text:
The Expression and Significance of mTORC1 in Diabetic Retinopathy
Yanli Liu, Yarong Zheng, Yekai Zhou, Yi Liu, Mengjuan Xie, Wenjing Meng, and 1 more
https://doi.org/10.21203/rs.2.18087/v2
published 20 Jul, 2020
Read the published version in BMC Ophthalmology →
posted 25 Feb, 2020
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Background: To investigate the expression and significance of mechanistic target of rapamycin complex 1(mTORC1) in diabetic retinopathy(DR), and to find new targets and new methods for the treatment of DR.
Methods: A DR rat model was prepared by general feeding combined with intraperitoneal injection of 10% streptozotocin (60 mg/kg). The rats were randomly divided into a control group (NDM group) and a diabetes group (DM group). Three months later, the degrees of retinopathy was determined using hematoxylin and eosin staining, and the levels of p-S6, VEGF, and PEDF proteins were detected by immunohistochemistry and western blotting. Human retinal capillary endothelial cells (HRCECs) were cultured in high glucose(HG) conditions, then treated with rapamycin or transfected with siTSC1.The protein levels of p-S6 were assessed by western blotting. The 5-ethynyl-2´-deoxyuridine assay was used to detect cell proliferation, and the Transwell assay was used to detect cell migration.
Results: A DM rat model was successfully developed. The expressions of p-S6 and VEGF proteins were significantly increased in the DM group (p < 0.05), and the expression of PEDF protein was significantly decreased compared with the NDM group (p < 0.05). In vitro, the p-S6 protein, as well as cell proliferation and migration, in HG induced HRCECs were increased (p < 0.05) compared with the control (normal glucose) group (p < 0.05). After transfection with siTSC1 to activate mTORC1, the expression of p-S6, as well as cell proliferation and migration, were increased. In contrast, rapamycin decreased p-S6 expression, as well as proliferation and migration, in HG induced HRCECs compared to the control group (p < 0.05). Conclusion: mTORC1 plays an important role in DR. After activation, mTORC1 induced expression of the p-S6 protein, regulated the expressions of VEGF and PEDF proteins, and changed the proliferation and migration of endothelial cells. The mTORC1 can therefore be used as a new target,as well as in the treatment of DR.
mTORC1
p-S6
PEDF
Cell proliferation and migration
Diabetic retinopathy (DR), which is a microvascular complication of diabetes mellitus (DM), is the most common retinal vascular disease, and is one of the major blinding eye diseases for patients over 50 years of age[1]. However, the present treatment options for DR are limited[2].Studies have confirmed that the destruction of pancreatic beta-cells in a high glucose (HG) environment leads to DM[3]. The retina is in a HG environment for a long time, which leads to the destruction of the blood-retinal barrier, and induction of excessive production of pro-inflammatory cytokines, such as TNF-α,and IL-1β[4], which stimulate excessive production of reactive oxygen species in the mitochondrial electron transfer chain, to cause oxidative stress and to limit the production of energy[5], resulting in the inhibition of cell autophagy[6]. This series of processes eventually leads to retinopathy[7], promoting the release of a large number of cytokines[8], which leads to the occurrence of DR.
The mammalian target of rapamycin (mTOR) is a highly conserved serine/threonine protein kinase in structure and function, involving mTORC1, and is a central signaling molecule that integrates various pathways inside and outside cells, regulates cell growth and metabolism, and provides an important molecular link between nutritional signals and metabolic processes necessary for cell growth. It mainly promotes cell growth, proliferation and differentiation by activating key anabolic processes. Improper regulation of mTORC1 is the basis of many human diseases, including cancer, diabetes, autoimmune diseases, and nervous system diseases[9]. Several recent studies have demonstrated that mTOR may play a vital role in DR pathophysiology. The research by Calton and Vollrath proved that inhibition of mTOR reduced migration of retinal pigment epithelial cells [10]. Fort and colleagues found that mTORC1 caused an independent reduction of retinal protein synthesis in type 1 diabetes. However, the effect of mTORC1 activation on DR development has not been reported [11]. The roles of mTORC1 in aberrant endothelial cell proliferation and migration, and the crucial events in DR progression, as well as its underlying mechanisms, are not known.
In the present study, the rat DR model and the human retinal capillary endothelial cells (HRCECs) HG model were constructed. To determine the role of the mTORC1 signaling pathway in the pathogenesis of DR, as well as to find new targets and methods of treatment for this disorder, we first measured the expression level of mTORC1 downstream phospo-S6 ribosomal protein (p-S6).We thenanalyzed its relationship with the expression level of vascular endothelial growth factor (VEGF) and recombinant human pigment epithelium-derived factor (PEDF), and characterized retinal proliferation and migration.
Animals Healthy male SPF SD rats, weighing 200±20 g(n=12),were obtained from the Animal Laboratory Center, Southern Medical University[license No. SCXK (Guangdong, China) 2016-0041].All experimental animals were fed and followed-up in the animal room of the Medical Research Center of the Third Affiliated Hospital of Southern Medical University. The experimental protocols were approved by the Animal Ethics Committee of Southern Medical University.
Diabetes Induction The rats were randomly divided into a non-diabetes mellitus (NDM) group and diabetes mellitus(DM) group. After adaptive feeding for 3 days, the DM group(n=6) was injected intraperitoneally with 10% streptozotocin(STZ) at a dose of 60mg/kg body weight, STZ was dissolved in a citric acid-sodium citrate buffer solution of 0.1mmol/L and pH of 4.4, which was protected from light and placed on ice[12.13]. The NDM group(n=6) received the same dose of citric acid-sodium citrate buffer. In the DM model rats, animals with blood sugar ≥ 16.7 mmol/L were used for tail venous blood tests. All animals were euthanized at 3 months by intraperitoneal injection of pentobarbital sodium, and their blood samples and retinas were harvested for protein preparation, and the eye balls were removed for paraffin sections.
Major Reagents STZ, citric acid, and sodium citrate (Sigma-Aldrich, St. Louis, MO, USA), anti-VEGF mouse monoclonal antibody (Abcam, Cambridge, MA, USA),1:3000[14.15], anti-PEDF rabbit polyclonal antibody (ABclonal, Wuhan, China),1:3000,anti-PS6 rabbit monoclonal antibody (Ser235/236; Cell Signaling Technology, Danvers, MA, USA)1:1500[16], anti-S6 rabbit polyclonal antibody (Cell Signaling Technology),1:5000[17], anti β-tubulin mouse monoclonal antibody (Beijing Kangwei Century Biotechnology, Beijing, China;1:5000), anti-mouse secondary antibody and anti-rabbit secondary antibody (Beijing Ruikang Biotechnology, Beijing, China;1:3000), Endothelial Cell Medium (ECM; Sciencell, Carlsbad, CA, USA), and rapamycin (APExBIO; Boston, MA, USA) were used in this study.
Trypsin Digest Preparation of Retinal Vasculature Retinal vasculature was prepared according to the protocol written by Jonathan C. Chou [18] Briefly, the eyeballs were enucleated and fixed in 4% paraformaldehyde for 24 hours. The retinas were dissected from the eyeballs, washed in water overnight, and digested in 3% trypsin (Solarbio, Beijing, China) for 2 hours at 37°C. The tissues were repeatedly washed in water to remove debris, transfered onto clean slides and unfolded under a dissection microscope, stained with hematoxylin & eosin (Solarbio, Beijing, China) after natural drying, then dehydrated and mounted. The prepared retinal vessels were photographed by microscope and 5 pictures were selected from each group. The number of endothelial cells and pericytes from images were counted and the ratio(E/P) was calculated to assess the degree of retinopathy.
Cell Culture HRCECs were from Guangzhou Jennio Biotechnology (Guangzhou, China) and were cultured in media supplemented with 1% endothelial cell growth supplement1% penicillin/streptomycin solution, and 5% fetal bovine serum (FBS) at 37°C, and were incubated in a humidified incubator with 5% CO2. When HRCECs reached 80%–90% confluence, they were digested with 0.25% trypsin without EDTA and passed at a ratio of 1:2. The concentration of glucose in the ECM was 1 g/L (5.5 mmol/L), which was similar to the normal blood glucose concentration of the human body. HRCECs were cultured in the same normal glucose concentration as the control group (NG group). D-(+)- glucose was added to the ECM , and the final concentration of glucose was adjusted to 4.5 g/L (25 mmol/L) to simulate the diabetic microenvironment of the human body, which was used to develop a HRCEC HG model (HG group)[19]. The final concentration of rapamycin (inhibitor of the mTORC1 pathway) in HG-ECM used to treat HRCECs was 50 nM (HG + rapamycin). Cells treated under different conditions were placed in a constant temperature incubator for culturing, and the medium was changed every day for subsequent protein extractions.
Transfection The siTSC1 (sense, 5'-CCAAAUCUCAGCCCGCUUUTT-3' and antisense, 5'-AAAGCGGGCUGAGAUUUGGTT-3') were purchased from Sangon Biotech (Shanghai, China). They were separately transfected into HRCECs using Lipofectamine 3000 reagent (Life Technologies, Carlsbad, CA, USA) according to the manufacturer's instructions.
Transwell Assay After HRCECs were treated with different interventions for 48 h, 1 × 105 cells/mL were diluted with serum-free ECM and transferred into the upper chamber of a Transwell insert (Corning, Corning, NY, USA). ECM containing 5% FBS was added to the lower chamber. After 24 h of incubation in a CO2 incubator at 37°C, the non-migrating cells were gently removed from the upper chamber. Cells that had migrated through the membrane were fixed with 4% paraformaldehyde for 20 min and stained with a 0.5% Crystal Violet solution for 10 min. The migrated cells were imaged using an inverted optical microscope, and five fields of view were randomly selected to count cell numbers.
5-ethynyl-2´-deoxyuridine (EdU) Assay HRCECs were inoculated into 15 mm glass-bottomed dishes. After becoming adherent and reaching 60%–70% confluency after 6 h, they were separately treated with different interventions. After 48 h of treatment, the cell proliferative capacity was assayed with a kFluor488-EdU assay kit (KeyGen, Nanjing, China) according to the manufacturer's instructions. Samples were incubated with 50 µM EdU working solution for 2 h. The cells were then imaged using a fluorescence microscope. Five fields of view were randomly selected to calculate the positive rate.
Statistical Method All experiments were performed in triplicate and observed by independent observations. SPSS statistical software for Windows, version 19.0 (SPSS, Chicago, IL, USA) was used for statistical analysis. The experimental data are expressed as the average number ± standard deviation (x ± s). Each test sample was provided with two secondary wells. The t-test was used for comparison between two groups. The difference was statistically significant with a value of p < 0.05.
Establishment of a diabetic rat model
In the NDM group, the blood glucose level of rats was always≤ 16.7 mmol/L. Before eating and drinking the same amount, the rats gradually gained weight and had clean and shiny fur. After 1 week, the blood glucose levels of the DM group rats were all ≥16.7 mmol/L. The blood glucose level of the DM group rats was significantly increased, the intake of food was increased, and the amount of drinking water was increased, with approximately twice that of the healthy rats. However, weight gain was not obvious in DM rats within 3 months, and several even lost weight, with sallow fur and bent backs (Figure 1A).
In NDM rat retinas, the structures of each layer were clear and distinct after hematoxylin and eosin staining. In the DM group, the structure of the retinal layers was disordered, the inner limiting membrane was swollen, dilated blood vessels could be seen in the ganglion cell layer, and more blood vessels could be seen in the outer plexiform layer (Figure 1-B).
As showed in the retinal vasculature, the nucleuses of endothelial cells were big, oval or irregular which paralleled with the vasculature in long axis (Fig1C, white arrow); the nucleuses of pericytes were small and round, being triangle, located at one side of the capillary (Fig1C, black arrow). In DM rat, the ratio of the number of endothelial cells to the number of pericytes(E/P) was significantly increased compared with NDM rat(p<0.0001,Fig1C).NDM rat showed normal vascular architecture, while diabetic rat retinas exhibited increased acellular capillaries (Fig1C, triangle).
mTORC1 was highly activated in retinas of diabetic rats when compared with nondiabetic rats
Rats were euthanized 12 weeks after successful modeling, and retinal tissues were obtained. We next determined whether mTOR was activated in diabetic rats compared with non-diabetic rats. Immunofluorescence analysis revealed significantly upregulated phosphorylation of S6 (S235/236; a downstream effector of mTORC1 and S6K1) expression in retinas of diabetic rats, when compared with non-diabetic rats (Figure 2A). We also found that VEGF was highly expressed in the retinas of diabetic rats, while PEDF was significantly decreased in the retinas of diabetic rats, when compared with non-diabetic rats (Figure 2B, C). These results were confirmed by western blotting (Figure 2D). Together, these results showed that mTOR signaling, mTORC1 in particular, was highly activated in retinas of diabetic rats.
