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Deposition of islet amyloid polypeptide (IAPP) as amyloid in the pancreatic islet occurs in ~90% of individuals with type 2 diabetes and is associated with decreased islet ß-cell mass and function. Human IAPP (hIAPP), but not rodent IAPP, is amyloidogenic and toxic to islet ß cells. In addition to IAPP, islet amyloid deposits contain other components, including heparan sulfate proteoglycans (HSPGs). The small molecule 2-acetamido-1,3,6-tri-O-acetyl-2,4-dideoxy-α-D-xylo-hexopyranose (WAS-406) inhibits HSPG synthesis in hepatocytes and blocks systemic amyloid A deposition in vivo.
To determine whether WAS-406 inhibits localized amyloid formation in the islet, we incubated hIAPP transgenic mouse islets for up to seven days in 16.7 mM glucose (conditions that result in amyloid deposition), plus increasing concentrations of the inhibitor. WAS-406, at doses of 0, 10, 100 and 1000 μM resulted in a dose-dependent decrease in amyloid deposition (% islet area occupied by amyloid: 0.66±0.14, 0.10±0.06, 0.09±0.07 and 0.004±0.003%, p<0.001) and an increase in ß-cell area in hIAPP transgenic islets (55.0±2.6 vs. 60.6±2.2 % islet area for 0 vs. 100 μM inhibitor, p=0.05). Glycosaminoglycan, including heparan sulfate, synthesis was inhibited in both hIAPP transgenic and non-transgenic islets (the latter a control that do not develop amyloid), while O-linked protein glycosylation was also decreased, and WAS-406 treatment tended to decrease islet viability in non-transgenic islets. Azaserine, an inhibitor of the rate limiting step of the hexosamine biosynthesis pathway, replicated the effects of WAS-406, resulting in reduction of O-linked protein glycosylation and glycosaminoglycan synthesis and inhibition of islet amyloid formation. In summary, interventions that decrease both glycosaminoglycan synthesis and O-linked protein glycosylation are effective in reducing islet amyloid formation, but their utility as pharmacological agents may be limited due to adverse effects on the islet.
Islet amyloid deposition is a pathogenic hallmark of the islet in type 2 diabetes, occurring in the vast majority of individuals with the disease (33), and is associated with decreased ß-cell mass and function (5, 32). The unique amyloidogenic component of islet amyloid is the ß-cell peptide islet amyloid polypeptide (IAPP, amylin) (6, 35). Human IAPP (hIAPP) is amyloidogenic and in vitro studies have shown that early aggregates or oligomers of hIAPP are cytotoxic, leading to ß-cell death via apoptosis (12, 22). In contrast, the rodent (rat and mouse) forms of IAPP differ from hIAPP in a number of critical amino acids, rendering rodent IAPP non-amyloidogenic and non-toxic (34). Due to these species-specific differences, several groups have produced transgenic mice expressing hIAPP in their pancreatic islet ß-cells in order to create models of islet amyloid deposition. In our colony of hIAPP transgenic mice, male mice develop islet amyloid deposits in vivo following one year of high fat feeding (29). We have also recently developed a rapid in vitro model of islet amyloid deposition by culturing isolated islets from our hIAPP transgenic mice in high glucose for seven days (10, 38).
Besides the amyloidogenic peptide IAPP, islet amyloid contains other components that are common to all amyloidoses, including those formed in Alzheimer's disease (Aß amyloid) and chronic inflammation (AA amyloid). These include apolipoprotein E (4), serum amyloid P component (24) and heparan sulfate proteoglycans (HSPGs) (36), all of which may contribute to hIAPP amyloidogenesis and its related cytotoxicity.
HSPGs in particular may play a role in islet amyloidogenesis. The HSPG perlecan has been shown to be present in human ß cells from individuals with and without type 2 diabetes (13) and the ß cell synthesizes several HSPGs that are capable of binding amyloidogenic hIAPP but not non-amyloidogenic rodent IAPP (25). Further, binding of amyloidogenic peptides, including IAPP, to HSPGs via their heparan sulfate (HS) glycosaminoglycan (GAG) chains has been shown to stimulate amyloid fibril formation (2, 3). Thus, HSPGs may play a critical role in islet amyloid formation and evidence that decreasing GAG synthesis reduces islet amyloid formation would provide further evidence to support this hypothesis.
We have generated a series of N-acetylglucosamine analogs that act as small molecule inhibitors of GAG synthesis (17-20). These compounds are effective in reducing amyloid formation in a mouse model of AA amyloidosis (20), and in a transgenic mouse model of CNS Aβ amyloid (16). In the present study we examined the effect of one of these compounds, 2-acetamido-1,3,6-tri-O-acetyl-2,4-dideoxy-α-D-xylo-hexopyranose (WAS-406), on ß-cell GAG synthesis and on islet amyloid formation in vitro.
Precursors for GAG synthesis are synthesized via the hexosamine biosynthesis pathway (HBP). The HBP is a nutrient sensing pathway that has many additional effects in the cell including regulation of O-linked protein glycosylation. Azaserine, an inhibitor of glutamine:fructose-6-phosphate amidotransferase (GFAT), the rate-limiting enzyme of the HBP, has previously been shown to have no effect on GAG synthesis in arterial smooth muscle cells (28). Therefore, we compared the effects of azaserine and WAS-406 on GAG synthesis and islet amyloid formation in vitro.
Hemizygous hIAPP transgenic and non-transgenic mice on a F1 C57BL/6 × DBA/2 background were bred and utilized under protocols approved by the Institutional Animal Care and Use Committee of the VA Puget Sound Health Care System. Eight to ten-week old male and female mice were anesthetized with sodium pentobarbital (100 mg/kg i.p.), and pancreatic islets were isolated by collagenase digestion (Collagenase P, 0.5 mg/ml, Roche Applied Science, Indianapolis, IN) via bile duct cannulation, followed by pancreas excision. Islets were purified on a Histopaque gradient, hand picked and cultured overnight in RPMI-1640 containing 10% fetal bovine serum, 100 U/ml penicillin, 100 μg/ml streptomycin and 11.1 mM glucose. Islets were then cultured for up to seven days in medium containing 16.7 mM glucose alone or together with WAS-406 (10 - 1000 μM for dose response studies, 100 μM thereafter). In a subset of experiments, islets were also cultured in the presence of the HBP inhibitor azaserine (20 μM). Stock solutions of WAS-406 (100 mM) and azaserine (20 mM) were prepared in sterile water, and then diluted 1:1000 in culture medium. Culture medium was changed, and thus new compound was supplied to islets, every 48 hours.
At the end of each experiment, islets were fixed in 4% (w/v) phosphate-buffered paraformaldehyde. Islets were embedded in agar, re-fixed in 4% paraformaldehyde, embedded in paraffin and processed for histology. Five-μm sections were cut throughout the islet pellet and sections at 100 μm intervals were stained for amyloid with thioflavin S and for insulin as previously described (9). Islet area was determined by circumscribing each islet image with a video cursor; the outline of islets is clearly visible when viewed in the thioflavin S channel. Islet-, thioflavin S-positive- and insulin-positive areas were determined for each islet cross-section in an average of 25 islets per experimental condition. From these data, the following measures were determined: islet amyloid prevalence (% islets containing thioflavin S positive staining), islet amyloid severity (Σ thioflavin S area / Σ islet area × 100%) and ß-cell area (Σ insulin area / Σ islet area × 100%).
Insulin secretion was determined following seven days of culture. Islets (100-150 per condition) were loaded into a perifusion chamber and were pre-incubated in Krebs-Ringer bicarbonate buffer containing basal (1.67 mM) glucose for one hour, followed by measurement of basal insulin secretion at 1.67 mM glucose every 2 minutes for 8 minutes. Glucose-stimulated insulin secretion was then assessed by perifusion of islets with Krebs-Ringer bicarbonate buffer containing 16.7 mM glucose for 30 minutes (fractions collected every 2-5 minutes). Glucose-stimulated insulin secretion was expressed as the incremental area under the curve. Secretion data from these studies using only the hIAPP transgenic and non-transgenic islets cultured for seven days in 16.7 mM alone have been previously published (38).
For determination of insulin content islets were solubilized in acid ethanol (0.2 M HCl, 48 % (v/v) ethanol). Total protein was determined (Coomassie Plus Protein Assay; Pierce Biotechnology, Rockford, IL) and insulin content was measured by radioimmunoassay as described previously (10).
Islet cell viability after seven days of culture was assessed using the Cell Proliferation Kit I (Roche) according to the manufacturer's instructions. Twenty islets/well (triplicates for each condition) were incubated for four hours in culture medium containing 0.5mg/ml 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Islets were solubilized by overnight incubation in solubilization buffer and solubilized formazan was quantified spectrophotometrically (590 nm).
Islets were isolated from hIAPP transgenic and non-transgenic mice and recovered overnight as described above. The immortalized islet ß-cell line ß-TC3 was plated at 1.2×106 cells/ml and cultured for 5 days prior to study in DMEM containing 10% fetal bovine serum, 100 U/ml penicillin, 100 μg/ml streptomycin and 5.5 mM glucose. Islets (450 per plate) and ß-TC3 cells were then metabolically labeled for 48 hours with [35S]-Na2SO4 (100 μCi/ml; MP Biomedicals, Costa Mesa, CA) in medium containing 16.7 mM glucose alone or together with WAS-406 (100 μM for islets and 10 - 1000 μM for ß-TC3 cells) or azaserine (20 μM; in a subset of experiments). This approach labels newly synthesized GAG chains on proteoglycans.
Incorporation of [35S]-Na2SO4 into GAGs was assessed in combined medium + cell preparations by cetylpyridinium chloride precipitation (31). Labeled media were collected in the presence of protease inhibitors (5 mM benzamidine, 100 mM 6-aminohexanoic acid, and 0.1 mM phenylmethylsulfonyl fluoride) and labeled islets/cells were solubilized in 8 M urea buffer (8 M urea, 2 mM EDTA, 0.25 M NaCl, 50 mM Tris-HCl, and 0.5% Triton-X 100 detergent, pH 7.4) containing protease inhibitors.
