In order to explore south Arabia's role in the migratory episodes leaving Africa to Eurasia and back, high-resolution Y-chromosome analyses of males from the United Arab Emirates (164), Qatar (72) and Yemen (62) were performed. The distribution of specific haplogroups (E3bl-M35 and J1-M267) and their microsatellite-based age estimates in southern Arabia offer additional insight on their dissemination. With the exception of Yemen, southern Arabia displays high diversity in its Y-haplogroup substructure and share similarities with populations along the eastern coast of the Gulf of Oman, possibly serving as a coastal corridor for migrations. Elevated rates of consanguinity may have had an impact in Yemen and Qatar, which experience deficiencies in their ratios of observed to expected heterozygosity at 15 hypervariable autosomal STR loci. Higher diversity along the Gulf of Oman may be due to trade emanating from the kingdom of Oman involving East Africa, southern Pakistan and western India.

Current forensic comparisons of soil most often rely upon physical characterizations. We hypothesized that bacterial community profiles obtained by Amplicon Length Heterogeneity-Polymerase Chain Reaction (ALH-PCR) of the 16S rRNA genes would provide discriminating data for soil comparisons. Dual extractions and replicate amplifications were performed on each soil. Chemical characterization by elemental analysis, pH, moisture content, percent Carbon and percent Nitrogen were performed. Supervised classification of the microbial community profiles using a Support Vector Machine (SVM) learning tool was over 95 % accurate labeling a microbial community profile to its originating soil type. By comparison, the chemical analysis data yielded accuracies between 40 and 77 %. The results of this study support the application of this method in the comparison of casework size soil samples. Results of this study may also justify the future development of a database of microbial community profiles for inferring the possible origin of unknown soil samples.

The drugs studied in this work have been reportedly used to commit drug-facilitated sexual assault (DFSA), commonly known as "date rape". Detection of the drugs was performed using high-performance liquid chromatography with ultraviolet detection (HPLC/UV) and identified with high performance-liquid chromatography mass spectrometry (HPLC/MS) using selected ion monitoring (SIM). The objective of this study was to develop a single HPLC method for the simultaneous detection, identification and quantitation of these drugs. The following drugs were simultaneously analyzed: Gamma-hydroxybutyrate (GHB), scopolamine, lysergic acid diethylamide, ketamine, flunitrazepam, and diphenhydramine. The results showed increased sensitivity with electrospray (ES) ionization versus atmospheric pressure chemical ionization (APCI) using HPLC/MS. HPLC/ES/MS was approximately six times more sensitive than HPLC/APCI/MS and about fifty times more sensitive than HPLC/UV. A limit of detection (LOD) of 100 ppb was achieved for drug analysis using this method. The average linear regression coefficient of correlation squared (r2) was 0.933 for HPLC/UV and 0.998 for HPLC/ES/MS. The detection limits achieved by this method allowed for the detection of drug dosages used in beverage tampering. This method can be used to screen beverages suspected of drug tampering. The results of this study demonstrated that solid phase microextraction (SPME) did not improve sensitivity as an extraction technique when compared to direct injections of the drug standards.

Ascertaining the genetic relationships between Austronesian populations is pivotal to understanding their dispersal throughout the islands of the Pacific and Indian Oceans. The Austronesian expansion dates to approximately 6,000 years ago and from the linguistic and archeological evidence, the origin of this dispersal appears to be Taiwan. In this study, six polymorphic point mutation loci were studied in Taiwanese aborigines and compared with 32 other populations. The genetic relationships were characterized by maximum likelihood analysis, principal component maps, centroid gene flow plots, expected heterozygosities, power of discrimination values and pair wise G-tests. Following these analyses, it was apparent that genetic similarities existed between the Atayal and the Chinese, whereas the Ami displayed similarities with the Native Americans. Thus, the Atayal have little or no affinity for the Ami and other Austronesian populations. The large genetic differences between the two groups most likely arise from genetic isolation, and/or small population sizes.

This study evaluates the use of commercially available instruments for locating and collecting accelerants in the field. Electronic noses can be used to scan a fire scene for the possible presence of an accelerant. The TLV Sniffer® was found to be able to detect accelerants at low levels but did alert to some burned matrix alone. When subjected to a proficiency test designed for canines, the TLV Sniffer® was able to locate accelerants in two of the three tests. The tpi®Pocket was found not to be sensitive or selective enough to be useful in locating accelerants. Once the location of possible accelerants has been determined, they can be collected by dynamic headspace sampling in the field with the Portable Arson Sampler (PAS). The PAS was found to be able to collect a broad range of compounds from ignitable liquids and had comparable efficiency to a conventional method.

