Immunohistochemical detection of haem oxygenase in AA amyloidogenesis

Haem oxygenase (HO)-1, a rate-limiting enzyme in the degradation of haem, is increased in Alzheimer's disease and in inflammations such as AA amyloidosis. However, the specific association of HO-1 is poorly understood in AA amyloidosis. In this study, we designed the experiment to reveal the contribution and association of HO-1 in the spleen during experimental murine AA amyloidosis. Experimental murine AA amyloidosis was induced with injection of an emulsion consisting of Freund's complete adjuvant and Mycobacterium butyricum. The serum amyloid A level was highest on day 3. The distribution of cells containing iron, indicating an increase of HO-1 in the red pulp, was detected with Berlin blue staining. AA amyloid formation was immunohistochemically detected as a marker by chondroitin sulphate proteoglycan (CSPG), one of the components of AA amyloid fibrils. Immunolocalizations of HO-1 and CSPG indicated a conspicuous increase and scattering of positive cells in the red pulp of the spleen. Double positive cells were not detected. On day 7, amyloid deposition was detected with Congo red staining in the extracellular spaces in the marginal zone of the white pulp in the spleen and HO-1-positive cells accumulated near the amyloid deposition area. CSPG was detected within the cells and also localized in the amyloid deposition area. CSPG was still not localized in the HO-1-positive cells. Double positive cells of HO-1 and CSPG were localized in the red pulp and in the amyloid deposition area on day 14. X-ray microanalysis indicated the existence of iron in the electron-dense bodies of fibroblasts in the amyloid deposition areas. The fibroblasts extended amyloid fibrils into the extracellular spaces of the marginal zone. These results suggest that HO-1-positive fibroblasts, but not HO-1-positive macrophages, are associated with the late stage of amyloid fibril formation.     

SPATA18 Expression Predicts Favorable Clinical Outcome in Colorectal Cancer

Dysregulation of mitochondrial quality control has been reported to be associated with cancer and degenerative diseases. SPATA18 (spermatogenesis-associated 18, also known as Mieap) encodes a p53-inducible protein that can induce lysosome-like organelles within mitochondria that eliminate oxidized mitochondrial proteins and has tumor suppressor functions in mitochondrial quality control. In the present study, 268 primary colorectal cancers (CRCs) were evaluated immunohistochemically for SPATA18 expression to assess its predictive utility and its association with cellular proliferation activity. Furthermore, the association with p53 immunoreactivity, a surrogate marker for TP53 mutation, was analyzed. Non-neoplastic colonic mucosa showed cytoplasmic SPATA18 expression. Seventy-two percent of the lesions (193/268) displayed high SPATA18 expression in the cytoplasm of CRC cells. Univariate analyses revealed significant associations between SPATA18 expression and tumor size (p < 0.0001), histological differentiation (p = 0.0017), and lymph node metastasis (p = 0.00039). The log-rank test revealed that patients with SPATA18-high CRCs had significantly better survival than SPATA18-low patients (p < 0.0001). Multivariate Cox hazards regression analysis identified tubular-forming histology (hazard ratio [HR] = 0.25), age < 70 years (HR = 0.50), and SPATA18-high (HR = 0.55) as potential favorable factors. Lymph node metastasis (HR = 1.98) and peritoneal metastasis (HR = 5.45) were cited as potential independent risk factors. Cellular proliferation activity was significantly higher in SPATA18-high tumors. However, no significant correlation was detected between SPATA18 expression and p53 immunoreactivity or KRAS/BRAF mutation status. On the basis of our observations, SPATA18 immunohistochemistry can be used in the prognostication of CRC patients.     

Push-to-Peer Video-on-Demand System: Design and Evaluation

We propose Push-to-Peer, a peer-to-peer system to cooperatively stream video. The main departure from previous work is that content is proactively pushed to peers, and persistently stored before the actual peer-to-peer transfers. The initial content placement increases content availability and improves the use of peer uplink bandwidth. Our specific contributions are: (i) content placement and associated pull policies that allow the optimal use of uplink bandwidth; (ii) performance analysis of such policies in controlled environments such as DSL networks under ISP control; (iii) a distributed load balancing strategy for selection of serving peers.     