To determine the effects of WAS-406 to reduce GAG synthesis and its specificity for HS versus chondroitin/dermatan sulfate (CS/DS), labeled glycosaminoglycans were purified from ß-TC3 cells. [35S]-Na2SO4 labeling was performed as described above and cells solubilized in phosphate-buffered saline (PBS, pH 7.2) containing 1% (v/v) Triton X-100, pooled together with medium and incubated with pronase (Streptomyces griseus 100 μg/ml, Roche) overnight at 37°C. GAGs were isolated by application to DEAE Sephacel equilibrated in PBS and eluted over a 0.15 - 0.8 M sodium chloride gradient. Residual core protein fragments were removed by alkaline elimination and borohydride reduction and the resulting glycosaminoglycan preparations digested with no enzyme (control), heparinase I, II + III (0.8, 0.4 and 0.8 U per digestion respectively, Sigma St. Louis, MO), chondroitinase ABC (0.03 U per digestion, Seikagaku USA, Cape Cod, MA) or a combination of heparinase I, II, III + chondroitinase ABC for three hours at 37°C. Reaction products were analyzed by molecular sieve chromatography (Sepharose CL-6B, equilibrated in 0.2 M Tris, 0.2 M NaCl, pH 7.0).
Islet lysates (75 islets per culture condition) were prepared by sonication on ice in 20 mM Tris-HCl, 150 mM NaCl, 1% (v/v) Nonidet P-40, pH 7.5 followed by centrifugation for 20 minutes at 12,000g. Total protein concentration was determined using the Coomassie Plus Protein Assay (Pierce Biotechnology) and from this equal protein (15 μg) was loaded for each sample. Samples were separated by SDS-PAGE, transferred to polyvinylidene fluoride membrane and non-specific binding blocked by incubation in 50 mM Tris-HCl, 150 mM NaCl, 0.1% (v/v) Tween-20 and 5% (w/v) non-fat dry milk, pH 7.5. Membranes were probed with antisera directed against O-linked N-acetylglucosamine (RL2, Affinity BioReagents, Golden, CO; 1:100 dilution). Primary antibody binding was detected using peroxidase-conjugated anti-mouse IgGs followed by enhanced chemiluminescence (PerkinElmer, Wellesley, MA).
Data are expressed as mean ± SEM. For MTT islet viability, data are presented as % of non-transgenic islets cultured in 16.7 mM glucose due to variability among experiments resulting from the use of different lots of MTT kits. For metabolic labeling experiments n=2-3 proteoglycan preparations; for all other experiments n=3-8 islet preparations. Dose response data were compared by analysis of variance with Bonferroni post-hoc analysis. Two group comparisons were made by T-test or Mann Whitney U non-parametric test if the data were not normally distributed. A p≤0.05 was considered statistically significant.
Incubation of isolated hIAPP transgenic islets for seven days in 16.7 mM glucose and increasing concentrations of WAS-406 was associated with a marked, dose-dependent decrease in both the prevalence (Figure 1A) and severity (Figure 1B) of islet amyloid formation.
Based on the dose-response study, a dose of 100 μM of WAS-406 was selected for further assessments of islet morphology. The reduction in amyloid formation observed in hIAPP transgenic islets in the presence of WAS-406 was associated with an increase in ß-cell area as a proportion of islet area (Figure 2A). In contrast, the proportion of islet area comprised of ß-cells was not significantly altered in non-transgenic islets cultured in the presence or absence of 100 μM WAS-406 (Figure 2A). Islet area did not differ among treatment conditions or between hIAPP transgenic and non-transgenic islets (data not shown). Islet insulin content was not different in hIAPP transgenic islets compared to non-transgenic islets cultured in 16.7 mM glucose alone (Figure 2B). However, WAS-406 treatment resulted in a significant increase in insulin content in both hIAPP transgenic and non-transgenic islets (Figure 2B). Glucose-stimulated insulin secretion (n=4 per condition) was not significantly different with WAS-406 treatment in hIAPP transgenic islets (11.1±2.8 vs. 18.0±6.9 μU/islet.30 minutes for untreated vs. WAS-406) or non-transgenic islets (15.2±1.3 vs. 22.2±3.2 μU/islet.30 minutes for untreated vs. WAS-406, p=0.1). Islet viability was significantly lower in hIAPP transgenic islets compared to non-transgenic islets cultured in 16.7 mM glucose alone (Figure 2C) as we have previously shown (38), and WAS-406 treatment was associated with a tendency towards a reduction in viability in non-transgenic islets (p=0.065) but no change in viability in hIAPP transgenic islets.
WAS-406 decreased incorporation of [35S]-sulfate into newly synthesized GAGs in a dose-dependent manner in immortalized ß-TC3 cells (Figure 3A). GAG synthesis was reduced by 62% in ß-TC3 cells incubated with 100 μM WAS-406 (p<0.001 vs. untreated cells). GAG synthesis during a 48-hour label was similarly reduced with WAS-406 (100 μM) by 66% in both hIAPP transgenic and non-transgenic islets (Figure 3B). Ion exchange chromatography showed that ß-TC3 cell GAGs synthesized in the presence and absence of WAS-406 eluted from DEAE Sephacel at a similar salt concentration (0.45 M NaCl; Figure 3C), although, as expected, the abundance of GAGs synthesized in the presence of WAS-406 was much reduced compared to untreated cells.
To determine whether WAS-406 was specific for inhibition of heparan sulfate synthesis, equal numbers of counts of 35S-sulfate-labeled GAGs synthesized by ß-TC3 cells in the presence or absence of WAS-406 were digested with no enzyme (intact GAG control), heparinases I, II and III (to digest HS), chondroitinase ABC (to digest CS/DS) or the combination of heparinases I, II, III + chondroitinase ABC. If WAS-406 were specific for inhibition of HS synthesis, the residual GAGs synthesized in the presence of this compound would be expected to be insensitive to heparinase digestion, but sensitive to chondroitinase ABC treatment.
Analysis of reaction products by CL-6B Sepharose size exclusion chromatography showed that intact GAGs were of a similar size in control (Figure 4A) and WAS-406 (Figure 4E)-treated ß-TC3 cells. As we showed previously, ß-TC3 cells synthesize predominantly HS (25); thus a greater proportion of GAGs synthesized in control cells (without WAS-406) were sensitive to heparinase I, II and III digestion (Figure 4B; shaded area denotes digested material, in this case heparinase-sensitive material) than to chondroitinase ABC digestion (Figure 4C). As expected, no intact GAGs were present following digestion with the combination of heparinase I, II and III and chondroitinase ABC (Figure 4D). ß-TC3 GAGs synthesized in the presence of WAS-406 contained a similar proportion of heparinase I, II and III sensitive material (Figure 4F) and chondroitinase ABC sensitive material (Figure 4G) compared to control cells, and all material was sensitive to the combination of heparinase I, II and III and chondroitinase ABC treatment (Figure 4H).
Since WAS-406 is an analog of N-acetylglucosamine, an intermediate of the HBP, we analyzed flux through the HBP by measuring O-linked protein glycosylation in islets treated for seven days with 16.7 mM glucose alone or with WAS-406 (100 μM) or the HBP inhibitor azaserine (20 μM) as a positive control. WAS-406 and azaserine treatment in both non-transgenic islets (Figure 5) and hIAPP transgenic islets (not shown) resulted in a decrease in O-linked protein glycosylation as demonstrated by a reduced number of glycosylated proteins detected using an anti-O-linked N-acetylglucosamine antibody. The magnitude of the effect to decrease O-linked protein glycosylation was greater with WAS-406 than with azaserine.
Given the similar effects of WAS-406 and azaserine to decrease O-linked protein glycosylation, but the reported lack of an effect of azaserine to reduce GAG synthesis in arterial smooth muscle cells (28), we sought to determine the effect of azaserine on ß-cell GAG synthesis and on islet amyloid formation. Unexpectedly, azaserine treatment in ß-TC3 cells was associated with a significant reduction in GAG synthesis as determined by cetylpyridinium chloride precipitation (Figure 6A) and elution from DEAE Sephacel over a 0.15-0.8 M NaCl gradient (Figure 6B). Furthermore, incubation of hIAPP transgenic islets for seven days in 16.7 mM glucose and in the presence of azaserine (20 μM) was associated with a marked reduction in islet amyloid prevalence (78±5 vs 10±6 % in untreated vs treated islets, p<0.01) and islet amyloid severity (Figure 6C) and with an increase in the proportion of ß-cell area to islet area (Figure 6D).
We have shown, for the first time that interventions that decrease GAG synthesis and protein glycosylation in islets are capable of inhibiting islet amyloid deposition and preventing the amyloid-induced loss of ß-cell area in vitro. In the present study, WAS-406 and azaserine reduced both GAG synthesis and flux through the HBP, measured as O-linked protein glycosylation, resulting in a marked decrease in islet amyloid deposition.
