791 resultados para Games not play


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Unlicensed driving is a serious problem in many countries, despite ongoing improvements in traffic law enforcement practices and technology. Unlike alcohol impairment and speeding, unlicensed driving does not play a direct causative role in road crashes. However it represents a major problem for road safety in two respects. Firstly, it undermines the effectiveness of driver licensing systems by preventing the allocation of demerit points and reducing the impact of licence loss (Watson, 2004b). Secondly, there is a growing body of evidence linking unlicensed driving to a cluster of high-risk behaviours including drink driving, speeding, failure to wear seat belts and motorcycle use (Griffin & DeLaZerda, 2000; Harrison, 1997; Watson, 1997, 2004b). Consistent with this, utilising the quasi-induced exposure method, Watson (2004a) estimated that in Queensland, unlicensed drivers were almost three times more likely to be involved in a reported crash than licensed drivers.

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Unlicensed driving remains a serious problem for road safety, despite ongoing improvements in traffic law enforcement practices and technology. While it does not play a direct causative role in road crashes, unlicensed driving undermines the integrity of the driver licensing system and is associated with a range of high-risk behaviours. The Queensland Transport and Main Roads (TMR) commissioned a program of research with separate components relating to different aspects of unlicensed driving. Drawing on Australian and international studies, the Unlicensed and Unregistered Vehicle (UUV) project explores the nature of unlicensed driving in Queensland, consolidates the available research evidence and identifies gaps in current knowledge relating to the driving behaviours of unlicensed drivers.

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Colorectal cancer is one of the three most common cancers today, for both men and women. Approximately 90% of the cases are sporadic while the remaining 10% is hereditary. Among this 10% is hereditary nonpolyposis colorectal cancer (HNPCC), an autosomal dominant disease, accounting for up to 13% of these cases. HNPCC is associated with germline mutations in four mismatch repair (MMR) genes, MLH1, MSH2, MSH6, and PMS2, and is characterized by a familial accumulation of endometrial, gastric, urological, and ovarian tumors, in addition to colorectal cancer. An important etiological characteristic of HNPCC is the presence of microsatellite instability (MSI), caused by mutations of the MMR genes. Approximately 15% of sporadic cases share the MSI+ trait. Colon cancer is believed to be a consequence of an accumulation of mutations in tumor suppressor genes and oncogenes, eventually resulting in tumor development. This phenomena is accelerated in HNPCC due the presence of an inherited mutation in the MMR genes, accounting for one of the two hits proposed to be needed by Knudson (1971) in order for the manifestation of the MSI phenotype. MMR alterations alone, however, do not occur in the majority of sporadic colon cancers, prompting searches for other mechanisms. One such mechanism found to play a role in colon cancer development was DNA methylation, which is known to play a role in MLH1 inactivation. Our objective was clarification of mechanisms associated with tumor development in both HNPCC and sporadic colorectal cancer in relation to tumorigenic mechanisms. Of particular interest were underlying mechanisms of MSI in sporadic colorectal cancers, with attention to DNA methylation changes and their correlation to MSI. Of additional interest were the genetic and epigenetic events leading to the HNPCC tumor spectrum, chiefly colon and endometrial cancers, in regards to what extent the somatic changes in target tissue explained this phenomenon. We made a number of important findings pertaining to these questions. First, MSI tumor development differs epigenetically from stable tumor development, possibly underlying developmental pathway differences. Additionally, while epigenetic modification, principally DNA methylation, is a major mechanism in sporadic MSI colorectal cancer MLH1 inactivation it does not play a significant role in HNPCC tumors with germline MLH1 mutations. This is possibly an explanation for tumorigenic pathways and clinicopathological characteristic differences between sporadic and hereditary MSI colorectal cancers. Finally, despite indistinguishable genetic predisposition for endometrial and colorectal cancers, instability profiles highlighting organ-specific differences, may be important HNPCC tumor spectrum determinants.

