics and the better understanding of interactions between the membrane and foulants. The present results show that the effect of concentration polarization was dominant in the ultrafiltration of raw seawater, and various fouling components contribute to the total in the order of R cp > R sr > R m > R sads > R pads > R irr. Further, reversible fouling was much more significant than irreversible fouling. The experimental method also showed interrelation between the reversible and irreversible resistances, whereby part of R sr is transformed into R irr within 20min of filtration. The results of this study indicate that zirconium dioxide ultrafiltration pretreatment before RO desalination can achieve consistent permeate quality and low fouling potential at high permeate fluxes. [Copyright &y& Elsevier]

Abstract: This study applied the non-woven material from used diaper as the carrier for bio-film process to purify the recycled water from a landscape pond at the Tainan City Municipal Culture Center (TCMCC), Taiwan. An on-site system was installed and the experiment was accomplished through three stages in 192days with different time periods of 70days, 63days, and 59days, respectively. The results showed that the non-woven media is functional for SS removal. The average SS removal of stages 1, 2, and 3 were 91%, 96%, and 95%, respectively. The highest SCOD removal efficiency of 90% occurred at stage 3. A significant color improvement of the pond water was achieved through this non-woven bio-carrier treatment system. Whole system can be without any maintenance for 139days. The result indicated that the non-woven medium system was with a great potential in treating and recycling the pond water with stable operation and satisfactory removal performance. [Copyright &y& Elsevier]

Abstract: A pilot-scale study of pharmaceutical wastewater treatment by a membrane bioreactor (MBR) process in southern Taiwan is presented in this paper. A 10 m3/day capacity MBR plant consisting of an aeration tank and a membrane bioreactor was installed to remove organic matter (measured in terms of chemical oxygen demand (COD)). The performance of the MBR was monitored for a period of 140 days. The removal of COD was on average over 95%. The effluent did not contain any suspended solids. During the 140 days of operation, manual cleaning was carried out twice and chemical cleaning was carried out once. A natural logarithmic evolution of the viscosity with TSS concentration was observed. The results of SEM and EDX demonstrated that the fouling on the membrane outer surface was mainly due to microorganisms and/or the sludge physiological properties. The results indicated that the MBR system has potential as a means of treating high-strength and fluctuating strength wastewater with consistent performance. [Copyright &y& Elsevier]

Abstract: With the rapid development of the petrochemical industry in Taiwan, a significant amount of nitrogenous organic wastewater is generated. Some of this wastewater contains volatile residual monomers, such as acrylonitrile-butadienestyrene (ABS) manufacturing wastewater. Because of the high volatility of the acrylonitrile monomer, this chemical will be partly removed from the aeration system by the air stripping effect. An empirical model was developed for evaluating BOD removal by air stripping and biodegradation when the wastewater was treated in an aerobic submerged membrane bioreactor (ASMBR). The results showed that the removal of BOD from ABS wastewater by air stripping was in the range of 2–10%. These results also showed that the estimation of contribution of air stripping and biodegradation in the BOD removal in the MBR is very important in the optimum design of the MBR for ABS wastewater. [Copyright &y& Elsevier]

Abstract: In this study, the feasibility and the treatment efficiency of treating ABS industrial wastewater by an aerated submerged membrane bioreactor (ASMBR) was investigated. Through a long-term experiment, biomass, biological oxygen demand (BOD5,) chemical oxygen demand (COD), total organic carbon (TOC) and permeate flux were measured to evaluate the MBR performance. The results show that a hydraulic retention time (HRT) of 18 h leads to the highest biomass concentration, a maximum mixed liquor suspended solids (MLSS) value of approximately 35 g/L. Chemical membrane cleaning was employed twice, after 131 and 180 days of operation in the total experimental period of 204 days. The membrane bioreactor led to superior COD and BOD5 removal in ABS wastewater compared to the conventional biological treatment. [Copyright &y& Elsevier]

MHD micro-pumps circumvent the wear and fatigue caused by high pressure-drop across the check valves of mechanical micro-pumps in micro-fluidic systems. Early analyses of the fluid flow for MHD micro-pumps were mostly made possible by the Poiseuille flow theory; however, this conventional laminar approach cannot illustrate the effects of various channel sizes and shapes. This paper, therefore, presents a simplified MHD flow model based upon steady state, incompressible and fully developed laminar flow theory to investigate the characteristics of a MHD pump. Inside the pump, flowing along the channel is the electrically conducting fluid flowing driven by the Lorentz forces in the direction perpendicular to both dc magnetic field and applied electric currents. The Lorentz forces were converted into a hydrostatic pressure gradient in the momentum equations of the MHD channel flow model. The numerical simulations conducted with the explicit finite difference method show that the channel dimensions and the induced Lorentz forces have significant influences on the flow velocity profile. Furthermore, the simulation results agree well with the experimental results published by other researchers. [Copyright &y& Elsevier]

