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RAID: Redundant Arrays of Inexpensive Disks this discussion is based on the paper: on Management of Data (Chicago, IL), pp , 1988.
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1 : Redundant Arrays of Inexpensive Disks this discussion is based on the paper:» A Case for Redundant Arrays of Inexpensive Disks (),» David A Patterson, Garth Gibson, and Randy H Katz,» In Proceedings of the ACM SIGMOD International Conference on Management of Data (Chicago, IL), pp , Motivation single chip computers improved in performance by 40% per year RAM capacity quadrupled capacity every 2-3 years Disks (magnetic technology)» capacity doubled every 3 years» price cut in half every 3 years» raw seek time improved 7% every year Note: values presented in Pattersons paper are dated! Note: paper discusses pure, not smarter implementations, e.g. caching. 2
2 Amdahl s Law: Effective Speedup» f = fraction of work in fast mode» k = speedup while in fast mode Example:» assume 10% I/O operation» if CPU 10x => effective speedup is 5» if CPU 100x => effective speedup is % of potential speedup is wasted 3 Motivation compare mainframe mentality with todays possibilities, e.g. cost, configuration CPU Mainframe CPU Small Computer Memory Channel Memory DMA Controller SCSI 4
3 Reliability e.g. MTTF disk = 30,000 h MTTF 100 = 300 h ( < 2 weeks) MTTF 1000 = 30 h Bad news! Note, that these numbers are very dated. Today s drives are much better. MTBF > 300,000 to 800,000 hours. even if we assume higher MTTF of individual disks, the problem stays. 5 Reliability partition disks into reliability groups and check disks» D = total number of data disks» G = # data disks in group» C = # check disks in group 6
4 Target Systems Different solutions will benefit different target system configurations. Supercomputers» larger blocks of data, i.e. high data rate Transaction processing» small blocks of data» high I/O rate» read-modify-write sequences 7 5 levels 1: mirrored disks 2: hamming code for ECC 3: single check disk per group 4: independent read/writes 5: no single check disk 8
5 level 1: Mirrored Disks Most expensive option Tandem doubles controllers too Write to both disks Read from one disk Characteristics:» S = slowdown. In synchronous disks spindles are synchronized so that the corresponding sectors of a group of disks can be accessed simultaneously. For synchr. disks S = 1.» Reads = 2D/S, i.e. concurrent read possible» Write = D/S, i.e. no overhead for concurrent write of same data» R-Modify-Write = 4D/(3S)» Pat88 Table II (pg. 112) 9 10
6 level 2: Hamming Code DRAM => problem with α-particles Solution, e.g. parity for SED, Hamming code for SEC Recall Hamming Code Same idea using one disk drive per bit Smallest accessible unit per disk is one sector» access G sectors, where G = # data disks in a group If operation on a portion of a group is needed: 1) read all data 2) modify desired position 3) write full group including check info 11 Recall Hamming Code m = data bits k = parity bits 12
7 Compute Check 13 Allows soft errors to be corrected on the fly. Useful for supercomputers, not useful for transaction processing e.g. used in Thinking Machine (Connection Machine) Data Vault with G = 32, C = 8. Characteristics:» Pat88 Table III (pg 112) 14
8 15 level 3: Single Check Disk per Group Parity is SED not SEC! However, often controller can detect if a disk has failed» information of failed disk can be reconstructed» extra redundancy on disk, i.e. extra info on sectors etc. If check disk fails» read data disks to restore replacement If data disk fails» compute parity and compare with check disk» if parity bits are equal => data bit = 0» otherwise => data bit = 1 16
9 Since less overhead, i.e. one check disk only => Effective performance increases Reduction in disks over L2 decreases maintenance Performance same as L2, however, effective performance per disk increases due to smaller number of check disks Better for supercomputers, not good for transaction proc. Maxtor, Micropolis introduced first -3 in 1988 Characteristics:» Pat88 Table IV (pg 113) 17 18
10 level 4: Independent Reads/Writes Pat88 fig 3 pg. 113 compares data locations Disk interleaving has advantages and disadvantages Advantage of previous levels:» large transfer bandwidth Disadvantages of previous levels:» all disks in a group are accessed on each operation (R,W)» spindle synchronization if none => probably close to worse case average seek times, access times (tracking + rotation) Interleave data on disks at sector level Uses one parity disk 19 20
11 for small accesses» need only access to 2 disks, i.e. 1 data & parity» new parity can be computed from old parity + old/new data» compute: P new = data old XOR data new XOR P old e.g. small write 1) read old data + parity 2) write new data + parity Bottleneck is parity disk e.g. small read» only read one drive (data) Characteristics:» Pat88 Table V (pg 114) in parallel 21 22
12 level 5: No Single Check Disk Distributes data and check info across all disks, i.e. there are no dedicated check disks. Supports multiple individual writes per group Best of 2 worlds» small Read-Modify-Write» large transfer performance» 1 more disk in group => increases read performance Characteristics:» Pat88 Table VI (pg 114) 23 24
13 Patterson Paper discusses all levels on pure hardware problem refers to software solutions and alternatives, e.g. disk buffering with transfer buffer the size of a track, spindle synchronization of groups not necessary improving MTTR by using spares low power consumption allows use of UPS relative performance shown in Pat88 fig. 5 pg
14 Summary Data Striping for improved performance» distributes data transparently over multiple disks to make them appear as a single fast, large disk» improves aggregate I/O performance by allowing multiple I/Os to be serviced in parallel independent requests can be serviced in parallel by separate disks single multiple-block block requests can be serviced by multiple disks acting in coordination Redundancy for improved reliability» large number of disks lowers overall reliability of disk array» thus redundancy is necessary to tolerate disk failures and allow continuous operation without data loss 27 other s 0» employs striping with no redundancy at all» claim of fame is speed alone» has best write performance, but not the best read performance why? (other s can schedule requests on the disk with the shortest expected seek and rotational delay) 6 (P + Q Redundancy)» uses Reed-Solomon code to protect against up to 2 disk failures using the bare minimum of 2 redundant disks. 28
15 Source Che94 29» String management 30
16 Case Studies Thinking Machines Corp.: TMC ScaleArray» level 3 for CM-5 massively parallel processor (MPP)» high bandwidth for large files» OS provides file system that can deliver data from a single file to multiple processors from multiple disks» uses 4 SCSI-2 strings with 2 disks each (= 8 disks)» these 4 strings are attached to an 8MB disk buffer» 3 of these units are attached to the backbone (=> 3x8=24 disks)» normal configuration: 22 data, 1 parity, 1 spare 31 Case Studies HP: TickerTAIP/DataMesh» material shown is from The TickerTAIP Parallel Architecture, Cao et.al., ACM Trans. on Computer Systems, Vol. 12, No.3, August 1994, pp » traditional architecture host interface bottleneck single point of failure 32
17 Case Studies cont. TickerTAIP/DataMesh Issues» getting away from centralized architecture» different algorithms for computing parity» techniques for establishing request atomicity, sequencing, and recovery» disk-level request-scheduling algorithms inside the array 33 Case Studies HP: TickerTAIP/DataMesh» TickerTAIP array architecture TickerTAIP system environment 34
18 Case Studies HP: Auto» provide a that will provide excellent performance and storage effeciency in the presence of dynamically changing workloads» provides both level 1 and level 5» dynamically shift data to the appropriate level» dynamically shift data to level 5 if approaching maximum array capacity» parity logging» hot pluggable disks, spare controller, dynamically addapts to added capacity» Wilkes, J. et. al. The HP Auto hierarchical storage system, ACM Trans. on Comuter systems, 14, 1 (Feb.), , 35 Case Studies StorageTek: Iceberg 9200 Disk Array Subsystem» using 5.25-inch disks to look like traditional IBM mainframe disks» implements an extended level 5 and level 6 disk array» array consists of 13 data drives, P and Q drives, and a hot spare» data, parity and Reed-Solomon coding are stiped across the 15 active drives 36
19 other s because of limitations of each level on its own, several flavors of have appeared which attempt to combine the best performance attributes e.g. 0+1» combine 0 striping with 1 mirroring e.g. 10» several 1s striped over 0s is sometimes also called 1+0 source: 38
20 0+1 source: 39
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Plasma and Brain Matrix Metalloproteinase-9 After Acute Focal Cerebral Ischemia in Rats
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Background and Purpose—Plasma levels of matrix metalloproteinase-9 (MMP-9) have been proposed to be a useful biomarker for assessing pathological events in brain. Here, we examined the temporal profiles of MMP-9 in blood and brain using a rat model of acute focal cerebral ischemia.