Rapamycin inhibited the proliferation and migration of HG induced HRCECs.
Western blotting showed that the p-S6 contents were higher in HG-HRCECs than the NG group (Figure 3A). In HG-HRCECs transfected with siTSC1, the protein contents of p-S6 were higher than the HG control, and after treatment with rapamycin, the p-S6 contents were decreased in HG-HRCECs. In the Transwell assay, HG increased the migration ability of HRCECs, which could be transfected with siTSC1. After treatment with rapamycin, the migration ability decreased (Figure 3B). In the EdU assay, HG treatment induced a significant increase in the proliferation of HRCECs compared with the NG group, while treatment with rapamycin inhibited HG-induced proliferation (Figure 3C).
mTOR was first discovered by Heirman and others when analyzing the difference of resistance of beer yeast mutants to rapamycin[20]. The mTOR is a serine/threonine protein kinase,which is highly conserved in structure and function, belonging to a phosphatidylinositol 3-kinase (PI3K)-related family member[21]. mTOR mainly exists in the form of two complexes in vivo: mTORC1, which regulates cell proliferation and metabolic reactions and mTORC2. Abnormalities in any link can change mTORC1 activity[22], leading to the development of diseases, such as diabetes, cancer, and aging [23]. At present, a large number of studies have confirmed that the PI3K/Akt/mTOR signaling pathway is related to some complications of diabetes, such as diabetic nephropathy[24], neuropathy[25], and myocardial ischemia[26]. We therefore suspected that the occurrence and development of DR was related to mTORC1 activation. The mTORC1 is mainly composed of mTORC (core protein), RAPTOR (scaffold protein), DEPTOR (endogenous kinase inhibitor), PRAS40 (endogenous kinase inhibitor), and mLST8[27]. There is a dephosphorylated S6K downstream of the mTORC1 pathway, which is located on the eIF3 scaffold complex. Active mTORC1 is recruited onto the eIF3 scaffold and then phosphorylates S6K to activate it[28]. The mTORC1 phosphorylates at least two amino acid residues of S6K1, of which the most critical modification is located on the threonine residue (T389)[29].S6K1 activity can be determined by activating S6 ribosomal protein (phospo-S6 ribosomal protein, p-S6) and eIF4B , and the level of P-S6 in the body can be used as an indicator of the activation degree of the mTORC1 pathway[30].
In the present study, we used a STZ -induced rat model, which is frequently used for studies on diabetes and its complications. We found that the retinal structures of DM rats were more disordered than NDM rats, and that there were more blood vessels in the retinas of DM rats, which was consistent with the results of other studies. We also found that p-S6 and VEGF proteins were significantly increased in the DM group, and the expression of PEDF protein was significantly decreased compared with the control group. These results suggested that activation of the mTORC1 pathway may exist in DR. DR involves microangiopathy, and vascular endothelial cells are the primary cellular targets in DR. Thus, HRCECs were cultured in ECM with 25mmol/L glucose to simulate the diabetic microenvironment. In vitro, the p-S6 protein in HG-induced HRCECs was increased compared with the control (normal glucose)group. After transfection with siTSC1 to activate mTORC1, the expression level of p-S6 was increased, and the processes of proliferation and migration were increased, whereas rapamycin decreased the p-S6 expression in HG-induced HRCECs, and the processes of proliferation and migration were also decreased.
In summary, mTORC1 played an important role in DR. It was activated in DR to produce the p-S6 protein, to regulate the expressions of VEGF and PEDF proteins, and to change the proliferation and migration of endothelial cells, which are the main characters of DR development.
mTORC1 may be a new target for the treatment of diabetic retinopathy, and its specific inhibitors (such as rapamycin) may also provide a novel means of treatment.
mTOR: mammalian target of rapamycin
mTORC1: mechanistic target of rapamycin complex 1
DR: diabetic retinopathy
HG: high glucose
HRCECs: human retinal capillary endothelial cells
p-S6: phospo-S6 ribosomal protein
VEGF: vascular endothelial growth factor
PEDF: pigment epithelium-derived factor
STZ: streptozotocin
FBS: fetal bovine serum
EdU: The 5-ethynyl-2´-deoxyuridine
Ethics approval Human study was approved by the Ethics Committee of the Third Affiliated Hospital of Southern Medical University. All animal experiments were approved by the Southern Medical University Committee Animal Care and Use Committee.
Consent for publication Not applicable
Competing interests The authors declare that they have no competing interests
Funding This work was supported by the Science and Technology Planning Project of Guangzhou (No. 201604020105); and Science and Technology Planning Project of Guangdong Province (No. 2014A020212631). Meixia An is the person in charge of the above fundings and the corresponding author of this paper. This experiment is completed based on the above fundings.
Authors' contributions YL1 and MA conceived the ideas for experimental designs, analyzed data and wrote the manuscript. YZ1 and YZ2 conducted the majority of the experiments and helped with manuscript preparation. YL2 performed immunohistochemistry and immunofluorescence. MX and WM conducted cell cultures and western blot experiments. MA developed the concept, supervised the project, conceived the experiments and critically reviewed the manuscript. YL1, YZ1. and YZ2. contributed equally to this work. All authors read and approved the final manuscript.(YL1 corresponding to Yanli Liu while YL2 correspongding to Yi Liu;YZ1 corresponding to Yarong Zheng while YZ2 correspongding to Yekai Zhou.)
Acknowledgements Not applicable
Availability of data and materials The datasets during and analysed during the current study available from the corresponding author on reasonable request
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Not only is divorce a fairly expensive process but it takes away resources from that already expensive and time-consuming commitment that we all share called our day to day lives.
If you are considering a divorce and feel yourself badly in need of one I do not tell you that divorce is expensive in order to dissuade you from getting a divorce. I note that divorce is expensive in order to alert you to the fact that if you don't have your financial house in order a divorce will cause you to do so.
Failing to prioritize your spending based on your circumstances is recipe for a disaster in a divorce. I have seen most people going through a divorce find solace not in their support systems or family but in spending on unnecessary items. First of all this likely goes against the temporary or standing orders in your case- thus placing you in violation of a judge's orders. Secondly, you are taking your finite resources and spending them on frivolous things.
Use your divorce as an opportunity to constrain your spending, prioritize your goals and set a course for the remainder of the rest of your life. For the time being, consider that your monthly expenses will play a role in your divorce. This is especially true if you and your spouse cannot come to an agreement on temporary orders and need to proceed to a hearing in front of the judge. Today's blog post from the Law Office of Bryan Fagan, PLLC will get into this subject and a few others before the day is through.
In yesterday's blog post we discussed how income is calculated and considered in your divorce. Today we will shift gears and discuss what role expenses play in a divorce. When I say expenses I do not necessarily mean only legal expenses- although those are important as well. Expenses for the purposes of your divorce mean the day to day living expenses that we all encounter. Remember- a divorce is a family law case. It centers around the most sensitive and important topics in our lives.
Your attorney will counsel you on the specifics of filling out an expenses sheet that will need to be provided to your spouse and to the court. The more specific that you can be (and the more accurate that you can be) the better off you will be in the long run.
The reason being is that it can be used to help a judge identify the standard of living that you have been accustomed to. It will also identify how much money you would require to operate your household on a monthly basis. Depending on if you will be the spouse who is expected to pay temporary spousal support or receive the support, this can impact you a great deal.
It is not in your best interests to attempt to overestimate your monthly expenses in order to try and get a leg up in negotiations with your spouse. Every line of that document would be discussed in a hearing and the judge will ask you to account for each line item that you submit. If you cannot do so then a judge is likely to disregard that expense item and then look at you with less credibility on this subject.
On the other hand, if your divorce is one that proceeds into mediation (either for final or temporary orders) then your spouse is not the person that you should be exaggerating to when it comes to your household expenses. Doing so would likely cause your spouse to become frustrated and possibly lose interested in negotiating with you further. Be accurate and reasonable in your listed expenses and you can expect to end up in a good position when it is all said and done.
Estimated expenses are those that are based upon what you have actually experienced during the course of your marriage.
You take those previously incurred expenses and project them into the future to provide your spouse with an idea of what you expect your expenses to look like in the future. This is especially helpful in a situation where you believe that you will need spousal maintenance in order to sustain yourself after a divorce has been finalized.
Next, actual expenses are those that are fairly set in stone and not expected to change all that much from year to year. Rent, mortgage payments, some utilities, property taxes and the tuition for your children are examples to consider for actual expenses. Remember that spousal maintenance payments in Texas are limited in terms of duration and amount so projecting costs decades down the line likely will not be fruitful for you.
Finally, the proposed expenses are those expenses that in your married life were not incurred, but because of your divorce will be a part of your new reality. Child care costs jump to mind when discussing this subject. Whereas you may have been at home and able to care for your child during the day or after your child gets home from school you may not be able to now because of the need for you to work full time. Child Support is not intended to pay solely for daycare though you can use your child support to pay for any item related to your child.
Your family law court will want to see your expenses broken down into a monthly chart so that the costs are more easily understood. The items that we discussed above will all need to be disclosed in all likelihood in addition to internet, cable, insurance costs, food, vehicle-related costs and any other item that is a part of your list of monthly payments.
Failing to present a thorough list of expenses to the court can mean that a particular cost is not accounted for and therefore left unpaid by spousal maintenance. Be sure to meet with your attorney at least one time prior to submitting your expenses log so that you have a chance to go over the list in detail.
Can your spouse be ordered to pay your attorney's fees?
A comment that I receive quite a bit from clients is that because the divorce is not their idea or that because their spouse caused the divorce to happen due to their infidelity and bad behavior, that their spouse should be made to pay the attorney.
If your spouse has an ability to pay your attorney's fees and you display a lack of wherewithal to do so then you may be in a strong position to ask for and receive an award for attorney's fees and court costs. If you and your spouse are in similar financial situations then your position is weakened.
How is credibility related to disclosure of expenses?
You are playing the "long game" in a divorce. This means that you cannot focus on what is happening that day or even the following week. Rather, you are ultimately building the strength of your case for a final push in the trial- if you need to go that route. A judge is relying on your honesty and candor when it comes to stating your income and expenses.
Provide your attorney with all of the information needed to be fully honest and a judge should have no problems believing you to be an honest person.
If you are interested in how your digital life influences your real-world divorce then head back to our blog tomorrow. We will discuss the potential impacts of your online presence on your divorce in detail.
If you have any questions for the attorneys with the Law Office of Bryan Fagan, PLLC please do not hesitate to contact us today. We offer free of charge consultations with our licensed family law attorneys six days a week. We would love to hear from you and look forward to being able to serve you and your family.
How do family law attorneys in Texas bill their clients?


