Efficient Spread Research Articles

Oral Prion Neuroinvasion Occurs Independently of PrPC Expression in the Gut Epithelium.

The early replication of certain prion strains within Peyer's patches in the small intestine is essential for the efficient spread of disease to the brain after oral exposure. Our data show that orally acquired prions utilize specialized gut epithelial cells known as M cells to enter Peyer's patches. M cells express the cellular isoform of the prion protein, PrPC, and this may be exploited by some pathogens as an uptake receptor to enter Peyer's patches. This suggested that PrPC might also mediate the uptake and transfer of prions across the gut epithelium into Peyer's patches in order to establish infection. Furthermore, the expression level of PrPC in the gut epithelium could influence the uptake of prions from the lumen of the small intestine. To test this hypothesis, transgenic mice were created in which deficiency in PrPC was specifically restricted to epithelial cells throughout the lining of the small intestine. Our data clearly show that efficient prion neuroinvasion after oral exposure occurred independently of PrPC expression in small intestinal epithelial cells. The specific absence of PrPC in the gut epithelium did not influence the early replication of prions in Peyer's patches or disease susceptibility. Acute mucosal inflammation can enhance PrPC expression in the intestine, implying the potential to enhance oral prion disease pathogenesis and susceptibility. However, our data suggest that the magnitude of PrPC expression in the epithelium lining the small intestine is unlikely to be an important factor which influences the risk of oral prion disease susceptibility.IMPORTANCE The accumulation of orally acquired prions within Peyer's patches in the small intestine is essential for the efficient spread of disease to the brain. Little is known of how the prions initially establish infection within Peyer's patches. Some gastrointestinal pathogens utilize molecules, such as the cellular prion protein PrPC, expressed on gut epithelial cells to enter Peyer's patches. Acute mucosal inflammation can enhance PrPC expression in the intestine, implying the potential to enhance oral prion disease susceptibility. We used transgenic mice to determine whether the uptake of prions into Peyer's patches was dependent upon PrPC expression in the gut epithelium. We show that orally acquired prions can establish infection in Peyer's patches independently of PrPC expression in gut epithelial cells. Our data suggest that the magnitude of PrPC expression in the epithelium lining the small intestine is unlikely to be an important factor which influences oral prion disease susceptibility.

Host Protein BAG3 is a Negative Regulator of Lassa VLP Egress.

Lassa fever virus (LFV) belongs to the Arenaviridae family and can cause acute hemorrhagic fever in humans. The LFV Z protein plays a central role in virion assembly and egress, such that independent expression of LFV Z leads to the production of virus-like particles (VLPs) that mimic egress of infectious virus. LFV Z contains both PTAP and PPPY L-domain motifs that are known to recruit host proteins that are important for mediating efficient virus egress and spread. The viral PPPY motif is known to interact with specific host WW-domain bearing proteins. Here we identified host WW-domain bearing protein BCL2 Associated Athanogene 3 (BAG3) as a LFV Z PPPY interactor using our proline-rich reading array of WW-domain containing mammalian proteins. BAG3 is a stress-induced molecular co-chaperone that functions to regulate cellular protein homeostasis and cell survival via Chaperone-Assisted Selective Autophagy (CASA). Similar to our previously published findings for the VP40 proteins of Ebola and Marburg viruses, our results using VLP budding assays, BAG3 knockout cells, and confocal microscopy indicate that BAG3 is a WW-domain interactor that negatively regulates egress of LFV Z VLPs, rather than promoting VLP release. Our results suggest that CASA and specifically BAG3 may represent a novel host defense mechanism, whereby BAG3 may dampen egress of several hemorrhagic fever viruses by interacting and interfering with the budding function of viral PPxY-containing matrix proteins.