Methods—Plasma and brain levels of MMP-2 and MMP-9 were quantified at 3, 6, 12, and 24 hours after permanent middle cerebral artery occlusion in male Sprague-Dawley rats. Infarct volumes at 24 hours were confirmed with 2,3,5-triphenyl-tetrazolium-chloride staining.
Results—In plasma, zymographic bands were detected between 70 and 95 kDa corresponding to pro-MMP-2, pro-MMP-9, and activated MMP-9. A higher 135-kDa band was also seen that is likely to be NGAL-conjugated MMP-9. After ischemia, there were no significant changes in pro-MMP-2, but plasma levels of pro-MMP-9 steadily increased over the course of 24 hours. Activated MMP-9 levels in plasma were significantly elevated only at 24 hours. Plasma NGAL-MMP-9 complexes showed a transient elevation between 3 to 6 hours, after which levels decreased back down to pre-ischemic baselines. In brain homogenates, pro-MMP-2, pro-MMP-9, and activated MMP-9 were seen but no NGAL-MMP-9 bands were detected. Compared to the contralateral hemisphere, MMP-2 and MMP-9 levels in ischemic brain progressively increased over the course of 24 hours. Overall levels of MMP-9 in plasma and brain were significantly correlated, especially at 24 hours. Plasma levels of pro-MMP-9 at 24 hours were correlated with final infarct volumes.
Conclusions—Elevated plasma levels of MMP-9 appear to be correlated with brain levels within 24 hours of acute cerebral ischemia in rats. Further investigation into clinical profiles of MMP-9 in acute stroke patients may be useful.
Matrix metalloproteinases (MMP) have been implicated in stroke pathophysiology.1–3 MMP-2 and MMP-9 are rapidly upregulated in ischemic brain in animal models and stroke patients.3–6 Pharmacological inhibition or genetic knockdown of MMP reduces neuronal death, blood–brain barrier damage, edema, and hemorrhage.4,7–11
In this context, circulating plasma levels of MMP have been proposed to serve as useful biomarkers for stroke.12 Plasma MMP-2 and MMP-9 were positively correlated with stroke severity measured with the National Institutes of Health Stroke Scale score and ischemic lesion volumes measured on diffusion-weighted imaging scans.13,14 However, a recent experimental study in rats reported that plasma MMP-9 peaked at 4 hours after ischemia and then decreased rapidly, whereas brain MMP-9 peaked later at 24 hours and persisted until 72 hours after ischemic onset.15 Furthermore, it is now known that blood cells can contribute to MMP signatures after brain injury.16 How well plasma MMP reflects brain MMP and the progression of infarction after stroke remains to be fully dissected. In this study, we used a rat model of focal cerebral ischemia to examine the temporal profile of blood vs brain MMP and their relationship with brain infarction.
Methods and Materials
Animal Model
All experiments were performed following an institutionally approved protocol in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals. Adult male Sprague-Dawley rats (Charles River Laboratories, Wilmington, Mass), weighing 260 to 290 grams, were subjected to permanent focal cerebral ischemia using the standard intraluminal occlusion method.7 General anesthesia was maintained with 2.0% isoflurane in 30% oxygen and 70% nitrous oxide via face mask. The rectal temperature was monitored and maintained at 37°C with heating pad. Laser Doppler flowmetry (Perimed) was used to confirm adequate ischemia. Only rats that showed at least 70% reduction of middle cerebral artery flow from baseline were included. Two separate studies were performed. In the first set of rats, we examined the temporal profile of plasma MMP by sequentially sampling blood from the left internal jugular vein just after anesthesia before ischemic surgery, and then 3, 6, 12, and 24 hours after middle cerebral artery occlusion. At the end of this study, all brains were removed for measurement of 24-hour infarction volumes. Out of 11 rats initially assigned to this first experiment, 2 rats were excluded because of filament puncture, and 1 rat was excluded because laser Doppler flowmetry-regional cerebral blood flow (LDF-CBF) values did not decline to our prespecified ischemic levels. In the second set of rats, we examined the relationship between blood and brain MMP-9 by sampling blood from the left internal jugular vein in 6 or 7 rats each, at 3, 6, and 12 hours, and 13 rats at 24 hours after ischemia. Immediately after blood withdrawal, rats were killed and brains were removed. In all cases, sampled blood was centrifuged at 4500 rpm for 15 minutes within 5 minutes, and plasma was collected, and stored at −80°C for later zymography and Western blot analysis. Out of the 45 rats initially assigned to this experiment, 4 rats were excluded because of inadequate LDF-CBF reduction for proper cerebral ischemia; 8 rats died during surgery because of technical problems, including filament puncture and hemorrhage. In all experiments, <1 mL of blood was withdrawn at a single time. All rats tolerated this procedure without problems.
Gelatin Zymography
The levels of MMP-2 and MMP-9 in plasma and ischemic brain homogenates were measured by gelatin zymogram following previously described techniques.7 Rats were deeply anesthetized and then transcardially perfused with ice-cold phosphate-buffered saline. The brains were quickly removed, divided into ipsilateral ischemic hemispheres and contralateral nonischemic hemispheres, then frozen immediately in liquid nitrogen, and stored at −80°C. Samples were homogenized in lysis buffer including protease inhibitors on ice. After centrifugation, supernatant was collected, and total protein concentrations were determined using the bicinchoninic acid protein assay method. Prepared 50 μg protein samples were loaded and separated by 10% Tris-glycine gel with 0.1% gelatin as substrate. After electrophoresis, gels were placed in 2.7% Triton X-100 for 1 hour to remove SDS, and then incubated for 21 hours at 37°C in developing buffer (50 mmol/L Tris base, 40 mmol/L HCl, 200 mmol/L NaCl, 5 mmol/L CaCl2, and 0.2% Briji 35; Invitrogen) on a rotary shaker. After incubation, gels were stained in 30% methanol, 10% acetic acid, and 0.5% wt/vol Coomassie brilliant blue for 2 hours, followed by destaining. Gelatinolytic activity was manifested as horizontal white bands on a blue background. MMP bands were identified after standard techniques using molecular weight criteria and the loading of human MMP-9 control purchased from Chemicon.17
Western Blotting Analysis
To analyze the expression patterns of MMP-9 and neutrophil gelatinase-associated lipocalin (NGAL)-MMP-9 complexes in plasma and ischemic brains, protein concentration of the plasma and brain lysate were determined using the bicinchoninic acid protein assay method. Equal volume or amounts of proteins (plasma 6 μL, brain lysate 20 μg) were loaded onto 4% to 20% gradient gel or 8% Tris-Glycine SDS-PAGE under nonreducing conditions and transferred to polyvinylidene flouride membranes. The membrane was blocked with 10% nonfat dry milk in phosphate-buffered saline containing 0.1% Tween-20, followed by incubating with primary antibody at 4°C for 18 hours. After washing with phosphate-buffered saline containing 0.1% Tween-20, the membrane was incubated with peroxidase-conjugated secondary antibody at room temperature for 1 hour. Labeled proteins were detected by using chemical luminescence (ECL; Amersham Pharmacia Biotech). Rabbit antirat MMP-9 polyclonal antibody (Chemicon) and rabbit polyclonal NGAL (Santa Cruz Biotechnology) were used at 1:4000 and 1:2000 dilutions, respectively.
