Identification of adequate neurally adjusted ventilatory assist (NAVA) during systematic increases in the NAVA level

Neurally adjusted ventilatory assist (NAVA) delivers airway pressure (P(aw)) in proportion to the electrical activity of the diaphragm (EAdi) using an adjustable proportionality constant (NAVA level, cm·H(2)O/μV). During systematic increases in the NAVA level, feedback-controlled down-regulation of the EAdi results in a characteristic two-phased response in P(aw) and tidal volume (Vt). The transition from the 1st to the 2nd response phase allows identification of adequate unloading of the respiratory muscles with NAVA (NAVA(AL)). We aimed to develop and validate a mathematical algorithm to identify NAVA(AL). P(aw), Vt, and EAdi were recorded while systematically increasing the NAVA level in 19 adult patients. In a multistep approach, inspiratory P(aw) peaks were first identified by dividing the EAdi into inspiratory portions using Gaussian mixture modeling. Two polynomials were then fitted onto the curves of both P(aw) peaks and Vt. The beginning of the P(aw) and Vt plateaus, and thus NAVA(AL), was identified at the minimum of squared polynomial derivative and polynomial fitting errors. A graphical user interface was developed in the Matlab computing environment. Median NAVA(AL) visually estimated by 18 independent physicians was 2.7 (range 0.4 to 5.8) cm·H(2)O/μV and identified by our model was 2.6 (range 0.6 to 5.0) cm·H(2)O/μV. NAVA(AL) identified by our model was below the range of visually estimated NAVA(AL) in two instances and was above in one instance. We conclude that our model identifies NAVA(AL) in most instances with acceptable accuracy for application in clinical routine and research.     

Structure-function studies of an engineered scaffold protein derived from Stefin A. II: Development and applications of the SQT variant

Constrained binding peptides (peptide aptamers) may serve as tools to explore protein conformations and disrupt protein-protein interactions. The quality of the protein scaffold, by which the binding peptide is constrained and presented, is of crucial importance. SQT (Stefin A Quadruple Mutant-Tracy) is our most recent development in the Stefin A-derived scaffold series. Stefin A naturally uses three surfaces to interact with its targets. SQT tolerates peptide insertions at all three positions. Peptide aptamers in the SQT scaffold can be expressed in bacterial, yeast and human cells, and displayed as a fusion to truncated pIII on phage. Peptides that bind to CDK2 can show improved binding in protein microarrays when presented by the SQT scaffold. Yeast two-hybrid libraries have been screened for binders to the POZ domain of BCL-6 and to a peptide derived from PBP2', specific to methicillin-resistant Staphylococcus aureus. Presentation of the Noxa BH3 helix by SQT allows specific interaction with Mcl-1 in human cells. Together, our results show that Stefin A-derived scaffolds, including SQT, can be used for a variety of applications in cellular and molecular biology. We will henceforth refer to Stefin A-derived engineered proteins as Scannins.     

Nanoporous artificial proboscis for probing minute amount of liquids

We describe a method of fabrication of nanoporous flexible probes which work as artificial proboscises. The challenge of making probes with fast absorption rates and good retention capacity was addressed theoretically and experimentally. This work shows that the probe should possess two levels of pore hierarchy: nanopores are needed to enhance the capillary action and micrometer pores are required to speed up fluid transport. The model of controlled fluid absorption was verified in experiments. We also demonstrated that the artificial proboscises can be remotely controlled by electric or magnetic fields. Using an artificial proboscis, one can approach a drop of hazardous liquid, absorb it and safely deliver it to an analytical device. With these materials, the paradigm of a stationary microfluidic platform can be shifted to the flexible structures that would allow one to pack multiple microfluidic sensors into a single fiber.     

Complexes of Silver(I) Ions and Silver Phosphate Nanoparticles with Hyaluronic Acid and/or Chitosan as Promising Antimicrobial Agents for Vascular Grafts

Polymers are currently widely used to replace a variety of natural materials with respect to their favourable physical and chemical properties, and due to their economic advantage. One of the most important branches of application of polymers is the production of different products for medical use. In this case, it is necessary to face a significant disadvantage of polymer products due to possible and very common colonization of the surface by various microorganisms that can pose a potential danger to the patient. One of the possible solutions is to prepare polymer with antibacterial/antimicrobial properties that is resistant to bacterial colonization. The aim of this study was to contribute to the development of antimicrobial polymeric material ideal for covering vascular implants with subsequent use in transplant surgery. Therefore, the complexes of polymeric substances (hyaluronic acid and chitosan) with silver nitrate or silver phosphate nanoparticles were created, and their effects on gram-positive bacterial culture of Staphylococcus aureus were monitored. Stages of formation of complexes of silver nitrate and silver phosphate nanoparticles with polymeric compounds were characterized using electrochemical and spectrophotometric methods. Furthermore, the antimicrobial activity of complexes was determined using the methods of determination of growth curves and zones of inhibition. The results of this study revealed that the complex of chitosan, with silver phosphate nanoparticles, was the most suitable in order to have an antibacterial effect on bacterial culture of Staphylococcus aureus. Formation of this complex was under way at low concentrations of chitosan. The results of electrochemical determination corresponded with the results of spectrophotometric methods and verified good interaction and formation of the complex. The complex has an outstanding antibacterial effect and this effect was of several orders higher compared to other investigated complexes.     

