Abstract This thesis mainly researches in the Internet development and impact of Mainland China. With the theory of corporatism, it also analyzes the development of internet and how the control measures of the Communist Party of China change the relation between state and society . This thesis has reviewed why the Communist Party of China developed the Internet and its restrictions and present situation of Internet. However, the Internet users have tried everything to obtain the unaccessible message. Recently, every leader of the Communist Party of China has declared for the development of Internet sequentially. At the same time, they still insist the restriction of Internet and even aggravated it with the technology of western network information corporations. In the past two years, the Mainland China has established the association of China Internet made up of Internet Services Providers as a medium to control increasing Internet users by staging self-control actions and settin report procedures. But the Communist Party of China still fails to get rid of the dilemma of controlling or developing the Internet.

The image resolution of atomic force microscopy (AFM) is still less superior to that of the electron microscopy (EM). However AFM operated in liquids complemented by Tapping-mode (TM) detection proves to be more suitable for imaging biomolecules in physiological-like environments. Nevertheless, manipulation of AFM in solution turned out to be non-trivial, several technical difficulties were encountered. In the thesis, I report using divalent cation-containing buffer as a feasible method to immobilize DNA molecules effectively for imaging in liquid media. AFM operating conditions, such as cantilever oscillating drive frequency, setpoint amplitude, feedback control parameters and scan rates were studied to obtain the optimized function. Various AFM images of Ssp I-linearized pUC19 DNA/EcoR I restriction enzyme complexes were captured, revealing the molecular details of their complex machineries. For example, the intermediate stage of the enzyme cleavage action was displayed by images showing that DNA was bent by an acute angle at the active site in the presence of one single EcoR I molecule. Some evidence for a jumping, sliding or intersegmental transfer mechanism is achieved. To trace the enzyme-DNA interaction dynamic in real time, preliminary results were obtained, but further improvements are required.

­^¤åºK­n Multiplex PCR amplification of 16S rRNA gene¡BvirA¡Btpl¡Band H1d genes was developed enabling simultaneous detection in Escherichia coli¡Aan indicator of fecal contamination and food-borne microbial pathogens¡AShigella flexneri¡BCitrobacter freundii¡BSalmonella typhi¡BVibrio cholerae¡BVibrio parahaemolyticus¡Band Staphylococcus aureus¡CEach of the nine pairs of oligonucleotide primers was found to support PCR amplifications of only its targeted gene¡CThe optimized multiplex PCR reaction utilized a primer annealing temperature of 59 ¢Jand used agarose gel electrophoresis for detection of the PCR-amplified products¡CSelection of appropriate target genes¡Boligonucleotide primers ¡BPCR reaction¡Band cycling parameters resulted in the amplification of four target genes simultaneously in a single PCR reaction with the sensitivity of detection was 102 CFU after 32 cycles¡CMultiplex PCR amplification followed by differential PCR for E. coli / Shigella¡A and Citrobacter / Salmonella¡Asequenced for the PCR-amplified products of 16S rRNA gene of the seven pathogens in this study¡Aand used restriction endonuclease AfaI to confirm the PCR-amplified products of V. cholerae¡AV. parahaemolyticus and Staphylococcus aureus¡Ahas been shown to be an sensitive¡Aspecific¡Aand rapid method to detect food-borne bacterial pathogens¡C