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I joined itsu in 2002. I was the manager of a sushi restaurant and am now the Director of Shops at itsu. I work with a quick, decisive and inspirational team. If you're great with people and hard working, you'll probably love itsu too.
Joining itsu has changed my life in more ways that one. I first started back in 2013 as a Team Member. I could hardly speak any English [just enough to get by] and now I'm a Training Manager, running masterclasses in English to hundreds of people each year! I found a new family, I found a new career and I couldn't be happier!
I joined itsu in January 2012 to be a General Manager. I actually took a step back from Cluster Manager in a previous job, because sometimes you take a step back to take a step forward and I recognised great opportunity with itsu. Itsu has been fantastic for me and in my 6 years I have had so many opportunities to grow and I now lead itsu USA.


Poster House is a new museum dedicated to the global history and design of posters. Before launch, they are partnering with the largest library in the world, The Library of Congress, to highlight important pieces of poster history. Choose one of 31 posters from the Library of Congress "free to use and re-use" collection, and animate it in any way you can imagine, bringing new life to these poignant historical vignettes. The competition is open to absolutely everyone: professionals, students, and dabblers alike.
Twenty winning works chosen by a panel of design legends will populate the museum's storefront in Manhattan leading up to its grand opening. Winners will also receive free museum membership, their names shown alongside their work in the museum's window and all social/PR/web publicity, and the chance for a mentorship hour or portfolio review from one of our esteemed judges. For complete rules, regulations, and image options see posterhouse.org. Submissions due no later than December 31!


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We provide professional carpet steam cleaning services. Our Carpet Steam Cleaners offer guaranteed results. Our Steam Carpet Cleaning Services include FREE carpet deodorising and Sanitising. Our carpet cleaners are certified and available in northern, southern, eastern and western suburbs for your home carpet steam cleaning. There are many reasons to book Fresh Carpet Cleaning Docklands.
Fresh Carpet Cleaning Docklands also offers same day and emergency carpet cleaning at a very reasonable price. Get in touch with us to know more!
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We offer the lowest prices for carpet cleaning services in Docklands.
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A rare find. On 1.23 acres near the heart of Lexington, on Meriam Street. Others have suggested that this property might be sub-dividable, although any buyer should exercise due diligence in this regard. More than a acre of land on one of Lexington's finest streets. A single family residence built in 1956 sits on the property.


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Guidance and Policy (2138)
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Results for all evidence | Guidance | British Society of Gastroenterology - BSG 1 - 10 of 194 sorted by relevance / date
Guidelines for the investigation of chronic diarrhoea in adults: BSG, 3rd edition
Remove: British Society of Gastroenterology - BSG source - 11 March 2018 - Publisher: British Society of Gastroenterology
Chronic diarrhoea is a common problem, hence clear guidance on investigations is required. This is an updated guideline from 2003 for the investigations of chronic diarrhoea commissioned by the...
- Remove: Guidance filter
The diagnosis of death by neurological criteria in infants less than two months old [PDF]
Remove: Royal College of Paediatrics and Child Health - RCPCH source - 24 April 2015 - Publisher: Royal College of Paediatrics and Child Health (RCPCH)
This report provides recommendations on the diagnosis of death by neurological criteria (DNC) in infants from 37 weeks corrected gestation (post menstrual) to two months (post term) of age.
Diagnosis and management of acute lower gastrointestinal bleeding: guidelines from the British Society of Gastroenterology. [PDF]
Remove: British Society of Gastroenterology - BSG source - 01 February 2019 - Publisher: British Society of Gastroenterology
This is the first UK national guideline to concentrate on acute lower gastrointestinal bleeding (LGIB) and has been commissioned by the Clinical Services and Standards Committee of the British...
Endoscopy in patients on antiplatelet or anticoagulant therapy, including direct oral anticoagulants: British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) guidelines
These guidelines refer to patients undergoing elective endoscopic gastrointestinal procedures. Management of antiplatelet therapy and direct oral anticoagulants (DOACs) in acute gastrointestinal...
UK guideline on transition of adolescent and young persons with chronic digestive diseases from paediatric to adult care
Remove: British Society of Gastroenterology - BSG source - 21 April 2017 - Publisher: British Society of Gastroenterology
The risks of poor transition include delayed and inappropriate transfer that can result in disengagement with healthcare. Structured transitioncare can improve control...
UK guidelines on the management of variceal haemorrhage in cirrhotic patients
The nature of variceal haemorrhage in cirrhotic patients with its complex range of complications makes rigid guidelines inappropriate. These guidelines deal specifically with the management of...
British Society of Gastroenterology / Association of Coloproctologists of Great Britain and Ireland guidelines for the management of large non-pedunculated colorectal polyps
Remove: British Society of Gastroenterology - BSG source - 23 June 2015 - Publisher: British Society of Gastroenterology;Association of Coloproctology of Great Britain and Ireland (ACPGBI)
These guidelines provide an evidence-based framework for the management of patients with large non-pedunculated colorectal polyps (LNPCPs), in addition to identifying key performance indicators...
Updated guideline on the management of common bile duct stones (CBDS)
Remove: British Society of Gastroenterology - BSG source - 23 May 2017 - Publisher: British Society of Gastroenterology
Common bile duct stones (CBDS) are estimated to be present in 10-20% of individuals with symptomatic gallstones. They can result in a number of health problems, including pain, jaundice, infection...
Guidelines on the management of abnormal liver blood tests
Remove: British Society of Gastroenterology - BSG source - 15 October 2017 - Publisher: British Society of Gastroenterology
These updated guidelines on the management of abnormal liver blood tests have been commissioned by the Clinical Services and Standards Committee (CSSC) of the British Society of Gastroenterology...
The management of children and young people with an acute decrease in conscious level [PDF]
Decreased conscious level can be considered an acute neurological emergency characterised by significant brain impairment, necessitating a rapid and methodical approach to evaluation and treatment.