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The clinical overlap between monogenic Familial Hemiplegic Migraine (FHM) and common migraine subtypes, and the fact that all three FHM genes are involved in the transport of ions, suggest that ion transport genes may underlie susceptibility to common forms of migraine. To test this leading hypothesis, we examined common variation in 155 ion transport genes using 5257 single nucleotide polymorphisms (SNPs) in a Finnish sample of 841 unrelated migraine with aura cases and 884 unrelated non-migraine controls. The top signals were then tested for replication in four independent migraine case-control samples from the Netherlands, Germany and Australia, totalling 2835 unrelated migraine cases and 2740 unrelated controls. SNPs within 12 genes (KCNB2, KCNQ3, CLIC5, ATP2C2, CACNA1E, CACNB2, KCNE2, KCNK12, KCNK2, KCNS3, SCN5A and SCN9A) with promising nominal association (0.00041 < P < 0.005) in the Finnish sample were selected for replication. Although no variant remained significant after adjusting for multiple testing nor produced consistent evidence for association across all cohorts, a significant epistatic interaction between KCNB2 SNP rs1431656 (chromosome 8q13.3) and CACNB2 SNP rs7076100 (chromosome 10p12.33) (pointwise P = 0.00002; global P = 0.02) was observed in the Finnish case-control sample. We conclude that common variants of moderate effect size in ion transport genes do not play a major role in susceptibility to common migraine within these European populations, although there is some evidence for epistatic interaction between potassium and calcium channel genes, KCNB2 and CACNB2. Multiple rare variants or trans-regulatory elements of these genes are not ruled out.

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Ptilotus nobilis (Lindl.) F. Muell. has potential in the floriculture industries as a cut flower crop. Ethylene production and respiration rates, fresh weight changes and volatile scent production from cut inflorescences of P. nobilis cultivars Passion (dark pink flowers) and Purity (white-green flowers) were measured during vase life. Inflorescence weight loss was significant (P<0.001) during vase life with wilting and colour loss being the primary reasons for loss of vase life. Inflorescences ready for the cut market stored and at 22 degrees C had vase lives of >12 d. Ethylene production by inflorescences was low to negligible. Treatment with silverthiosulphate (STS) and ethylene had no effects on vase life. Evidently, ethylene did not play a role in determining the postharvest longevity of cut P. nobilis flowers. Respiration rates of inflorescences were high at harvest (>700 mg CO2 kg(-1) FW h(-1)) and declined gradually there-after during vase life. Total volatile emissions followed a similar pattern. For Passion, respiration rates of immature florets were significantly greater (P=0.02) than florets from other developmental stages while the calyx produced the most CO2. For Purity, respiration rates of florets of different maturities did not differ and the reproductive tissue produced the most CO2. Only fully opened mature florets with their stigma and anthers revealed, emitted significant quantities of volatiles (P<0.001) and primarily from the calyx tissue for both cultivars. The individual volatiles differed somewhat for the two cultivars. However, both produced significant quantities of benzaldehyde, 3,5-dimethoxytoluene and benzyl alcohol. These. compounds have previously been associated with desirable floral scent. (C) 2013 Elsevier B.V. All rights reserved.

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Salt-fog tests as per International Electrotechnical Commission (IEC) recommendations were conducted on stationtype insulators with large leakage lengths. Later, tests were conducted to simulate natural conditions. From these tests, it was understood that the pollution flashover would occur because of nonuniform pollution layers causing nonuniform voltage distribution during a natural drying-up period. The leakage current during test conditions was very small and the evidence was that the leakage current did not play any significant role in causing flashovers. In the light of the experimental results, some modification of the test procedure is suggested.

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Ptilotus nobilis (Lindl.) F. Muell. has potential in the floriculture industries as a cut flower crop. Ethylene production and respiration rates, fresh weight changes and volatile scent production from cut inflorescences of P. nobilis cultivars Passion (dark pink flowers) and Purity (white-green flowers) were measured during vase life. Inflorescence weight loss was significant (P < 0.001) during vase life with wilting and colour loss being the primary reasons for loss of vase life. Inflorescences ready for the cut market stored and at 22 °C had vase lives of >12 d. Ethylene production by inflorescences was low to negligible. Treatment with silverthiosulphate (STS) and ethylene had no effects on vase life. Evidently, ethylene did not play a role in determining the postharvest longevity of cut P. nobilis flowers. Respiration rates of inflorescences were high at harvest (>700 mg CO2 kg−1 FW h−1) and declined gradually thereafter during vase life. Total volatile emissions followed a similar pattern. For Passion, respiration rates of immature florets were significantly greater (P = 0.02) than florets from other developmental stages while the calyx produced the most CO2. For Purity, respiration rates of florets of different maturities did not differ and the reproductive tissue produced the most CO2. Only fully opened mature florets with their stigma and anthers revealed, emitted significant quantities of volatiles (P < 0.001) and primarily from the calyx tissue for both cultivars. The individual volatiles differed somewhat for the two cultivars. However, both produced significant quantities of benzaldehyde, 3,5-dimethoxytoluene and benzyl alcohol. These compounds have previously been associated with desirable floral scent.