Measurement of Infarct Volume
Eight rats were euthanized at 24 hours after focal ischemia in first experiment. Seven coronal sections per brain of 2-mm thickness were made and stained with 2,3,5-triphenyltetrazolium-chloride. Infarct volumes were quantified with standard computer-assisted image analysis technique (Image J version 1.3). To exclude possible confounding effects of brain swelling, an indirect method was used to calculate the lesion volumes.7,18
Statistical Analysis
Data from serial blood levels of MMP-9 and MMP-2 were tested with repeated measures 1-way ANOVA followed by least significant difference corrections for multiple comparisons to assess MMP levels at different time points. Brain levels of MMP were analyzed with paired t test compared with the contralateral hemisphere. Pearson and Spearman correlation coefficients were used to analyze the association between the level of plasma MMP-9 and the level of brain MMP-9 and acute infarct volume, respectively. P<0.05 was considered statistically significant. The data are expressed as mean±SEM.
Temporal Profile of Plasma MMP-9
Serial plasma samples taken from rats before arterial occlusion were compared with samples taken at 3, 6, 12, and 24 hours after permanent focal cerebral ischemia. Gelatin zymography showed typical bands corresponding to pro-MMP-2 (72 kDa), pro-MMP-9 (95 kDa), and activated MMP-9 (92 kDa; Figure 1A). The presence of MMP-9 protein was confirmed with immunoblotting (Figure 1B). Besides the expected MMP-2 and MMP-9 bands, zymograms also revealed higher bands near 135 kDa (Figure 1A). Subsequent immunoblotting against MMP-9 and NGAL protein suggested that these might represent covalent complexes of NGAL and MMP-9 (Figure 1C), because both immunoreactivities (probed with antibodies against MMP-9 and against NGAL) migrated at a similar molecular weight of ≈135 kDa.
For quantitative analysis, optical density was measured in all zymographic gels. No significant changes in pro-MMP-2 were noted. However, plasma levels of pro-MMP-9 and total MMP-9 steadily increased over time (Figure 2A,C). In contrast, activated MMP-9 did not become significantly elevated until 24 hours after ischemic onset (Figure 2B). NGAL-MMP-9 levels were more variable and showed a transient response, with plasma levels peaking between 3 and 6 hours, and then declining back to baseline by 24 hours (Figure 2D).
Temporal Profile of Brain MMP
Zymography of brain homogenates showed the expected bands, corresponding to 72 kDa pro-MMP-2, 92 kDa activated MMP-9 and 95 kDa pro-MMP-9 (Figure 3A). However, no 135 kDa NGAL-MMP-9 bands were detected at any time in the rat brains (Figure 3A). Compared to the contralateral hemisphere, ischemic brain levels of pro-MMP-9, activated MMP-9, and total MMP-9 were all significantly increased over the 24-hour period after ischemic onset (Figure 3B–D). Pro-MMP-2 was also slightly elevated over time (Figure 3E).
Correlations Between Brain MMP-9, Plasma MMP-9, and Final Infarction
An overall analysis including all time points showed that blood and brain MMP-9 (total, pro, and activated forms) were significantly correlated (r=0.643, P<0.001 in total MMP-9; r=0.561, P=0.001 in pro-MMP-9; r=0.540, P=0.001 in activated MMP-9; Figure 4A–C). Furthermore, a dependence on time was observed. Subsequent analysis showed that the strongest correlation between plasma and brain MMP-9 was found at 24 hours (r=0.560, P=0.046 for total MMP-9; r=0.585, P=0.036 for pro-MMP-9). Interestingly, no correlation was found for activated MMP-9 at 24 hours. Individual correlations for all time points are presented in the Table.
The mean infarct volume at 24 hours after focal cerebral ischemia was 499±157 mm3. No correlation was found between plasma pro-MMP-2 and infarct volume at any time point (see Table). However, a pattern of correlations was detected between plasma pro-MMP-9 and final infarct volumes (Table). This reached statistical significance for 24-hour plasma pro-MMP-9 and 24-hour final infarct volumes (r=0.762, P=0.028). Overall, however, these relationships between plasma MMP and brain infarct volumes were limited by the small numbers available for this portion of the study.
By degrading neurovascular substrates, MMP promote blood–brain barrier leakage that may underlie cerebral edema and hemorrhage.1,5,6 By disrupting cell–cell and cell–matrix signaling, MMP may trigger brain cell dysfunction and death.19,20 Furthermore, it is now recognized that tissue plasminogen activator can upregulate MMP, perhaps mediating some of the hemorrhagic complications of delayed thrombolysis.21,22 Taken together, the data suggest that MMP, especially the gelatinases MMP-2 and MMP-9, play important roles in the pathophysiology of cerebral ischemia and hemorrhage. Hence, measuring MMP and finding ways to target these proteases may lead to useful diagnostic and therapeutic approaches for stroke.9
In experimental stroke models, MMP in brain are easy to identify and quantify for specific hypothesis testing. In recent years, emerging data suggest that similar MMP signatures may also be detected in clinical stroke patients. The majority of these findings have come from measurements of circulating MMP in plasma. Levels of MMP-9 within the acute (<24–48 hours) periods of ischemic strokes were found to be correlated with worsened NIH stroke scores, larger infarct volumes, and increased risk of hemorrhagic conversion.13,14,21,23,24 However, all of these clinical studies were unable to demonstrate a clear temporal progression of these MMP signals over time. Levels at very early 3- to 6-hour time points were not significantly different from those at later 24- to 48-hour time points. Together with the heterogenous characteristics of human stroke (comorbidities and various risk factors in patients vs controls, variable infarct size, location, and severity), this raises the question as to whether MMP in blood can truly serve as causative biomarkers of stroke pathophysiology or if they are only nonspecific markers of tissue injury.
Surprisingly, there has only been 1 previous study that tried to compare blood vs brain levels of MMP in cerebral ischemia. In a rat model of focal cerebral ischemia, Koh et al15 found that plasma levels of MMP-9 peaked very early at 4 hours, then declined back to baseline by 24 hours. In contrast, they found that brain levels of MMP-9 progressively increased and peaked at 24 hours. These data would suggest that there is no good correlation between plasma and brain MMP-9 responses after cerebral ischemia. Our findings here are different. In our rat focal ischemia model, plasma levels of pro-MMP-9 progressively increased and remained elevated at 24 hours, in parallel with brain levels. Plasma levels of activated MMP-9 showed a late peak only at 24 hours, whereas in ischemic brain, activated MMP-9 increased at 12 and 24 hours. Overall, total MMP-9 levels in plasma and brain were highly correlated. There may be several potential reasons for the discrepancy between our data and the Koh et al15 study. First, we used a model of permanent ischemia, whereas Koh et al15 used a model of transient ischemia. It is conceivable that reperfusion may lead to differential MMP responses in blood vs brain. Second, it was not clear how pro vs activated MMP-9 forms were quantified in the previous study. In our experiments, we found significant differences between pro and activated MMP-9 bands in blood vs brain. For some reason, activated MMP-9 bands were not markedly elevated in blood until 24 hours, long after these corresponding levels were increased in brain tissue. Further studies will be required to examine the reason for these intriguing differences. However, it should be noted that activated forms of MMP-9 are much less stable than inactive proforms of this enzyme and consequently more difficult to visualize on zymography analysis. In this regard, one might speculate that all else being equal, proforms of MMP-9 may be easier to interpret when considering biomarkers for clinical stroke. Nevertheless, how blood MMP levels relate to actual brain infarction remains to be unequivocally resolved, especially for active MMP-9 levels. In brain, these steadily increase over time, whereas in plasma, only 24-hour samples show significantly elevated active MMP-9 forms. It is possible that these profiles may be related to different sources of MMP-9 in periphery vs brain parenchyma. A recent report showed that after transient focal cerebral ischemia in rats, 24-hour MRI lesion volumes correlated with brain MMP-9 levels but not plasma MMP-9.11 Further studies are required to separate how much of plasma MMP levels come leaked from damaged brain vs how much might come form activated blood cells and nonlocal endothelium.