Effects of anions of Zn salts and additives in the plating baths, current densities and modes of electroplating on the anodic stripping behavior of Zn deposits were investigated for the possible application to Zn-based batteries. The anodic stripping behavior was examined using linear sweep voltammetry (LSV) in a 0.5 M Na2SO4 solution containing 0.5 M ethylene-diamine-tetraacetic acid (EDTA). Effects of the above deposition variables on the discharge efficiency of Zn deposits were systematically compared on the basis of the chronopotentiometric (CP) curves measured galvanostatically at 1 C. Morphologies of all deposits were examined by scanning electron microscopy (SEM). Formation of Zn dendrites is depressed significantly by employing suitable additives (e.g., potassium sodium tartrate, tetrahydrate (PSTT)) as well as by using a cyclic voltammetric (CV) deposition. From the results of SEM and CP analyses, Zn deposit plated in CV mode shows the highest discharge efficiency, attributable to cubic grains with very clear boundaries, which is expected to easily strip under the anodic polarization. [Copyright &y& Elsevier]

The environmental factors such as hot-wet and pre-compression may lead to degradation in energy absorption properties of polystyrene foam in protective helmets. In this paper, an experimental study on the mechanical properties of Expanded Polystyrene (EPS) foam was conducted using high precision micro-force compression tests. Tests were conducted with foam specimens from actual helmets at pre-compression strain ranging from 10% to 50% and hot-wet conditions at 60 °C with different relative humidity (RH) levels between 40% and 85%. The load–displacement behavior of EPS foam was carefully recorded for determining the compressive stress–strain curves. The test results indicated that when the pre-compression strain exceeded 10%, the elastic stiffness and plastic yielding region (plateau region) decreased and the plastic yielding point increased dramatically. When the pre-compression strain reached 50%, the plateau region vanished from the stress–strain curves. High humidity has a significant effect on lowering the plastic yield point, but has little effect on the plateau region range. The stress–strain curves from these tests were successfully implemented into a validated helmet finite element model to simulate guided helmet free drop experiments. Headform peak decelerations and head injury criterion (HIC) values were obtained from simulation and analyzed to estimate the energy absorption degradation in EPS foam. The finite element analysis predictions showed that pre-compression significantly degrades the energy absorption properties of EPS foam. The maximum permissible pre-compression strain should not exceed 10%. High humidity levels lead the helmet to transmit a lower HIC value but wider HIC duration to the head. [Copyright &y& Elsevier]

Cognitive dysfunction is one of the core symptoms in schizophrenia, and it is predictive of functional outcomes and therefore useful for treatment targets. Rather than improving cognitive deficits, currently available antipsychotics mainly focus on positive symptoms, targeting dopaminergic/serotoninergic neurons and receptors in the brain. Apart from investigating the neural mechanisms underlying schizophrenia, emerging evidence indicates the importance of glial cells in brain structure development and their involvement in cognitive functions. Although the etiopathology of astrocytes in schizophrenia remains unclear, accumulated evidence reveals that alterations in gene expression and astrocyte products have been reported in schizophrenic patients. To further investigate the role of astrocytes in schizophrenia, we highlighted recent progress in the investigation of the effect of astrocytes on abnormalities in glutamate transmission and impairments in the blood–brain barrier. Recent advances in animal models and behavioral methods were introduced to examine schizophrenia-related cognitive deficits and negative symptoms. We also highlighted several experimental tools that further elucidate the role of astrocytes. Instead of focusing on schizophrenia as a neuron-specific disorder, an additional astrocytic perspective provides novel and promising insight into its causal mechanisms and treatment. The involvement of astrocytes in the pathogenesis of schizophrenia and other brain disorders is worth further investigation. [ABSTRACT FROM AUTHOR]

