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Thank you for visiting Lane Crawford's ("Lane Crawford", "we" or "us") website(s) (including www.lanecrawford.com and www.lanecrawford.com.cn) (collectively, the "Site"). Access to and use of the Site and related services (collectively, the "Services") are made available to you in accordance with the following Terms of Service and any other rules and policies posted on the Site, including the Privacy Policy (collectively, the "Terms Of Service" or "TOS"). By using the Services, such as browsing or placing orders on the Site, you are agreeing to all of the Terms of Service.
We will collect, use and store any personal data provided by you in accordance with the Privacy Policy.
This agreement does not acknowledge any relationship between you and Lane Crawford (partnership, collaboration, employment, or otherwise). It does not entitle you to hold yourself as a representative of Lane Crawford.
Lane Crawford reserves the right to make changes to the Site or any part of the TOS at any time. Please visit this page from time to time to check for any updates or changes to any part of the TOS (including the said rules and policies and the Privacy Policy).
If you have any comment about the Site or this TOS please Contact Us.
You will need to register an account to use some of the Services available to you on the Site. In registering an account and in your use of the Site, you agree to (where necessary) provide information about yourself that is true, accurate, current, and complete in all respects. Please refer to our Privacy Policy for more information on how we use your personal data.
If you are under 18, by registering for an account with us or otherwise using our Services, you agree that you have informed your parents and guardians about the TOS prior to such registration or use, and they have approved of such registration or use by you on the terms of the TOS. Lane Crawford reserves the right to only accept orders from you if you are aged 18 or over.
We will never ask you for your account's password either in writing (via email or otherwise), in person or on the phone. In using the Site, you are responsible for: (i) safeguarding any passwords used to access your account and our Services, and (ii) all use of our Services under your account. Please take reasonable care in protecting access to your account from any unauthorized use. If you suspect that the security of your account has been compromised or if there is unauthorised use of your account, please Contact Us immediately.
We may take actions against your account for activities including, but not limited to:
• Submitting material (including, but not limited to text, images, music or video) of which you do not have the full right to grant the license specified in the "Submitted Content" section above.
• Using any technology to attempt to hide the use of multiple accounts or disrupt any of our Services in any way.
• Initiating communications that contain any unlawful, harmful, threatening, abusive, harassing, defamatory, vulgar, obscene, profane, hateful, or racially, ethnically or otherwise objectionable material.
• Advertising or sending unsolicited messages of any kind.
• Impersonating others or providing any kind of false information.
• Starting or forwarding chain letters of any kind.
Lane Crawford reserves the right to terminate any account at its sole discretion. We may send you an email to inform you of the termination of your account in such event.
All software and "Content" (which is defined as, or includes, any text, audio or music, video, graphics, photographs, and image) are the intellectual property of Lane Crawford and are protected by intellectual property and copyright laws and international treaty provisions.
The Site is for your personal and non-commercial use only. Any non-personal and/or commercial use of the Content is only permitted when expressly authorised by Lane Crawford and/or its third party licensors. You may not distribute, reproduce, publish, sell or license any Content contained within the Site without prior consent or authorization of Lane Crawford. Any such unauthorized actions may result in civil consequences or criminal penalties.
Lane Crawford reserves the right to withdraw or amend any item of the Services without notice. We will not be liable if for any reason the Site is unavailable at any time and for any period.
The Site may include links to other websites or resources that are not operated or prepared by Lane Crawford. We have no control over such sites and resources and we will not accept responsibility for them or be liable for any loss or damage caused or alleged to be caused by or in connection with your use of them.
Lane Crawford is not responsible for the content or accuracy of any off-Site pages, which include but is not limited to advertisers of the Site. Use of these external websites or resources will be at your own risk and subject to the terms of use and service contained within each of such sites.
In order to place orders with us, you must meet our conditions of eligibility:
• Be aged 18 years of age or over
• Be in possession of a valid credit/debit card issued by a licensed bank acceptable to Lane Crawford for payment
• Providing personal and payment details that are warranted by you to be both valid and accurate (email address, real name, phone number, billing information and other requested information as indicated on the Site).