Thus far, our data are not inconsistent with the possibility that plasma levels of pro and activated MMP-9 forms may partially derive from ischemic brain parenchyma and activated cerebral endothelium. However, it is increasingly recognized that systemic blood cells may also be highly reactive after stroke.25 Neutrophils can be an especially potent source of MMP-9 and in the human circulation this leukocyte type is certainly the most abundant one.16 Recent studies in experimental models of cerebral ischemia showed that neutrophils can secrete MMP-9 into ischemic brain areas.26,27 In the present study, we attempted to look for higher molecular weight zymographic bands of NGAL-conjugated MMP-9 as a surrogate marker for neutrophil-derived MMP-9.28 In ischemic brain homogenates, we were unable to detect covalent NGAL–MMP-9 complexes at the examined time points. But in plasma, NGAL–MMP-9 forms were clearly detected, and these signals transiently peak at ≈3 to 6 hours and then decreased back to baseline levels. In most clinical studies, MMP-9 assays are performed using enzyme-linked immunosorbent assays, which may not be able to distinguish between the various pro, activated, and NGAL-conjugated MMP-9 isoforms. How neutrophil-derived MMP-9 contributes to clinical plasma signals warrants further investigation.
Overall, our study suggests that in rat focal cerebral ischemia, plasma and brain levels of MMP-9 may be correlated. However, there are several important caveats to be considered. First, our data remain comparative and correlative, and we cannot truly assess causality. We can only say that our plasma MMP measurements seem interesting as potential biomarkers. Second, we cannot determine cell source. Although we were able to detect NGAL–MMP-9, which most likely comes from activated neutrophils, the rest of our zymographic data are noncell-specific. Third, we cannot say anything about specific mechanisms of brain injury. We only compared MMP levels with overall tissue infarction. Further studies are required to examine how plasma MMP may or may not truly track the evolution of blood–brain barrier damage and other specific mechanisms of pathophysiology within the neurovascular unit. Fourth, our numbers and time points are relatively limited. We detected a significant correlation between plasma and brain pro-MMP-9 at 24 hours, and between 24-hour plasma pro-MMP-9 and 24-hour infarct volumes. But it is possible that higher numbers may have increased our power to pull out correlations at different time points. Besides, we have no long-term follow-up. Delayed changes in MMP-2 will be missed in our study. And we cannot be sure how our so-called biomarkers may or may not correlate with actual functional outcomes after stroke. Fifth, our study only examined MMP profiles in permanent ischemia. How these MMP biomarkers respond to reperfusion will have to be carefully investigated, especially in the context of thrombolytic therapy. Finally, our analysis is focused on MMP-9. Future studies using protein arrays may be needed to examine the network response of all MMP in cerebral ischemia. For biomarker purposes, a broader signature of multiple MMP may generate more power than reliance on a single protease alone.
In conclusion, our study showed that in a rat model of focal cerebral ischemia, plasma and brain levels of MMP-9 were correlated with each other, both plasma and brain MMP-9 progressively increased over the first 24 hours after ischemia, and 24-hour plasma pro-MMP-9 levels are correlated with 24-hour brain infarction. But, it is important to emphasize that mechanisms and causality remain unproven, so that more careful investigation of clinical MMP profiles in stroke patients would be useful.
Sources of Funding
This study was supported in part by NIH grants R37-NS37074, R01-NS48422, R01-NS56458, P01-NS55104, and P50-NS51343, and grant 2006-34 from the Medical Research Institute, Pusan National University.
- Received April 4, 2009.
- Accepted April 27, 2009.
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Zhao BQ, Tejima E, Lo EH. Neurovascular proteases in brain injury, hemorrhage and remodeling after stroke. Stroke. 2007; 38: 748–752.
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Romanic AM, White RF, Arleth AJ, Ohlstein EH, Barone FC. Matrix metalloproteinase expression increases after cerebral focal ischemia in rats: Inhibition of matrix metalloproteinase-9 reduces infarct size. Stroke. 1998; 29: 1020–1030.
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Rosenberg GA, Estrada EY, Dencoff JE. Matrix metalloproteinases and timps are associated with blood-brain barrier opening after reperfusion in rat brain. Stroke. 1998; 29: 2189–2195.
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Nagel S, Su Y, Horstmann S, Heiland S, Gardner H, Koziol J, Martinez-Torres FJ, Wagner S. Minocycline and hypothermia for reperfusion injury after focal cerebral ischemia in the rat: Effects on bbb breakdown and mmp expression in the acute and subacute phase. Brain Res. 2008; 1188: 198–206.
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Whiteley W, Tseng MC, Sandercock P. Blood biomarkers in the diagnosis of ischemic stroke. A systematic review Stroke. 2008; 39: 2902–2909.
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Montaner J, Alvarez-Sabin J, Molina C, Angles A, Abilleira S, Arenillas J, Gonzalez MA, Monasterio J. Matrix metalloproteinase expression after human cardioembolic stroke: Temporal profile and relation to neurological impairment. Stroke. 2001; 32: 1759–1766.
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Opdenakker G, Van den Steen PE, Dubois B, Nelissen I, Van Coillie E, Masure S, Proost P, Van Damme J. Gelatinase b functions as regulator and effector in leukocyte biology. J Leukoc Biol. 2001; 69: 851–859.
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Lin TN, He YY, Wu G, Khan M, Hsu CY. Effect of brain edema on infarct volume in a focal cerebral ischemia model in rats. Stroke. 1993; 24: 117–121.
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Gu Z, Kaul M, Yan B, Kridel SJ, Cui J, Strongin A, Smith JW, Liddington RC, Lipton SA. S-nitrosylation of matrix metalloproteinases: Signaling pathway to neuronal cell death. Science. 2002; 297: 1186–1190.
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Ning M, Furie KL, Koroshetz WJ, Lee H, Barron M, Lederer M, Wang X, Zhu M, Sorensen AG, Lo EH, Kelly PJ. Association between tpa therapy and raised early matrix metalloproteinase-9 in acute stroke. Neurology. 2006; 66: 1550–1555.
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Aoki T, Sumii T, Mori T, Wang X, Lo EH. Blood-brain barrier disruption and matrix metalloproteinase-9 expression during reperfusion injury: Mechanical versus embolic focal ischemia in spontaneously hypertensive rats. Stroke. 2002; 33: 2711–2717.
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Castellanos M, Leira R, Serena J, Pumar JM, Lizasoain I, Castillo J, Davalos A. Plasma metalloproteinase-9 concentration predicts hemorrhagic transformation in acute ischemic stroke. Stroke. 2003; 34: 40–46.
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Horstmann S, Kalb P, Koziol J, Gardner H, Wagner S. Profiles of matrix metalloproteinases, their inhibitors, and laminin in stroke patients: Influence of different therapies. Stroke. 2003; 34: 2165–2170.
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Amantea D, Corasaniti MT, Mercuri NB, Bernardi G, Bagetta G. Brain regional and cellular localization of gelatinase activity in rat that have undergone transient middle cerebral artery occlusion. Neuroscience. 2008.
