ASOptimizer: Optimizing antisense oligonucleotides through deep learning for IDO1 gene regulation.

Recent studies have highlighted the effectiveness of using antisense oligonucleotides (ASOs) for cellular RNA regulation, including targets that are considered undruggable; however, manually designing optimal ASO sequences can be labor intensive and time consuming, which potentially limits their broader application. To address this challenge, we introduce a platform, the ASOptimizer, a deep-learning-based framework that efficiently designs ASOs at a low cost. This platform not only selects the most efficient mRNA target sites but also optimizes the chemical modifications for enhanced performance. Indoleamine 2,3-dioxygenase 1 (IDO1) promotes cancer survival by depleting tryptophan and producing kynurenine, leading to immunosuppression through the aryl-hydrocarbon receptor (Ahr) pathway within the tumor microenvironment. We used ASOptimizer to identify ASOs that target IDO1 mRNA as potential cancer therapeutics. Our methodology consists of two stages: sequence engineering and chemical engineering. During the sequence-engineering stage, we optimized and predicted ASO sequences that could target IDO1 mRNA efficiently. In the chemical-engineering stage, we further refined these ASOs to enhance their inhibitory activity while reducing their potential cytotoxicity. In conclusion, our research demonstrates the potential of ASOptimizer for identifying ASOs with improved efficacy and safety.

Molecular Self-Assembly and Adsorption Structure of 2,2'-Dipyrimidyl Disulfides on Au(111) Surfaces.

The effects of solution concentration and pH on the formation and surface structure of 2-pyrimidinethiolate (2PymS) self-assembled monolayers (SAMs) on Au(111) via the adsorption of 2,2'-dipyrimidyl disulfide (DPymDS) were examined using scanning tunneling microscopy (STM) and X-ray photoelectron spectroscopy (XPS). STM observations revealed that the formation and structural order of 2PymS SAMs were markedly influenced by the solution concentration and pH. 2PymS SAMs formed in a 0.01 mM ethanol solution were mainly composed of a more uniform and ordered phase compared with those formed in 0.001 mM or 1 mM solutions. SAMs formed in a 0.01 mM solution at pH 2 were composed of a fully disordered phase with many irregular and bright aggregates, whereas SAMs formed at pH 7 had small ordered domains and many bright islands. As the solution pH increased from pH 7 to pH 12, the surface morphology of 2PymS SAMs remarkably changed from small ordered domains to large ordered domains, which can be described as a (4√2 × 3)R51° packing structure. XPS measurements clearly showed that the adsorption of DPymDS on Au(111) resulted in the formation of 2PymS (thiolate) SAMs via the cleavage of the disulfide (S-S) bond in DPymDS, and most N atoms in the pyrimidine rings existed in the deprotonated form. The results herein will provide a new insight into the molecular self-assembly behaviors and adsorption structures of DPymDS molecules on Au(111) depending on solution concentration and pH.

Molecular Characteristics of Catalytic Nitrogen Removal from Coal Tar Pitch over γ-Alumina-Supported NiMo and CoMo Catalysts.

The removal of nitrogen from coal tar pitch (CTP) through the hydrodenitrogenation (HDN) of CTP and its molecular behavior were evaluated in the presence of NiMo/γ-alumina and CoMo/γ-alumina catalysts. Fourier transform ion cyclotron resonance mass spectrometry with atmospheric pressure photoionization was used to analyze the complicated chemical classes and species of CTP and the treated products at the molecular level. Nitrogen species were qualitatively analyzed before and after hydrotreatment. A single-stage hydrotreatment with an HDN catalyst resulted in a high sulfur removal performance (85.6-94.7%) but a low nitrogen removal performance (26.8-29.2%). Based on relative abundance analyses of nitrogen and binary nitrogen species, CcHh-NnSs was the most challenging species to remove during HDN treatment. Furthermore, prior hydrodesulfurization was combined with HDN treatment, and the dual hydrotreatments yielded a significantly improved nitrogen removal performance (46.4-48.7%).