Epigenetic regulation and mitochondrial dysfunction are essential to the progression of idiopathic pulmonary fibrosis (IPF). Curcumin (CCM) in inhibits the progression of pulmonary fibrosis by regulating the expression of specific miRNAs and pulmonary fibroblast mitochondrial function; however, the underlying mechanism is unclear. C57BL/6 mice were intratracheally injected with bleomycin (5 mg/kg) and treated with CCM (25 mg/kg body weight/3 times per week, intraperitoneal injection) for 28 days. Verhoeff–Van Gieson, Picro sirius red, and Masson's trichrome staining were used to examine the expression and distribution of collagen and elastic fibers in the lung tissue. Pulmonary fibrosis was determined using micro-computed tomography and transmission electron microscopy. Human pulmonary fibroblasts were transfected with miR-29a-3p, and RT-qPCR, immunostaining, and western blotting were performed to determine the expression of DNMT3A and extracellular matrix collagen-1 (COL1A1) and fibronectin-1 (FN1) levels. The expression of mitochondrial electron transport chain complex (MRC) and mitochondrial function were detected using western blotting and Seahorse XFp Technology. CCM in increased the expression of miR-29a-3p in the lung tissue and inhibited the DNMT3A to reduce the COL1A1 and FN1 levels leading to pulmonary extracellular matrix remodeling. In addition, CCM inhibited pulmonary fibroblasts MRC and mitochondrial function via the miR-29a-3p/DNMT3A pathway. CCM attenuates pulmonary fibrosis via the miR-29a-3p/DNMT3A axis to regulate extracellular matrix remodeling and mitochondrial function and may provide a new therapeutic intervention for preventing pulmonary fibrosis. [Display omitted] • Curcumin mitigates pulmonary fibrosis. • Regulation of miR-29a-3p/DNMT3A axis. • Attenuates ECM remodeling & mitochondrial dysfunction. • Promising therapeutic approach for IPF. [ABSTRACT FROM AUTHOR]

Nitrogen doping and amino-group functionalization through chemical modification can engender enhance electron donation. Using a homemade femtosecond titanium:sapphire laser optical system operated at a low energy and short photoexcitation time [power: 200.0 nJ pixel−1; scanning frequency: 150 scans (∼0.80–1.33 s); excitation wavelength: 870, 910, or 970 nm], this study conducted these processes on the large π-conjugated system of graphene quantum dot (GQD)-based materials functioning as electron donors; this improved the efficiency of charge transfer to the prepared amino-N-GQDs, resulting in enhanced two-photon absorption, excitation-wavelength-independent photoluminescence (EWI-PL), radiative efficiency, excitation absolute cross section, and excitation from the near-infrared (NIR)-I to the NIR-II region. The lifetime decreased and quantum yield (QY) increased. The sorted amino-N-GQDs exhibited two-photon EWI-PL emissions between the ultraviolet and NIR-I regions, leading to the generation of reactive oxygen species (ROS), which functioned as two-photon photosensitizers for photodynamic therapy (PDT). Increasing the mean lateral size of the particles increased the N-functionality-dependent photochemical and electrochemical activities, which improved the PL QY and thus enhanced the efficiency of two-photon PDT. Additionally, a polystyrene sulfonate (PSS) coating was applied (forming sorted amino-N-GQD-PSS); the sulfur atoms introduced by the PSS induced the radiative recombination of localized electron–hole pairs and then improved the sorted amino-N-GQD surfaces by strengthening the quantum confinement of their emissive energy. Thus, compared with the sorted amino-N-GQDs that were not coated, the PSS-coated materials had superior two-photon properties. No ROS were detected. Accordingly, these materials are suitable for use as two-photon contrast probes for analyte tracking and localization. [Display omitted] [ABSTRACT FROM AUTHOR]

Temporal focusing-based multiphoton excitation microscopy (TFMPEM) just provides the advantage of widefield optical sectioning ability with axial resolution of several micrometers. However, under the plane excitation, the photons emitted from the molecules in turbid tissues undergo scattering, resulting in complicated background noise and an impaired widefield image quality. Accordingly, this study constructs a general and comprehensive numerical model of TFMPEM utilizing Fourier optics and performs simulations to determine the superior spatial frequency and orientation of the structured pattern which maximize the axial excitation confinement. It is shown experimentally that the optimized pattern minimizes the intensity of the out-of-focus signal, and hence improves the quality of the image reconstructed using the Hilbert transform (HT). However, the square-like reflection components on digital micromirror device leads to pattern residuals in the demodulated image when applying high spatial frequency of structured pattern. Accordingly, the HT is replaced with Hilbert–Huang transform (HHT) in order to sift out the low-frequency background noise and pattern residuals in the demodulation process. The experimental results obtained using a kidney tissue sample show that the HHT yields a significant improvement in the TFMPEM image quality. [ABSTRACT FROM AUTHOR]