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Rosell A, Cuadrado E, Ortega-Aznar A, Hernandez-Guillamon M, Lo EH, Montaner J. Mmp-9-positive neutrophil infiltration is associated to blood-brain barrier breakdown and basal lamina type iv collagen degradation during hemorrhagic transformation after human ischemic stroke. Stroke. 2008; 39: 1121–1126.
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Kjeldsen L, Johnsen AH, Sengelov H, Borregaard N. Isolation and primary structure of NGAL, a novel protein associated with human neutrophil gelatinase. J Biol Chem. 1993; 268: 10425–10432.
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- Plasma and Brain Matrix Metalloproteinase-9 After Acute Focal Cerebral Ischemia in RatsKyung-Pil Park, Anna Rosell, Christian Foerch, Changhong Xing, Woo Jean Kim, Seoul Lee, Ghislain Opdenakker, Karen L. Furie and Eng H. LoStroke. 2009;40:2836-2842, originally published July 27, 2009http://dx.doi.org/10.1161/STROKEAHA.109.554824
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- Plasma and Brain Matrix Metalloproteinase-9 After Acute Focal Cerebral Ischemia in RatsKyung-Pil Park, Anna Rosell, Christian Foerch, Changhong Xing, Woo Jean Kim, Seoul Lee, Ghislain Opdenakker, Karen L. Furie and Eng H. LoStroke. 2009;40:2836-2842, originally published July 27, 2009http://dx.doi.org/10.1161/STROKEAHA.109.554824
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- Myeloperoxidase Inhibition Increases Neurogenesis after Ischemic Stroke
- Gelatinase activity imaged by activatable cell-penetrating peptides in cell-based and in vivo models of stroke
- Essential Role of Program Death 1-Ligand 1 in Regulatory T-Cell-Afforded Protection Against Blood-Brain Barrier Damage After Stroke
- Effects of Minocycline Plus Tissue Plasminogen Activator Combination Therapy After Focal Embolic Stroke in Type 1 Diabetic Rats
- Valproic Acid Attenuates Blood-Brain Barrier Disruption in a Rat Model of Transient Focal Cerebral Ischemia: The Roles of HDAC and MMP-9 Inhibition
- Increased Plasma and Tissue MMP Levels are Associated with BCSFB and BBB Disruption Evident on Post-Contrast FLAIR after Experimental Stroke


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Popular Irish dance rock trio Two Door Cinema Club return to Singapore for their biggest concert yet.
Continue reading LIVE NEWS: TWO DOOR CINEMA CLUB – LIVE IN SINGAPORE
Popular Irish dance rock trio Two Door Cinema Club return to Singapore for their biggest concert yet.
Continue reading LIVE NEWS: TWO DOOR CINEMA CLUB – LIVE IN SINGAPORE
Before the rock underground can thrive, one must first have a successful pop mainstream. So the sheer amount of Singapore pop music getting traction amongst the young in 2016 is cause for optimism. So check out the new S-POP darlings with new releases.
Continue reading SINGAPORE MUSIC SPOTLIGHT FT. HUBBABUBBAS & THELIONCITYBOY
We were (and still are) quite mystified by this lineup. Cambodian Space Project is a psychedelic rock band, whose style is steeped in Retro-Pop and most of their songs are in the Khmer language! (Not quite the formula to draw in the local hipstas, eh?)
Continue reading LIVE NEWS: CONCERTS ON THE HILL – CAMBODIAN SPACE PROJECT + BITTYMACBETH X EVAN LOW
Maricelle's latest instalment comes with the bonus of new music!
Dear Kevin,
I've been away for awhile now, time and wifi are scarce on the road. I think I've seen a number of lighthouses on this trip, more than I can count, more than I've ever seen, and it's an interesting thought to have seen so many different lighthouses. It seems to remind me that I'm not home anymore, but there's something guiding me somewhere else, if that makes sense. The journey's been rough, but good. Like the famous Gaga song, if it ain't rough it isn't love.
Continue reading MARICELLE: ATLAS TOUR DIARY 180716 – LIGHTHOUSE MV
2016 – the year that has finally seen Singapore-English pop acts headlining at venues that were previously beyond them. In June, Gentle Bones performed at two sold out nights at the Esplanade Concert Hall (capacity: 1,600). On 22nd July it is the turn of The Sam Willows to expand the boundaries of what a Singapore-English pop act can achieve by playing at The Coliseum, Resort World Sentosa – a venue that can hold 5,000 people, although record label Sony Music expects about 3,000 fans to attend that night.
Continue reading SINGAPORE MUSIC SPOTLIGHT – THE SAM WILLOWS TAKE HEART TOUR SINGAPORE
Gentle Bones (a.k.a. Joel Tan) returns with his second EP, Geniuses and Thieves.
bittymacbeth (aka Beth Yap) launches her debut album Beauty for Ashes at the Esplanade Recital Studio tomorrow night. Guess what? SOLD OUT! In any case, Beth was kind enough to take part in our PoP Ten for our reading pleasure. Enjoy!
As much as we would confess to an aversion to what passes for pop music in 2016, the UK singer-songwriter Jessie J has always intrigued with her songwriting and unconventional style. There is a genuine earthy quality about Jessie J amidst the obligatory glitz and glamour of modern pop that endears, somewhat.
Continue reading LIVE REVIEW: SINGTEL AND SAMSUNG PRESENTS UP CLOSE WITH JESSIE J
Incredibly, this past week 50 years ago, saw the release of two landmark pop albums that changed the face of rock music viz. The Beach Boys' Pet Sounds and Bob Dylan's Blonde on Blonde.
Icelandic hipster band returned to Singapore for a full concert, having previously appeared at Laneway 2013. Considering the type of young fans OMAM attracts, the audience were mostly surprisingly laid back, dress-wise, with many fans donning OMAM t-shirts.
Continue reading LIVE REVIEW: OF MONSTERS & MEN – LIVE IN SINGAPORE
Two electropop icons – France's Jean-Benoit Dunckel (Air / Tomorrow's World) and Icelandic composer Bardi Johannsson (Bang Gang, Lady & Bird) make up Starwalker.
Here's a fresh sound for your listening pleasure. Eddy got in touch with us to share his new single, "All For You", and we are simply digging its simple, straight-forward infectiousness. Now, this is the kind of pop music that we can can thoroughly get into. Enjoy!
Continue reading MUSIC NEWS: EDDY FAULKNER'S NEW SINGLE 'ALL FOR YOU' IS OUT NOW!
Girl groups have been a staple of pop music since the 60s – what is important are the songs – and of course, how hot the girls happen to be!
Continue reading LIVE NEWS: LITTLE MIX – THE GET WEIRD TOUR – LIVE IN SINGAPORE
Back in 2011, in a public Facebook note, singer-songwriter iNCH (a.k.a Inch Chua) criticised Singaporean attitudes toward local music. iNCH even moved out of Singapore (to the US) in order to pursue her musical career. Four years later, back in Singapore, as a packed audience demonstrates their hearty approval, iNCH is moved to tears by a post-gig video filled with expressions of congratulations, love, admiration and celebration for the launch of iNCH's new EP, Letters to Ubin.
Continue reading LIVE REVIEW: iNCH – LETTERS TO UBIN EP LAUNCH
The state of pop circa 2015. The record-breaking new album from British songstress encapsulates all you need to know about pop music in the here and now. It's about songwriting collaborations – Adele co-wrote the songs with eleven other songwriters/producers – including Max Martin, Greg Kurstin and Tobias Jesso Jr.
Ian Axel and Chad King of piano pop band A Great Big World (AGBW) seem to have hit on that elusive formula that makes their songs both irresistibly catchy AND strikingly authentic.
A mere 12 hours after hearing their sophomore album When The Morning Comes in its entirety, I was already easily singing along to the big melodic hooks and memorable choruses of every song. At the same time, the unique vulnerability in the words being sung was reeling me in, giving these (otherwise pretty simple) lyrics an emotional depth you wouldn't normally expect from "happy clappy" pop tunes.
