Nitrogen plasma modification boosts up the hemocompatibility of new PVDF-carbon nanohorns composite materials with potential cardiological and circulatory system implants application.

To design new material for blood-related applications one needs to consider various factors such as cytotoxicity, platelet adhesion, or anti-thrombogenic properties. The aim of this work is the design of new, highly effective materials possessing high blood compatibility. To do this, the new composites based on the poly(vinylidene fluoride) (PVDF) support covered with a single-walled carbon nanohorns (CNHs) layer were prepared. The PVDF-CNHs composites were subsequently used for the first time in the hemocompatibility studies. To raise the hemocompatibility a new, never applied before for CNHs, plasma-surface modifications in air, nitrogen and ammonia were implemented. This relatively cheap, facile and easy method allows generating the new hybrid materials with high effectiveness and significant differences in surface properties (water contact angle, surface ζ-potential, and surface functional groups composition). Changing those properties made it possible to select the most promising samples for blood-related applications. This was done in a fully controlled way by applying Taguchi's "orthogonal array" procedure. It is shown for the first time that nitrogen plasma treatment of new surfaces is the best tool for hemocompatibility rise and leads to very low blood platelet adhesion, no cytotoxicity, and excellent performance in thromboelastometry and hemolysis tests. We propose a possible mechanism explaining this behavior. The optimisation results are coherent with biological characterisation and are supported with Hansen Solubility Parameters. New surfaces can find potential applications in cardiological and circulatory system implants as well as other blood-related biomaterials.

Surfaces with Adjustable Features-Effective and Durable Materials for Water Desalination.

Materials based on PVDF with desirable and controllable features were successfully developed. The chemistry and roughness were adjusted to produce membranes with improved transport and separation properties. Membranes were activated using the novel piranha approach to generate OH-rich surfaces, and finally furnished with epoxy and long-alkyl moieties via stable covalent attachment. The comprehensive materials characterization provided a broad spectrum of data, including morphology, textural, thermal properties, and wettability features. The defined materials were tested in the air-gap membrane distillation process for desalination, and improvement compared with pristine PVDF was observed. An outstanding behavior was found for the PVDF sample equipped with long-alkyl chains. The generated membrane showed an enhancement in the transport of 58-62% compared to pristine. A relatively high contact angle of 148° was achieved with a 560 nm roughness, producing a highly hydrophobic material. On the other hand, it was possible to tone the hydrophobicity and significantly reduce adhesion work. All materials were highly stable during the long-lasting separation process and were characterized by excellent effectiveness in water desalination.

Highly effective enzymes immobilization on ceramics: Requirements for supports and enzymes.

Enzyme immobilization is a well-known method for the improvement of enzyme reusability and stability. To achieve very high effectiveness of the enzyme immobilization, not only does the method of attachment need to be optimized, but the appropriate support must be chosen. The essential necessities addressed to the support applied for enzyme immobilization can be focused on the material features as well as on the stability and resistances in certain conditions. Ceramic membranes and nanoparticles are the most widespread supports for enzyme immobilization. Hence, the immobilization of enzymes on ceramic membrane and nanoparticles are summarized and discussed. The important properties of the supports are particle size, pore structure, active surface area, volume to surface ratio, type and number of reactive available groups, as well as thermal, mechanical, and chemical stability. The modifiers and the crosslinkers are crucial to the enzyme loading amount, the chemical and physical stability, and the reusability and catalytical activity of the immobilized enzymes. Therefore, the chemical and physical methods of modification of ceramic materials are presented. The most popular and used modifiers (e.g. APTES, CPTES, VTES) as well as activating agents (GA, gelatin, EDC and/or NHS) applied to the grafting process are discussed. Moreover, functional groups of enzymes are presented and discussed since they play important roles in the enzyme immobilization via covalent bonding. The enhanced physical, chemical, and catalytical properties of immobilized enzymes are discussed revealing the positive balance between the effectiveness of the immobilization process, preservation of high enzyme activity, its good stability, and relatively low cost.

Studying the Complex Formation of Sulfonatocalix[4]naphthalene and Meloxicam towards Enhancing Its Solubility and Dissolution Performance.

