SensAA-Design and Verification of a Cloud-Based Wearable Biomechanical Data Acquisition System.

Exoskeletons designed to assist patients with activities of daily living are becoming increasingly popular, but still are subject to research. In order to gather requirements for the design of such systems, long-term gait observation of the patients over the course of multiple days in an environment of daily living are required. In this paper a wearable all-in-one data acquisition system for collecting and storing biomechanical data in everyday life is proposed. The system is designed to be cost efficient and easy to use, using off-the-shelf components and a cloud server system for centralized data storage. The measurement accuracy of the system was verified, by measuring the angle of the human knee joint at walking speeds between 3 and 12 km/h in reference to an optical motion analysis system. The acquired data were uploaded to a cloud database via a smartphone application. Verification results showed that the proposed toolchain works as desired. The system reached an RMSE from 2.9° to 8°, which is below that of most comparable systems. The system provides a powerful, scalable platform for collecting and processing biomechanical data, which can help to automize the generation of an extensive database for human kinematics.

Application of the Adverse Outcome Pathway Concept to In Vitro Nephrotoxicity Assessment: Kidney Injury due to Receptor-Mediated Endocytosis and Lysosomal Overload as a Case Study.

Application of adverse outcome pathways (AOP) and integration of quantitative in vitro to in vivo extrapolation (QIVIVE) may support the paradigm shift in toxicity testing to move from apical endpoints in test animals to more mechanism-based in vitro assays. Here, we developed an AOP of proximal tubule injury linking a molecular initiating event (MIE) to a cascade of key events (KEs) leading to lysosomal overload and ultimately to cell death. This AOP was used as a case study to adopt the AOP concept for systemic toxicity testing and risk assessment based on in vitro data. In this AOP, nephrotoxicity is thought to result from receptor-mediated endocytosis (MIE) of the chemical stressor, disturbance of lysosomal function (KE1), and lysosomal disruption (KE2) associated with release of reactive oxygen species and cytotoxic lysosomal enzymes that induce cell death (KE3). Based on this mechanistic framework, in vitro readouts reflecting each KE were identified. Utilizing polymyxin antibiotics as chemical stressors for this AOP, the dose-response for each in vitro endpoint was recorded in proximal tubule cells from rat (NRK-52E) and human (RPTEC/TERT1) in order to (1) experimentally support the sequence of key events (KEs), to (2) establish quantitative relationships between KEs as a basis for prediction of downstream KEs based on in vitro data reflecting early KEs and to (3) derive suitable in vitro points of departure for human risk assessment. Time-resolved analysis was used to support the temporal sequence of events within this AOP. Quantitative response-response relationships between KEs established from in vitro data on polymyxin B were successfully used to predict in vitro toxicity of other polymyxin derivatives. Finally, a physiologically based kinetic (PBK) model was utilized to transform in vitro effect concentrations to a human equivalent dose for polymyxin B. The predicted in vivo effective doses were in the range of therapeutic doses known to be associated with a risk for nephrotoxicity. Taken together, these data provide proof-of-concept for the feasibility of in vitro based risk assessment through integration of mechanistic endpoints and reverse toxicokinetic modelling.

Portable and low-cost biosensor towards on-site detection of diclofenac in wastewater.

Wastewater treatment plants are the main release sources of pharmaceutical compounds present in surface waters. Even at low concentrations, many of these substances have long-term adverse effects on the environment. For an efficient control of pharmaceutical removal, a real-time recognition is a prerequisite. Currently, quantification of such compounds is done in special equipped laboratories and is rather time-consuming and expensive. Here, we introduce a novel biosensor for the detection of the pharmaceutical compound diclofenac, which can be produced with low costs, is easy in handling and can be applied directly on-site. Recognition of diclofenac is based on genetically engineered yeast cells which produce green fluorescent protein in a diclofenac concentration-dependent manner. Centerpiece of the sensor is a foil-based microfluidic flow cell, which allows supply with nutrient solution and analyte while preventing loss of reporter cells. Readout of data is accomplished by a newly developed spectrometric detection unit. With this device, we are able to determine diclofenac concentrations in a range from 10 to 50 µM.

In operando x-ray imaging of nanoscale devices: Composition, valence, and internal electrical fields.

We introduce a method for directly imaging depletion layers in operando with elemental specificity and chemical speciation at sub-100 nm spatial resolution applicable to today's three-dimensional electronic architectures. These typically contain complex, multicomponent designs consisting of epitaxial heterostructures, buried domains, or nanostructures with different shapes and sizes. Although the variety of devices is immense, they commonly rely on carrier separation in a built-in potential induced by composition or strain gradients. To image these, we scanned a focused synchrotron x-ray nanobeam over a single semiconductor nanowire heterostructure and simultaneously measured the current through the device and the emitted characteristic x-rays as a function of the incoming hard x-ray energy. With these results, it is possible to identify the compositional and molecular structure as well as localize the electrical fields present under typical working conditions. This information allows us to draw an energy band diagram consistent with the elemental distribution and a high-resolution chemical speciation map.

Synthesis, Morphological, and Electro-optical Characterizations of Metal/Semiconductor Nanowire Heterostructures.