Effective Removal of Acetaldehyde Using Piperazine/Nitric Acid Co-Impregnated Bead-Type Activated Carbon.

Acetaldehyde (CH3CHO) in the atmosphere is associated with adverse health effects. Among the various options for use in removing CH3CHO, adsorption is often employed because of its convenient application and economical processes, particularly when using activated carbon. In previous studies, the surface of activated carbon has been modified with amines to remove CH3CHO from the atmosphere via adsorption. However, these materials are toxic and can have harmful effects on humans when the modified activated carbon is used in air-purifier filters. Therefore, in this study, a customized bead-type activated carbon (BAC) with surface modification options via amination was evaluated for removing CH3CHO. Various amounts of non-toxic piperazine or piperazine/nitric acid were used in amination. Chemical and physical analyses of the surface-modified BAC samples were performed using Brunauer-Emmett-Teller measurements, elemental analyses, and Fourier transform infrared and X-ray photoelectron spectroscopy. The chemical structures on the surfaces of the modified BACs were analyzed in detail using X-ray absorption spectroscopy. The amine and carboxylic acid groups on the surfaces of the modified BACs are critical in CH3CHO adsorption. Notably, piperazine amination decreased the pore size and volume of the modified BAC, but piperazine/nitric acid impregnation maintained the pore size and volume of the modified BAC. In terms of CH3CHO adsorption, piperazine/nitric acid impregnation resulted in a superior performance, with greater chemical adsorption. The linkages between the amine and carboxylic acid groups may function differently in piperazine amination and piperazine/nitric acid treatment.

Active Control of Contact Angles of Various Liquids from the Response of Self-Assembled Thiol Molecules to Electric Current.

The ability to change wettability in situ would realize active surfaces that can change their functionality and adapt to different environments. This article reports a new and easy method that controls surface wettability in situ. In doing so, three hypotheses were to be proven. First, thiol molecules with dipole moments at the end that were adsorbed onto gold could change the contact angles of nonpolar or slightly polar liquids when an electric current was provided at the gold surface without having to ionize the dipole. It was also hypothesized that the molecules would undergo conformation changes as their dipoles would align with the magnetic field induced by the applied current. Second, the ability to change contact angles was modified by mixing ethanethiol, a much shorter thiol with no dipole, with the abovementioned thiol molecules because it would provide space for the thiol molecules to undergo conformation changes. Third, the indirect evidence of the conformation change was verified with attenuated total reflection Fourier transform infrared (FT-IR) spectroscopy. Four thiol molecules that controlled the contact angles of deionized water and hydrocarbon liquids were identified. The abilities of those four molecules in changing the contact angles were modified by adding ethanethiol. A quartz crystal microbalance was used to infer the possible change in the distance between the adsorbed thiol molecules by investigating adsorption kinetics. The changes in FT-IR peaks with respect to applied currents were also presented as indirect evidence for the conformation change. This method was compared with other reported methods that control wettability in situ. The differences between the voltage-driven method to induce conformation changes of thiol molecules and the method presented in this paper were further discussed to emphasize that the mechanism by which the conformation change was induced in this article was most likely because of the dipole-electric current interaction.

Investigation of the Trajectory of Muscle and Body Mass as a Prognostic Factor in Patients With Colorectal Cancer: Longitudinal Cohort Study.