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Don Beneventi's Incredible Chevy Collection Is Heading To Auction
Amie Williams
May 25, 2020, 3:10 PM ·16 min read
⚡ Read the full article on Motorious
A large and unique collection of cars will be auctioned off on Saturday, July 25th - many being true time capsules.
Way back in 1932, the Beneventi family opened their Chevrolet dealership to serve Iowa and beyond. Due to their love for Chevy cars and pickups, Don and his family ran the Chevrolet dealership for 88 years, but now it belongs to the Willis Auto Group. A large collection of 21 GM vehicles that Don had collected throughout the years will be crossing the stage through VanDerBrink Auctions on Saturday, July 25th, 2020 at the location of his former dealership in Granger, Iowa. An open house will take place on Friday, July 24th, 2020 for anyone wanting to preview the Beneventi Collection beforehand.
Most of these cares still retain window stickers and MSO documentation, and some are true time capsules that have barely seen the road. Check out this amazing list of Chevys, and make sure you register to bid so you can take one home for yourself! Check out this list of amazing cars that made up Don Beneventi's collection.
1972 Chevy Monte Carlo Coupe (Lot #9D)
This low-mileage classic Monte Carlo Coupe was ordered brand new as a demo car in 1972, and over its lifespan the car has accumulated just 3,022 miles. In fantastic condition inside and out, this time capsule is finished in a shiny exterior hue that wasn't offered for the 1972 model year but was a special option code (01-01) for $39.00, also listed on the window sticker still attached to the car. This '72 Monte Carlo has a triple black combination with a black vinyl bench seat and top. Other features include four-season air conditioning, rally wheels, and tinted glass among other things. Under the hood is a 350-cubic-inch V8 engine with an output of 175-horsepower and backed by an automatic transmission. After Don sold his dealership, this car was titled, and there is a copy of the MSO and original invoice.
1974 Monte Carlo Landau Coupe (Lot #11D)
Here we have a car that is hard to find, a rare 1974 Chevrolet Chevelle Laguna S-3 Landau Coupe that is fully loaded and ready to go. Ordered as a demo, this car was sold and then traded back in 1980 and had just one owner before Don put the car back in his collection. Before storing it, he had the car repainted in red and had the rest of refreshed. Open the doors to reveal a sport cloth houndstooth interior with swivel seats. In great shape, this rare Monte Carlo only has 51,811 miles on the clock, and the car hasn't seen rain or snow since 1988. As mentioned above, this exact car is hard to find as many were turned into race cars. Under the hood sits a 454-cubic-inch V8 engine mated to an automatic transmission found on the console. This example will go up for bids with no reserve.
1987 Camaro RS Convertible (Lot #14D)
For the first time since the 1969 model year, the 1987 Camaro was the first to be reintroduced with a convertible top. This stunning '87 Chevrolet Camaro RS Convertible is another time capsule with just 1,150 actual miles, and it retains the shipping plastic on the carpet from the factory and the window sticker still attached. Don ordered this car with plenty of factory options. Equipped with the sport convertible package, this Chevy Camaro is finished in a nice red with a black convertible top. Inside the car is red vinyl bucket seats, AM/FM radio, air conditioning, and more. This car has tinted windows, and runs and drives like a brand new car. Tucked under the hood is a 5.0-liter 350-cubic-inch V8 engine topped with a four-barrel carburetor and backed by an automatic transmission with overdrive. This car has the invoice for order, the MSO, and it will sell without reserve.
1977 Camaro Z28 Coupe (Lot #12D)
This 1977 Chevrolet Camaro Z28 time capsule was never sold and just stashed away, so it's basically brand new in the wrapper. Don ordered the car for himself with plenty of options, and the tires have barely touched the road with just 456 miles to date. Finished in a beautiful silver color with contrasting orange Z28 striping, this Camaro runs and drives wonderfully. Outside, a set of rally wheels can be found all around, and it comes with a spare tire. Open the doors to a new interior with black bucket seats and plenty of options including cruise control, AM/FM radio, air conditioning, and more. Powering this gem is a 350-cubic-inch V8 engine fed by a four-barrel carburetor and shifted via an automatic transmission on the column that twists a Posi rear end. This incredible Camaro has the invoice, window sticker attached, a copy of the MSO, and was recently titled. No reserve.
1974 Corvette L82 Coupe (Lot #15D)
Yet another 'brand new' car in the wrapper, an incredible 1974 Chevrolet L-82 Corvette Coupe with just 3,522 miles. Sprayed in classic white, the exterior of this Corvette is also equipped with t-tops for perfect sunny cruises. A set of AL2 rally wheels can be found on the outside (not listed on the window sticker) that Don put on the car after accepting delivery. Given a custom interior, this Corvette was specially ordered with saddle tan bucket seats, and it has an AM/FM radio, power windows, air conditioning, power brakes, and power steering. The heart beats through a Turbo-Fire 350-cubic-inch V8 engine topped with a four-barrel carburetor with power shifted to the rear wheels via a console-shifted Turbo Hydro-matic transmission. The sale of this Corvette comes with original invoice, window sticker in window, a copy of the MSO, and it was recently titled. No reserve.
1978 Corvette Silver 25th Anniversary (Lot #16D)
Continuing with the 'new' theme is this exquisite 1978 Chevrolet Corvette Coupe Silver Anniversary with just 478 miles, another car ordered for Don and never licensed for the road. This silver and gray two-toned beauty comes with t-tops, sport mirrors, and a power antenna. Inside the car is a contrasting red leather interior (ARR2) with bucket seats, cruise control, power windows, AM/FM radio, rear defogger, air conditioning, and cruise. Tucked under the hood is a 350-cubic-inch V8 engine with a console-shifted automatic transmission. The runs and drives beautifully. The sale comes with invoice, window sticker in the window, copy of the MSO, and it is titled. Also selling without reserve.
1975 Caprice Classic Convertible (Lot #18D)
Another new car is this beautiful 1975 Caprice Classic Convertible with just 1,240 miles on the clock, another car that was never licensed for the road. The owner ordered this fully loaded gem new from Yanson Chevrolet Company in Chicago Heights, Illinois, and had it shipped to him on July 7th, 1975. Slathered in an attractive Baby Blue with a white convertible top and boot, the exterior also features wire wheels. Open the doors to a matching white vinyl bench seat on the inside, and it includes options such as power steering, power seat, and power brakes. Also, this vintage gem has electric windows, locks, and stereo. Don purchased this car on December 8th, 2000 with just 491 miles on the clock. The sale of the car comes with original window sticker on door glass, copy of MSO, and it is now titled. Selling at no reserve.
1970 Chevelle SS 396 Coupe (Lot #8D)
An iconic muscle car that many enthusiasts dream of owning is the 1970 Chevrolet Chevelle SS 396 Coupe. Purchased by Don in 1987, this stunning example was give a repaint in its original color and is the product of an older restoration and features 396 badging all around and a cowl induction hood. While this car hasn't been confirmed to have matching numbers, it does have the original black vinyl interior complete with bucket seats, console, and a factory 8-track tape player/radio, and the cabin is in excellent condition. With just 57,830 miles on the odometer, this Chevelle is full of rare options such as factory air, power steering, power brakes, and the windshield monitoring light system. Under the hood is a 396/402 V8 engine and a console-shifted AT transmission, and it generates 350-horsepower. This beauty runs and drives flawlessly, and it will be auctioned off without reserve.
1987 IROC Camaro Coupe (Lot #13D)
A sight to behold, this gorgeous 1987 Chevrolet Camaro IROC Coupe was sold new at the Beneventi dealership and had acquired just two owners before Don stashed it away after a trade-in. With just 31,082 original miles, this IROC is slathered in a maroon hue and given IROC Z28 gold striping. More features include the t-tops, red cloth buckets, AM/FM cassette, factory air conditioning, and electric windows and locks. Only the 1987 and 1998 model years allowed for the combination of a 350-cubic-inch V8 engine (tuned port) and t-tops. Car will sell without reserve.
1979 Chevrolet Monte Carlo Landau Coupe (Lot #19D)
Another car that was ordered as a demo was this unique 1979 Chevrolet Monte Carlo T-Top Coupe for another dealership. This '79 Monte Carlo was traded in at Beneventi Chevrolet in June of 1989, and it has remained in Don's personal stash ever since. With 79,505 miles on the clock, this car is cloaked in a special two-tone paint combination with t-tops and features wire wheel covers. Peek inside the car to a matching green vinyl interior complete with bucket seats and given plenty of options including power steering, power brakes, CB radio, and stereo. Under the hood sits a 305-cubic-inch V8 backed by an automatic transmission. No reserve.
1981 DeLorean DMC-12 (Lot #17D)
Here we have a 1981 DeLorean DMC-12, the very first year the car was in production. The original owner traded in the car on a 1984 Corvette back in '83. Featuring that iconic brushed stainless steel exterior, this DeLorean only has 4,243 miles on the odometer. Inside the car is a grey interior with vinyl bucket seats, console, and an AM/FM radio. Powering the DeLorean is the Volvo 1.7-liter V6 engine mated to an automatic transmission. This car is in very good condition and is selling with no reserve.
1997 Tahoe 2-Door Sport (Lot #21D)
Here we have an attractive and capable 1997 Chevrolet Tahoe 2-Door Sport that originated from Salt Lake City, Utah. Both the body and interior are original including the red paint that has been buffed, and the lower grey portion has been repainted. Loaded with options, this Tahoe Sport is in excellent shape inside and out. Wheels from a later model were added to all four corners. The front suspension was redone and a Certa automatic transmission was installed about 17k miles ago. Inside the SUV is a grey leather interior with some wear. Under the hood is the original 350-cubic-inch V8 engine that has logged 206,000 miles, and it runs and drives very good. Kick this baby into four-wheel-drive and go. No reserve.
1982 Cadillac Seville Diesel (Lot #20D)
Don purchased this incredible 1982 Cadillac Seville Diesel at a GM sale in 1983 with just 3,462 miles, and this one served as a factory executive car. Now the car has just 17,769 miles on the clock. Another example that was never licensed for the road, this car still smells like new and runs like a dream. The body of the car is finished in a custom two-tone paint in silver and white, and the interior is tan leather and loaded with options. Under the hood is a diesel engine shifted via an automatic transmission, and it is selling with no reserve.
1957 Chevy Fuel-Injected Belair (Lot #7D)