Significance: Line scanning-based temporal focusing multiphoton microscopy (TFMPM) has superior axial excitation confinement (AEC) compared to conventional widefield TFMPM, but the frame rate is limited due to the limitation of the single line-to-line scanning mechanism. The development of the multiline scanning-based TFMPM requires only eight multiline patterns for full-field uniform multiphoton excitation and it still maintains superior AEC. Aim: The optimized parallel multiline scanning TFMPM is developed, and the performance is verified with theoretical simulation. The system provides a sharp AEC equivalent to the line scanning-based TFMPM, but fewer scans are required. Approach: A digital micromirror device is integrated in the TFMPM system and generates the multiline pattern for excitation. Based on the result of single-line pattern with sharp AEC, we can further model the multiline pattern to find the best structure that has the highest duty cycle together with the best AEC performance. Results: The AEC is experimentally improved to 1.7 μm from the 3.5 μm of conventional TFMPM. The adopted multiline pattern is akin to a pulse-width-modulation pattern with a spatial period of four times the diffraction-limited line width. In other words, ideally only four π / 2 spatial phase-shift scans are required to form a full two-dimensional image with superior AEC instead of image-size-dependent line-to-line scanning. Conclusions: We have demonstrated the developed parallel multiline scanning-based TFMPM has the multiline pattern for sharp AEC and the least scans required for full-field uniform excitation. In the experimental results, the temporal focusing-based multiphoton images of disordered biotissue of mouse skin with improved axial resolution due to the near-theoretical limit AEC are shown to clearly reduce background scattering. [ABSTRACT FROM AUTHOR]

We fabricated nanomaterials comprising amino-functionalized and nitrogen-doped graphene quantum dots (amino-N-GQDs) and investigated their photostability and intrinsic luminescence in the near-infrared spectrum to determine their suitability as contrast agents in two-photon imaging (TPI). We observed that amino-N-GQDs with a higher amount of bonded nitrogen and amino-functionalized groups (6.2%) exhibited superior two-photon properties to those with a lower amount of such nitrogen and groups (4.9%). These materials were conjugated with polymers containing sulfur (polystyrene sulfonate, PSS) and nitrogen atoms (polyethylenimine, PEI), forming amino-N-GQD–PSS–PEI specimens (amino-N-GQD-polymers). The polymers exhibited a high quantum yield, remarkable stability, and notable two-photon properties and generated no reactive oxygen species, rendering them excellent two-photon contrast agents for bioimaging. An antiepidermal growth factor receptor (AbEGFR) was used for labeling to increase specificity. Two-photon imaging (TPI) of amino-N-GQD (6.2%)-polymer-AbEGFR-treated A431 cancer cells revealed remarkable brightness, intensity, and signal-to-noise ratios for each observation at a two-photon excitation power of 16.9 nJ pixel−1 under 30 scans and a three-dimensional (3D) depth of 105 µm, indicating that amino-N-GQD (6.2%)-polymer-AbEGFR-treated cells can achieve two-photon luminescence with 71 times less power required for two-photon autofluorescence (1322.8 nJ pixel−1 with 500 scans) of similar intensity. This economy can minimize photodamage to cells, rendering amino-N-GQD-polymers suitable for noninvasive 3D bioimaging. [ABSTRACT FROM AUTHOR]

A stream of wastewater from a synthetic-fibers manufacturing plant with high amount of tetrahydrofuran (THF), 3-buten-1-ol (BTO) and 1,4-butanediol (BDO) results in high chemical oxygen demand (COD). A pilot high rate up-flow anaerobic sludge blanket (UASB) reactor, which recirculation rate was set at three times of feed flowrate, was conducted on-site and continuously run for 108 days. Volumeric organic loading rates were gradually adjusted from to 1.3 ± 0.2 to 21.5 ± 1.8 kg-COD·m−3 d−1 while corresponding COD in the influent increased from 1704 to the maximum up to 30700 mg L−1. Average removals of COD were 75.8%, while temperature, pH, dissolved oxygen, and oxidation reduction potential were intensively monitored throughout the pilot study. Average THF removals of 89.1% and complete BTO removals showed successful biodegradation in the UASB reactor. Meanwhile, average BDO removals increased significantly from 43.2% to 95.8%. In addition, increasing of biomass and food-to-microorganism ratios were performed well by rational regressions. Anaerobic granules were also developed well to the final size of 3–4 mm. Moreover, total biogas production rates were increased by operation days. The main biogas component (CH 4) increases five times while the other two (CO 2 and N 2) were kept steady. In general, start-up of the UASB for biodegradting real wastewaters containing high concentration of C4 chemicals was firstly demonstrated in the pilot study. • A high-rate UASB reactor was designed for real synthetic-fibers wastewater treatment. • Simultaneous biodegradation of THF, BTO and BDO was first time conducted. • Four key operational parameters (pH, temperature, DO and ORP) were monitored. • Start-up of the pilot plant was performed and good performances were achieved. • Main biogas produced in the pilot was identified as methane, and size of anaerobic granules were measured. [ABSTRACT FROM AUTHOR]