BACKGROUND: Skeletal muscle and BMI are essential prognostic factors for survival in colorectal cancer (CRC). However, there is a lack of understanding due to scarce studies on the continuous aspects of these variables. OBJECTIVE: This study aimed to evaluate the prognostic impact of the initial status and trajectories of muscle and BMI on overall survival (OS) and assess whether these 4 profiles within 1 year can represent the profiles 6 years later. METHODS: We analyzed 4056 newly diagnosed patients with CRC between 2010 to 2020. The volume of the muscle with 5-mm thickness at the third lumbar spine level was measured using a pretrained deep learning algorithm. The skeletal muscle volume index (SMVI) was defined as the muscle volume divided by the square of the height. The correlation between BMI status at the first, third, and sixth years of diagnosis was analyzed and assessed similarly for muscle profiles. Prognostic significances of baseline BMI and SMVI and their 1-year trajectories for OS were evaluated by restricted cubic spline analysis and survival analysis. Patients were categorized based on these 4 dimensions, and prognostic risks were predicted and demonstrated using heat maps. RESULTS: Trajectories of SMVI were categorized as decreased (812/4056, 20%), steady (2014/4056, 49.7%), or increased (1230/4056, 30.3%). Similarly, BMI trajectories were categorized as decreased (792/4056, 19.5%), steady (2253/4056, 55.5%), or increased (1011/4056, 24.9%). BMI and SMVI values in the first year after diagnosis showed a statistically significant correlation with those in the third and sixth years (P<.001). Restricted cubic spline analysis showed a nonlinear relationship between baseline BMI and SMVI change ratio and OS; BMI, in particular, showed a U-shaped correlation. According to survival analysis, increased BMI (hazard ratio [HR] 0.83; P=.02), high baseline SMVI (HR 0.82; P=.04), and obesity stage 1 (HR 0.80; P=.02) showed a favorable impact, whereas decreased SMVI trajectory (HR 1.31; P=.001), decreased BMI (HR 1.23; P=.02), and initial underweight (HR 1.38; P=.02) or obesity stages 2-3 (HR 1.79; P=.01) were negative prognostic factors for OS. Considered simultaneously, BMI >30 kg/m2 with a low SMVI at the time of diagnosis resulted in the highest mortality risk. We observed improved survival in patients with increased muscle mass without BMI loss compared to those with steady muscle mass and BMI. CONCLUSIONS: Profiles within 1 year of both BMI and muscle were surrogate indicators for predicting the later profiles. Continuous trajectories of body and muscle mass are independent prognostic factors of patients with CRC. An automatic algorithm provides a unique opportunity to conduct longitudinal evaluations of body compositions. Further studies to understand the complicated natural courses of muscularity and adiposity are necessary for clinical application.

Pancreatoduodenectomy following neoadjuvant chemotherapy in duodenal adenocarcinoma.

A 51-year-old male patient had four times of massive hematochezia episode three days before arrival. Carbohydrate antigen (CA) 19-9 level was extremely elevated. Computed tomography, magnetic resonance imaging, and positron emission tomography-computed tomography identified 5.7 cm sized periampullary duodenal cancer with regional metastatic lymph nodes and vascular invasion to aberrant right hepatic artery, main portal vein, and superior mesenteric vein. Diagnosed as duodenal adenocarcinoma through endoscopic biopsy, 16 times of FOLFIRI (5-fluorouracil, leucovorin, irinotecan) was conducted. The regimen changed to XELOX (capecitabine, oxaliplatine), four times of administration was done, and the CA19-9 level dramatically decreased. The tumor decreased to 2.1 cm. After R0 laparoscopic pylorus preserving pancreatoduodenectomy, no adjuvant therapy was given. No sign of recurrence or metastasis was reported, and the patient reached complete remission after five years. We reported a case where neoadjuvant chemotherapy for locally advanced duodenal adenocarcinoma was shown to be effective.

Association between Serum Prolactin Levels and Neurodegenerative Diseases: Systematic Review and Meta-Analysis.