An adaptive efficient memristive ink drop spread (IDS) computing system

Active Learning Method (ALM) is one of the powerful tools in soft computing and it is inspired by the human brain capabilities in approaching complicated problems. ALM, which is in essence an adaptive fuzzy learning algorithm, tries to model a Multi-Input Single-Output system with several single-input single-output subsystems. Each of these subsystems is then modeled by an ink drop spread (IDS) plane. IDS operator, which is the main processing engine of ALM, extracts two kinds of informative features, Narrow Path and Spread, from each IDS plane without complicated computations. These features from all IDS planes are then aggregated in the inference engine. Despite the great performance of ALM in different applications, an efficient hardware implementation has remained a challenge, which is mainly due to considerably high memory requirement of IDS operation. In this paper, in a novel approach to IDS operation, we propose an abstract representation of the IDS planes which minimizes the memory requirement and the computational cost, and consequently, benefits the hardware implementation in terms of area and speed. The proposed approach is fully compatible with memristor-crossbar implementation with an adaptive learning capability. Simpler learning algorithm and higher speed make our proposed algorithm suitable for applications where real-time process, low-cost and small implementation are of high priority. Applications in the classification of real-world datasets and function approximation are provided to confirm the effectiveness of the algorithm. Eventually, the paper concludes that the proposed computing structure provides a synergy between artificial neural networks and fuzzy domains.

STAT2-Dependent Immune Responses Ensure Host Survival despite the Presence of a Potent Viral Antagonist.

ABSTRACTA pathogen encounter induces interferons, which signal via Janus kinases and STAT transcription factors to establish an antiviral state. However, the host and pathogens are situated in a continuous arms race which shapes host evolution toward optimized immune responses and the pathogens toward enhanced immune-evasive properties. Mouse cytomegalovirus (MCMV) counteracts interferon responses by pM27-mediated degradation of STAT2, which directly affects the signaling of type I as well as type III interferons. Using MCMV mutants lacking M27 and mice lacking STAT2, we studied the opposing relationship between antiviral activities and viral antagonism in a natural host-pathogen pair in vitro and in vivo. In contrast to wild-type (wt) MCMV, ΔM27 mutant MCMV was efficiently cleared from all organs within a few days in BALB/c, C57BL/6, and 129 mice, highlighting the general importance of STAT2 antagonism for MCMV replication. Despite this effective and relevant STAT2 antagonism, wt and STAT2-deficient mice exhibited fundamentally different susceptibilities to MCMV infections. MCMV replication was increased in all assessed organs (e.g., liver, spleen, lungs, and salivary glands) of STAT2-deficient mice, resulting in mortality during the first week after infection. Taken together, the results of our study reveal the importance of cytomegaloviral interferon antagonism for viral replication as well as a pivotal role of the remaining STAT2 activity for host survival. This mutual influence establishes a stable evolutionary standoff situation with fatal consequences when the equilibrium is disturbed.IMPORTANCE The host limits viral replication by the use of interferons (IFNs), which signal via STAT proteins. Several viruses evolved antagonists targeting STATs to antagonize IFNs (e.g., cytomegaloviruses, Zika virus, dengue virus, and several paramyxoviruses). We analyzed infections caused by MCMV expressing or lacking the STAT2 antagonist pM27 in STAT2-deficient and control mice to evaluate its importance for the host and the virus in vitro and in vivo. The inability to counteract STAT2 directly translates into exaggerated IFN susceptibility in vitro and pronounced attenuation in vivo. Thus, the antiviral activity mediated by IFNs via STAT2-dependent signaling drove the development of a potent MCMV-encoded STAT2 antagonist which became indispensable for efficient virus replication and spread to organs required for dissemination. Despite this clear impact of viral STAT2 antagonism, the host critically required the remaining STAT2 activity to prevent overt disease and mortality upon MCMV infection. Our findings highlight a remarkably delicate balance between host and virus.

