Assessment of the role of alpha2-adrenoceptor subtypes in the antinociceptive, sedative and hypothermic action of dexmedetomidine in transgenic mice

1. The role of alpha2-adrenoceptor (AR) subtypes in the modulation of acute nociception, motor behaviour and body temperature, has been investigated by determining the activity of the alpha2AR selective agonist dexmedetomidine (Dex) in mice devoid of individual alpha2AR subtypes through either a point (alpha2A) or null (alpha2B/alpha2C) mutation ('knock-out'). 2. In a rodent model of acute thermal nociception, the mouse tail immersion test, Dex, in wild type (WT) control animals, produced a dose-dependent increase in the threshold for tail withdrawal from a 52 degrees C water bath with mean ED50 values of 99.9+/-14.5 (alpha2A), 94.6+/-17.8 (alpha2B) and 116.0/-17.1 (alpha2C) microg kg(-1), i.p. 3. In comparison to the WT controls, Dex (100-1000 microg kg(-1), i.p.), was completely ineffective as an antinociceptive agent in the tail immersion test in the alpha2A AR D79N mutant animals. Conversely, in the alpha2B AR and alpha2C AR knock-outs, Dex produced a dose-dependent antinociceptive effect that was not significantly different from that observed in WT controls, with ED50 values of 85.9+/-15.0 (P>0.05 vs WT control) and 226.0+/-62.7 (P>0.05 vs WT control) microg kg(-1) i.p., respectively. 4. Dex (10-300 microg kg(-1), i.p.) produced a dose-dependent reduction in spontaneous locomotor activity in the alpha2A, alpha2B and alpha2C AR WT control animals with ED50 values of 30.1+/-9.0, 23.5+/-7.1 and 32.3+/-4.6 microg kg(-1), i.p., respectively. Again, Dex (100-1000 microg kg(-1), i.p.) was ineffective at modulating motor behaviour in the alpha2A AR D79N mutants. In the alpha2B AR and alpha2C AR knock-out mice, Dex produced a dose-dependent reduction in spontaneous locomotor activity with ED50 values of 29.1+/-6.4 (P>0.05 vs WT control) and 57.5+/-11.3 (P>0.05 vs WT control) microg kg(-1), respectively. 5. Dex was also found to produce a dose-dependent reduction in body temperature in the alpha2A, alpha2B and alpha2C AR WT control mice with ED50 values of 60.6+/-11.0, 16.2+/-2.5 and 47.2+/-9.1 microg kg(-1), i.p., respectively. In the alpha2A AR D79N mutants, Dex had no effect on body temperature at a dose (100 microg kg(-1), i.p.) that produced a significant reduction (-6.2+/-0.5 degrees C; P<0.01 vs vehicle) in temperature in WT controls. However, higher doses of Dex (300 and 1000 microg kg(-1), i.p) produced a small, but statistically significant decrease in temperature corresponding to -1.7+/-0.4 degrees C and -2.4+/-0.3 degrees C (both P<0.01 vs vehicle), respectively. In the alpha2B AR and alpha2C AR knock-out mice, Dex produced a dose-dependent reduction in body temperature with ED50 values of 28.4+/-4.8 (P>0.05 vs WT control) and 54.1+/-8.0 (P>0.05 vs WT control) microg kg(-1), respectively. 6. In conclusion, the data are consistent with the alpha2A AR being the predominant subtype involved in the mediation of the antinociceptive, sedative and hypothermic actions of Dex. This profile would appear to indicate that an alpha2A AR subtype selective analgesic will have a narrow therapeutic window, particularly following systemic administration.     

Trust‐based secure routing and the prevention of vampire attack in wireless ad hoc sensor network

The recent development in technologies is the driving force for development in sensors, especially in military applications. Due to the openness nature of the ad hoc sensor network, the system gets easily affected, which may lead to some packet drop, transmission delay, high network overhead, and more energy consumption. In this paper, the security during data transmission is provided to the network by using the proposed Secure Atom Search Routing (SASR) algorithm, which is adopted from the behavior of molecular dynamics. For global optimization problems, this algorithm provides an effective solution based on the constraint and interaction force of atoms. Moreover, the performance of SASR is improved by providing a proper balance between exploitation and exploration. Since the knowledge base processes all the data, the computational complexity is reduced and the lifetime of the network is increased. The simulation and performance are carried out for the proposed Knowledge and Intrusion Detection based Secure Atom Search Routing (KID‐SASR) protocol and is compared with the existing methods based on the metrics trust, delay, throughput, energy, packet delivery ratio, network lifetime, trust detection rate, and communication cost. The results obtained show improvement in the overall performance of the system.     

