Magnetically Guidable Proteinaceous Adhesive Microbots for Targeted Locoregional Therapeutics Delivery in the Highly Dynamic Environment of the Esophagus

The esophagus is a tubular-shaped muscular organ where swallowed fluids and muscular contractions constitute a highly dynamic environment. The turbulent, coordinated processes that occur through the oropharyngeal conduit can often compromise targeted administration of therapeutic drugs to a lesion, significantly reducing therapeutic efficacy. Here, magnetically guidable drug vehicles capable of strongly adhering to target sites using a bioengineered mussel adhesive protein (MAP) to achieve localized delivery of therapeutic drugs against the hydrodynamic physiological conditions are proposed. A suite of highly uniform microparticles embedded with iron oxide (IO) nanoparticles (MAP@IO MPs) is microfluidically fabricated using the genipin-mediated covalent cross-linking of bioengineered MAP. The MAP@IO MPs are successfully targeted to a specific region and prolongedly retained in the tubular-structured passageway. In particular, orally administered MAP@IO MPs are effectively captured in the esophagus in vivo in a magnetically guidable manner. Moreover, doxorubicin (DOX)-loaded MAP@IO MPs exhibit a sustainable DOX release profile, effective anticancer therapeutic activity, and excellent biocompatibility. Thus, the magnetically guidable locomotion and robust underwater adhesive properties of the proteinaceous soft microbots can provide an intelligent modular approach for targeted locoregional therapeutics delivery to a specific lesion site in dynamic fluid-associated tubular organs such as the esophagus.     

Optimization of Pathogen Capture in Flowing Fluids with Magnetic Nanoparticles

Magnetic nanoparticles have been employed to capture pathogens for many biological applications; however, optimal particle sizes have been determined empirically in specific capturing protocols. Here, a theoretical model that simulates capture of bacteria is described and used to calculate bacterial collision frequencies and magnetophoretic properties for a range of particle sizes. The model predicts that particles with a diameter of 460 nm should produce optimal separation of bacteria in buffer flowing at 1 L h⁻¹. Validating the predictive power of the model, Staphylococcus aureus is separated from buffer and blood flowing through magnetic capture devices using six different sizes of magnetic particles. Experimental magnetic separation in buffer conditions confirms that particles with a diameter closest to the predicted optimal particle size provide the most effective capture. Modeling the capturing process in plasma and blood by introducing empirical constants (c_e), which integrate the interfering effects of biological components on the binding kinetics of magnetic beads to bacteria, smaller beads with 50 nm diameters are predicted that exhibit maximum magnetic separation of bacteria from blood and experimentally validated this trend. The predictive power of the model suggests its utility for the future design of magnetic separation for diagnostic and therapeutic applications.     

Solid phase crystallization of amorphous silicon on glass by thin film heater for thin film transistor (TFT) application

A new process for solid phase crystallization (SPC) of amorphous silicon (a-Si) using thin film heater is reported. With this localized Ti silicide thin film heater, we successfully crystallized 500 Å-thick a-Si in a few minutes without any thermal deformation of glass substrate. The size of crystallized silicon grain was abnormally big (30-40 μm). Polycrystalline thin film transistors (TFT) fabricated using this unique thin film heater showed better mobility than those of conventional ones by furnace annealing.     

Mutational analysis of the three cysteines and active-site aspartic acid 103 of ketosteroid isomerase from Pseudomonas putida biotype B