The interaction between meloxicam and sulfonatocalix [4] naphthalene was investigated to improve the meloxicam solubility and its dissolution performance. Solubility behavior was investigated in distilled water (DW) and at different pH conditions. Besides, solid systems were prepared in a 1:1 molar ratio using coevaporate, kneading, and simple physical mixture techniques. Further, they were characterized by PXRD, FT-IR, DCS, and TGA. In vitro dissolution rate for coevaporate, kneaded, and physical mixture powders were also investigated. Solubility study revealed that meloxicam solubility significantly increased about 23.99 folds at phosphate buffer of pH 7.4 in the presence of sulfonatocalix [4] naphthalene. The solubility phase diagram was classified as AL type, indicating the formation of 1:1 stoichiometric inclusion complex. PXRD, FT-IR, DCS, and TGA pointed out the formation of an inclusion complex between meloxicam and sulfonatocalix [4] naphthalene solid powders prepared using coevaporate technique. In addition, in vitro meloxicam dissolution studies revealed an improvement of the drug dissolution rate. Furthermore, a significantly higher drug release (p ≤ 0.05) and a complete dissolution was achieved during the first 10 min compared with the other solid powders and commercial meloxicam product. The coevaporate product has the highest increasing dissolution fold and RDR10 in the investigated media, with average values ranging from 5.4-65.28 folds and 7.3-90.7, respectively. In conclusion, sulfonatocalix [4] naphthalene is a promising host carrier for enhancing the solubility and dissolution performance of meloxicam with an anticipated enhanced bioavailability and fast action for acute and chronic pain disorders.

How Can the Desert Beetle and Biowaste Inspire Hybrid Separation Materials for Water Desalination?

Highly effective, hybrid separation materials for water purification were generated following a bioinspired system available in nature. The desert beetle was the inspiration for the generation of separation materials. Using the hydrophobic poly(vinylidene fluoride) (PVDF) membrane as the basis, the membrane was first activated and then furnished with silane-based linkers, and the covalent anchoring of chitosan was successfully accomplished. The obtained surface architecture was a copy of the desert beetle's armor possessing a hydrophobic matrix with hydrophilic domains. The modification was done in the presence or the lack of catalyst (N,N-diisopropylethylamine) that made it possible to tune easily wettability, roughness, and material as well as adhesive features. The membrane morphology and surface chemistry were studied by applying a series of analytical techniques. As a result of chitosan attachment, substantial improvement in transport and separation was reported. Pristine PVDF was characterized by a water flux of 5.28 kg m-2 h-1 and an activation energy of 48.16 kJ mol-1. The water flux and activation energy for a hybrid membrane with chitosan were equal to 15.55 kg m-2 h-1 and 33.98 kJ mol-1, respectively. The hybrid materials possessed enhanced stability and water resistance that were maintained after 10 cycles of membrane distillation tests.

Molecular Decoration of Ceramic Supports for Highly Effective Enzyme Immobilization-Material Approach.

A highly effective method was developed to functionalize ceramic supports (Al2O3 powders and membranes) using newly synthesized spacer molecules. The functionalized materials were subsequently utilized for Candida antarctica lipase B enzyme immobilization. The objective is to systematically evaluate the impact of various spacer molecules grafted onto the alumina materials will affect both the immobilization of the enzymes and specific material surface properties, critical to enzymatic reactors performance. The enzyme loading was significantly improved for the supports modified with shorter spacer molecules, which possessed higher grafting effectiveness on the order of 90%. The specific enzyme activity was found to be much higher for samples functionalized with longer modifiers yielding excellent enantioselectivity >97%. However, the enantiomeric ratio of the immobilized lipase was slightly lower in the case of shorter spacer molecules.

Investigation of Bifurcation Effect on Various Microfluidic Designs for Blood Separation.

In this project, a microfluidic device for blood separation will be designed and tested in order to separate plasma from whole blood for diagnostic purposes. The design will be based on previously implemented designs that will be further discussed in the next sections. When designing microfluidic devices, it is essential to consider the different physical phenomena that arise from switching from the macro scale to the micro scale. Parameters such as the Reynolds number and the forces affecting the fluid must be studied in order to produce a suitable and effective design. Finite element methods have been implemented prior to the production of the microfluidic devices. Various geometries/designs have been tested using Fluent ANSYS software. Later on, the successful design was fabricated using micromachining on an acrylic substrate and was tested using simulated blood through of a syringe pump.