In placing an order with us, you authorise Lane Crawford to process a charge or charges on your credit/debit card in the amount of the total purchase price of your order. You also expressly authorise us to use personal information provided by you to perform appropriate anti-fraud checks such as credit checks and also to, where necessary, transmit or obtain information about you to or from third parties including, but not limited to, credit reference or fraud-prevention agencies, which may keep a record of that information. Please refer to our Privacy Policy for further information about how we use your data.
All orders are subject to stock availability and confirmation of the order price. Items in your shopping basket are not reserved and may be purchased by other customers.
The Site is for your personal use only. You may not purchase goods from the Site for reselling purposes or commercial exploitation.
Lane Crawford will endeavour to ensure that the Content and the product descriptions on the Site are as accurate and complete as possible. We however do not warrant that "Content" and product descriptions are accurate, complete, current or error-free. Please refer to our Returns policy if you feel a product offered by Lane Crawford is not as described.
Prices are shown on the Site in Hong Kong Dollars (HKD) in Hong Kong or US Dollars (USD) for the rest of the world, depending on the shipping country as shown in the upper-left corner on the Site or indicated by you while placing an order. Please note that orders shipped to China can only be made from Lane Crawford's China Site where products are priced in Renminbi (RMB), and this Site has its own TOS. All orders placed in and shipped from Lane Crawford's China Site are subject to its own TOS. Lane Crawford's China website can be accessed at: www.lanecrawford.com.cn. For the purpose of these Terms of Service, China excludes Hong Kong SAR, Macau SAR and Taiwan.
Prices displayed on the Site at the time your order is accepted will be honoured except in the case of obvious error. Whilst we use our best endeavours to ensure that all prices appearing on the Site are accurate, we do not guarantee that they are error-free and reserve our right to rectify any errors. If we discover an error in the price of any products that you have ordered, we will inform you as soon as possible and offer you the option of reconfirming or cancelling your order. If we are unable to contact you, we will treat the order as cancelled.
If your credit/debit card is not denominated in Hong Kong Dollars (HKD) or US Dollars (USD), the final price charged in your currency will be calculated by your issuing bank in accordance with the applicable exchange rate on the day your card issuer processes the transaction.
Taxes and duties applicable to your order depend on the shipping country of your order:
• Hong Kong orders are not subject to taxes and duties.
• Orders from countries served on a Delivery Duty Paid (DDP) basis will incur relevant import tax and duty and will be included in the final purchase price. This one-step process is for your convenience. Please note that the import tax and duty charges would be passed to the relevant local Customs authorities and are therefore non-refundable in the event of a return or exchange. You will only be charged taxes and duties once for exchanges; Lane Crawford will cover the cost of taxes and duties for the replacement.
Please refer to SHIPPING for the most up-to-date list of countries served on a DDP basis.
• Customers placing orders from countries served on a Delivery Duty Unpaid (DDU) basis will only be charged for the price of the product(s) purchased (excluding taxes and duties) and the delivery costs. Customers will be responsible for the payment of all import tax and duties levied by the country to which the products are shipped and payment of the said tax and duties is necessary for the release of the products ordered from the Customs on arrival. Our courier, DHL, will contact customers about the details of any import duty to pay. We advise you to contact your local customs authority to determine the cost of import tax and duties of your order prior to your placing orders with us.
We accept payments made by Visa, MasterCard, American Express and JCB for all international orders. Orders shipped to Hong Kong can also be paid using major cards supported by China Unionpay (CUP).
By placing an order using one of the above Credit/Debit card payment methods, you confirm that the Credit/Debit card(s) used is yours or that you have been authorised by the owner to use it. If your card issuer refuses to authorise payment to Lane Crawford, we will not be liable for any delay or non-delivery.
For CUP payments, payment will be debited immediately when the order is placed. For all other payments, payment will only be debited and cleared from your account once your order has been accepted and dispatched.