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Ptilotus nobilis (Lindl.) F. Muell. has potential in the floriculture industries as a cut flower crop. Ethylene production and respiration rates, fresh weight changes and volatile scent production from cut inflorescences of P. nobilis cultivars Passion (dark pink flowers) and Purity (white-green flowers) were measured during vase life. Inflorescence weight loss was significant (P < 0.001) during vase life with wilting and colour loss being the primary reasons for loss of vase life. Inflorescences ready for the cut market stored and at 22 °C had vase lives of >12 d. Ethylene production by inflorescences was low to negligible. Treatment with silverthiosulphate (STS) and ethylene had no effects on vase life. Evidently, ethylene did not play a role in determining the postharvest longevity of cut P. nobilis flowers. Respiration rates of inflorescences were high at harvest (>700 mg CO2 kg−1 FW h−1) and declined gradually thereafter during vase life. Total volatile emissions followed a similar pattern. For Passion, respiration rates of immature florets were significantly greater (P = 0.02) than florets from other developmental stages while the calyx produced the most CO2. For Purity, respiration rates of florets of different maturities did not differ and the reproductive tissue produced the most CO2. Only fully opened mature florets with their stigma and anthers revealed, emitted significant quantities of volatiles (P < 0.001) and primarily from the calyx tissue for both cultivars. The individual volatiles differed somewhat for the two cultivars. However, both produced significant quantities of benzaldehyde, 3,5-dimethoxytoluene and benzyl alcohol. These compounds have previously been associated with desirable floral scent.

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Investigations of different superconducting (S)/ferromagnetic (F) heterostructures grown by pulsed laser deposition reveal that the activation energy (U) for the vortex motion in a high T-c superconductor is reduced remarkably by the presence of F layers. The U exhibits a logarithmic dependence on the applied magnetic field in the S/F bilayers suggesting the existence of decoupled two-dimensional (2D) pancake vortices. This result is discussed in terms of the reduction in the effective S layer thickness and the weakening of the S coherence length due to the presence of F layers. In addition, the U and the superconducting T-c in YBa2Cu3O7-delta/La0.5Sr0.5CoO3 bilayers are observed to be much lower than in the YBa2Cu3O7-delta/La0.7Sr0.3MnO3 ones. This in turn suggests that the degree of spin polarization of the F layer might not play a crucial role for the suppression of superconductivity due to a spin polarized induced pair-breaking effect in S/F bilayers.

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Use of adverse drug combinations, abuse of medicinal drugs and substance abuse are considerable social problems that are difficult to study. Prescription database studies might fail to incorporate factors like use of over-the-counter drugs and patient compliance, and spontaneous reporting databases suffer from underreporting. Substance abuse and smoking studies might be impeded by poor participation activity and reliability. The Forensic Toxicology Unit at the University of Helsinki is the only laboratory in Finland that performs forensic toxicology related to cause-of-death investigations comprising the analysis of over 6000 medico-legal cases yearly. The analysis repertoire covers most commonly used drugs and drugs of abuse, and the ensuing database contains also background information and information extracted from the final death certificate. In this thesis, the data stored in this comprehensive post-mortem toxicology database was combined with additional metabolite and genotype analyses that were performed to complete the profile of selected cases. The incidence of drug combinations possessing serious adverse drug interactions was generally low (0.71%), but it was notable for the two individually studied drugs, a common anticoagulant warfarin (33%) and a new generation antidepressant venlafaxine (46%). Serotonin toxicity and adverse cardiovascular effects were the most prominent possible adverse outcomes. However, the specific role of the suspected adverse drug combinations was rarely recognized in the death certificates. The frequency of bleeds was observed to be elevated when paracetamol and warfarin were used concomitantly. Pharmacogenetic factors did not play a major role in fatalities related to venlafaxine, but the presence of interacting drugs was more common in cases showing high venlafaxine concentrations. Nicotine findings in deceased young adults were roughly three times more prevalent than the smoking frequency estimation of living population. Contrary to previous studies, no difference in the proportion of suicides was observed between nicotine users and non-nicotine users. However, findings of abused substances, including abused prescription drugs, were more common in the nicotine users group than in the non-nicotine users group. The results of the thesis are important for forensic and clinical medicine, as well as for public health. The possibility of drug interactions and pharmacogenetic issues should be taken into account in cause-of-death investigations, especially in unclear cases, medical malpractice suspicions and cases where toxicological findings are scarce. Post-mortem toxicological epidemiology is a new field of research that can help to reveal problems in drug use and prescription practises.