Background: Long-term consumption of an excessive fat and sucrose diet (Western diet, WD) has been considered a risk factor for metabolic syndrome (MS) and cardiovascular disease. Caveolae and caveolin-1 (CAV-1) proteins are involved in lipid transport and metabolism. However, studies investigating CAV-1 expression, cardiac remodeling, and dysfunction caused by MS, are limited. This study aimed to investigate the correlation between the expression of CAV-1 and abnormal lipid accumulation in the endothelium and myocardium in WD-induced MS, and the occurrence of myocardial microvascular endothelial cell dysfunction, myocardial mitochondrial remodeling, and damage effects on cardiac remodeling and cardiac function. Methods: We employed a long-term (7 months) WD feeding mouse model to measure the effect of MS on caveolae/vesiculo-vacuolar organelle (VVO) formation, lipid deposition, and endothelial cell dysfunction in cardiac microvascular using a transmission electron microscopy (TEM) assay. CAV-1 and endothelial nitric oxide synthase (eNOS) expression and interaction were evaluated using real-time polymerase chain reaction, Western blot, and immunostaining. Cardiac mitochondrial shape transition and damage, mitochondria-associated endoplasmic reticulum membrane (MAM) disruption, cardiac function change, caspase-mediated apoptosis pathway activation, and cardiac remodeling were examined using TEM, echocardiography, immunohistochemistry, and Western blot assay. Results: Our study demonstrated that long-term WD feeding caused obesity and MS in mice. In mice, MS increased caveolae and VVO formation in the microvascular system and enhanced CAV-1 and lipid droplet binding affinity. In addition, MS caused a significant decrease in eNOS expression, vascular endothelial cadherin, and β-catenin interactions in cardiac microvascular endothelial cells, accompanied by impaired vascular integrity. MS-induced endothelial dysfunction caused massive lipid accumulation in the cardiomyocytes, leading to MAM disruption, mitochondrial shape transition, and damage. MS promoted brain natriuretic peptide expression and activated the caspase-dependent apoptosis pathway, leading to cardiac dysfunction in mice. Conclusion: MS resulted in cardiac dysfunction, remodeling by regulating caveolae and CAV-1 expression, and endothelial dysfunction. Lipid accumulation and lipotoxicity caused MAM disruption and mitochondrial remodeling in cardiomyocytes, leading to cardiomyocyte apoptosis and cardiac dysfunction and remodeling. [ABSTRACT FROM AUTHOR]

Ultrafast lasers concentrate the energy in a short pulse with a duration of several tens to hundreds of femtoseconds. The resulting high peak power induces various nonlinear optical phenomena that find use in many different fields. However, in practical applications, the optical dispersion broadens the laser pulse width and spreads the energy in time, thereby reducing the peak power. Accordingly, the present study develops a piezo bender-based pulse compressor to compensate for this dispersion effect and restore the laser pulse width. The piezo bender has a rapid response time and a large deformation capacity and thus provides a highly effective means of performing dispersion compensation. However, due to hysteresis and creep effects, the piezo bender is unable to maintain a stable shape over time and hence the compensation effect is gradually degraded. To address this problem, this study further proposes a single-shot modified laterally sampled laser interferometer to estimate the parabolic shape of the piezo bender. The curvature variation of the bender is then sent as a feedback signal to a closed-loop controller to restore the bender to the desired shape. It is shown that the steady-state error of the converged group delay dispersion is around 530 fs2. Moreover, the ultrashort laser pulse is compressed from 1620 fs in the original condition to 140 fs in the compressed condition, corresponding to a 12-fold improvement. [ABSTRACT FROM AUTHOR]

In this paper, an easily implementable adaptive optics system (AOS) based on a real-time field programmable gate array (FPGA) platform with state-space multichannel control programmed by LabVIEW has been developed, and also integrated into a laser focusing system successfully. To meet the requirements of simple programming configuration and easy integration with other devices, the FPGA-based AOS introduces a standard operation procedure including AOS identification, computation, and operation. The overall system with a 32-channel driving signal for a deformable mirror (DM) as input and a Zernike polynomial via a lab-made Shack-Hartmann wavefront sensor (SHWS) as output is optimally identified to construct a multichannel state-space model off-line. In real-time operation, the FPGA platform first calculates the Zernike polynomial of the optical wavefront measured from the SHWS as the feedback signal. Then, a state-space multichannel controller according to the feedback signal and the identified model is designed and implemented in the FPGA to drive the DM for phase distortion compensation. The current FPGA-based AOS is capable of suppressing low-frequency thermal disturbances with a steady-state phase error of less than 0.1 π within less than 10 time steps when the control loop is operated at a frequency of 30 Hz. [ABSTRACT FROM AUTHOR]