This study examined helping and hindering factors that influence the experiences of forensic psychiatric patients in the forensic system, and describes implications for practice. A qualitative approach was used to delineate which factors patients report are helpful and which ones are reported as hindering within a forensic inpatient hospital. Ten participants were interviewed using Critical Incident Technique to elicit their experiences since coming to a Forensic Psychiatric Inpatient Hospital. Results indicated that the factors that were helpful were: talking with staff, programming and services, and taking prescribed medications. Hindering factors included: exposure to illicit drugs, exposure to violence, programming and services, stigmatism, living on a maximum security ward, lack of respect from the staff, and concerns involving prescribed medication. The results of this research are discussed in light of how this present research supports the extant research and theories. Implications and recommendations at both a clinician and system level within forensic psychiatric services are offered. / Education, Faculty of / Educational and Counselling Psychology, and Special Education (ECPS), Department of / Graduate

The ReJI29 murine model of muscular dystrophy was employed to investigate the properties of skeletal muscle plasmalemma and calcium ion movements during muscle wastage, with the intention of determining the route of calcium influx, and the efficacy of calcium ion blockers in preventing this influx. Electrophysiological parameters (Resting membrane potential [RMP] and input resistance) reached adult magnitude in normal soleus and extensor digitorum longus (EDL) by 4 weeks and 3 weeks respectively. Electrophysiological parameters in dystrophic soleus developed in a similar maimer to normal muscle, but RMP in dystrophic EDL was reduced and input resistance was elevated suggesting the presence of a population of regenerating fibres. Twitch and contracture tension development reached mature levels by 4 weeks in normal soleus muscle, but development was prolonged to 10 weeks in EDL, due to the slower development of type II fibres. Contracture tension was markedly smaller in EDL possibly due to fibre type-related differences in the concentrations of calcium sequestering proteins. Twitch and contracture tension in dystrophic soleus was identical to normal. In dystrophic EDL, 4 week old muscle did not generate tension from either electrical or chemical stimulation. Older muscles generated tension but smaller than their normal counterparts. Twitch and contracture tomography revealed similarities between dystrophic EDL and immature normal EDL corroborating with the conclusions made from the electrophysiological experiments. Caffeine contractures generated in glycinerated normal soleus muscle, incubated in low calcium saline, and then bathed in high calcium saline reached 115-185% the magnitude of caffeine contractures generated prior to incubation. 4 week dystrophic soleus attained similar sized contractures, but contractures were reduced to 77-90% in older muscles. This technique was found to be inappropriate in the study of EDL. Caffeine contractures generated by normal soleus in normal saline, after incubation in low calcium saline, reached the magnitude of contractures generated in high calcium saline after 30 minutes. Contractures generated by dystrophic soleus remained identical to those generated in high calcium saline suggesting that the sarcoplasmic reticulum in these fibres was unable to cope with a high calcium load. This result gave the first indication that soleus muscle was affected by muscular dystrophy. Membrane bound calcium derived from 45Calcium influx studies was 2nmoles/mg tissue/30 minutes in soleus and 1 Snmoles/mg tissue weight/30 minutes in EDL. Intracellular influx was 0.5-0.6nmoles/mg tissue weight/ 30 minutes in both muscles. Membrane bound calcium was elevated in dystrophic EDL to 2.5-3.8nmoles/mg tissue weight/30 minutes, but influx was normal in both dystrophic soleus and EDL, casting doubt on whether the plasmalemma is more permeable to calcium. The increase in membrane bound calcium may be artefactual. Cadmium blocked influx in both normal and dystrophic muscles. Blot weights showed continual growth in normal muscles although the rate decreased after 10 weeks. In dystrophic muscles growth ceased after 10 weeks. NCP data was limited but did show a decrease in dystrophic muscle, followed by an increase. Tension as a function of tissue mass, revealed that the contractile apparatus in normal soleus matured within 2 weeks, and by 10 weeks in EDL due to the differences in myosin isoforms present in each fibre type. These ratios were elevated in dystrophic muscle indicating calcium accumulation in the sarcoplasmic reticulum. The results showed that EDL muscle was more severely affected by muscular dystrophy. Between 2 and 4 weeks, the muscle underwent degeneration via an unidentified process. There was regeneration, and the regenerating fibres appeared to be normal. Soleus muscle appeared resistant to the disease but succumbed under unusual chemical stresses. Some aspects of development of normal muscle were also considered.

