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Purpose: This study compared the clinical and radiology results of arthrodesis between the anterior and transfibular approaches with a lateral malleolar-saving procedure in ankle arthritis. Materials and Methods: This study was a retrospective study of 31 cases who underwent ankle arthrodesis with the anterior approach (14 cases) and trans-fibular approach (17 cases). The remnant lateral malleolus was fixed during the trans-fibular procedure. The patients included 17 females and 14 males with a mean age of 57.2 (range 41~73) years; the mean follow-up was 30.4 (range 15~68) months. The clinical and radiology outcomes, including the American Orthopedic Foot & Ankle Society (AOFAS) scores, visual analog scale (VAS), and union time, were recorded. The complications and subjective satisfaction degrees were also recorded and compared between the two groups. Results: Clinically, the preoperative mean AOFAS score and VAS in the anterior approach group were 39.3 and 7.4, respectively, which changed to 61.9 and 3.1 postoperatively. In the trans-fibular approach group, the mean AOFAS score and VAS increased from 36.6 to 64.2 and 7.1 to 2.4, respectively. On the other hand, no significant differences in the clinical results were observed between the two groups. The time to achieve union was 9.2 and 11.6 weeks in the anterior and transfibular approach groups, respectively. Three patients (21%) complained of tenderness and discomfort around the fibular tip in the anterior approach group, and seven patients (41%) showed a gap between the talus and remnant lateral malleolus in the trans-fibular approach group. Conclusion: There was no difference in the clinical and radiological results between the anterior and transfibular approaches with a lateral malleolar saving procedure in ankle arthrodesis. Careful selection of the approach method according to the patient's preoperative condition is needed to prevent remnant discomfort or nonunion around the lateral malleolus. [ABSTRACT FROM AUTHOR]

Radioactive decontamination waste generated by remediation following the Fukushima nuclear power plant accident was recently transported from its temporary storage sites to interim storage facilities as a pilot test. A transportation plan for the radioactive decontamination waste will be developed based on this pilot transportation experience and radiological safety assessment of pilot transportation. The objective of this study was to assess radiation doses to the public and crew workers released during incident-free pilot transportation. External dose rates around a transportation vehicle were calculated by using the Monte Carlo N-Particlc code. Collective doses and maximally exposed individual doses to the public and effective doses to crew workers were calculated by using INTERTRAN. Two transportation routes, Asakawa-machi to Okuma-machi ajid Iwaki-shi to Okuma-machi, were considered. The maximum radioactivity concentration in the decontamination waste was calculated to be 660 kBqkg-1 which meets the value laid down by the guidelines of Japan's Ministry of the Environment. The collective doses to the public per shipment were 1.9-10-3 pcrson-mSv for the Asakawa route and 2.210-4 pcrson-mSv for the Iwaki route. Maximally exposed individual doses to the public were 9.6-10-7 mSv for the Asakawa route and 2.7-10-5 mSv for the Iwaki route. The total effective doses to crew workers were 0.27 mSv for the Asakawa route assuming five shipments per worker and 1.07 mSv for the Iwaki route assuming 45 shipments per worker. The radiation dose levels to the public and workers evaluated in this study were much lower than the annual dose limits for the general public and radiation workers. These study results can be used to develop transportation plans and guidelines for decontamination waste transportation. [ABSTRACT FROM AUTHOR]

Hyper-O-GlcNAcylation is a general feature of cancer which contributes to various cancer phenotypes, including cell proliferation and cell growth. Quercetin, a naturally occurring dietary flavonoid, has been reported to reduce the proliferation and growth of cancer. Several reports of the anticancer effect of quercetin have been published, but there is no study regarding its effect on O-GlcNAcylation. The aim of this study was to investigate the anticancer effect of quercetin on HeLa cells and compare this with its effect on HaCaT cells. Cell viability and cell death were determined by MTT and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling assays. O-GlcNAcylation of AMPactivated protein kinase (AMPK) was examined by succinylated wheat germ agglutinin pulldown and immunoprecipitation. Immunofluorescence staining was used to detect the immunoreactivitiy of O-linked N-acetylglucosamine transferase (OGT) and sterol regulatory element binding protein 1 (SREBP-1). Quercetin decreased cell proliferation and induced cell death, but its effect on HaCaT cells was lower than that on HeLa cells. O-GlcNAcylation level was higher in HeLa cells than in HaCaT cells. Quercetin decreased the expression of global O-GlcNAcylation and increased AMPK activation by reducing the O-GlcNAcylation of AMPK. AMPK activation due to reduced O-GlcNAcylation of AMPK was confirmed by treatment with 6-diazo-5-oxo-L-norleucine. Our results also demonstrated that quercetin regulated SREBP-1 and its transcriptional targets. Furthermore, immunofluorescence staining showed that quercetin treatment decreased the immunoreactivities of OGT and SREBP-1 in HeLa cells. Our findings demonstrate that quercetin exhibited its anticancer effect by decreasing the O-GlcNAcylation of AMPK. Further studies are needed to explore how quercetin regulates O-GlcNAcylation in cancer. [ABSTRACT FROM AUTHOR]