INTRODUCTION: Prolactin (PRL) exerts inflammatory and anti-inflammatory properties and is also thought to play an important role in the pathogenesis of neurodegenerative diseases (NDs). However, serum PRL levels in patients with NDs were inconsistent in the research literature. OBJECTIVE: We aimed to assess the serum PRL levels in patients with NDs. METHODS: Electronic databases, including MEDLINE, Embase, Cochrane Library database, clinicaltrials.gov, Web of Science, and Google Scholar, and reference lists of articles were searched up to December 31, 2020. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by fixed-effect or random-effect model analysis. RESULTS: A total of 36 comparisons out of 29 studies (3 RCTs and 26 case controls) focusing on NDs (including Parkinson's disease, Alzheimer's disease, Huntington's disease [HD], multiple sclerosis [MS], and epilepsy) were reported. The meta-analysis showed that there was no statistically significant difference in serum PRL levels between patients with NDs and healthy controls (SMD = 0.40, 95% CI: -0.16 to 0.96, p = 0.16). Subgroup analysis showed that serum PRL levels in patients with HD and MS were higher than those of healthy controls. Furthermore, patients with NDs aged <45 years had higher serum PRL levels (SMD = 0.97, 95% CI: 0.16-1.78, p = 0.018) than healthy controls. High serum PRL levels were found in subgroups such as the microenzymatic method, Asia, and the Americas. CONCLUSIONS: Our meta-analysis showed serum PRL levels in patients with HD and MS were significantly higher than those in healthy controls. Serum PRL levels were associated with age, region, and detection method. Other larger sample studies using more uniform detection methods are necessary to confirm our results.

The shape and dynamics of deformations of viscoelastic fluids by water droplets.

Many studies on the deformation of soft films by liquids confirmed the increase in the radius of the deformation and the decrease in the apparent contact angle. However, due to the thinness, the dynamics of the deformation could not be observed until the thermodynamic equilibrium. Thus, the dynamics on thick soft materials was studied until equilibrium to contrast the effect of different interfacial energy between different soft materials and water. Therefore, we prepared two different polymeric fluids with similar rheology by cross-linking monomers, yet with different contact angles with water. Sometime after water droplets were placed on these thick polymers, 3D profiles of the deformation were recorded. Though the effect of the surface tension was not verified, the same trend in the dynamics was observed as with thin films, except for the decrease in the radius after the initial increase. The three-phase boundaries (TPBs) were found not at the apex of the ridges formed during the transition to equilibrium. By calculating the surface tensions and angles of each interface at the equilibrium, we found that the temporary imbalance among surface tensions induced the slip of the TPBs toward the center of water droplets, thus dislocating the TPBs and decreasing the radius.

The Use of Mobile Personal Health Records for Hemoglobin A1c Regulation in Patients With Diabetes: Retrospective Observational Study.

BACKGROUND: The effectiveness of personal health records (PHRs) in diabetes management has already been verified in several clinical trials; however, evidence of their effectiveness in real-world scenarios is also necessary. To provide solid real-world evidence, an analysis that is more accurate than the analyses solely based on patient-generated health data should be conducted. OBJECTIVE: This study aimed to conduct a more accurate analysis of the effectiveness of using PHRs within electronic medical records (EMRs). The results of this study will provide precise real-world evidence of PHRs as a feasible diabetes management tool. METHODS: We collected log data of the sugar function in the My Chart in My Hand version 2.0 (MCMH 2.0) app from Asan Medical Center (AMC), Seoul, Republic of Korea, between December 2015 and April 2018. The EMR data of MCMH 2.0 users from AMC were collected and integrated with the PHR data. We classified users according to whether they were continuous app users. We analyzed and compared their characteristics, patterns of hemoglobin A1c (HbA1c) levels, and the proportion of successful HbA1c control. The following confounders were adjusted for HbA1c pattern analysis and HbA1c regulation proportion comparison: age, sex, first HbA1c measurement, diabetes complications severity index score, sugar function data generation weeks, HbA1c measurement weeks before MCMH 2.0 start, and generated sugar function data count. RESULTS: The total number of MCMH 2.0 users was 64,932, with 7453 users having appropriate PHRs and diabetes criteria. The number of continuous and noncontinuous users was 133 and 7320, respectively. Compared with noncontinuous users, continuous users were younger (P<.001) and had a higher male proportion (P<.001). Furthermore, continuous users had more frequent HbA1c measurements (P=.007), shorter HbA1c measurement days (P=.04), and a shorter period between the first HbA1c measurement and MCMH 2.0 start (P<.001). Diabetes severity-related factors were not statistically significantly different between the two groups. Continuous users had a higher decrease in HbA1c (P=.02) and a higher proportion of regulation of HbA1c levels to the target level (P=.01). After adjusting the confounders, continuous users had more decline in HbA1c levels than noncontinuous users (P=.047). Of the users who had a first HbA1c measurement higher than 6.5% (111 continuous users and 5716 noncontinuous users), continuous users had better regulation of HbA1c levels with regard to the target level, 6.5%, which was statistically significant (P=.04). CONCLUSIONS: By integrating and analyzing patient- and clinically generated data, we demonstrated that the continuous use of PHRs improved diabetes management outcomes. In addition, the HbA1c reduction pattern was prominent in the PHR continuous user group. Although the continued use of PHRs has proven to be effective in managing diabetes, further evaluation of its effectiveness for various diseases and a study on PHR adherence are also required.