Direct formation of transfer-free graphene as current spreading layers on n-ZnO nanorods/p-GaN light-emitting diodes

Transfer-free graphene has been directly grown on ZnO nanorods (NRs)/p-GaN LEDs by a feasible approach involving rapid thermal annealing of amorphous carbon and nickel layers. Compared with conventional ZnO NRs/p-GaN LEDs without a current spreading layer, the current–voltage characteristic and electroluminescence performance are enhanced, mainly attributed to more efficient current spreading by the transfer-free graphene that conformally covers the entire surface of ZnO NRs, leading to better carrier injection. It is hence expected that our scheme will be of great importance for nanostructured LED arrays with large-scale fabrication.

Melt spreading behavior, microstructure evolution and wear resistance of selective laser melting additive manufactured AlN/AlSi10Mg nanocomposite

The AlN/AlSi10Mg nanocomposites were successfully fabricated by selective laser melting using the mixture powder of AlSi10Mg and AlN particles with the weight ratio of 99:1. The surface morphology, densification behavior, microstructure features of the distribution state and size of nanoscale AlN particles combined with the grain sizes and the thickness of the eutectic phase within the matrix and the wear resistance were highly sensitive to the processing parameters. The appearance of the oxidation on the melt would promote the formation of defects due to the contrast variation of the surface tension gradient and the resultant radially inward flow, resulting in the formation of the continuous gaps between solidified tracks. However, the efficient melt spreading, the wetting behavior and the resultant high surface quality and the high densification rate were realized for the application of the high scan speed (>200 mm/s), due to the surface tension gradient and the resultant radially outward convection. The AlN nanoparticles tended to distribute in the grain border and the center region while the aggregation into clusters at high scan speed due to the high viscosity and the insufficient rearrangement. At the optimized laser volume energy density of 420 J/mm3, the nanocomposite showed the strain-hardened adherent tribolayer with the lowest wear rate of 3.4 × 10−4 mm3 N−1 m−1due to the high densification rate, nanoscale AlN particle and fine grain size of the matrix.

Nonenvelopment Role for the ESCRT-III Complex during Human Cytomegalovirus Infection.

Secondary envelopment of human cytomegalovirus (HCMV) occurs through a mechanism that is poorly understood. Many enveloped viruses utilize the endosomal sorting complexes required for transport (ESCRTs) for viral budding and envelopment. Although there are conflicting reports on the role of the ESCRT AAA ATPase protein VPS4 in HCMV infection, VPS4 may act in an envelopment role similar to its function during other viral infections. Because VPS4 is normally recruited by the ESCRT-III complex, we hypothesized that ESCRT-III subunits would also be required for HCMV infection. We investigated the role of ESCRT-III, the core ESCRT scission complex, during the late stages of infection. We show that inducible expression of dominant negative ESCRT-III subunits during infection blocks endogenous ESCRT function but does not inhibit virus production. We also show that HCMV forms enveloped intracellular and extracellular virions in the presence of dominant negative ESCRT-III subunits, suggesting that ESCRT-III is not involved in the envelopment of HCMV. We also found that as with ESCRT-III, inducible expression of a dominant negative form of VPS4A did not inhibit the envelopment of virions or reduce virus titers. Thus, HCMV does not require the ESCRTs for secondary envelopment. However, we found that ESCRT-III subunits are required for efficient virus spread. This suggests a role for ESCRT-III during the spread of HCMV that is independent of viral envelopment.IMPORTANCE Human cytomegalovirus (HCMV) is a prevalent opportunistic pathogen in the human population. For neonatal and immunocompromised patients, HCMV infection can cause severe and possibly life-threatening complications. It is important to define the mechanisms of the viral replication cycle in order to identify potential targets for new therapies. Secondary envelopment, or acquisition of the membrane envelope, of HCMV is a mechanism that needs further study. Using an inducible fibroblast system to carefully control for the toxicity associated with blocking ESCRT-III function, this study determines that the ESCRT proteins are not required for viral envelopment. However, the study does discover a nonenvelopment role for the ESCRT-III complex in the efficient spread of the virus. Thus, this study advances our understanding of an important process essential for the replication of HCMV.