Various types and massive amounts of data are collected in the automotive industry. Such data proliferation facilitates and improves the design of services for vehicle operations management (VOM). A VOM service is a service that helps drivers drive safely, conveniently, and pleasurably with the use of VOM-related data. Despite the applicability of big data to VOM service design, few efforts have been made to establish a big data-based design process for VOM services. To fill the research gap, this study proposes an approach to analyzing and utilizing VOM-related data for designing VOM services. The proposed approach aids service designers in designing VOM services by using VOM-related data. A case study on the design of an eco-driving service, a popular VOM service, is presented to demonstrate the feasibility and effectiveness of the approach. The proposed approach could facilitate the design of VOM services and provide a foundation for data-driven service innovations. [ABSTRACT FROM AUTHOR]

Automated external defibrillators (AEDs) are portable devices that defibrillate and diagnose sudden-cardiac-arrest patients. Therefore, AEDs are widely installed in public places such as airports, schools, sport complexes, etc., and the installation of AEDs is required by law in these places. However, despite their usefulness, AEDs are mostly installed indoors with limited coverage outdoors. Hence, this study conducts research in the placement of AEDs in outdoor locations. This study considers a complicated urban environment using a pedestrian network dataset and network barriers. We draw on the Teitz and Bart's (1968) heuristic method that was built in the location-allocation solver in ArcMap. The results of this study found that a total of 455 AEDs, including 227 pre-installed AEDs, could be placed in the study area, thus providing an additional 228 devices. Compared with 10 different installation methods that were set as experimental groups, our test results found that additional installations were able to cover 10% to 30% more actual out-of-hospital cardiac-arrest cases. The main contribution of this study is the proposal of a new method in locating AEDs in optimal areas while considering complicated urban environments. We predict that the cardiac-arrest-related mortality rate would be reduced through implementing the findings of this study. [ABSTRACT FROM AUTHOR]

The development of miniaturized robotic swimmers is hindered by technical limitations in microand nanofabrication. To circumvent these limitations, we investigated the minimal geometrical requirements for swimming in low Reynolds number. Micro- and nanofabrication of complex shapes, such as helices, on a massive scale requires sophisticated state of the art technologies and has size limitations. In contrast, simple shaped structures, such as spherical particles, can be fabricated massively using chemical synthesis with relative ease. Here, simple microswimmers were fabricated using two microparticles with debris attached to their surface. The debris on the microswimmer's surface creates a geometry with two or more planes of symmetry, allowing the microswimmer to swim in bulk fluid at low Reynolds number. The microswimmers are magnetically actuated and controlled via a uniform rotating magnetic field generated by an approximate Helmholtz electromagnetic coil system. We characterized the microswimmer's velocity profile with respect to rotating frequency and analyzed the motion of the microswimmer using image processing. Finally, we demonstrated the controllability of the microswimmers by freely steering them in any desired directions. [ABSTRACT FROM AUTHOR]

A new composite structural system that is able to enhance constructability and is suitable for realization of long-span structures was developed. Steel beams, steel reinforced concrete columns, reinforced concrete drop panels, and slabs are placed in the system. To determine the structural performance of the system, the gravity and lateral load resisting properties of the system were investigated. It was found that the presence of a reinforced concrete drop panel at the top of a column brings about a reduction of the negative moment at the top of the column. Also, it was observed that a reinforced concrete drop panel on the top of the column significantly affected the deflection-control of the beam. In a lateral load resisting test, cracks in slabs of the new structural system disperse in a better manner than is the case for crack patterns in the conventional composite system. Also, via push-over analysis using a package of structural analysis software, it was found that the developed structural system is effective in the prevention of stress concentration in the column zone. [ABSTRACT FROM AUTHOR]