Dietary manipulations and their pharmacological outcomes have been increasingly studied in neurodegenerative diseases. However, a systematic comparison among different methods in validated animal models of Alzheimer's disease is made necessary due to several different approaches applied in recent studies. Moreover, despite the large body of evidence on the effects of calorie restriction (CR) and ketogenic diets (KDs) on amyloid pathology, no consistent data is available on the effects of calorie restriction, ketogenic diet or ketone supplements on tau pathology in transgenic models of AD. Moreover, the ketogenic diet used in our studies was custom made with low carbohydrate content and rich in medium chain triglyceride (MCT) oils, known to be rapidly metabolized in the liver, resulting in sustained peripheral ketosis. Chapter 1 tested the ability of KD to induce significant ketosis in a mouse model of amyloid deposition. We showed that, despite the mild ketosis induced, KD fed APP mice presented subtle behavioral improvement shown as faster learning in the radial arm water maze, making less errors than APP mice kept on a control diet. Additionally, we observed decreased Aβ immunoreactivity in the anterior cortex of KD fed versus control fed APP mice, despite the lack of changes in congophilic deposits. Due to the mild ketosis induced, a modified ketogenic diet was devised with decreased maltodextrin content and showed greater peripheral levels of β-hydroxybutyrate. Chapter 2 investigated the effects of a ketogenic diet in two transgenic mouse models of Alzheimer's pathology. Interestingly, we found that both transgenic lines, regardless of diet, weighed less than nontransgenic mice, despite their elevated food intake. The reduced body weight may, in part, be explained by the increased locomotor activity shown by both transgenic lines in both the open field and y-maze. Moreover, KD fed mice performed significantly better on the rotarod compared to mice on the control diet independent of genotype. We did not observed KD-induced changes in spatial or associative memory in the radial arm water maze or contextual fear conditioning, respectively. Furthermore, immunohistochemical levels of amyloid, tau, astrocytic and microglial markers showed no differences between animals fed KD or the control diet. Chapter 3 studied the effects of calorie restriction on a mouse model of tau deposition. We show here that 35% body weight reduction in Tg4510 mice did not prevent increased locomotor activity in the open field, previously reported in chapter 2. Similarly, CR did not affect motor performance or spatial memory assessed by the rotarod and radial arm water maze, respectively. Interestingly, CR Tg4510 mice showed improved short-term memory tested by the novel object recognition despite spending a minimal percentage of the trial time interacting with the objects presented. However, this improvement was not observed when the test was modified to replace the objects with mice. In this case, we noticed that nontransgenic mice spent most of the trial time interacting with the novel mouse whereas Tg4510 mice spent roughly the same amount of time at any of the areas in the test chamber. Moreover, no changes in histopathological or biochemical levels of tau, astrocytic, microglial or synaptic markers were observed. Chapter 4 sought to investigate alternative approaches to inducing ketosis in the brain by either administering BHB intracerebroventricularly (i.c.v.) or by using the acetoacetate (AcAc) diester as a dietary supplement in mice. We observed that i.c.v administration of BHB in 20 months old APP mice did not affect body weight or food intake. Consistent with the lack of effects on behavioral performance, amyloid and congophilic load were not different between APP mice infused with either saline or BHB. We also found that enteral administration of AcAc diester was well tolerated and induced peripheral ketosis for at least 3 hours. Acute ketosis, however, was not sufficient to attenuate behavioral deficits in old APP mice. Chronic dietary supplementation with AcAc was tested in control tet mice and was shown to effectively induce ketosis in mice fed a diet with normal contents of carbohydrates. Nonetheless, we observed that AcAc-induced ketosis was not significantly greater than levels induced by the ketogenic diet tested in our lab. Considering that KD did not rescue behavioral or histopathological features of either amyloid or tau depositing mouse models, we anticipated that dietary supplementation with AcAc would not likely modify the phenotype of the same mouse models tested previously. Taken together, our findings show that our custom made ketogenic diet was effective in inducing and sustaining ketosis and may play an important role in enhancing motor performance in mice. However, the lack of changes on the cognitive and histopathological phenotype of the models studied suggests that KD may not be a disease modifying therapeutic approach to AD. Moreover, calorie restriction showed inconsistent effects on behavioral and histopathological outcomes of a mouse model of tauopathies. Furthermore, dietary supplementation with acetoacetate diester was successful in inducing peripheral ketosis to the same extend as a ketogenic diet even in the context of normal carbohydrate intake, suggesting that it may be of therapeutic interest for diseases of hypometabolism but not a disease modifying therapy in mouse models of Alzheimer's pathology.