Sensitivity Enhancement of Point-of-Care for Cardiac Markers Detection using Micro-Impedimetric Immunosensor Arrays.

This paper describes the development and characterisation of a novel, electrical impedance spectroscopy-based (EIS) immunosensor array for point-of-care applications. EIS is a highly sensitive, label-free, real time technique suitable for single use, point-of-care cardiac marker detection devices. However, the underlying source of the observed change in EIS immunoassay response has not been well characterised or understood. A full understanding of the relationship between target binding and impedance response would significantly advance biosensor design and most probably increase detection limit sensitivity. The development of micro-/nano- structured electrodes for multi-frequency EIS procedure propose substantial benefits over classical macro-structured systems.Countless manipulations of electrode features and inter-electrode spacing will enhance the electrode surface area, increase the charge-transfer resistance and reduce the double-layer capacitance. These in turn give rise to improved signal-to-noise ratios, therefore affording greater sensitivity, lower detection limits and faster detection times.The sensor sensitivity range was within that required for human myoglobin determination, following acute myocardial infarction (heart attack). Real-time MyAb-MyAg interaction monitoring, permitted the determination of the binding events in less than one minute.

Detection of Human Chorionic Gonadotropin (hCG) Hormone using Digital Lateral Flow Immunoassay.

The main goal of this work was to establish a hybrid device incorporating an electrochemical-based transducer on a conventional lateral flow assay strip in order to perform an on-chip fast testing method for the detection of various bio-analyses. In this context, the expected development of the digital lateral-flow immunoassay to be considered a reliable low-cost instrument improves the future of the very simple and flexible approach oflateral-flow assays. It is anticipated to achieve a digital quantitative lateral-flow immunoassay by exploring the electrochemical transducers alongwith recognition elements for digitization of commercially available rapid tests. As a preliminary step, the described technique will be validated using two standard electrochemical measurements (amperometric and impedimetric) across two electrodes fixed onto the surface of LFA strip. The LFA strips were prepared at the factory for pregnancy tests and modified by adding two parallel copper electrodes at the lab. These strips were proven by in-vitro experiments to be reusable lasting for 20-30 multiple days. Further on, the detection of hCG Ab-Ag interaction using these strips was performed. Two different types of measurements, namely amperometric and impedimetric, were used which yielded similar results to those reported in literature with screen-printed micro-electrodes. In addition, different concentrations of NaCl and hCG Ag solution were investigated. However, the expected linear concentration response was obtained. A promising proof-of-concept have been achieved through this study. Further studies are needed to complete the development of fully printed disposable electrochemical devices that are able to either display a digital result directly or transmit data to a mobile phone using RFID/NFC.

Advanced Material-Ordered Nanotubular Ceramic Membranes Covalently Capped with Single-Wall Carbon Nanotubes.

Advanced ceramic materials with a well-defined nano-architecture of their surfaces were formed by applying a two-step procedure. Firstly, a primary amine was docked on the ordered nanotubular ceramic surface via a silanization process. Subsequently, single-wall carbon nanotubes (SWCNTs) were covalently grafted onto the surface via an amide building block. Physicochemical (e.g., hydrophobicity, and surface free energy (SFE)), mechanical, and tribological properties of the developed membranes were improved significantly. The design, preparation, and extended characterization of the developed membranes are presented. Tools such as high-resolution transmission electron microscopy (HR-TEM), single-area electron diffraction (SAED) analysis, microscopy, tribology, nano-indentation, and Raman spectroscopy, among other techniques, were utilized in the characterization of the developed membranes. As an effect of hydrophobization, the contact angles (CAs) changed from 38° to 110° and from 51° to 95° for the silanization of ceramic membranes 20 (CM20) and CM100, respectively. SWCNT functionalization reduced the CAs to 72° and 66° for ceramic membranes carbon nanotubes 20 (CM-CNT-20) and CM-CNT-100, respectively. The mechanical properties of the developed membranes improved significantly. From the nanotribological study, Young’s modulus increased from 3 to 39 GPa for CM-CNT-20 and from 43 to 48 GPa for pristine CM-CNT-100. Furthermore, the nanohardness increased by about 80% after the attachment of CNTs for both types of ceramics. The proposed protocol within this work for the development of functionalized ceramic membranes is both simple and efficient.

