Physicochemical characterization of dapagliflozin and its solid-state behavior in stress stability test.

As an active pharmaceutical ingredient, dapagliflozin propanediol monohydrate (D-PD) has been used in the solvated form consisting of dapagliflozin compounded with (S)-propylene glycol and monohydrate at a 1:1:1 ratio. However, dapagliflozin propanediol loses the solvent's reduced lattice structure at slightly higher temperatures. Due to its sensitive solid-state stability, the temperature and humidity are strictly controlled during the production and storage of dapagliflozin. Thus, crystalline molecular complexes containing pharmaceutical salts, solvates, monohydrates, and cocrystals have recently been developed as alternative strategies. This study investigated the dapagliflozin free base (D-FB), D-PD, and dapagliflozin l-proline cocrystals (D-LP). Their solid-state behavior was also evaluated in stress stability studies. The compounds were analyzed using scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), Fourier-transform infrared (FT-IR) spectroscopy, dynamic vapor sorption (DVS), and powder rheology testing. In addition, Carr's index, the Hausner ratio, contact angle, and intrinsic dissolution rate were calculated. Dapagliflozin exhibited distinct physical properties depending upon the differences in solid form and also showed significant differences in solid-state behavior in the stress stability test. In conclusion, D-LP was superior to D-FB or D-PD in physicochemical and mechanical properties.

Economical Auto Moment Limiter for Preventing Mobile Cargo Crane Overload.

This study presents a computational method called economical auto moment limiter (eAML) that prevents a mobile cargo crane from being overloaded. The eAML detects and controls, in real time, crane overload without using boom stroke sensors and load cells, which are expensive items inevitable to existing AML systems, hence, being competitive in price. It replaces these stroke sensors and load cells that are used for the crane overload measurement with a set of mathematical formula and control logics that calculates the lifting load being handled under crane operation and the maximum lifting load. By calculating iterative them using only a pressure sensor attached under the derrick cylinder and the boom angle sensor, the mathematical model identifies the maximum descendible angle of the boom. The control logic presents the control method for preventing the crane overload by using the descendible angle obtained by the mathematical model. Both the mathematical model and the control logic are validated by rigorous simulation experiments using MATLAB on two case instances each of which eAML is used and not used, while changing the pressures on the derrick cylinder and the boom angle. The effectiveness and validity of the method are confirmed by comparing the outputs obtained by the controlled experiments performed by using a 7.6 ton crane on top of SCS887 and a straight-type maritime heavy-duty crane along with eAML. The effects attributed to the load and the wind speed are quantified to verify the reliability of eAML under the changes in external variables.

Stomata-Inspired Photomechanical Ion Nanochannels Modified by Azobenzene Composites.

A low-powered and highly selective photomechanical sensor system mimicking stomata in the epidermis of leaves harvested from nature is demonstrated. This device uses a light-responsive composite consisting of 4-amino-1,1'-azobenzene-3,4'-disulfonic acid monosodium salt (AZO) and poly(diallyldimethylammonium chloride) (PDDA) coated on a membrane with tens of nanometer-size pores. The ionic current change through the pore channels as a function of pore size variation is then measured. The tran-cis isomerism of AZO-PDDA during light irradiation and the operation mechanism of photomechanical ion channel sensor are discussed and analyzed using UV-vis spectroscopy and atomic force microscopy analysis. It presents the discriminative current levels to the different light wavelengths. The response time of the photoreceptor is about 0.2 s and it consumes very low operating power (≈15 nW) at 0.1 V bias. In addition, it is found that the change of the pore diameter during the light irradiation is due to the photomechanical effect, which is capable of distinguishing light intensity and wavelength.

Sub-5 nm nanostructures fabricated by atomic layer deposition using a carbon nanotube template.