While WAS-406 has been shown to be effective in reducing other amyloidoses (16, 20), it was not clear that the same would hold true for islet amyloid formation. In the present study, we found that incubation of hIAPP transgenic islets with this compound resulted in a marked, dose-dependent decrease in both the prevalence and severity of islet amyloid; and this was associated with an increase in ß-cell area. We also found that WAS-406 was effective in reducing [35S]-sulfate incorporation into GAGs synthesized both by intact primary islets and by immortalized ß-TC3 cells, in line with previous data that this compound also decreased GAG synthesis in hepatocytes; reducing both [35S]-sulfate and [3H]-glucosamine incorporation into glycosaminoglycans (20). In ß-TC3 cells, residual GAGs synthesized in the presence of WAS-406 were sensitive to both heparinase and chondroitinase treatment, with the proportions of HS and CS/DS being similar to control cells. These data suggest that WAS-406 is not specific for HS synthesis, which is not unexpected, given that the CS/DS disaccharide constituent N-acetylgalactosamine is formed by the epimerization of N-acetyglucosamine (a component of the repeating disaccharide in HS) and that levels of these two compounds exist in equilibrium, such that any intervention that perturbs the levels of one compound would also be expected to affect levels of the other. Since HS and CS/DS are important components of the cell and extracellular matrix, it is possible that the effect of decreased GAG synthesis with WAS-406 may have confounded the results of the present study. The inclusion of non-transgenic islets treated with WAS-406 allowed us to distinguish the effects of these compounds to decrease amyloid formation from other effects due to decreased GAG synthesis, but the potential adverse effects of long term use of WAS-406 may limit its utility as a pharmacological agent, as described in more detail below.
Previously, we have shown that a radiolabeled analog of N-acetylglucosamine, similar to WAS-406, can be incorporated into growing GAG chains, blocking their extension (20). It is possible that WAS-406 acts via this mechanism in ß cells, although in the present study we did not evaluate whether it was directly incorporated into GAGs. Alternatively, WAS-406 may reduce islet GAG synthesis via down-regulation of the HBP, the biosynthetic pathway responsible for N-acetyglucosamine and N-acetylgalactosamine synthesis. The observed marked decrease in O-linked protein glycosylation following incubation of islets for seven days with WAS-406 is consistent with down-regulation of the HBP.
Unexpectedly, incubation of islets with azaserine also resulted in a reduction of GAG synthesis in ß-TC3 cells. This differs from a previous study showing no effect of azaserine in the presence of high glucose to alter GAG synthesis in arterial smooth muscle cells (28). This may be due to the fact that, in that cell type, substrate supply through the HBP was not rate limiting for GAG synthesis at high glucose. However, increasing glucose concentrations have been associated with increased HBP activity in other cell types (7) and this is likely also the case in ß cells, since ß-cell glucose metabolism is regulated by the high Km enzyme glucokinase. Thus, as our data suggest, azaserine would be predicted to be more effective at inhibiting GAG synthesis at high glucose in ß cells than in smooth muscle cells. The decreases in GAG synthesis and O-linked protein glycosylation with azaserine were smaller in magnitude than those seen with WAS-406, which is likely a result of the lower dose of azaserine (20 μM vs. 100 μM for WAS-406). This lower dose of azaserine was chosen based on previous studies in mouse islets (37), with a higher dose being avoided due to concerns of toxicity. However, this lower dose of azaserine was extremely effective in inhibiting islet amyloid formation, suggesting that modulation of flux through the HBP is important for islet amyloid formation.
While it is possible that the effects of WAS-406 and azaserine to downregulate HBP flux in general, rather than a specific effect on GAG synthesis, may explain their ability to reduce islet amyloid formation, other lines of evidence support our hypothesis that decreased GAG, and particularly HS, synthesis is critical for the deposition of amyloid. First, several in vitro studies have shown that the HSPG perlecan, HS and the related glycosaminoglycan heparin can bind amyloidogenic peptides including hIAPP (2, 3, 25) and that this interaction leads to increased amyloid fibril formation (2, 3). HS is more effective in increasing hIAPP fibril formation than CS/DS (2), suggesting a specific effect for HS in fibril formation. More direct evidence comes from studies using a murine model of AA amyloidosis together with over-expression of the enzyme heparanase that results in in vivo fragmentation of HS, but does not target CS/DS (21). Transgenic mice overexpressing heparanase showed marked resistance to hepatic and renal amyloid deposition but developed amyloid deposition in the spleen in a model of AA amyloidosis. The differential organ sensitivity in this transgenic mouse was inversely correlated with the organ expression of the transgene. That is, the heparanase transgene and its protein were expressed in kidney and liver but not the spleen. Thus, in the same animal fragmentation of HS was observed in kidney and liver but not the spleen rendering only the spleen sensitive to AA amyloid deposition. This argues for a clear role of HS in amyloidogenesis.
Our observation that decreasing glycosaminoglycan synthesis with an N-acetylglucosamine analog results in reduced islet amyloid formation is in keeping with findings that these compounds reduce amyloid formation in mouse models of AA and CNS amyloidosis (16, 20). However, while these effects were similar and amyloid deposits derived from different amyloidogenic peptides contain several invariant components, it is important to recognize that the role of these components in amyloid formation is not equivalent among different amyloidoses. For example, apolipoprotein E is important in the development of Aß amyloid, as shown by delayed and reduced amyloid deposition in a mouse model of Aß deposition lacking one or both apolipoprotein E alleles (1). In contrast, we found that while apolipoprotein E is a component of islet amyloid, apolipoprotein E deficiency had no effect on islet amyloid formation in human IAPP transgenic mice (30). Further, we found that apolipoprotein E is not synthesized by islet ß-cells (30), suggesting that it may be trapped during the deposition of islet amyloid, perhaps by binding to proteoglycans, but that it appears to have no causative role in islet amyloidogenesis.
While we have observed that WAS-406 and azaserine are capable of decreasing amyloid formation, an important aspect of our findings is that they highlight the need for specificity in the development of amyloid inhibitors. While increased flux through the HBP has been shown to be detrimental to the ß cell (14, 27), protein glycosylation is critical for normal cellular function, such that decreased protein glycosylation is associated with impaired insulin secretion (37). Thus, the effects of chronic down-regulation of the HBP by WAS-406 or azaserine may have effects on the cell that are unrelated to their ability to reduce islet amyloid formation and may be detrimental to the ß cell. Islet viability tended to be decreased in non-transgenic islets treated with WAS-406, and islet viability did not improve when islet amyloid was inhibited with WAS-406 in contrast to our findings with other amyloid inhibitors (Zraika S et al, unpublished observation), consistent with a detrimental effect of WAS-406 on islet viability. In contrast, insulin content was significantly increased in both hIAPP transgenic and non-transgenic islets with WAS-406 treatment, a finding seemingly at odds with the viability data. However, glucose-stimulated insulin secretion was not significantly altered (in islets from either genotype) in the presence of WAS-406, despite this significant increase in insulin content. Thus, we speculate that the increase in insulin content may occur, at least in part, due to a failure to adequately increase insulin secretion following WAS-406 treatment, consistent with a role of WAS-406 to decrease ß-cell secretory function and impair islet viability.
Even in the absence of down-regulation of the HBP, systemic down-regulation of GAG synthesis would also be expected to have detrimental effects on the cell, as GAGs at the cell surface and in the extracellular matrix are important for sequestration and signaling of growth factors and chemokines (11). Thus, alternative approaches to reduce islet amyloid deposition have to be pursued. To date these have mainly targeted the amyloidogenic peptide IAPP. Several groups have described peptide-based inhibitors that are effective at reducing fibril formation and/or cytotoxicity of synthetic hIAPP (15, 26). However, the bioavailability and thus applicability of these compounds have not been studied in models of de novo islet amyloid formation. Similarly, small molecules such as Congo red and rifampicin have also been shown to reduce hIAPP fibril formation (8, 23), but further work is required to investigate their toxicity and/or efficacy in long-term studies.
In summary, our data demonstrate that small molecules such as WAS-406 and azaserine are highly effective inhibitors of islet amyloid formation. However, further studies with more specific interventions will be required to definitively prove that HS is required for islet amyloid deposition. Understanding of the actions of compounds that are capable of inhibiting islet amyloid will be useful in developing therapeutic interventions to reduce amyloid formation that occurs as part of the islet lesion in type 2 diabetes.
We thank Jeanette Teague, Rebekah Koltz, Rahat Bhatti, Robin Vogel, Shani Wilbur and Michael Peters for excellent technical support. We are grateful to Michael Kinsella for helpful discussion in the preparation of this manuscript. This work was supported by the Department of Veterans Affairs (SEK), NIH grants DK17047 (RLH), DK74404 (RLH) and RR16066 (SEK) and the American Diabetes Association (SEK). Preparation and development of WAS-406 was funded by the Canadian Institutes for Health Research grant MOP-3153 (RK), the Natural Sciences and Engineering Research Council of Canada (WAS) and the Institute for the Study of Aging (RK and WAS)
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Jim Jefferies (comedian)
|Jim Jefferies
Jefferies in 2012
|Birth name
|Geoffrey James Nugent
14 February 1977
Sydney, New South Wales, Australia
|Alma mater
|Western Australian Academy of Performing Arts
Geoffrey James Nugent (born 14 February 1977),[1] known professionally as Jim Jefferies (and previously Jim Jeffries), is an Australian stand-up comedian, actor, and writer.
Jefferies first achieved international attention after he was attacked onstage while performing at the Manchester Comedy Store.[2][3] At one time, Jefferies incorporated the incident, including its video recording, into his act: this can be seen on his 2008 DVD Contraband. He became well known in the US after his popular debut stand-up special on HBO.[4]
Jefferies has performed at numerous festivals, including the Edinburgh Fringe, Just for Laughs Festival, South African Comedy Festival Cape Town, Reading and Leeds Festivals and the Glastonbury Festival. He has appeared on British comedy panel shows such as Never Mind the Buzzcocks, Have I Got News for You, The Heaven and Earth Show and 8 Out of 10 Cats and the US comedy panel show The Green Room with Paul Provenza. Jefferies has also performed spots on The World Stands Up, Comedy Blue and Edinburgh and Beyond for Comedy Central.