Long-Distance Spread of Verticillium dahliae Through Rivers and Irrigation Systems.

Verticillium dahliae Kleb. is a soilborne pathogen causing Verticillium wilt disease on several hosts. The pathogen survival structure (i.e., microsclerotia) can be efficiently spread by different dispersal methods. In the present study, the medium to long dispersal spread of the pathogen through rivers and irrigation canals was investigated. Samples of sediments (n = 29) were gathered from eight Lebanese rivers and three regional irrigation canals, in addition to samples of soil particles and plant residues (n = 14) from irrigation filters in commercial orchards. Specific conventional and real-time nested polymerase chain reaction assays detected the pathogen in six rivers-Al Kabir, Al Bared, Litani, Al Awali, Ostwan, and Litani South-and in all sampled canals-Ostwan, Al Bared, and Litani Canal 900. Starting DNA quantities ranged from 0.2 pg to 21.318 ng and an inoculum density, determined by a traditional plating method, varied between nondetectable and 0.2 microsclerotia/g. Viable V. dahliae microsclerotia were also found in residues collected from mesh-type irrigation filters of five commercial orchards. This study confirms that water is an important inoculum source of V. dahliae, being involved in the efficient spread of microsclerotia in Lebanese agricultural areas.

Incidence of Grapevine Leafroll Disease: Effects of Grape Mealybug (Pseudococcus maritimus) Abundance and Pathogen Supply.

Studies of spatiotemporal dynamics are central to efforts to characterize the epidemiology of infectious disease, such as mechanism of pathogen spread and pathogen or vector sources in the landscape, and are critical to the development of effective disease management programs. To that end, we conducted a multi-year study of 20 vineyard blocks in coastal northern California to relate the dynamics of a mealybug vector, Pseudococcus maritimus (Ehrhorn) (Hemiptera: Pseudococcidae), to incidence of grapevine leafroll disease (GLD). In each vineyard block, a subset of vines were scored visually for relative mealybug abundance, disease was quantified by visual assessment, and virus presence was verified using standard laboratory molecular assays. GLD incidence was analyzed with a classification and regression tree, and with a hierarchical model that also captured variability among blocks and heterogeneity within blocks. Both analyses found strong interannual variability in incidence, with the hierarchical model also capturing substantial between- and within-block heterogeneity, but with significant contributions of vector abundance and pathogen supply (prior disease incidence) to the frequency of newly diseased vines. These results strengthen further the conclusion that mealybug vectors are causally related to pathogen spread in this system and are therefore an important target for management. Moreover, they are consistent with relatively efficient secondary spread of the pathogen, suggesting an important role for the removal of diseased vines as a tool to mitigate further damage.

The fastest spreader in SIS epidemics on networks

Identifying the fastest spreaders in epidemics on a network helps to ensure an efficient spreading. By ranking the average spreading time for different spreaders, we show that the fastest spreader may change with the effective infection rate of a SIS epidemic process, which means that the time-dependent influence of a node is usually strongly coupled to the dynamic process and the underlying network. With increasing effective infection rate, we illustrate that the fastest spreader changes from the node with the largest degree to the node with the shortest flooding time. (The flooding time is the minimum time needed to reach all other nodes if the process is reduced to a flooding process.) Furthermore, by taking the local topology around the spreader and the average flooding time into account, we propose the spreading efficiency as a metric to quantify the efficiency of a spreader and identify the fastest spreader, which is adaptive to different infection rates in general networks.

