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Limonene is a monoterpenoid compound, which is founded in a lot of plants&rsquo, essential oils with good antibacterial activity against food-borne pathogens, but it has an ambiguous antimicrobial susceptibility and mechanism against Listeria monocytogenes (L. monocytogenes). In this study, the antimicrobial susceptibility of Limonene to L. monocytogenes was studied, and some new sights regarding its antibacterial mechanism were further explored. Scanning electron microscopy (SEM) verified that limonene caused the destruction of the cell integrity and wall structure of L. monocytogenes. The increase in conductivity and the leakage of intracellular biomacromolecules (nucleic acids and proteins) confirmed that limonene had an obvious effect on cell membrane permeability. The results of Propidium Iodide (PI) fluorescence staining were consistent with the results of the conductivity measurements. This indicated that limonene treatment caused damage to the L. monocytogenes cell membrane. Furthermore, the decrease in ATP content, ATPase (Na+K+-ATPase, Ca2+-ATPase) activity and respiratory chain complex activity indicated that limonene could hinder ATP synthesis by inhibiting the activity of the respiratory complex and ATPase. Finally, differential expression of proteins in the respiratory chain confirmed that limonene affected respiration and energy metabolism by inhibiting the function of the respiratory chain complex.

Dictionary of Contemporary Chinese (DCC) is an authoritative, human-oriented dictionary that defines word senses in natural language. The Contemporary Chinese Grammatical Knowledge Base (GKB) uses detailed syntactic information to describe word senses. The combination of DCC and GKB will be helpful for studying the problem of word sense distinction and word sense disambiguation (WSD). In this paper, we defined the types of alignment of the individual word sense and the types of word sense granularity correspondence. We also designed semi-auto algorithm that used the similarity of definitions and example sentences to compute words sense alignment. The algorithm turned definitions and example sentences into word sequences, and then used sememes of HowNet to compute the similarity of word sequences. The individual word sense alignment and word sense granularity correspondence are constructed based on the similarity. This algorithm was used to construct the individual word sense alignment table and word sense granularity correspondence relation of intersection words of the two dictionaries. The results of word sense granularity correspondence relation analyzing showed that the word sense alignment between DCC and GKB are quite complicated. The completely “equal” sense mainly exists in the monosemy. Generally speaking, the word sense granularity of GKB is larger than that of DCC. There are “no correspondence” word senses in both dictionaries. The integration of semantic meaning and syntactic information of the two dictionaries can be achieved based on sense alignment and will be helpful for solving natural language processing problems such as WSD.

The meaning expressed by elements of negation, degree, tense and aspect, modality and mood in a sentence attached to the basic predicate-centered proposition is called logic complement semantics, which is embodied as semantic constraints of logic semantic operators to the predicate. Logic complement semantics is the effective supplement to the basic logic meaning, and is important for deep understanding of sentence semantics. In this paper, a Chinese logic complement semantics annotation framework aimed for deep semantic comprehension is preliminarily practiced, which constructed a classification system including negation, degree, tense and aspect, and mood on the basis of existing research results, built the operator dictionary, established rules for annotation, and annotated logic complement semantics operators of a sentence which have been tagged with basic propositional arguments. Finally, the statistics of the annotation result are presented, and the problems in annotation process are analyzed.

With the progress in space technologies, the future integrated network incorporating ground internet and spatial network is emerging as the times require. The particularity of space application requires secure transmission and storage of mass data. These data contain a lot of repeating data, which occupy an enormous storage space and many network bandwidth resources. How to efficiently delete the repeating data while ensuring the data confidentiality poses a great challenge to the data deduplication technology. This paper proposes a secure data deduplication scheme to be implemented in the integrated network. In this scheme, many key servers are distributed into the entire network so that the client can be linked to several nearby key servers at any time. Then a key generated by a key server is chosen randomly. The key fingerprint is saved to the key fingerprint server to ensure that the data with the same attributes can be encrypted by the same key for the purpose of ciphertext deduplication. The theoretical analysis shows that, compared with DupLESS and threshold blind signature, this scheme improves the security of the deduplication system, avoids a single point of failure, simplifies the signature verification, and thus reduces the computational overhead at the client side.

