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The following research and subsequent study look at identity construction and intergroup differences during computer-mediated communication (CMC) across two platforms with varying degrees of anonymity: Twitter and Yik Yak. A review of research conducted mainly within the framework of the social identity model of deindividuation (SIDE) demonstrates that, counter to popular beliefs heralding the individual freedoms of anonymity, anonymous environments act to strengthen salient social identities and perpetuate group norms. In a medium with such variability and flexibility, drawing comparisons across platforms based solely on content can lead to error. In an attempt to circumvent this difficultly, a linguistics analysis of function words was conducted in each condition. Statistical tests point to changes in usage frequencies of i, impersonal pronouns, you, and they as distinctive between the individuating environment of Twitter and anonymous Yik Yak, while an almost identical underlying proportional framework seen in both platforms brings new context to understanding the role of societal norms in language construction.

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Cimetidine is a histamine H2-receptor antagonist that is among the most widely prescribed drugs in the world. In addition to its inhibitory action on gastric acid secretion, a possible role in kidney tubulointerstitial disease has been suggested. Isolated reports have also suggested an association between cimetidine administration and acute interstitial nephritis. The present study examined the effect of cimetidine on renal function in the rat. The nine rats used in this study had normal renal function and urinalyses before treatment with cimetidine. The cimetidine treated rats then developed a clinical picture of weakness, hematuria, proteinuria, casturia, oliguria, and increases in serum blood urea nitrogen and creatinine.Following the 6 weeks treatment period, all rats were sacrificed and their kidneys prepared for microscopic study. Histologically, the patchy, intense tubulointerstitial infiltration of lymphocytes, plasma cells, and other cells observed in the cortex of the rat kidneys is quite similar to findings described in human cases of drug-induce hypersensitivity tubulointerstitial disease. In addition, other pathologic conditions which can cause tubulointerstitial disease were adequately ruled out. Specifically, bacterial pyelonephritis was excluded as a result of the consistently sterile urine test. In conclusion, the author feels that the clinical, aboratory, and histologic findings in this study strongly suggests an association between of tubulointerstitial disease and the use of cimetidine. / Department of Physiology and Health Science

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Purpose: The aim of this study was to investigate the usefulness of formulation approaches to minimise injection site reactions for poorly soluble drugs. The specific objectives were to modify the injection site reactions by identification of irritant components in the formulation and control of their release kinetics; and to gain understanding of formulation approaches to create a favourable microenvironment in the tissues allowing better tissue tolerance and drug absorption. Methods: Physicochemical properties of the model drug, ricobendazole (RBZ) were characterised using conventional methods. Three formulation approaches to minimise irritancy of the low pH RBZ solution were assessed. An in vitro method using 96-well microplates and a microtiter plate reader was used for detection of drug precipitation on dilution for formulation characterisation. Cellular damage by the formulations was investigated in L929 fibroblasts using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy phenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) and lactate dehydrogenase (LDH) assays. Tissue tolerance and pharmacokinetics were simultaneously investigated after subcutaneous injection in sheep. A low pH RBZ solution was used as a reference formulation. Results: Preformulation studies showed that RBZ was practically insoluble in water and oils, and was slightly soluble in commonly used co-solvents. Solubility was slightly improved by complexation with hydroxypropyl-β-cyclodextrin (HP-β-CD, K₁:₁ = 311 M⁻�) or a combination of low pH (> 2) with surfactants or co-solvents. A U-shaped pH-solubility profile in aqueous solutions indicated that RBZ is an ampholyte. pKa values measured by absorbance spectroscopy and pH solubility methods were 3.45 and 3.76 (basic) and 9.82 and 9.53 (acidic) respectively. The partition coefficient was 14.3 - 15.2 at pH 6 - 9 and less at higher or lower pH. In aqueous solutions, RBZ showed a V-shaped pH-degradation rate profile and was most stable at pH 4.8. Degradation pathways were identified as hydrolysis and oxidation. Three RBZ injectables (5%) were obtained by modification of the low pH RBZ solution; addition of 20% HP-β-CD, incorporation into a w/o emulsion, and a microemulsion (ME). On dilution with SPB, the onset time of drug precipitation was prolonged and the rate was reduced in the presence of HP-β-CD. The w/o emulsion had a low viscosity (< 60 mPa.s) and exhibited Newtonian flow. Drug release versus the square root of time was linear and the release rate could be adjusted by phase ratio and droplet size. Drug release was found to be by diffusion. A coarse emulsion layer appeared at the interface between the ME and buffer. Drug release from the ME was faster than from the emulsion and was linear with the square root of time. On titration into SPB, the three formulations showed controlling effects on the release of H₃O⁺ compared to the reference formulation. RBZ (0.1 mg/ml) was more toxic to L929 cells than the co-solvent propylene glycol (50 mg/ml). The formulations showed greater cytotoxicity than their vehicles in the order: ME > RBZ solution = emulsion > HP-β-CD. HP-β-CD and emulsion excipients showed little or no cytotoxicity. The MEs exhibited more toxicity in the LDH assay than in the MTS assay. A reversed phase HPLC assay for simultaneous determination of RBZ and its metabolite in sheep plasma using an isocratic system with UV detection was developed and used in the pharmacokinetic studies. Plasma samples were prepared by solid phase extraction. A suitable internal standard was selected by quantitative structure-retention relationships analysis. The composition of a ternary mobile phase was optimised with the assistance of multiple linear regression. The assays were linear over the concentration range 10 - 1000 ng/ml for both analytes (r > 0.999) with satisfactory inter-day and intra-day precision and accuracy (CV < 10%). The recoveries for all analytes were > 96%. A pilot study in sheep suggests that injection of the vehicles (the CD, emulsion and ME) caused virtually no pain on injection or site reactions. Both the reference formulation and its vehicle induced pain on injection and resulted in swollen tissues. Histology after two weeks showed granulation for the formulation, but not the vehicle. In contrast, animals showed virtually no injection site reactions with the ME and emulsion. The HP-β-CD formulation gave transient pain on injection but a two-fold increase in bioavailability compared with the reference. The emulsion produced sustained drug release and increased drug absorption. In the main study, the HP-β-CD vehicle showed good tissue compatibility. Irritation by the HP-β-CD formulation was attributed to the low pH. Cmax, tmax and AUC0-[infinity] for the reference formulation were 1.3 � 0.3 [mu]g/ml, 9.6 � 2.9 h and 36.7 � 9.2 [mu]g�h/ml respectively, while the corresponding data for the HP-β-CD formulation were 2.9 � 0.8 [mu]g/ml, 5.0 � 0.6 h and 54.5 � 15.3 [mu]g�h/ml respectively. The half-life following the injection of the HP-β-CD formulation (5.5 � 2.8 h) was shorter than that of the reference formulation (8.5 � 3.4 h). Conclusions: Injection site reactions may be minimised by identification of irritant components in a formulation and by controlling their release. Controlling the burst release of the poorly water soluble drug RBZ in a low pH solution could improve tissue tolerance and minimise post-injection precipitation, and hence increase drug bioavailability. In addition, HP-β-CD was a useful local injectable carrier which significantly enhanced the absorption of RBZ after subcutaneous injection in sheep.