Investigations were made into the role of blood-borne substances affecting myocardial contractility. Isolated left and right guinea-pig au -ia were used as bioassay for the detection of endogenous cardiotonic substances in bovine serum. Results show that serum that had been buffer exchanged to Krebs-Henseleit by dialysis or Sephadex G-25, produced positive inotropic and positive chronotropic effects on the isolated guinea-pig au-ia. The hypodynamic state was not a prerequisite for the detection of cardioactivity. The cardioactive effectswere not blocked by the combined presence of propranolol and methysergide (both 10 6M) and were also dissimilar in time course from other known cardiotonic agents such as noradrénaline, isoprenaline, 5-hydroxytryptamine and cardiac glycosides. After ultrafiltration on Amicon diaflo membranes (XM100A and PM30A) activity was found solely in the retentate fractions. The ultrafiltrates were devoid of positive inotropic and chronotropic actions. Since the molecular weight cut-off of the XM100A membranes was 100 Kilodaltons, it is probable that the active principle is greater than 100 kilodaltons. Alternatively, a smaller active substance may be bound to a large protein. The cardioaciive factor in whole bovine serum was heat labile and lost after 30 minutes incubation at 70 0C or boiling for 10 minutes. Activity of whole bovine serum was not cold labile during a 30 minute incubation at 0°C. Activity was also present after dialysis at 4-8 °C for up to 48 hours. Cardioactivity of whole serum was lost following acidification to pH 5.0 at 4-8 0C for 24 hours. This experiment was extended to include a wider range of pH values between 4.5 and 75. The positive inotropic and chronotropic activities of serum were markedly reduced at acidic pH values. The cardioactive factor was also lost after equilibration of serum to physiological buffers of a low ionic strength. The loss of activity was independent of the nature of the buffer and was prevented by raising the ionic strength with the addition of NaCl. The cardiotonic principle was also sensitive to the addition of KBr but not equimolar (or higher) concentrations of KCI or NaCl. The above results taken together would be consistent with a proteinaceous nature of the active substance. The major purification methods therefore employed included precipitation techniques involving (NH4)2SO4 and polyethyleneglycol-8000, ion exchange, hydrophobic interaction chromatography and gel filtration. Attempts to isolate and purify the cardiotonic agent were largely unsuccessful due, particularly, to the labile nature of the active molecule when exposed to non-physiological experimental conditions. Investigations in to the cellular mechanism of action of the cardioactive factor in buffer exchanged serum suggested that the effects may perhaps be mediated by increases in the level of endogenous cyclic AMP and not via inhibition of the N a+,Kt ATPase. In conclusion, the present study has demonstrated the existence of a factor in bovine serum that produced positive inotropic and chronotropic effects on the isolated guinea-pig au-ia. Properties of the cardioactive factor suggest the existence of a novel proteinaceous substance with some previously unidentified characteristics.

Integral membrane proteins often possess lipophilic a-helical regions of approximately 21 amino acid residues that are able to traverse the bilayer. These may either be amphiphilic or predominantly hydrophobic (such as those found in the photoreaction centres). Such helices are distinguished by low charge densities and large mean hydrophobicities. Several hydrophobicity measures (scales) and algorithms for identification of these segments have been developed. Here, a survey of currently available hydrophobicity scales and prediction techniques has been conducted and a brief description of each of the techniques is reported. The hydrophobic moment methodology, even after twenty years of existence, appears to be the most widely used technique for amphiphilic helical structure prediction. The reliability of this methodology at predicting structure and function relationship in membrane proteins was tested using proteins and peptides from different but known classes. In predicting structure, the hydrophobic moment appears to make predictions consistent with those from other researchers using other prediction techniques based on other alternative properties. However, the predictions for function were not consistent with the role of proteins in some cases. Scatterplots of mean hydrophobicity and mean hydrophobic moment for different window sizes revealed that there is a negative association between the two variates and, that mean hydrophobic moment decreases as window size increases. It was also deduced from 99% bootstrap confidence intervals for the correlation coefficients, that short window sizes (7-15) are more discriminative than tong ones (16-20). Angular frequencies between 95° and 107 0 were also investigated for all window sizes and it was observed that different window lengths have different optimum angular frequencies. Variation in both window size and angular frequency were seen to affect prediction with window sizes 7-15 residues giving better prediction. A data set of 403 transmembrane segments was assembled. The compositionat and distributional properties of constituent amino acids were investigated. It was observed that transmembrane segments tend to posses high occurrence of charged amino acid residues at the interface, large planar molecules just within the membrane interior and smalt hydrophobic residues in the central region. When the amino acid residue compositions of the boundaries of transmembrane a-helices were compared statisticatly, it was observed that at the 5% significant level there is no difference between the boundaries within, or between classes of transmembrane spans. It was also observed that the assumed length of twenty-one residues is, on average, reasonable for uncleaved sequences but that twenty-two may be appropriate for stop transfer sequences. When the presence of a hydrophobicity gradient in transmembrane a-hetices was examined, 25% of the sequences in the data set showed the distribution of hydrophobicity which is observed in typical transmembrane spans (tow-high-low). However, 13% showed the distribution of hydrophobicity which is similar to that seen in tilted peptides. It would appear that some transmembrane a-helices do have a hydrophobicity gradient, but this has not been related to any biological role. A new measure of amphiphilicity, which takes into account the third dimension of a helix, was also developed and compared to the conventional hydrophobic moment using bootstrap and regression modelling with a categoricat predictor. From the 95% bootstrap confidence intervals for estimates of model parameters, it was concluded though that there is no difference between the two measures, implying that the loss of spatial information in the conventional hydrophobic moment model, is not significant.