Antibody-dependent activation of myeloid cells within the glomerulus plays a central role in rapidly progressive forms of glomerulonephritis. The spleen tyrosine kinase (Syk) is expressed by all leukocytes, except mature T cells, and is required for signalling via the B-cell receptor, Fc receptors, and some integrins. Syk has been proposed as a therapeutic target in glomerulonephritis. However, little is known of Syk activation in human kidney disease, while studies in experimental glomerulonephritis using non-selective Syk inhibitors require validation via conditional gene deletion. The current study addressed both of these important points. Syk activation (Tyr(525/526) phosphorylation) was examined in a cohort of 96 patients with different glomerulonephritides. Syk activation was evident in infiltrating leukocytes, mainly neutrophils and macrophages, in 36/40 cases of rapidly progressive glomerulonephritis. In contrast, non-proliferative diseases showed little or no Syk activation. Glomerular and interstitial cells exhibiting Syk activation correlated with renal function and systemic inflammation. Next, we examined mice with conditional Syk gene deletion in myeloid cells (Syk(My) ) versus Syk(f/f) littermate controls in nephrotoxic serum nephritis - a model of rapidly progressive glomerulonephritis. Control Syk(f/f) mice featured a transient neutrophil influx at 3 h and severe disease on day 9 of nephrotoxic serum nephritis, with crescent formation, macrophage infiltration, inflammation, kidney fibrosis, and renal dysfunction. In contrast, Syk(My) mice had significantly reduced neutrophil and macrophage infiltration despite equivalent glomerular deposition of humoral reactants. Syk(My) mice exhibited reduced crescent formation, inflammation, and fibrosis, with improved renal function on day 9 of nephrotoxic serum nephritis. In conclusion, Syk activation is prominent in infiltrating myeloid cells in human rapidly progressive glomerulonephritis, and functional studies demonstrate that Syk deletion in myeloid cells is protective in mouse nephrotoxic serum nephritis.

Background Organ transplantation into sensitized patients with preexisting donor-specific antibodies (DSA) is very challenging. Spleen tyrosine kinase (Syk) promotes leukocyte recruitment and activation via signaling through various cell surface receptors. We investigated whether a selective Syk inhibitor (GS-492429) could suppress antibody-mediated rejection (AMR) in a rat model of AMR in sensitized recipients. Methods Recipient Lewis rats (RT1) were immunized with donor (Dark Agouti, RT1) spleen cells (day -5). Recipients underwent bilateral nephrectomy and orthotopic renal transplantation (day 0). Cellular rejection was minimized by tacrolimus treatment from day -1. Groups received GS-492429 (30 mg/kg, twice a day) (n = 11) or vehicle (n = 12) from 1 hour before transplantation until being killed on day 3. Results Vehicle-treated recipients developed graft dysfunction on day 1 which rapidly worsened by day 3. Histology showed severe damage (thrombosis, acute tubular injury, capillaritis) and infiltration of many Syk leukocytes. GS-492429 did not affect graft dysfunction on day 1, but treatment reduced allograft damage and prevented the rapid deterioration of graft function on day 3. GS-492429 reduced the prominent macrophage infiltrate and reduced the M1 proinflammatory response. Neutrophil and NK cell infiltration and capillary thrombosis were also significantly reduced by GS-492429 treatment. Serum DSA levels and the deposition of IgG and C4d in the allograft were equivalent in the 2 groups. Conclusions Treatment with a Syk inhibitor significantly reduced renal allograft injury in a model of severe antibody-mediated damage in highly sensitized recipients. Further studies are warranted to determine whether Syk inhibition is a potential adjunctive treatment in clinical AMR.

Three indoor (residential home, dormitory, and office) and one outdoor concentrations of PM

Modality is the speaker’s subject idea processed and expressed for sentence objective express system. Modal meaning is important for deep understanding of sentence semantics. In this paper, a Chinese modality annotation framework aimed for deep semantic understanding is preliminarily practiced, which constructed a modal meaning classification system on the basis of existing research results, built the modal operator dictionary, established rules for annotation, and annotated modal operators of a sentence which have been tagged basic proposition arguments.

