Neuroprotection for Ischemic Stroke: Moving Past Shortcomings and Identifying Promising Directions

The translation of neuroprotective agents for ischemic stroke from bench-to-bedside has largely failed to produce improved treatments since the development of tissue plasminogen activator (tPA). One possible reason for lack of translation is the failure to acknowledge the greatest risk factor for stroke, age, and other common comorbidities such as hypertension, obesity, and diabetes that are associated with stroke. In this review, we highlight both mechanisms of studying these factors and results of those that have been addressed. We also discuss the potential role of other lifestyle factors associated with an increased stroke risk such as sleep fragmentation and/or deprivation. Furthermore, many proposed therapeutic agents have targeted molecular mechanisms occurring soon after the onset of ischemia despite data indicating delayed patient presentation following ischemic stroke. Modulating inflammation has been identified as a promising therapeutic avenue consistent with preliminary success of ongoing clinical trials for anti-inflammatory compounds such as minocycline. We review the role of inflammation in stroke and in particular, the role of inflammatory cell recruitment and macrophage phenotype in the inflammatory process. Emerging evidence indicates an increasing role of neuro-immune crosstalk, which has led to increased interest in identification of peripheral biomarkers indicative of neural injury. It is our hope that identification and investigation of factors influencing stroke pathophysiology may lead to improved therapeutics.     

Non-thermal dielectric barrier discharge plasma induces angiogenesis through reactive oxygen species

Vascularization plays a key role in processes such as wound healing and tissue engineering. Non-thermal plasma, which primarily produces reactive oxygen species (ROS), has recently emerged as an efficient tool in medical applications including blood coagulation, sterilization and malignant cell apoptosis. Liquids and porcine aortic endothelial cells were treated with a non-thermal dielectric barrier discharge plasma in vitro. Plasma treatment of phosphate-buffered saline (PBS) and serum-free medium increased ROS concentration in a dose-dependent manner, with a higher concentration observed in serum-free medium compared with PBS. Species concentration inside cells peaked 1 h after treatment, followed by a decrease 3 h post treatment. Endothelial cells treated with a plasma dose of 4.2 J cm^–2 had 1.7 times more cells than untreated samples 5 days after plasma treatment. The 4.2 J cm^–2 plasma dose increased two-dimensional migration distance by 40 per cent compared with untreated control, while the number of cells that migrated through a three-dimensional collagen gel increased by 15 per cent. Tube formation was also enhanced by plasma treatment, with tube lengths in plasma-treated samples measuring 2.6 times longer than control samples. A fibroblast growth factor-2 (FGF-2) neutralizing antibody and ROS scavengers abrogated these angiogenic effects. These data indicate that plasma enhanced proliferation, migration and tube formation is due to FGF-2 release induced by plasma-produced ROS. Non-thermal plasma may be used as a potential tool for applying ROS in precise doses to enhance vascularization.     

Peptide-Driven Targeted Drug-Delivery System Comprising Turn-On Near-Infrared Fluorescent Xanthene–Cyanine Reporter for Real-Time Monitoring of Drug Release

Targeted drug delivery (TDD) is an efficient strategy for cancer treatment. However, the real-time monitoring of drug delivery is still challenging because of a pronounced lack of TDD systems capable of providing a near-infrared (NIR) fluorescence signal for the detection of drug-release events. Herein, a new TDD system, comprising a turn-on NIR fluorescent reporter attached to an anticancer drug and targeting peptide, is reported. This system provides both TDD and NIR fluorescence monitoring of drug-release events in target tissue. In this TDD system, a new carboxy-derivatized xanthene–cyanine (XCy) dye is attached to an anticancer drug, chlorambucil (CLB), through a hydrolytically cleavable ester linker and coupled to a targeting peptide, octreotide amide (OCTA), which is specific to somatostatin receptors SSTR-2 and STTR-5 overexpressed on many tumor cells. This OCTA-G-XCy-CLB (G: γ-aminobutyric acid) conjugate exhibits no detectable fluorescence, whereas, upon the hydrolytic cleavage of the ester linker, a bright NIR fluorescence appears at λ≈710 nm; this signals release of the drug. Real-time TDD monitoring is demonstrated for the example of the human pancreatic cancer cell line overexpressing SSTR-2 and STTR-5, in comparison with the noncancerous Chinese hamster ovary cell line, which contains a reduced number of these receptors.     

Encryption performance and security of certain wide block ciphers

Journal of Computer Virology and Hacking Techniques - In a context of enhancing the performance of block encryption algorithms there are two well-known approaches. The first one relates to the...     

