Epigenetic inheritance is unfaithful at intermediately methylated CpG sites.

DNA methylation at the CpG dinucleotide is considered a stable epigenetic mark due to its presumed long-term inheritance through clonal expansion. Here, we perform high-throughput bisulfite sequencing on clonally derived somatic cell lines to quantitatively measure methylation inheritance at the nucleotide level. We find that although DNA methylation is generally faithfully maintained at hypo- and hypermethylated sites, this is not the case at intermediately methylated CpGs. Low fidelity intermediate methylation is interspersed throughout the genome and within genes with no or low transcriptional activity, and is not coordinately maintained between neighbouring sites. We determine that the probabilistic changes that occur at intermediately methylated sites are likely due to DNMT1 rather than DNMT3A/3B activity. The observed lack of clonal inheritance at intermediately methylated sites challenges the current epigenetic inheritance model and has direct implications for both the functional relevance and general interpretability of DNA methylation as a stable epigenetic mark.

Powerful, soft combustion actuators for insect-scale robots.

Insects perform feats of strength and endurance that belie their small stature. Insect-scale robots-although subject to the same scaling laws-demonstrate reduced performance because existing microactuator technologies are driven by low-energy density power sources and produce small forces and/or displacements. The use of high-energy density chemical fuels to power small, soft actuators represents a possible solution. We demonstrate a 325-milligram soft combustion microactuator that can achieve displacements of 140%, operate at frequencies >100 hertz, and generate forces >9.5 newtons. With these actuators, we powered an insect-scale quadrupedal robot, which demonstrated a variety of gait patterns, directional control, and a payload capacity 22 times its body weight. These features enabled locomotion through uneven terrain and over obstacles.

Multistable Metafluid based Energy Harvesting and Storage.

The thermodynamic properties of fluids play a crucial role in many engineering applications, particularly in the context of energy. Fluids with multistable thermodynamic properties may offer new paths for harvesting and storing energy via transitions between equilibria states. Such artificial multistable fluids can be created using the approach employed in metamaterials, which controls macro-properties through micro-structure composition. In this work, the dynamics of such "metafluids" is examined for a configuration of calorically-perfect compressible gas contained within multistable elastic capsules flowing in a fluid-filled tube. The velocity-, pressure-, and temperature-fields of multistable compressible metafluids is studied by both analytically and experimentally, focusing on transitions between different equilibria. The dynamics of a single capsule is first examine, which may move or change equilibrium state, due to fluidic forces. The interaction and motion of multiple capsules within a fluid-filled tube is then studied. It shows that such a system can be used to harvest energy from external temperature variations in either time or space. Thus, fluidic multistability allows specific quanta of energy to be captured and stored indefinitely as well as transported as a fluid, via tubes, at standard atmospheric conditions without the need for thermal isolation.

Tracking of thermal microbial shock proteins and genomic variation of Bacillus cereus due to some abiotic stresses.

Bacillus cereus is considered the most potent bacterial strain in terms of the increment in induced proteins during thermal treatment at 52 °C for 90 min. Protein production in food-born microorganism (Bacillus cereus) recovered from contaminated food was investigated in response to heat shock treatment. Bacterial tolerance towards pH, salinity, and temperature at various levels was also investigated. Heat-shock proteins (HSPs) produced when exposed to 52 °C for up to 60 minutes led to significant differences (30%) above the untreated control (37 °C), and the maximum difference was recorded at 52°C at 90 minutes. ISSR detected a higher number of bands/primer than RAPD (13.7 vs. 12.7, respectively), and more polymorphic bands (10.7 vs. 8.4 bands/primer, respectively). The untreated bacterial strain did not grow at pH levels lower than 3, whereas the thermally treated strain grew significantly at pH two. A consistent increase in HSPs was observed, with a gradual increase in salinity of less than 16%. Surprisingly, the gradual increase in temperature did not induce tolerance against higher temperatures. However, a significant growth rate was noticed in response to heat-shocked treatments. The untreated Bacillus cereus demonstrated antibiotic resistance to gentamycin and clindamycin (1.54 and 1.65 cm, respectively), much lower than the corresponding inhibition areas with preheat-treated test pathogen which were recorded (2.37 and 2.49 cm, respectively).

The role of intra-operative void score during transurethral resection of prostate as a marker of efficacy: a feasibility study.