Obesity is one the few modifiable risk factors for breast cancer. Hence, an evaluation of the metabolic and cancer inhibitory effects of the obesity reversing strategies, calorie restriction (CR) and exercise, is important for breast cancer prevention. Additionally, a better understanding of the mechanisms underlying the effects of these interventions on cancer will provide scientific basis for therapeutic recommendations, and facilitate the identification of therapeutic agents for breast cancer treatment in obese patients. We found that CR is more effective than exercise in reversing the metabolic and cancer enhancing effects of obesity. Even at comparable levels of adiposity, CR effects on insulin resistance, energy balance related hormones levels, and metabolic genes expression in adipose tissue were more profound than those of exercise. The mechanism by which CR influences tumor progression is thought to involve molecules that respond to energy balance changes and control cell growth, such as the insulin-like growth factor-1 (IGF-1) and the mammalian target of rapamycin (mTOR). The mTOR inhibitor rapamycin decreased mammary tumor burden to levels comparable to CR. While established tumors did not display decreased mTOR activity, constitutively active mTOR was capable of overcoming some of the inhibitory effects of CR on tumor cells invasion and migration. Effects of increasing levels of CR on gene expression indicate that 30% and 40% CR, but not 20% CR, induce beneficial metabolic changes in the liver. However, 40% CR also increases apoptosis of hepatic cells which appears to be detrimental for the liver. IGF-1 infusion partially overcame the beneficial effects of CR on expression of tumor-related genes in the mammary fat pad and on mammary tumor growth. Taken together, our data show that CR, but not exercise, is able to reverse the metabolic and tumorigenic effects of obesity. Furthermore, the IGF-1 and mTOR pathways may mediate, at least in part, many of the beneficial effects of CR on metabolism and tumor progression. / text

Obesity is an established risk and progression factor for many types of cancer, including pancreatic and colon cancer, and is characterized by abnormal metabolic hormone production and a chronic low-grade state of inflammation. However, the links between obesity, hormones, inflammation and tumorigenesis in colon and pancreatic tissue are poorly understood. Calorie restriction (CR), an anti-obesity dietary regimen with potent anticancer effects, reduces serum metabolic hormones and protumorigenic cytokines. Insulin-like growth factor (IGF)-1 is a metabolic hormone that activates NF-[kappa]B, a key regulator of inflammation. NF-[kappa]B is a transcription factor that mediates transcription of many cancer- and inflammation-related genes and is upregulated in both colon and pancreatic cancer. We hypothesized that CR inhibits colon and pancreatic tumor cell growth through modulation of hormone-stimulated NF-[kappa]B activation and protumorigenic gene expression. To test this hypothesis, we used CR and ad libitum feeding to generate a lean and overweight (control) phenotype, respectively; in C57BL/6 mice transplanted with MC38 colon cancer cells or Panc 02 pancreatic cancer cells, and analyzed the effect of diet on circulating hormone levels, markers of inflammation, and tumor growth. We also investigated the in vitro effects of IGF-1 on NF-[kappa]B activation and downstream protumorigenic gene expression in MC38 and Panc 02 cells. CR, relative to control diet, reduced body weight, circulating IGF-1 levels, and transplanted MC38 and Panc 02 tumor growth, as well as protumorigenic gene expression in the MC38 and Panc 02 tumor microenvironment. IGF-1 increased cell viability, NF-[kappa]B nuclear translocation and DNA binding, transcriptional activation, and downstream gene expression of inflammation and other protumorigenic genes in MC38 colon cancer cells and Panc 02 pancreatic cancer cells in vitro. Knockdown studies of NF-[kappa]B in Panc 02 cells using si-RNA established that the IGF-1-induced increase in protumorigenic gene expression is mediated, at least partially, through an NF-[kappa]B-dependent mechanism. In conclusion, these findings in models of pancreatic and colon cancer help clarify the links between obesity, IGF-1, NF-[kappa]B-mediated inflammation, and cancer. This work provides the underpinnings for several new molecular targets and strategies to test in model systems and translational studies for preventing or controlling obesity-related cancer. / text

