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- Open Access
Over-expression of a poor prognostic marker in prostate cancer: AQP5 promotes cells growth and local invasion
World Journal of Surgical Oncology volume 12, Article number: 284 (2014)
The aquaporins (AQPs), water channel proteins, are known playing a major role in transcellular and transepithelial water movement; they also exhibit several properties related to tumor development. The aim of the present study is to elucidate whether the expression of AQP5 is a strong prognostic biomarker for prostate cancer, and the potential role in the progression of prostate cancer cells.
AQP5 expression was measured in 60 prostate cancer tissues and cells (both PC-3 and LNCaP) by immunohistochemistry and immunofluorescence assay. AQP5 gene amplification was detected with FISH (fluorescence in situ hybridization). Proliferation and migration of cells and AQP5 siRNA cells were detected with MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and Boyden chambers. Circulating tumor cells (CTCs) were detected by imFISH staining (CEP8-CD45-DAPI) assay.
The results showed that in 60 tumor specimens, 19 (31.7%) patients showed high level of AQP5 expression, while 30 (50.0%) showed a moderate, intermediate level of staining, and 11 (18.3%) showed an absence of AQP5 staining, respectively. High-expression of AQP5 protein frequently accompanied gene amplification detection with FISH. The AQP5 over-expression was also associated with TNM stage (P = 0.042), and lymph node metastasis (P = 0.001). The relationships between age or tumor size with the expression of AQP5 were not significant (P > 0.05). A positive correlation between the number of CTCs and AQP5 expression (P < 0.05) was demonstrated. In addition, patients who were negative for AQP5 had superior cumulative survival rate than those who were positive for it. Over-expression of AQP5 protein was also found in prostate cancer cells and cell proliferation and migration were significantly attenuated by AQP5-siRNA.
We concluded that AQP5 in prostate cancer was an independent prognostic indicator. AQP5 over-expression was likely to play a role in cell growth and metastasis. These conclusions suggest that AQP5 may be an effective therapeutic target for prostate cancer.
Prostate cancer (PCa) is the second most frequent cause of cancer-related deaths among males in the USA . Despite the widespread presence of clinically insignificant tumors in elderly men, PCa commonly has an aggressive phenotype that requires prompt intervention . Therefore, it is extremely important to seek novel targets for therapeutic intervention.
Recently, studies have shown that tumor growth, development, invasion and metastasis depend on tumor microenvironment and tumor metabolism. Specifically, the water balance between the inside and outside of cells is essential to maintain the malignant epithelial cell function. Water can permeate the plasma membrane by simple diffusion, but bulk water flow is mediated by a channel mechanism through aquaporin (AQP) enzymes . AQPs belong to a family of water-transporting proteins. Up to now, 13 members of the AQPs have been identified and can be subdivided into two groups on the basis of their permeability: AQP1, 2, 4, 5 and 8 are water-selective transporters, while AQP3, 7, 9 and 10, termed aquaglyceroporins, transport water as well as glycerol and other small solutes [4–6].
The role of AQPs in tumor pathogenesis has been identified. The study showed that aquaporin 3 was found to be over-expressed in malignant prostate tissue and may be involved in tumor progression [7, 8]. The expression of AQP1 is confined to prostate cancer cells and may be involved in microvascular alteration during tumor angiogenesis . The over-expression of AQP5 was examined recently and showed that AQP5 is significantly associated with cervical cancer, ovarian cancer, and breast cancer progression . It was shown that AQP5 plays a key role in cell proliferation. A recent study showed that AQP5 expression in colorectal cancer is significantly associated with lung metastasis that is possibly mediated by the activation of Ras, mitogen activated protein kinase (MAPK) and Rb signaling pathways . However, the expression of AQP5 in prostate cancer and its clinical significance remain unexplored. To evaluate the potential of AQP5 as a novel prognostic marker of prostate cancer, we employed immunohistochemical, immunofluorescence, and FISH methods to detect the expression and amplification of AQP5 gene in clinical samples and prostate cancer cells, and immunofluorescence in situ hybridization (imFISH) staining to detect CTCs. We first analyzed the correlations between the expression of AQP5 and clinicopathologic features, CTCs, and prognosis of prostate cancer. Then, we also analyzed the effects of AQP5 knockdown on the cell proliferation and migration with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and Boyden chambers.
From January 2009 to June 2013, 60 patients were recruited from the Department of Urology Surgery, Second Affiliated Hospital of the Xi’an Jiaotong University. Samples were fixed with 4% formalin for histological studies. Of the 60 patients, median age at the time of surgery was 56.7 years (range 40 to 76 years). Tumor stage was recorded according to the classification of the International Union against Cancer (TNM stage). There were 7 patients with stage I tumors, 22 with stage II, 27 with stage III, and 4 with stage IV. All patients underwent operative surgical therapy, including partial resection or radical excision at the Department of Urinary Surgery, Second Affiliated Hospital of the Xi’an Jiaotong University. All patients were followed up and the median duration of follow-up was 23 months (4 to 52 months). All the studies were approved by the Human Subjects Committee of the Xi’an Jiaotong University, China. Written informed consent was obtained from the patient for the publication of this report and any accompanying images
PC-3 and LNCaP prostate cancer cell lines (obtained from the American Tissue Type Collection, USA) were maintained in DMEM (GIBCO, Grand Island, NY, USA) and 10% heat-inactivated FBS and incubated in 5% CO2 humidified atmosphere at 37°C. Cells were grown to 80% confluency prior to treatment.
AQP5 protein was detected immunohistochemically using a standardized streptavidin-peroxidase (SP) method. Tissue sections (4 μm) were incubated overnight with primary monoclonal antibody (1:100 dilution). Then the slides were incubated for 30 minutes with biotinylated goat anti-rabbit IgG (1:200 dilution). Color was developed using 0.02% 3,3’-diaminobenzidine (DAB) for 5 to 7 minutes. Negative controls for immunostaining replaced the primary antibody with nonimmune goat or rabbit serum. The staining was scored semiquantitatively as negative (0; no staining or < 10% staining), moderate (1; either diffuse weak staining or strong staining in less than 30% of cells per core), or strong (2; defined as strong staining of 30% or more of the cells). The antibodies against AQP5, and β-actin were purchased from Santa Cruz Biotechnology (Santa Cruz, CA, USA).
Tissue sections (4 μm) were incubated overnight. Slides were incubated with CY3-labeled anti-AQP5 (1:100) overnight. Fluorescent imaging was obtained with a confocal laser scanning microscope (Carl Zeiss MicroImaging, Inc., Thornwood, NY, USA). Exponentially growing cells were seeded on 25-mm square glass cover slips. Cells were fixed with 4% formaldehyde for 5 minutes, permeabilized with 0.2% solution of Triton X-100 in PBS, and blocked with 2% BSA-PBS for 30 minutes. Slides were incubated with CY3- or FITC-labeled anti-AQP5 (1:100) overnight, respectively. Cell nuclei were counterstained by 4’,6-diamidino-2-phenylindole (DAPI). Fluorescent imaging was obtained with a confocal laser scanning microscope (Carl Zeiss MicroImaging, Inc., Thornwood, NY, USA).
Fluorescence in situ hybridization
AQP5 gene amplification was detected with dual-color fluorescence in situ hybridization (FISH) using a Passvision AQP5 DNA probe kit (Vysis Inc. Downers Grove, IL, USA) according to its manufacturer’s instructions. Sections were baked overnight at 56°C, and were then deparaffinized followed by enzyme digestion and fixation. The slides were then denatured in 70% formamide/2 × standard saline citrate. After a buffer wash, 10 μl of a mixture of two directly labeled probes were added and hybridization was carried out at 37°C for 14 to 18 hours. The slides were then counterstained with DAPI, mounted, and stored in the dark before signal enumeration. AQP5-spectrum red probe contains a DNA sequence specific for the AQP5 gene. CEP17 (chromosome enumeration probe 17)/spectrum green probe containing alpha-satellite DNA that hybridizes to the D17Z1 locus (centromere region of chromosome 17) was used as a control. Gene amplification was scored when a minimum of 20 cancer cell nuclei exhibited AQP5/CEP17 ratio ≥ 2, or when AQP5 signal cluster was observed.
Cell viability assay
Cells were seeded (5 × 103/well) in 96-well plates and cultured overnight. Then the MTT assay was used to determine cell viability. siRNA was added to the cells and further cultured for 24 hours. Then, MTT reagent (5 mg/ml) was added and incubation continued for an additional 4 hours. The reaction was terminated with 150 μl of dimethylsulfoxide (DMSO, Sigma-Aldrich, St Louis, MO, USA) per well. Absorbance values were determined using an MRX Revelation 96-well multiscanner (Dynex Technologies, Chantilly, VA, USA).
RT-PCR (Reverse transcription-polymerase chain reaction)
Total RNA from cells was isolated using TRIzol reagent (GIBCO BRL, Grand Island, NY, USA). First-strand cDNA was synthesized from 2 μg of total RNA using the RevertAid Kit. The PCR primers that were used for the detection of AQP5 was synthesized as follows: 5’-CAG CTG GCA CTC TGC ATC TT-3’ (sense) and 5’-TGA ACC GAT TCA TGA CCA CC-3’ (antisense) and 5’-ATC GTG CGT GAC ATT AAG GAG AAG-3’ (sense) and 5’-AGG AAG AAG GCT GGA AGA GTG-3’ (antisense) for β-actin (179 bp). The PCR conditions were as follows: one cycle of denaturing at 94°C for 3 minutes, followed by 35 cycles at 94°C for 30 seconds, 55°C for 30 seconds, and 72°C for 35 seconds before a final extension at 72°C for 5 minutes.
Briefly, 5 × 105 cells were incubated on ice for 30 minutes in 0.5 ml of ice-cold whole-cell lysate buffer. The protein content of the cell was determined, and the cellular lysates were separated by 10% SDS-PAGE, and electro-transferred onto nitrocellulose membranes. After being blocked with 5% non-fat milk in tris-buffered saline and Tween (TBST), the membranes were incubated with primary antibodies at 4°C overnight, followed by secondary antibody for 2 hours. Immunoreactive bands were visualized using an enhanced chemiluminescence kit (Amersham Pharmacia Biotech, Piscataway, NJ, USA). The Western blot signals were quantitated by densitometric analysis using Total Lab Nonlinear Dynamic Image analysis software (Nonlinear, Durham, NC, USA).