Optimising in-situ nitridation in piled aluminium flakes for novel closed cell composites with high fracture stress and toughness

Modified aluminium foams, such as syntactic aluminium foams (SAFs) that contain tiny ceramic hollow spheres, are widely used for the protection of modern lightweight vehicles in mechanical impacts. Due to the typical compromises between strength and toughness, conventional SAFs absorb <5 J g−1 of mechanical energy before fracture.In this study, we demonstrate that a nacre-like structure of piled aluminium flakes with in-situ grown AlN layers can provide a specific toughness of up to ~50 J g−1. At the optimum toughness, the compressive yield strength σ0.2%, fracture strength σT and strain εT reach ≈110 MPa, 481 MPa and 0.35, respectively. The improved properties originate from the efficient nitridation-driven spreading of the partially melted Al of the flakes through the permeable nitride layers. In an N2 atmosphere at about 833 K, an optimal composite structure is formed with a porosity ϕE and AlN volume fraction vAlN of 0.26 and 0.12, respectively. The pre- and post-optimal annealing temperatures lead to a relatively small area of Al-AlN bonding, as a result of overgrowth and undergrowth of the AlN surfaces, respectively.This straightforward technology offers an affordable way to produce novel lightweight composites for state-of-the-art protection of vehicles and dynamic machinery in many industrial areas.

Dynamic Logistic Map Based Spread Spectrum Modulation in Wireless Channels

Generation of an efficient spreading code in Spread Spectrum Modulation (SSM) is always challenging due to considerations like optimum sequence length, physical layout of registers and power requirements. In this article, a design of a dynamic chaotic spreading sequence for application in a Direct Sequence Spread Spectrum (DS SS) based system with the considerations of wireless channels (Rayleigh and Rician) are presented. Generation of dynamic chaotic sequence for application in linear and nonlinear channels is done and a comparison with static chaotic sequence is presented. Evaluation of performance is done in terms of bit error rate (BER), computational time, mutual information and signal power for faded channel taking into considerations of different modulation schemes, which finally dictates the efficiency of the generated code. The performance of the generated dynamic logistic map-based sequence is compared to that obtained from Gold code under equivalent conditions.

On the emergent dynamics and synchronization of β-cells networks in response to space-time varying glucose stimuli

Recent findings based on calcium fluorescence imaging of pancreatic islets, also combined with optogenetic techniques, showed that β-cells synchronization underlie a small-world and scale-free functional organization, where specified hubs are responsible of the emergent coordination in electrical activity. Despite these features were suggested to be linked to an efficient spreading of information and calcium waves, it is still unclear from what they emerge, if they can still be observed when different dynamical variables are used to build functional networks, and how they vary upon changes in control parameters. In this work we investigate this aspect with a novel hybrid discrete-continuum mathematical model, coupling the stochastic electrical dynamics of β-cell clusters to nonlinear reaction–diffusion of glucose. By analyzing cells activity with the use of dynamical functional networks computed on the correlations between cells membrane voltage signals, we recover functional features in accordance to experimental observations. We further show that such properties are observed during specific phases of the complex electrical bursting oscillation, and are affected by glucose diffusion. These results suggest that functional properties derived from experimental calcium signals, on a time scale on the order of tens of seconds, are also recovered at a much faster time scale, i.e., on the order of hundreds of milliseconds. We finally describe how such functional features are strongly linked to synchronization patterns, in which coordinated sub-clusters of cells naturally emerge from the underlying dynamics.

Bacterial Surface Spreading Is More Efficient on Nematically Aligned Polysaccharide Substrates.