Depletion and adoptive transfer studies have demonstrated that macrophages induce glomerular lesions in experimental anti-glomerular basement membrane (anti-GBM) glomerulonephritis. However, there is no current therapeutic strategy that can rapidly and selectively remove these cells from the glomerulus in order to halt disease development. This study examined whether inhibition of the receptor for macrophage colony-stimulating factor (known as c-fms), which is selectively expressed by monocyte/macrophages, can eliminate the macrophage infiltrate in a rat model of crescentic anti-GBM glomerulonephritis. Wistar-Kyoto rats were treated with 10 or 30 mg/kg bid of fms-I (a selective c-fms kinase inhibitor) from the time of anti-GBM serum injection until being killed 1, 5 or 14 days later. fms-I treatment had only a minor effect upon the glomerular macrophage infiltrate on day 1 and did not prevent the subsequent induction of proteinuria. However, fms-I treatment reduced the glomerular macrophage infiltrate by 60% at day 5 and completely reversed the macrophage infiltrate by day 14. In addition, fms-I treatment downregulated the glomerular expression of pro-inflammatory molecules (TNF-α, NOS2, MMP-12, CCL2 and IL-12) on days 1 and 5, suggesting a suppression of the macrophage M1-type response. Despite a significant early loss of glomerular podocytes, ongoing proteinuria and glomerular tuft adhesions to Bowman's capsule, the reversal of the macrophage infiltrate prevented the development of glomerulosclerosis, crescent formation, tubulointerstitial damage and renal dysfunction. In conclusion, this study has identified c-fms kinase inhibition as a selective approach to target infiltrating macrophages in acute glomerular injury, which may have therapeutic potential in rapidly progressive crescentic glomerulonephritis.

Non-selective inhibitors of spleen tyrosine kinase (SYK) efficiently suppress disease in T cell-dependent models of crescentic glomerulonephritis. However, the therapeutic potential of selective SYK inhibitors in this disease has not been established. In addition, we lack knowledge regarding SYK expression in non-myeloid cells in glomerulonephritis. We addressed these two issues in a rat model of nephrotoxic serum nephritis (NTN) using a SYK inhibitor, GS-492429. Disease was induced in Sprague-Dawley rats (Study 1) or Wistar-Kyoto (WKY) rats (Study 2) by immunization with sheep IgG and administration of sheep anti-rat nephrotoxic serum. Animals were untreated or received GS-492429 (30 mg/kg/bid) or vehicle treatment from 2 h before nephrotoxic serum injection until being killed 3 or 24 h later (Study 1) or 14 days later (Study 2). Two-colour confocal microscopy found that SYK expression in NTN kidney was restricted to myeloid cells and platelets, with no evidence of SYK expression by T cells, mesangial cells, podocytes or tubular epithelial cells. In Study 1, GS-492429 treatment significantly reduced glomerular neutrophil and macrophage infiltration, with protection from glomerular thrombosis and proteinuria. In Study 2, GS-492429 treatment reduced glomerular crescent formation by 70% on day 14 NTN in conjunction with reduced glomerular thrombosis, glomerulosclerosis and tubular damage. This was accompanied by a marked reduction in markers of inflammation (CCL2, TNF-α, NOS2, MMP-12). Importantly, the protective effects of GS-492429 were independent of T cell infiltration and activation and independent of JAK/STAT3 signalling. In conclusion, this study demonstrates that a SYK inhibitor can suppress the development of crescentic glomerulonephritis through effects upon myeloid cells and platelets.