To inhibit the expression of AQP5, we used siRNA oligonucleotide sequence: 5’-CGG UGG UCA UGA AUC GGU UTT-3’ (sense) and 5’-AAC CGA UUC AUG ACC ACC GCA-3’ (antisense). The oligonucleotides for negative siRNA were synthesized as sense 5’-UUC UCC GAA CGU GUC ACG UTT-3’, antisense 5’-ACG UGA CAC GUU CGG AGA ATT-3’. The PC-3 cells (2 × 106) were transfected with siRNA targeted against AQP5 (100 nm/l) or a control siRNA (Qiagen, Valencia, CA, USA) using Lipofectamine 2000 (Invitrogen, Carlsbad, CA, USA). Cells were covered overnight before starvation.
Cell invasion assay
Cell invasion assay was performed by employing Boyden chambers coated with 50 μg/ml of Matrigel solution. The cells were first seeded in 12-well plates at a concentration of 2.5 × 105 per well and were cultured for 48 hours. The Matrigel invasion chamber was incubated for 24 hours in a humidified tissue culture incubator. After 24 hours, the noninvasive cells were removed from the upper surface of the separating membrane by gentle scrubbing with a cotton swab, and the invading cells were fixed in 100% methanol and stained with 0.1% crystal violet solution. They were then counted under a microscope at 200× magnification.
Blood sampling and enrichment of circulating tumor cells
Seven and half milliliters of peripheral blood collected in BD Vacutainer tube (Becton, Dickinson and Company, Franklin, NJ, USA) were washed with PBS. All samples were collected after discarding the first 2 ml of blood. Red blood cells were removed. Resulting cell pellet was resuspended in PBS and subsequently incubated with 0.5 ml of antileukocyte surface marker CD45 monoclonal antibody coated magnetic beads for 30 minutes, followed by separation of magnetic beads using a magnetic stand (Promega, Madison, WI, USA). Supernatants were transferred into a new tube, and subsequently centrifuged at 800 g for 3 minutes. Cell pellets were spotted on glass slides, and then followed with imFISH (immuno- fluorescence in situ hybridization) staining.
imFISH staining (CEP8-CD45-DAPI)
Tumor cells were negative enriched by immunomagnetic beads method, followed by identification with cytology analysis. FISH was performed using centromere DNA probes of chromosome 8 (yellow) (Vysis Inc. Downers Grove, IL, USA), and immunofluorescence assay was performed using anti-CD45 (red) (Santa Cruz Biotechnology Inc., Santa Cruz, CA, USA). The slides were washed three times with TBS. Cells were mounted with mounting medium containing the nuclear dye DAPI. A blinded review of the fluorescent images by three technicians confirmed the identity of the CTCs from 3-color fluorescent images that were magnified x400. Evaluation criteria for CTC identification from fluorescent images included both CEP8 ≥ 3 and CD45 (−) staining pattern overlying the DAPI staining of the nucleus.
Statistical analysis and patient outcome
Data were analyzed by chi-square test (χ2) or two-sided Fisher’s exact test, as appropriate. Pearson correlation coefficient was used to measure the strength of the association among AQP5 gene amplification. Survival rate was calculated by the Kaplan-Meier method, and differences were examined by the log-rank test. Factors found to be significant were then selected for a stepwise Cox’s multivariate proportional hazard model to determine their prognostic values. P < 0.05 was considered statistically significant. All statistical analyses were performed using SPSS Version 13.0 statistical software (SPSS, Chicago, IL, USA).
Protein expression and gene amplification of AQP5 in prostate cancer
To examine the expression status of AQP5 in prostate cancer, we first used immunohistochemical evaluation. The results highlight the difference observed in AQP5 immunostaining in the compartment (Figure 1A). In 19/60 (31.7%) patients, AQP5 expression was strong and in 30/60 (50.0%) patients AQP5 expression was moderate in the cancer group. AQP5 expression was only occasionally detected in paraneoplastic 11/60 (16.7%) and normal tissues 8/60 (13.3%).To further determine AQP5 expression, prostate tissue was stained with fluorescence immunostaining and analyzed by confocal microscopy. The results showed that AQP5 fluorescence signal is substantially increased in the cancer group compared to the paraneoplastic and normal group (Figure 1B). The above results further suggest that AQP5 is over-expressed in prostate cancer.
Because FISH is a more accurate and sensitive assay (usually regarded as the gold standard) for detecting gene amplification compared to gene expression using immunohistochemistry, we further detected AQP5 amplification status using FISH. Interestingly, strong AQP5 expression had a positive correlation with AQP5 gene amplification (r = 0.774, P = 0.009; Figure 1C; Table 1). In contrast, the expression of AQP5 was weak or absent where the AQP5 gene was not amplified.
Relationships between AQP5 expression and clinicopathological parameters
Table 2 summarizes the associations of AQP5 protein expression and the clinicopathological parameters of prostate cancer. The strong expression of AQP5 was seen in 5 of 29 stage I to II cases (17.2%) and was significantly lower than that in stage III (37.0%, 10 of 27 cases) and stage IV (100.0%, 4 of 4 cases) cases (P < 0.05). AQP5 expression was also associated with lymph node metastasis (P = 0.001). We also investigated the relationship between age, tumor size with expression of AQP5, however, but no significant relationships were observed between these factors (P > 0.05).
Prognostic value of AQP5 in patients with prostate cancer
In order to determine the prognostic value of AQP5 for prostate cancer, we analyzed the cumulative survival of patients according to their AQP5 status (Figure 2). The AQP5-weak and non-staining specimens were merged as AQP5-negative, and strongly staining was regarded as AQP5-positive. The cumulative survival rate in AQP5-negative patients (n = 41) at 3 years was 64.3% (n = 26.4 median time 65.2 months). In contrast, the cumulative survival rate in AQP5-positive patients (n = 19) was 23.2% (n = 4.4 median time 20.7 months), a difference that is highly statistically significant (P < 0.05).
Multivariate analysis in our study revealed that lymph node metastasis (P = 0.048) and ABCD stage (P = 0.037) were the independent prognostic factors for overall survival time in patients with prostate cancer. Tumor diameter and other clinical parameters were also not independent prognostic factors.
Expression of AQP5 correlates with CTCs enumeration
CTCs are shed from the primary tumor into the circulation. This has long been associated with metastasis and poor survival. In view of the obvious clinical relevance, CTCs have been recently recommended by the American Society of Clinical Oncology as an acceptable cancer marker. To further determine whether or not AQP5 is an adverse prognostic biomarker, the correlation between AQP5 expression and the number of CTCs was analyzed. CTCs were detected in 65.00% (13/20) of prostate cancer patients with strong AQP5 expression versus 30.00% (12/40) with low and absent AQP5 expression (P < 0.05; Figure 3).
AQP5 expression in prostate cancer cells
To further determine AQP5 expression in prostate cancer cells, PC-3 and LNCaP cells were stained with fluorescence immunostaining and analyzed by confocal microscopy. The endothelial cell ECV-304 was used as a negative control and human lung cancer cell line A549, the AQP5-expressing cancer cell line was used as a positive control for AQP5 expression. Immunoblotting analysis revealed that both prostate cancer cell lines express AQP5 protein (Figure 4). AQP5 fluorescence signal in PC-3 is substantially stronger than LNCaP, so this cell was used for the further study.
Proliferation and migration of PC-3 cells were inhibited in response to AQP5 silencing
To examine whether AQP5 expression plays a role in the progression of prostate cancer, proliferation and migration of prostate cancer cells were examined in response to siRNA-mediated knockdown of AQP5. AQP5 mRNA and protein expression in PC-3 cell was significantly decreased by AQP5 siRNA transduction. The MTT result demonstrated that proliferation ability of PC-3 cell was significantly decreased with AQP5 silencing. Moreover, the number of migrated PC-3 cells was significantly decreased in response to AQP5 silencing (Figure 5).
Prostate cancer is one of the most aggressive and intractable malignant tumors, and its incidence and mortality have also rapidly increased in the United States . Unfortunately, the mechanisms contributing to its carcinogenesis and progression are still poorly understood. In the present study, we aimed to determine the clinical significance of AQP5 expression in prostate cancer patients. AQP5, as a water channel protein, is also a predictor of early tumor recurrence, lymph node metastasis, and poor clinical outcome in cancer patients . Our results revealed that AQP5 is up-regulated in prostate cancer and this expression is accompanied by AQP5 DNA amplification. AQP5 protein was also expressed in prostate cancer cell lines, PC-3 and LNCaP. Our results also suggested that AQP5 is closely correlated with advanced TNM stage, CTCs, and poor prognosis. Cell culture experiments also revealed the role of AQP5 in tumor cell proliferation and migration. These findings extend our understanding of AQP5 role as a negative prognostic marker.
Aquaporins (AQPs) are a family of small membrane transport proteins . Compelling new evidence has implicated several members of the AQP family, including AQP5, in tumorigenesis. Moreover, intensive studies have been focused on the modulation of AQP5 expression in tumor cells and its effects on tumorigenesis, tumor growth and progression [15–18]. AQP5, a 21 to 24 kDa protein, is a component of caveolae, invaginated microdomains of the plasma membrane. AQP5 was initially described as the main structural protein in caveolae and was believed to be a key molecule involved in oncogenic transformation and malignant progression . AQP5 plays an important regulatory role in several signaling pathways in cellular transformation, including those mediated by the Src family of tyrosine kinases, epidermal growth factor receptor, protein kinase C, Wnt, and Erk1/2 . AQP5 has been suggested to act either as a tumor suppressor or as an oncogene, depending on the tumor type. These various effects may be explained by the activation status of different domains of AQP5 or the expression levels of other molecules that interact with AQP5 in these different signaling pathways . Recently, Lee et al. reported that AQP5 over-expression was significantly associated with lymph node involvement and a poorer prognosis in patients with breast cancer . Huang et al. also verified that AQP5 promoted the proliferation and migration of human gastric carcinoma cells. Interestingly , Fischer et al. performed differential display to find that AQP5 was expressed only in normal colonic tissue and not, or to a lesser extent, in cancer cells . The clinical significance of AQP5 in prostate cancer remains largely unexplored. Our results showed that AQP5 was mainly expressed in prostate cancer cells. The expression patterns of AQP5 in prostate tissues that we detected are consistent with the results of previous studies [6, 10, 11, 22]. Furthermore, we determined that high levels of expression of AQP5 were correlated with gene amplification in our limited cases study, which is the first reported in prostate cancer. In addition, in the present study, we also demonstrated significantly decreased cell proliferation and migration of prostate cancer cells with AQP5 silencing. Osmolar changes have been revealed to affect cell proliferation, as previously demonstrated by the negative effect of hypertonicity on cell proliferation . Tumor cells bind to the basal membrane surface, and the formation of pseudopodial protrusions at the leading edge of migrating cells is the earliest step in locomotion. Studies have suggested that AQP-facilitated water permeability in cell protrusions enhances their formation and thus the rate of cell migration. AQP expression and tumor cell water permeability are potentially important determinants for tumor spread and metastasis [24–26]. However, the possibility that AQP5 may promote cancer cell migration by other mechanisms could not be excluded. Further studies are required to elucidate the specific underlying molecular mechanisms.