Ultrasonic sculpting of virtual optical waveguides in tissue.

Optical imaging and stimulation are widely used to study biological events. However, scattering processes limit the depth to which externally focused light can penetrate tissue. Optical fibers and waveguides are commonly inserted into tissue when delivering light deeper than a few millimeters. This approach, however, introduces complications arising from tissue damage. In addition, it makes it difficult to steer light. Here, we demonstrate that ultrasound can be used to define and steer the trajectory of light within scattering media by exploiting local pressure differences created by acoustic waves that result in refractive index contrasts. We show that virtual light pipes can be created deep into the tissue (>18 scattering mean free paths). We demonstrate the application of this technology in confining light through mouse brain tissue. This technology is likely extendable to form arbitrary light patterns within tissue, extending both the reach and the flexibility of light-based methods.

Time-Dependent Physicochemical Changes of Carbonate Surfaces from SmartWater (Diluted Seawater) Flooding Processes for Improved Oil Recovery.

Over the past few decades, field- and laboratory-scale studies have shown enhancements in oil recovery when reservoirs, which contain high-salinity formation water (FW), are waterflooded with modified-salinity salt water (widely referred to as the low-salinity, dilution, or SmartWater effect for improved oil recovery). In this study, we investigated the time dependence of the physicochemical processes that occur during diluted seawater (i.e., SmartWater) waterflooding processes of specific relevance to carbonate oil reservoirs. We measured the changes to oil/water/rock wettability, surface roughness, and surface chemical composition during SmartWater flooding using 10-fold-diluted seawater under mimicked oil reservoir conditions with calcite and carbonate reservoir rocks. Distinct effects due to SmartWater flooding were observed and found to occur on two different timescales: (1) a rapid (<15 min) increase in the colloidal electrostatic double-layer repulsion between the rock and oil across the SmartWater, leading to a decreased oil/water/rock adhesion energy and thus increased water wetness and (2) slower (>12 h to complete) physicochemical changes of the calcite and carbonate reservoir rock surfaces, including surface roughening via the dissolution of rock and the reprecipitation of dissolved carbonate species after exchanging key ions (Ca2+, Mg2+, CO32-, and SO42- in carbonates) with those in the flooding SmartWater. Our experiments using crude oil from a carbonate reservoir reveal that these reservoir rock surfaces are covered with organic-ionic preadsorbed films (ad-layers), which the SmartWater removes (detaches) as flakes. Removal of the organic-ionic ad-layers by SmartWater flooding enhances oil release from the surfaces, which was found to be critical to increasing the water wetness and significantly improving oil removal from carbonates. Additionally, the increase in water wetness is further enhanced by roughening of the rock surfaces, which decreases the effective contact (interaction) area between the oil and rock interfaces. Furthermore, we found that the rate of these slower physicochemical changes to the carbonate rock surfaces increases with increasing temperature (at least up to an experimental temperature of 75 °C). Our results suggest that the effectiveness of improved oil recovery from SmartWater flooding depends strongly on the formation of the organic-ionic ad-layers. In oil reservoirs where the ad-layer is fully developed and robust, injecting SmartWater would lead to significant removal of the ad-layer and improved oil recovery.