Continue reading ALBUM REVIEW: A GREAT BIG WORLD – WHEN THE MORNING COMES
Some respite for true pop lovers from the onslaught of the prefabricated anti-music dominating the current Billboard charts in the form of a new Squeeze album! Yes! When frontman Glenn Tilbrook was in Singapore last year, he mentioned that the band was recording a new album and here it is – Cradle to the Grave – the band's first album of new material since 1998!
Continue reading ALBUM REVIEW: SQUEEZE – CRADLE TO THE GRAVE
It's always intriguing to have two opposing ideas build up to a contrast in a music video. And this is why the music video for THELIONCITYBOY's new single "All Night Feat Sezairi, Mr Boo" works despite the inevitable clunky acting.
The song itself is quite lightweight pop with local crooner Sezairi providing the sweetness but there is a edgy underbelly when you appreciate where THELIONCITYBOY's lyrics are coming from. It's a refreshing take on hip hop's usual concerns about partying and hooking up with the opposite sex.
The video is altogether a different proposition. Ostensibly, it may seem corny and cliched to come up with a horror story before Halloween but it seems that the zombie motif is really a deep commentary on relationships and it resonates when the actress involved is THELIONCITYBOY's own better half, Aarika Lee.
A masterstroke!
I mean, that scene where she's asking her zombie partner why he's so slow (riding his bicycle at the beach – what a twist on the cliche!) is hilarious. So when the ending comes, it makes so much sense and the viewer is nodding in a knowing agreement. Which is why I have always appreciated THELIONCITYBOY's work – it lures you in with superficial hip hop tropes but then slays you with a meaningful thought-provoking message.
An excellent sign that Singapore music is slowly (but surely) permeating the mainstream consciousness is the clutch of music events to be held in the upcoming Singapore Writers Festival, from October 30th to November 8th 2015, organised by the National Arts Council.
Kicking off is Island of Dreams, an instrumental rock concert at the Victoria Theatre on 30th October, featuring In Each Hand a Cutlass and I Am David Sparkle, two heavyweights in the local indie scene.
From epic rock bombast, the music gets all stripped down and fragile with Story Songs by Tiny Ruins. Kiwi Hollie Fullbrook returns to Singapore on 1st November at the Chamber, the Arts House.
Finally, we have Dimensions and Demons, with artists from literary and musical disciplines collaborating on works to be presented on 5th November at the Esplanade Recital Studios. Writers Dave Chua, Daren Shiau and Stephanie Ye have been rehearsing with musicians weish (.gif), Riot !n Magenta and Ferry (Giants Must Fall) for the past few months for this co-presentation with The Esplanade.
Power of Pop will be in the thick of the action with reviews and interviews but so can you. The Festival organisers have kindly offered a pair of tickets to each of the above events to lucky PoP visitors.
Now, you can only select one of these events to apply to – simply write in to firstname.lastname@example.com with a 5o-word note on why you love Power of Pop so much! (Also include your full name and NRIC No., please) Oh and let us know which event you would like to attend and voilà (!) you could be on your way. (Winning entries will be published here! Be warned!!)
First come, first served and all that jazz. The decision of Power of Pop regarding the identity of the lucky recipients shall be final & conclusive. Closing date is 27th October.
More info at https://www.singaporewritersfestival.com/nacswf/nacswf.html
Into their second single for Sony Music, it's clear that The Sam Willows have honed their pop technique to a tight construct with "For Love" – the chorus comes with soaring banks of vocals even if the familiar melody does not move listeners that much.
The song recalls Imagine Dragons, Of Monsters & Men and even the quartet's own "Glasshouse". Not quite as incongruous as its predecessor "Take Heart", this time the electro-pop elements complement the song rather well.
The message behind the video is strong and to the band's credit maintains a personal emotional connection. It might be too close to the bone for many people but if pop music can be used to touch hearts, minds and souls in this manner then kudos to The Sam Willows for at least, taking their best shot at making a statement!
Pre-order the album Take Heart:
I am so sick and tired of defending 'classic' pop songwriting – why should the age of a genre ever come into the assessment of good music.
Anyways, thankfully I have a musical representation of this argument in the form of Pop4's brilliant album Summer. Comprising of Scott McPherson, KC Bowman, Kirk Adams and Andrea Perry – a power pop brain trust, for those in the know – Pop4 exploits the diverse strengths of its members to provide one of the finer pop albums of 2015.
Highlights include the droll putdown "You're No Aimee Mann" (which Mann herself approves of, it seems!), the delightfully ELO-channelling "Einstein and Sunshine" and the warm pastoral "Beautiful".
There's no doubt that we need more sophisticated melodic albums like Summer – no irony, no pretension, no pastiche – I am glad to declare that this is the real deal.
Pop band WALK THE MOON claim to be inspired by 80s bands like The Police and Talking Heads but one listen to their latest album, Talking is Hard, will make it clear that apart from taking their name from a Police song, there is no similarity whatsoever.
Actually, they remind me of crassly commercial fare like Modern Talking and Wang Chung, y'know the really shitty 80s bands. Which is fine but why can't we call a spade a spade? This is certainly not indie rock, by any stretch of the imagination.
But of course, that's not going to stop the horde of pop fans out there from enjoying this show when the band play in Singapore on 19th Jan 2016.
So… get your tickets kiddos from SISTIC now!
Although it mainly consists of vocals, guitar, strings and a smattering of piano notes, there is a certain dynamism and power that distinguishes Brett Randell's new single "Rise". Randell's voice isn't too sugary and in fact is rather nasal at times but it conveys the emotion well on this uplifting song of encouragement. I like how Randell resists the temptation of cluttering up the arrangement and keeps things very spare so that his lyrics shine through. In fact, I almost expect it to break out into a pop-punk anthem but thankfully that never happens. Definitely one to savour, if you are into edgy ballads that carry the weight of a meaningful life message.


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Reviews for China Station
Latest MenuPix Reviews
Knot2L8 posted on 12/27/2013
Rating & Review:
Had "Wo Won Ton Soup" good stuff and enough. Filling won ton So-so. Broth with too salty of a base and heavy on MSG.
Egg FooYoung, somewhat tasteless . Heavy on gravy. Egg was dense, tofu look, cut up and added to sauce, vegs, bean sprout mixture. Guessing, better dishes here, just not ours!
Egg FooYoung, somewhat tasteless . Heavy on gravy. Egg was dense, tofu look, cut up and added to sauce, vegs, bean sprout mixture. Guessing, better dishes here, just not ours!
Billy Bob posted on 07/31/2010
Rating & Review:
About 3 months ago I discovered China Station and was amazed at thier service and great food, especially thier shrimp fried rice but I was dissapointed the last time I went because we where given less food and the foor did not taste the same. I realized then that the original cook was waiting tables and someone else was cooking. This is bad for business because the taste and portions should not change. I will return, but if I don't see the original cook, IM WALKING OUT.
Latest Yelp Reviews
Overall Rating:
Based on 102 Reviews
Based on 102 Reviews
The F. posted on 08/01/2016
Rating & Review:
I'm going to level with you . . . this place is damn good. You're not getting fancy here. This isn't foodie heaven, this isn't selfie worthy, this isn't... read more
Emily K. posted on 07/10/2016
Rating & Review:
We tried this place for lunch. We ordered the chow mein, fried rice, orange chicken, broccoli beef, and fried prawns. The rice was the best dish of those.... read more
Derek A. posted on 10/23/2016
Rating & Review:
Love the Chow Fun just like Hong Kong..just wish they had more seafood on menu but overall food is Always made fresh to order. Good Service read more
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Neutrogena LIP PLUSH in Petal #20 (V67109-E0) - [ Roxanne Anjou Closet ]
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**A Great Additional Discount Is Available!!---Click on my Name Above ( "Listed by...") to learn about my Multi-Sale Discount Offer in my Closet Profile** This never-used, flawless tube of Neutrogena's 'so natural' "Petal" shade is 'you'...just better. For full lip color wear of fairer skin tones it adds a deeply attractive and natural look. For women of olive to dark skin tones, it is the perfect center lip fill-in when lips are lined or a darker shade of lipstick is used on the outer/inner perimeter.