This rare 1957 Chevrolet Fuel-Injected Belair is bound to turn some heads, and it has an amazing history. A GM factory test car in Phoenix, Arizona, this car was tested with a 1958 fuel injection unit that was installed on this car. When the injection unit was rebuilt, markings were apparent on the underside and they worked to find the car. A man bought the car after it was put back into inventory, and GM called because they wanted the car and the fuel injection unit back. The car was traded again, and this time Don found it, purchased the unique Belair, and brought it back to Iowa. Given a repaint in a beautiful turquoise, this car runs like a dream. Inside the car is a turquoise and black bench seat, clock, and AM radio. Tucked in the bay is a 283-cubic-inch V8 engine with the GM experimental fuel injection for 1958 that was never returned, and it is equipped with a mild cam that lopes beautifully at idle. Shifting comes from an automatic transmission. Just 49,765 miles grace the clock, and it will sell without reserve.
1955 Chevrolet Belair Convertible (Lot #6D)
This stunning classic 1955 Chevrolet Belair convertible is a California car that was given a complete frame-off restoration. Painted in Gypsy Red and Shoreline Beige over a matching red and white interior, this beauty won Best In Show at Hot August Nights in Reno, Nevada. The interior of this Belair features an AM radio and clock along with '55 accessory floor mats over the carpet. More features include the fender skirts, manual windows, manual locks, and dual exhaust. Featuring the Powerpack option, the heart beats through a 265-cubic-inch V8 topped with a four-barrel carburetor and shifted via a 3-speed manual column-shift transmission with overdrive. Selling with no reserve.
This is an absolutely stunning 1954 Chevrolet Belair convertible that is the product of a complete frame-off restoration from back in 1993, and it has been well maintained. Finished in a brilliant Gypsy Red and White theme with a matching new white convertible top (with new motor) installed by Don, this '55 Chevy Belair runs and drives beautifully. All of the stainless is in excellent shape, and inside the car is a contrasting red and white tuck-and-roll interior featuring an AM radio and clock. Powering this beauty is a 235-cubic-inch V6 engine backed by a manual 3-speed transmission. No reserve.
1954 Chevrolet 3100 Series Short-Box Pickup (Lot #4D)
This incredible 1954 Chevrolet 3100 Series Short-Box Pickup was given a complete frame-off restoration. Accepted in as a trade, this pickup truck hasn't seen rain or snow since Don has owned it. With 47,503 miles on the clock, this beauty runs and drives flawlessly. The exterior features a chrome grille, bumper options, white-wall tires, and '54 Belair wheel covers with the optional side-mounted spares on the box. Powering this vintage Chevy pickup is a V6 motor shifted via a manual transmission, and it still has the original wood in the box. No reserve.
1947 Chevrolet Fleetline 4-Door Sport Sedan (Lot #3D)
This is a beautiful example of a 1947 Chevrolet Fleetline 4-Door Sport Sedan, and this one has been very well cared for. Slathered in a beautiful black paint, this car is in fantastic condition including all of the stainless. Inside the car is the original upholstery on the seats along with the original interior, and it shows in fantastic condition. Under the hood is a V6 engine backed by a manual 3-speed transmission. No reserve.
1937 Chevrolet GB Series Master Sedan (Lot #2D)
Sold brand new by Beneventi back in 1937, this '37 Chevrolet 2-Door GB Series Master Sedan was traded back into the dealership in 1963 for a Chevrolet Nova and has been in a part of the collection ever since. With 76,842 actual miles on the clock, this beauty runs and drives as it should. Even better, since it has been under Don's watch it hasn't seen snow or rain. Equipped with the 37-1211 body style, this classic beauty was repainted in a stunning green that sits over a cloth interior. Under the hood is a V6 motor shifted via a manual transmission. No reserve.
1932 Chevrolet 5-Window Coupe (Lot #1D)
The model year of this car marks the same year that the dealership started selling Chevrolet vehicles, this being a 1932 Chevrolet Deluxe 5-Window Coupe-Confederate. Under Don's watch, this three-owner gem was given a complete body- and frame-off restoration, and all of the mechanicals have been gone through which happened in around 1985. Finished in an amazing Maroon paint with black fenders and given beautiful brightwork, this car runs and drives flawlessly with 54,445 miles under its belt. This classic features all the original wood framing in the doors, a grey cloth bench seat, wire spoke wheels, and a rear-mounted spare. This car does not have a rumble seat. Tucked in the bay is an inline-six motor backed by a manual transmission.
1949 Chevrolet 6400 Series Short-Wheel-Base Dump Truck (Lot #22D)
This is an original 1949 Chevrolet 6400 Series Short-Wheel-Base Dump Truck that has been buffed to make that brilliant red pop, especially with its white pinstripes. The body is in great condition, and it features an unusual 5-window cab. According to the listing, there are no brakes on the truck as it needs a master cylinder, and it would make a fantastic farm truck once finished with the brake project. It has a hoist dump box, a new gas tank, a redone carburetor, and a clean original interior with a bench seat. This truck is powered by a V6 motor backed by a manual transmission, and the odometer reads 53,159 miles.
That concludes the amazing list of Chevrolet cars and pickups from the Don Beneventi collection. Bidding is also available online, so make sure to register if one of these GM beauties has caught your eye. These vehicles will cross the auction stage through VanDerBrink Auctions on Saturday, July 25th.
Source: VanDerBrink
Read More Chevrolet Car News Here...
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This truck is ready for cruising and showing! -------------------------------------------------------------------------------- Pickup trucks continue to grow in popularity in regards to the classic car market, and this 1963 Chevrolet C10 [https://buy.motorious.com/vehicles/189678/1963-chevrolet-c10-resto-mod-pickup/…
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Moonlight and Oranges by Elise Stephens
Release Date: November 2011
Moonlight and Oranges is Stephens' debut novel about a modern-day romance based on Greek mythology's very own Cupid and Psyche.
Beautiful, 20-something Lorona Connelly attends a raving Halloween party with her best friend, but feels instantly out of place outside of her usually sheltered and bookish environment. Shortly after arriving to the party, Lorona is confronted by sexy ladies' man Kestrin Feather, who feels mysteriously compelled to protect this fragile, bookish girl from a throng of seemingly vindictive party-goers. After sharing a vodka screwdriver, Lorona and Kestrin kiss, and sparks fly.
Hours after their magical kiss, Lorona and Kestrin can't seem to shake off their cravings for orange juice - and each other. Finding their way back to each other with the help of mutual friends, and now passionately in love (lust?), Lorona and Kestrin enter quickly into marriage without knowing much about each other's pasts. When Lorona finds and reads Kestrin's secret journal that contains entries about a woman he is destined to marry, Lorona leaves him in a fit of rage, assuming he wrote the entries to trick women into his bed. And so the melodrama continues, until Lorona and Kestrin submit to their destiny, and finally settle on happily ever after - and each other.
A book reviewer's purpose is to analyze and review the book for what it is; NOT for what it could have been, which is a common mistake made by many bloggers and reviewers. I will deviate from this rule for this one instance to state that Moonlight and Oranges would have made much more sense (and perhaps would have been more enjoyable) had Stephens' Author's Note been placed at the beginning of the novel, rather than at the end.
Had I known ahead of time that Moonlight and Oranges was a modern-day retelling of Cupid and Psyche, I would have taken a lighter approach to the story. With Greek mythology not exactly being a personal interest of mine at any point, the novel made no logical sense to me, and I was appalled by the characters and their actions. I'm not a fan of Shakespeare either, however, I still enjoy literary parodies and movies that are based on his works, mainly because I know going into them that they are not meant to be taken too seriously.
Entering into a marriage after a few days, weeks, or even months with a person you hardly know based on intuition, attraction, and lust and expecting it to work like magic just doesn't work in real life. I'm not being cynical or pessimistic here, but it's actually just hehavioral science, plain and simple. Even those without tons of dating experience know that the lust and honeymoon phase wears off after time, and to make a relationship work, you need commitment.
Why do I digress into this particular tirade? Because it makes me nervous to think that young adults and teens could read this book and be charmed by the relationship between Lorona and Kestrin, as there is nothing charming, magical, or awesome about it.
Clearly Lorona was not ready for marriage and commitment, seeing as she left Kestrin in a heartbeat and like a true coward without even taking the time to speak directly with Kestrin about the journal. Then of course, if Lorona had been a mature adult and faced Kestrin responsibly, there probably wouldn't have been a story.
Aside from the marriage and commitment flaws, the characters' personalities are extremely entertaining because they think of themselves as world-weary souls (in their 20s!), yet are incredibly immature; Kestrin with his "many, many years" as a womanizer and being tired of the scene (sure thing, James Bond), and Lorona with her "many, many years" leading a sheltered, quiet life. Apparently without ever having tasted a vodka screwdriver, either.
I definitely do not recommend Moonlight and Oranges to young adults or teens, especially with marriage being glorified, and then cast aside so easily when one of the partners decides she doesn't like what she reads in a lame journal.
I DO, however, recommend Moonlight and Oranges to mature, adult readers who are true fans of Greek mythology and understand that the novel is loosely based on the story of Cupid and Psyche.
Readers who enjoyed Moonlight and Oranges may also like A Writer's Love Story by Robert Wacaster.
This book has a pretty cover, but it sounds like it sucks! Oh well, at least the author was courageous and brave and wrote it anyways. I've got to give her that.
This review is everything I felt after reading it. I definitely agree that the Author's Note should have been at the beginning. The Cupid and Psyche myth is actually one of my favorites (I completely read this by chance), but as I read the book not knowing it was based off the myth, I felt entirely thrown off by everything that you described above that was wrong with it. Once I read the Note, it suddenly clicked why the characters acted in those ways. Because you really don't get a good understanding of the characters and their drives that lead them to do all of those silly things (especially Kestrin's mother). The characters were, in a sense, forced to act those ways in order to conform to the original myth. It's sad, but the story just doesn't hold up on its own.
Sarah Ann July 16, 2012 at 8:59 PM
Thank you for your comments, Anonymous readers!
Anonymous #2: I'm pleased to see that you agree with the "Note" aspect! My experience with this novel would have been entirely different had I been made aware ahead of time that the story was based on the myth!
Take care, and happy reading!
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A Wedding in December by Anita Shreve
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text:
package com.fiap.lucene.service.setup;