To meet the demands of high-frequency wireless communications and Internet of Things (IoT) applications, modern integrated circuit (IC) packages should support operating frequencies in the GHz range and be implemented on fine substrate structures. Glass has many advantages as an interposer material for three-dimensional IC (3D-IC) designs, including tunable electrical and mechanical properties, amenability to large-scale processing, and high optical transparency in the visible range. Moreover, glass is easily processed to produce the through-glass vias (TGVs) required to realize high-frequency circuit designs and microelectromechanical systems devices. The present study proposes a method for patterning TGVs on glass substrates via a nonlinear multiphoton-assisted modification process performed using single-pulse irradiation by a 1030-nm picosecond laser. A theoretical model is additionally proposed to describe the glass substrate modification mechanism induced by the nonlinear multiphoton excitation effect. The feasibility of the proposed method is demonstrated by patterning a TGV array with a high aspect ratio of 1:10 and a taper angle of ∼2° on a Corning SGW3 glass substrate. [ABSTRACT FROM AUTHOR]

In this study, we report to prepare six modified inorganic mineral materials, including bentonite, attapulgite, montmorillonite, kaolinite and diatomite, in a novel semidry-method. Compared with traditional wet-method, this semidry-method requires fewer procedures and, thus, consumes shorter reaction time and less energy. In addition, the modified materials were found to have larger surfactant concentrations, which could result in higher removal efficiency to organic contaminants. Among these six materials, the modified bentonite (organobentonite) performed the best adsorption efficiency to 2,4-dichlorophenol (2,4-D) from aqueous solution and the removal efficiency reached 97.0%. Among four surfactants, hexadecyltrimethylammonium (HDTMA), a cationic and long hydrophobic tail surfactant, was found to be the most efficient modifier. Compared with raw bentonite, the removal efficiency of 2,4-D by HDTMA-modified bentonite (HDTMA-Bent) was enhanced up to more than 40%. The characterizations of raw bentonite and HDTMA-Bent indicated that there were smaller but more separated lamella in the HDTMA-Bent and the basal spacing could be enlarged by 128% as HDTMA inserting into the interlayers of bentonite. After being modified by HDTMA, the Zeta-potential of bentonite was transformed from negative to positive, and this variation of Zeta-potential was also consistent with the change of 2,4-D removal efficiency. [ABSTRACT FROM AUTHOR]

Nitrogen doping and amino group functionalization through chemical modification lead to strong electron donation. Applying these processes to a large π-conjugated system of graphene quantum dot (GQD)-based materials as electron donors increases the charge transfer efficiency of nitrogen-doped amino acid-functionalized GQDs (amino-N-GQDs), resulting in enhanced two-photon absorption, post-two-photon excitation (TPE) stability, TPE cross-sections, and two-photon luminescence through the radiative pathway when the lifetime decreases and the quantum yield increases. Additionally, it leads to the generation of reactive oxygen species through two-photon photodynamic therapy (PDT). The sorted amino-N-GQDs prepared in this study exhibited excitation-wavelength-independent two-photon luminescence in the near-infrared region through TPE in the near-infrared-II region. The increase in size resulted in size-dependent photochemical and electrochemical efficacy, increased photoluminescence quantum yield, and efficient two-photon PDT. Therefore, the sorted amino-N-GQDs can be applicable as two-photon contrast probes to track and localize analytes in in-depth two-photon imaging executed in a biological environment along with two-photon PDT to eliminate infectious or multidrug-resistant microbes. [ABSTRACT FROM AUTHOR]

Abstract: This work deals with a facile approach to fabricate a novel nanofiltration (NF) membrane consisting of a dense active layer from polyethyleneimine (PEI) cross-linking on a porous polysulphone (PS) substrate which was modified by self-polymerized dopamine (DA). Inspired by the bioadhesion principle, a composite membrane with a poly(dopamine) (poly(DA)) layer was fabricated by simply dipping the PS substrate into DA aqueous solution. Later, the modified PS substrate was thermal-treated and then impregnated into PEI solution for PEI grafting on the poly(DA) layer. Finally, PEI cross-linking was performed and as a result a composite PS/DA/PEIc membrane with a dense cross-linked DA/PEI layer was obtained, which exhibited a typical NF property. Several parameters such as PEI grafting, thermal treatment, cross-linkers and operating conditions were investigated to obtain the optimum composite membrane with an excellent NF performance. The results showed that the optimum NF membrane yielded a permeation flux of 43.96L/m2 h and a rejection of 89.27% when 2000mg/L MgCl2 solution was used as a feed solution at 0.8MPa, whereas a permeation flux of 49.21L/m2 h and a rejection of 27.30% were obtained for a feed NaCl concentration of 2000mg/L. These results show the promising use of such NF membranes in water softening. [Copyright &y& Elsevier]