Insights into the Adhesive Mechanisms of Tree Frogs using Artificial Mimics

Elastic, microstructured surfaces (hydrophobic and hydrophilic) mimicking the surface structure of tree‐frog toe‐pads are fabricated. Their adhesion and friction behaviour in the presence of a liquid layer is evaluated and compared to flat controls. Tree‐frog‐like patterns are beneficial for wet adhesion only if the liquid does not wet the surface. The situation is different in friction, where the surface structure lead to significantly higher friction forces only if the liquid does wet the surface. Taking into account that tree‐frog attachment pads are hydrophilic and that their secretion wets all kind of surfaces, our results indicate that the surface structure in tree‐frog toe‐pads has been developed for climbing, when shear (friction) forces are involved. These results evidence the benefits and limitations of the surface design (microstructure and hydrophilicity) for adhesion and friction under wet conditions.     

CdTe/CdS thin film solar cells grown in substrate configuration

The ability to grow efficient CdTe/CdS solar cells in substrate configuration would not only allow for the use of non‐transparent and flexible substrates but also enable a better control of junction formation. Yet, the problems of barrier formation at the back contact as well as the formation of a p–n junction with reduced recombination losses have to be solved. In this work, CdTe/CdS solar cells in substrate configuration were developed, and the results on different combinations of back contact materials are presented. The Cu content in the electrical back contact was found to be a crucial parameter for the optimal CdCl₂‐treatment procedure. For Cu‐free cells, two activation treatments were applied, whereas Cu‐containing cells were only treated once after the CdTe deposition. A recrystallization behavior of the CdTe layer upon its activation similar to superstrate configuration was found; however, no CdTe–CdS intermixing could be observed when the layers were treated consecutively. Remarkably high V_OC and fill factor of 768 mV and 68.6%, respectively, were achieved using a combination of MoO₃, Te, and Cu as back contact buffer layer resulting in 11.3% conversion efficiency. With a Cu‐free MoO₃/Te buffer material, a V_OC of 733 mV, a fill factor of 62.3%, and an efficiency of 10.0% were obtained. Copyright © 2012 John Wiley & Sons, Ltd.     

Multiple Organolithium Generation in the Continuous Flow Synthesis of Amitriptyline

A continuous flow protocol for the preparation of the tricyclic antidepressant (TCA) amitriptyline is reported. The advantages of flow chemistry when handling organometallic agents as well as when performing reaction with gases are demonstrated. Continuous multilithiation combined with carboxylation and the Parham cyclization, a Grignard addition and thermolytic water elimination by inductive heating are key features of the multistep protocol.

     

Giant Magnetoelectric Effect in Thin‐Film Composites

Highly sensitive AC magnetic field sensors are presented using magnetoelectric composites consisting of magnetostrictive and piezoelectric phases. They are offering passive nature, high sensitivity, large effect enhancement at mechanical resonance, and large linear dynamic range. Thin‐film magnetoelectric 2‐2 composites benefit from perfect coupling between the piezoelectric and magnetostrictive phases and from the reduction in size which is essential for high spatial resolution. Their design uses AlN and a plate capacitor or PZT with interdigital electrodes and magnetostrictive amorphous FeCoSiB single layers or exchanged biased multilayers. At mechanical resonance and depending on the geometry, extremely high ME coefficients of up to 9.7 kV/cm Oe in air and up to 19 kV/cm Oe under vacuum were obtained. To avoid external DC magnetic bias fields, composites consisting of exchanged biased multilayers serving as the magnetostrictive component with a maximum magnetoelectric coefficient at zero magnetic bias field are employed. Furthermore, the anisotropic response of these exchanged biased composites can be utilized for three‐dimensional vector field sensing. Sensitivity and noise of the sensors revealed limits of detection as good as to 2.3 pT/Hz^1/2 at mechanical resonance. Sensitivity between 0.1 and 1000 Hz outside resonance can be enhanced through frequency conversion using AC magnetic bias fields.     

Oxidative Stress and NADPH Oxidase: Connecting Electromagnetic Fields,Cation Channels and Biological Effects

Electromagnetic fields (EMFs) disrupt the electrochemical balance of biological membranes, thereby causing abnormal cation movement and deterioration of the function of membrane voltage-gated ion channels. These can trigger an increase of oxidative stress (OS) and the impairment of all cellular functions, including DNA damage and subsequent carcinogenesis. In this review we focus on the main mechanisms of OS generation by EMF-sensitized NADPH oxidase (NOX), the involved OS biochemistry, and the associated key biological effects.     

Effects of Combining Biofactors on Bioenergetic Parameters,Aβ Levels and Survival in Alzheimer Model Organisms

Increased amyloid beta (Aβ) levels and mitochondrial dysfunction (MD) in the human brain characterize Alzheimer disease (AD). Folic acid, magnesium and vitamin B6 are essential micro-nutrients that may provide neuroprotection. Bioenergetic parameters and amyloid precursor protein (APP) processing products were investigated in vitro in human neuroblastoma SH-SY5Y-APP695 cells, expressing neuronal APP, and in vivo, in the invertebrate Caenorhabditis elegans (CL2006 & GMC101) expressing muscular APP. Model organisms were incubated with either folic acid and magnesium-orotate (ID63) or folic acid, magnesium-orotate and vitamin B6 (ID64) in different concentrations. ID63 and ID64 reduced Aβ, soluble alpha APP (sAPPα), and lactate levels in SH-SY5Y-APP695 cells. The latter might be explained by enhanced expression of lactate dehydrogenase (LDHA). Micronutrient combinations had no effects on mitochondrial parameters in SH-SY5Y-APP695 cells. ID64 showed a significant life-prolonging effect in C. elegans CL2006. Incubation of GMC101 with ID63 significantly lowered Aβ aggregation. Both combinations significantly reduced paralysis and thus improved the phenotype in GMC101. Thus, the combinations of the tested biofactors are effective in pre-clinical models of AD by interfering with Aβ related pathways and glycolysis.