Multifunctional Dielectric Metasurfaces Consisting of Color Holograms Encoded into Color Printed Images

A hologram records the wavefront of light from an object, but it is usually not an image itself, and looks unintelligible under diffuse ambient light. Here a new paradigm to encode a color hologram onto a color printed image is experimentally demonstrated. The printed image can be directly viewed under white light illumination, while a low‐crosstalk color holographic image can be seen when the device is illuminated with red (R), green (G), and blue (B) laser beams. The device is a dielectric metasurface that consists of titanium dioxide (TiO₂) cones on a glass substrate. The dimensions of the TiO₂ cones are chosen to allow them to support visible‐wavelength resonances, thereby producing the desired reflection spectra and thus the color printed image. The detour phase method is furthermore used to encode the hologram into the metasurface. The approach is conceptually different from previously demonstrated color printed images or holograms and presents opportunities for optical document security and data storage applications.     

Synthesis and characterization of bulk and coatings of hydroxyapatite using methanol precursor

Hydroxyapatite, an important bioceramic was synthesized in the bulk form and developed as a coating by a sol-gel route using alcoholic precursor. The bioactive coating was developed on bio-inert α-alumina and yttria stabilized zirconia substrates. The apatite phase began to form after the heat treatment of the precursor at 500 °C for 10 min. The complete crystallization of the apatite was obtained at 800 °C heat treatment for 10 min. The phase composition of the bulk and the coatings was identified by FT-IR spectroscopic and powder X-ray diffraction (XRD) techniques. Surface morphology was determined by scanning electron microscopy. The study indicates different surface textures for the powder and for the coatings on α-alumina and yttria stabilized zirconia substrates.     

The Trp-cage: optimizing the stability of a globular miniprotein

The Trp-cage, as the smallest miniprotein, remains the subject of numerous computational and experimental studies of protein folding dynamics and pathways. The original Trp-cage (NLYIQWLKDGGPSSGRPPPS, Tm = 42 degrees C) can be significantly stabilized by mutations; melting points as high as 64 degrees C are reported. In helical portions of the structure, each allowed replacement of Leu, Ile, Lys or Ser residues by Ala results in a 1.5 (+/-0.35) kJ/mol fold stabilization. No changes in structure or fluxionality of the core results upon stabilization. Contrary to the initial hypothesis, specific Pro/Trp interactions are not essential for core formation. The entropic advantage of Pro versus Ala (DeltaDeltaS(U) = 11 +/- 2 J/mol K) was measured at the solvent-exposed P17 site. Pro-Ala mutations at two of the three prolines (P12 and P18) that encage the indole ring result in less fold destabilization (2.3-3.4 kJ/mol). However, a P19A mutation reduces fold stability by 16 kJ/mol reflecting a favorable Y3/P19 interaction as well as Trp burial. The Y3/P19 hydrophobic staple interaction defines the folding motif as an 18-residue unit. Other stabilizing features that have been identified include a solvent-exposed Arg/Asp salt bridge (3.4-6 kJ/mol) and a buried H-bonded Ser side chain ( approximately 10 kJ/mol).     

Computer simulation of an automatic classification procedure for digitally modulated communication signals with unknown parameters

The surveillance and control of the broadcasting activity, especially in the HF band, is a difficult task for the authorities like the post-office for example. Even experienced people with modern special equipment are often unable to classify unknown, differently modulated signals in real time. In this paper a procedure is described which allows an automatic real time classification of the following modulation types: Amplitude-Shift Keying (ASK), Frequency-Shift Keying (FSK) with small frequency deviation, and Phase-Shift Keying (PSK). The procedure has been tested by simulation on a computer and has proven to be reliable and robust against the expected perturbing factors such as noise, mismatch of centre frequency or bandwidth, and cross-talk of signals in adjacent frequency channels. A more detailed discussion is contained in [1].     

Optimal control of a linear system subject to partially specified input noise

One of the most basic problems in control theory is that of controlling a discrete‐time linear system subject to uncertain noise with the objective of minimizing the expectation of a quadratic cost. If one assumes the noise to be white, then solving this problem is relatively straightforward. However, white noise is arguably unrealistic: noise is not necessarily independent, and one does not always precisely know its expectation. We first recall the optimal control policy without assuming independence and show that, in this case, computing the optimal control inputs becomes infeasible. In the next step, we assume only the knowledge of lower and upper bounds on the conditional expectation of the noise and prove that this approach leads to tight lower and upper bounds on the optimal control inputs. The analytical expressions that determine these bounds are strikingly similar to the usual expressions for the case of white noise.