He has also been featured on various radio programmes, including BBC Radio 5 Live's Saturday morning sports show, and Opie and Anthony Fighting Talk.[5]
Jefferies ran a podcast, Jim and Eddie Talkin' Shit, twice a week with his fellow comedian and friend Eddie Ifft. It was recorded from Ifft's home in Los Angeles. In December 2012, Jefferies left the podcast due to his work schedule filming his television series, Legit.[6]
Jefferies's comedy series Legit premiered on 17 January 2013 on FX. A second season premiered on 26 February 2014, having been moved to FXX.[7] The series received positive attention among the disabled community for its portrayal of people with mental and physical disabilities.[8] The series was cancelled after two seasons.[9]
In February 2014 he starred in a low budget Australian feature film called Me and My Mates vs the Zombie Apocalypse with Australian comedians Greg Fleet and Alex Williamson, which premiered in Australian cinemas on 25 July 2015.[10] It was released in DVD and on Vimeo in Australia and New Zealand in late 2015,[11] in the UK on 2 May 2016 and will be released in the US only on 5 July 2016.
In November 2014 Jim guest starred on Bad Judge in the episode "The Cat's Out of the Bag."
Jefferies is perhaps best known for a bit from his Netflix special Bare about guns titled "Guns Are Not Protection". The 14-minute bit has been cited by gun control advocates and websites, and the bit is frequently shared on social media after mass shootings in the United States, such as the Umpqua Community College shooting[12][13] and the 2016 Orlando nightclub shooting.[14]
Stand-up comedy specials[edit]
- Jim Jeffries: Hell Bound: Live at The Comedy Store London – Released: 2008
- Contraband – (5000 limited editions) Released: 10 November 2008 (UK Home Video)
- I Swear to God – Broadcast: 16 May 2009; Released: 13 October 2009 (US Home Video)
- Alcoholocaust – Released: 8 November 2010 (Comedy Central UK DVD)
- Fully Functional – Release: October 2012
- Bare – Release: 29 August 2014 (Netflix)
- FreeDumb – Release: 1 July 2016 (Netflix)
Personal life[edit]
After eight years living in Manchester, England, Jefferies moved to Los Angeles, California, where he now lives.[15] While living in England, his home was robbed.[16]
Jefferies is in a relationship with actress Kate Luyben. The couple has one child.[17]
He is a fan of Fulham F.C. and the Los Angeles Dodgers.[18]
- ^ Powder Blue Internet Business Solutions. "Jim Jefferies". chortle.co.uk.
- ^ Comic attacked on stage : News 2007 : Chortle : The UK Comedy Guide. Chortle (16 April 2007). Retrieved on 5 April 2012.
- ^ "Jim Jeffries: How I got a scar on the back of my head". WZLX. 2011-09-16. Retrieved 2016-02-04.
- ^ Jim Jefferies: I Swear to God: Home. HBO. Retrieved on 5 April 2012.
- ^ BBC Radio 5 live – Fighting Talk. BBC Online. Retrieved on 5 April 2012.
- ^ Jim Jefferies & Eddie Ifft Talk Shit Podcast. Jimandeddietalkshit.com. Retrieved on 5 April 2012.
- ^ Legit on FXX
- ^ Couch, Aaron. "How FX's 'Legit' Became the Darling of the Disabled Community". The Hollywood Reporter. Retrieved 28 April 2013.
- ^ Pedersen, Erik (14 May 2014). "FXX's 'Legit' & FX's 'Chozen' Cancelled". Deadline.com. Retrieved 15 May 2014.
- ^ "Me and My Mates vs. The Zombie Apocalypse (2015)". IMDb. 14 April 2015.
- ^ "Me And My Mates vs The Zombie Apocalypse". Titan View. 2015. Retrieved 2016-02-04.
- ^ Reiher, Andrea (2015-10-05). "Jim Jefferies' gun control stand-up bit goes viral in wake of Oregon shooting". Zap2It. Retrieved 2016-07-13.
- ^ Pang, Evan (2015-10-05). "Australian Comedian Jim Jefferies Sums Up Argument Against Gun Control". The Huffington Post. Retrieved 2016-07-13.
- ^ Barclay, Douglas (2016). "Comedian Jim Jefferies was lost for words after the Orlando shooting". Rare. Retrieved 2016-07-13.
- ^ "LiveSV - Your Silicon Valley Arts, Culture & Entertainment Calendar". livesv.com. Retrieved 28 February 2016.
- ^ "Comedian Jim Jefferies on getting robbed". CNN. Time Warner. 19 August 2011. Retrieved 13 March 2016.
- ^ Legit – Jim Jefferies & girlfriend Kate Luyben. YouTube; retrieved on 15 May 2013.
- ^ "Kevin Pollack Chat Show: Jim Jefferies". 19 June 2013. Retrieved 25 July 2015.


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Michy Batshuayi realised 'childhood dream' with move to Chelsea
Michy Batshuayi says he has fulfilled a "childhood dream" by joining Chelsea.
The 22-year-old completed his move from Marseille earlier this month, and the Belgium international left for the U.S. on Sunday for their preseason tour in the International Champions Cup.
Batshuayi, who already scored for his new club in a friendly against Austrian side Atus Ferlach last week, said he can already tell the Chelsea have lofty goals for the upcoming season.
"It feels fantastic to be here, it's a...


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Singles Case Manager and Hypothermia Program Assistant
FACETS Inc
Email: a***@***.org
10565 Fairfax Blvd. Suite 10
Fairfax, Virginia 22030
United States
FACETS was founded in 1988 to respond to the diverse and multiple needs of homeless and low-income people living in Fairfax, Virginia. It began as an outreach project by its founder, Linda D. Wimpey, and three Episcopalian churches. Today, more than 80 lo... more
Single Adults Team Leader and Hypothermia Program Coordinator
Singles Services Team Leader and Senior Case Manager
TRIUMPH Supportive Housing
Policy Intern
» Our Staff
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FACETS worked with other organizations to ensure that nobody was left in the cold during the bone-chilling weather last week.
"Since the program started, in Fairfax County we have not had any hypothermia related deaths, so it is obviously a very effective program," Dunner said.
FACETS runs one of four hypothermia shelters in Fairfax County, and is the only organization that lacks its own shelter.
The organization partners with local churches to host those in need.
The FACETS shelter opens at 5:30 p.m. and guests must exit by 7 a.m.
"We are using completely donated space, so we are not able to stay during the day, but we try to make other arrangements, and they may go to drop in centers and things like that so they can stay out of the cold during the day," Dunner said.
ST. ANDREW'S EPISCOPAL CHURCH in Burke hosted one of the hypothermia shelters the week of Jan. 6, when the "Polar Vortex" came to Fairfax County.
Churches hosting a hypothermia shelter are required to provide shelter and food, but most go above and beyond, Dunner said.
"They provide entertainment, they provide services like gift cards, they upload smart trip cards so guests can get around, and they provide entertainment like choirs or bands.
They really go out of their way to make this an enjoyable experience for guests," Dunner said.
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Rotator Cuff Injury / Surgery Manhattan, NYC
If you have suffered a severe rotator cuff injury and are in need of surgery, it is important to consider who you are visiting for treatment. Columbia Center for Shoulder, Elbow and Sports Medicine has the ability to reconstruct the damaged tissue in the shoulder restoring use and function once again. If you are living in Manhattan, NYC or Northern New Jersey and are suffering with a rotator cuff injury, call Columbia Center for Shoulder, Elbow and Sports Medicine today.
Depending on the level of rotator cuff injury, surgery is not always necessary. However with heavy injuries such as a tear in the labral tissue, to relieve pain and discomfort, surgery is almost always a must. Arthroscopic methods are used for doctors to treat the shoulder while reducing the down time post-op. The procedure is conducted using several small tools which are inserted into the rotator cuff via small incisions. Among the devices is a special camera which gives the surgeon sight into the joint. This style of treatment is a great benefit, allowing the surgeon greater accuracy and having less down time.
Joint rehabilitation and reconstruction surgery are the most common operations conducted at Columbia Center for Shoulder, Elbow and Sports Medicine. Surgery for rotator cuff injuries, torn ACL's and hip joint injuries are commonplace. Upon visiting Columbia, each patient recieves the same care as if they were a professional ball player. The staff using their knowledge and experience has helped professional teams such as the New York Yankee's and other collegate athletic teams keep playing in top shape. This standard of treatment is what is recieved upon visiting Columbia for treatment. Their physicians and surgeons are committed to seeing each patient succeed and return to their fullest working capability.
The Doctors at Columbia Center for Shoulder, Elbow and Sports Medicine are experts in administering orthopedic solutions in:
- Arthroscopic Shoulder Surgery
- General Orthopaedics
- Sports Medicine
- Joint Replacement
- Shoulder, Elbow, and Arm surgery
If you have suffered a rotator cuff injury and are wondering what treatment you should receive, consider visiting the experts at Columbia Center for Shoulder, Elbow and Sports Medicine in Manhattan, NYC. Their expertise will ensure that you receive surgery only when you need it. If you are living in Northern New Jersey or anywhere else in the tri-state area, call today to schedule an appointment.