We evaluate a method for biofilm disinfection by raising biofilm temperature using the photothermal effect of a gold nanorod cluster. Gold nanorods (GNRs) are capable of generating enough heat to lyse bacteria by heating biofilm via laser irradiation. To test this, GNRs are synthesized using wet chemistry and a single GNR cluster is fabricated using photo-lithography technique. The GNR cluster is directly applied to the biofilm and its effects on bacteria are measured before and after laser irradiation. The photothermal effect of GNRs on the biofilm structure results in a considerable reduction of cell viability and biofilm thickness. Several quantitative measurements of bacterial mortality and biofilm destruction show an increase in efficacy with increasing durations of laser irradiation. Scanning electron microscopy images of the irradiated bacteria show obvious morphological damage such as rupture or collapse of the bacterial cell membrane in the biofilm. These results indicate that GNRs are useful and a potential material for use in photothermal treatments, particularly biofilm disinfection. [ABSTRACT FROM AUTHOR]

The effect of bacterial motion on the diffusion of a molecule of high molecular weight is studied by observing the mixing of two streams of fluid in a microfluidic flow cell. We show that the presence of motile E. coli bacteria in one of the streams results in a marked increase in the effective diffusion coefficient of Dextran, which rises linearly with the concentration of bacteria from a baseline value of 0.2×10-7 to 0.8×10-7 (cm2/s) at a concentration of 2.1×109/ml (approximately 0.5% by volume). Furthermore, we observe that the diffusion process is also observed to undergo a change from standard Fickian diffusion to a superdiffusive behavior in which the diffusion exponent rises from 0.5 to 0.55 as the concentration of bacteria rises from 0 to 2.1×109/ml. [ABSTRACT FROM AUTHOR]

This paper describes the use of gold nanoparticles to study particle translocation dynamics through silicon nitride solid-state nanopores. Gold nanoparticles were dispersed in 20 mM KCl solution containing nonionic surfactant Triton X-100 and their translocation was studied at different applied voltages. The use of low electrolyte concentration resulted in current enhancement upon particle translocation. The counterion cloud around the nanoparticles is proposed to be the reason for current enhancement phenomena because associated counterion cloud is believed to increase the ion density inside the pore during particle translocation. Further, single particle diffusion events were also recorded at 0 mV voltage bias and 0 pA background ionic current with high signal-to-noise ratio as the particles moved down their concentration gradient. The ability of nanopore sensors to detect single particle diffusion can be extended to field-free analysis of biomolecules in their native state and at or near physiological salt concentrations. [ABSTRACT FROM AUTHOR]

To gain a more thorough understanding of the dynamics of swarming bacteria, a nonlabeled cell tracking algorithm was used to study the velocity field of flagellated bacteria, Serratia marcescens, swarming on a soft agar plate. The average velocities for local regions regularly arranged over the entire flow field were investigated. The velocity field of the bacteria typically featured the combination of curvilinear translation and vortex modes. They repeated these patterns for short periods of time, forming several groups and dissipating. To further investigate the flow patterns generated by the collective motion of the swarming bacteria, the velocity field on the swarm was spatially correlated. The highest velocities and correlation lengths have been found to occur in the region from 0.5 to 1 mm from the swarm edge, followed by a steady decline as distance from the edge increases, and a sudden decrease in motion typically occurs between 2 and 4 mm from the swarm edge. [ABSTRACT FROM AUTHOR]

Although it is uncommon, hepatic artery (HA) complications including pseudoaneurysm, dissection, and flow steal phenomenon as well as stenosis and thrombosis may occur after living donor liver transplantation (LDLT). A timely diagnosis is of utmost importance for graft and patient survival, because it may result in serious complications, such as life-threatening hemorrhage, severe graft dysfunction or even failure, bile duct necrosis or stricture. Multidetector row CT (MDCT), with superb spatial- and time-resolution, may facilitate the diagnosis of HA complications in LDLT recipients. However, little attention has been paid to MDCT findings of various HA complications following LDLT. For an early recognition and accurate diagnosis of HA complications, radiologists should be familiar with their MDCT findings. In this essay, we present a comprehensive review of various HA complications after LDLT and illustrate their MDCT findings. [ABSTRACT FROM AUTHOR]