CTCs are tumor cells shed from the primary tumor into the circulation. The presence of CTCs in the peripheral blood of patients has long been associated with metastasis and poor survival and is now considered an acceptable cancer marker. Yet, current techniques are limited [27, 28]. The only commercially available CTC test (CellSearch; Veridex LLC, North Raritan, NJ, USA) has a detection rate of 50% in late-stage patients [29, 30]. In the current study, we detected CTCs harboring negative enrichment using an immunomagnetic beads method, followed by identification with cytologic analysis, immunofluorescence, and imFISH. This combination of methods resulted in detection rates up to 65.00% in patients with AQP5 over-expression, suggesting that imFISH staining could be used as a detection method for CTCs in future studies. In addition, our study verified that AQP5 over-expression is associated with the likelihood of metastasis compared to lower expression of AQP5.
The AQP5 protein is up-regulated in prostate cancer and is closely related to advanced ABCD stage, lymph node metastasis, CTCs and poor prognosis. Moreover, AQP5 expression was associated with cell proliferation and migration. Although the mechanisms require further elucidation, AQP5 might be used as a novel biomarker for prostate cancer aggressiveness.
bovine serum albumin
circulating tumor cells
Dulbecco’s modified Eagle’s medium
fluorescence in situ hybridization
immunofluorescence in situ hybridization
mitogen activated protein kinase
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide
reverse transcription-polymerase chain reaction
tris-buffered saline and Tween.
Snyder A, Tepper JE, Slovin SF: Perspectives on immunotherapy in prostate cancer and solid tumors: where is the future?. Semin Oncol. 2013, 40: 347-360. 10.1053/j.seminoncol.2013.04.009.
Bhavsar T, McCue P, Birbe R: Molecular diagnosis of prostate cancer: are we up to age?. Semin Oncol. 2013, 40: 259-275. 10.1053/j.seminoncol.2013.04.002.
Sekine S, Shimada Y, Nagata T, Moriyama M, Omura T, Watanabe T, Hori R, Yoshioka I, Okumura T, Sawada S, Fukuoka J, Tsukada K: Prognostic significance of aquaporins in human biliary tract carcinoma. Oncol Rep. 2012, 27: 1741-1747.
Burghardt B, Elkaer ML, Kwon TH, Racz GZ, Varga G, Steward MC, Nielsen S: Distribution of aquaporin water channels AQP1 and AQP5 in the ductal system of the human pancreas. Gut. 2003, 52: 1008-1016. 10.1136/gut.52.7.1008.
Delporte C, Steinfeld S: Distribution and roles of aquaporins in salivary glands. Biochim Biophys Acta. 2006, 1758: 1061-1070. 10.1016/j.bbamem.2006.01.022.
McCoy E, Sontheimer H: Expression and function of water channels (aquaporins) in migrating malignant astrocytes. Glia. 2007, 55: 1034-1043. 10.1002/glia.20524.
Ismail M, Bokaee S, Morgan R, Davies J, Harrington KJ, Pandha H: Inhibition of the aquaporin 3 water channel increases the sensitivity of prostate cancer cells to cryotherapy. Br J Cancer. 2009, 100: 1889-1895. 10.1038/sj.bjc.6605093.
Wang J, Tanji N, Kikugawa T, Shudou M, Song X, Yokoyama M: Expression of aquaporin 3 in the human prostate. Int J Urol. 2007, 14: 1088-1092. 10.1111/j.1442-2042.2007.01901.x. 1092
Mobasheri A, Airley R, Hewitt SM, Marples D: Heterogeneous expression of the aquaporin 1 (AQP1) water channel in tumors of the prostate, breast, ovary, colon and lung: a study using high density multiple human tumor tissue microarrays. Int J Oncol. 2005, 26: 1149-1158.
Woo J, Lee J, Chae YK, Kim MS, Baek JH, Park JC, Park MJ, Smith IM, Trink B, Ratovitski E, Lee T, Park B, Jang SJ, Soria JC, Califano JA, Sidransky D, Moon C: Overexpression of AQP5, a putative oncogene, promotes cell growth and transformation. Cancer Lett. 2008, 264: 54-62. 10.1016/j.canlet.2008.01.029.
Kang SK, Chae YK, Woo J, Kim MS, Park JC, Lee J, Soria JC, Jang SJ, Sidransky D, Moon C: Role of human aquaporin 5 in colorectal carcinogenesis. Am J Pathol. 2008, 173: 518-525. 10.2353/ajpath.2008.071198.
Clyne M: Prostate cancer: androgen deprivation causes EMT in the prostate. Nat Rev Urol. 2012, 9: 4-
Lee SJ, Chae YS, Kim JG, Kim WW, Jung JH, Park HY, Jeong JY, Park JY, Jung HJ, Kwon TH: AQP5 Expression Predicts Survival in Patients with Early Breast Cancer. Ann Surg Oncol. 2013, 21 (2): 375-383.
Shen L, Zhu Z, Huang Y, Shu Y, Sun M, Xu H, Zhang G, Guo R, Wei W, Wu W: Expression profile of multiple aquaporins in human gastric carcinoma and its clinical significance. Biomed Pharmacother. 2010, 64: 313-318. 10.1016/j.biopha.2009.12.003.
Yang JH, Yu YQ, Yan CX: Localisation and expression of aquaporin subtypes in epithelial ovarian tumours. Histol Histopathol. 2011, 26: 1197-1205.
Wang W, Li Q, Yang T, Bai G, Li D, Li Q, Sun H: Expression of AQP5 and AQP8 in human colorectal carcinoma and their clinical significance. World J Surg Oncol. 2012, 10: 242-10.1186/1477-7819-10-242.
Zhang ZQ, Zhu ZX, Bai CX: Lung fluorescence imaging to evaluate tumor metastasis induced by AQP5 expression in murine model. Med Oncol. 2012, 29: 205-211. 10.1007/s12032-010-9788-5.
Chae YK, Kang SK, Kim MS, Woo J, Lee J, Chang S, Kim DW, Kim M, Park S, Kim I, Keam B, Rhee J, Koo NH, Park G, Kim SH, Jang SE, Kweon IY, Sidransky D, Moon C: Human AQP5 plays a role in the progression of chronic myelogenous leukemia (CML). PLoS One. 2008, 3: e2594-10.1371/journal.pone.0002594.
Woo J, Lee J, Kim MS, Jang SJ, Sidransky D, Moon C: The effect of aquaporin 5 overexpression on the Ras signaling pathway. Biochem Biophys Res Commun. 2008, 367: 291-298. 10.1016/j.bbrc.2007.12.073.
Huang YH, Zhou XY, Wang HM, Xu H, Chen J, Lv NH: Aquaporin 5 promotes the proliferation and migration of human gastric carcinoma cells. Tumour Biol. 2013, 34: 1743-1751. 10.1007/s13277-013-0712-4.
Fischer H, Stenling R, Rubio C, Lindblom A: Differential expression of aquaporin 8 in human colonic epithelial cells and colorectal tumors. BMC Physiol. 2001, 1: 1-10.1186/1472-6793-1-1.
Chae YK, Woo J, Kim MJ, Kang SK, Kim MS, Lee J, Lee SK, Gong G, Kim YH, Soria JC, Jang SJ, Sidransky D, Moon C: Expression of aquaporin 5 (AQP5) promotes tumor invasion in human non small cell lung cancer. PLoS One. 2008, 3: e2162-10.1371/journal.pone.0002162.
Burg MB, Ferraris JD, Dmitrieva NI: Cellular response to hyperosmotic stresses. Physiol Rev. 2007, 87: 1441-1474. 10.1152/physrev.00056.2006.
Saadoun S, Papadopoulos MC, Hara-Chikuma M, Verkman AS: Impairment of angiogenesis and cell migration by targeted aquaporin-1 gene disruption. Nature. 2005, 434: 786-792. 10.1038/nature03460.
Hu J, Verkman AS: Increased migration and metastatic potential of tumor cells expressing aquaporin water channels. FASEB J. 2006, 20: 1892-1894. 10.1096/fj.06-5930fje.
Verkman AS: More than just water channels: unexpected cellular roles of aquaporins. J Cell Sci. 2005, 118: 3225-3232. 10.1242/jcs.02519.
Onstenk W, Gratama JW, Foekens JA, Sleijfer S: Towards a personalized breast cancer treatment approach guided by circulating tumor cell (CTC) characteristics. Cancer Treat Rev. 2013, 39: 691-700. 10.1016/j.ctrv.2013.04.001.
Attard G, Crespo M, Lim AC, Pope L, Zivi A, De Bono JS: Reporting the capture efficiency of a filter-based microdevice: a CTC is not a CTC unless it is CD45 negative -letter. Clin Cancer Res. 2011, 17: 3048-3049. 10.1158/1078-0432.CCR-10-3234. 3050
Coumans FA, Ligthart ST, Uhr JW, Terstappen LW: Challenges in the enumeration and phenotyping of CTC. Clin Cancer Res. 2012, 18: 5711-5718. 10.1158/1078-0432.CCR-12-1585.
Lustberg M, Jatana KR, Zborowski M, Chalmers JJ: Emerging technologies for CTC detection based on depletion of normal cells. Recent Results Cancer Res. 2012, 195: 97-110. 10.1007/978-3-642-28160-0_9.
We thank the staff of the Biology and Genetics Laboratory, Xi’an Jiaotong University for their technical assistance in these studies.
The authors declare that they have no competing interests.
ZMW carried out experimental procedures and drafted the manuscript. JPL, TC, HWC, HCL, GL, XQZ and YFL participated in the study design and were involved in the collection of clinical data and specimens. JPL designed the study and gave conceptual advice. All authors read and approved the final manuscript.
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Li, J., Wang, Z., Chong, T. et al. Over-expression of a poor prognostic marker in prostate cancer: AQP5 promotes cells growth and local invasion. World J Surg Onc 12, 284 (2014). https://doi.org/10.1186/1477-7819-12-284
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Alcalá la Real
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Alcalá la Real(älkälä` lä rāäl`), town (1990 pop. 21,128), Jaén prov., S Spain, in Andalusia. It has well-known mineral springs. The town played an important part in the conquest of Granada from the Moors (15th cent.). In 1810 it was the site of a French victory in the Peninsular War.
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Late this afternoon the Sault Ste. Marie Police Service received information that Halloween treats were tampered with.
The Sault Ste. Marie Police Service has received a report of a sewing needle being located inside a small chocolate bar after a child bit into it. The child was not injured.
The investigation is in the preliminary stages and anyone who may have discovered tampered candy is urged to contact the Sault Ste. Marie Police Service at 705-949-6300. An officer from Investigation Services has been assigned to this investigation.
The initial information suggests the candy was handed out in the Lorna Drive, Copernicus Drive and Kerr Drive area; but may be a wider area.
Parents are urged to use caution and take a second look at your child’s candy. It is suggested that before anyone bites into any candy it is cut into small pieces first.