Our payment processes meet the stringent international security standards set down by the Payment Card Industry to make your shopping experience safe and secure. If you have registered an account on the Site and have decided to save your card details with us, your details will be fully encrypted, solely used to process card transactions that you have initiated and securely stored on our systems. In the absence of negligence on our part, we will not be liable for any loss you may suffer if any third party procures unauthorised access to any data you provide when using our Services.
Once you have entered your personal and payment details to place your order, we will send you an email acknowledging the receipt of your order request. This email is only a confirmation of receipt of your order request and does not constitute an acceptance of your order.
Your order will be accepted and the contract between you and Lane Crawford will be completed when we send you an email to confirm the goods have been dispatched to you and your payment has been accepted. Only the goods listed in the confirmation email sent at the time of dispatch are subject of the sale contract. All sales contracts are made in Hong Kong (SAR) and are written in English.
Lane Crawford reserves its right not to accept an order for any reason in its sole discretion (including, but not limited to, any of the following):
• The product you ordered is out of stock, or is withdrawn due to its failure to meet our quality standards or due to the shipping restrictions applicable to one or all of the ordered items.
• We identify a pricing or product description error.
• We are unable to obtain authorisation for your payment.
• You do not meet the eligibility criteria to purchase the Product in accordance with our Terms and Conditions of Service.
Our Customer Service team will contact you as soon as possible if there are any problems with your order.
We endeavour to dispatch all products ordered within 24 hours after the order has been placed and accepted by us. You will be given an indication of the expected delivery time when you place your order online. Lane Crawford's teams will try their best to meet these estimates but cannot guarantee that such estimates must be met.
Alternatively, you may choose to collect the products ordered by you in Hong Kong at the concierge of our Canton Road store or ifc mall store, Hong Kong. You need to present the order confirmation email, the credit card (or a copy of the credit card) you used to place your order and a photo ID of the person named as collector when the order is collected.
Lane Crawford insures each order through transit up until it is delivered to you or is collected. You need to sign a confirmation of receipt of the products when the products are collected and by doing so, you accept the responsibility for the products ordered from that moment on. If the recipient or collector is not the original purchaser, or in case of delivery of a gift, then you accept this signature as an evidence of delivery and fulfilment of your order by Lane Crawford. You also accept the associated transfer of responsibility in the same way.
This Returns Policy applies to purchases with Lane Crawford Hong Kong and Lane Crawford China.
Any customer who violates Lane Crawford Store Operations Policies, abuses Lane Crawford Returns Policy (including without limitation demonstrating a high incidence of returns of Merchandise after purchase), or engages in inappropriate behaviour (including without limitation abuse of Lane Crawford staff), or illegal activities (including parallel importing or passing off of Merchandise purchased at Lane Crawford) may suffer the following consequences:
• Customer may be black listed by Lane Crawford and future custom refused;
• Return or exchange of Merchandise may be declined;
• Customer who is a holder of Privilege Card may be disqualified from the Privilege Card Programme together with members resident at the same address as the Customer;
• Customer and any individual resident at the same address as the Customer may be refused membership of the Privilege Programme.
The decision as to whether a customer has violated Lane Crawford Store Operations Policies or abused Lane Crawford Returns Policy or engaged in inappropriate behaviour remains within Lane Crawford's sole discretion and its decision shall be final. Suspected illegal activities will be referred to Lane Crawford's legal department for further investigation and action.
Unless otherwise stated, this Returns Policy applies to both in-Store purchases and online purchases.
Merchandise may be exchanged (subject to stock availability) or returned within 7 days of purchase (in the case of in-Store purchases) or receipt (in the case of online purchases) of Merchandise provided that:
(1) all tags, certificates, warranties, care instructions, product labelling, authenticity cards, extra buttons, hangers, dust bags and boxes (in the case of shoes) are intact and returned together with the Merchandise;
(2) the original invoice is presented; in the case of returns or exchanges of online purchases in Store, the credit card used to purchase the Merchandise must also be presented;
(3) the Merchandise does not fall within the category of "Excluded Items" as defined below;
(4) the Merchandise is in Sellable Condition as defined below; and
(5) a completed returns form is presented (only for returns or exchanges on orders made in China).