Antibody-dependent activation of myeloid cells within the glomerulus plays a central role in rapidly progressive forms of glomerulonephritis. The spleen tyrosine kinase (Syk) is expressed by all leukocytes, except mature T cells, and is required for signalling via the B-cell receptor, Fc receptors, and some integrins. Syk has been proposed as a therapeutic target in glomerulonephritis. However, little is known of Syk activation in human kidney disease, while studies in experimental glomerulonephritis using non-selective Syk inhibitors require validation via conditional gene deletion. The current study addressed both of these important points. Syk activation (Tyr(525/526) phosphorylation) was examined in a cohort of 96 patients with different glomerulonephritides. Syk activation was evident in infiltrating leukocytes, mainly neutrophils and macrophages, in 36/40 cases of rapidly progressive glomerulonephritis. In contrast, non-proliferative diseases showed little or no Syk activation. Glomerular and interstitial cells exhibiting Syk activation correlated with renal function and systemic inflammation. Next, we examined mice with conditional Syk gene deletion in myeloid cells (Syk(My) ) versus Syk(f/f) littermate controls in nephrotoxic serum nephritis - a model of rapidly progressive glomerulonephritis. Control Syk(f/f) mice featured a transient neutrophil influx at 3 h and severe disease on day 9 of nephrotoxic serum nephritis, with crescent formation, macrophage infiltration, inflammation, kidney fibrosis, and renal dysfunction. In contrast, Syk(My) mice had significantly reduced neutrophil and macrophage infiltration despite equivalent glomerular deposition of humoral reactants. Syk(My) mice exhibited reduced crescent formation, inflammation, and fibrosis, with improved renal function on day 9 of nephrotoxic serum nephritis. In conclusion, Syk activation is prominent in infiltrating myeloid cells in human rapidly progressive glomerulonephritis, and functional studies demonstrate that Syk deletion in myeloid cells is protective in mouse nephrotoxic serum nephritis.

p38 mitogen-activated protein kinase (MAPK) signaling promotes diabetic kidney injury. Apoptosis signal-regulating kinase (ASK)1 is one of the upstream kinases in the p38 MAPK-signaling pathway, which is activated by inflammation and oxidative stress, suggesting a possible role for ASK1 in diabetic nephropathy. In this study, we examined whether a selective ASK1 inhibitor can prevent the induction and progression of diabetic nephropathy in mice. Diabetes was induced in hypertensive endothelial nitric oxide synthase (Nos3)-deficient mice by five low-dose streptozotocin (STZ) injections. Groups of diabetic Nos3−/− mice received ASK1 inhibitor (GS-444217 delivered in chow) as an early intervention (2–8 weeks after STZ) or late intervention (weeks 8–15 after STZ). Control diabetic and nondiabetic Nos3−/− mice received normal chow. Treatment with GS-444217 abrogated p38 MAPK activation in diabetic kidneys but had no effect upon hypertension in Nos3−/− mice. Early intervention with GS-444217 significantly inhibited diabetic glomerulosclerosis and reduced renal dysfunction but had no effect on the development of albuminuria. Late intervention with GS-444217 improved renal function and halted the progression of glomerulosclerosis, renal inflammation, and tubular injury despite having no effect on established albuminuria. In conclusion, this study identifies ASK1 as a new therapeutic target in diabetic nephropathy to reduce renal inflammation and fibrosis independent of blood pressure control.

Background/Aim Steroidal mineralocorticoid receptor antagonists (MRAs) are effective in the treatment of kidney disease; however, the side effect of hyperkalaemia, particularly in the context of renal impairment, is a major limitation to their clinical use. Recently developed non-steroidal MRAs have distinct characteristics suggesting that they may be superior to steroidal MRAs. Therefore, we explored the benefits of a non-steroidal MRA in a model of rapidly progressive glomerulonephritis. Methods Accelerated anti-glomerular basement membrane (GBM) glomerulonephritis was induced in groups of C57BL/6J mice which received no treatment, vehicle or a non-steroidal MRA (BR-4628, 5mg/kg/bid) from day 0 until being killed on day 15 of disease. Mice were examined for renal injury. Results Mice with anti-GBM glomerulonephritis which received no treatment or vehicle developed similar disease with severe albuminuria, impaired renal function, glomerular tuft damage and crescents in 40% of glomeruli. In comparison, mice which received BR-4628 displayed similar albuminuria, but had improved renal function, reduced severity of glomerular tuft lesions and a 50% reduction in crescents. The protection seen in BR-4628 treated mice was associated with a marked reduction in glomerular macrophages and T-cells and reduced kidney gene expression of proinflammatory (CCL2, TNF-α, IFN-γ) and profibrotic molecules (collagen I, fibronectin). In addition, treatment with BR-4626 did not cause hyperkalaemia or increase urine Na+/K+ excretion (a marker of tubular dysfunction). Conclusions The non-steroidal MRA (BR-4628) provided substantial suppression of mouse crescentic glomerulonephritis without causing tubular dysfunction. This finding warrants further investigation of non-steroidal MRAs as a therapy for inflammatory kidney diseases.