Biofilm-forming bacteria typically deposit layers of polysaccharides on the surfaces they inhabit; hence, polysaccharides are their immediate environment on such surfaces. Previously, we showed that many biofilm-forming bacteria preferentially spread in the direction of aligned and densely packed polysaccharide fibers in compressed substrates, a behavior we referred to as polymertropism. This arrangement of polysaccharide fibers is likely to be similar to that found in the "slime" trails deposited by many biofilm-forming bacteria and would explain previous observations that bacteria tend to follow these trails of polysaccharides. Here, we show that groups of cells or flares spread more rapidly on substrates containing aligned and densely packed polysaccharide fibers. Flares also persist longer, tend to hold their trajectories parallel to the long axes of polysaccharide fibers longer, and ultimately show an increase in displacement away from their origin. On the basis of these findings and others, we propose a model for polymertropism. Namely, we suggest that the packing of the aligned polymers increases the efficiency of surface spreading in the direction of the polymer's long axes; therefore, bacteria tend to spread more rapidly in this direction. Additional work suggests that bacteria can leverage polymertropism, and presumably more efficient surface spreading, for a survival advantage. In particular, when two bacterial species were placed in close proximity and in competition with each other, the ability of one species to move rapidly and directly away from the other by utilizing the aligned polymers of compressed agar substrates led to a clear survival benefit.IMPORTANCE The directed movement of bacteria on compressed substrates was first described in the 1940s and referred to as elasticotaxis (R. Y. Stanier, J Bacteriol 44:405-412, 1942). More recently, this behavior was referred to as polymertropism, as it seems to be a response to the nematic alignment and tight packing of polymers in the substrate (D. J. Lemon, X. Yang, P. Srivastava, Y. Y. Luk, A. G. Garza, Sci Rep 7:7643, 2017, https://doi.org/10.1038/s41598-017-07486-0). The data presented here suggest that bacteria are more efficient at surface spreading when the polymers in the substrate are arranged in this manner. These data also suggest that bacteria can leverage polymertropism, and presumably more efficient surface spreading, for a survival advantage. Namely, one bacterial species was able to use its strong polymertropism response to escape from and survive competition with another species that normally outcompetes it.

Broadcasting multiple messages in the 1-in port model in optimal time

In the 1-in port model, every vertex of a synchronous network can receive at most one message in each time unit. We consider simultaneous broadcasting of multiple messages from the same source or from distinct sources in such networks with an additional restriction that every received message can be sent out to neighbors only in the next time unit and never to already informed vertex. We use a general concept of level-disjoint partitions developed for this scenario. Here we introduce a subgraph extension technique for efficient spreading information within this concept. Surprisingly, this approach with so called biwheels leads to simultaneous broadcasting of optimal number of messages on a wide class of graphs in optimal time. In particular, we provide tight results for bipartite tori, meshes, hypercubes, Knodel graphs, circulant graphs. We also propose several open problems and conjectures.

Enhancing the Spreading Behavior on Pulmonary Mucus Mimicking Subphase via Catanionic Surfactant Solutions: Toward Effective Drug Delivery through the Lungs.

Effective and efficient spreading of drug formulations on the pulmonary mucosal layer is key to successful delivery of therapeutics through the lungs. The pulmonary mucus layer, which covers the airway surface, acts as a barrier against therapeutic agents, especially in the case of chronic lung diseases due to increased thickness and viscosity of the mucus. Therefore, spreading of the drug formulations on the airways gets harder. Although spreading experiments have been conducted with different types of formulations on mucus-mimicking subphases, a highly effective formulation is yet to be discovered. Adding surfactant to such formulations decreases the surface tension and triggers the Marangoni forces to enhance the spreading behavior. In this study, catanionic (cationic + anionic) surfactant mixtures composed of dodecyltrimethylammonium bromide (DTAB) and dioctyl sulfosuccinate sodium salt (AOT) mixed at various mole ratios are prepared and their spreading behavior on both mucin and cystic fibrosis (CF) mucus models is investigated for the first time in the literature. Synergistic interaction is obtained between the components of the DTAB/AOT mixtures, and this interaction has enhanced the spreading of the formulation drop on both the mucin and CF mucus models when compared with the spreading performances of selected conventional surfactants. It is proposed that the catanionic surfactant mixtures, especially when mixed at the molar ratios of 8/2 and 7/3 (DTAB/AOT), improve the spreading even on the cystic fibrosis sputum model. As it is vital to transport a sufficient amount of drug to the targeted region for the treatment of diseases, this study presents an important application of the fundamentals of colloidal science to pharmaceutical nanotechnology.