A Brain Machine Interface for command based control of a wheelchair using conditioning of oscillatory brain activity.

In this research a new method of wheelchair control using a Brain Computer Interface (BCI) is proposed, in an attempt to bridge the gap between in-lab and real life applications, we believe it would provide a high level control over the BCI instead of the normal low level commands. It is anticipated to emphasis on mu rhythm to provide the control signals. The wheelchair is equipped with a mapping system, which scans the area and provides a map containing information about the user's current location and next possible destinations, then provides an optimized list of possible trajectories to reach the destination. The paradigm allows users to control the interface using motor imagery and issue commands to switch between possible trajectories and then confirm the choice. Commands trigger the motion of the wheelchair to the intended destination using a user selected path with speed up to 0.5 m/s. The interface also allows the user to interact with different robots through a common robotic system. Evaluation results indicate that this paradigm is indeed usable and could lead to promising outcomes.

Molecular Grafting of Fluorinated and Nonfluorinated Alkylsiloxanes on Various Ceramic Membrane Surfaces for the Removal of Volatile Organic Compounds Applying Vacuum Membrane Distillation.

Four main tasks were presented: (i) ceramic membrane functionalization (TiO2 5 kDa and 300 kDa), (ii) extended material characterization (physicochemistry and tribology) of pristine and modified ceramic samples, (iii) evaluation of chemical and mechanical stability, and finally (iv) assessment of membrane efficiency in vacuum membrane distillation applied for volatile organic compounds (VOCs) removal from water. Highly efficient molecular grafting with four types of perfluoroalkylsilanes and one nonfluorinated agent was developed. Materials with controllable tribological and physicochemical properties were achieved. The most meaningful finding is associated with the applicability of fluorinated and nonfluorinated grafting agents. The results of contact angle, hysteresis of contact angle, sliding angle, and critical surface tension as well as Young's modulus, nanohardness, and adhesion force for grafting by these two modifiers are comparable. This provides insight into the potential applicability of environmental friendly hydrophobic and superhydrophobic surfaces. The achieved hydrophobic membranes were very effective in the removal of VOCs (butanol, methyl-tert-butyl ether, and ethyl acetate) from binary aqueous solutions in vacuum membrane distillation. The correlation between membrane effectiveness and separated solvent polarity was compared in terms of material properties and resistance to the wetting (kinetics of wetting and in-depth liquid penetration). Material properties were interpreted considering Zisman theory and using Kao diagram. The significant influence of surface chemistry on the membrane performance was noticed (5 kDa, influence of hydrophobic nanolayer and separation controlled by solution-diffusion model; 300 kDa, no impact of surface chemistry and separation controlled by liquid-vapor equilibrium).

Anti-spermatogenic activities of Taraxacum officinale whole plant and leaves aqueous extracts.

Taraxacum officinale has been used in Jordan folk medicine to treat male infertility. A recent study has proved a contradictory effect of the whole plant aqueous extract. The aim of the current study was to determine if the leaves of T. officinale have similar anti-fertility activities, and whether this effect is mediated through the regulation of spermatogonial stem cells (SSCs). Fifty adult male rats were divided into five groups. Two groups were gavaged with 1/10 of LD50 of T. officinale whole plant (1.06 g kg(-1) body weight) or leaves (2.30 g kg(-1) body weight) aqueous extract; while two groups were gavaged with 1/20 of LD50 of T. officinale whole plant (2.13 g kg(-1)) or leaves (4.60 g kg(-1)) extract. The control group received distilled water. Oral administration of T. officinale (whole plant and leaves aqueous extract) caused a significant decrease in testis and seminal vesicle weight, a reduction in serum testosterone concentration, impaired sperm parameters, and a decrease in pregnancy parameters. Testicular histology of treated rats showed structural changes such as hypoplasia of germ cells, reduction in the thickness of germinal epithelium, arrest of spermatogenesis at spermatid stage (late maturation arrest) and reduction in the number of Leydig cells. Gene expression levels of two SSCs markers (GFRα1 and CSF1) responsible for self-renewal were relatively counter-balanced. In conclusion, T. officinale whole plant and leaves aqueous extracts changed the gene expression of two SSCs markers leading to the imbalance between spermatogonia self-renewal and differentiation causing late maturation arrest.