import org.springframework.context.annotation.Bean;
import org.springframework.context.annotation.Configuration;
import org.springframework.data.redis.connection.RedisConnectionFactory;
import org.springframework.data.redis.connection.jedis.JedisConnectionFactory;
import org.springframework.data.redis.core.RedisTemplate;

@Configuration
public class ServiceConfiguration {

	private final String REDIS_IP = "52.67.240.49";
	private final int REDIS_PORT = 6379;

	@Bean
	public RedisConnectionFactory connectionFactory() {
		JedisConnectionFactory factory = new JedisConnectionFactory();
		factory.setHostName(REDIS_IP);
		factory.setPort(REDIS_PORT);

		return factory;
	}

	@Bean
	public RedisTemplate<?, ?> redisTemplate(RedisConnectionFactory connectionFactory) {
		RedisTemplate<byte[], byte[]> template = new RedisTemplate<byte[], byte[]>();
		template.setConnectionFactory(connectionFactory);

		return template;
	}

}

redpajama_set_name: RedPajamaGithub


BTOB will be making their awaited comeback on September 19th!
Earlier today, BTOB released some image teasers for their upcoming comeback slated for September 19th, 2016. In the images the seven BTOB members were seen wearing dapper suits while sitting on a chair. Although no hints were revealed just yet, however as the comeback date gets closer and closer Cube Entertainment will definitely give us some information!
Make sure you continue supporting BTOB!


Danny is still very much on mind. I miss you, my friend. "Even though in this world we may know grief and suffering, our dreams shall never die."
My deepest condolences to you and your family. May God bless you and keep you always.