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Hotel Rubens - Grote Markt, Antwerp
- Free breakfast and free WiFi
Main amenities
- 36 guestrooms
- Bar/lounge
- Self parking
- 2 meeting rooms
- Terrace
- 24-hour front desk
- Air conditioning
- Daily housekeeping
- Garden
- Laundry service
- Meeting rooms
- Multilingual staff
What's around
- In Old Town
- Antwerp Market Square (0.1 mi / 0.2 km)
- Butcher's Hall (0.1 mi / 0.2 km)
- Cathedral of Our Lady (0.1 mi / 0.2 km)
- Antwerp City Hall (0.2 mi / 0.3 km)
- Plantin-Moretus Museum (0.4 mi / 0.6 km)
Hotel Rubens - Grote Markt, Antwerp
Hotel Info: 866-539-8117from $93
- Penthouse Suite
- Junior Suite, Garden View
- Junior Suite, Terrace, Garden Area
- Standard Double Room, Smoking
- Deluxe Single Room, Garden View
- Deluxe Double Room
- Deluxe Room, Terrace, Garden Area
- Deluxe Double Room, Garden View
- Standard Double Room, City View
- Deluxe Double Room, City View
- Deluxe Single Room
- Standard Double Room
Also popular with travelers from the USA
At a glance
Key facts
Hotel size
- This hotel has 36 rooms
- This hotel is arranged over 4 floors
- Check-in time 2 PM-midnight
- Check-out time is noon
- Express check-in
Required at check in
- Credit card or cash deposit required
- Government-issued photo ID required
Travelling with others
- Pets allowed (dogs only) *
- Specific rooms only, restrictions apply *
- Free WiFi and wired Internet access in public areas
- Free WiFi in rooms
- Self parking *
Nearby Four Star Antwerp hotels
In the hotel
- Free breakfast
- Bar/lounge
- Room service (during limited hours)
- Number of meeting rooms - 2
- Meeting rooms
- 24-hour front desk
- Concierge services
- Dry cleaning/laundry service
- Laundry facilities
- Free newspapers in lobby
- Luggage storage
- Multilingual staff
- Number of buildings/towers - 1
- Year Built 1992
- Elevator/lift
- Garden
- Terrace
- Television in common areas
In the room
- In-room climate control (air conditioning)
- Air conditioning
- Minibar
- Coffee/tea maker
- Iron/ironing board (on request)
- Hypo-allergenic bedding available
- Blackout drapes/curtains
- Individually decorated
- Private bathroom
- Deep soaking bathtub
- Free toiletries
- Hair dryer
- 40-inch LCD TV
- Satellite TV channels
- Desk
- Free weekday newspaper
- Free WiFi
- Phone
- Daily housekeeping
- In-room safe (laptop compatible)
Top Antwerp hotels
Recently reviewed hotels in Antwerp
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Nearby hotels
Hotel Rubens - Grote Markt, Antwerp's small print
Also known as
- Hotel Rubens
- Hotel Rubens Grote Markt
- Hotel Rubens Grote Markt Antwerp
- Rubens Grote Markt
- Rubens Grote Markt Antwerp
Guests must contact this hotel in advance to reserve onsite parking. Please contact the office using the information on the reservation confirmation received after booking.
Pet-friendly rooms can be requested by contacting the property at the number on the booking confirmation.
Parking height restrictions apply.
Special cancellation policies or charges may apply for group reservations (more than 8 rooms for the same hotel / stay dates).
Mandatory fees
You'll be asked to pay the following charges at check in or check out:
- A tax is imposed by the city: EUR 2.39 per person, per night
Optional extras
Self parking costs EUR 18.00 per day
Rollaway beds are available for an additional charge
Pets are allowed for an extra charge of EUR 15 per pet, per day
We have included all charges provided to us by this hotel. However, charges can vary, for example, based on length of stay or the room you book.
Recent reviews
Excellent 4.1 /5 from 190 reviews
Hotel is just a couple of blocks away from Antwerp Groten Markt, which is nice, a lot of restaurants and sites to see just steps away from the hotel, the hotel is nice, I cannot complaint about the age since it is an old building, but they can do a better service in room cleanliness, our bathroom (separate from the shower) was really smelly and when we asked to be cleaned they promised us that it would be taken care of but it wasn't. I might stay at this hotel again if I had no choice but it is definitely not worth the price.
excellent location - close to the Cathedral and center of tourist Antwerp
Lumpy bed, fantastic location.
The central location of this hotel is great to see Grote Markt with lively side streets full of dining options. We enjoyed being greeted by the receptionist with a shot of port, who also let us know that our travel mates had just arrived 15 min earlier. They were happy to provide good dining recommendations. Nice breakfast included with assorted breads, meats, cheese, fruit, cereal, juices and coffee / cappuccino / espresso. A cozy hotel.
The hotel was decent and was centrally located in the old section of Antwerp. There wasn't anything standout in the rooms or service, but neither was there anything poor or sub-standard. The price of the room was similar to other locations and quality of hotels I've stayed at in the area.
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- Anónimo
- Holanda, Homem, 18-24
- Nómada principiante
- 2 Comentários
We had a great stay at Giovanna's hostel! The family that runs it are the best! They really want to make you enjoy your stay and are always prepared to help. It is a bit far from split but there is a bus line that takes care of that problem. If you are lucky (like us) you get the room at the top floor with balcony which has an beautifull view! Would definitely visit again!
- Anónimo
- EUA, Homem, 31-40
- Nómada principiante
- 1 comentário
The family are extremely friendly and accommodating. I bought groceries at a local market within walking distance of the house in order to cook in the guest kitchen, and my hosts provided their own spices. The rooms are comfortable and appointed like home bedrooms rather than a hostel. The only downside is that the house is located fairly far from the city center, but this could also be a benefit because of the beautiful sceneet and quiet at night.
- Anónimo
- Austrália, Casal, 18-24
- Nómada principiante
- 5 Comentários
such a lovely place to stay, the hosts were very nice and very welcoming. Its about 30min bus ride from Split and the beach is about 10-15mins away by foot. Thanks for the great stay and hospitality!
- Anónimo
- Nova Zelândia, Casal, 25-30
- Viajante frequente
- 11 Comentários
Really friendly hosts, willing to help out. However the room smelt like stale smoke and the linen smelt and looked very dirty. The bathrooms weren't overly clean either. Not an ideal location
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May 24th, 2016 | Rachel Parry
When asked to think of a metallic styled wedding, visions of a glitzy and glamorous celebration with lots of sparkling décor might well spring to mind. However, brides looking for a more muted palette should not instantly rule out metallics, as hues of bronze, gold and silver can be easily stripped back for a more natural and dreamy finish.
Particularly well suited to outdoor and ethereal style weddings, there is a clear trend emerging for muted metal tones that provide opulence without the OTT element.
We love to see elegant table set ups of mercury glass vases and worn metal candelabras mixed in with earthy foliage for an almost Midsummer Night's Dream meets Lord of the Rings feel. And it's not just the décor were these fanciful hues can be added to the big day – what about a gold embellished wedding dress, silver muted heels or bonze bridesmaid dresses?
So to help spread a little metallic magic here on the blog, today we're sharing three swoon-worthy metal inspired mood boards…
Clockwise from top left: image source| image source| image source, photography by Katie Bryant Photography, Love Ya Jess| image source| image source| image source| image source, photography by Amy Fanton Photography| image source| image source, photography by Ashley Ludaescher Photography| image source.
Though associated with third place, bronze can be a winning choice of colour scheme, particularly for those wanting to incorporate lots of foliage into their big day as its darker tone sits beautifully alongside earthy greens.
Bronzes also have lovely worn qualities whilst still retaining an element of shine, giving a sense of luxury but that isn't too polished.
For table settings think long timber tables with trailing centrepieces that creep along, interspersed with bronze candle stick holders and table wear. Elsewhere hanging decorations work particularly well with ethereal metallic themes and can easily be suspended from branches if marrying in the open air, or from beams if, for example, marrying in a barn-style venue.
In terms of attire bronze is a bold and untraditional choice for a bride and therefore those wanting to incorporate the hue are more likely to do so through accessories, such as shoes and jewellery. There is also the option of bronze bridesmaids, with its warming tones complementing many complexions and hair colours.
Clockwise from top left: image source, photography by Mi Amore Photo| image source| image source| image source, photography by Jen Wojcik Photography| image source| image source| image source| image source, photography by Conforti Photography| image source| image source.
To achieve an ethereal look with silver it's best to mix varying finishes; from shiny silverware, to worn pewter and varying tones of grey. This way there is a good mix of depth, interest and texture, which will prevent the premium hue looking too glam.
The level of décor detailing is up to the individual with the option to strip things right back to bare wooden tables dotted with small shiny and muted pots of cactuses or succulents, or to go all out with large glass and mercury vases and urns over spilling with greenery and linked up with leaves and moss. Given that it's done effectively the latter should look natural and uniformed rather than cluttered and messy.
Large pewter lanterns are an effective way to add ambience whilst remaining on theme and can look incredibly effective when used outdoors to line pathways, entrances or the aisle.
Dresses embellished with dainty detail in silver beads and sequins are not unusual on the bridal catwalks, giving brides the option to venture beyond traditional ivory for their big day. The men can easily be included in the theming too with grey being among the most popular choice when it comes to grooms picking their suits. For added interest the groom and his groomsmen can pick varying shades of suits as well as ties/Dicky bows.
To keep things simple those wanting metallic maids should look to dresses with simple shiny detailing, rather than top-to-toe sparkle.
Clockwise from top left: image source| image source| image source| image source| image source| image source| image source| image source| image source| image source, photography by Conforti Photography.
Perfect for those wanting a stripped back outdoor wedding but still with a hint of elegance; simple touches of gold be the perfect way to add an opulent edge.
Similar to bronze, gold works well with leafy green plants as it provides a complementary contrast between raw and regal.
For the décor little pops of gold works best – so you might want to add metallic finished cutlery, glass wear or napkin rings. Also, stationery such as name places and menus can bring a hint of shimmer with gold leafing detail – as can the cake. Gold antique mirrors are also an excellent choice to create unusual seating plans and signage.
Just as we've seen silver embellished dresses grace the catwalks, gold detail dresses are no stranger to designers' collections either, with the likes of Jenny Packham well known for her metallic creations. If however, that's a little too glitzy for the bride, a simple gold Game of Thornes style head piece or botanical detail shoe or jewellery can be the perfect way to give a discreet nod to the theme.
May 12th, 2016 | Julia Braime
Daffodil Waves Photography
We're big believers in it being the little details that bring the overall look and feel of a wedding together. We're therefore over the moon to be introducing another fabulous Brides Up North Featured Supplier to the blog this afternoon, who happen to know a thing or two about styling a wedding.
Prepare to go slightly weak at the knees as we say hello to The Wedding of My Dreams and their fabulous wedding prop and décor offering.
