Free Vibration Analysis of a Tunable Micro-Fabrication Device Comprising Asymmetric L-Shaped Membranes.

Membrane sensors have been widely used in various fields owing to their multifunctionality and cost-effectiveness. However, few studies have investigated frequency-tunable membrane sensors, which could enable versatility in the face of different device requirements while retaining high sensitivity, fast response times, and high accuracy. In this study, we propose a device comprising an asymmetric L-shaped membrane with tunable operating frequencies for microfabrication and mass sensing applications. The resonant frequency could be controlled by adjusting the membrane geometry. To fully understand the vibration characteristics of the asymmetric L-shaped membrane, the free vibrations of the membrane are first solved by a semi-analytical treatment combining domain decomposition and variable separation methods. The finite-element solutions confirmed the validity of the derived semi-analytical solutions. Parametric analysis results revealed that the fundamental natural frequency decreases monotonically with the increase in length or width of the membrane segment. Numerical examples revealed that the proposed model can be employed to identify suitable materials for membrane sensors with specific frequency requirements under a given set of L-shaped membrane geometries. The model can also achieve frequency matching by changing the length or width of membrane segments given a specified membrane material. Finally, performance sensitivity analyses for mass sensing were carried out, and the results showed that the performance sensitivity was up to 0.7 kHz/pg for polymer materials under certain conditions.

A micromechanical study on the effects of precipitation on the mechanical properties of CoCrFeMnNi high entropy alloys with various annealing temperatures.

The CoCrFeMnNi high entropy alloys remain an active field over a decade owing to its excellent mechanical properties. However, the application of CoCrFeMnNi is limited because of the relatively low tensile strength. Here we proposed a micromechanical model which adopted from the theory of dislocation density to investigate the strengthening mechanisms of precipitation of chromium-rich non-equiatomic CoCrFeMnNi alloy. The microstructures of CoCrFeMnNi were obtained directly from SEM-BSE images with different annealing temperatures. The proposed framework is validated by comparing simulations with experiments of uniaxial tensile tests on the CoCrFeMnNi alloys under different annealing temperatures. The stress-strain curves indicate that the precipitate has greater influence on post-yield hardening than the initial yielding strength. In addition, we identified that the particle distribution, controlled by the average size of the particle and the volume fraction of precipitation, can significantly enhance the strengthening effect. The numerical results indicate that HEAs with a precipitate distribution closer to a normal distribution and with smaller average size will tend to have higher strength and ductility.

Chronic intermittent hypoxia worsens brain damage and sensorimotor behavioral abnormalities after ischemic stroke: Effect on autonomic nervous activity and sleep patterns.

OBJECTIVE: Sleep apnea (SA) is characterized by intermittent hypoxia (IH), which increases sympathetic activity and sleep fragmentation, thus increasing the risk of stroke. SA is a highly prevalent disease and can worsen prognosis in patients with stroke. However, the correlation of changes in the cardiac autonomic nervous system and sleep patterns under IH with sensorimotor behavior and cerebral infarction after stroke remains unclear. We hypothesized that dysregulated autonomic activity and unstable sleep patterns induced by IH and correlated with cerebral infarction and abnormal sensorimotor behavior after middle cerebral artery occlusion (MCAO). METHODS: Wistar-Kyoto rats (WKY) were divided into IH (hypoxia: 5 % O2, 8 h/day) and RA group (room air) for 2 weeks and both groups were subjected to MCAO. After MCAO, the IH group was continuously exposed to IH for 1 week. The 24-h physiological signals, blood pressure, and sensorimotor behavior were recorded at baseline (Bas), the first and second weeks during IH (RA/IH1W and RA/IH2W, respectively), and poststroke. RESULTS: Before MCAO, IH caused sympathetic activity during sleep and parasympathetic activity of active waking (AW) to increase. Moreover, IH reduced the accumulated time and duration of paradoxical sleep (PS) and increased the interruption during sleep. After MCAO, IH increased blood pressure, more severe brain damage, and poor sensorimotor performance. Moreover, IH reduced autonomic activity after MCAO and decreased sympathetic activity was associated with poor sensorimotor performance. CONCLUSION: Autonomic activity and sleep patterns affected by IH were correlated with increased cerebral infarction and poor sensorimotor behavior after MCAO.

High-Dimensional Phase Space Reconstruction with a Convolutional Neural Network for Structural Health Monitoring.