(6) Apple products and Gift Card is excluded.
Returns or exchanges outside 7 days of purchase or receipt of Merchandise (as the case may be) may be accepted at the sole discretion of Lane Crawford.
For online purchases, international returns must be sent via DHL Express. Customers will take full responsibility for the returns if they do not send the Merchandise via DHL Express. Lane Crawford reserves the right to refuse returns that are not made via DHL Express.
For online purchases, returns or exchanges in Stores can only be made in the Stores of the country where the online orders are made. For orders made online in China, returns or exchanges may be made at Lane Crawford China stores.
"Sellable Condition" means that the Merchandise is still in its original packaging with the original labels, garment tags, price tags and return tags still attached; that the Merchandise is unworn, unused, unwashed, unaltered and in the condition originally sold (in the case of shoes that the soles are not scratched or dirty); and that the Merchandise is not damaged in any way.
The decision as to whether the Merchandise is in Sellable Condition remains within Lane Crawford's sole discretion and its decision shall be final.
For returns of online purchases, if Lane Crawford receives a return that cannot be accepted, the customer has the option either to collect the Merchandise again from one of Lane Crawford Stores or to have the Merchandise re-shipped to the customer at his/her sole cost.
No return or exchange will be accepted for jewellery, vintage jewellery, watches, vintage watches, luxury hand phones, luxury headsets or men's luxury accessories, lingerie, men's underwear, hosiery, swimwear, pillows, mattresses, fur, bespoke or made-to-measure Merchandise, custom orders, vintage Merchandise, antiques, unsealed CDs, DVDs, tapes or other recording media, software or videos, unique or fragile Merchandise invoiced as "no refund" "no return no exchange", Pre-sale, Sale or Aged Stock Merchandise invoiced as "no return no exchange", or perishable goods, including food, beverages, hampers, and cosmetics, personal grooming products and fragrances that are not in Sellable Condition (specifically Merchandise in the cosmetics, grooming or fragrance category will not be accepted for return if the packaging has been opened), (the "Excluded Items").
The only exception permitted in the case of Excluded Items is in the case of faulty or damaged items ("Defective Merchandise"). In this case the Merchandise will be returned to the Supplier or for independent assessment by a third party to determine whether the Merchandise is defective. Merchandise damaged as a result of fair wear and tear will not be accepted as defective. If the Merchandise is determined to be Defective Merchandise, the customer will be entitled to repair or full refund as appropriate within the circumstances at the sole expense of the Supplier. Lane Crawford will use its best efforts to secure such repairs or refund on behalf of the customer but accepts no liability whatsoever howsoever arising for the defective items supplied by the Supplier.
Refunds will be made for the original purchase amount, on presentation by the customer, of the original invoice within 7 days of purchase (in the case of in-Store purchases) or within 7 days of receipt of the Merchandise (in the case of online purchases). Except for refunds for Defective Merchandise (see below Return of Defective Merchandise), all refunds for in-Stores and online purchases will be made in the form of a Lane Crawford Electronic Gift Card ("EGC"), which is subject to applicable terms and conditions found at www.lanecrawford.com/giftcard. Cash or credit card refunds are not available.
For refunds for online purchases, initial shipping, taxes and duties will not be refunded unless the Merchandise is defective in which case a full refund will be made subject to inspection and compliance with the policy under "Return of Defective Merchandise" below. No credit may be issued on credit i.e. Merchandise purchased with a GC will not be refunded or exchanged.
Any free promotional gift issued with the returned Merchandise must also be returned.
For in-Store purchases, any Defective Merchandise must be presented at the relevant counter of purchase at Lane Crawford with the original invoice within 7 days of purchase and must be photographed by Lane Crawford staff on receipt and return to the customer. Customers must sign a waiver to indicate their acceptance that Lane Crawford assumes no liability in respect of the Defective Merchandise but will present it for inspection to the Supplier or an independent third party for assessment. This procedure is known as the "in and out waiver" procedure.