BACKGROUND: To assess the feasibility of a novel intra-operative void scoring technique. To determine if intra-operative void score (VS) could act as a marker for post-operative success following TURP. METHODS: Fifteen patients undergoing TURP were included in this single-centre feasibility study. All patients had indwelling urinary catheters for recurrent retention due to benign prostatic hyperplasia (BPH). In theatre, immediately before- and after TURP, an intra-operative VS was measured and graded 0-5. Primary outcomes were the feasibility of measuring intra-operative VS and its accuracy in predicting surgical outcome. RESULTS: A combined pre- and post-score with a threshold ≥6 correctly predicted 82% of those who were catheter free (sensitivity) and 100% of those who were not catheter free (specificity) at follow up and the positive predictive value was 100% and negative predictive value 60%. CONCLUSION: Intra-operative void score during TURP is simple, reproducible, fast and requires minimal resources. In TURP it may predict successful outcomes by identifying patients who will be catheter free post-operatively as opposed to those who will be catheter dependent despite the procedure.

A metafluid with multistable density and internal energy states.

Investigating and tailoring the thermodynamic properties of different fluids is crucial to many fields. For example, the efficiency, operation range, and environmental safety of applications in energy and refrigeration cycles are highly affected by the properties of the respective available fluids. Here, we suggest combining gas, liquid and multistable elastic capsules to create an artificial fluid with a multitude of stable states. We study, theoretically and experimentally, the suspension's internal energy, equilibrium pressure-density relations, and their stability for both adiabatic and isothermal processes. We show that the elastic multistability of the capsules endows the fluid with multistable thermodynamic properties, including the ability of capturing and storing energy at standard atmospheric conditions, not found in naturally available fluids.

Fluid-Driven Traveling Waves in Soft Robots.

Many marine creatures, gastropods, and earthworms generate continuous traveling waves in their bodies for locomotion within marine environments, complex surfaces, and inside narrow gaps. In this work, we study theoretically and experimentally the use of embedded pneumatic networks as a mechanism to mimic nature and generate bidirectional traveling waves in soft robots. We apply long-wave approximation to theoretically calculate the required distribution of pneumatic network and inlet pressure oscillations needed to create desired moving wave patterns. We then fabricate soft robots with internal pneumatic network geometry based on these analytical results. The experimental results agree well with our model and demonstrate the propagation of moving waves in soft robots, along with locomotion capabilities. The presented results allow fabricating soft robots capable of continuous moving waves using the common approach of embedded pneumatic networks and requiring only two input controls.

Valveless microliter combustion for densely packed arrays of powerful soft actuators.

Existing tactile stimulation technologies powered by small actuators offer low-resolution stimuli compared to the enormous mechanoreceptor density of human skin. Arrays of soft pneumatic actuators initially show promise as small-resolution (1- to 3-mm diameter), highly conformable tactile display strategies yet ultimately fail because of their need for valves bulkier than the actuators themselves. In this paper, we demonstrate an array of individually addressable, soft fluidic actuators that operate without electromechanical valves. We achieve this by using microscale combustion and localized thermal flame quenching. Precisely, liquid metal electrodes produce sparks to ignite fuel lean methane-oxygen mixtures in a 5-mm diameter, 2-mm tall silicone cylinder. The exothermic reaction quickly pressurizes the cylinder, displacing a silicone membrane up to 6 mm in under 1 ms. This device has an estimated free-inflation instantaneous stroke power of 3 W. The maximum reported operational frequency of these cylinders is 1.2 kHz with average displacements of ∼100 µm. We demonstrate that, at these small scales, the wall-quenching flame behavior also allows operation of a 3 × 3 array of 3-mm diameter cylinders with 4-mm pitch. Though we primarily present our device as a tactile display technology, it is a platform microactuator technology with application beyond this one.

Microscale Hydrodynamic Cloaking and Shielding via Electro-Osmosis.

We demonstrate theoretically and experimentally that injection of momentum in a region surrounding an object in microscale flow can yield both "cloaking" conditions, where the flow field outside the cloaking region is unaffected by the object, and "shielding" conditions, where the hydrodynamic forces on the object are eliminated. Using field-effect electro-osmosis as a mechanism for injection of momentum, we present a theoretical framework and analytical solutions for a range of geometrical shapes, validate these both numerically and experimentally, and demonstrate the ability to dynamically switch between the different states.

Shortening the Early Treatment Diabetic Retinopathy Study visual acuity test utilizing a novel computer software: reproducibility in control and patient eyes.

PURPOSE: To describe and compare a method of computerized visual acuity (VA) testing software to the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. METHODS: Setting: Single tertiary institution. STUDY POPULATION: Prospective study including right eyes of volunteers (N = 109) and patients (N = 126). INTERVENTION: Subjects were tested in a random order twice with the ETDRS chart and twice with the VA software. For ETDRS, we calculated the final VA separately for each run, using four different test termination criteria (1-miss in a row, 2-miss in a row, 50% miss and per-letter). For software testing, we calculated final VA with a variety of number of letters presented. MAIN OUTCOME MEASURES: The main outcome measures were reproducibility and number of letters required to exceed ETDRS reproducibility. RESULTS: For ETDRS, the average number of letters presented was 55.1 ± 9, 54.3 ± 10, 53.1 ± 10 and 70 for the 1-miss, 2-miss, 50% termination and per-letter criterion. The test-retest variability (TRV) of ETDRS was 0.29, 0.42, 0.17 and 0.141 for the 1-miss in a row, 2-miss in a row, 50% and per-letter termination criteria. For the software VA test, TRV was 0.202, 0.138 and 0.112 after presenting 6, 11 and 20 letters. The reproducibility of the software was equal to the ETDRS at 11 letters and thereafter surpassed. Similar results were achieved in the patient group. CONCLUSIONS: This study demonstrates that by utilizing a VA testing software, based on advanced threshold testing algorithms we were able to duplicate, and surpass, the reproducibility of the ETDRS chart while presenting much fewer letters.