In order to accurately diagnose the health of high-order statically indeterminate structures, most existing structural health monitoring (SHM) methods require multiple sensors to collect enough information. However, comprehensive data collection from multiple sensors for high degree-of-freedom structures is not typically available in practice. We propose a method that reconciles the two seemingly conflicting difficulties. Takens' embedding theorem is used to augment the dimensions of data collected from a single sensor. Taking advantage of the success of machine learning in image classification, high-dimensional reconstructed attractors were converted into images and fed into a convolutional neural network (CNN). Attractor classification was performed for 10 damage cases of a 3-story shear frame structure. Numerical results show that the inherently high dimension of the CNN model allows the handling of higher dimensional data. Information on both the level and the location of damage was successfully embedded. The same methodology will allow the extraction of data with unsupervised CNN classification to be consistent with real use cases.

Development of Novel Lightweight Dual-Phase Al-Ti-Cr-Mn-V Medium-Entropy Alloys with High Strength and Ductility.

A novel lightweight Al-Ti-Cr-Mn-V medium-entropy alloy (MEA) system was developed using a nonequiatiomic approach and alloys were produced through arc melting and drop casting. These alloys comprised a body-centered cubic (BCC) and face-centered cubic (FCC) dual phase with a density of approximately 4.5 g/cm3. However, the fraction of the BCC phase and morphology of the FCC phase can be controlled by incorporating other elements. The results of compression tests indicated that these Al-Ti-Cr-Mn-V alloys exhibited a prominent compression strength (~1940 MPa) and ductility (~30%). Moreover, homogenized samples maintained a high compression strength of 1900 MPa and similar ductility (30%). Due to the high specific compressive strength (0.433 GPa·g/cm3) and excellent combination of strength and ductility, the cast lightweight Al-Ti-Cr-Mn-V MEAs are a promising alloy system for application in transportation and energy industries.

Ultrasound-responsive NIPAM-based hydrogels with tunable profile of controlled release of large molecules.

Episodic release of bioactive compounds plays an important role in biological systems. "On-demand" release systems which based on polymeric materials and activated by external stimuli may provide the necessary functionality. Here we describe an ultrasound-responsive hydrogel based on N-isopropylacrylamide (NIPAM) and N,N'-methylenebisacrylamide (MBAm), which is suitable for triggered release of two large molecules: bovine serum albumin (BSA, 66kDa) and dextran (3-5kDa). It is shown that the release amount of these two large molecules increased with increasing hydrogel temperature, and the application of ultrasound further increased the release. By simply adjusting the contents of NIPAM and MBAm, the difference of BSA release between the presence and absence of ultrasound could be adjusted from 2.7 to 84 folds. There was also a positive correlation between the ultrasound intensity and release amount. These properties made the NIPAM-based hydrogel a tunable platform for focal drug delivery.

Anti-melasma codrug of retinoic acid assists cutaneous absorption with attenuated skin irritation.

Melasma treatment with combined retinoic acid (RA) and hydroquinone (HQ) usually causes unsatisfactory outcomes and safety concerns. This study attempted to evaluate the cutaneous absorption and skin tolerance of the codrug conjugated with RA and HQ via ester linkage. The codrug's permeation of the pig skin was estimated using Franz diffusion cell. The codrug and parent drugs were comparatively examined for anti-inflammatory activity and tyrosinase inhibition. In vivo cutaneous irritation was assessed on nude mouse skin. Chemical conjugation of RA with HQ increased the lipophilicity and thus the skin absorption. The codrug absorption produced a 5.5- and a 60.8-fold increment compared to RA skin deposition at an equimolar (1.2mM) and saturated solubility dose, respectively. The cumulative amount of HQ derived from the codrug in the receptor was comparable to or less than that of topically applied HQ. The RA-HQ codrug was partly hydrolyzed on penetrating the skin. The hydrolysis rate in intact skin was significantly lower than that in esterase medium and skin homogenates. The codrug showed an interleukin (IL)-6 inhibition activity comparable to RA. A therapeutic index 6-fold greater than RA was obtained with the topical codrug. The tyrosinase inhibition percentage of the codrug and HQ was 13% and 21%, respectively. The skin tolerance test determined by transepidermal water loss (TEWL), redness, and histopathology had exhibited minor skin irritation caused by the codrug compared to the physical mixture of RA and HQ at an equivalent dose. Topical codrug delivery not only promoted RA absorption, but also diminished the adverse effects of the parent agents.

Determination of salicylic acid using a magnetic iron oxide nanoparticle-based solid-phase extraction procedure followed by an online concentration technique through micellar electrokinetic capillary chromatography.