The use of atomically thin graphene for molecular sensing has attracted tremendous attention over the years and, in some instances, could displace the use of classical thin films. For nanopore sensing, graphene must be suspended over an aperture so that a single pore can be formed in the free-standing region. Nanopores are typically drilled using an electron beam (e-beam) which is tightly focused until a desired pore size is obtained. E-beam sculpting of graphene however is not just dependent on the ability to displace atoms but also the ability to hinder the migration of ad-atoms on the surface of graphene. Using relatively lower e-beam fluxes from a thermionic electron source, the C-atom knockout rate seems to be comparable to the rate of carbon ad-atom attraction and accumulation at the e-beam/graphene interface (i.e., Rknockout ≈ Raccumulation). Working at this unique regime has allowed the study of carbon ad-atom migration as well as the influence of various substrate materials on e-beam sculpting of graphene. We also show that this information was pivotal to fabricating functional graphene nanopores for studying DNA with increased spatial resolution which is attributed to atomically thin membranes. [ABSTRACT FROM AUTHOR]

Advances in microrobotics for biological applications are often limited due to their complex manufacturing processes, which often utilize cytotoxic materials, as well as limitations in the ability to manipulate these small devices wirelessly. In an effort to overcome these challenges, we investigated a facile method for generating biocompatible hydrogel based robots that are capable of being manipulated using an externally generated magnetic field. Here, we experimentally demonstrate the fabrication and autonomous control of loaded-alginate microspheres, which we term artificial cells. In order to generate these microparticles, we employed a centrifuge-based method in which microspheres were rapidly ejected from a nozzle tip. Specifically, we used two mixtures of sodium alginate; one containing iron oxide nanoparticles and the other containing mammalian cells. This mixture was loaded into a needle that was fixed on top of a microtube containing calcium chloride, and then briefly centrifuged to generate hundreds of Janus microspheres. The fabricated microparticles were then magnetically actuated with a rotating magnetic field, generated using electromagnetic coils, prompting the particles to roll across a glass substrate. Also, using visionbased feedback control, a single artificial cell was manipulated to autonomously move in a programmed pattern. [ABSTRACT FROM AUTHOR]

Microorganisms can effectively generate propulsive force at the microscale where viscous forces overwhelmingly dominate inertia forces; bacteria achieve this task through flagellar motion. When swarming bacteria, cultured on agar plates, are blotted onto the surface of a microfabricated structure, a monolayer of bacteria forms what is termed a "bacterial carpet," which generates strong flows due to the combined motion of their freely rotating flagella. Furthermore, when the bacterial carpet coated microstructure is released into a low Reynolds number fluidic environment, the propulsive force of the bacterial carpet is able to give the microstructure motility. In our previous investigations, we demonstrated motion control of these bacteria powered microbiorobots (MBRs). Without any external stimuli, MBRs display natural rotational and translational movements on their own; this MBR self-actuation is due to the coordination of flagella. Here, we investigate the flow fields generated by bacterial carpets, and compare this flow to the flow fields observed in the bulk fluid at a series of locations above the bacterial carpet. Using microscale particle image velocimetry, we characterize the flow fields generated from the bacterial carpets of MBRs in an effort to understand their propulsive flow, as well as the resulting pattern of flagella driven self-actuated motion. Comparing the velocities between the bacterial carpets on fixed and untethered MBRs, it was found that flow velocities near the surface of the microstructure were strongest, and at distances far above, the surface flow velocities were much smaller. [ABSTRACT FROM AUTHOR]

Solid-state nanopore devices with integrated electrodes are an important class of single-molecule biosensors, with potential applications in DNA, RNA, and protein detection and sequence analysis. Here we investigate solid-state nanopore sensors with an embedded gold film, fabricated using semiconductor processing techniques and focused ion beam milling. We characterize their geometric structure in three dimensions on the basis of experimental conductance studies and modeling as well as transmission electron microscopy imaging and tomography. We used electrodeposition to further shrink the pores to effective diameters below 10 nm and demonstrate how bipolar electrochemical coupling across the membrane can lead to significant contributions to the overall pore current and discuss its implications for nanopore sensing. Finally, we use metallized nanopores modified with homocysteine for the detection of insulin. We show that adsorption of the protein to the chemically modified nanopores slows down the translocation process to tens of milliseconds, which is orders of magnitude slower than expected for conventional electrophoretic transport. [ABSTRACT FROM AUTHOR]