Run by mother and daughter team, Karen and Gemma, this easy to navigate website is an Aladdin's cave of pretty details for your wedding day. Better still, as well as shopping till you drop on the site, The Wedding of my Dreams also offers an abundance of stunning big day inspiration to really crank up the creativity… and they are giving an exclusive 5% discount to all Brides Up North readers, just enter the code BUN5 at the checkout.
To tell us more about all the pretty on offer, we'll now hand over the blog to one half of the dream team…
Daffodil Waves Photography
Can you give us a little overview of The Wedding of my Dreams?
gemma says: I'm the younger half of the mother and daughter team who founded The Wedding of my Dreams in 2010. My amazing mum, Karen Morgan, runs the award winning wedding florist Passion for Flowers, which I got more and more involved with after graduating from uni. I'd help on busy weekends picking up floristry skills as I went along, learning only from the best, and developed a real passion for floristry, styling weddings and to be honest everything wedding related! My job at the time was in digital marketing and social media, I knew a thing or two
At the time Passion for Flowers couples were hiring an array of props and decorations from us to complement their florals, saying they couldn't find anything as lovely elsewhere in the market. Mum and I both love sourcing decorations and wanted couples all over the country to have access to the props and decorations we had searched so hard to find and so The Wedding of my Dreams was born.
Going into business with my mum was the best decision I've ever made, we both love going to work every day and both now work across the two companies. It's so rewarding to see how far we've come and how both businesses have blossomed. All the hard work and late nights have really paid off. In 2015 Passion for Flowers was voted best wedding florist in England in The Wedding Industry Awards and The Wedding of my Dreams has won numerous awards since its launch.
Daffodil Waves Photography
What services and products do you offer to wedding couples?
The Wedding of my Dreams is an online shop brimming with beautiful wedding decorations and details to style your tables and venue. We sell table decorations, centrepieces, tea light holders, table plans, favours, and signs, oh and so much more.
Our blog runs alongside our website and we use it as a way to show styling ideas and how our products can be used at weddings. If you're a crafty DIY bride we have a number of free printables and step-by-step guides on our blog too, so you can make your own bits and pieces. Check it out our blog here.
Posted in Featured Supplier, Wedding Decorations, WEDDING DISCOUNT, Wedding Inspiration, Wedding Planning | Filed Under | leave a comment.
April 29th, 2016 | Rachel Parry
image by Helen Russell Photography
As couples continue to bend the 'wedding rules' in order to have a big day that's done their way, we are seeing more traditions fall by the wayside.
Previously through The Big Debate we've discussed whether or not couples should stick with tradition by spending the night before the wedding together or part. It's a contentious issue as superstition has it that it's bad luck for the bride and groom to see each other before the ceremony. But for some couples it's all about feeling comfortable and at ease, rather than running scared of marriage day myths.
This desire to feel relaxed on the day of the wedding has now also led to some couples opting for what's known as a 'first look' prior to the ceremony. So instead of setting eyes on each other as 'bride' and 'groom' for the first time at the altar, the couple share a private moment together ahead of taking their vows where they can see and speak to each other, calming any pre-wed nerves. In most cases the couple's photographer would join them for the first look moment to document the 'big reveal' emotions, just as they would usually capture it at the beginning of the ceremony.
So today we discuss if ditching tradition in this case will make that big reveal moment more, or less, special?
Image by JPR Shah Photography
rachel says: save it for the ceremony
During our previous debate on the night before the wedding I said I was willing to risk the bad luck factor of spending the night with my hubby-to-be in order to get a good night's sleep ahead of the big day. However I stipulated that I'd still want to go our separate ways on the morning of the wedding in order to achieve that highly-anticipated entrance at the ceremony, in front of both the groom and the guests, and I stand by that.
I'm certain I'll suffer wedding-morning nerves, as in case you didn't know I'm a worrier by nature, (I worry about worrying!) but I fear that seeing the groom just minutes before the ceremony would turn me into even more of an emotional wreck than I'll already be.
Also, I've found that the brides we feature on the blog often say their favourite part of the wedding day was meeting their partner at the altar – the expression on their face and perhaps any words they exchanged is what they remember most. I realise you can still get this with a first look, but I think the big reveal is one of the most memorable parts of the wedding for guests too, and something that they feel blessed to be a part of. For example last year when my cousin got married, she cried as she reached the front of the church and watching the groom wipe away her tears, put a tender arm over her shoulder and make her laugh and smile instantly showed us onlookers how perfect they were for each other – and that moment is now etched in my mind!
There's no doubt that emotions will run high, but that's all part and parcel of a wedding day and I don't think the bride and groom need to keep such moments to themselves. So along with not walking under ladders, smashing any mirrors or putting up umbrellas indoors, I'll be avoiding bad luck by saving the first look for the ceremony!
image by Sarah Brabbin
julia says: just the two of us
Prior to my own wedding day, I wouldn't have been game for a sneaky peek, or "first look". I was firmly of the opinion that the arrival of the bride should be met with awe and wonder at the end of an aisle… veil down, music high, anticipation huge.
That's until I learned that my nervous new husband had spent the best part of the wedding morning literally almost throwing up with nerves. Worries about marrying me? Never! Slight hangover? Possibly. Crowd shy? Very.
When we got hitched waaaaaay back in 2010, the whole wedding scene was still pretty traditional compared to now. A first look wasn't even mentioned, let alone properly discussed. If it had been, I probably would have discounted it (hey, it was "my moment"!) but in retrospect, it might have worked very nicely for us – him especially – whilst also allowing us a special photo opportunity and a lovely moment of togetherness and anticipation before the ceremony itself.
Some might think that its bad luck to meet before the service, but it's hardly cheating if it's on hallowed (or licensed!) ground, is it? For me, a first look only ups the excitement factor, is cute and romantic and is all about togetherness – a stolen moment for just the two of you to cherish.
And hey, if you still want to do the whole big entrance thing, your partner can always sneak in the side-door as The Bridal March starts up. In fact, no one need ever know it happened at all…
image by Laura Calderwood Photography
what you said on social:
Natalia says: "We are only having a very intimate wedding of 20 guests so I don't see the need for a first look ahead of the ceremony as I will be comfortable with everyone that will be present."
Jenny says: "I'm not good at being centre of attention so we've decided to have a first look to help ease my nerves. I know seeing my partner will calm me down and give me the confidence I need to make a good entrance."
Clare says: "I'm totally superstitious so won't be taking any chances! I'll be spending the night before away from the groom and then won't see him until I get to the altar. I think doing it any other way would lessen the magic and excitement that builds while you are apart!"
February 16th, 2016 | Rachel Parry
For some couples giving their wedding day a theme makes it feel a little gimmicky, and so they prefer to keep things simple by coordinating the details to a chosen colour scheme instead. But which hues to choose?
Some brides will simply go with their favourite colour(s), while others will pick shades which complement the season of the year in which they will wed. Those needing inspiration meanwhile can always turn to colour experts Pantone, who forecast the top colours each year based on a snapshot of what is taking place in our culture.
For the first time ever, Pantone has introduced two colours for 2016 – rose quartz & serenity – both of which make dreamy wedding colour schemes, either alone or when combined together. So today we're giving you, our lovely brides-to-be, ideas on how to pull off the perfect Pantone palette for your big day…
rose quartz
Clockwise from top left: image source| image source, photography by Masha Golub| image source, photography by Laura Gordon Photography| image source| image source, photography by Matthew Morgan Photography| image source, photography by Elizabeth Messina| image source, photography by Ryon Lockhart| image source, photography by Sarah Mellor| image source| image source.
Described as a warm tone that reflects wellness by Pantone, this stunning dusky shade of rose pink is particularly elegant and would suit various styles of weddings, from classic to contemporary.
Sweet and soft in its appearance this shade is the epitome of love and romance and is also gentle on many skin tones, making it an ideal choice for bridesmaids. It's also an option for brides looking for a subtle alternative to ivory, with a growing number of designers introducing blush gowns to their collections.
Brides sticking to tradition however can still incorporate the rosy hue into their attire through their shoe and accessory choices; whether it be a blush garter, pink pearl necklace or dusky stone drop earrings.
Thankfully when it comes to flowers, there are plenty of pink blooms for brides to choose from, such as peonies, lilies, astilbe and anemones. In addition to bouquets and button holes, such blooms can be incorporated into the décor and even the cake design. It would also be a nice play on the colour scheme to feature roses in the theming, both in terms of the flowers and design of elements like the stationery.
Weddings that are light, soft and delicate in their appearance will work best with this girly hue so just be sure to keep things simple, clean and classy.
Clockwise from top left: image source| image source| image source, photography by Ben Yew Photography| image source, photography by Fuller Photography| image source, photography by Anastasia Belik| image source| image source| image source| image source, photography by Amaranth Photography| image source.
Every bride needs a something blue for her big day, so why not choose Pantone's serenity for an on-trend and elegant colour scheme.
Described as tranquil and soothing by the colour forecasters, this is an ideal choice for those wanting a laid-back yet loved-up feel for their wedding.
Though not the most popular choice with brides, we have seen an increase in the number of steely blue dress designs hitting the bridal catwalks, notably from top designers such as Ian Stuart and Monique Lhuillier. Brides wanting to play it safe meanwhile could go for the classic something blue in the form of their shoes, adding a pop of colour to their attire.
For bridesmaids the cool tone could be a little tricky to match to varying complexions and so a mix of differing blue tone dresses might work best, whilst also adding depth and interest.
Grooms can also get in on the blue colour scheme for their attire. Though serenity is a mid to lighter shade of blue, which many men might not feel comfortable in, there is the option of a navy suit matched with a tie or dicky bow in a similar shade to serenity, whether it be plain or patterned.
Elsewhere blue can be reflected through flower choices such as hydrangeas, thistles, eucalyptus and iris. Cake designs can also feature the hue, with watercolour, ombre and wedgewood styles lending themselves particularly well.