In this study, a magnetic iron oxide nanoparticle-based solid-phase extraction procedure combined with the online concentration and separation of salicylic acid (SA) through micellar electrokinetic chromatography-UV detection (MEKC-UV) was developed. Under optimal experimental conditions, a good linearity in the range of 0.01-100µmolL-1 was obtained with a coefficient of correlation of 0.9999. The detection sensitivity of the proposed method exhibited an approximately 1026-fold improvement compared with a single MEKC method without online concentration, and the detection limit (S/N=3) was 3.80nmolL-1. The repeatability of the method was evaluated using intraday and interday RSDs (11.5% and 17.0%, respectively). The method was used to determine SA concentrations in tobacco leaves (Nicotiana tabacum L. cv. Samsun) from the NN genotype, nn genotype, and Nt-NahG mutant strains, as well as in shampoo and ointment samples. Rapid extraction and separation (<50min), acceptable repeatability (RSD<17.0%), and high spiked recoveries (95.8%-102.4%) were observed for plants, detergents, and pharmaceuticals.

Solvothermal synthesis of Ag hybrid BiPO4 heterostructures with enhanced photodegradation activity and stability.

In this study, Ag hybrid BiPO4 (Ag/BiPO4) heterostructures were synthesized using a solvothermal method. The morphologies and optical properties of the Ag/BiPO4 heterostructures were drastically different from those of BiPO4 and were highly dependent on the AgNO3:BiPO4 weight percent during the synthesis. The three formulated heterostructures were evaluated for their photocatalytic degradation of methylene blue (MB) under UV light illumination; the 0.5%Ag/BiPO4 heterostructure was observed to result in 99% degradation of MB within 60min, a remarkably higher level of photodegradation activity than the levels caused by TiO2 and BiPO4. Furthermore, even after use for five cycles of MB degradation, the 0.5%Ag/BiPO4 heterostructure showed no observable loss in photodegradation activity and no change in XRD patterns, demonstrating its chemical and structural stability. According to the results of a systematic experimental investigation, the enhanced photodegradation activity of this Ag/BiPO4 heterostructure could be ascribed to the high position of its valence band and the highly efficient separation of photogenerated electrons and holes. Moreover, hydroxyl radicals and holes were found to be the major reactive species. Successful photodegradation of standard dye solutions, including acid blue 1, methyl orange, fast green, rhodamine B, rhodamine 6G, and MB, in real water samples was demonstrated with the 0.5%Ag/BiPO4 heterostructure, providing clear evidence of its utility for treating waste water containing organic dyes.

Non-ablative fractional laser assists cutaneous delivery of small- and macro-molecules with minimal bacterial infection risk.

Use of the ablative laser has been approved to enhance topical drug penetration. Investigation into the usefulness of the non-ablative laser for assisting drug delivery is very limited. In this study, we explored the safety and efficacy of the non-ablative fractional erbium:glass (Er:glass) laser as an enhancement approach to promote drug permeation. Both pig and nude mouse skins were employed as transport barriers. We histologically examined the skin structure after laser exposure. The permeants of 5-aminolevulinic acid (ALA), imiquimod, tretinoin, peptide, dextrans and quantum dots (QD) were used to evaluate in vitro and in vivo skin passage. The fractional laser selectively created an array of photothermal dots deep into the dermis with the preservation of the stratum corneum and epidermis. The barrier function of the skin could be recovered 8-60h post-irradiation depending on the laser spot densities. The application of the laser caused no local infection of Staphylococcus aureus and Pseudomonas aeruginosa. Compared to intact skin, ALA flux was enhanced up to 1200-fold after laser exposure. The penetration enhancement level by the laser was decreased following the increase of permeant lipophilicity. The skin accumulation of tretinoin, an extremely lipophilic drug, showed only a 2-fold elevation by laser irradiation. The laser promoted peptide penetration 10-fold compared to the control skin. Skin delivery of dextrans with a molecular weight (MW) of at least 40kDa could be achieved with the Er:glass laser. QD with a diameter of 20nm penetrated into the skin with the assistance of the non-ablative laser. The confocal microscopic images indicated the perpendicular and lateral diffusions of dextrans and nanoparticles via laser-created microscopic thermal zones. Controlled Er:glass laser irradiation offers a valid enhancement strategy to topically administer the permeants with a wide MW and lipophilicity range.

Effects of an implant on temperature distribution in tissue during ultrasound diathermy.

The effects of an implant on temperature distribution in a tissue-mimicking hydrogel phantom during the application of therapeutic ultrasound were investigated. In vitro experiments were conducted to compare the influences of plastic and metal implants on ultrasound diathermy and to calibrate parameters in finite element simulation models. The temperature histories and characteristics of the opaque (denatured) areas in the hydrogel phantoms predicted by the numerical simulations show good correlation with those observed in the in vitro experiments. This study provides an insight into the temperature profile in the vicinity of an implant by therapeutic ultrasound heating typically used for physiotherapy. A parametric study was conducted through numerical simulations to investigate the effects of several factors, such as implant material type, ultrasound operation frequency, implant thickness and tissue thickness on the temperature distribution in the hydrogel phantom. The results indicate that the implant material type and implant thickness are the main parameters influencing the temperature distribution. In addition, once the implant material and ultrasound operation frequency are chosen, an optimal implant thickness can be obtained so as to avoid overheating injuries in tissue.