Genomic properties of variably methylated retrotransposons in mouse.

BACKGROUND: Transposable elements (TEs) are enriched in cytosine methylation, preventing their mobility within the genome. We previously identified a genome-wide repertoire of candidate intracisternal A particle (IAP) TEs in mice that exhibit inter-individual variability in this methylation (VM-IAPs) with implications for genome function. RESULTS: Here we validate these metastable epialleles and discover a novel class that exhibit tissue specificity (tsVM-IAPs) in addition to those with uniform methylation in all tissues (constitutive- or cVM-IAPs); both types have the potential to regulate genes in cis. Screening for variable methylation at other TEs shows that this phenomenon is largely limited to IAPs, which are amongst the youngest and most active endogenous retroviruses. We identify sequences enriched within cVM-IAPs, but determine that these are not sufficient to confer epigenetic variability. CTCF is enriched at VM-IAPs with binding inversely correlated with DNA methylation. We uncover dynamic physical interactions between cVM-IAPs with low methylation ranges and other genomic loci, suggesting that VM-IAPs have the potential for long-range regulation. CONCLUSION: Our findings indicate that a recently evolved interplay between genetic sequence, CTCF binding, and DNA methylation at young TEs can result in inter-individual variability in transcriptional outcomes with implications for phenotypic variation.

Fluid Mechanics of Pneumatic Soft Robots.

Pressurization of gas within embedded channels and cavities is a popular method for actuating soft robots. Various previous works examined the effects of internal fluid mechanics on this actuation approach, as well as on leveraging viscous effects to extend the capabilities of soft robots. However, no existing works studied the combined effects of fluid viscosity and compressibility, relevant to miniaturized configurations, which is the aim of the current work. We derive a general model for compressible viscous flow in an elastic media representing a simplified miniaturized soft robot. We illustrate applying this model to periodic configurations, simplifying it via a long-wave approximation. Steady, and time-dependent solutions are obtained, allowing to model the flow and to provide insight into the actuation dynamics of miniaturized pneumatic soft robots.

Underactuated fluidic control of a continuous multistable membrane.

This work addresses the challenge of underactuated pattern generation in continuous multistable structures. The examined configuration is a slender membrane which can concurrently sustain two different equilibria states, separated by transition regions, and is actuated by a viscous fluid. We first demonstrate the formation and motion of a single transition region and then sequencing of several such moving transition regions to achieve arbitrary patterns by controlling the inlet pressure of the actuating fluid. Finally, we show that nonuniform membrane properties, along with transient dynamics of the fluid, can be leveraged to directly snap through any segment of the membrane.

Nonuniform Electro-osmotic Flow Drives Fluid-Structure Instability.

We demonstrate the existence of a fluid-structure instability arising from the interaction of electro-osmotic flow with an elastic substrate. Considering the case of flow within a soft fluidic chamber, we show that above a certain electric field threshold, negative gauge pressure induced by electro-osmotic flow causes the collapse of its elastic walls. We combine experiments and theoretical analysis to elucidate the underlying mechanism for instability and identify several distinct dynamic regimes. The understanding of this instability is important for the design of electrokinetic systems containing soft elements.

Single-Input Control of Multiple Fluid-Driven Elastic Actuators via Interaction Between Bistability and Viscosity.

A leading concept in soft robotics actuation, as well as in microfluidics applications such as valves in lab-on-a-chip devices, is applying pressurized flow in cavities embedded within elastic bodies. Generating complex deformation patterns typically requires control of several inputs, which greatly complicates the system's operation. In this study, we present a novel method for single-input control of a serial chain of bistable elastic chambers connected by thin tubes. Controlling a single flow rate at the chain's inlet, we induce an irreversible sequence of transitions that can reach any desired state combination of all bistable elements. Mathematical formulation and analysis of the system's dynamics reveal that these transitions are enabled, thanks to bistability combined with pressure lag induced by viscous resistance. The results are demonstrated through numerical simulations combined with experiments for chains of up to five chambers, using water-diluted glycerol as the injected fluid. The proposed technique has a promising potential for development of sophisticated soft actuators with minimalistic control.