As to not make the overall look too cold and controlled, try to keep to the powder side of blue and soften décor with the use of pretty petals and bows.
blue & blush
Clockwise from top left: image source, photography by Into the Light| image source, photography by Loft Photographie| image source, photography by Natalie Bray Photography| image source, photography by Rebecca Amber Photography| image source, photography by NJ Wedding Photographer Kay English| image source, photography by Eve Photography| image source| image source, photography by Tiffany Hughes Photography| image source, photography by Caroline Tran| image source.
Finally for a complete colour contrast, couples can fully embrace Pantone's picks of 2016 by incorporating both blush rose and serenity blue into their big day.
Focusing on gender equality, Pantone points out that bringing the two shades together creates something of a gender blur, though for weddings it could be seen as both a reflection of the bride and groom through both a feminine and masculine colour combination.
Working in perfect harmony Rose Quartz and Serenity are particularly appealing for those wanting a sweet, surgery and elegant look to their wedding.
Bridesmaids can be mixed and matched in the two colours, or alternatively kept in one shade for their dresses and then have the contrasting colour for either their bouquets and/or heels.
In terms of décor, coordinating and contrasting blooms and vases, jars or bottles work well, as do pretty paper pompoms or lanterns in the two shades. Crockery and glassware can also be mismatched to reflect the scheme, and in pastel shades can work particularly well with vintage and afternoon tea style settings.
February 12th, 2016 | Julia Braime
It's mid month and we're all feeling the pinch, right..? When payday feels like such a long time away, it's often easy to worry about how you're going to be able to afford that dream day that everyone keeps mentioning.
We're huge advocates here of doing things your own way on your wedding day, and achieving the perfect day (your version of it!) within your own budget, whatever that might be. Yes, its a super important day in your life, but it really is just one day – don't give yourself a lifetime of debt to furnish 100 guests with the perfect wedding favours! Unless you're very comfortable financially or The Bank of Mum & Dad is paying out big time, we think it might be time to get saving.
Luckily, our sponsors at TSB have come up with some handy tips for saving for your wedding without breaking the bank. Take a look, and here are some of our favourite tips, combined with a few of our own…
set a budget
It's important to be realistic and set a budget for the big day, but also all the smaller elements of it too. Be strict, because if you go over budget on each part, you might find yourself in trouble when it comes to paying the registrar! TSB advise that setting a limit on the amount you can spend on your dress is a good place to start.
"Budget before you go and be realistic by only trying on dresses that are within your budget," says Phil of Phil Collins Bridal. "You don't want to be disappointed by falling in love with a dress you can't afford."
limit the numbers
Yes, obviously, less bums on chairs will bring the overall cost down, but you might like to consider the number of people in the actual wedding party very carefully too. The cost of six adult bridesmaid dresses can really add up. Consider keeping the number of attendants and groomsmen on the smaller side, or ask if they would mind contributing to the cost of their outfits if you are prepared to give them some flexibility in the style stakes.
double up
TSB suggest cutting costs by using your flowers and decorations at both your ceremony and reception venue, if they are separate (ushers at the ready)! It's wise to make sure you have factored in absolutely all costs – as well as the cost of hiring the venue, remember any decor you may wish to use; flowers, the photographer and transport.
September 29th, 2015 | Rachel Parry
Having set your budget, booked your venue, sent out your save the dates and secured your photographer and entertainment, it's time to move onto tasks that many brides deem as the more enjoyable and exciting parts of the planning schedule.
This is because it's time to start thinking about how to style yourself and your venue for the big day to come! So in today's wedding planning post we'll be talking blooms, bridal boutiques and bridesmaids.
Check out our earlier posts in this series by clicking here (the early stages) and clicking here (the next steps).
flower power
Today beautiful blooms tend to stretch way beyond bouquets and button holes with many couples opting to incorporate pretty petals into their décor too. From dainty pew ends to grand floral chandeliers, the possibilities are pretty much endless, though you will need to find a florist that shares your botanical visions in order for them to become reality.
When searching for the right florist, it's important to look for a trusted supplier with good testimonials from previous couples. You will also want to view examples of their recent work to get an idea of the styles and arrangements that they can achieve. So it might be that you are looking for a florist known for loose, natural and rustic designs, or perhaps neat and elegant arrangements or those that can wow with modern, striking floral structures.
Once you have whittled down a short list meet up with the florist to see how you 'click' and if they share your visions on bouquets and floral decorations. They might even suggest great ideas you'd never even thought of.
the one
In many cases shopping for the dream dress is a bride's favourite part of the planning, though it can be daunting and frustrating at times too with so many options to choose from.
Having done your initial wedding dress research using magazines, blogs and websites to get an idea of the type of gown you might like and to suss out which designers fall into your dress budget, it's time to search for boutiques that stock your chosen designers and make appointments to visit.
When attending bridal boutique appointments it can be easy for brides to get carried and invite a small entourage to accompany them but it really is best to keep numbers to a minimum to avoid becoming confused by differing opinions. Take those who know you and your style best and will give you an honest opinion – so perhaps mum, sister and maid of honour.
Though it's good to have an idea of the type of dress you might like, it's also good to be open minded at your appointment as a style that you've never considered just might turn out to be 'the one'. Bridal stylists know their stuff so if they make a suggestion to try a certain gown on, go with it but don't feel pressured – the decision is ultimately yours.
leading ladies
Once your dress is sorted you can move onto finding the right gowns for your maids. Again, though most ladies love to shop, bridesmaid dress hunting can be far from retail therapy with bridesmaids clashing on what they would and wouldn't want to wear.
To avoid shopping centre tantrums it's a good idea to get together with/speak to your bridesmaids about what type of design and colour you were hoping to dress them beforehand, giving them an opportunity to express any concerns early on. If you have maids of varying figures you could dress them in one colour but different styles of dresses to suit their individual shapes. Alternatively, if you have maids of varying hair colours and complexions, you could ask them all to wear the same design but in varying complementary colours, to suit both them and the wedding styling.
Also, when picking suitable colours for the maids' dresses think about the styles and tones of flowers you've picked and how they will work together.
At this point in the planning process it's also a good idea to get the catering search underway if the venue you've booked won't be providing the food.
Over time wedding breakfast menus have been extended beyond traditional meat and vegetables, meaning that there are now lots exciting options to whet your appetite. Some couples base their food choices on their personal preferences while others make their decisions by the season of the wedding. There's also the option to pick menus that complement the style of the wedding, so for example afternoon tea for a rustic, country themed wedding, or street food, such as pizza or Mexican, for informal outdoor weddings.
Whatever you decide look for caterers with good reputations and find out what is included in the price, such as waiting staff and glass/crockery hire, to avoid any hidden costs. Then it's time to sample the goods with a tasting session so you'll know exactly how the food will look and taste when it's served up on the day.
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Whatever that political culture valued most highly, achieving good results clearly was not it. Now the same seems true of today's Republican Party, whose base lies in that same region. And how can one expect indifference to good results to lead to anything but damage to the nation?
Technology isn't just advancing in the way we manage our histories or in the kind of machines and techniques we use for diagnosis and treatment. Interconnectedness is also giving us new ways to interact with our healthcare providers, no matter where we are.
I'm sitting here at the very bottom of the medical food chain wondering why it's not illegal for pharmaceutical companies to price gauge the products that save our lives. If the price of my daughter's medication wasn't so high, would we have the drugs in hand quicker?
There could be a problem with current incentives and funding for support structures for accountable care organizations (ACO). This "spoonful of sugar"...
This is a complicated story, but an important one. It's a story of determination, of progress and of creativity. It's part of the rich history of the larger social justice movement for LGBTQ communities in our country -- one that has not been at the forefront of the conversation.
The relentless Republican campaign to demonize the Affordable Care Act has put their candidates in a political bind, with no escape hatch. With so many people now benefitting from the ACA, Republicans candidates are forced to propose a replacement plan.
Now that he has declared his candidacy for president, after flirting with one in 2012, it is galling to see him rise in the polls presumably due to his telling it like it is, which a lot of people find refreshing, punctuating his hyperbole with cheap insults hurled at anyone who challenges him.
Should these latest anti-competitive takeover moves go unchallenged by the Obama Justice Department when there is little doubt that the trend of double digit premium increases will accelerate?
Companies will not automatically, dollar for dollar, increase taxable wages to compensate for cost increases passed on to employees. That doesn't occur now when businesses are forced to pass increased health-care costs to its workforce.
Whether race relations have actually worsened or whether that perception stems from more information reaching more people, it is obvious that we must re-dedicate ourselves and our government to eliminating injustice and promoting equality.
I'm an addict -- wrong, right or indifferent, I will always be an addict. Yet what makes me understand my addiction more is that I suffer with a men...
On June 25, 2015 the Supreme Court upheld President Obama's hotly debated Affordable Care Act in a 6-3 decision. For those following the debate intently, it is understood that the verdict now authorizes federal tax credits for eligible Americans living in states with their own exchanges and also those in the 34 states with federal marketplaces.
As part of a pledge to protect the middle class, Hillary Clinton is taking a second look at aspects of the ACA that hurt working men and women. That's good news, and the only responsible position for politicians interested in providing more and better healthcare at lower cost.
When the CEOs of Aetna and Humana announced a few days ago that they had agreed to a deal in which Aetna will pay $37 billion for Louisville-based Humana, Senate Majority Leader Mitch McConnell of Kentucky pointed the finger of blame straight at Obamacare.
Healthcare as a right has been debated over many years, but is still not in place for all Americans as this country remains an outlier among advanced industrial countries around the world.
The Supreme Court's recent blessing of Obamacare has precipitated a rush among the nation's biggest health insurers to consolidate into two or three behemoths. The result will be good for their shareholders and executives, but bad for the rest of us -- who will pay through the nose for the health insurance we need.