For online purchases, customers should contact Lane Crawford in respect of any Defective Merchandise immediately by emailing the Customer Care team at firstname.lastname@example.com. Shipping, tax and duties'costs on the Defective Merchandise will not be charged. Lane Crawford reserves the right to request photographic support regarding Defective Merchandise before authorising a return. If requested, the Customer shall sign a waiver to indicate their acceptance that Lane Crawford assumes no liability in respect of the Defective Merchandise but will present it for inspection to the Supplier or an independent third party for assessment.
Refunds for the original purchase amount of the Defective Merchandise will be paid by Lane Crawford on behalf of the Supplier of the Defective Merchandise directly to the customer, in the form of an EGC or at Lane Crawford's sole discretion, the original purchase amount will be credited back to the credit card used by the customer to purchase the Defective Merchandise (if purchased by credit card). Cash refunds are not available.
Customers may present Merchandise that has been damaged after purchase for repair by the Supplier at the customer's sole cost provided that the customer agrees to accept Lane Crawford's "in and out waiver"procedure pursuant to which the customer signs a waiver to indicate their acceptance that Lane Crawford assumes no liability in respect of the damaged Merchandise but will present it for inspection to the Supplier for assessment for repair and quotation for the customer's approval and at the customer's sole cost. Lane Crawford will only undertake repairs requiring replacement of spare parts for current season Merchandise purchased from Ladies Shoes and Accessory departments.
Customers are permitted to exchange Merchandise other than Excluded Items for a different size in the same colour and style based on stock availability. If a different size is unavailable then an alternative style and colour may be considered. If the customer selects Merchandise of lower value than the original Merchandise purchased then a GC will be issued.
For exchanges of online purchases, shipping, taxes and duties on size-exchange replacements will not be charged after the initial delivery.
Merchandise that has been purchased as a Gift may be exchanged or returned within 7 days of purchase (in the case of in-Store purchases) or receipt (in the case of online purchases) provided that:
(1) all certificates, warranties, care instructions, product labelling, dust bags and boxes (in the case of shoes) are intact and returned together with the Gift;
(2) the original gift receipt is presented;
(3) the Gift is in Sellable Condition; and
(4) the Gift does not fall within the category of Excluded Items.
Returns or exchanges outside 7 days of purchase (in the case of in-Store purchases) or receipt (in the case of online purchases) shall be accepted at the sole discretion of Lane Crawford.
The refund shall be issued by GC for the value of the original invoice amount.
To return or exchange Merchandise that have been delivered at a pre-arranged delivery time, for example large or bulky goods or furniture, please contact our Customer Care team at email@example.com to arrange collection or replacement. Lane Crawford reserves the right to make a charge of up to HK$1000 to cover the collection cost, which will be deducted from the amount to be refunded, except when the Merchandise is defective. Customers will be notified of this amount at the time of cancellation.
Please contact Customer Care team at firstname.lastname@example.com regarding questions about this Returns Policy.
Nothing in the TOS is intended to affect your rights under the Law in Hong Kong SAR.
Views expressed in any media by the designers, companies or third parties, whose products are sold at our stores or on the Site or with whom we are associated, are their own. Lane Crawford takes no responsibility for any such views as they do not necessarily reflect ours.
Lane Crawford does not guarantee that the use of the Site and Services will be error-free or that the Site or the servers that make it available are free of viruses or other harmful components. We recommend all users of the Site to ensure they have up-to-date software, including anti-virus, installed.
Some events may happen beyond our reasonable control, such as adverse weather. Under such conditions, Lane Crawford will always do its best to aim at maintaining its Services but will not be responsible for failing to meet any obligations in this TOS.
At our request, you agree to compensate us fully and hold us, Lane Crawford (including its officers, directors, agents, affiliates, licensors, and suppliers), harmless from and against all liabilities, claims, expenses, damages and losses, including legal fees, arising from any breach of the TOS by you. This includes the use of the Site by any other persons using your account caused by your action or inaction.
