Innate and Adaptive Immunity in Orolabial Herpes Simplex

Oral mucosa is a frequent site of primary herpes simplex virus type 1 (HSV-1) infection, whereas intraoral recurrent disease is very rare. Instead, reactivation from latency predominantly results in asymptomatic HSV shedding to saliva or recurrent labial herpes (RLH) with highly individual frequency. The current study aimed to elucidate the role of human oral innate and acquired immune mechanisms in modulation of HSV infection in orolabial region. Saliva was found to neutralize HSV-1, and to protect cells from infection independently of salivary antibodies. Neutralization capacity was higher in saliva from asymptomatic HSV-seropositive individuals compared to subjects with history of RLH or seronegative controls. Neutralization was at least partially associated with salivary lactoferrin content. Further, lactoferrin and peroxidase-generated hypothiocyanite were found to either neutralize HSV-1 or interfere with HSV-1 replication, whereas lysozyme displayed no anti-HSV-1 activity. Lactoferrin was also shown to modulate HSV-1 infection by inhibiting keratinocyte proliferation. RLH susceptibility was further found to be associated with Th2 biased cytokine responses against HSV, and a higher level of anti- HSV-IgG with Th2 polarization, indicating lack of efficiency of humoral response in the control of HSV disease. In a three-dimensional cell culture, keratinocytes were found to support both lytic and nonproductive infection, suggesting HSV persistence in epithelial cells, and further emphasizing the importance of peripheral immune control of HSV. These results suggest that certain innate salivary antimicrobial compounds and Th1 type cellular responses are critically important in protecting the host against HSV disease, implying possible applications in drug, vaccine and gene therapy design.

Exploring Adaptive Implementation of On-Chip Networks

As technology geometries have shrunk to the deep submicron regime, the communication delay and power consumption of global interconnections in high performance Multi- Processor Systems-on-Chip (MPSoCs) are becoming a major bottleneck. The Network-on- Chip (NoC) architecture paradigm, based on a modular packet-switched mechanism, can address many of the on-chip communication issues such as performance limitations of long interconnects and integration of large number of Processing Elements (PEs) on a chip. The choice of routing protocol and NoC structure can have a significant impact on performance and power consumption in on-chip networks. In addition, building a high performance, area and energy efficient on-chip network for multicore architectures requires a novel on-chip router allowing a larger network to be integrated on a single die with reduced power consumption. On top of that, network interfaces are employed to decouple computation resources from communication resources, to provide the synchronization between them, and to achieve backward compatibility with existing IP cores. Three adaptive routing algorithms are presented as a part of this thesis. The first presented routing protocol is a congestion-aware adaptive routing algorithm for 2D mesh NoCs which does not support multicast (one-to-many) traffic while the other two protocols are adaptive routing models supporting both unicast (one-to-one) and multicast traffic. A streamlined on-chip router architecture is also presented for avoiding congested areas in 2D mesh NoCs via employing efficient input and output selection. The output selection utilizes an adaptive routing algorithm based on the congestion condition of neighboring routers while the input selection allows packets to be serviced from each input port according to its congestion level. Moreover, in order to increase memory parallelism and bring compatibility with existing IP cores in network-based multiprocessor architectures, adaptive network interface architectures are presented to use multiple SDRAMs which can be accessed simultaneously. In addition, a smart memory controller is integrated in the adaptive network interface to improve the memory utilization and reduce both memory and network latencies. Three Dimensional Integrated Circuits (3D ICs) have been emerging as a viable candidate to achieve better performance and package density as compared to traditional 2D ICs. In addition, combining the benefits of 3D IC and NoC schemes provides a significant performance gain for 3D architectures. In recent years, inter-layer communication across multiple stacked layers (vertical channel) has attracted a lot of interest. In this thesis, a novel adaptive pipeline bus structure is proposed for inter-layer communication to improve the performance by reducing the delay and complexity of traditional bus arbitration. In addition, two mesh-based topologies for 3D architectures are also introduced to mitigate the inter-layer footprint and power dissipation on each layer with a small performance penalty.

Adaptive Routing Approaches for Networked Many-Core Systems

Through advances in technology, System-on-Chip design is moving towards integrating tens to hundreds of intellectual property blocks into a single chip. In such a many-core system, on-chip communication becomes a performance bottleneck for high performance designs. Network-on-Chip (NoC) has emerged as a viable solution for the communication challenges in highly complex chips. The NoC architecture paradigm, based on a modular packet-switched mechanism, can address many of the on-chip communication challenges such as wiring complexity, communication latency, and bandwidth. Furthermore, the combined benefits of 3D IC and NoC schemes provide the possibility of designing a high performance system in a limited chip area. The major advantages of 3D NoCs are the considerable reductions in average latency and power consumption. There are several factors degrading the performance of NoCs. In this thesis, we investigate three main performance-limiting factors: network congestion, faults, and the lack of efficient multicast support. We address these issues by the means of routing algorithms. Congestion of data packets may lead to increased network latency and power consumption. Thus, we propose three different approaches for alleviating such congestion in the network. The first approach is based on measuring the congestion information in different regions of the network, distributing the information over the network, and utilizing this information when making a routing decision. The second approach employs a learning method to dynamically find the less congested routes according to the underlying traffic. The third approach is based on a fuzzy-logic technique to perform better routing decisions when traffic information of different routes is available. Faults affect performance significantly, as then packets should take longer paths in order to be routed around the faults, which in turn increases congestion around the faulty regions. We propose four methods to tolerate faults at the link and switch level by using only the shortest paths as long as such path exists. The unique characteristic among these methods is the toleration of faults while also maintaining the performance of NoCs. To the best of our knowledge, these algorithms are the first approaches to bypassing faults prior to reaching them while avoiding unnecessary misrouting of packets. Current implementations of multicast communication result in a significant performance loss for unicast traffic. This is due to the fact that the routing rules of multicast packets limit the adaptivity of unicast packets. We present an approach in which both unicast and multicast packets can be efficiently routed within the network. While suggesting a more efficient multicast support, the proposed approach does not affect the performance of unicast routing at all. In addition, in order to reduce the overall path length of multicast packets, we present several partitioning methods along with their analytical models for latency measurement. This approach is discussed in the context of 3D mesh networks.

Decision support systems in wood procurement. A Review

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