domain: law


text:
During my transition to a plant-based diet, it was critical for me to have a “go-to” meal that I truly enjoyed, so I would not be tempted to go back to old favorite dishes that included animal ingredients. So, I created Smashed Olive Pasta!
We’ve partnered with renowned online education provider eCornell, to offer a revolutionary program to help you understand the importance of diet and nutrition for your life. In a few short weeks arm yourself with the knowledge you need to improve your overall health, learn new skills, or even inspire a career change. Hear what people are saying.

domain: food


Kusters Calico Machinery Pvt Ltd (KCM), a producer and exporter of open width wet textile processing machines for both woven and knitted fabrics, inaugurated its upgraded manufacturing facility on April 11, 2018. With this new upgraded manufacturing facility, KCM aims to provide timely delivery and high quality German products to customers in India and abroad.
With strong backing of its German parent, the Jagenberg Group, which now holds 100% controlling stake in Kusters Calico since February 2018, KCM started the upgradation exercise two years back and has invested close to Rs. 10 crores, with plans to invest another Rs. 5 crores in 2018.
Now, the company has set a goal to reach revenues of Rs 120 crores in the next few years, as against Rs 85 crores currently.
The inaugural function was graced by Shri Rajendra Trivedi, Honâ€™ble Speaker, Gujarat Legislative Assembly, Shri Mansukh Vasava, Member of Parliament and Shri Satish Patel, Ex Member of Gujarat Legislative Assembly.
The function was also attended by Dr. Erich Broeker, Group CEO, Jagenberg AG and Managing Director Kleinewefers GmbH, Germany, Mr Sushil Verma, Managing Director, Kusters Calico Machinery Pvt. Ltd and employees of KCM.
Under the upgradation program, KCM has constructed a new 22,000 sq. feet assembly shed, one double column 4 metre x 1.5 metre 4 axis rotating head machining centre, converted all lathe machines to CNC and commissioned separate blasting and painting booths, for both MS and SS. Also, successfully commissioned SAP B1, HRMS and PLM software. These are just a few of the more than 100 projects, KCM has initiated.
â€œKCM has always strived to offer better products and services to its customers and has been working to further improve various processes, infrastructure, facilities to upgrade our product range to meet customer expectations and requirements of high end technologies. This new upgraded facility will help better all the above and more,â€ Mr Sushil Verma, Managing Director at KCM said.
In textile wet processing machines, KCM manufactures Washing, Dyeing, Bleaching, Singeing, Mercerizing, Finishing, Desizing and Dye Padders. It also manufactures Converting machines for Coating and Lamination lines, which are used, for converting plastic films or foils to packaging material or for further processing by creating barriers for air, moisture and light by coating with various materials.
KCM has installed around 500 wet processing textile machinery in various countries worldwide, which includes Germany, Turkey, Russia, USA, Middle East, Egypt, Iran, Bangladesh, Vietnam, Thailand, Malaysia, Indonesia, and Africa besides selling to all major textile companies in India. This year KCM is exploring markets in other countries like Uzbekistan, Sri Lanka and Myanmar.
In coming years, several Jagenberg AG Group companies want to introduce their products in India and Kusters Calico is evaluating the manufacturing of these products in India under the â€˜Make in Indiaâ€™ concept of our Honâ€™ble Prime Minister. This will further increase the production capacity of KCM in coming years.
A weekly report covering market and price information on the entire chain of polyester along with online access to daily polyester chain prices.
One-time reports that are issued annually cover the demand and supply trends in individual products including polyester, nylon, acrylic, viscose, and cotton.
One-time reports that are issued annually cover the demand and supply trends in the individual country's natural and manmade fiber/filament industries.
Countries Served Worldwide


text:
- What are the bile and pancreatic ducts?
- Is cystic duct the same as bile duct?
- Which side is pancreas pain?
- What does pancreatic pain feel like?
- What causes pancreatic duct blockage?
- What makes the common bile duct?
- How long is the common bile duct?
- Where is the pancreatic duct located?
- How is a blocked pancreatic duct treated?
- How long can you live with a blocked bile duct?
- How can I clean my bile duct naturally?
- What are the symptoms of bile duct problems?
- Will a CT scan show blocked bile ducts?
- What duct connects the gallbladder to the common bile duct?
- What are the symptoms of your pancreas not working properly?
- What are the symptoms of gallstones in the bile duct?
- Can a blocked bile duct cause weight gain?
- Does the common bile duct go through the pancreas?
What are the bile and pancreatic ducts?
The pancreas and bile duct (biliary) systems together form an important part of the digestive system.
The pancreas and liver produce juices (pancreatic juice and bile) which help in the process of digestion (i.e.
the breakdown of foods into parts which can be absorbed easily and used by the body)..
Is cystic duct the same as bile duct?
A tube that carries bile from the gall bladder. It joins the common hepatic duct to form the common bile duct. It is part of the biliary duct system.
Which side is pancreas pain?
The main symptom of pancreatitis is pain felt in the upper left side or middle of the abdomen. The pain: May be worse within minutes after eating or drinking at first, more commonly if foods have a high fat content. Becomes constant and more severe, lasting for several days.
What does pancreatic pain feel like?
Acute pancreatitis signs and symptoms include: Upper abdominal pain. Abdominal pain that radiates to your back. Abdominal pain that feels worse after eating.
What causes pancreatic duct blockage?
Potential causes of pancreatic ductal obstruction include: (1) anatomical congenital variations of the biliopancreatic ductal system; (2) acquired obstructive conditions at the level of major/minor papilla, the level of the main pancreatic duct (MPD), or the level of the duodenal wall; (3) pancreatic sphincter of Oddi …
What makes the common bile duct?
The common bile duct, sometimes abbreviated CBD, is a duct in the gastrointestinal tract of organisms that have a gallbladder. It is formed by the union of the common hepatic duct and the cystic duct (from the gallbladder). It is later joined by the pancreatic duct to form the ampulla of Vater.
How long is the common bile duct?
The common bile duct is formed at the junction of the common hepatic duct with the cystic duct. At adults, the length was between 55–150 mm and the diameter between 4–14 mm, for males, and the length was between 50–95 mm and the diameter between 4–8 mm, for females.
Where is the pancreatic duct located?
Front View of the Pancreas The pancreas is about 6 inches long and sits across the back of the abdomen, behind the stomach. The head of the pancreas is on the right side of the abdomen and is connected to the duodenum (the first section of the small intestine) through a small tube called the pancreatic duct.
How is a blocked pancreatic duct treated?
Treatment is aimed at correcting the underlying cause. The primary objective of medical or surgical treatment is to alleviate the blockage. Some of the treatment options include a cholecystectomy and an ERCP. A cholecystectomy is the removal of the gallbladder if there are gallstones.
How long can you live with a blocked bile duct?
Death from obstructive jaundice in the first few weeks of its course is quite rare and is only occasionally observed. After a period varying from four to six months, however, patients suffering from occlusion of the common bile duct usually deteriorate rapidly and die.
How can I clean my bile duct naturally?
What are the claimed benefits of a gallbladder cleanse?Lemon juice and olive oil. This method involves not eating for 12 hours during the day and then, at 7 p.m., drinking four tablespoons of olive oil and one tablespoon of lemon juice — eight times every 15 minutes.Apple juice and vegetable juice.
What are the symptoms of bile duct problems?
Signs and Symptoms of Bile Duct CancerJaundice. Normally, bile is made by the liver and released into the intestine. … Itching. Excess bilirubin in the skin can also cause itching. … Light-colored/greasy stools. … Dark urine. … Abdominal (belly) pain. … Loss of appetite/weight loss. … Fever. … Nausea and vomiting.
Will a CT scan show blocked bile ducts?
CT scans can show gallstones, or complications such as infection and blockage of the gallbladder or bile ducts. However, CT scans also can miss gallstones that you may have.
What duct connects the gallbladder to the common bile duct?
The common hepatic duct then joins with the cystic duct from the gallbladder to form the common bile duct. This runs from the liver to the duodenum (the first section of the small intestine). However, not all bile runs directly into the duodenum.
What are the symptoms of your pancreas not working properly?
What Are the Symptoms of Your Pancreas Not Working Properly?Abdominal pain.Nausea.Vomiting.Bloating.Diarrhea or oily stools.Fever.Weight loss.Malnutrition.More items…•
What are the symptoms of gallstones in the bile duct?
Symptoms of Gallstones and Bile Duct StonesNausea.Fever.Chills.Yellow skin or eyes (from the build up of bilirubin, a waste product in blood)Dark urine.Itching.Fatigue.Weight loss.More items…
Can a blocked bile duct cause weight gain?
Or the problem could start in the liver, with stasis of bile there via the formation of sludge or tiny calculi, which slows bile flow. Constipation and weight gain can also be symptoms of gallbladder problems, though these are not usually as relatable to fat intake.
Does the common bile duct go through the pancreas?
The common bile duct passes through part of the pancreas before it joins with the pancreatic duct and empties into the first part of the small intestine (the duodenum) at the ampulla of Vater.

domain: biology


text:
The Rock Brook at Bessie Grover Memorial Park During a Flash Flood
The Rock Brook at Bessie Grover Memorial Park During a Flash Flood.
I “discovered” Bessie Grover Park while driving around looking for fast moving water during a flash flood in Skillman. This part of the Rock Brook runs past the park along Camp Meeting. The water was moving quite rapidly and as you can see had already covered a secion of the brook that normally sees no water.
NIKON CORPORATION NIKON D5100 + Tokina AT-X 116 PRO DX II 11-16mm F2.8 @ 14 mm,20.0 sec at ƒ / 10,ISO 100 . . . . . . #skillmanNJ #MontgomeryTownship #NewJersey #Water #Trees #Leaves #Branch #LongExposure