Coupled nanomechanical resonators have recently attracted great attention for both practical applications and fundamental studies owing to their sensitive sympathetic oscillation dynamics. A challenge to the further development of this architecture is the coherent manipulation of the coupled oscillations. Here, we demonstrate strong dynamic coupling between two GaAs-based mechanical resonators by periodically modulating (pumping) the stress using a piezoelectric transducer. This strong coupling enables coherent transfer of phonon populations between the resonators, namely phonon Rabi oscillations. The nature of the dynamic coupling can also be tuned from a linear first-order interaction to a nonlinear higher-order process in which more than one pump phonon mediates the coherent oscillations (that is, multi-pump phonon mixing). This coherent manipulation is not only useful for controlling classical oscillations but can also be extended to the quantum regime, opening up the prospect of entangling two distinct macroscopic mechanical objects. [ABSTRACT FROM AUTHOR]

• Three-step deformable mirror identification is proposed to solve channel coupling problem. • Deformable mirror is identified to generate 15 Zernike modes with over 20 dB contrast. • 200 Hz parallel model-based closed-loop controllers manipulate Zernike modes independently. • Axial remote focusing is achieved while eliminating aberrations in presence of heat flow. Remote focusing using a deformable mirror (DM) provides a rapid and responsive technique for performing axial scanning. However, to maintain the laser focusing quality, the aberrations within the system must be adequately controlled. Accordingly, the present study proposes a low control complexity model-based adaptive optics (AO) approach for remote focusing with zero aberrations. Based on the Zernike coefficients measured by a self-built Shack-Hartmann wavefront sensor (SHWS), 15 independent closed-loop controllers (one for each Zernike mode according to Wyant expansion scheme) execute a three-step DM identification process to determine the control vectors required to actuate the DM in such a way as to restore the Zernike coefficients of the wavefront to their required values. The experimental results show that the controllers converge within four time steps (20 ms) and reduce the converged wavefront variance by nearly 475 times. Moreover, the controller used to manipulate the Z 3 (defocus) Zernike coefficient converges within just three time steps (15 ms). Given a static disturbance of the wavefront, the proposed AO control method enables the defocus laser spot to be driven precisely along a target sinusoidal trajectory while maintaining all the other Zernike modes at zero. The control system shows a similar performance in compensating the dynamic aberrations produced by a low-frequency thermal disturbance within the system. Overall, the results indicate that the proposed model-based AO controller facilitates remote focusing with simultaneous aberration elimination and improves the central intensity of the focus laser spot by around 3.1 times compared to the case in which the controller is not applied. [ABSTRACT FROM AUTHOR]

In ultrashort pulse laser applications, optical dispersion seriously affects the energy concentration in the laser pulse duration and lowers the peak power. Accordingly, this study proposes a rapid dispersion estimation mechanism to facilitate the compensation of optical dispersion using a closed-loop control system. In the proposed approach, the optical dispersion information of the laser pulse is estimated directly from a frequency-resolved optical gating trace without the need for an iterative pulse-retrieval algorithm. In particular, the group delay dispersion (GDD) is determined from frequency and delay marginals, which are related to the laser spectrum and intensity autocorrelation, respectively, using a simple lookup table approach. The accuracy of the estimated GDD results is confirmed via a comparison with the spectral phase distribution of the electric field reconstructed using the principal component generalized projections algorithm. It is shown that the computation time of the proposed direct estimation method is around 13 times faster than that of the traditional iterative algorithm. It thus provides a feasible approach for enabling the real-time compensation of ultrafast laser pulse compression. Moreover, in a multiphoton-excited fluorescence imaging application, the proposed pulse compression mechanism yields an effective improvement in the intensity and contrast of the reconstructed image due to the increased nonlinear optical excitation efficiency of the optimized laser pulses. [ABSTRACT FROM AUTHOR]