text:
Is Pinduoduo Catching Up to Alibaba and JD.com?
Shares of Pinduoduo (NASDAQ: PDD) recently surged after the Chinese e-commerce company's second-quarter numbers smashed analysts' estimates. Its revenue rose 169% annually to RMB 7.29 billion ($1.06 billion), beating expectations by $187 million.
Pinduoduo remains unprofitable, but its adjusted net loss narrowed year over year from RMB 673.4 million to RMB 411.3 million ($59.9 million), or $0.04 per share -- which beat expectations by $0.15. Do those numbers indicate that Pinduoduo is catching up to market leaders Alibaba (NYSE: BABA) and JD.com (NASDAQ: JD)?
Image source: Pinduoduo.
A rapidly growing underdog
Pinduoduo mostly sells cheaper generic products to lower-income shoppers. It gives shoppers bulk order discounts if they can convince their friends, family members, and co-workers to make a "team" purchase. Pinduoduo lets shoppers share links via social media platforms like WeChat, which feeds its "social shopping" experience.
That approach has helped Pinduoduo gain ground across China's lower-tier cities, and it's making progress in top-tier cities like Beijing, Shanghai, and Hangzhou. It recently stated that orders from those top-tier cities accounted for 48% of its total order value in June, up from 37% in January. Its total GMV (gross merchandise volume), or the value of all goods sold across its platform, surged 171% to RMB 709.1 billion ($100 billion).
Pinduoduo's average monthly active users (MAUs) rose 88% annually to 366 million during the quarter, and its number of active buyers over the past 12 months rose 41% to 483 million. Those numbers indicate that it has more active shoppers than JD, which grew its number of annual active customers just 2% to 321 million last quarter. Alibaba remains in the lead with 755 million mobile MAUs across its Chinese marketplaces.
Those numbers seem to indicate that Pinduoduo is bigger than JD, but it generates only about 5% as much quarterly revenue as JD because its order sizes are much lower. Like Alibaba, Pinduoduo doesn't take on any inventories. JD takes on inventories and handles logistics as a direct retailer (which enables it to generate higher e-commerce revenues than Pinduoduo or Alibaba), but that approach requires much more capital.
However, the average active buyer on Pinduoduo spent RMB 1,467.5 ($206.90) on the platform over the past 12 months -- a 92% jump from a year earlier. This indicates that Pinduoduo's push into higher-tier cities -- Alibaba and JD's core markets -- is paying off. Moreover, the economic slowdown in China could benefit Pinduoduo as shoppers rein in their spending and hunt for deeper discounts.
Pinduoduo's growth might be sustainable
Last November, I told investors to avoid Pinduoduo because its losses were widening at an alarming rate. However, Pinduoduo's second-quarter numbers indicate that it's keeping its costs under control.
Its adjusted cost of revenues accounted for 22% of its revenues, compared to 19% in the first quarter and 14% a year earlier. Yet its adjusted sales and marketing expenses accounted for only 81% of its revenues in the second quarter, compared to 103% in the first quarter and 108% a year earlier.
Pinduoduo's robust revenue growth and lower marketing expenses offset its higher cost of revenues and narrowed its net loss -- which indicates that its business might be more sustainable than I initially thought. Its cash position is also strong -- it ended the quarter with RMB 40.7 billion ($5.9 billion) in cash and equivalents, up from RMB 30.5 billion at the end of 2018.
But big challenges still loom on the horizon
Pinduoduo's second-quarter numbers were encouraging, but I'm still reluctant to buy this stock for two reasons. First, it will face much tougher competition from Alibaba and JD as it pushes into top-tier cities -- and both rivals are profitable companies with deeper pockets and bigger ecosystems.
Second, it still faces claims that its platform carries counterfeit goods. Pinduoduo and Alibaba's Taobao are still listed on the U.S. Trade Representative's notorious blacklist of counterfeit marketplaces, which claims that many of Pinduoduo's "price-conscious shoppers are reportedly aware of the proliferation of counterfeit products" on the platform, but are "nevertheless attracted to the low-priced goods."
The report also notes that "several brands issued public notices to warn consumers that products listed on Pinduoduo.com under their brand names are counterfeits." That reputation makes it a soft target for U.S. and Chinese regulators as the trade war focuses on IP violations.
Pinduoduo is becoming a major rival for Alibaba and JD, but its shaky reputation and lack of profits prevent me from recommending it as an investment. Until I see narrower losses and a clearer focus on flushing counterfeit products from its marketplace, I'll stick with profitable market leaders like Alibaba and JD instead.
10 stocks we like better than Pinduoduo Inc.
David and Tom just revealed what they believe are the ten best stocks for investors to buy right now... and Pinduoduo Inc. wasn't one of them! That's right -- they think these 10 stocks are even better buys.
Leo Sun owns shares of JD.com. The Motley Fool owns shares of and recommends JD.com. The Motley Fool has a disclosure policy.
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Local complications of femoral arterial catheterization like hematomas, pseudoaneurysm (PSA) and arteriovenous fistula (AVF) are increasing in incidence due to the large number of patients undergoing diagnostic and therapeutic angiographic procedures through this route [1 - 3] (see figure 1). A PSA refers to a confined collection of thrombus and blood associated with tear of one or more layers of an arterial wall . An iatrogenic AVF occurs when an arterial puncture inadvertently extends to involve an adjacent vein leading to a communication between the two. Color flow Doppler ultrasound is the imaging modality of choice for the diagnosis and assessment of a PSA, with a high sensitivity and specificity .
Incidence of post-angiographic femoral PSA and AVF varies between 0.07-9% , . The risk factors include age more than 65 years, low or high femoral arterial puncture, anticoagulation and use of a large arterial sheath size .
Ecchymosis of the right thigh and lower abdominal wall.
In the femoral region, turbulence is seen within either the common femoral or profunda femoral vein with arterialized signals shown on the Doppler spectrum (see Figure 2A). The fistulous communication can be seen on color flow Doppler, although it may be difficult to localize with duplex ultrasound alone (see Figure 2B). The turbulence associated with the fistula can be confused with turbulent signals due to extrinsic compression of the vein by hematoma or PSA, which is also a common complication following catheterization. The characteristic findings of a PSA include a slow swirling flow [Yin -Yang sign] within a hypoechoic lesion which is connected to the parent artery via a neck (see Figure 3 A-D). The latter displays a characteristic "to-and-fro" high velocity flow . Doppler features of an AVF include a region of aliasing interposed between an artery and vein with increased diastolic flow in the artery and turbulent flow within the vein .
(A) Color Doppler image depicts arterial signals within the FV waveform indicating an arterio-venous communication; (B) Color Doppler image showing turbulent waveform within the AV fistula.
(A) Grey scale image showing the pseudoaneurysm as an oblong sonolucent structure anterior to the right FA (arrow); (B) Color Doppler image shows swirling flow within it the" Yin -Yang sign" (arrow); C) The connection (neck) between the FA and PSA (arrow); and (D) Pulsed wave Doppler image of the PSA neck depicts to-and-fro flow within it.
Visualization of the communicating channel allows a confident diagnosis of AVF rather than extrinsic venous compression by the surrounding hematoma or PSA. The use of computerized axial tomography (CTA) can resolve the problem (see Figure 4 A-B).
(A) CT angiography axial image depicts a thin linear communication (long arrow) between the posterior wall of FA and FV with opacification of the latter and the proximal great saphenous vein (short arrow); and (B) Coronal reformatted image showing the PSA (arrow) arising from the FA. The CFV and the external iliac veins are opacified due to presence of the AV fistula.
Transcutaneous therapy aimed at achieving closure of the fistula has been described using ultrasound monitoring and by applying pressure over the fistula for periods of 20 to 60 minutes success rates are 30% or lower .
Any patient who experiences local site pain disproportionate to that expected after an angiographic procedure should be evaluated with duplex ultrasound to rule out the presence of a PSA and/or AVF. Color Doppler ultrasound and spectral analysis has a high sensitivity [94%] and specificity [97%] for detection of a PSA .
Untreated PSA can lead to progressive lesion enlargement, infection, compression neuropathy and rupture . Until the early nineties, surgery was the only treatment available for PSA and AVF closure. Presently it is only rarely employed to treat the post catheterisation PSA, when other treatment options fail or if a complication develops .
In 1991 Fellmeth et al. described a method of ultrasound guided compression (USGC) for closing post catheterization femoral PSA and AVF . Subsequent studies confirmed a high rate of success [varying from 75% to >90%] for closure of PSA by this method [14 - 15]. In patients on anticoagulants, the success rate is reported to be between 30%-73 % [14 - 17]. Success rate for AVF closure is described between 33%-50% [12 - 16].
The mechanical compression is exerted using the ultrasound probe and is positioned directly over the neck of the PSA or the tract in case of the AVF . It is titrated so as to obliterate blood flow within them. At all times an adequate flow is maintained in the concerned artery. The compression is usually continued for cycles of 10 minutes each with intermittent release to assess for closure of the neck. This can be repeated till the neck is closed or else discontinued if the physician/patient develops fatigue .
The only limiting factor in USGC method is the time it takes to induce thrombosis to close the PSA or AVF tract . Patient may experience intra-procedural pain which responds to intravenous analgesia . Complications are rare and include vasovagal reactions, PSA rupture, skin necrosis and DVT .
Successful post compression thrombosis of the PSA &AVF.
Successful obliteration o the PSA and the AVF is the main goal of the whole procedure (see Figure 5). This is the major goal every treating physician should achieve for better patient management and treatment.
Ultrasound guided compression of the post-angiographic femoral arterial injuries is a technically simple and relatively safe method.


text:
Kane & Lynch 2: Dog Days – gra z gatunku third-person shooter, której światowa premiera odbyła się 17 sierpnia 2010 roku. Gra została wyprodukowana przez IO Interactive, oraz wydana przez Square-Enix i Eidos na PlayStation 3, Xbox 360, oraz Windows.

Gra wieloosobowa
W Kane & Lynch 2: Dog Days przygotowano tryb kooperacji dla dwóch graczy w trybie fabularnym, oraz trzy inne tryby:
 Gliniarze kontra Złodzieje
 Kruchy Sojusz
 Tajniak

DLC
Do tej pory do gry Kane & Lynch 2: Dog Days wydano 3 dodatki DLC:
 Alliance Weapon Pack – wydany 31 sierpnia 2010 pakiet siedmiu broni: Dorett z tłumikiem, Steele 870, TOQ SBR, Kaliningrad 47, PAC 10 z tłumikiem, N 77P z tłumikiem oraz TOQ Elite.
 Multiplayer Masks Pack – wydany 31 sierpnia 2010 pakiet ośmiu dodatkowych masek.
 The Doggie Bag – wydany 31 sierpnia 2010 pakiet składający się z dwóch nowych map i pięciu dodatkowych broni.

Przypisy

Linki zewnętrzne
 Oficjalna strona gry

2010 w grach komputerowych
Gry na platformę PlayStation 3
Gry na platformę Xbox 360
Strzelanki trzecioosobowe
Gry na platformę Windows
Gry na platformę OnLive
Gry komputerowe wyprodukowane w Danii

redpajama_set_name: RedPajamaWikipedia


text:
Q: Subtracting references in perl I am trying to subtract two set of data that are too large to be in arrays. I would like to subtract them like normal arrays shown below below.
@x = (1, 2, 3);
@x2= (2, 3, 4);

my @delta = map { my $diff = $_; map { $diff - $_ } @x2 } @x;

to get:
1-2
1-3
1-4
2-2
2-3
2-4

etc.
I'm currently using this:
my $i = 0;
my $j = 0;
my $prot_x_var;
my $lipid_x_var;

#this section count the line in a file containing data. $#data is magnitude of the array of data.
for ( my $count = 0; $count <= $#data; ++$count ) {

#this searches the data for a specific string so $protein is not important but to define the string.
    if ( $data[$count] =~ m/\s+$protein\s+/ ) {
        ++$i;    #adds up the $i foreach specific string found
        $prot_x_var = $protein_xyz_coords->[0]->[$i]->{'x'};    #this flips through all the data points.
        #print "$prot_x_var \n";
    }

    #$POPS and $POPC are just use to find a string.
    if ( ( $data[$count] =~ m/\s+$POPS\s+/ ) || ( $data[$count] =~ m/\s+$POPC\s+/ ) ) {
        ++$j;                                                   #same as $i but for a different string
        $lipid_x_var = $lipid_xyz_coords->[1]->[$j]->{'x'};     #same as above
        #print "$lipid_x_var \n";
    }
}

I now want to subtract each $lipid_x_var or $lipid_xyz_coords->[1]->[$j]->{'x'} from each $prot_x_var or $protein_xyz_coords->[0]->[$i]->{'x'} like the way the above array did. I have a previous question that someone tried helping me with that is similar but now have to come back to using this idea because of the size of the data.