The World Wide Web has become the primary means for information dissemination. Due to the limited resources of the network bandwidth, users always suffer from long time waiting. Web prefetching and web caching are the primary approaches to reducing the user perceived access latency and improving the quality of services. In this paper, a Stochastic Petri Nets (SPN) based integrated web prefetching and caching model (IWPCM) is presented and the performance evaluation of IWPCM is made. The performance metrics, access latency, throughput, HR (hit ratio) and BHR (byte hit ratio) are analyzed and discussed. Simulations show that compared with caching only model (CM), IWPCM can further improve the throughput, HR and BHR efficiently and reduce the access latency. The performance evaluation based on the SPN model can provide a basis for implementation of web prefetching and caching and the combination of web prefetching and caching holds the promise of improving the QoS of web systems.

Kidney allografts induce strong T-cell and antibody responses which mediate acute rejection. Spleen tyrosine kinase (Syk) is expressed by most leucocytes, except mature T cells, and is involved in intracellular signalling following activation of the Fcγ-receptor, B-cell receptor and some integrins. A role for Syk signalling has been established in antibody-dependent native kidney disease, but little is known of Syk in acute renal allograft rejection. Sprague-Dawley rats underwent bilateral nephrectomy and received an orthotopic Wistar renal allograft. Recipient rats were treated with a Syk inhibitor (CC0482417, 30 mg/kg/bid), or vehicle, from 1 h before surgery until being killed 5 days later. Vehicle-treated recipients developed severe allograft failure with marked histologic damage in association with dense leucocyte infiltration (T cells, macrophages, neutrophils and NK cells) and deposition of IgM, IgG and C3. Immunostaining identified Syk expression by many infiltrating leucocytes. CC0482417 treatment significantly improved allograft function and reduced histologic damage, although allograft injury was still clearly evident. CC0482417 failed to prevent T-cell infiltration and activation within the allograft. However, CC0482417 significantly attenuated acute tubular necrosis, infiltration of macrophages and neutrophils and thrombosis of peritubular capillaries. In conclusion, this study identifies a role for Syk in acute renal allograft rejection. Syk inhibition may be a useful addition to T-cell-based immunotherapy in renal transplantation.

Treebank is an important resource for Natural Language Processing. Most existing treebanks are monolingual, but bilingual treebanks are the important basis of syntactical model in machine translation. In this paper, a bilingual phrase structure Treebank aimed for the application of machine translation was preliminarily constructed, which chose POS tagset and syntactic tagset of U-Penn English Treebank and Chinese Treebank as its tagging system. Chinese- English sentence pairs which were drawn from machine translation evaluation data in the treebank were pre-processed, with POS tagged, phrase structure annotated, and all processed data were proofread. Through the analysis of phrase structures which were modified in the proofreading process, it was found that Chinese functional words usages play an important role in Chinese phrase structure grammar.

Integrated scheduling algorithm based on dynamic essential short path, calculates essential path length of operations on the same device and schedules operation on essential short path previously, so it can avoid the problem of forming essential long path and extending the product finishing time effectively; Reverse dynamic critical paths integrated scheduling algorithm, schedules father nodes firstly, then schedules son nodes, so it can make many son node operations fully parallel processing and improve the parallelism of operations. Reverse integrated scheduling algorithm based on dynamic reverse essential short path is proposed in this paper by combining the two algorithms. The algorithm adopts dynamic long-path strategy and dynamic reverse essential short path strategy to confirm reverse essential schedule operation and schedules the reverse essential schedule operation by first fit scheduling method. Examples show that the algorithm can optimize the above two scheduling algorithms and improve the production efficiency without increasing algorithm complexity.