1. Investigations have been carried out in two parts (a) in vitro studies into the roles of Mg2 in ACh and CCK3-evoked Ca 2 mobilisation assàciated with the secretory process and (b) in vitro and in vivo studies into the effects and mechanisms of action of phorbol esters (and related compounds) on secretagogueevoked 3H-protein release (ACh & CCK8) and pancreatic juice secretion (CCK8 & Secretin) in the rat pancreas. 2. Modifications in extracellular Mg 2 affected ACh-evoked 45Ca2 influx, efflux and intracellular free C a2+ mobilisation. Elevated extracellular Mg2+ (10 mM) depressed whereas, zero extracellular Mg2+ (0 mM) augmented these parameters in comparison to normal extracellular Mg2+ (1.13 mM). ACh also elicited simultaneous transmembrane movement of Ca2+ (influx) and Mg2+ (efflux). Parallel secretory effects under the same conditions were observed when monitoring ct-aniylase and total protein outputs. Similar results were obtained for CCK8. Mg2+ facilitates control over the secretory process which occurs primarily through modifications in Ca 2 mobilisation. 3. The phorbol ester TPA (12-0-tetradecanoyl phorbol-l3-acetate) alone induced 3 H-protein release from permeabilised pancreatic acini but when combined with ACh a synergistic secretory response resulted at an intracellular free [Ca 2+]i = 10 4M. Lowering intracellular free [Ca 2+]i to 10 7M removed the potentiatory action of TPA but did not abolish AC!, induced secretion. Whereas, at [Ca2t] of 104M combining TPA with CCK8 resulted in complete depression of the CCK8-induced 3H-protein release. The action of TPA on CCK8-evoked 311-protein release was mediated through protein kinase C activation as Polymyxin B, an inhibitor of protein kinase C, reversed the effects of TPA. However, the potentiatory action of TPA on ACh-elicited 3 H-protein secretion was not mediated through protein kinase C activation or increases in cellular cyclic GMP. Hence, another cellular mechanism or mediator independent of protein kinase C activation possibly exists to account for both ACh-evoked secretion and the potentiatory action of TPA. 4. ACh and CCK8-evoked dose-dependent increases in intracellular free [Ca 2 ]. The dose-dependency of the Ca2+ transients elicited by these secretagogues showed a degree of correlation with their known secretory activity. Incubation of the pancreatic acini with TPA inhibited CCK8-induced but NOT ACh-induced intracellular Ca2+ transients. Therefore, protein kinase C may facilitate to some extent its secretory modulatory activity through changes in intracellular C a2+ mobilisation. 5. In vivo administration of TPA to the anaesthetised rat resulted in increases in pancreatic juice secretion. Secretin administration caused marked increases in pancreatic juice flow but not of protein or u-amylase. Whereas, CCK8 administration induced marked increases in juice flow, protein and ct-amylase secretion. TPA combined with secretin or CCK8 differentially suppressed the secretory activity of these secretagogues. Inhibition of protein kinase C reversed to some extent the inhibitory activity of TPA. Hence, it is believed that protein kinase C can physiologically initiate and modulate the quantity and quality of secretagogue-evoked pancreatic juice secretion irrespective of the intracellular pathway utilised in the pancreas of the rat. 6. In conclusion, the present study has demonstrated that Mg2+ plays an important role in stimulus-secretion coupling and therefore requires greater consideration when evaluating secretory events. Protein kinase C has been shown to possess an essential modulatory role in the whole secretory process. Furthermore, the possibility exists that an as yet uncharacterised intracellular pathway may be responsible for the protein kinase independent actions of TPA.