The fabrication of nanostructures having diameters of sub-5 nm is very a important issue for bottom-up nanofabrication of nanoscale devices. In this work, we report a highly controllable method to create sub-5 nm nano-trenches and nanowires by combining area-selective atomic layer deposition (ALD) with single-walled carbon nanotubes (SWNTs) as templates. Alumina nano-trenches having a depth of 2.6 âˆ¼ 3.0 nm and SiO2 nano-trenches having a depth of 1.9 âˆ¼ 2.2 nm fully guided by the SWNTs have been formed on SiO2/Si substrate. Through infilling ZnO material by ALD in alumina nano-trenches, well-defined ZnO nanowires having a thickness of 3.1 âˆ¼ 3.3 nm have been fabricated. In order to improve the electrical properties of ZnO nanowires, as-fabricated ZnO nanowires by ALD were annealed at 350 °C in air for 60 min. As a result, we successfully demonstrated that as-synthesized ZnO nanowire using a specific template can be made for various high-density resistive components in the nanoelectronics industry.

Ambivalent Effect of Thermal Reduction in Mass Rejection through Graphene Oxide Membrane.

We report ambivalent rejection behavior of a graphene oxide membrane (GOM) having a reduced interlayer spacing. Ultrathin GOMs having a thickness of 50 nm were fabricated using a vacuum filtration method followed by subjecting the samples to thermal reduction at 162 °C. The interlayer spacing of GOMs was reduced by 1 Å on thermal reduction as compared with that of the natural GOMs. The rejection rate with dye molecules was tested using dyes having three different types of charges in a dead-end filtration instrument. Rejection rate of the reduced GOM with the dyes having an opposite charge was improved up to 99.7%, indicating the dominant effect of the physical sieving diameter. In contrast, in the case of ion permeation of natural GOM, a higher rejection rate for several metal ions was observed as compared with that of GOMs having 1 Å smaller interlayer spacing, indicating the dominant effect of surface charges on the GOM samples.

Ultrasensitive and selective fluorimetric detection of copper ions using thiosulfate-involved quantum dots.

A simple and effective quantum dots (QDs)-based sensing method for copper ion (Cu(2+)) in water is developed with improved selectivity and ultrahigh sensitivity in the presence of thiosulfate. For this, hexadecyl trimethylammonium bromide (CTAB) modified CdSe/ZnS QDs is used as a fluorescent probe. In the absence of thiosulfate, mercury and silver ions show strong interference with Cu(2+) ions even though the sensitivity can be obtained within a few nanomolar. By using our method, the lowest detected concentration for Cu(2+) is 0.15 nM in the presence of thiosulfate in DI water. Also, it is successfully demonstrated for Cu(2+) ion detection in practical application (tap water) down to lowest detection limit, 0.14 nM. This method provides a good potential for copper ions detection with simplicity, rapidity, ultrahigh sensitivity, and excellent selectivity.

Highly conductive and stretchable Ag nanowire/carbon nanotube hybrid conductors.

Fabricating stretchable conductors through simple, cost-effective and scalable methods is a challenge. Here, we report on an approach used to develop nanowelded Ag nanowire/single-walled carbon nanotube (AgNW/SWCNT) hybrid films to be used as high-performance stretchable conductors. Plasmonic welding, which was done at the junctions of AgNWs in order to form hybrid AgNW/SWCNT conductors on an Ecoflex substrate, enabled excellent electrical and mechanical stability under large tensile strains of over 480% without the need to pre-strain. Furthermore, we demonstrate highly stretchable circuits that are used to power LED arrays. The LED arrays are formed using the plasmonic-welded AgNW/SWCNT/Ecoflex hybrid material, which demonstrates suitability for interconnector applications in flexible electronics.

Frequency-Selective, Multi-Channel, Self-Powered Artificial Basilar Membrane Sensor with a Spiral Shape and 24 Critical Bands Inspired by the Human Cochlea.

A spiral-artificial basilar membrane (S-ABM) sensor is reported that mimics the basilar membrane (BM) of the human cochlea and can detect sound by separating it into 24 sensing channels based on the frequency band. For this, an analytical function is proposed to design the width of the BM so that the frequency bands are linearly located along the length of the BM. To fabricate the S-ABM sensor, a spiral-shaped polyimide film is used as a vibrating membrane, with maximum displacement at locations corresponding to specific frequency bands of sound, and attach piezoelectric sensor modules made of poly(vinylidene fluoride-trifluoroethylene) film on top of the polyimide film to measure the vibration amplitude at each channel location. As the result, the S-ABM sensor implements a characteristic frequency band of 96-12,821 Hz and 24-independent critical bands. Using real-time signals from discriminate channels, it is demonstrated that the sensor can rapidly identify the operational noises from equipment processes as well as vehicle sounds from environmental noises on the road. The sensor can be used in a variety of applications, including speech recognition, dangerous situation recognition, hearing aids, and cochlear implants, and more.