If you breach the TOS and we take no action against you, it is no wavier for us to exercise our rights and remedies in any other situation where you breach the TOS.
We have our complaints handling procedure that we will use to try to resolve any disputes when they first arise. Please contact our Customer Care team for any order related complaints or comments.
Lane Crawford respects the intellectual property of others. If you have reason to believe your work may have been used in the Site without your permission, please contact us following this complaints handling procedure.
The TOS, together with all our policies and procedures, are governed by and construed in accordance with Hong Kong SAR law. The relevant courts of Hong Kong SAR will have exclusive jurisdiction in the event of any dispute or claim associated with these TOS.


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Practice Report: Sunday
The Devils held a short practice session today in Los Angeles, according to Tom Gulitti of Fire and Ice.
Gulitti notes that everyone was on the ice for Devils. The lines and defensive pairings remained the same as last night's game ended.
Parise-Zajac-Kovalchuk; Elias-Henrique-Zubrus; Ponikarovsky-Josefson-Clarkson; Carter-Gionta-Bernier; Boulton-Sykora-Janssen
Greene-Fayne; Salvador-Zidlicky; Volchenkov-Harrold; Tallinder-Larsson.
Brodeur, Hedberg

subset: commoncrawl


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April 26, 2014
Star Entertainment
Foreigners Invade Container Satdazs
conributed Photographs
The latest edition of the Magnum Container Satdazs
The party was flooded by locals and foreigners alike. Patrons from Europe, mainly Germany and Finland, and also from the Dominican Republic, were in attendance. And ace disc jock Ikel Marvlus, alongside Flabba Dabba, didn't allow them to be just mere spectators.
He requested the British Bling Girls from Clarendon to test the mettle of the foreign men, and they didn't disappoint. Needless to say, the crowd loved the spectacle that unfolded.
The overseas patrons said they loved the vibe of the party, and were glad they came. "We love to party,
There were numerous giveaways, including buckets filled with Magnum Tonic wine, Red Bull accessories, clothing from Keisha Wholesale, movie tickets for Carib Cinema, among other goodies.
Magnum Kings and Queens of Dancehall finalists Candy K and Hydal also gave cameo performances.
Home | Gleaner Blogs | Gleaner Online | Go-Jamaica | Go-Local | Feedback | Disclaimer | Advertisement | Privacy Policy | Contact Us


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Para-Aortic Lymph Nodal Staging and Evaluation of Treatment Outcome by 18F-Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) in Advanced Cancer Cervix
Recruitment status was Recruiting
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
18F-fluorodeoxyglucose Positron Emission Tomography (FDG-PET) Imaging has been extensively used in the evaluation of various malignancies and is rapidly being recognized as a mandatory investigations. 18F-fluorodeoxyglucose Positron Emission Tomography (FDG-PET) Imaging has also been tried in cervical cancers with excellent results for detection of both pelvic and extra-pelvic disease in terms of sensitivity and specificity. Till date, PET Imaging has been reported to have highest sensitivity and specificity for detection of disease and treatment failures compared to other non-invasive investigations available. Treatment decisions (Localized RT Vs Extended RT) will be according to the results of PET Scans. The treatment response, outcome and follow-up will be labelled according to the PET Scan results and will be directed for treatment accordingly.