Controllable propulsion of microscale and nanoscale devices enhanced with additional functionality would enable the realization of miniaturized robotic swimmers applicable to transport and assembly, actuators, and drug delivery systems. Following biological examples, existing magnetically actuated microswimmers have been designed to use flexibility or chirality, presenting fabrication challenges. Here we show that, contrary to biomimetic expectations, magnetically actuated geometries with neither flexibility nor chirality can produce propulsion, through both experimental demonstration and a theoretical analysis, which elucidates the fundamental constraints on micropropulsion via magnetetic rotation. Our results advance existing paradigms of low-Reynoldsnumber propulsion, possibly enabling simpler fabrication and design of microswimmers and nanoswimmers. [ABSTRACT FROM AUTHOR]

Untethered robotic microswimmers are very promising to significantly improve various types of minimally invasive surgeries by offering high accuracy at extremely small scales. A prime example is drug delivery, for which a large number of microswimmers is required to deliver sufficient dosages to target sites. For this reason, the controllability of groups of microswimmers is essential. In this paper, we demonstrate simultaneous control of multiple geometrically similar but magnetically different microswimmers using a single global rotating magnetic field. By exploiting the differences in their magnetic properties, we triggered different swimming behaviors from the microswimmers by controlling the frequency and the strength of the global field, for example, one swim and the other does not while exposed to the same control input. Our results show that the balance between the applied magnetic torque and the hydrodynamic torque can be exploited for simultaneous control of two microswimmers to swim in opposite directions, with different velocities, and with similar velocities. This work will serve to establish important concepts for future developments of control systems to manipulate multiple magnetically actuated microswimmers and a step towards using swarms of microswimmers as viable workforces for complex operations. [ABSTRACT FROM AUTHOR]

In recent years, microbial fuel cells (MFCs) have gained much attention due to their potential to generate energy in a sustainable manner from living microorganisms. Research has shown that electrode design is a critical factor for MFCs power enhancement. In this study, we designed and fabricated MFCs energy-harvesting devices with living bacteria, and we investigated the effect of the surface roughness of the electrodes on power generation. In batch experiments of our MFCs, we found that the total power delivered could be enhanced using electrodes having rough surfaces with protruded micro-structures relative to that of electrodes with a flat surface. This was due to the delayed acidification resulting from the changes in bio-film formation between them. [ABSTRACT FROM AUTHOR]

We present an improvement in the electrical properties of silica nanotubes by coating metal nanoparticles on their surfaces. The silica nanotubes are formed from bacterial flagella bio-templates having a tubular structure. Successive depositions of metal nanoparticles on the silica nanotubes are performed through easily functionalized silica surfaces. The results show uniform metal nanoparticle sizes and a high surface area coverage. By incorporating gold, palladium and iron oxide nanoparticles, the metallized silica nanotubes gain electrical properties with the potential to create unique nanoelectronic materials. In this study, the metallized silica nanotubes with network structures are aligned and their electrical behaviors are investigated in both dry and wet conditions. The metallized silica nanotubes are found to be electrically conductive along the network structures. The current-voltage characteristics show remarkably improved electrical conductivities depending on the type of metal nanoparticle loading and nanotube network concentration. [ABSTRACT FROM AUTHOR]

Partially or fully disordered proteins are instrumental for signal-transduction pathways; however, many mechanistic aspects of these proteins are not well-understood. For example, the number and nature of intermediate states along the binding pathway is still a topic of intense debate. To shed light on the conformational heterogeneity of disordered protein domains and their complexes, we performed single-molecule experiments by translocating disordered proteins through a nanopore embedded within a thin dielectric membrane. This platform allows for single-molecule statistics to be generated without the need of fluorescent labels or other modification groups. These studies were performed on two different intrinsically disordered protein domains, a binding domain from activator of thyroid hormone and retinoid receptors (ACTR) and the nuclear coactivator binding domain of CREB-binding protein (NCBD), along with their bimolecular complex. Our results demonstrate that both ACTR and NCBD populate distinct conformations upon translocation through the nanopore. The folded complex of the two disordered domains, on the other hand, translocated as one conformation. Somewhat surprisingly, we found that NCBD undergoes a charge reversal under high salt concentrations. This was verified by both translocation statistics as well as by measuring the ζ-potential. Electrostatic interactions have been previously suggested to play a key role in the association of intrinsically disordered proteins, and the observed behavior adds further complexity to their binding reactions. [ABSTRACT FROM AUTHOR]