The rapid increase in the use of embedded systems for performing secure transactions, has proportionally increased the security threats which are faced by such devices. Side channel attack, a sophisticated security threat to embedded devices like smartcards, mobile phones and PDAs, exploits the external manifestations like processing time, power consumption and electromagnetic emission to identify the internal computations. Power analysis attack, introduced by Kocher in 1998, is used by adversaries to eavesdrop on confidential data while the device is executing a secure transaction. The adversary observes the power trace dissipated/consumed by the chip during the encryption/decryption of the AES cryptographic program and predicts the secret key used for encryption by extracting necessary information from the power trace. Countermeasures proposed to overcome power analysis are data masking, table masking, current flattening, circuitry level solutions, dummy instruction insertions, balancing bit-flips, etc. All these techniques are either susceptible to multi-order side channel attacks, not sufficiently generic to cover all encryption algorithms, or burden the system with high area cost, run-time or energy consumption. The initial solution presented in this thesis is a HW/SW based randomised instruction injection technique, which infuses random instructions at random places during the execution of an application. Such randomisation obfuscates the secure information from the power profile, not allowing the adversary to extract the critical power segments for analysis. Further, the author devised a systematic method to measure the security level of a power sequence and used it to measure the number of random instructions needed, to suitably confuse the adversary. The proposed processor model costs 1.9% in additional area for a simplescalar processor, and costs on average 29.8% in runtime and 27.1% in additional energy consumption for six industry standard cryptographic algorithms. This design is extended to a processor architecture which automatically detects the execution of the most common encryption algorithms, starts to scramble the power waveform by adding randomly placed instructions with random register accesses, and stops injecting instructions when it is safe to do so. This approach has less overheads compared to previous solutions and avoids software instrumentation, allowing programmers with no special knowledge to use the system. The extended processor model costs an additional area of 1.2%, and an average of 25% in runtime and 28.5% in energy overheads for industry standard cryptographic algorithms. Due to the possibility of removing random injections using large number of samples (due to the random nature, a large number of samples will eliminate noise), the author proposes a multiprocessor 'algorithmic' balancing technique. This technique uses a dual processor architecture where two processors execute the same program in parallel, but with complementary intermediate data, thus balancing the bitflips. The second processor works in conjunction with the first processor for balancing only when encryption is performed, and both processors carry out independent tasks when no encryption is being performed. Both DES and AES cryptographic programs are investigated for balancing and the author shows that this technique is economical, while completely preventing power analysis attacks. The signature detection unit to capture encryption is also utilised, which is used in the instruction injection approach. This multiprocessor balancing approach reduces performance by 0.42% and 0.94% for AES and DES respectively. The hardware increase is 2X only when balancing is performed. Further, several future extensions for the balancing approach are proposed, by introducing random swapping of encryption iterations between cores. FPGA implementations of these processor designs are briefly described at the end of this thesis.