A solution strategy for optimizing the dynamic systems with flexible inequality constraints is proposed. To apply fuzzy inference in solution, the flexible portion in the problem is treated as fuzzy constraints. After functional values are bounded in a region, the objective function of this problem can also be fuzzified easily. When the problem is formulated as a fuzzy dynamic optimization problem, the iterative dynamic programming integrated with fuzzy inference is adopted to find the solution. Two examples are employed, demonstrating the facility of the proposed algorithm. [ABSTRACT FROM AUTHOR]

Liquid mixing in periodically curved microchannels with strong curvature is studied mainly using a random-walk particle-tracking method. The method uses a large number of particles to simulate fluid mixing. These particles are advected according to the velocity obtained by a grid-based method and undergo a random-walk to simulate the diffusion. For comparison purpose, the convective–diffusive equation for concentration is also solved by a grid-based method and a particle-tracking simulation with an approximate diffusion model (ADM). The present results show that the concentration distributions obtained by the random-walk particle-tracking method and the particle-tracking simulation with an ADM are in good agreement with each other. The details of concentration distribution at the exit of micromixers with strong curvature at higher Peclet numbers can be obtained by the present method. Multi-directional vortices due to large flow rate and strong curvature stretch and distort the interface between different species, and so improve fluid mixing effectively. The results reveal that the influence of channel curvature on fluid mixing increases with the increase of Reynolds number and higher mixing performance appears in the case with stronger curvature at higher Reynolds numbers. [ABSTRACT FROM AUTHOR]

Exosomes are implicated in cancer cell development, migration and invasion. Pigment epithelium-derived factor (PEDF) is a secreted anticancer protein that can regulate lung cancer progression; however, the role of PEDF in non-small cell lung cancer (NSCLC), including metastasis and cancer cell-derived exosome secretion, is unclear. In this study, we analyzed the effects of PEDF on exosome-mediated migration, invasion, and tumorigenicity of cultured NSCLC cells. The results showed that PEDF overexpression significantly reduced NSCLC invasion and migration, while inducing cell aggregation, whereas PEDF knockdown had the opposite effects. Exosomes from NSCLC cells treated with recombinant PEDF had a significantly reduced ability to promote cancer cell motility, migration, and invasion compared to exosomes from untreated cells. Exosomes from PEDF-treated cells contained thrombospondin 1 (THBS1), which inhibited cytoskeletal remodeling and exosome-induced lung cancer cell motility, migration, and invasion. Furthermore, PEDF-overexpressing NSCLC cells formed smaller xenograft tumors with higher THBS1 expression compared to control tumors. Our findings indicate that PEDF decreases the metastatic potential of NSCLC cells through regulation of THBS1 release in cancer cell-derived exosomes, thus uncovering a new mechanism of lung cancer progression. [ABSTRACT FROM AUTHOR]

Reactive oxygen species is the main contributor to photodynamic therapy. The results of this study show that a nitrogen-doped graphene quantum dot, serving as a photosensitizer, was capable of generating a higher amount of reactive oxygen species than a nitrogen-free graphene quantum dot in photodynamic therapy when photoexcited for only 3 min of 670 nm laser exposure (0.1 W cm -2 ), indicating highly improved antimicrobial effects. In addition, we found that higher nitrogen-bonding compositions of graphene quantum dots more efficiently performed photodynamic therapy actions than did the lower compositions that underwent identical treatments. Furthermore, the intrinsically emitted luminescence from nitrogen-doped graphene quantum dots and high photostability simultaneously enabled it to act as a promising contrast probe for tracking and localizing bacteria in biomedical imaging. Thus, the dual modality of nitrogen-doped graphene quantum dots presents possibilities for future clinical applications, and in particular multidrug resistant bacteria. [ABSTRACT FROM AUTHOR]

Neuronal oscillations at beta frequencies (20-50 Hz) in the cortico-basal ganglia circuits have long been the leading theory for bradykinesia, the slow movements that are cardinal symptoms in Parkinson's disease (PD). The beta oscillation theory helped to drive a frequency-based design in the development of deep brain stimulation therapy for PD. However, in contrast to this theory, here we have found that bradykinesia can be completely dissociated from beta oscillations in rodent models. Instead, we observed that bradykinesia is causatively regulated by the burst-firing pattern of the subthalamic nucleus (STN) in a feed-forward, or efferent-only, mechanism. Furthermore, STN burst-firing and beta oscillations are two independent mechanisms that are regulated by different NMDA receptors in STN. Our results shift the understanding of bradykinesia pathophysiology from an interactive oscillatory theory toward a feed-forward mechanism that is coded by firing patterns. This distinct mechanism may improve understanding of the fundamental concepts of motor control and enable more selective targeting of bradykinesia-specific mechanisms to improve PD therapy. [ABSTRACT FROM AUTHOR]