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My wife and I have been living in the Rogers Park neighborhood for 7 yrs. We reside on Fargo just west of Ashland. I have been a realtor for almost 10 yrs but all of my experience comes from the leasing side. The rental market in Chicago can be unpredictable but doesn't look like its slowing down anytime soon. The rental market in Rogers Park for a rehabbed/new construction 2 bed 1.5-2 bath are $1300 to $1450. One of my neighbors had me help them rent their place out 3 yrs ago. They rented it in 2 days for $1350 and have had the same tenant since. That is obviously not a typical situation. It also depends on if you plan to rent your own place or have a professional help you out. My wife and and I are currently weighing our options of whether we should rent our current place out or put it on the market to sell. We are expecting our 2nd child and have out grown our current place. The rental market in Chicago is good from May to Sept. The strongest from June to Sept. You need to actively list your property 60 days in advance. If you have any further questions please feel free to respond. Thanks.
Good luck with your search, and if you need our assistance please feel free to call on us. FYI: our new office opens December 1 and we also have offices at 5650 N Broadway.
Rusty A. Payton, Broker
iMove Chicago
5650 N Broadway
Chicago, Illinois 60660
773-961-8819 [Office]
773-289-0806 [Fax]
773-682-5210 [Mobile]
e. firstname.lastname@example.com
blog: iMoveBlog.com
In addition to the comments already posted here you will also need to consider your competition and show condition (obviously in relation to price).
If your competition shows better then they will rent out before you do if it's priced appropriate for the market. Rentals are really hot in Chicago and Rogers Park has always been a renters haven.
Work with a leasing agent that can best guide you as to pricing and show you what you're up against.
Good luck!
2 It depends more on the supply demand RP has been a decent rental market, but not one of the best for landlords. Some buildings are more popular for rentals than others. There are many factors that affect rentals.
3 There is nothing normal anywhere in Chicago
Rogers Park is located between two Universities, Loyola and Northwestern, you won't have a problem renting out your unit if you do decide to purchase then rent. These units, with the amenities you described and sqft, can rent out between the price range of $1350-$1575, depending on the condition of the building and unit. They usually rent out quickly before the fall semester starts however I noticed in Rogers Park units rent out pretty quickly between 15-36 days most of the year, winter months rents slow down a bit throughout Chicago. About the crime, well crime's everywhere sadly to say but my advice check out the Chicago Police's website or call the district, the 24th district covers most of Rogers Park. Good luck to you, if you have anymore questions send me an email at firstname.lastname@example.com
2. Depends on what you equate as good condition. If you are referring to granite, stainless steel appliances, hardwood floors, etc. then average would be around $1200+ depending on the layout and sq ft.
3. I have to refer you to the local municipality for exact statistics for crimce
Sohail A. Salahuddin | Broker Associate | Visionary
Innovative Property Consultants Team | Sales and Leasing
Jameson Sotheby's International Realty
425 W. North Ave. | Chicago, IL 60610

"Locally Known, Globally Recognized"


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Acer T232HL Touch 23in monitor
Add a touchscreen to your Windows 8 PC or notebook with this 23in monitor from Acer
- Good touch responsiveness
- Useful tilt angle
- Good colours and clarity
- Reflections can be very annoying
- Menu buttons aren't great
Bottom Line
Acer's 23in Touch monitor is a good one to go for if you've got a Windows 8 PC or notebook that doesn't already have a touchscreen monitor. We like its image quality and the fact that it can be tilted until it's almost flat.
Price$ 699.00 (AUD)
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Using Windows 8 without a touchscreen means you don't get to experience the new operating system in the way that it was intended, primarily by swiping back and forth on the Start screen and tapping on icons to launch apps. If you've just bought a new PC or non-touch laptop and now you want to add touch capability, you can consider a monitor like the Acer T232HL.
Acer's T232HL is a 23in, Full HD (1920x1080-pixel), LED-backlit monitor that supports 10 multi-touch inputs and it has a relatively funky design that's the same as what we saw on Acer's Aspire U Series all-in-one PC. The front of the monitor features edge-to-edge glass that has been extended down seamlessly to create part of the stand for the monitor. Rather than make the screen look like it's floating (as it was meant to look like on the all-in-one PC), the clear glass on this monitor is tinted and gives off more of a grey look than see-through look. The rear of the monitor has a single, angled arm that allows the monitor to be tilted back and forth quite easily with one hand. It tilts down 60 degrees, which is a good angle for performing touch-based tasks.
We typed up this part of the review using that screen position, but it did take us much longer than using a physical keyboard, and we were a little frustrated that we couldn't make the Windows 8 on-screen keyboard bigger. Basically, it's not a practical way to type; the lower angle is more suited for playing games with on-screen controls or for interacting with music, photo and video software. In fact, tilting the screen back and using your finger to swipe back and forth while leaning over the screen is a great way to view images on this monitor (as long as reflections don't get in the way). We had no problems with the accuracy of the touch inputs. Our Windows 8 swipe-in gestures were recognised easily, as were taps and dragging operations of windows and files. The only thing that could be a problem is friction on the screen's surface as you drag your finger across it.
The video inputs are located under the rear lip of the monitor and they include HDMI, DVI and VGA; there is also a 3.5mm audio input. As is the case with most monitors, these ports can be a little hard to get to; you'll have to tilt the monitor forward a little so that you can see them, or just use your fingers to feel for the port that you're after. There is a USB host port that needs to be connected to your PC in order for the touch functionality to work, and it also enables the three USB 3.0 ports that are located on the left side of the monitor. Stereo speakers are built in to the monitor, but they are only for very basic listening. If you want louder and better quality sound, you'll still need to use a good pair of external speakers.
On the right side you get some control buttons that can be awkward to use. The power button sits in the same line of menu and navigation buttons and it's too easy to hit it when you want to try and enter the monitor's menu. The buttons aren't even labelled apart from the power button. However, you can press any of them to bring up a menu that correlates to the position of the buttons and then shows you which one to press depending on the feature that you want to access. For example, the top button allows you to access the main menu, the button under it allows you to change video input, and the two buttons below that are for navigation. It's not too difficult to navigate once you get the hang of it, but it can be frustrating when you're uninitiated.
From the on-screen menu, you can change the brightness, contrast, colour temperature, and also select from one of Acer's pre-defined colour profiles, including 'eco' mode, which reduces the brightness. We used the 'standard' setting for our tests and found the monitor to be perfectly fine for everyday tasks (viewing photos, watching videos, working on documents and playing games). Colours looked rich and pictures looked sharp. We noticed the screen's angles to be wide and we were able to view the screen from the sides, above and below without any colour shift or too much loss in detail. That's a good thing considering the tilt angle that's supported. The brightness is good enough so that the screen can be viewed comfortably in a well-lit room, but reflections might still be a nuisance in some environments.
The thin design of this monitor makes it look elegant and it keeps the unit light so that you can tilt it back to make proper use of its touch interface. It's good monitor to choose if you are after something that will enable touch input on your Windows 8 PC or laptop and its image quality is very good to boot. It has a 5ms response time, which should make it okay for gaming — we had fun playing games such as Riptide GP from the Windows 8 store, which is a fast-paced racing game, and didn't notice any ill motion effects. We're only concerned about the reflections that come off the screen, which could get annoying depending on your environment, and we don't like the control buttons, but the chances are that the controls won't need to be played with very often, if at all. It comes with an external power brick that's similar to a laptop's power supply, and it has a rating of 64W.
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First impression on unpacking the Q702 test unit was the solid feel and clean, minimalist styling.
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For work use, Microsoft Word and Excel programs pre-installed on the device are adequate for preparing short documents.
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The screen was particularly good. It is bright and visible from most angles, however heat is an issue, particularly around the Windows button on the front, and on the back where the battery housing is located.
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Oh-So Resourceful Kid Uses Everyday Objects to Make Killer Drum Set
This kid rocks the drums without even playing them.
This kid rocks the drums without even playing them.
The squabbles of a husband and wife are private matters and shouldn't be the business of anyone else. However, this situation may be an exception since the end result of this disagreement can be plainly seen in their front yard, and it could be life-threatening.
Touchdowns are worth six points, but maybe this team should've gotten a few style points, too.
Some 10-year old girls are content playing with dolls and apps, but this Texas sharp-shooter decided to use her spare time to hunt down a 13-foot alligator. Here's how it happened.
The intense flooding that rocked South Carolina over the weekend was nothing for one motorist.
A stray pregnant dog was saved from a most unusual -- and frightening -- place.
Something that hadn't happened since 1982 took place Sunday night. If you missed it, prepare to be awed.
This GoPro has gone on the journey of a lifetime.


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Category: "Anne Hathaway"
Anne Hathaway is really feeling Beyonce's Lemonade: try-hard or fine?
James Franco was trying to 'subvert' the Oscars when he co-hosted in 2011
Anne Hathaway & Adam Shulman welcome baby boy Jonathan Rosebanks
Anne Hathaway wore leather pants to her baby shower, got quite a gift haul
Star: Anne Hathaway didn't get 'Mary Poppins' because her British accent sucks
Anne Hathaway in Naeem Khan at the VF Oscar party: stunning & '70s?
2016 Oscars Open Post: Hosted by pregnant Anne Hathaway
Emily Blunt is probably going to be the new Mary Poppins: love it or hate it?
Anne Hathaway defends Jennifer Lawrence after the weird Golden Globes incident
Anne Hathaway & Adam Shulman are expecting, she's in her second trimester


text: Looking for the news.I'm pissed, because my limit order for 2k shares I placed this past weekend never got filled (before a nearly 100% runup).On the other hand, I still have a bunch of shares that I bought a while back, so this is really great news for me. I just wish the runup had happened a few days later *sigh*I may have to buy some more anyhow, but I was hoping to pick them up really cheap (rather than just cheap)...Please post any info if anyone hears anything. I don't trust rumors, so I won't change my decisions, but I'm very curious.