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Sei Stelle Bed & Breakfast, Sulmona
- Free hot/cold buffet breakfast and WiFi
Main amenities
- 6 guestrooms
- Rooftop terrace
- Valet parking
- Airport shuttle
- Air conditioning
- Daily housekeeping
- Library
- Luggage storage
- Limited hour front desk
- Tour/ticket assistance
- TV in a common area
Feel at home
- Cookware, dishware, and utensils
- Private bathroom
- Free toiletries
- Daily housekeeping
- Hair dryer
- In-room climate control (air conditioning)
What's around
- Heart of Sulmona
- Campo di Giove Ski Resort (13.2 mi / 21.3 km)
- Monte Pratello Gondola (20.4 mi / 32.8 km)
- Vallone Ski Lift (20.4 mi / 32.8 km)
- Rivisondoli-Monte Pratello Ski Resort (20.4 mi / 32.8 km)
- Pizzalto Ski Lift (23.5 mi / 37.7 km)
Sei Stelle Bed & Breakfast, Sulmona
Hotel Info: 866-539-8117from $87
- Double or Twin Room
- Quadruple Room
- Triple Room
More great choices
At a glance
Key facts
Hotel size
- This hotel has 6 rooms
- This hotel is arranged over 1 floor
- Check-in time 11:30 AM-8 PM
- Check-out time is 10 AM
Required at check in
- Cash deposit required
- Government-issued photo ID required
Travelling with others
- Pets not allowed
- Free WiFi and wired Internet access in public areas
- Free WiFi in rooms
- Airport shuttle *
- Valet parking *
- Free nearby parking
- Area shuttle *
Nearby One Star Sulmona hotels
In the hotel
- Free hot/cold buffet breakfast daily
- Bicycle rentals nearby
- Front desk (limited hours)
- Tours/ticket assistance
- Luggage storage
- Number of buildings/towers - 1
- Year Built 1376
- Designated smoking areas
- Rooftop terrace
- Library
- Television in common areas
In the room
- In-room climate control (air conditioning)
- Air conditioning
- Iron/ironing board (on request)
- Individually decorated
- Private bathroom
- Rainfall showerhead
- Shower only
- Bidet
- Free toiletries
- Hair dryer
- Free WiFi
- Cookware, dishware, and utensils
- Daily housekeeping
- In-room safe
Top Sulmona hotels
Recently reviewed hotels in Sulmona
- Hotel Don LuisFrom
"Hotel Don Luis closed for the season 30 September. We were moved to a sister property, Hotel Sport Village, for our reservation 1 and 2 October. Sport Village is in the…"Oct 5, 2016
- Casa RosatiFrom
"This B&B is more like a great escape. You can only appreciate it if you love silence and beauty. If you are looking for night life or meeting someone famous, forget about it and…"Oct 4, 2016
- Il Vecchio MulinoFrom
"Camillo, Andrea and their parents, are the nicest people.....she make the best breakfast pastries, I asked her to mail one of the apple pies! Plus, more family is next door at…"Oct 2, 2016
- Hotel AcqueviveFrom
"Lago de Scanno is very serene. Went after season was over. Room was fine - no frills. Hotel is older but the small staff was great. Had wine outside on their patio in the evening…"Sep 29, 2016
Sei Stelle Bed & Breakfast, Sulmona's small print
Also known as
- Sei Stelle
- Sei Stelle Bed & Breakfast
- Sei Stelle Bed & Breakfast Sulmona
- Sei Stelle Sulmona
All guests, including children, must be present at check-in and show their government-issued photo ID card or passport.
Cash transactions at this property cannot exceed EUR 2999.99, due to national regulations. For further details, please contact the property using information in the booking confirmation.
This property does not have elevators.
For transfers, guests must contact the property before arrival at the number on the booking confirmation.
Optional extras
Valet parking costs EUR 6,00 per day
Rollaway beds are available for EUR 20,00 per stay
Cribs/Infant beds are available for EUR 10,00 per night
Airport shuttle service is offered for an extra charge of EUR 250 per vehicle (one way)
Area shuttle service is offered for an extra charge
We have included all charges provided to us by this hotel. However, charges can vary, for example, based on length of stay or the room you book.
Also popular with travelers from the USA
Recent reviews
Outstanding 4.9 /5 from 11 reviews
What a unique, awesome, B&B!!! Right on the main piazza with the arches of a medieval aqueduct running through it! The manager Davide, his wife, and mother-in-law were wonderful and we were fortunate also to meet the owner Filippo (he happened to be in town while we were there) who was amazingly helpful in helping my husband track down info about his ancestors from the area. Breakfast (with eggs cooked to order -- and make sure to ask for the fried cheese or "scamozza" to go with them!) on the rooftop terrace overlooking the piazza was fantastic and so was having access to the kitchen (to eat Franca's homemade cakes or make a pot of tea). We were made to feel welcome and totally at home. Large rooms, great shower! Only downside -- no wifi in the rooms, but the lounge area where it is available is close by. Hope to come back to Sulmona and if we do there's no question where we'll stay!
Manager, David, made an extra effort to assist us and also prepared an exceptional colazione (breakfast) for us. I am 87 years old and handicapped and David helped my mobility.
Plesent place on the main plaza of the city. Great hospitale. Little noisy.
David could not do enough to make your stay great. Many things that helped make the stay very nice. Way past the B and B. Helped with local needs and recommendations. We really enjoyed out stay.
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Property Name: Studio Village Naturiste
Property Address: 7 Avenue de la Joliette Cap d'Agde, , 34300
Property Description: Featuring air conditioning, Studio Village Naturiste offers pet-friendly accommodation in Cap d'Agde. Aqualand Cap d'Agde is 2. 7 km away. Free private parking is available on site. Some units feature a terrace and/or balcony with sea or garden views. There is also a kitchen, equipped with a microwave, refrigerator and stovetop. Studio Village Naturiste features free WiFi . Towels are available. Studio Village Naturiste also includes a sun terrace. You can engage in various activities, such as golfing and cycling. The nearest airport is Montpellier - Mediterranee Airport, 47 km from Studio Village Naturiste.
Property Facts: Total Number of Rooms: 1Year of Last Renovation: N/A


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This is why I love astronomy!!!!!!
The Universe And Your Place In It
Sep. 5, 2014 Hubble Sees Spiral in Serpens. This new NASA/ESA Hubble Space Telescope image shows a beautiful spiral galaxy known as PGC 54493, located in the constellation of Serpens (The Serpent). This galaxy is part of a galaxy cluster that has been studied by astronomers exploring an intriguing phenomenon known as weak gravitational lensing. European Space Agency ESA/Hubble & NASA, Acknowledgement: Judy Schmidt


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Specials Page
Series: Super Why!
This series focuses on the adventures of four fairytale friends who transform into reading-powered superheroes: Alpha Pig with Alphabet Power, Wonder Red with Word Power, Princess Presto with Spelling Power, Super Why with the Power to Read and Super YOU with the Power to Help. Together, they are the "Super Readers!"
The Super Readers jump into books (literally) to find answers to everyday preschool challenges and embark on exciting adventures, where they play interactive reading games to overcome obstacles and save the day. In every episode, young viewers dive directly into a pop-up story to experience a brightly-illustrated children's tale brought to magical life.