A: I have no idea what your code has to do with your question. I'll just answer the question.
The following is a solution that doesn't store the result in memory.
my @x1 = (1, 2, 3);
my @x2 = (2, 3, 4);

for my $x1 (@x1) {
   for my $x2 (@x2) {
      print("$x1-$x2 = ", $x1-$x2, "\n");
   }
}

Or if you want an iterator,
use Algorithm::Loops qw( NestedLoops );

my @x1 = (1, 2, 3);
my @x2 = (2, 3, 4);

my $iter = NestedLoops([ \@x1, \@x2 ]);

while (my ($x1, $x2) = $iter->()) {
   print("$x1-$x2 = ", $x1-$x2, "\n");
}

A: So your arrays are too large to store in memory?  Hmm... I would try putting both of your arrays in files, then read them in line by line, perform the subtraction and print the output to a new file that way you never store any of the full arrays in memory.
ex:

x1.dat
1
2
3

x2.dat
2
3
4

test.pl
#!/usr/bin/perl

use strict;
use warnings;

# create output file
open (OUTPUT, '>', 'output.dat') or die "Failed to open output file: $!";

# loop through x1 values
open (X1, '<', 'x1.dat') or die "Failed to get x1 data: $!";
while (<X1>) {

    # get x1 value
    my $x1 = $_;

    # loop through x2 values
    open (X2, '<', 'x2.dat') or die "Failed to get x2 data: $!";
    while (<X2>) {

        # get x2 value
        my $x2 = $_;

        # get difference
        my $diff = $x1 - $x2;

        # store in output file
        print OUTPUT "$diff\n";
    } close X2;
} close X1;

# close output file
close OUTPUT;

output.dat
-1
-2
-3
0
-1
-2
1
0
-1

This won't store any giant arrays in memory, instead it will just keep track of a simple index into each file.  Judging by the size of your arrays though you may want to add print statements within the loops so you can see that progress is being made (it may take a very long time to process that much data).  Hope this helps!

EDIT:
Even better solution that doesn't involve reopening and closing the X2 file every time through the loop! Use seek to reread the file from the start again.
#!/usr/bin/perl

use strict;
use warnings;

# open input files
open (X1, '<', 'x1.dat') or die "Failed to get x1 data: $!";
open (X2, '<', 'x2.dat') or die "Failed to get x2 data: $!";

# create output file
open (OUTPUT, '>', 'output.dat') or die "Failed to open output file: $!";

# loop through x1 values
while (<X1>) {

    # get x1 value
    my $x1 = $_;

    # loop through x2 values
    seek X2, 0, 0;
    while (<X2>) {

        # get x2 value
        my $x2 = $_;

        # get difference
        my $diff = $x1 - $x2;

        # store in output file
        print OUTPUT "$diff\n";
    }
}

# close input files
close X1;
close X2;

# close output file
close OUTPUT;

redpajama_set_name: RedPajamaStackExchange


text:
Racism, Cultural Relativism and Women's Rights
cultural relativism, racism and 'Islamophobia'
Speech at a panel discussion organised by the Action Committee on Women's Rights in Iran and Amnesty International's Women's Action Network
Many times you hear that the discussion around cultural relativism versus the universality of women's rights is a theoretical and unnecessary debate, which is a waste of time. Often one finds many, some of who consider themselves women's rights activists, who strongly defend the concept. For me though, this debate is not only a theoretical one; it is more importantly a practical one that affects the real lives of countless women and girls.
Let us be clear about what cultural relativism is. It is a profoundly racist phenomenon, which values and respects all cultural and religious practices, irrespective of their consequences for women. It asserts that the rights of people, women and girls are relative to where they are born, "their" cultures and religions. There is no right or wrong according to cultural relativists. As a result, cultural relativism supports and maintains sexual apartheid and violence against women in Islam-stricken societies like Iran because it is "their culture and religion" and it creates ghettoized, regressive "minority" communities in the West where women and girls continue to face apartheid and Islamic laws and customs.
Cultural relativism doesn't merely ignore violations; it actually legitimizes them. Moreover, it never opposes any cultural or religious practices. Cultural relativism not only makes it unnecessary to oppose violations and lack of women's rights, but also makes it racist and against freedom of choice to do so! I want to give examples of cultural relativism applied to the status of women living in Iran and Iranian women asylum seekers living in the West to show how it legitimizes women's lack of rights and silences opposition.
There are innumerable examples of its promotion in the heart of the secular West where different laws and customs apply to women who have fled Islam stricken societies. As a result of this racism, the veiling of girls becomes acceptable in the heart of Europe and men who kill women in the name of honour are given reduced sentences. The German government forcibly veils women asylum seekers it wants to deport to allow the Iranian embassy to prepare their travel documents. When a woman like Roya Mosayebi refuses to be veiled, she is beaten and forcibly veiled. When she complains to a German court, the court rules that the police acted in accordance with the law.
Holland is another good example. In 1997, when the Dutch government wanted to deport 1300 Iranian asylum seekers back to Iran, it produced a report to justify the deportations, which made numerous assertions on women that reveal how far cultural relativists will go to deny women's rights. [The IFIR along with other progressive groups managed to push back the government's assault but its justifications are telling nonetheless.] On stoning the Dutch Foreign Ministry said: "as at least four witnesses are required in order to prosecute for adultery, there are not in practice any actual prosecutions brought. We are not aware of any cases of stoning to death for adultery." They further stated: "while the legal and practical disabilities faced by women in Iran have been well documented, it is now clear that some change has been effected in recent years and that there are a number of signs that further and substantive improvements may be on the way." They also said that: "the presence of women is more visible on the streets and than in surrounding Islamic countries," and that "While the dress code is mandatory, there are hardly any women voluntarily covering their face with a veil or wearing the traditional burqah… unlike Islamic countries such as Saudi Arabia." On the fact that women have only temporary child custody they said: "This system stems from Sharia law and is applicable in most Islamic countries."
This is one example of how outrageous acts of brutality and repression by the Iranian government are denied and excused. This is how a system of sexual apartheid and lack of rights become mere disabilities. This is how they credit women's own resistance to the abuser. In Iran, women not only don't cover their faces but they continuously transgress mandatory veiling. The fact that women are 'improperly veiled' every day on the streets has nothing to do with the regime or Khatami; it just shows that women are protesting and opposing compulsory veiling despite its risks. Hundreds of thousands of women have been flogged, imprisoned, had their bodies slashed with razors, and had acid thrown in their faces so that they could walk down the streets with their veils pushed back. Moreover, when they need to, cultural relativists always compare the situation of women with the worst possible example. Why not compare the situation of women in Iran with the best possible example? When all else fails, they state that a discriminatory law is applicable in most so-called Islamic countries and that's that, which basically means women are well off enough, this is their Islamic culture, at least they don't cover their faces like in Saudi Arabia, so don't oppose, leave it be, stay silent…
Western governments, the media and cultural relativists say that Iranian society is Islamic, implying that people choose to live the way they are forced to. Just as in Canada, however, there are people with various beliefs in Iran as well. The difference is that in Iran Islam is in power, enforcing its culture on every one. 25 years ago when the Shah's dictatorial regime was in power, no one called Iran a Muslim country. If Iranian society were truly Islamic, 150,000 people would not have been executed for opposing the Islamic Republic of Iran, the Islamic regime would not need such extensive tools for repression, and the regime would not need to control people's private lives – from their sexual activities, to what they wear. If the entire society is Muslim, why did Maryam Ayoobi enter a voluntary sexual relationship for which she was buried in a ditch and stoned to death? Why are thousands of women rounded up in the streets for "improper" veiling if it's their culture and religion? In fact, these prove that this is not people's culture but the regime's culture, the ruling class's culture imposed on women and people.
Cultural relativism maintains the Islamic regime in Iran, justifies its violations, defends the abuser and even goes so far as to credit the abuser for any gains made through people's own resistance. It also aims to silence any opposition by making it seem racist to do so. It further implies that if women "choose" to live without rights then to defend their rights means that you are against their freedom of choice!
Clearly, civil rights, freedom and equality are universal concepts that have been fought for by progressive social movements and the working class in various countries. They belong to every one irrespective of where they were born and where that struggle took place. We still see the positive effects of a Bolshevik revolution, a Paris Commune, even the Iranian revolution, before it was brutally suppressed and expropriated by the Islamic regime, in various parts of the world today. That people and women worldwide, including in Iran, continue to struggle for equality and freedom and to overcome their lack of rights and repressive regimes is a confirmation of this universality.
Time and time again, we have seen that reaction has been pushed back not by respecting, legitimizing and justifying it but by struggling against and eradicating it. Progressive norms today are the result of enlightenment and just struggles by real people like us; real people who defended humanity and human standards.
The issue at stake is important. Where we each stand is important. Supporters of women's rights must strongly and unconditionally oppose cultural relativism, reactionary religious and cultural beliefs and practices, governments like the Islamic regime of Iran, Political Islam and the racist policy of ghettoization in order to make advances in women's rights. Secularism and universal rights must become a minimum norm.
Adele Crabb
Every one of us comes with a proper comprehension of the information supplied to the general public, so that I really liked the article and expected you to supply us with additional things similar to this .
Violence in Genoa condemned
The right to move, live and work anywhere


Tapan Saha, the director, is soon going to release a woman-centric movie entitled Amrita.
Sampoorna Entertainment World, the director's own company, would be the banner for the movie. The film basically showcases the predicament of a gentle, truthful, and righteous woman, who is put down by her own family members.
There was a press conference held at the Tolly Club, where the cast and crew came together and talked about their original project. The film has Bengali movie legend Supriya Devi along with veterans like Victor Banerjee, Labony Sarkar and others. The movie also features Biswajit Chakraborty and funny man Kanchan Mullick. Amrita also features fresh faces like Mainak Banerjee and Raj Banerjee.
Amrita stands out from its peers for another reason; it features the much acclaimed Indian soap queen Smriti Zubin Irani who captured fame through her portrayal of Tulsi in the fanatically popular 'Kyuki Saas Bhi Kabhi Bahu Thi' serial. She is the protagonist and this is her first Bengali movie.
Tapan Saha is also handling the script of the film that is supposed to have an August release.