LEGO Mindstorms NXT for elderly and visually impaired people in need: A platform.

This paper presents the employment of LEGO Mindstorms NXT robotics as core component of low cost multidisciplinary platform for assisting elderly and visually impaired people. LEGO Mindstorms system offers a plug-and-play programmable robotics toolkit, incorporating construction guides, microcontrollers and sensors, all connected via a comprehensive programming language. It facilitates, without special training and at low cost, the use of such device for interpersonal communication and for handling multiple tasks required for elderly and visually impaired people in-need. The research project provides a model for larger-scale implementation, tackling the issues of creating additional functions in order to assist people in-need. The new functions were built and programmed using MATLAB through a user friendly Graphical User Interface (GUI). Power consumption problem, besides the integration of WiFi connection has been resolved, incorporating GPS application on smart phones enhanced the guiding and tracking functions. We believe that developing and expanding the system to encompass a range of applications beyond the initial design schematics to ease conducting a limited number of pre-described protocols. However, the beneficiaries for the proposed research would be limited to elderly people who require assistance within their household as assistive-robot to facilitate a low-cost solution for a highly demanding health circumstance.

Engineering of a highly efficient Xe2*-excilamp (xenon excimer lamp, λmax=172 nm, η=40%) and qualitative comparison to a low-pressure mercury lamp (LP-Hg, λ=185/254 nm) for water purification.

Excilamps are mercury-free gas-discharge sources of non-coherent VUV or UV radiation with high radiant power and a long lifetime. The most efficient excilamp that is currently available on the market is a VUV xenon excilamp system (Xe2(*)-excimer lamp, λ(max) = 172 nm) with a stated radiant efficiency η of 40% at an electrical input power P(el) of 20 W, 50 W or 100 W. In this paper, the use of this highly efficient Xe2(*)-excilamp (P(el) = 20 W) for water treatment is demonstrated using a recirculating laboratory photoreactor system with negative radiation geometry. The efficiency in the 172 nm initiated bleaching of aqueous solutions of Rhodamine B is compared to that initiated by a common low-pressure mercury (LP-Hg) lamp (185 nm, TNN 15/32). The dependence of the pseudo zero order rate constant k´ of decolorization of RhB on the flow rate and on the initial concentration of RhB was investigated. Both lamps exhibited dependences of k´ on the initial concentration of RhB, which represents a typical saturation kinetical behavior. The saturation kinetics was very prominent in the case of the Xe2(*)-excilamp. Also, the Xe2(*)-excilamp treatment exhibited a significant influence on the flow rate of the RhB aqueous solution, which was not the case during the LP-Hg lamp initiated bleaching of RhB. The results of this paper demonstrate that Xe2(*)-excilamps can be used for VUV-initiated water purification. However, to reach the maximum efficacy of the Xe2(*)-excilamp for photo-initiated water purification further engineering optimization of the photoreactor concept is necessary.

Artificial neural networks for dihedral angles prediction in enzyme loops: a novel approach.

Structure prediction of proteins is considered a limiting step and determining factor in drug development and in the introduction of new therapies. Since the 3D structures of proteins determine their functionalities, prediction of dihedral angles remains an open and important problem in bioinformatics, as well as a major step in discovering tertiary structures. This work presents a method that predicts values of the dihedral angles φ and ψ for enzyme loops based on data derived from amino acid sequences. The prediction of dihedral angles is implemented through a neural network based mining mechanism. The amino acid sequence data represents 6342 enzyme loop chains with 18,882 residues. The initial neural network input was a selection of 115 features and the outputs were the predicted dihedral angles φ and ψ. The simulation results yielded a 0.64 Pearson's correlation coefficient. After feature selection through determining insignificant features, the input feature vector size was reduced to 45, while maintaining close to identical performance.

Flexible, polymer-supported synthesis of sphingosine derivatives provides ceramides with enhanced biological activity.