The Emerging Threat of Antifungal Resistance in Transplant Infectious Diseases

The global emergence of antifungal resistance among Candida spp. and Aspergillus spp. will disproportionately affect transplantation recipients, who are prone to invasive fungal disease. Invasive candidiasis is increasingly caused by non-albicans Candida species with reduced susceptibility to first-line antifungals. Echinocandin resistance in Candida glabrata is increasing in some settings. Candida auris has rapidly emerged as a global concern due to multidrug resistance and efficient nosocomial spread in healthcare settings. Azole-resistant Aspergillus fumigatus is already an important concern in some European countries and is increasingly reported elsewhere, possibly driven by agricultural use of triazole fungicides. Antifungal resistance is anticipated to expand among these and other common fungal pathogens. Culture-independent detection methods will become more important for rapid diagnosis and to guide empiric therapy. Antifungal stewardship is of critical importance to conserve our limited antifungal armamentarium for transplantation recipients and other vulnerable patients.

Human-Specific Adaptations in Vpu Conferring Anti-tetherin Activity Are Critical for Efficient Early HIV-1 Replication In Vivo

The HIV-1-encoded accessory protein Vpu exerts several immunomodulatory functions, including counteraction of the host restriction factor tetherin, downmodulation of CD4, and inhibition of NF-κB activity to facilitate HIV-1 infection. However, the relative contribution of individual Vpu functions to HIV-1 infection invivo remained unclear. Here, we used a humanized mouse model and HIV-1 strains with selective mutations in vpu to demonstrate that the anti-tetherin activity of Vpu is a prerequisite for efficient viral spread during the early phase of infection. Mathematical modeling and gain-of-function mutations in SIVcpz, the simian precursor of pandemic HIV-1, corroborate this finding. Blockage of interferon signaling combined with transcriptome analyses revealed that basal tetherin levels are sufficient to control viral replication. These results establish tetherin as a key effector of the intrinsic immune defense against HIV-1, and they demonstrate that Vpu-mediated tetherin antagonism is critical for efficient viral spread during the initial phase of HIV-1 replication.

Effects of Different Material Total Solid on Biogas Production Characteristics

In China, livestock manure emission has resulted in severe pollution to the environment and it is an efficient spreading agent of diseases. For this reason, the biogas has gotten a rapid development in the past few decades. As a kind of renewable and clean energy, many studies have indicated the prospect of biogas to replace fossil fuels in the future. However, the methane industrial production process is unstable due to various factors. Therefore, it is necessary to enhance the biogas fermentation efficiency. In this paper, the influences of the raw materials and the total solids (TS) concentration on biogas production characteristics are studied, where the utilization of raw materials can be reflected by the biogas production rate in the results. The results showed the anaerobic fermentation cycle is prolonged and biogas yield increases, but the utilization decreases with TS increases.

Chapter 5 - The role of the immune system in prion infection

Prion diseases are a unique group of chronic neurodegenerative diseases that affect humans and certain domestic and free-ranging animal species. Many natural prion diseases are acquired peripherally, such as by ingestion of contaminated food or pasture. Although the pathology during prion disease appears to be restricted to the central nervous system, where it causes extensive neurodegeneration, some prion diseases accumulate to high levels within the secondary lymphoid tissues of the host's immune system as they make their journey from the site of infection to the brain. The replication of prions within these tissues is essential for the efficient spread of disease to the brain. Moreover, the immune system has a profound influence on the development of disease within the central nervous system. This chapter describes the interactions between prions and the host's immune system. Particular emphasis is given to studies which have helped to identify the key tissues, cells, and molecules which the prions exploit to facilitate their propagation from peripheral sites of exposure (such as the intestine) to the brain. This chapter also describes how prion disease pathogenesis and susceptibility may be influenced by inflammation, co-infection with other pathogens, and aging. A thorough understanding of the factors which influence prion disease susceptibility is important as it may help to identify important targets for therapeutic intervention and to help determine the risk of susceptibility to novel peripherally acquired prion diseases.