Single-molecule experimental techniques have recently shown to be of significant interest for use in numerous applications in both the research laboratory and industrial settings. Although many single-molecule techniques exist, the nanopore platform is perhaps one of the more popular techniques due to its ability to act as a molecular sensor of biological macro- molecules. For example, nanopores offer a unique, new method for probing various properties of proteins and can contribute to elucidating key biophysical information in conjunction with existing techniques. In the present study, various forms of bovine serum albumin (BSA) are detected including thermally refolded BSA, urea-denatured BSA, and multiple forms of BSA detected at elevated electric field strengths (with and without urea). We also provide excluded volume measurements for each of these States that normally are difficult to obtain due to unknown and unstable protein conformations. [ABSTRACT FROM AUTHOR]

Although Candida species are the fourth most common cause of nosocomial blood stream infections in the United States, early diagnostic tools for invasive candidemia are lacking. Due to an increasing rate of candidemia, a new screening system is needed to detect the Candida species in a timely manner. Here we describe a novel method of detection using a solid-state micro-scale pore similar to the operational principles of a Coulter counter. With a steady electrolyte current flowing through the pore, measurements are taken of changes in the current corresponding to the shape of individual yeasts as they translocate or travel through the pore. The direct ultra-fast low concentration electrical addressing of C. albicans has established criteria for distinguishing individual yeast based on their structural properties, which may reduce the currently used methods' complexity for both identification and quantification capabilities in mixed blood samples. [ABSTRACT FROM AUTHOR]

The optothermal properties of nanoparticles are of interest for biosensors and highly sensitive biochip applications. In this respect, the longitudinal resonance of Au nanorods was used to transform near infrared energy into thermal energy in a microfluidic chip. The resulting heat generated effectively caused pathogen lysis. Consequently the DNA was extracted out of the cell body and transferred to a PCR system. This resulted in the successful demonstration of a one step real-time PCR system for pathogen detection without removal or changing of reagents. [ABSTRACT FROM AUTHOR]

We describe a novel approach for optically detecting DNA translocation events through an array of solid-state nanopores that potentially allows for ultra high-throughput, parallel detection at the single-molecule level. The approach functions by electrokinetically driving DNA strands through sub micrometer-sized holes on an aluminum/silicon nitride membrane. During the translocation process, the molecules are confined to the walls of the nanofluidic channels, allowing 100% detection efficiency. Importantly, the opaque aluminum layer acts as an optical barrier between the illuminated region and the analyte reservoir. In these conditions, high-contrast imaging of single-molecule events can be performed. To demonstrate the efficiency of the approach, a 10 pM fluorescently labeled -DNA solution was used as a model system to detect simultaneous translocation events using electron multiplying CCD imaging. Single-pore translocation events are also successfully detected using single-point confocal spectroscopy. [ABSTRACT FROM AUTHOR]

In this study, we manipulated the swimming direction of bacteria and controlled the switching off movement by using dc and ac galvanotaxis. The microstructures blotted by Serratia marcescens could be spontaneously manipulated and switched off at the desired position. The optimum ac frequency for switching off the microstructural motion was 7 Hz. We built a mathematical model to analyze and understand the oscillating motion of microstructure. [ABSTRACT FROM AUTHOR]

For biomedical applications, such as single cell manipulation, it is important to fabricate microstructures that can be powered and controlled wirelessly in fluidic environments. In this letter, we describe the construction and operation of truly micron-sized, biocompatible ferromagnetic microtransporters driven by external magnetic fields. Microtransporters were fabricated using a simple, single step fabrication method and can be produced in large numbers. We demonstrate that they can be navigated to manipulate single cells with micron-size precision without disturbing the local environment. [ABSTRACT FROM AUTHOR]

This paper describes a general approach for transferring clean single-layer graphene onto silicon nitride nanopore devices and the use of the electron beam of a transmission electron microscope (TEM) to drill size-controlled nanopores in freely suspended graphene. Besides nanopore drilling, we also used the TEM to heal and completely close the unwanted secondary holes formed by electron beam damage during the drilling process. We demonstrate electron beam assisted shrinking of irregularly shaped 40–60 nm pores down to 2 nm, exhibiting an exquisite control of graphene nanopore diameter. Our fabrication workflow also rendered graphene nanopores hydrophilic, allowing easy wetting and use of the pores for studying protein translocation and protein–protein interaction with a high signal to noise ratio. [ABSTRACT FROM AUTHOR]