Visible cathodoluminescence of quantum dot films by direct irradiation of electron beam and its materialization as a field emission device.

The field emission (FE) device based on quantum dot (QD) films as a cathodoluminescent (CL) material has not emerged yet due to the relatively low quantum efficiency and weak photostability of nanocrystals (NCs). Here we improve film stability and luminescence yields by preparing neat films of well-packed core-multishell QDs using spray coating method and then using low-temperature atomic layer deposition (ALD) to infill the pores of these films with metal oxides to produce inorganic nanocomposites. The ALD coatings to protect oxidation and degradation by electrons prevent internal atomic and molecular diffusion and decrease surface trap densities of QD films. Furthermore, the CL of the core-multishell QD films is 2.4 times higher than before ALD infilling. We fabricate the FE device by combining cathode structure with carbon nanotube (CNT) emitters and anode plates with QD thin film and successfully can get brilliant images of the light-emitting FE device. Our research opens a way for developing new quantum optoelectronics with high-performance.

Alumina/polymer-coated nanocrystals with extremely high stability used as a color conversion material in LEDs.

The long-term stability of quantum dot (QD)-based devices under harsh environmental conditions has been a critical bottleneck to be resolved for commercial use. Here, we demonstrate an extremely stable QD/alumina/polymer hybrid structure by combining internal atomic layer deposition (ALD) infilling with polymer encapsulation. ALD infilling and polymer encapsulation of QDs synergistically prohibit the degradation of QDs in terms of optical, thermal and humid attacks. Our hybrid QD/alumina/polymer film structure showed no noticeable reduction in photoluminescence even in a commercial grade test (85% humidity at 85°C) over 28 days. In addition, we successfully fabricated a QD-based light-emitting device with excellent long-term stability by incorporating hybrid QD/alumina/polymer film as a color conversion material on light-emitting diode chips.

Screening of dihydropyrimidine dehydrogenase genetic variants by direct sequencing in different ethnic groups.

Dihydropyrimidine dehydrogenase (DPYD) is an enzyme that regulates the rate-limiting step in pyrimidine metabolism, especially catabolism of fluorouracil, a chemotherapeutic agent for cancer. In order to determine the genetic distribution of DPYD, we directly sequenced 288 subjects from five ethnic groups (96 Koreans, 48 Japanese, 48 Han Chinese, 48 African Americans, and 48 European Americans). As a result, 56 polymorphisms were observed, including 6 core polymorphisms and 18 novel polymorphisms. Allele frequencies were nearly the same across the Asian populations, Korean, Han Chinese and Japanese, whereas several SNPs showed different genetic distributions between Asians and other ethnic populations (African American and European American). Additional in silico analysis was performed to predict the function of novel SNPs. One nonsynonymous SNP (+199381A > G, Asn151Asp) was predicted to change its polarity of amino acid (Asn, neutral to Asp, negative). These findings would be valuable for further research, including pharmacogenetic and drug responses studies.

Artificial Action Potential and Ionic Power Device Inspired by Ion Channels and Excitable Cell.

In vivo, the membrane potential of the excitable cell working by ion gradients plays a significant role in bioelectricity generation and nervous system operation. Conventional bioinspired power systems generally have adopted ion gradients, but overlook the functions of ion channels and Donnan effect to generate efficient ion flow in the cell. Here, cell-inspired ionic power device implementing the Donnan effect using multi-ions and monovalent ion exchange membranes as artificial ion channels is realized. Different ion-rich electrolytes on either side of the selective membrane generate the ion gradient potentials with high ionic currents and reduce the osmotic imbalance of the membrane. Based on this device, the artificial neuronal signaling is presented by the mechanical switching system of the ion selectivity like mechanosensitive ion channels in a sensory neuron. Compared with reverse electrodialysis, which requires a low concentration, a high-power device with ten times the current and 8.5 times the power density is fabricated. This device activates grown muscle cells by increasing power through serial connection like an electric eel, and shows the possibility of an ion-based artificial nervous system.