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Since the identification of the double-helix structure of DNA, the scientific field of genetics has developed and found applications in many diverse industries. First discovered in the late 1990s, small-interfering RNA (siRNA) has been important within many applications in the post-genomic era. This article will discuss what siRNA is and the challenges which face its therapeutic use.
Image Credit: Explode / Shutterstock.com
siRNA – an overview
siRNA is a double-stranded RNA molecule that is non-coding. It is also known as silencing RNA and short interfering RNA. It is similar to microRNA (miRNA) and the structure is short and well-defined, usually between 20 and 24 base pairs or thereabouts. Their structure has hydroxylated 3’ and phosphorylated 5’ ends.
siRNA production is catalyzed by an enzyme known as the Dicer enzyme. This is a powerful tool in drug targeting and therapeutics development as it is used to modulate gene expression through transcriptional or translational repression.
In principle, any gene can be silenced by a synthetic siRNA with a complementary sequence. This makes them an important tool for drug targeting and validating gene function. There have been many important studies into the application of siRNA to different areas of medical research.
Mechanism of siRNA action
The method by which siRNA causes the silencing of genes is as follows:
- Double-stranded RNA is cleaved by the Dicer enzyme. This forms siRNA.
- The double-stranded siRNA enters the cell and forms the RNA-induced silencing complex (RISC) with other proteins.
- This is unwound, which forms the single-stranded siRNA.
- The strand of RNA with the 5’ end base pairing that is thermodynamically less stable remains part of the RISC complex. This strand can now scan for complementary mRNA.
- Once this anti-sense strand binds to the target mRNA, mRNA cleavage is induced.
- The foreign mRNA is recognized by the host cell as abnormal and is degraded. No translation is possible, and therefore the gene is silenced.
siRNAs have very tight target specificity as they cleave the mRNA before translation, compared to the similar miRNA which silences genes by repressing translation. siRNA has 100% complementarity to its target mRNA. siRNA has also been found to activate gene expression.
However, there are challenges associated with the use of siRNA. For example, sometimes cleaving is not achieved due to mismatches between the siRNA and areas of the target mRNA near the cleaving site. There are other nonspecific effects when using siRNA.
RNAi intersects with other pathways, leading to the occasional triggering of these nonspecific effects. Challenges include:
- Mammalian cells mistaking double-stranded RNA such as siRNA for viral by-products and mounting an immune response.
- Thermodynamic properties of siRNA being chemically modified and leading to a loss of single nucleotide specificity.
- Unintended off-targeting. This is due to the inadvertent downregulation of genes with incomplete complementarity. This leads to problems such as data interpretation issues and potential toxicity.
- Too many siRNAs being introduced, leading to activation of the host’s innate immune responses. Evidence suggests that this is due to the activation of PKR, a dsRNA sensor, amongst other responses.
Methods to mitigate these adverse effects have been developed in recent years. For example, off-targeting can be partially addressed by designing appropriate control experiments and algorithms which produce siRNAs that are free from off-targeting. Algorithms can be further refined by genome-wide expression analysis, such as microarray technology.
There are also continuing challenges with the intracellular delivery of siRNA. Common methods for delivery include transfection, electroporation, and viral-mediated delivery. The most widely applied of these is transfection, though it is not compatible with all cell types and has low in vivo efficiency. There is ongoing research into how these delivery methods can be improved.
Whilst challenges in intracellular delivery exist, and siRNA has weak stability and pharmacokinetic behavior, there has been a growing interest in the therapeutic applications of the technology. There has been heavy investment by the pharmaceutical sector in the research and development of siRNA therapies for a variety of medical conditions and diseases.
As they are small in size at around 20 base pairs, siRNAs can pass through areas in the body where larger genetic therapies would not be able to pass. This includes the blood-brain barrier, which has historically presented large challenges for drug delivery.
Generation and action of siRNAs and miRNAs
In conclusion: siRNAs as therapeutics – the next frontier?
siRNAs may represent one of the next frontiers in medical science. They are currently being evaluated as to how they can be exploited in the drug development process and as therapeutic agents.
If the challenges that currently exist in siRNA development and delivery can be addressed, siRNAs could be used to target virtually any gene for therapeutic intervention. The field is an exciting one and the pharmaceutical sector is likely to continue funding its research over the coming years.

domain: medical


text:
A clear introduction to the implications of the Darwinian revolution for our understanding of human nature. Fosters skills in thinking about human nature and critical discussion of Darwin's arguments and those of his key commentators. illustrations
Human Nature After Darwin is an original investigation of the implications of Darwinism for our understanding of ourselves and our situation. It casts new light on current Darwinian controversies, also providing an introduction to philosophical reasoning and a range of philosophical problems. Janet Radcliffe Richards claims that many current battles about Darwinism are based on mistaken assumptions about the implications of the rival views. Her analysis of these implications provides a much-needed guide to the fundamentals of Darwinism and the so-called Darwin wars, as well as providing a set of philosophical techniques relevant to wide areas of moral and political debate. The lucid presentation makes the book an ideal introduction to both philosophy and Darwinism as well as a substantive contribution to topics of intense current controversy. It will be of interest to students of philosophy, science and the social sciences, and critical thinking.
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domain: library


text:
Create and deploy web apps that will enable anyone to explore Earth from orbit! Visualize Earth science satellites and mission data using interactive virtual globes, such as NASA’s Web WorldWind. Use data sets from NASA’s Open Data Portal to present fire, ice, clouds, meteorites, or water temperature spectra.
The Sky is Falling
An educational web application aimed to help everyone learn about past and future meteorite landings on Earth!
Using NASA's data for meteorite landings, we mapped the data location on the globe.
We used NASA's GeoJson source and Meteorite Landings on NASA's open data source to create our web application.


text:
20 Then the Lord said to Moses, “Rise up early in the morning and present yourself to Pharaoh, as he goes out to the water, and say to him, ‘Thus says the Lord, “Let my people go, that they may serve me. 21 Or else, if you will not let my people go, behold, I will send swarms of flies on you and your servants and your people, and into your houses. And the houses of the Egyptians shall be filled with swarms of flies, and also the ground on which they stand. 22 But on that day I will set apart the land of Goshen, where my people dwell, so that no swarms of flies shall be there, that you may know that I am the Lord in the midst of the earth.[e] 23 Thus I will put a division[f] between my people and your people. Tomorrow this sign shall happen.”’” 24 And the Lord did so. There came great swarms of flies into the house of Pharaoh and into his servants’ houses. Throughout all the land of Egypt the land was ruined by the swarms of flies.
25 Then Pharaoh called Moses and Aaron and said, “Go, sacrifice to your God within the land.” 26 But Moses said, “It would not be right to do so, for the offerings we shall sacrifice to the Lord our God are an abomination to the Egyptians. If we sacrifice offerings abominable to the Egyptians before their eyes, will they not stone us? 27 We must go three days’ journey into the wilderness and sacrifice to the Lord our God as he tells us.” 28 So Pharaoh said, “I will let you go to sacrifice to the Lord your God in the wilderness; only you must not go very far away. Plead for me.” 29 Then Moses said, “Behold, I am going out from you and I will plead with the Lord that the swarms of flies may depart from Pharaoh, from his servants, and from his people, tomorrow. Only let not Pharaoh cheat again by not letting the people go to sacrifice to the Lord.” 30 So Moses went out from Pharaoh and prayed to the Lord. 31 And the Lord did as Moses asked, and removed the swarms of flies from Pharaoh, from his servants, and from his people; not one remained. 32 But Pharaoh hardened his heart this time also, and did not let the people go.
9:1 Then the Lord said to Moses, “Go in to Pharaoh and say to him, ‘Thus says the Lord, the God of the Hebrews, “Let my people go, that they may serve me. 2 For if you refuse to let them go and still hold them, 3 behold, the hand of the Lord will fall with a very severe plague upon your livestock that are in the field, the horses, the donkeys, the camels, the herds, and the flocks. 4 But the Lord will make a distinction between the livestock of Israel and the livestock of Egypt, so that nothing of all that belongs to the people of Israel shall die.”’” 5 And the Lord set a time, saying, “Tomorrow the Lord will do this thing in the land.” 6 And the next day the Lord did this thing. All the livestock of the Egyptians died, but not one of the livestock of the people of Israel died. 7 And Pharaoh sent, and behold, not one of the livestock of Israel was dead. But the heart of Pharaoh was hardened, and he did not let the people go.
8 And the Lord said to Moses and Aaron, “Take handfuls of soot from the kiln, and let Moses throw them in the air in the sight of Pharaoh. 9 It shall become fine dust over all the land of Egypt, and become boils breaking out in sores on man and beast throughout all the land of Egypt.” 10 So they took soot from the kiln and stood before Pharaoh. And Moses threw it in the air, and it became boils breaking out in sores on man and beast. 11 And the magicians could not stand before Moses because of the boils, for the boils came upon the magicians and upon all the Egyptians. 12 But the Lord hardened the heart of Pharaoh, and he did not listen to them, as the Lord had spoken to Moses. (Exodus 8:20–9:12, ESV)

domain: literature


text: Our Save the Dates have finally arrived! I found our sweet little design from the awesome website that is Minted. They have a lot of cute wedding invites and save the dates for a good price, plus each design is made by an independent artist. Addressing has been really fun so far, its amazing to see how all over the map our wedding guest are. From Chicago, to Boston, to California, to Kansas, and more. I think that more than half of our guests are from all over the country, I am hoping they make a trip out of our wedding and explore the great state of Washington.


text:
The producers of the agricultural and agro-industrial sector now can enjoy the exemption of 15% regarding to the Sales Tax.
Through Legislative Decree No. 119-2016, published in La Gaceta, the Official Newspaper, on August 25th, article 15 subsection e) of the Sales Tax Law was amended, in which the goods and services exempt of the payment of the 15% are extended, it also exonerates the payment of such tax in the import or purchase of machinery, equipment and implements, accessories and spare parts, equipment and irrigation materials, irrigations systems for agriculture, industrial cleaning, packing materials and containers, which are involved in the agro-industrial production.
Furthermore, the Ministry of Finance in coordination with the Tax Administration, issued the Tax-Customs Instructive for the application of the article 15 subsection e) of the Sales Tax Law, through Executive Agreement 440-2016, published in the Official Newspaper “La Gaceta" on October 11th. The document establishes eight categories of goods between raw material, supplies, equipment and machinery for the agricultural and agro-industrial production.
This tax incentive’s objective is to promote the growth of the agro-industrial and agriculture activity in the country, for the purpose of influencing the final products on the national market and allowing growth of exports to other countries.
If you need more information, do not hesitate in contacting us.