In this letter, we demonstrate the formation of unique Ga/GaAs/Si nanowire heterostructures, which were successfully implemented in nanoscale light-emitting devices with visible room temperature electroluminescence. Based on our recent approach for the integration of InAs/Si heterostructures into Si nanowires by ion implantation and flash lamp annealing, we developed a routine that has proven to be suitable for the monolithic integration of GaAs nanocrystallite segments into the core of silicon nanowires. The formation of a Ga segment adjacent to longer GaAs nanocrystallites resulted in Schottky-diode-like I/V characteristics with distinct electroluminescence originating from the GaAs nanocrystallite for the nanowire device operated in the reverse breakdown regime. The observed electroluminescence was ascribed to radiative band-to-band recombinations resulting in distinct emission peaks and a low contribution due to intraband transition, which were also observed under forward bias. Simulations of the obtained nanowire heterostructure confirmed the proposed impact ionization process responsible for hot carrier luminescence. This approach may enable a new route for on-chip photonic devices used for light emission or detection purposes.

Anomalous Plastic Deformation and Sputtering of Ion Irradiated Silicon Nanowires.

Silicon nanowires of various diameters were irradiated with 100 keV and 300 keV Ar(+) ions on a rotatable and heatable stage. Irradiation at elevated temperatures above 300 °C retains the geometry of the nanostructure and sputtering can be gauged accurately. The diameter dependence of the sputtering shows a maximum if the ion range matches the nanowire diameter, which is in good agreement with Monte Carlo simulations based on binary collisions. Nanowires irradiated at room temperature, however, amorphize and deform plastically. So far, plastic deformation has not been observed in bulk silicon at such low ion energies. The magnitude and direction of the deformation is independent of the ion-beam direction and cannot be explained with mass-transport in a binary collision cascade but only by collective movement of atoms in the collision cascade with the given boundary conditions of a high surface to volume ratio.

Erythropoietin gene expression in renal carcinoma is considerably more frequent than paraneoplastic polycythemia.

Signalling by erythropoietin (EPO) is increasingly recognised as a relevant mechanism in tumour biology, potentially leading to enhanced proliferation, angiogenesis and therapy resistance. Paraneoplastic polycythemia by cancerous overproduction of EPO is a rare event, but most frequently seen in patients with renal cell carcinoma (RCC). The majority of clear cell RCC displays a strong activation of the transcription factor regulating EPO, the Hypoxia-inducible Factor (HIF). Therefore, it is unclear why only a small minority of patients develop polycythemia. We studied 70 RCC for EPO gene and HIFalpha isoform expression. 34% of all RCC showed expression of EPO mRNA in RNase protection assays, which were almost exclusively of the clear cell type. Only 1 patient presented with polycythemia. In situ hybridisation revealed that expression of EPO was in the tumour cells. Expression of EPO mRNA was always associated with activation of HIF, which could involve HIF-1alpha and/or HIF-2alpha. The frequency of EPO gene expression in RCC is therefore much higher than the prevalence of polycythemia. Furthermore, activation of HIF appears necessary for EPO gene expression in RCC, but is clearly not the only determinant. Further to the reported expression of EPO receptors in tumour tissues, the finding of widespread expression of EPO in RCC supports the recent notion of an involvement of this system in paracrine or autocrine effects of tumour cells.

Explicit versus implicit risk assessment for the indication of antithrombotic prophylaxis in acutely ill medical in-patients.

QUESTIONS UNDER STUDY: The indication of venous thromboembolism (VTE) prophylaxis in acutely ill patients admitted to medical departments is not well-defined. Consensus groups have published recommendations and guidelines, addressing this issue. We investigated whether a guideline (explicit risk assessment) would improve the formerly used implicit risk assessment. METHODS: We compared two groups of patients consecutively admitted to our department during a 4-months period each. Group 1 was assessed prospectively and treated according to a guideline (explicit assessment). Group 2 consisted of the patients hospitalised in the four months prior to the introduction of the guideline (implicit assessment). Their data were abstracted retrospectively from the medical charts. Main outcome measures were symptomatic VTE and major bleedings, and the consumption of unfractionated (UFH) and fractionated (LMWH) heparins. Follow-up lasted until 90 days after hospital discharge. RESULTS: Symptomatic VTE occurred in 5/686 (0.7%) patients of group 1 vs 9/622 (1.4%) patients of group 2 during the hospital phase (p>0.05), and in 9/646 (1.4%) vs 10/572 (1.7%) during the whole study period (p>0.05). In group 1, 350 (51%) patients did not qualify for thromboprophylaxis according to the guideline, and none of them experienced any symptomatic VTE event. Three patients (0.5%) in group 1 and 4 patients (0.6%) in group 2 experienced a major bleeding event (p>0.05). Average consumption of UFH and LMWH did not differ between the groups. CONCLUSIONS: The introduction of a guideline for explicit assessment of thromboembolic risk was not significantly superior to the formerly used implicit assessment. However, based on the small number of events observed in this study, a minor advantage cannot be ruled out. Targeted indication for thromboprophylaxis, whether explicit or implicit, avoided application of UFH or LMWH in half of the patients in our setting.