Corrugated surface microparticles with chitosan and levofloxacin for improved aerodynamic performance.

Corrugated surface microparticles comprising levofloxacin (LEV), chitosan and organic acid were prepared using the 3-combo spray drying method. The amount and the boiling point of the organic acid affected the degree of roughness. In this study, we tried to improve the aerodynamic performance and increase aerosolization by corrugated surface microparticle for lung drug delivery efficiency as dry powder inhaler. HMP175 L20 prepared with 175 mmol propionic acid solution was corrugated more than HMF175 L20 prepared with 175 mmol formic acid solution. The ACI and PIV results showed a significant increase in aerodynamic performance of corrugated microparticles. The FPF value of HMP175 L20 was 41.3% ± 3.9% compared with 25.6% ± 7.7% of HMF175 L20. Corrugated microparticles also showed better aerosolization, decreased x-axial velocity, and variable angle. Rapid dissolution of drug formulations was observed in vivo. Low doses administered to the lungs achieved higher LEV concentrations in the lung fluid than high doses administered orally. Surface modification in the polymer-based formulation was achieved by controlling the evaporation rate and improving the inhalation efficiency of DPIs.

Surface-plasmon-based colorimetric detection of Cu(II) ions using label-free gold nanoparticles in aqueous thiosulfate systems.

We report colorimetric, label-free and non-aggregation-based gold nanoparticle (AuNP) probes for the highly selective detection of Cu(II) ions in aqueous environments. This detection scheme relies on the ability of Cu(II) ions to catalyze the leaching of gold at room temperature in the presence of thiosulfate species and ammonia. This simple and cost-effective probe provides rapid detection of Cu(II) ions at concentrations as low as 10 ppm. A similar detection method using AuNPs in ammonia-free thiosulfate solution is also viable at moderate reaction temperature (50 °C). The ammonia-free method also leads to marked damping and red-shifting of the surface plasmon resonance signal of the AuNP dispersion. The two methods clearly differ in the nature of the surface plasmon damping phenomenon, and their working mechanisms are plausibly explained based on the experimental investigations.

Successive and large-scale synthesis of InP/ZnS quantum dots in a hybrid reactor and their application to white LEDs.

We report successive and large-scale synthesis of InP/ZnS core/shell nanocrystal quantum dots (QDs) using a customized hybrid flow reactor, which is based on serial combination of a batch-type mixer and a flow-type furnace. InP cores and InP/ZnS core/shell QDs were successively synthesized in the hybrid reactor in a simple one-step process. In this reactor, the flow rate of the solutions was typically 1 ml min(-1), 100 times larger than that of conventional microfluidic reactors. In order to synthesize high-quality InP/ZnS QDs, we controlled both the flow rate and the crystal growth temperature. Finally, we obtained high-quality InP/ZnS QDs in colors from bluish green to red, and we demonstrated that these core/shell QDs could be incorporated into white-light-emitting diode (LED) devices to improve color rendering performance.

Macrodispersion of multi-walled carbon nanotubes for conductive films.

Understanding of the effect of the multi-walled carbon nanotube (MWCNT) dispersion process on physical properties of MWCNT film is crucial in process optimization of MWCNT film-based products. In the present work, the electrical conduction property of MWCNT films according to various conditions in MWCNT dispersion is investigated. Spectroscopic analysis of dispersed MWCNTs show that the electrical resistance of the MWCNT conductive film is affected by an increase in the electrical contacts between adjacent CNTs due to CNT debundling and physical damage caused by ultrasonic processing. Based on the two conflicting parameters, dispersion guidelines for highly conductive MWCNT film are presented.

A Wearable All-Gel Multimodal Cutaneous Sensor Enabling Simultaneous Single-Site Monitoring of Cardiac-Related Biophysical Signals.