domain: agronomy


text:
By Rishabh Naudiyal Last Updated:
After months of speculation and rumours, on May 14, 2022, Zoya Akhtar finally dropped the first look of her upcoming film, The Archies, an Indian adaptation of the famous comic universe by the same name. The poster and first look of the film are already trending on multiple social media platforms, and all the 90s kids are on cloud nine to finally get their eyes on the much-awaited adaption of their favourite animated series.
The film is all set to introduce Bollywood's King Khan, Shah Rukh Khan's daughter, Suhana Khan, Amitabh Bachchan's grandson, Agastya Nanda and Boney Kapoor and late Sridevi's daughter, Khushi Kapoor, to the Hindi film industry. While the first look is receiving a positive response, the audience is already excited to see the work of these popular celeb kids, who have a lot of expectations on their shoulders.
On May 14, 2022, Suhana Khan took to her Instagram handle and blessed her massive fanbase with the first look of her debut film, The Archies, directed by critically acclaimed director, Zoya Akhtar. In the 1 minute 34-second video, Suhana looked breathtaking and can be seen alongside many renowned newcomers like Dot, Yuvraj Menda, Vedang Raina, Agastya Nanda and Khushi Kapoor. The three popular celeb kids clearly overshadowed other actors in the first look of the film. While Suhana looked gorgeous in a gold rust coloured jumpsuit, Khushi can be seen donning an orange-coloured floral dress, and Agastya looked dapper in an orange striped T-shirt and khaki pants. Along with the first look, Suhana penned in the caption:
"Ain't nothing like old school Grab your gang 'cause the Archies are coming soon on @netflix_in!"
As soon as the first look of The Archies went live on social media, the newcomers received immense love from their family members and loved ones. Suhana Khan's mother, Gauri Khan reshared the first look on her IG handle and wrote, "Congratulations… all the best to all the amazing kids and team of #TheArchies . And who better than @zoieakhtar to guide them through this journey!! You did it @suhanakhan2!!!!!!!" in the caption. Also, Agastya Nanda's grandfather, Amitabh Bachchan penned a lovely note in the caption while sharing the teaser of The Archies on his Instagram handle. Big B's heartfelt caption can be read as:
"Another SONrise .. my GrandSON .. all the blessings Agastya .. love you. Get ready to take a trip down memory lane 'cause The Archies by @zoieakhtar is coming soon only on @netflix_in."
For Agastya Nanda, the congratulatory messages didn't stop there as his mother, Shweta Bachchan Nanda also shared his debut film, The Archies' first look on her IG handle and penned, "This is their story!" in the caption. However, the sweetest wish came from Agasyta's sister, Navya Naveli Nanda who shared a picture of her brother on her IG stories and wrote a few lines atop it that can be read as "Hey Jr. This is you moment. Don't let anyone take it away from you!! Love you! So much pride." Also, Suhana and Khushi's BFF, Ananya Pandey congratulated her besties and wrote, "Just the cutest thing in the world!! Cannot wait!" atop one IG story and penned, "My little bird!!! I love you so much!" atop the second story.
For the unversed, The Archies will stream on Netflix in 2023.

domain: entertainment


text:
With the involvement of the European Choral Association and an emphasis on communal involvement, the festival has more plenary sessions – including keynote addresses and opportunities for both singing and hearing singing – as well as workshop sessions, a trade exhibition and three conducting courses.
- performances from choirs including the National Youth Choir of Hungary, London Youth Choir, Town Hall Gospel Choir, Singing Community of Choirs and Lutley Community Voices
- sessions with composers, David Bednall, Paul Mealor and Owain Park
- singing sessions with John Rutter and David Lawrence
- the launch of a new peer-reviewed academic research journal, published by abcd, aimed at promoting research-informed practice and a scholarly approach to choral work

domain: artistic


text:
Also known as Kilwa Kisiwani (Kilwa on the Island). Situated on a small island at the mouth of an estuary
on the coast of Tanzania
about 250km south of Dar es Salaam
, Kilwa was once a rich and powerful trading hub controlling the east coast of Africa
as far south as Sofala
in modern-day Mozambique
. The glory days have long since passed and now it's little more than a village
; but many of its medieval
structures remain and the island was designated a World Heritage Site
Occupation of the island dates back at least as far as the 9th century AD but it first began to flourish in the 11th century with the establishment of a settlement by one Ali bin al-Hasan (spelling may vary); copper coins bearing his name are apparently still regularly found in
the sand of Kilwa's beaches. It has been suggested that Ali bin al-Hasan was from Shiraz in Persia, and that he, with his six sons, fled south to escape conflicts over the naming of a rightful Caliph, or successor, to
the prophet Mohammed. Certainly Kilwa had strong links with the Persian Gulf, the Red Sea and the more northern Swahili coast, including Mafia, Zanzibar, Pemba, Mombasa, Malindi, Lamu and other settlements.
The first foundation of Kilwa's wealth was gold: gold mined further south around Great Zimbabwe was transported overland to Sofala, shipped to Kilwa (along with the copper for Ali bin al-Hasan's coins) and thence to the Gulf and Europe, where demand grew rapidly during the late thirteenth and early fourteenth centuries. Historian JEG Sutton notes that, in Europe, "with the growth of population alongside the rise of industry and commerce... together with the expanding demand for spices and other Oriental products and the corresponding development of banking and
credit systems, the trend towards a gold standard proved irreversible". So, thanks to the princes of Florence and their like, Kilwa boomed.
The great ruler al-Hasan bin Sulaiman presided over this party in the fourteenth century, leaving behind Kilwa's main architectural treasures: the palace of Husuni Kubwa, never
wholly completed, and an expanded Great Mosque. He was famed abroad as Abu al-Mawahib, the Father of Gifts and minted more copper coins of his own for later generations of archaeologists and treasure hunters to discover. It was around this time that the great traveller Ibn Battuta visited Kilwa, describing it as one of the most beautiful cities in the world. Kilwa's fortunes dipped after this --
Europe's Black Death and the accompanying economic depression probably played a role -- but revived in the 15th century, when many of the existing wooden
houses described by Ibn Battuta were replaced by stone and coral structures.
Many of those were destroyed in their turn by the Portuguese on their rampage around the coast of Africa in the 16th century. Although these explorers were eloquent in their praise of the city's fine dwellings and prosperous merchants, and lovingly catalogued its riches -- ivory, perfumes, clothes of silk and cotton, amber, musk and pearls -- it all added up to just one thing: loot.
In 1502 Vasco da Gama extracted from the sultan a promise to pay 1,500 ounces of gold each year as tribute to the Portuguese king; in 1505 Dom Francisco d'Almeida followed threats with action when the sultan proved reluctant to pay. Hans Mayr, who accompanied d'Almeida's fleet, describes the sack of Kilwa with admirable economy:
"At dawn on Thursday, 24 July, the vigil of the feast of St. James the Apostle, all went in their boats to the shore. The first to land was the Grand-Captain, and he was followed by the others. They went straight to the royal palace, and on the way only those Moors who did not fight were granted their lives..... As soon as the town had been taken without opposition (?), the Vicar-General and some of the Franciscan fathers came ashore carrying two crosses in procession and singing the Te Deum. They went to the palace, and there the cross was put down and the Grand-Captain prayed. Then everyone started to plunder the town of all its merchandise and provisions."
Kilwa never truly recovered -- in fact none of the once-great ports of the Swahili Coast really survived the opening up of the new sea route to India. Its economy did experience one more revival, though, for an ugly
reason: in the early stages of the Industrial Revolution
, when the demand for slaves
to work the sugar
plantations of the New World
was at its peak, Kilwa did well. During the early 19th century the port was moved to Kilwa Kivinje on the mainland, the terminus of the southern slave route from Lake Nyasa (now Lake Malawi
). It is said that 20,000 slaves a year were shipped out from Kilwa Kivinje as late as the 1860s.
All long gone: today Kilwa is a village with some nice ruins for tourists to visit. It has some good beaches.
With thanks to newafrica.com, the Modern History Sourcebook, UNESCO
, JEG Sutton, the Encyclopedia Britannica and the Tanzania Tourist Board.


CE248A (HP / Option Parts)
Use the HP LaserJet MFP automatic document feeder maintenance kit to ensure your device operates at peak performance.
Get back to business and ensure smooth automatic document feeder functionality with an HP automatic document feeder maintenance kit. Perform simple repairs and upkeep.
Sustain the exceptional paper-handling performance of the automatic document feeder on HP LaserJet MFPs. Keep up to speed—automatic document feeder maintenance helps ensure years of reliable operation.
Simply maintain the automatic document feeder on your MFP with a kit that includes user-friendly parts. Follow the prompts on your MFP and use the kit for easy upkeep.


The County Insider
11/10/20 @ 9:00 a.m. – A new 4-way stop has been installed at the intersection of Simmons Road and First Avenue in Fernandina Beach. This was done following a warrant analysis determining that the intersection meets the criteria of the Federal Highway Administration. Please watch this video to learn more.
County Manager’s Office


text:
First Encounter is a beautiful beach on the bay with shallow water and plenty of space make for a great learning area. Kiteboarders are lucky to have their own designated kite launch area, which is farther away from the main beach. A huge area of this beach is technically the swim zone, which we are not allowed to kite in. So make note of where the buoys are and do not kite around bathers or even people walking out towards the waters at low tides.
No kiting in the river during the Summer.
There is a small kiteboarding launch area south of the main beach. Drive to the end of the road and park there. There is a sign with a map.
RULES AND REGULATIONS FOR KITE BOARDING/WINDSURFING No kites/equipment are allowed to be unattended on the beach or in the water. Kite boarders/windsurfers must set-up and launch from the designated area (Identified by signage on beach). Kite boarders/windsurfers in the water must stay 200 feet beyond the inner buoy at all times when not launching or returning to launch area. No KiteBoarding/Windsurfing on Bees River from June 15 to Labor Day. No Kite Boarders/Windsurfers are allowed near people or within restricted areas. All Kite boarders/windsurfers must identify themselves at the Gate House. They will subsequently be directed to the appropriate area and given written regulations. No rigging is allowed nor shall occur within the dunes at any beach, or in the parking area. Kite boarders/windsurfers must yield to beach-goers and swimmers.
Watch out for oyster beds to the south in mid-tides.
$15/day in season
High tide conditions
Choppy, not much beach to launch from
Low tide conditions
at dead-low tide you have to walk over a half mile to get to the water. Mid-tide is best.
Forecast: Wind Statistics:

domain: travel


First Look: 2015 Polaris ATV & SxS Lineup
Polaris has become the leader in the off-road industry by continually improving its off-road product offering and Model Year 2015 is another big year of new products and further refinement of the current product lines. RZR launches its biggest line-up ever, bringing all-new products and significant innovations to every single segment, for every type of […] More »
Polaris has become synonymous with versatility and it’s looking like 2014, the tradition will continue. “Polaris has become the industry leader by aggressively introducing new products and continuing to innovate our current product lines,” said David Longren, Polaris Off-Road Division’s Vice President. “Model Year 2014 is bringing several new products and more enhancements to the […] More »
With the 2013 model year fast approaching, it’s with great enthusiasm that we’re able to pass along what Polaris has in the works for their extensive ATV lineup. New ATV’s for youngn’s and more experienced riders abound. Check ’em out!