Assembly of Lock-and-Key Colloids Mediated by Polymeric Depletant.

Polymer-mediated lock-and-key assembly via depletion attraction is purely a shape-recognition process without any molecular bonding. Since the depletion attraction relates to osmotic pressure and excluded volume, the binding tendency in a dispersion of lock-and-key colloids can be controlled by adjusting the characteristics of polymeric depletants. In this work, dissipative particle dynamics accounting for explicit solvents, polymers, and multiple lock-key pairs are performed to investigate the influences of the polymer concentration, chain length, solvent quality, and chain stiffness. As the polymer concentration associated with osmotic pressure is increased, the binding free energy (E(b)) between a lock-key pair rises linearly and the binding fraction (θ(LK)) in the dispersion grows sigmoidally. Moreover, the increases in the chain length, solvent quality, and chain stiffness lead to the expansion of the polymer size associated with excluded volume and thus both E(b) and θ(LK) rise accordingly. However, E(b) and θ(LK) grow to be insensitive to the chain length for long enough polymer coils but still can be enhanced if the polymer becomes rod-like. As the solvent quality is varied, θ(LK) can be dramatically altered, although the radius of gyration of polymers is slightly changed.

Reusable tissue-mimicking hydrogel phantoms for focused ultrasound ablation.

The ability of N-isopropylacrylamide (NIPAM)-based hydrogel phantoms to mimic tissues with different acoustic and thermal properties under high-intensity focused ultrasound (HIFU) ablation was investigated. These phantoms were designed to model the formation of thermal lesions in tissues above the threshold temperature of protein denaturation. By adjusting the concentration of acrylic acid (AAc) in the NIPAM-based hydrogel phantoms, the cloud point (i.e., lower critical solution temperature) of the phantoms could be tailored to produce HIFU thermal lesions similar to those formed in different swine tissues in terms of size and shape. Additionally, energy thresholds for inducing transient or permanent bubbles in the phantoms during HIFU ablation were also identified to shed light on the onset of cavitation or material damage. The NIPAM-based hydrogel phantoms developed in this study possess major advantages such as transparent, reusable and tailorable properties, and are practical tools for characterizing an ablative device (or treatment) to determine its efficacy and safety.

Ultrasound thermal mapping based on a hybrid method combining physical and statistical models.

Non-invasive temperature measurement of tissues deep inside the body has great potential for clinical applications, such as temperature monitoring during thermal therapy and early diagnosis of diseases. We developed a novel method for both temperature estimation and thermal mapping that uses ultrasound B-mode radiofrequency data. The proposed method is a hybrid that combines elements of physical and statistical models to achieve higher precision and resolution of temperature variations and distribution. We propose a dimensionless combined index (CI) that combines the echo shift differential and signal intensity difference with a weighting factor relative to the distance from the heat source. In vitro experiments verified that the combined index has a strong linear relationship with temperature variation and can be used to effectively estimate temperature with an average relative error <5%. This algorithm provides an alternative for imaging guidance-based techniques during thermal therapy and could easily be integrated into existing ultrasound systems.

Ultrasound thermal mapping based on a hybrid method combining cross-correlation and zero-crossing tracking.

A hybrid method for estimating temperature with spatial mapping using diagnostic ultrasound, based on detection of echo shifts from tissue undergoing thermal treatment, is proposed. Cross-correlation and zero-crossing tracking are two conventional algorithms used for detecting echo shifts, but their practical applications are limited. The proposed hybrid method combines the advantages of both algorithms with improved accuracy in temperature estimation. In vitro experiments were performed on porcine muscle for preliminary validation and temperature calibration. In addition, thermal mapping of rabbit thigh muscle in vivo during high-intensity focused ultrasound heating was conducted. Results from the in vitro experiments indicated that the difference between the estimated temperature change by the proposed hybrid method and the actual temperature change measured by the thermocouple was generally less than 1 °C when the increase in temperature due to heating was less than 10 °C. For the in vivo study, the area predicted to experience the highest temperature coincided well with the focal point of the high-intensity focused ultrasound transducer. The computational efficiency of the hybrid algorithm was similar to that of the fast cross-correlation algorithm, but with an improved accuracy. The proposed hybrid method could provide an alternative means for non-invasive monitoring of limited temperature changes during hyperthermia therapy.