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Bile acids are important steroid-derived molecules essential for fat absorption in the small intestine. They are produced in the liver and secreted into the bile. Bile acids are transported by bile flow to the small intestine, where they aid the digestion of lipids. Most bile acids are reabsorbed in the small intestine and return to the liver through the portal vein. The whole recycling process is referred to as the enterohepatic circulation, during which only a small amount of bile acids are removed from the body via faeces. The enterohepatic circulation of bile acids involves the delicate coordination of a number of bile acid transporters expressed in the liver and the small intestine. Organic anion transporting polypeptide 1B1 (OATP1B1), encoded by the solute carrier organic anion transporter family, member 1B1 (SLCO1B1) gene, mediates the sodium independent hepatocellular uptake of bile acids. Two common SNPs in the SLCO1B1 gene are well known to affect the transport activity of OATP1B1. Moreover, bile acid synthesis is an important elimination route for cholesterol. Cholesterol 7α-hydroxylase (CYP7A1) is the rate-limiting enzyme of bile acid production. The aim of this thesis was to investigate the effects of SLCO1B1 polymorphism on the fasting plasma levels of individual endogenous bile acids and a bile acid synthesis marker, and the pharmacokinetics of exogenously administered ursodeoxycholic acid (UDCA). Furthermore, the effects of CYP7A1 genetic polymorphism and gender on the fasting plasma concentrations of individual endogenous bile acids and the bile acid synthesis marker were evaluated. Firstly, a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the determination of bile acids was developed (Study I). A retrospective study examined the effects of SLCO1B1 genetic polymorphism on the fasting plasma concentrations of individual bile acids and a bile acid synthesis marker in 65 healthy subjects (Study II). In another retrospective study with 143 healthy individuals, the effects of CYP7A1 genetic polymorphism and gender as well as SLCO1B1 polymorphism on the fasting plasma levels of individual bile acids and the bile acid synthesis marker were investigated (Study III). The effects of SLCO1B1 polymorphism on the pharmacokinetics of exogenously administered UDCA were evaluated in a prospective genotype panel study including 27 healthy volunteers (Study IV). A robust, sensitive and simple HPLC-MS/MS method was developed for the simultaneous determination of 16 individual bile acids in human plasma. The method validation parameters for all the analytes met the requirements of the FDA (Food and Drug Administration) bioanalytical guidelines. This HPLC-MS/MS method was applied in Studies II-IV. In Study II, the fasting plasma concentrations of several bile acids and the bile acid synthesis marker seemed to be affected by SLCO1B1 genetic polymorphism, but these findings were not replicated in Study III with a larger sample size. Moreover, SLCO1B1 polymorphism had no effect on the pharmacokinetic parameters of exogenously administered UDCA. Furthermore, no consistent association was observed between CYP7A1 genetic polymorphism and the fasting plasma concentrations of individual bile acids or the bile acid synthesis marker. In contrast, gender had a major effect on the fasting plasma concentrations of several bile acids and also total bile acids. In conclusion, gender, but not SLCO1B1 or CYP7A1 polymorphisms, has a major effect on the fasting plasma concentrations of individual bile acids. Moreover, the common genetic polymorphism of CYP7A1 is unlikely to influence the activity of CYP7A1 under normal physiological conditions. OATP1B1 does not play an important role in the in vivo disposition of exogenously administered UDCA.