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Explore Gallery of Waldron 5 Light Globe Chandeliers
Showing Photo About Della 5-Light Globe Chandelier Intended for Waldron 5-Light Globe Chandeliers
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It could be crucial to find waldron 5-light globe chandeliers which usually good, useful, stunning, and comfortable parts that show your personal style and mix to make a perfect chandeliers. For these reasons, it happens to be important to put your personal style on this chandeliers. You would like your chandeliers to show you and your characteristic. For this reason, it is actually advisable to buy the chandeliers to beautify the design and feel that is most important to your space.

domain: design


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206-17C - Lucky (Domestic Short Hair Cat aged 12 years 4 months)
ucky and Domino back into the Centre as they did not get on with the dog in the household. They are lovely friendly older cats who are looking for a home where they can relax: They must be the only animals in the household.
To be re-homed together!
GET IN TOUCH
Llys Nini Animal Centre, Penllergaer, Swansea, SA4 9WB

domain: pet


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Most coffee drinkers in the consuming countries know coffee primarily as a beverage, secondarily as a ground or powdered substance which, when mixed with water, will yield that beverage. The coffee that we drink is made from ground roasted beans, but since so much coffee is sold ground, very few people get to see whole bean coffee.
These green beans are the hulled and dried seeds of the coffee tree. The tree flowers and bears a red cherry; the cherry has pits; the pits are the seeds; the seed are the beans. They are very hard, unperishable; unplantable, and without coffee flavor or aroma.
The Cultivation of Coffee
The species of coffee which has traditionally provided the world with most of its crops is Coffeea arabica. While Coffea arabica continues to dominate the world supplies, in recent years Coffea robusta has become more and more important. They can be successfully cultivated at lower altitudes than those suitable for Coffea arabica.
Arabica trees generally do not bear fruits until their 5th year, while yields of robusta are generally realized 2 or 3 years after planting. Robusta is more resistant to diseases than Arabica and fares better against the ravages of frost.
The flavors of Robusta does not compare favorably with Arabica, but its robust nature, rapid growth and high yields make it popular with farmers.
A third species of coffee is Coffea liberica. It grows large, sturdy, and is resistant to diesease. but its product finds little favor outside Liberia, where it grows in the lowlands. Its low yield makes it unattractive to farmers. So far it has not become commercially important.
The coffee plant is a small tree or a large shrub, depending on how you look at it- which if allowed to attain its full height would grow to between 14 to 15 feet. It is usually pruned to a height of between 5 and 12 feet. The plant has glossy, deep green, simple leaves, opposed to each other in alternating pairs.
Though sometimes called an evergreen, it is not; its leaves last only from 3 -5 years. As there are no drastic changes in the tropical and subtropical climates where coffee grows, the trees bear flowers and fruit at various times during the year.
The flowers are small, white, and delicately fragrant. These blossoms, whose perfume has been compared to the scent of orange blossoms and jasmine, fall from the trees after only a few days, to be replaced by tiny clusters of green cherries. As the cheeries ripen, they get larger and turn into deeper red. When the cherries have turned a deep purplish red, they are ripe and ready for picking.
The number of times a tree flowers and bears fruit in a year depends on the temperature and moisture of its environment. At the higher and cooler semi-dry altitudes flowering and fruiting may occur only once a year.
Each cherry normally contains 2 locules (chambers); each locule contains a "seed" and its parchment covering. The seeds or beans are usually round-oval shaped, flat on one side, and amrked longitudinally by a shallow incision. When a cherry has one locule and contains only one seed, that seed is usually round and is called the peaberry or male berry.
Cherries containg peaberries are usually found at the extremities of the branches. The peaberry coffee was prized because the round beans could be shaken around in the pan and were easy to roast evenly.
The cultivation of coffee starts with the seed. The finest seeds, those known to produce hardy trees with high yields of good flavored coffee, are selected for planting. The seed used for planting has its parchment- like covering- stripped of that covering, it becomes the green coffee bean of commerce.
Seeds are usually given a start in a nursery on the plantation. Planting can be done anytime during the year. The seedlings are permitted to grow in the nursery for about a year, until they have reached a height of 18 to 24 inches. They are then transplanted in the coffee grove in rows ten to twelve feet apart, in much the same fashion as apple trees are planted.
Coffee grows at all levels from sea to 7000 feet, Robusta coffee seems to thrive in the hotter, wetter lowlands ( upto 3000 ft), while coffee the fine flavored Arabicas come from trees growing at the cooler higher altitudes. Coffee cultivated at higher altitudes mature more slowly and develops more and better flavored oils. Hilly gorunds has the advantage of offering the kind of exposure that coffee trees need- sunlight part of the day, shade for the rest.
The soil should be rich in potassium, nitrogen, and phosphoric acid. The soil should be moist and loose enough to accept rain while allowing excess moisture to drain quickly away. Well drained land is important to the health of the tree.
A coffee tree raised from seed generally begins flowering in its 3rd year. A good crop can be expected from the tree in its 5th or 6th year, and it will continue to produce a good crop through its 15th year.
It takes around 2.5 kgs of cherries to produce 0.5 kg of beans.


Out Of Ten Podcast
About This Show
Out Of Ten is a music review podcast where we discuss and review recent album and track releases from various genres such as Indie Rock, Rap/Hip-Hop, and Mainstream Pop…and of course, rate the music out of ten. Out Of Ten is hosted by Sage Jordan and Michael Vallejos-Sevilla, and based out of Ottawa, Ontario.
Most Recent Episode
Out Of Ten | Episode 23 – Sign Of The Times (With Olivia Ferderber)
3 days ago
On Episode 23 of Out Of Ten, we’re joined by One Direction Expert Olivia Ferderber to review Harry Styles’ debut album. We also review Paramore’s “After Laughter”, discuss the PWR BTTM situation, Miley Cyrus’ hottest looks, and we have the classic debate of Chris vs. Liam Hemsworth.
Follow Olivia on Instagram at @viaferderb
Playlist of songs mentioned on this week’s episode: Spotify
Harry Styles – Harry Styles (2:32)
Paramore – After Laughter – (30:22)
Miley Cyrus – Malibu (45:47)
Calvin Harris – Rollin feat. Khalid & Future (58:40)
PWR BTTM – Pageant (1:07:15)
Nick Murphy – Missing Link EP (1:18:15)
Brock Berrigan – Point Pleasant (1:20:30)
Actress – AZD (1:23:45)
Scott Helman – Hotel de Ville (1:25:25)
Website – www.outoftenpodcast.com
Facebook – Out Of Ten Podcast
Twitter – @SageJordan and @MichaelValSev
Instagram – @Outoftenpodcast, @thesagejordan and @michaelvs13
Theme song is San Dingo – Presence. Listen to the Neon Highway EP here.
About Out Of Ten:
Out Of Ten is a music review podcast where we discuss and review new album releases and tracks, and of course…rate them Out Of Ten. Out Of Ten is hosted by Sage Jordan and Michael Vallejos-Sevilla, and based out of Ottawa, Ontario.
Episodes of This Show
7 days ago


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Zeon Black is another icon pack from the artist responsible for the Gai and Ditoni icon packs. This time around, we're looking at something that is a little more rustic, designed to be more fun and bring a human touch to your smartphone or tablet. It's not just available in Black, it's also available in Pink, Red, Green, Blue and White. There are over 1,600 handmade icons here, with the ability to request icons to be made for those that aren't included here and there's also a Dashboard app with wallpapers and even Muzei support, too. So, this looks like yet another quality icon pack from RayphoDesign, but read on to get a closer look at what's on offer.
As with any icon pack, you'll need to download Zeon Black from the Play Store. If you'd like a different color there are also Blue, Green, Pink, Red and White icon packs available in the Zeon theme. You can then go ahead and launch the Dashboard app to take a look at the icons as well as the matching wallpapers.
There are 1,600+ icons available in the Zeon Black theme and you can use the Dashboard app to take a look at them.
Right away we can see that Zeon is a theme that's been put together by hand and feels like the sketchings you'd find in a notebook. It's going to be to everyone's taste, but it's certainly a nice change from the hyper-professional look of other themes. If, for whatever reason, you feel like there are icons missing you can easily request them from within the app.
You can easily set the icon pack from the Dashboard app, but as I'm using Aviate I just changed it from within the settings. Zeon Black worked great with Aviate and certainly helped liven up a launcher which some believe to be boring.
There's also a selection of wallpapers available to download and set whenever you want.
While I felt that a lot of the more colorful photograph wallpapers here didn't quite fit with the icons exactly, there were some really nice lightning wallpapers included that I feel made my homescreen look pretty cool with the black hand drawn icons.
All-in-all, Zeon Black is a nice change of pace from icons that are designed to look all neat and tidy. There are so many of those out there that those types of icon packs can grow a little tiresome. What I like about Zeon Black in particular, is that it brings a laid-back look to Android which is more Human and almost relaxing. When talking specifically about the Black version of Zeon, it'll work great with the Google Now Launcher and the white app drawer, so that's many Lollipop users covered, but it also works well with a monochrome theme if you're using more whites than you are blacks. As I've said though, there is the option for a white theme as well as more colorful versions of the same icons. A nice breath of fresh air if you're fed up of all the neat and tidy options out there, Zeon Black is well worth taking a look at.
- Speed (4/5) – No problems here, everything runs nice and quickly and there's no risk of this slowing down your phone.
- Features (4/5) – Much like other icon packs, Zeon Black features a quality Dashboard app that's easy to use and with 1,600+ icons on hand and a good selection of wallpapers, this has more than enough on offer.
- Theme (5/5) – I thought that I wouldn't take to this style at first, but it's an excellent change from the usual icon packs that fit into circles, flat design or some sort of take on a Linux set. Instead, Zeon Black feels freehand and fun, it makes my smartphone feel a little more human and it's a stark change to the default Android theme, too.
- Overall (4/5) – A solid icon pack that looks excellent and ticks all the right boxes, Zeon Black is only really held back by a somewhat mismatched selection of wallpapers, but that's not a major problem as you can use whichever wallpaper you want.
- Available in more than just Black, including Pink, Blue, Green, red and White, too.
- With 1,600+ icons, there's a lot on offer here and you can definitely tell the developer has put some real work into this.
- Rustic, human look and feel will bring your homescreen back to life, especially if you're fed up of the usual suspects.
- Easy to request new icons if you feel that some of your favorite apps are missing, but the icon mask does work well here, too.
- Wallpaper selection doesn't feel well matched with Zeon in Black or in White, but this is more a matter of taste than variety.
- One pack to get all the different colors in one would be nice to see.
For those looking for something a little different and a little offbeat, Zeon Black is definitely something to look at. if you're not into the dark look of this one, then you can always take a look at the other colors available from RayphoDesign. All-in-all, Zeon Black is a rustic, fun-loving theme that's easy to like and well worth taking a look at.