Micro-Blog is a kind of important media on the Internet, which conveys the users’ point of view in simple and convenient ways. The research related to micro-blog has got extensive attention from the academic and industrial areas. This paper aims to study on the analysis of Chinese micro-blog emotion, proposing a template-based algorithm for the automatic discovery of micro-blog emotional neologisms. It uses a combination method of dictionaries and rules on Chinese micro-blog sentiment analysis.

Foreign students learning Chinese grammar make errors for many reasons, among which the inappropriate use of functional words maintains a great proportion. Methods for the automatic recognition of the errors are limited. We start with the conjunctions in Chinese functional words knowledge base, analyze and summarize the appropriate usage and problematic usage of conjunctions, and propose a usage-based method to detect the grammar errors which are caused by inappropriate use of conjunctions. The results based on HSK prove that the method is simple and effective. It will be of great help in teaching Chinese as a second language.

Automatic recognition of prepositional usage is of great significance in parsing and syntax analysis. Many researches have been focused on preposition usage. In this paper, we introduce the triune knowledge base (usage dictionary, usage rule and usage corpus) of Contemporary Chinese preposition that we have finished .On this basis, we firstly adopt rule-based method to automatically annotate the prepositions in the corpus of People's Daily, in which the precision rate achieves 68.68%. Then to the prepositions whose precision rate is less than 80%, we use statistics-based method to annotate them with different models, features and context windows. The best precision rate achieves 90.86%. Experiments show that the statistics-based method can efficiently meet the need of the automatic recognition of prepositions' usage.

CT scanner simulation virtually simulates the projection process of CT without actually scanning. It is very useful to design, evaluate and develop CT systems which are evolving into some directions. However, in order to simulate multiple detector rows, multiple x-ray energy and other dimensions simultaneously, it becomes time consuming because of large amount of computation. In this paper, we present a solution to this problem with CUDA architecture on GPU. Our solution contains three steps. First, CPU prepares the data that will be used by GPU. Then, GPU kernel is launched to calculate the projection of all rays through the phantom data in parallel. In order to get maximum memory bandwidth, we optimized the data storage by padding 2D arrays to ensure the global memory access coalesced. Finally, post processing is done on CPU. Our experiment environment includes a dual core CPU and a NVIDIA Quadro FX 1800 GPU with CUDA compute capability 1.1. We used three kinds of phantom data to test the performance. It is found that our solution gets the same image quality in double precision but gains a speed increase of more than 10 times faster than using CPU only.

According to the existing research of noncoherent dual point-source counteracting ARM, attacking target radiant point model without controlling of ARM disturbed by dual point-source is improved, based on decoying principle of ARM decoys system and the limitation of PRS. Simulation is presented to validate the model. The effect of angle error to the distance choice and decoying error is studied in detail. These conclusions have great significances in improving the campaign efficiency of the active decoying system.

SUMMARY: Aim: A number of growth factors have been shown to induce proliferation of renal cell types in animal models of kidney disease. In vitro studies suggest that many such growth factors induce renal cell proliferation through the extracellular signal-regulated kinase (ERK) pathway. The aim of this study was to determine the functional role of ERK signalling in cell proliferation in the obstructed kidney. Methods: Unilateral ureteric obstruction was induced in C57BL/6J mice which then received an ERK inhibitor drug (U0126 100 mg/kg t.i.d.), vehicle (DMSO) or no treatment, starting at day 2 after unilateral ureteric obstruction surgery and continuing until animals were killed on day 5. Cell proliferation was assessed by uptake of bromodeoxyuridine (BrdU). Results: In normal mice, phosphorylation (activation) of ERK (p-ERK) was restricted to collecting ducts. Western blotting identified a marked increase in p-ERK in the obstructed kidney in the no-treatment and vehicle-treated groups. Immunostaining showed strong p-ERK staining in many tubules and in interstitial cells. U0126 treatment inhibited ERK phosphorylation as assessed by western blot and immunostaining. The number of BrdU+ cortical tubular cells was reduced by vehicle treatment but was not further changed by U0126 treatment. In contrast, interstitial cell proliferation in the obstructed kidney was unaltered by vehicle treatment, but this was significantly inhibited by U0126. This was associated with a reduction in interstitial macrophage accumulation, but no effect was seen upon interstitial accumulation of α-SMA+ myofibroblasts. Renal fibrosis, as assessed by collagen deposition, was unaffected by U0126 or vehicle treatment. Conclusion: These studies show that accumulation of interstitial macrophages in the obstructed kidney is, in part, dependent upon the ERK signalling pathway.