Triple Function Lubricant Additives Based on Organic-Inorganic Hybrid Star Polymers: Friction Reduction, Wear Protection, and Viscosity Modification.

Polymer-based lubricant additives for friction reduction, wear protection, or viscosity improvement have been widely studied. However, single additives achieving all three functions are rare. To address this need, we have explored the combination of polymer topology with organic-inorganic hybrid chemistry to simultaneously vary the temperature- and shear-dependent properties of polymer additives in solution and at solid surfaces. A topological library of lubricant additives, based on statistical copolymers of stearyl methacrylate and methyl methacrylate, ranging from linear to branched star architectures, was prepared using ruthenium-catalyzed controlled radical polymerization. Control over the polymerization yielded additives with low dispersity and comparable molecular weights, allowing evaluation of the influence of polymer architecture on friction reduction, wear protection, and bulk viscosity improvement in a commercial base oil (Yubase 4). Structure-performance relationships for these functions were assessed by a combination of a high-speed surface force apparatus (HS-SFA) experiments, wear track profilometry, quartz crystal microbalance analysis, and solution viscometry. The custom-built HS-SFA provides a unique experimental environment to measure the boundary lubrication performance under extreme shear rates (≈107 s-1) for prolonged times (24 h), mimicking the extreme conditions of automotive applications. These experiments revealed that the performance of the additives as boundary lubricants and wear protectants scales with the degree of branching. The branched architectures prohibit ordering of the additives in thin films under high-load conditions, leading to a thicker absorbed polymer brush boundary layer and therefore enhanced film fluidity and lubricity. Additionally, star polymers with increasing arm number lead to bulk viscosity modification, reflected by a significant increase in the viscosity index compared to the commercial base oil. Although outperformed by linear polymers for bulk viscosity improvement, the (hybrid) star polymers successfully combine the three distinct lubricant additive functions: friction reduction, wear protection, and bulk viscosity improvement-in a single polymeric structure. It should also be noted that, judging from HS-SFA experiments, hybrid stars carrying a silicate-based core outperform their fully organic analogues as boundary lubricants. The enhanced performance is most likely driven by attractive forces between the silicate cores and the employed metallic surfaces. Combining three function in one minimizes formulation complexity and thus opens a route to fundamentally understand and formulate key design parameters for the development of novel multifunction lubricant additives.

Rates of cavity filling by liquids.

Understanding the fundamental wetting behavior of liquids on surfaces with pores or cavities provides insights into the wetting phenomena associated with rough or patterned surfaces, such as skin and fabrics, as well as the development of everyday products such as ointments and paints, and industrial applications such as enhanced oil recovery and pitting during chemical mechanical polishing. We have studied, both experimentally and theoretically, the dynamics of the transitions from the unfilled/partially filled (Cassie-Baxter) wetting state to the fully filled (Wenzel) wetting state on intrinsically hydrophilic surfaces (intrinsic water contact angle <90°, where the Wenzel state is always the thermodynamically favorable state, while a temporary metastable Cassie-Baxter state can also exist) to determine the variables that control the rates of such transitions. We prepared silicon wafers with cylindrical cavities of different geometries and immersed them in bulk water. With bright-field and confocal fluorescence microscopy, we observed the details of, and the rates associated with, water penetration into the cavities from the bulk. We find that unconnected, reentrant cavities (i.e., cavities that open up below the surface) have the slowest cavity-filling rates, while connected or non-reentrant cavities undergo very rapid transitions. Using these unconnected, reentrant cavities, we identified the variables that affect cavity-filling rates: (i) the intrinsic contact angle, (ii) the concentration of dissolved air in the bulk water phase (i.e., aeration), (iii) the liquid volatility that determines the rate of capillary condensation inside the cavities, and (iv) the presence of surfactants.