Ignition timing control apparatus for internal combustion engine
Ignition control system for an internal combustion engine
System and method for controlling ignition timing for internal combustion engine
Traction control system for vehicles
Controller and control method for engine ignition timing
Monitor for lean capable engine
Vehicle drive power control apparatus, and control method Patent #: 6401022
ApplicationNo. 10031862 filed on 03/09/2001
US Classes:477/101, Engine ignition control for transmission change477/106, Initiation inhibited by sensed condition477/107, Engine controlled by transmission123/406.59, Speed responsive timing control123/335, By electric means180/197, WITH MEANS FOR DETECTING WHEEL SLIP DURING VEHICLE ACCELERATION AND CONTROLLING IT BY REDUCING APPLICATION OF POWER TO WHEEL123/306, MEANS TO WHIRL FLUID BEFORE, UPON, OR AFTER ENTRY INTO COMBUSTION CHAMBER123/295, Combustible mixture stratification means701/54Engine output control
ExaminersPrimary: Ho, Hoai
Attorney, Agent or Firm
Foreign Patent References
1. A method for controlling the timing of ignition in each of a plurality of cylinders of an internal combustion engine used to power a transmission having a plurality of gears through a crankshaft, the method comprising the steps of:
identifying one of the plurality of gears transmitting power generation from the internal combustion engine;
measuring a speed of operation for the internal combustion engine by measuring the revolutions per minute of the crankshaft of the internal combustion engine to establish a measured revolution per minute value;
identifying timing parameters using a look-up table;
determining whether the measured revolution per minute value is represented in the look-up table; and
generating the timing parameter for ignition for each of the cylinders of the internal combustion engine.
2. A method set forth in claim 1 including the step of interpolating the timing parameters from member values of the look-up table close to the measured revolution per minute value.
3. A method as set forth in claim 2 including the step of collecting values for revolutions per minute from cells in the look-up table that are close to the measured revolution per minute value.


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Health & Wellness
TORONTO—A woman from British Columbia is the first person in North America to be diagnosed with H7N9 bird ’flu, after apparently contracting the virus while travelling in China earlier this month, Canadian health officials said yesterday.
Her husband, who had been travelling with her, also was sick with an influenza-like illness around the same time.
NEW YORK — The milk industry is fed up with all the sourness over dairy.
As a guy who built heating systems for spacesuits, Mark Aramli found it perplexing that there was no good way to get the temperature right for his mom when she was laid up during a recent Rhode Island winter.
“I kept astronauts warm in space, and this was just a bed,” the former NASA engineer says. “Everything was too hot or too cold.”
STOCKHOLM, Sweden—In socially-liberal Sweden, an educational video for children featuring dancing genitals has become an online hit—and even drawn criticism for not being progressive enough.
The one-minute animated video by public broadcaster SVT, promoting a television series about the human body, has been seen by more than four million YouTube viewers.
TORONTO—Most people are able to feel empathy for a friend experiencing physical or emotional pain.
But it’s trickier when the person is a stranger—and researchers suggest a major reason for that lack of fellow-feeling may be stress.
TORONTO — Children permitted to play outdoors on their own or with friends are getting more physical activity than kids who are constantly supervised, a new Canadian study suggests.
TORONTO—Sitting on one’s butt for a major part of the day may be deadly in the long run—even with a regimen of daily exercise, researchers say.
An Ontario aboriginal girl who refused to continue with chemotherapy, and opted for alternative healing methods to treat her cancer, has died.
Makayla Sault’s family said the 11-year-old suffered a stroke Sunday.
In a statement issued in the Two Row Times, a weekly newspaper covering indigenous issues, Sault’s parents say their daughter died early yesterday.
TORONTO — Seniors who develop a bout of pneumonia severe enough to require hospitalization are at higher risk of having a heart attack, stroke or dying of heart failure for years after the event, a new study suggests.
TORONTO — Sitting on one’s butt for a major part of the day may be deadly in the long run — even with a regimen of daily exercise, researchers say.

domain: news


text:
People and Skills: A Potential Risk in ICT Infrastructure Management
This paper describes an approach used to reveal dynamics operating in supply of, and demand for, skilled Information and Communications Technology (ICT) employees. The impacts of changing demographics of the work force and society are investigated. The paper is much about what is needed to achieve implementation success as it is about the effective application job allocation strategy. The work force skill projecting model has been proposed which includes the conceptual matrix of IT and domain skills: a space diagram where the various IT and IT related professional could be placed.


Sen. Kerry intervenes on town hall passport issue
Local towns may get a break from new passport restrictions if U.S. Sen. John Kerry’s request for a waiver is granted.
A State Department policy – issued as a security measure in the wake of the Sept. 11, 2001, terror attacks – banned town clerks from processing passports if they also handled birth certificates. The goal was to prevent document fraud.
Those town clerk offices that already were handling both tasks were given a temporary exemption provided they not create the birth certificate that accompanied a passport application. But they were told they would have to abide by the new regulation as of May 1.
Kerry wrote to Assistant Secretary of State for Consular Affairs Janice Jacobs, saying the policy “may have adversely affected a number of Massachusetts cities and towns” by preventing them from processing passport applications.
“We hope to get a response on the waiver request as soon as possible,” Kerry’s press secretary, Whitney Smith, told The Enterprise on Friday.
Local town clerks were pleased to hear the senator intervened on the issue.
“We’d be thrilled if a waiver comes through,” said East Bridgewater Town Clerk Marcia Weidenfeller.
“Right now, there are three of us doing passports and if we are not allowed to continue doing them, our veterans agent will be doing them and he’s only one person,” said Weidenfeller.
“Often, we get a family of four at one time and it takes time to do the photos and process the paperwork, so one person doing them means a longer wait for people,” said Weidenfeller.
Passport revenue is a bonus for many towns.
According to Weidenfeller, the East Bridgewater town clerk’s office processed 890 passports from September 2009 until October 2010, accruing more than $22,000 in revenue plus the charges for taking passport photos.
“It’s significant,” said Weidenfeller.
West Bridgewater Town Clerk Nancy Morrison said she was also happy about the request of the waiver.
“I felt it was unnecessary that they didn’t want us to do them,” she said. “I would be pleased to continue with the job we were trained for.”
Morrison said earlier that she processed 224 passports from October 2009 through September 2010, bringing in $5,600 for the town.
Kerry said he understood the need to prevent document fraud, but noted that a fraud-protection mechanism is already in place with the state’s Registry of Vital Records and Statistics.
Brockton does not process passports through its clerk’s office.
If the regulation does go into effect, cities and towns that continue processing passports will be visited by analysts from the State Department’s Acceptance Facility Oversight Program after the May 1 deadline.
Passports and passport renewals can also be obtained at many offices of the US. Postal Service and through the State Department website at http://travel.state.gov/passport.
Many travel experts recommend that passports or renewals be secured at least six months before the departure date for a trip to avoid security concerns about newly issued documents.


- Manufacturer: Microvision
robot parts from microvision inspection system. no pc controller with system.
- Manufacturer: Microvision ESI
wafer robot with flat finder. sold untested as is with 14 day right to return.
- Manufacturer: East
this microvision spotseeker 30 multiple-axis motorized positioning display analysis system features an olympus q-color 3 video camera with edmund industrial optics 75mm f4 lens, as shown. the motorized positionin...
- Manufacturer: Deckel Maho
tool setting manufacturer: dmg mori microset type: uno 115 microvision year: 2012 range: 230 mm measuring length: 370 mm microvision i with 18 "tft color screen - edge-finder for fast focusing of the tool cutting...
Get email updates for microvision


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The Independent Petroleum Marketers Association of Nigeria (IPMAN) has allayed the fears of Nigerians concerning the scarcity of petrol ahead of yuletide.
The president of the association, Mr. Chinedu Okoronkwo calmed the nerves in a chat with newsmen on Friday, November 12 in Lagos.
He stated that the problem they were facing was bridging which is the transportation of petrol from the depot to another depot that is experiencing supply shortfall due to distance.
Okoronkwo maintained that marketers were afraid of bridging because they were not confident of getting paid due to the recent scrapping of the Petroleum Equalisation Fund. However, the president said that the issue had been resolved as NMDPRA had promised the marketers that they would be compensated for their services.
He said: “We met with Mr. Farouk Ahmed, Chief Executive Officer, NMDPRA and resolved the issue.
Download NAIJA NEWS app:

domain: economics


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Wednesday 6th December 2017, 7:30pm - Thursday 7th December 2017, 7:30pm
Milford National School
presents EMERALD ADVENTURES WITH PETER PAN
On Sale Tuesday 31st October at 10am
Milford National School is 35 years young and the students of 2017 will celebrate in spectacular style this December.
Prepare to be enchanted by the music, dance and costumes of the Forever Young, in their epic Emerald Adventures.
This show, professionally directed and choreographed by Jean, Pam and Gerdi McGlynn, is
especially for the Young at Heart.