Awareness of European practitioners toward uncommon tropical diseases: are we prepared to deal with mass migration? Results of an international survey.

PURPOSE: The recent rise in migration from Africa through the Mediterranean basin into Europe has resulted in an increased incidence of uncommon diseases such as schistosomiasis and genito-urinary tuberculosis, which were previously largely unknown in this region. This study aimed to evaluate the insight of European urologists into diagnosing and managing these disease conditions and to determine whether they were adequately prepared to deal with the changing disease spectrum in their countries. METHODS: A survey including specific questions about the diagnosis and management of 'tropical' urological diseases was distributed among urologists working in Europe and Africa. Multivariate logistic regression models were performed to detect the continent (African or European) effect on knowledge of and insight into tropical urological diseases. RESULTS: A total of 312 surveys were administered. African and European respondents accounted for 109 (36.09%) and 193 (63.91%) respondents, respectively. The multivariate logistic regression analysis demonstrated a significant deficiency in the knowledge of tropical urological diseases in the European cohort compared with the African cohort (p < 0.05). Moreover, in the European cohort, markedly superior knowledge of tropical urological diseases was observed for respondents who had previously worked in a developing country. CONCLUSIONS: Though European urologists are not required to have the same insight as African urologists, they showed a very unsatisfactory knowledge of tropical urological diseases. The experience of working in a developing country could improve the knowledge of European urologists regarding tropical urological diseases.

Leveraging Viscous Peeling to Create and Activate Soft Actuators and Microfluidic Devices.

The research fields of microfluidics and soft robotics both involve complex small-scale internal channel networks, embedded within a solid structure. This study examines leveraging viscous peeling as a mechanism to create and activate soft actuators and microchannel networks, including complex elements such as valves, without the need for fabrication of structures with micron-scale internal cavities. We consider configurations composed of an internal slender structure embedded within another elastic solid. Pressurized viscous fluid is introduced into the interface between the two solids, thus peeling the two elastic structures and creating internal cavities. Since the gap between the solids is determined by the externally applied pressure, the characteristic size of the fluid network may vary with time and be much smaller than the resolution of the fabrication method. This study presents a model for the highly nonlinear elastic-viscous dynamics governing the flow and deformation of such configurations. Fabrication and experimental demonstrations of micron-scale valves and channel networks created from millimeter scale structures are presented, as well as the transient dynamics of viscous peeling-based soft actuators. The experimental data are compared with the suggested model, showing very good agreement.

Inter-rater reliability in the radiological classification of renal injuries.

INTRODUCTION: Although many radiologists invoke the surgical classification of renal injury proposed by the American Association for Surgery in Trauma (AAST), there has been only limited work on the role of the AAST system as an imaging stratification. The aim was to determine the inter-rater reliability (IRR) amongst radiologists and urologists using the AAST system. METHODS: A 1-year retrospective study of consecutive patients with computed tomography (CT) evidence of renal trauma managed at a Level 1 trauma center. Three radiologists and three urologists independently stratified the presentation CT findings according to the AAST renal trauma classification. Agreement between independent raters and mutually exclusive groups was determined utilizing weighted kappa coefficients. RESULTS: One hundred and one patients were included. Individual inter-observer agreements ranged from 54/101 (53.4%) to 62/101 (61.4%), with corresponding weighted kappa values from 0.61 to 0.69, constituting substantial agreement. Urologists achieved intra-disciplinary agreement in 49 cases (48.5%) and radiologists in 36 cases (35.6%). Six-reader agreement was achieved in 24 cases (23.7%). The AAST grade I injuries had the highest level of agreement, overall. CONCLUSION: The finding of substantial IRR amongst radiologists and urologists utilizing the AAST system supports continued use of the broad parameters of the AAST system, with some modification in specific categories with lower agreement.

Leveraging Internal Viscous Flow to Extend the Capabilities of Beam-Shaped Soft Robotic Actuators.

Elastic deformation of beam-shaped structures due to embedded fluidic networks (EFNs) is mainly studied in the context of soft actuators and soft robotic applications. Currently, the effects of viscosity are not examined in such configurations. In this work, we introduce an internal viscous flow and present the extended range of actuation modes enabled by viscosity. We analyze the interaction between elastic deflection of a slender beam and viscous flow in a long serpentine channel embedded within the beam. The embedded network is positioned asymmetrically with regard to the neutral plane and thus pressure within the channel creates a local moment deforming the beam. Under assumptions of creeping flow and small deflections, we obtain a fourth-order integro-differential equation governing the time-dependent deflection field. This relation enables the design of complex time-varying deformation patterns of beams with EFNs. Leveraging viscosity allows to extend the capabilities of beam-shaped actuators such as creation of inertia-like standing and moving wave solutions in configurations with negligible inertia and limiting deformation to a small section of the actuator. The results are illustrated experimentally.