A polymer-supported route for the synthesis of sphingosine derivatives is presented based on the C-acylation of polymeric phosphoranylidene acetates with an Fmoc-protected amino acid. The approach enables the flexible variation of the sphingosine tail through a deprotection-decarboxylation sequence followed by E-selective Wittig olefination cleavage. d-Erythro-sphingosine analogs have been synthesized by diastereoselective reduction of the keto group employing LiAlH(O-tBu)3 as reducing agent. The effect of ceramides and keto-ceramides on the proliferation of three cancer cell lines HEP G-2, PC-12 and HL-60 was investigated and a ceramide containing an aromatic sphingosine tail was identified as being most active.

Soluble peptidyl phosphoranes for metal-free, stereoselective ligations in organic and aqueous solution.

Protocols for solid-phase syntheses of soluble peptidyl phosphoranes are presented. Various supported phosphoranylidene acetates were prepared on Rink amide or via alkylation of trialkyl- and triarylphosphines with bromoacetyl Wang ester. C-Acylation was conducted racemization-free with activated Fmoc-amino acids, followed by SPPS (solid-phase peptide synthesis). Acidic conditions released decarboxylated peptidyl phosphoranes into solution. The protocol allowed for the electronic variation of peptidyl phosphoranes which were investigated in ligation reactions with azides in organic and aqueous solvents.

Peptide aldehyde inhibitors challenge the substrate specificity of the SARS-coronavirus main protease.

SARS coronavirus main protease (SARS-CoV M(pro)) is essential for the replication of the virus and regarded as a major antiviral drug target. The enzyme is a cysteine protease, with a catalytic dyad (Cys-145/His-41) in the active site. Aldehyde inhibitors can bind reversibly to the active-site sulfhydryl of SARS-CoV M(pro). Previous studies using peptidic substrates and inhibitors showed that the substrate specificity of SARS-CoV M(pro) requires glutamine in the P1 position and a large hydrophobic residue in the P2 position. We determined four crystal structures of SARS-CoV M(pro) in complex with pentapeptide aldehydes (Ac-ESTLQ-H, Ac-NSFSQ-H, Ac-DSFDQ-H, and Ac-NSTSQ-H). Kinetic data showed that all of these aldehydes exhibit inhibitory activity towards SARS-CoV M(pro), with K(i) values in the µM range. Surprisingly, the X-ray structures revealed that the hydrophobic S2 pocket of the enzyme can accommodate serine and even aspartic-acid side-chains in the P2 positions of the inhibitors. Consequently, we reassessed the substrate specificity of the enzyme by testing the cleavage of 20 different tetradecapeptide substrates with varying amino-acid residues in the P2 position. The cleavage efficiency for the substrate with serine in the P2 position was 160-times lower than that for the original substrate (P2=Leu); furthermore, the substrate with aspartic acid in the P2 position was not cleaved at all. We also determined a crystal structure of SARS-CoV M(pro) in complex with aldehyde Cm-FF-H, which has its P1-phenylalanine residue bound to the relatively hydrophilic S1 pocket of the enzyme and yet exhibits a high inhibitory activity against SARS-CoV M(pro), with K(i)=2.24±0.58 µM. These results show that the stringent substrate specificity of the SARS-CoV M(pro) with respect to the P1 and P2 positions can be overruled by the highly electrophilic character of the aldehyde warhead, thereby constituting a deviation from the dogma that peptidic inhibitors need to correspond to the observed cleavage specificity of the target protease.

Determination of Glucose Concentration in Aqueous Solution Using ATR-WT-IR Technique.

Fourier transformation infrared (FT-IR) spectroscopy has been used to measure glucose concentrations in different matrices. The accuracy of the FT-IR technique does not meet the requirements of medical applications, so we have developed a new, efficient and precise method based on attenuated total reflectance coupled with wavelet transformation (ATR-WT-IR). One thousand interferograms, divided into training- and testing-sets, have been recorded from four glucose concentrations using an ATR-IR unit. Signals were subjected to (WT) and neural network (NN) study in order to design correlation algorithm. The Pearson's Correlation Coefficient (PCC) obtained by judging the predicted- against the real-concentrations was 0.9954, with a mean square error of 8.4e-005. The proposed ATR-WT-IR method shows efficiency in glucose prediction and could possibly to be integrated into a non-invasive monitoring technique.