In order to clarify the roles of three cysteines in ketosteroid isomerase (KSI) from Pseudomonas putida biotype B, each of the cysteine residues has been changed to a serine residue (C69S, C81S, and C97S) by site-directed mutagenesis. All cysteine mutations caused only a slight decrease in the k(cat) value, with no significant change of Km for the substrate. Even modification of the sulfhydryl group with 5,5'-dithiobis(2-nitrobenzoic acid) has almost no effect on enzyme activity. These results demonstrate that none of the cysteines in the KSI from P. putida is critical for catalytic activity, contrary to the previous identification of a cysteine in an active-site-directed photoinactivation study of KSI. Based on the three-dimensional structures of KSIs with and without dienolate intermediate analog equilenin, as determined by X-ray crystallography at high resolution, Asp-103 was found to be located within the range of the hydrogen bond to the equilenin. To assess the role of Asp-103 in catalysis, Asp-103 has been replaced with either asparagine (D103N) or alanine (D103A) by site-directed mutagenesis. For D103A mutant KSI there was a significant decrease in the k(cat) value: the k(cat) of the mutant was 85-fold lower than that of the wild-type enzyme; however, for the D103N mutant, which retained some hydrogen bonding capability, there was a minor decrease in the k(cat) value. These findings support the idea that aspartic acid 103 in the active site is an essential catalytic residue involved in catalysis by hydrogen bonding to the dienolate intermediate.     

Phacoemulsification with a bevel-down phaco tip: phaco-drill

We present a technique for in situ lens nucleus emulsification using low phaco power and high vacuum, a continuous curvilinear capsulorhexis, and hydrodelineation. Emulsification is done with the phaco tip slanted down 30 or 45 degrees. Cutting and aspiration do not cause an undesirable energy loss. This technique can be combined with the nuclear chopping or divide and conquer methods because of its ability to drill and hold the nucleus. Posterior capsular rupture is prevented because the separated epinucleus acts as a barrier between the nucleus and the cortex. The low power used minimizes the energy transfer to the corneal endothelium. This technique is particularly useful in eyes with brunescent cataract.     

A study on the degree of deliberation and meditation of cyber poll respondents for nuclear-related decision making

Public participation is essential in each step of the nuclear-related decision-making process. Recently, the electronic systems using the Internet have become quite popular, and have emerged as a good medium for communicating with the public. In this study, a comprehensive utilization of electronic public participation was used to analyze public opinion on a given nuclear-related decision-making process. The degree of deliberation and meditation of the public participating in an electronic poll survey was evaluated, and the decision-making factors representing the personal characteristics of the poll respondents such as age, income, education, residence, degree of knowledge and concern were carefully incorporated when preparing the poll-survey questionnaire for its evaluation. Fuzzy analysis was used to assess and aggregate the responses to each decision-making factor. As a case study, this procedure was used to analyzing public opinion on the location of a low-level radioactive waste disposal facility on the campus of Seoul National University. The results show that there is a tendency of respondents who are on the negative side of the argument to be more deliberate and meditative in their decision-making process than those on the positive side. Knowledge and residence were found to be important decision-making factors.     

Fracture initiation at a crack or notch in a viscoplastic material under high rate loading

The two-dimensional problem of an edge crack in a half space or plate is considered. The body is loaded by a suddenly applied, spatially uniform normal velocity imposed on the plane boundary of the body on one side of the edge crack. Otherwise, the boundary of the body, including the crack faces, is traction free. Both cases of an initially sharp crack tip and a narrow notch with small but nonzero notch root radius are considered. The material is modeled as elastic viscoplastic, including strain hardening, rate sensitivity and thermal softening. The applied loading produces predominantly mode II loading in the crack tip region. Under these conditions it is possible to nucleate an adiabatic shear band at the crack tip as a precursor to a mode II fracture. On the other hand, because of the rate sensitivity of the material and the high rate of loading, it may be possible under certain conditions to generate tensile stresses in the crack tip region sufficiently large to nucleate brittle tensile fracture. The problem is solved numerically by means of the finite element method in order to investigate the competition between these two possible fracture initiation mechanisms. The magnitude of the impact velocity imposed on the edge of the plate and the notch tip acuity have an effect on processes near the crack tip. For given material, the inception of crack growth is determined by the competition between a stress-based brittle fracture condition, associated with rate sensitivity and strain hardening, and a strain based criterion, associated with high strain rate and thermal softening.