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Field-effect EIS (electrolyte-insulator-semiconductor) sensors modified with a positively charged weak polyelectrolyte layer have been applied for the electrical detection of DNA (deoxyribonucleic acid) immobilization and hybridization by the intrinsic molecular charge. The EIS sensors are able to detect the existence of target DNA amplicons in PCR (polymerase chain reaction) samples and thus, can be used as tool for a quick verification of DNA amplification and the successful PCR process. Due to their miniaturized setup, compatibility with advanced micro- and nanotechnologies, and ability to detect biomolecules by their intrinsic molecular charge, those sensors can serve as possible platform for the development of label-free DNA chips. Possible application fields as well as challenges and limitations will be discussed.
In a special paired sample case, Hotelling’s T² test based on the differences of the paired random vectors is the likelihood ratio test for testing the hypothesis that the paired random vectors have the same mean; with respect to a special group of affine linear transformations it is the uniformly most powerful invariant test for the general alternative of a difference in mean. We present an elementary straightforward proof of this result. The likelihood ratio test for testing the hypothesis that the covariance structure is of the assumed special form is derived and discussed. Applications to real data are given.
Hotelling’s T² tests in paired and independent survey samples are compared using the traditional asymptotic efficiency concepts of Hodges–Lehmann, Bahadur and Pitman, as well as through criteria based on the volumes of corresponding confidence regions. Conditions characterizing the superiority of a procedure are given in terms of population canonical correlation type coefficients. Statistical tests for checking these conditions are developed. Test statistics based on the eigenvalues of a symmetrized sample cross-covariance matrix are suggested, as well as test statistics based on sample canonical correlation type coefficients.
In this study, we show that synthetic sapphire (Al₂O₃), an established implant material, can also serve as a platform material for biosensors comparable to nanocrystalline diamond. Sapphire chips, beads, and powder were first modified with (3-aminopropyl) triethoxysilane (APTES), followed by succinic anhydride (SA), and finally single-stranded probe DNA was EDC coupled to the functionalized layer. The presence of the APTES-SA layer on sapphire powders was confirmed by thermogravimetric analyis and Fourier-transform infrared spectroscopy. Using planar sapphire chips as substrates and X-ray photoelectron spectroscopy (XPS) as surface-sensitive tool, the sequence of individual layers was analyzed with respect to their chemical state, enabling the quantification of areal densities of the involved molecular units. Fluorescence microscopy was used to demonstrate the hybridization of fluorescently tagged target DNA to the probe DNA, including denaturation- and re-hybridization experiments. Due to its high thermal conductivity, synthetic sapphire is especially suitable as a chip material for the heat-transfer method, which was employed to distinguish complementary- and non-complementary DNA duplexes containing single-nucleotide polymorphisms. These results indicate that it is possible to detect mutations electronically with a chemically resilient and electrically insulating chip material.
Based on an identifying Volterra type integral equation for randomly right censored observations from a lifetime distribution function F, we solve the corresponding estimating equation by an explicit and implicit Euler scheme. While the first approach results in some known estimators, the second one produces new semi-parametric and pre-smoothed Kaplan–Meier estimators which are real distribution functions rather than sub-distribution functions as the former ones are. This property of the new estimators is particular useful if one wants to estimate the expected lifetime restricted to the support of the observation time.
Specifically, we focus on estimation under the semi-parametric random censorship model (SRCM), that is, a random censorship model where the conditional expectation of the censoring indicator given the observation belongs to a parametric family. We show that some estimated linear functionals which are based on the new semi-parametric estimator are strong consistent, asymptotically normal, and efficient under SRCM. In a small simulation study, the performance of the new estimator is illustrated under moderate sample sizes. Finally, we apply the new estimator to a well-known real dataset.
The Saturnian moon Enceladus with its extensive water bodies underneath a thick ice sheet cover is a potential candidate for extraterrestrial life. Direct exploration of such extraterrestrial aquatic ecosystems requires advanced access and sampling technologies with a high level of autonomy. A new technological approach has been developed as part of the collaborative research project Enceladus Explorer (EnEx). The concept is based upon a minimally invasive melting probe called the IceMole. The force-regulated, heater-controlled IceMole is able to travel along a curved trajectory as well as upwards. Hence, it allows maneuvers which may be necessary for obstacle avoidance or target selection. Maneuverability, however, necessitates a sophisticated on-board navigation system capable of autonomous operations. The development of such a navigational system has been the focal part of the EnEx project. The original IceMole has been further developed to include relative positioning based on in-ice attitude determination, acoustic positioning, ultrasonic obstacle and target detection integrated through a high-level sensor fusion. This paper describes the EnEx technology and discusses implications for an actual extraterrestrial mission concept.