A Comparison of Hard-State and Soft-State Signaling Protocols

One of the key infrastructure components in all telecommunication networks, ranging from the telephone network to VC-oriented data networks to the Internet, is its signaling system. Two broad approaches towards signaling can be identified: so-called hard-state and soft-state approaches. Despite the fundamental importance of signaling, our understanding of these approaches-their pros and cons and the circumstances in which they might best be employed-is mostly anecdotal (and, occasionally, religious). In this paper, we compare and contrast a variety of signaling approaches ranging from "pure" soft state to soft-state approaches augmented with explicit state removal and/or reliable signaling, to a "pure" hard state approach. We develop an analytic model that allows us to quantify state inconsistency in singleand multiple-hop signaling scenarios, and the "cost" (both in terms of signaling overhead and application-specific costs resulting from state inconsistency) associated with a given signaling approach and its parameters (e.g., state refresh and removal timers). Among the class of soft-state approaches, we find that a soft-state approach coupled with explicit removal substantially improves the degree of state consistency while introducing little additional signaling message overhead. The addition of reliable explicit setup/update/removal allows the soft-state approach to achieve comparable (and sometimes better) consistency than that of the hard-state approach     

Effect of uniaxial drawing of soy protein isolate biopolymer film on structure and mechanical properties

The effect of uniaxial drawing of biodegradable soy protein isolate (SPI) polymer film on mechanical properties was investigated to accelerate the efforts to develop SPI films with improved properties. The films containing 0–30 wt% glycerol were drawn uniaxially up to a draw ratio of 2.5. The mechanical properties of the SPI film increased significantly after uniaxial drawing. The tensile strength of the undrawn film (49.7 MPa) was approximately doubled by subjecting the film to uniaxial drawing to a D.R. of 2.5. Wide‐angle X‐ray diffraction and differential scanning calorimetry measurements did not show evidence of generation of a crystal phase in the drawn SPI films. ATR‐FTIR revealed that the protein film contained mainly α‐helix and β‐sheets secondary structures. Microwave molecular orientation analysis showed that birefringence increased with increasing draw ratios. Mechanical anisotropy of the SPI film via orientation of α‐helix and β‐sheets structure is thought to be responsible for the enhancement of mechanical properties with uniaxial drawing of the SPI films. POLYM. ENG. SCI., 47:374–380, 2007. © 2007 Society of Plastics Engineers.     

SIG-1451, a Novel,Non-Steroidal Anti-Inflammatory Compound,Attenuates Light-Induced Photoreceptor Degeneration by Affecting the Inflammatory Process

Age-related macular degeneration is a progressive retinal disease that is associated with factors such as oxidative stress and inflammation. In this study, we evaluated the protective effects of SIG-1451, a non-steroidal anti-inflammatory compound developed for treating atopic dermatitis and known to inhibit Toll-like receptor 4, in light-induced photoreceptor degeneration. SIG-1451 was intraperitoneally injected into rats once per day before exposure to 1000 lx light for 24 h; one day later, optical coherence tomography showed a decrease in retinal thickness, and electroretinogram (ERG) amplitude was also found to have decreased 3 d after light exposure. Moreover, SIG-1451 partially protected against this decrease in retinal thickness and increase in ERG amplitude. One day after light exposure, upregulation of inflammatory response-related genes was observed, and SIG-1451 was found to inhibit this upregulation. Iba-1, a microglial marker, was suppressed in SIG-1451-injected rats. To investigate the molecular mechanism underlying these effects, we used lipopolysaccharide (LPS)-stimulated rat immortalised Müller cells. The upregulation of C-C motif chemokine 2 by LPS stimulation was significantly inhibited by SIG-1451 treatment, and Western blot analysis revealed a decrease in phosphorylated I-κB levels. These results indicate that SIG-1451 indirectly protects photoreceptor cells by attenuating light damage progression, by affecting the inflammatory responses.     

Packet audio playout delay adjustment: performance bounds and algorithms

In packet audio applications, packets are buffered at a receiving site and their playout delayed in order to compensate for variable network delays. In this paper, we consider the problem of adaptively adjusting the playout delay in order to keep this delay as small as possible, while at the same time avoiding excessive “loss” due to the arrival of packets at the receiver after their playout time has already passed. The contributions of this paper are twofold. First, given a trace of packet audio receptions at a receiver, we present efficient algorithms for computing a bound on the achievable performance of any playout delay adjustment algorithm. More precisely, we compute upper and lower bounds (which are shown to be tight for the range of loss and delay values of interest) on the optimum (minimum) average playout delay for a given number of packet losses (due to late arrivals) at the receiver for that trace. Second, we present a new adaptive delay adjustment algorithm that tracks the network delay of recently received packets and efficiently maintains delay percentile information. This information, together with a “delay spike” detection algorithm based on (but extending) our earlier work, is used to dynamically adjust talkspurt playout delay. We show that this algorithm outperforms existing delay adjustment algorithms over a number of measured audio delay traces and performs close to the theoretical optimum over a range of parameter values of interest.