The human cutaneous sensory organ is a highly evolved biosensor that is efficient, sensitive, selective, and adaptable. Recently, with the development of various materials and structures inspired by sensory organs, artificial cutaneous sensors have been widely studied. In this study, the acquisition of biophysical signals is demonstrated at one point on the body using a wearable all-gel-integrated multimodal sensor composed of four element sensors, inspired by the slow/rapid adapting functions of the skin sensory receptors. The gel-type sensors ensure flexibility, compactness, portability, adherence, and integrity. The wearable all-gel multimodal sensor is easily attached to the wrist and simultaneously gathers blood pressure (BP), electrocardiogram (ECG), electromyogram (EMG), and mechanomyogram (MMG) signals related to cardiac and muscle health. Human activity causes muscle contraction, which affects blood flow; therefore, the relationship between the muscle and heart is crucial for screening and predicting heart health. Cardiac health is monitored by obtaining the two types of phase time differences (i.e., Δtbe : BP and ECG, Δtem : ECG and MMG) generated during muscle movement. The suggested multimodal sensor has potential applicability in monitoring biophysical conditions and diagnosing cardiac-related health problems.

Inhalable Nano-Dimpled Microspheres Containing Budesonide-PLGA for Improved Aerodynamic Performance.

Introduction: Dry powder inhalations are an attractive pharmaceutical dosage form. They are environmentally friendly, portable, and physicochemical stable compared to other inhalation forms like pressurized metered-dose inhalers and nebulizers. Sufficient drug deposition of DPIs into the deep lung is required to enhance the therapeutic activity. Nanoscale surface roughness in microparticles could improve aerosolization and aerodynamic performance. This study aimed to prepare microspheres with nanoscale dimples and confirm the effect of roughness on inhalation efficiency. Methods: The dimpled-surface on microspheres (MSs) was achieved by oil in water (O/W) emulsion-solvent evaporation by controlling the stirring rate. The physicochemical properties of MSs were characterized. Also, in vitro aerodynamic performance of MSs was evaluated by particle image velocimetry and computational fluid dynamics. Results: The particle image velocimetry results showed that dimpled-surface MSs had better aerosolization, about 20% decreased X-axial velocity, and a variable angle, which could improve the aerodynamic performance. Furthermore, it was confirmed that the dimpled surface of MSs could cause movement away from the bronchial surface, which helps the MSs travel into the deep lung using computational fluid dynamics. Conclusion: The dimpled-surface MSs showed a higher fine particle fraction value compared to smooth-surface MSs in the Andersen Cascade Impactor, and surface roughness like dimples on microspheres could improve aerosolization and lung deposition.

Asymmetric Dichroic Colors in Stretchable Film with Embedded Au/Ag Alloy Nanoparticles.

We present a new type of stretchable dichroic film in which Au and Ag alloy nanoparticles (NPs) are dispersed in polydimethylsiloxane (PDMS). The alloy NPs are synthesized with different atomic compositions and sizes to modulate their plasmonic resonance frequencies and absorption and scattering cross sections. The PDMS dichroic film in which 100 nm alloy NPs with a Au/Ag ratio of 7:3 are dispersed shows exotic optical properties under tensile strain. When 40% tensile strain is applied, the film exhibits a strain-sensitive transmission and strain-insensitive reflection behavior in which the transmittance is increased up to 2.6 times, whereas the reflectance remains unchanged. Moreover, we demonstrate a stretchable anticounterfeiting film and a flexible dichroic sculpture fabricated with the PDMS composite. This work demonstrates a new type of plasmonic application that has great potential in various applications, such as special-purpose optical films, security patterns, and smart windows.

Strong and Tough Nacre-Inspired Graphene Oxide Composite with Hierarchically Similar Structure.

We report a graphene oxide (GO)-based composite, featuring GO/cross-linking agent (CA) nanoparticles, inspired by a nacre-like hierarchical structure present in nature. The as-prepared GO/CA composite was powdered to nanoscale particles and then mixed with pure GO to be GO/CA/GO (GCG) composite forming hierarchical GO/CA nanoasperities on the GO surface. The strength and toughness of the nacre-inspired GCG composite films were simultaneously improved by adjusting the nanoparticle concentration and hierarchical level of the GO-based films. Compared to pristine GO films and GO/CA composites, which exhibit a low level of hierarchy in their structures, the tensile strength and toughness of the GCG composites with higher hierarchy were enhanced 3.1 and 1.6 times and 47.6 and 10.9 times, respectively. Furthermore, a plausible mechanism of increasing mechanical properties based on nanoscale asperities and homogeneous interactions between GO and CA has been discussed.