The World Wide Web has become the primary means for information dissemination. Due to the limited resources of the network bandwidth, users always suffer from long time waiting. Web prefetching and Web caching are the primary approaches to reducing the user perceived access latency and improving the quality of service. In this paper, a SPN (Stochastic Petri Nets) model of Web prefetching and caching system is constructed, and based on which, the performance analysis of the integrated Web prefetching and caching model are made. The performance metrics latency, throughput are compared and analyzed theoretically. Simulations show that compared with caching mechanism, Web prefetching mechanism can further reduce the access latency, improve the throughput and the hit ratio efficiently. The performance evaluation based on the SPN model provides an implementation basis for Web prefetching and caching.

A fine-grained enhanced fuzzy timing Petri net model is proposed to model the indeterminacy and fuzziness in distributed multimedia presentations. A sufficient condition is given to satisfy the maximum tolerable jitter. Different conditions are analyzed to find a proper granularity in inter-object synchronization. Exceptions are detected and corrected as early as possible using a restricted blocking method.

Activation of the c-Jun NH2-terminal kinase (JNK) signaling pathway is involved in the immune response; however, little is known of its role in immune-induced renal injury. In this study, we examine JNK signaling in the rat anti-glomerular basement membrane (GBM) disease model using CC-401, a specific JNK inhibitor. Animals were given CC-401, vehicle alone or no treatment starting before anti-GBM serum injection and continued treatment until killing. In acute disease, CC-401 blocked JNK signaling and reduced proteinuria in the first 24 h. The transient neutrophil influx seen at 3 h of disease was not affected, however. Continued CC-401 treatment suppressed glomerular and tubulointerstitial damage usually seen at 14 days. The protective effect may be due to modulation of macrophage activation, as CC-401 had no effect upon glomerular macrophage infiltration at day 14 despite the suppression of glomerular lesions and a marked reduction in renal tumor necrosis factor-alpha and inducible nitric oxide synthase messenger RNA levels. Treatment with CC-401 had no apparent effect on T cell or humoral immune responses. These studies suggest that JNK signaling promotes renal injury in acute and progressive rat anti-GBM disease. JNK inhibitors may be a novel therapeutic approach for the treatment of human glomerulonephritis.

Renal fibrosis and tubular apoptosis are common mechanisms of progressive kidney disease. In vitro studies have implicated the c-Jun amino-terminal kinase (JNK) pathway in these processes. Both of the major JNK isoforms, JNK1 and JNK2, are expressed in the kidney, but their relative contribution to JNK signaling is unknown. This study investigated the role of JNK signaling in renal fibrosis and tubular apoptosis in the unilateral ureteral obstruction model using two different approaches: (1) Mice that were deficient in either JNK1 or JNK2 and (2) a specific inhibitor of all JNK isoforms, CC-401. Western blotting and immunostaining identified a marked increase in JNK signaling in the obstructed kidney, with substantial redundancy between JNK1 and JNK2 isoforms. Administration of CC-401 blocked JNK signaling in the rat obstructed kidney and significantly inhibited renal fibrosis in terms of interstitial myofibroblast accumulation and collagen IV deposition. This effect was attributed to suppression of gene transcription for the profibrotic molecules TGF-beta1 and connective tissue growth factor. CC-401 treatment also significantly reduced tubular apoptosis in the obstructed kidney. Genetic deletion of JNK1 or JNK2 did not protect mice from renal fibrosis in the unilateral ureteral obstruction model, but JNK1 deletion did result in a significant reduction in tubular cell apoptosis. In conclusion, this is the first study to demonstrate that JNK signaling plays a pathogenic role in renal fibrosis and tubular apoptosis. Furthermore, JNK1 plays a nonredundant role in tubular cell apoptosis. These studies identify the JNK pathway as a potential therapeutic target in progressive kidney disease.