Printed Receive Coils with High Acoustic Transparency for Magnetic Resonance Guided Focused Ultrasound.

In magnetic resonance guided focused ultrasound (MRgFUS) therapy sound waves are focused through the body to selectively ablate difficult to access lesions and tissues. A magnetic resonance imaging (MRI) scanner non-invasively tracks the temperature increase throughout the tissue to guide the therapy. In clinical MRI, tightly fitted hardware comprised of multichannel coil arrays are required to capture high quality images at high spatiotemporal resolution. Ablating tissue requires a clear path for acoustic energy to travel but current array materials scatter and attenuate acoustic energy. As a result coil arrays are placed outside of the transducer, clear of the beam path, compromising imaging speed, resolution, and temperature accuracy of the scan. Here we show that when coil arrays are fabricated by additive manufacturing (i.e., printing), they exhibit acoustic transparency as high as 89.5%. This allows the coils to be placed in the beam path increasing the image signal to noise ratio (SNR) five-fold in phantoms and volunteers. We also characterize printed coil materials properties over time when submerged in the water required for acoustic coupling. These arrays offer high SNR and acceleration capabilities, which can address current challenges in treating head and abdominal tumors allowing MRgFUS to give patients better outcomes.

Contact Angle and Adhesion Dynamics and Hysteresis on Molecularly Smooth Chemically Homogeneous Surfaces.

Measuring truly equilibrium adhesion energies or contact angles to obtain the thermodynamic values is experimentally difficult because it requires loading/unloading or advancing/receding boundaries to be measured at rates that can be slower than 1 nm/s. We have measured advancing-receding contact angles and loading-unloading adhesion energies for various systems and geometries involving molecularly smooth and chemically homogeneous surfaces moving at different but steady velocities in both directions, ±V, focusing on the thermodynamic limit of ±V → 0. We have used the Bell Theory (1978) to derive expressions for the dynamic (velocity-dependent) adhesion energies and contact angles suitable for both (i) dynamic adhesion measurements using the classic Johnson-Kendall-Roberts (JKR, 1971) theory of "contact mechanics" and (ii) dynamic contact angle hysteresis measurements of both rolling droplets and syringe-controlled (sessile) droplets on various surfaces. We present our results for systems that exhibited both steady and varying velocities from V ≈ 10 mm/s to 1 nm/s, where in all cases but one, the advancing (V > 0) and receding (V < 0) adhesion energies and/or contact angles converged toward the same theoretical (thermodynamic) values as V → 0. Our equations for the dynamic contact angles are similar to the classic equations of Blake & Haynes (1969) and fitted the experimental adhesion data equally well over the range of velocities studied, although with somewhat different fitting parameters for the characteristic molecular length/dimension or area and characteristic bond formation/rupture lifetime or velocity. Our theoretical and experimental methods and results unify previous kinetic theories of adhesion and contact angle hysteresis and offer new experimental methods for testing kinetic models in the thermodynamic, quasi-static, limit. Our analyses are limited to kinetic effects only, and we conclude that hydrodynamic, i.e., viscous, and inertial effects do not play a role at the interfacial velocities of our experiments, i.e., V < (1-10) mm/s (for water and hexadecane, but for viscous polymers it may be different), consistent with previously reported studies.

Wireless Recording in the Peripheral Nervous System with Ultrasonic Neural Dust.