Background/Aims: Common systems for the quantification of cellular contraction rely on animal-based models, complex experimental setups or indirect approaches. The herein presented CellDrum technology for testing mechanical tension of cellular monolayers and thin tissue constructs has the potential to scale-up mechanical testing towards medium-throughput analyses. Using hiPS-Cardiac Myocytes (hiPS-CMs) it represents a new perspective of drug testing and brings us closer to personalized drug medication. Methods: In the present study, monolayers of self-beating hiPS-CMs were grown on ultra-thin circular silicone membranes and deflect under the weight of the culture medium. Rhythmic contractions of the hiPS-CMs induced variations of the membrane deflection. The recorded contraction-relaxation-cycles were analyzed with respect to their amplitudes, durations, time integrals and frequencies. Besides unstimulated force and tensile stress, we investigated the effects of agonists and antagonists acting on Ca²⁺ channels (S-Bay K8644/verapamil) and Na⁺ channels (veratridine/lidocaine). Results: The measured data and simulations for pharmacologically unstimulated contraction resembled findings in native human heart tissue, while the pharmacological dose-response curves were highly accurate and consistent with reference data. Conclusion: We conclude that the combination of the CellDrum with hiPS-CMs offers a fast, facile and precise system for pharmacological, toxicological studies and offers new preclinical basic research potential.
We present an electromechanically coupled computational model for the investigation of a thin cardiac tissue construct consisting of human-induced pluripotent stem cell-derived atrial, ventricular and sinoatrial cardiomyocytes. The mechanical and electrophysiological parts of the finite element model, as well as their coupling are explained in detail. The model is implemented in the open source finite element code Code_Aster and is employed for the simulation of a thin circular membrane deflected by a monolayer of autonomously beating, circular, thin cardiac tissue. Two cardio-active drugs, S-Bay K8644 and veratridine, are applied in experiments and simulations and are investigated with respect to their chronotropic effects on the tissue. These results demonstrate the potential of coupled micro- and macroscopic electromechanical models of cardiac tissue to be adapted to experimental results at the cellular level. Further model improvements are discussed taking into account experimentally measurable quantities that can easily be extracted from the obtained experimental results. The goal is to estimate the potential to adapt the presented model to sample specific cell cultures.
Bonding of polymer-based microfluidics to polymer substrates still poses a challenge for Lab-On-a-Chip applications. Especially, when sensing elements are incorporated, patterned deposition of adhesives with curing at ambient conditions is required. Here, we demonstrate a fabrication method for fully printed microfluidic systems with sensing elements using inkjet and stereolithographic 3D-printing.
On-line monitoring of the metabolic activity of microorganisms involved in intermediate stages of biogas production plays an important role to avoid undesirable “down times” during the biogas production. In order to control this process, an on-chip differential measuring system based on the light-addressable potentiometric sensor (LAPS) principle combined with a 3D-printed multi-chamber structure has been realized. As a test microorganism, Escherichia coli K12 (E. coli K12) were used for cell-based measurements. Multi-chamber structures were developed to determine the metabolic activity of E. coli K12 in suspension for a different number of cells, responding to the addition of a constant or variable amount of glucose concentrations, enabling differential and simultaneous measurements.
Plate osteosynthesis of displaced proximal phalangeal neck fractures of the hand allows early mobilization due to a stable internal fixation. Nevertheless, joint stiffness—because of soft tissue irritation—represents a common complication leading to high complication rates. Del Pinal et al. recently reported promising clinical results for a new, minimally invasive fixation technique with a cannulated headless intramedullary compression screw. Hence, the aim of this study was to compare plate fixation of proximal phalangeal neck fractures to less two less invasive techniques: Crossed k-wire fixation and intramedullary screw fixation. We hypothesized that these fixation techniques provide inferior stability when compared to plate osteosynthesis.
Treatment of posttraumatic osteoarthritis of the radial column of the elbow joint remains a challenging yet common issue.
While partial joint replacement leads to high revision rates, radial head excision has shown to severely increase joint instability. Shortening osteotomy of the radius could be an option to decrease the contact pressure of the radiohumeral joint and thereby pain levels without causing valgus instability. Hence, the aim of this biomechanical study was to evaluate the effects of radial shortening on axial load distribution and valgus stability of the elbow joint.
Surgical reconstruction of the interosseous membrane (IOM) could restore longitudinal forearm stability to avoid persisting disability due to capituloradial and ulnocarpal impingement in Essex Lopresti lesions. This biomechanical study aimed to assess longitudinal forearm stability of intact specimens, after sectioning of the IOM and after reconstruction with a TightRope construct using either a single or double bundle technique.
While plate fixation of proximal ulna fractures might lead to superior clinical results compared to tension band wiring, regular plates represent an established risk factor for wound complications. The olecranon double plates (Medartis, Basel, CH) might decrease complications related to the osteosynthesis because of their low profile and better anatomical fit. This study aimed to evaluate the biomechanical performance and clinical results of the olecranon double plates.