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During lightning strike to a tall grounded object (TGO), reflections of current waves are known to occur at either ends of the TGO. These reflection modify the channel current and hence, the lightning electromagnetic fields. This study aims to identify the possible contributing factors to reflection at a TGO-channel junction for the current waves ascending on the TGO. Possible sources of reflection identified are corona sheath and discontinuity of resistance and radius. For analyzing the contribution of corona sheath and discontinuity of resistance at the junction, a macroscopic physical model for the return stroke developed in our earlier work is employed. NEC-2D is used for assessing the contribution of abrupt change in radii at a TGO-channel junction. The wire-cage model adopted for the same is validated using laboratory experiments. Detailed investigation revealed the following. The main contributor for reflection at a TGO-channel junction is the difference between TGO and channel core radii. Also, the discontinuity of resistance at a TGO-channel junction can be of some relevance only for the first microsecond regime. Further, corona sheath does not play any significant role in the reflection.

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We study the phenomenon of electromagnetically induced transparency and absorption (EITA) using a control laser with a Laguerre-Gaussian (LG) profile instead of the usual Gaussian profile, and observe significant narrowing of the resonance widths. Aligning the probe beam to the central hole in the doughnut-shaped LG control beam allows simultaneously a strong control intensity required for high signal-to-noise ratio and a low intensity in the probe region required to get narrow resonances. Experiments with an expanded Gaussian control and a second-order LG control show that transit time and orbital angular momentum do not play a significant role. This explanation is borne out by a density-matrix analysis with a radially varying control Rabi frequency. We observe these resonances using degenerate two-level transitions in the D-2 line of Rb-87 in a room temperature vapor cell, and an EIA resonance with width up to 20 times below the natural linewidth for the F = 2 -> F' = 3 transition. Thus the use of LG beams should prove advantageous in all applications of EITA and other kinds of pump-probe spectroscopy as well.

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Recent observations of Sun-like stars, similar to our Sun in their surface temperature (5600-6000 K) and slow rotation (rotational period > 10 d), using the Kepler satellite by Maehara et al. (2012, Nature, 485, 478) have revealed the existence of superflares (with energy of 10(33)-10(35) erg). From statistical analyses of these superflares, it was found that superflares with energy of 10(34) erg occur once in 800 yr, and superflares with 10(35) erg occur once in 5000 yr. In this paper, we examine whether superflares with energy of 10(33)-10(35) erg could occur on the present Sun through the use of simple order-of-magnitude estimates based on current ideas related to the mechanisms of the solar dynamo. If magnetic flux is generated by differential rotation at the base of the convection zone, as assumed in typical dynamo models, it is possible that the present Sun would generate a large sunspot with a total magnetic flux of similar to 2 x 10(23) Mx (= G cm(2)) within one solar cycle period, and lead to superflares with an energy of 10(34) erg. To store a total magnetic flux of similar to 10(24) Mx, necessary for generating 10(35) erg superflares, it would take similar to 40 yr. Hot Jupiters have often been argued to be a necessary ingredient for the generation of superflares, but we found that they do not play any essential role in the generation of magnetic flux in the star itself, if we consider only the magnetic interaction between the star and the hot Jupiter. This seems to be consistent with Maehara et al.'s finding of 148 superflare-generating solar-type stars that do not have a hot Jupiter-like companion. Altogether, our simple calculations, combined with Maehara et al.'s analysis of superflares on Sun-like stars, show that there is a possibility that superflares of 10(34) erg would occur once in 800 yr on our present Sun.

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A layer-wise theory with the analysis of face ply independent of lamination is used in the bending of symmetric laminates with anisotropic plies. More realistic and practical edge conditions as in Kirchhoff's theory are considered. An iterative procedure based on point-wise equilibrium equations is adapted. The necessity of a solution of an auxiliary problem in the interior plies is explained and used in the generation of proper sequence of two dimensional problems. Displacements are expanded in terms of polynomials in thickness coordinate such that continuity of transverse stresses across interfaces is assured. Solution of a fourth order system of a supplementary problem in the face ply is necessary to ensure the continuity of in-plane displacements across interfaces and to rectify inadequacies of these polynomial expansions in the interior distribution of approximate solutions. Vertical deflection does not play any role in obtaining all six stress components and two in-plane displacements. In overcoming lacuna in Kirchhoff's theory, widely used first order shear deformation theory and other sixth and higher order theories based on energy principles at laminate level in smeared laminate theories and at ply level in layer-wise theories are not useful in the generation of a proper sequence of 2-D problems converging to 3-D problems. Relevance of present analysis is demonstrated through solutions in a simple text book problem of simply supported square plate under doubly sinusoidal load.