The emerging field of bioelectronic medicine seeks methods for deciphering and modulating electrophysiological activity in the body to attain therapeutic effects at target organs. Current approaches to interfacing with peripheral nerves and muscles rely heavily on wires, creating problems for chronic use, while emerging wireless approaches lack the size scalability necessary to interrogate small-diameter nerves. Furthermore, conventional electrode-based technologies lack the capability to record from nerves with high spatial resolution or to record independently from many discrete sites within a nerve bundle. Here, we demonstrate neural dust, a wireless and scalable ultrasonic backscatter system for powering and communicating with implanted bioelectronics. We show that ultrasound is effective at delivering power to mm-scale devices in tissue; likewise, passive, battery-less communication using backscatter enables high-fidelity transmission of electromyogram (EMG) and electroneurogram (ENG) signals from anesthetized rats. These results highlight the potential for an ultrasound-based neural interface system for advancing future bioelectronics-based therapies.

Model validation of untethered, ultrasonic neural dust motes for cortical recording.

A major hurdle in brain-machine interfaces (BMI) is the lack of an implantable neural interface system that remains viable for a substantial fraction of the user's lifetime. Recently, sub-mm implantable, wireless electromagnetic (EM) neural interfaces have been demonstrated in an effort to extend system longevity. However, EM systems do not scale down in size well due to the severe inefficiency of coupling radio-waves at those scales within tissue. This paper explores fundamental system design trade-offs as well as size, power, and bandwidth scaling limits of neural recording systems built from low-power electronics coupled with ultrasonic power delivery and backscatter communication. Such systems will require two fundamental technology innovations: (1) 10-100 µm scale, free-floating, independent sensor nodes, or neural dust, that detect and report local extracellular electrophysiological data via ultrasonic backscattering and (2) a sub-cranial ultrasonic interrogator that establishes power and communication links with the neural dust. We provide experimental verification that the predicted scaling effects follow theory; (127 µm)(3) neural dust motes immersed in water 3 cm from the interrogator couple with 0.002064% power transfer efficiency and 0.04246 ppm backscatter, resulting in a maximum received power of ∼0.5 µW with ∼1 nW of change in backscatter power with neural activity. The high efficiency of ultrasonic transmission can enable the scaling of the sensing nodes down to 10s of micrometer. We conclude with a brief discussion of the application of neural dust for both central and peripheral nervous system recordings, and perspectives on future research directions.

Miniaturizing Ultrasonic System for Portable Health Care and Fitness.

We present a miniaturized portable ultrasonic imager that uses a custom ASIC and a piezoelectric transducer array to transmit and capture 2-D sonographs. The ASIC, fabricated in 0.18 µm 32 V CMOS process, contains 7 identical channels, each with high-voltage level-shifters, high-voltage DC-DC converters, digital TX beamformer, and RX front-end. The chip is powered by a single 1.8 V supply and generates 5 V and 32 V internally using on-chip charge pumps with an efficiency of 33% to provide 32 V pulses for driving a bulk piezoelectric transducer array. The assembled prototype can operate up to 40 MHz, with beamformer delay resolution of 5 ns, and has a measured sensitivity of 225 nV/Pa , minimum detectable signal of 622 Pa assuming 12 dB SNR ( 4σ larger than the noise level), and data acquisition time of 21.3 ms. The system can image human tissue as deep as 5 cm while consuming less than 16.5 µJ per pulse-echo measurement. The high energy efficiency of the imager can enable a number of consumer applications.

Beamforming approaches for untethered, ultrasonic neural dust motes for cortical recording: a simulation study.

In this paper, we examine the use of beamforming techniques to interrogate a multitude of neural implants in a distributed, ultrasound-based intra-cortical recording platform known as Neural Dust. We propose a general framework to analyze system design tradeoffs in the ultrasonic beamformer that extracts neural signals from modulated ultrasound waves that are backscattered by free-floating neural dust (ND) motes. Simulations indicate that high-resolution linearly-constrained minimum variance beamforming sufficiently suppresses interference from unselected ND motes and can be incorporated into the ND-based cortical recording system.