3D Printing of Micrometer-Sized Transparent Ceramics with On-Demand Optical-Gain Properties

Transparent ceramics are usually polycrystalline materials, which are wildly used in many optical applications, such as lasers. As of today, the fabrication of transparent ceramic structures is still limited to conventional fabrication methods, which do not enable the formation of complex structures. A new approach for 3D printing of micrometer-size, transparent ceramic structures is presented. By using a solution of metal salts that can undergo a sol–gel process and photopolymerization by two-photon printing, micrometer-sized yttrium aluminum garnet (YAG) structures doped with neodymium (Nd) are fabricated. The resulting structures are not only transparent in the visible spectrum but can also emit light at 1064 nm due to the doping with Nd. By using solution-based precursors, without any particles, the sintering can be performed under air at ambient pressure and at a relatively low temperature, compared to conventional processes for YAG. The crystalline structure is imaged at atomic resolution by ultrahigh-resolution scanning transmission electron microscopy (STEM), indicating that the doped Nd atoms are located at the yttrium positions. Such miniaturized structures can be used for diverse applications, e.g., optical components in high-intensity laser systems, which require heat resistance, or as light sources in optical circuits.     

Anti-Melanoma Capability of Contactless Cold Atmospheric Plasma Treatment

In this study, we demonstrated that the widely used cold atmospheric plasma (CAP) jet could significantly inhibit the growth of melanoma cells using a contactless treatment method, The flow rate of helium gas was a key operational parameter to modulate electromagnetic (EM) effect on melanoma cells. Metal sheets with different sizes could be used as a strategy to control the strength of EM effect. More attractive, the EM effect from CAP could penetrate glass/polystyrene barriers as thick as 7 mm. All these discoveries presented the profound non-invasive nature of a physically based CAP treatment, which provided a solid foundation for CAP-based cutaneous/subcutaneous tumor therapy.     

Epoxidation of soybean oil in toluene with peroxoacetic and peroxoformic acids — kinetics and side reactions

The kinetics of the epoxidation of soybean oil and the extent of side reactions were studied at 40, 60, and 80 °C. Epoxidation was carried out in toluene with “in situ” formed peroxoacetic and peroxoformic acid and in the presence of an ion exchange resin as the catalyst. The reaction was found to be first‐order with respect to the double bond concentration. At higher temperatures and at higher conversions a deviation from the first‐order kinetics was observed. The rate constants for the epoxidation with peroxoacetic acid were 0.118 (h⁻¹) at 40 °C, 0.451 (h⁻¹) at 60 °C and 1.278 (h⁻¹) at 80 °C, while those for peroxoformic acid were 0.264, 0.734, and 1.250 (h⁻¹). The activation energy was found to be 54.7 kJ/mol for the epoxidation with peroxoacetic acid and 35.9 kJ/mol for that with peroxoformic acid. Three factors indicated that side reactions did not occur on a large scale: The absence of an OH band in the IR spectra, the formation of less than 2% of higher molecular weight products from gel permeation chromatography and the selectivity values between 0.9 and 1.     

Refolding of Lysozyme in Glycerol as Studied by Fast Scanning Calorimetry

The folding of lysozyme in glycerol was monitored by the fast scanning calorimetry technique. Application of a temperature–time profile with an isothermal segment for refolding allowed assessment of the state of the non-equilibrium protein ensemble and gave information on the kinetics of folding. We found that the non-equilibrium protein ensemble mainly contains a mixture of unfolded and folded protein forms and partially folded intermediates, and enthalpic barriers control the kinetics of the process. Lysozyme folding in glycerol follows the same or similar triangular mechanism described in the literature for folding in water. The unfolding enthalpy of the intermediate must be no lower than 70% of the folded form, while the activation barrier for the unfolding of the intermediate (ca. 140 kJ/mol) is about 100 kJ/mol lower than that of the folded form (ca. 240–260 kJ/mol).     

Graduate Students and Federated Searching

In the fall of 2009 and spring of 2010, 20 New Mexico State University graduate students were interviewed using a “think-aloud” protocol to describe their experiences with a federated search tool. Students found federated searching to be most effective when looking for very specific information and article abstracts and least effective when searching general terms and resources other than journal articles (i.e., books, media). Students used the federated search tool and Google together to find relevant citations and full text journal articles. Students indicated that they were highly satisfied with federated search despite some doubt as to how the search worked and what library resources were included in the search.     

Joint Multi-Frequency Beam Shaping and Steering via Space–Time-Coding Digital Metasurfaces

Digital programmable metasurfaces provide a very powerful and versatile platform for implementing spatio-temporal modulation schemes that are of great interest within the emerging framework of space–time metastructures. In particular, space–time-coding digital metasurfaces have been successfully applied to advanced wavefront-manipulations in both the spatial and spectral domains. However, conventional space–time-coding schemes do not allow the joint syntheses of the transmission/scattering angular responses at multiple frequencies, which are potentially useful in a variety of applications of practical interest. Here, a strategy is put forward to lift this limitation, thereby enabling joint multi-frequency beam shaping and steering, that is, the independent and simultaneous syntheses of prescribed scattering patterns at given harmonic frequencies. The proposed approach relies on a more sophisticated space–time coding, with suitably designed, and temporally intertwined coding sub-sequences, which effectively disentangles the joint multi-frequency syntheses. The power and versatility of the approach are illustrated via a series of representative application examples, including multi-beam, diffuse-scattering, and orbital-angular-momentum patterns. Theoretical predictions are experimentally validated by means of microwave measurements. The outcomes of this study hold promising potentials for applications to future imaging, information, and mobile-communication systems.