Related: Episodes
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The team teaches a Little Ghost who is scared that there's more to Halloween than meets the eye!
Monday, October 31, 2016 - 11:00am
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Red's new puppy is whimpering and the heroes ask for advice from a boy who can talk to animals.
The Story of Mother Goose
Red gets stuck writing a new song. The heroes meet Mother Goose just as she's starting her poems.
Alice In Wonderland
The heroes tumble down the rabbit hole to catch up with a famous white rabbit who is very late!
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The superheroes help Duckling accept himself as he is and Pig learns a lesson about getting bigger.
The Muddled-Up Fairytales
Things get wacky when a young dragon eager to find a legend of his own moves in with The Three Pigs.
The Story of the Tooth Fairy
Whyatt has lost his very first tooth! The reading heroes set off to meet the Tooth Fairy in person.
The Comic Book: Attack of the Eraser
The super readers must stop the diabolical Eraser from wiping out all of the words in Reader Valley.
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The heroes help Whyatt bake a birthday cake by getting the recipe from a very silly rhyming chef.
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The team goes on a swashbuckling scavenger hunt adventure filled with clues, pirates and treasure!
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Whyatt goes to a pet adoption fair and meets a little puppy. A new Super Reader joins the team!
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Charlie is a bear who is scared of just about anything. The heroes shed some light on the problem.
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The Super Readers head into a story to meet a ballerina doll named Molly who has stage fright.
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The superheroes meet a king who only wants to eat spaghetti and convince him to taste new foods.
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The Super Readers explore ancient Egypt and help Naila unravel a mysterious code to find a treasure.
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The Super Readers lend a hand to a baby dinosaur who is searching for his mommy.
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The Super Readers fly into the story of a princess with a silly sense of humor and a big job to do.
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The team meets a lucky lad and dive inside his magic lamp to speak to a genie who grants wishes.
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Quality shows - on your schedule
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Follow Us On
Watch Secretly Greatly English Sub OnlineSecretly Greatly Watch Online in HD. You can find English Subbed Secretly Greatly Korean Drama Movies Episodes here. Just click on the episode number and watch Secretly Greatly English sub online
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You Are Here : Drama.net > Secretly Greatly
Secretly GreatlyAlternative Titles : Covertness Cast : Kim Soo-Hyun, Park Ki-Woong, Lee Hyun-Woo, Son Hyun-Joo, Park Hye-Sook, Hong Kyoung-In, Kim Sung-Kyun, Ko Chang-Seok, Lee Chae-Young, Park Eun-Bin Episodes : Finished Category: Korean Drama Movies Genres : Comedy, Action Type : Movie Release : 2013 Status : Finished Description : Won Ryu-Hwan (Kim Soo-Hyun) trained in the North Korean Special Forces. He can speak five languages and is also a lethal killing machine. Two years ago, he received orders to deploy to South Korea as a spy.
While wondering in a poor neighborhood in Seoul, Won Ryu-Hwan passed out and was awakened by a worried old mother. The woman then allowed him to live in a small apartment above her modest convenient store and let him work in her store. His identity in South Korea is now Bang Dong-Gu and he has taken up the persona of a goofy, mentally challenged young man. Since that time, Bang Dong-Gu has gotten to know everybody in the neighborhood and has become attached to the woman who treats him like her second son.
One evening, Bang Dong-Gu receives a visitor in his small apartment. His visitor is Lee Hae-Rang (Park Ki-Woong), who trained in the same North Korean Special Forces Unit. Lee Hae-Rang has also received orders from North Korea to work covertly as a spy in South Korea. His persona is that of a young wannabe rock star. Lee Hae-Rang finds it difficult, because he never played the guitar before. Shortly later, Ri Hae-Jin (Lee Hyun-Woo), also a member of their special forces team in North Korea, arrives in the same neighborhood. While the three young men live unnoticed among their neighbors, they await orders from North Korea. Their order finally arrives.
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General Contractors in Rouses Point, NY
General contractors in Rouses Point, NY are worth taking a close look at if you are planning on remodeling a certain area of your home in the near future. These contractors will be able to do the work you need to transform your kitchen, bathroom, basement or another part of your house for the better. Hiring an experienced Rouses Point general contractor will virtually guarantee that you get the quality services you need when it comes to home remodeling or renovation project, and you won't have to do any of the work yourself.
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You will find that Rouses Point general contractors have all the necessary manpower, skills and tools to complete your remodeling project without any issues whatsoever. If you want to improve the way a specific area of your house looks by giving it an updated look and functionality, these professionals will most definitely be able to help. While it is true that you can attempt the remodeling project yourself, you will instead want to look into hiring a general contractor in Rouses Point, NY. Those who hire these contractors are usually very glad they did so, in the end you will find they can meet all of your home improvement needs.
Trahan Construction Inc13 Elm St Rouses Point, NY 12979
Trombley Gerry Construction610 Route 9 Champlain, NY 12919
Barcomb's United Fisheries & Construction41 Gamlaw Rd Champlain, NY 12919
Monette Cabinetry Inc80 Bay Rd Alburgh, VT 05440
Murnane Building Contractors80 Maple St Rouses Point, NY 12979
Bourgeois Construction9446 State Route 9 Chazy, NY 12921


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Hotels in Porto do Son
Hotel reservation
Porto do Son
Hotel rooms in Porto do Son
There are not so many hotel rooms in Porto do Son, just 4, still everyone can find an offer to suit his choice. The most common offers in this city are guest houses, they count 3 out of 4, and their prevalent location is central district. According to our practice, it is the most profitable to book a hotel in the north of Porto do Son, as it is the location of the hotels with optimal cost and quality offers along with the cheap hotels. Taking into account the small size of the city, there is no need to dwell hotel reservation on the location: the road to the city center would take less then half an hour, so one can book a hotel in any district of Porto do Son. The most populated with hotels district of Porto do Son is the center, 50% of cheap hotel rooms are concentrated here. However, even those who want to live in the north can choose from 1 variants of hotel rooms. Porto do Son is an ideal place for couple and family, such travellers rate hotels there 8.6 out of 10 on average. In Porto do Son one can enjoy the beauty of San Martino Pinario Monastery, Museum of the Galician People and Teatro Principal. Moreover, there is a choice of 0 hotels, located within a walking distance from these attractions, however they might not be the cheap ones. Apart from all these, hotels in Porto do Son offer their customers laundry service, pets allowed, business centre and bar. The most appreciated amenities in Porto do Son hotels are room and comfort. According to the visitors reviews, hotels in Porto do Son has clean, rather comfortable and fantastic service. Take a look at our selection of the cheap hotel rooms in Porto do Son to make a well-informed choice for your reservation!
Porto do Son cheap hotels
Guest Houses
Porto do Son
All cheap hotels in Porto do Son
Best hotels in Porto do Son
Hotels in Porto do Son are spread around the city within the distance of 47.2 kilometers, while 2 hotels are located directly in the city center. Those who are keen on antique should definitely fall in love with
Hotel Villa del Son
, the oldest hotel of Porto do Son, constructed in 2002. This hotel is located 0.1 km away from the city center. The most popular accommodations in Porto do Son is
PR La Fe
located in a 47.2 kilometers from the city center.
The best hotels are here and now. Try them!
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Integrated Development Environments (IDE) Software
Campus Management Information System
CMIS , this project was developed on java and thinwire framework, these application will be serve to the school or university to centralized there information system. and also can generate really time data.
Nexus WebIDE
WebIDE is a web-based IDE for developing and maintaining web applications and websites. It is not a CMS and should not be used as one. It allows you to edit any text-based file for your website or web application.
nO Webdesign software
New way for edit webpages for internet. A free option to Dreamweaver. Nova forma de editar páginas web para a internet. Opção gratuita ao Dreamweaver.
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