Sleep appears to play a critical role in regulating daytime functioning in children. However, few child-focused studies have used objective measures of sleep and examined its role in emotional functioning, memory, and attention. This dissertation consisted of 2 studies. Study 1 examined children’s typical sleep and how it correlates with daytime functioning in 32 typically developing children (14 boys, 18 girls), 8 to 12 years of age (M=9.8 y, SD=1.4). Participants wore actigraphs (recording devices that provide information about sleep and activity) for 1 week and then completed tasks to measure emotional functioning, memory, and attention. On average, children slept less than 9 h per night, which is approximately 1 h less than the recommended duration for this age. Older children had shorter sleep durations, higher sleep efficiency, and later sleep onset times. Correlational analyses revealed that within this group of typically developing children, small variations in sleep were associated with statistically significant effects on daytime functioning. Specifically, shorter sleep duration was associated with increased negative affective response, and lower sleep efficiency was associated with poorer performance on a divided attention task. Study 2 involved experimental manipulation of sleep duration in the same sample of children. Following a week of typical sleep, each child was randomly assigned to go to bed 1 h earlier for 4 nights (Extended condition) or 1 h hour later for 4 nights (Restricted condition) relative to their typical bedtime. Each child then completed the opposite condition. Following each condition, emotional functioning, memory, and attention were assessed using objective and subjective measures. The sleep manipulation was effective: the children slept significantly longer in the Extended (M=9.3 h, SD=0.6) versus Restricted (M=8.1 h, SD=0.7) condition, and children were significantly sleepier in the Restricted condition according to parent, child, and research assistant report. Positive affective response, emotion regulation, memory, and aspects of attention were worse in the Restricted, compared to Extended condition. These studies provide evidence that modest variations in sleep can have substantial effects on daytime functioning in children. Clinical implications are discussed, including the importance of identifying sleep problems and promoting healthy sleep habits in children.

Food restriction has been shown to affect responding for reward and has been manipulated to devalue reward. Reward density has been shown to alter responding in both first-order schedules and chain schedules. Devaluation has differential effects in first-order schedules and the links of chain schedules. The objective of the current study was to analyze the reward devaluation effect in a two-link chain schedule by manipulating food restriction and reward density in the proximal link; these variables had previously not been studied systematically. The chain schedule required rats to lever press according to a random interval 120-s schedule to turn on a light conditioned stimulus (CS). In the presence of the CS rats were rewarded for pulling a chain; the chain was active on a variable ratio (VR) 5 schedule of reinforcement for some rats, while the chain was on continuous reinforcement (CRF) for the other rats. Food restriction protocols were either 1-hr daily free feeding (1-hr feeding) or a daily ration to maintain weight at 80% of free feed controls (ration). Devaluing the CS while in the isolated proximal link was done by exposing trained rats to sessions of chain pulling in the presence of the CS but withholding reward. In subsequent lever press sessions without the CS, decreased responding was seen in rats that had undergone the devaluation procedure, but only in rats on the 1-hr feeding protocol. This devaluation effect was found in both the CRF and VR 5 schedules. Subsequent tests of lever pressing for the CS also revealed decreased responding. Post-test CS discrimination sessions demonstrated CS devaluation that has not been demonstrated previously. These results demonstrate that the isolated devaluation of the proximal link in a heterogeneous two-link chain schedule can result in decreased responding in the isolated first link. This effect is dependent on sufficient food restriction and demonstrates a measurable devaluation effect which is independent of the reward being present. This study also demonstrated that isolated devaluation of the second link can be subsequently measured in a post-test CS discrimination re-acquisition session regardless of food restriction, which had no significant effect in the session. The devaluation effect has not been demonstrated in a re-acquisition session before, rather responding in previous re-acquisition sessions were only affected by food restriction. / Thesis (Master, Psychology) -- Queen's University, 2007-09-11 11:49:20.814

To evaluate the impact of reduced truck tire pressure on strain response of low volume spring-restricted roads, research was conducted on two instrumented pavement sections in Manitoba, Canada. Tire pressure control systems tests were carried out at the sections in spring and fall 2009. Measured maximum tensile strain at the bottom of asphalt layer decreased by 15-20% when tire pressure was reduced by 50%. Measured strain at the bottom of asphalt layer in fall is about 50% less than in spring. The effects of gauge orientation, truck speed, and tire offset from the strain gauge were also analyzed. A finite element model with static load was developed and verified. The bearing capacity is lower in spring than in normal condition for flexible pavements subject to deep frost action. Reduced tire pressure is effective to reduce bottom up failure of the pavement, and is less effective to prevent rutting.

The present paper is an attempt to examine the restriction (determination) of the Process by circumstantial elements. Although the Process can be used absolutely, more often than not it is accompanied by other elements – non-circumstantial (objective complements) and circumstantial. The choice of a circumstantial element is mostly determined by the type of Process, tense and aspect. Two types of circumstantial elements are distinguished: 1) non-specific (i.e. circumstantial elements common to all Process types); 2) specific (i.e. circumstantial elements peculiar to a Process type).