Cancer of Cervix
Other: PET IMAGING
Phase 2
|Study Type:
|Study Design:
|Observational Model: Cohort
Time Perspective: Prospective
|Official Title:
|Para-Aortic Lymph Nodal Staging and Evaluation of Treatment Outcome by 18F-Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) in Advanced Cancer Cervix
- PET Scan for Para-Aortic Staging in Carcinoma Cervix [ Time Frame: 5 years ] [ Designated as safety issue: No ]
- Clinical (FIGO), MRI, and PET - Abdomen and Pelvis Correlation [ Time Frame: 5 years ] [ Designated as safety issue: No ]
- Volumetric Correlation of Local Disease by PET and MRI [ Time Frame: 5 years ] [ Designated as safety issue: No ]
- Radiotherapy Response Evaluation and Post therapy Surveillance by serial PET Scans [ Time Frame: 5 years ] [ Designated as safety issue: No ]
- overall survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
|Estimated Enrollment:
|Study Start Date:
|September 2005
|Estimated Study Completion Date:
|September 2010
Other: PET IMAGING
|Ages Eligible for Study:
|18 Years to 65 Years
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
|Sampling Method:
|Probability Sample
Patients with hisotologically proven cervical cancers with FIGO II-IIIB eligible for the study will be invited for the study
Inclusion Criteria:
- Histologically proven squamous carcinoma or adenocarcinoma of cervix
- Performance index WHO grade 0 or 1
- Patients below 65 years of age
- FIGO Stage IIB / IIIB
- Normal ECG and Cardiovascular system
- Normal hematological parameters
- Normal renal and liver function tests
- Normal Blood Sugar levels / Controlled Diabetes
Exclusion Criteria:
- Co-morbid conditions like medical renal disease
- Past History of Phobia for MRI Examination
- Medical or Psychological condition that would preclude Investigations / Treatment
- H/o Previous treatment / Pregnancy
- Patient unreliable for treatment completion and follow-up Investigations.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00193752
|Contact: Shyamkishore J Shrivastava, MD, DNB(RT)
|+91-22-2417 7163
|Contact: Umesh M Mahantshetty, MD, DNB (RT)
|+91-22-2417 7168
|Tata Memorial Hospital
|Mumbai, Maharastra, India, 400 012
|Contact: Shyamkishore J Shrivastava, MD, DNB (RT) +91-22-2417 7163 firstname.lastname@example.com
|Contact: Umesh M Mahantshetty, MD, DNB (RT) +91-22-2417 7168 email@example.com
|Principal Investigator: Shyamkishore J Shrivastava, MD, DNB (RT)
|Principal Investigator:
|Shyamkishore J Shrivastava, MD, DNB (RT)
|Professor & Head, Radiation Oncology, Tata Memorial Hospital
No publications provided
|Responsible Party:
|Dr SK Shrivastava, Tata Memorial Hospital
|ClinicalTrials.gov Identifier:
|NCT00193752 History of Changes
|Other Study ID Numbers:
|TMH/205/2004/Cx_PET STUDY
|Study First Received:
|September 13, 2005
|Last Updated:
|July 14, 2008
|Health Authority:
|India: Department of Atomic Energy
Keywords provided by Tata Memorial Hospital:
FDG-PET Imaging
Cervical Cancer
Post-treatment evaluation
Para-aortic Nodal Staging
Extended field Radiation
Extended field IMRT
Cancer of the Cervix
Cervix Cancer
Additional relevant MeSH terms:
Uterine Cervical Neoplasms
Genital Diseases, Female
Genital Neoplasms, Female
Neoplasms by Site
Urogenital Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Uterine Neoplasms
Fluorodeoxyglucose F18
Diagnostic Uses of Chemicals
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
ClinicalTrials.gov processed this record on October 06, 2015


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Illinois Legislator Wants to "Tweak" Homeschooling Rights
Chicago Senator Maloney introduced a bill two years ago that would require homeschool registration with the Illinois State Board of Education. Even after an estimated 4,000 homeschoolers showed up at the Capitol for an informational only hearing on this bill, Senator Maloney had a hard time letting the bill finally go. After hearing Senate Education Vice-Chair Lightford's interview responses related to her bill lowering the compulsory attendance age, I don't think the super-majority party is done with homeschoolers yet.
The Illinois homeschooling community thought we sent a clear and fair message we did not want our freedoms tampered with, we were obviously doing just fine in educating our children. The public school system should correct their gulf of educational failure, rather than worrying about any perceived cracks in parent-directed educations.
Below is what Senator Lightford said in the WTTW interview in the last minute. (more…)


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Dec 6, 2013 Shedding those holiday pounds can be tough, but maybe a financial incentive can give you that extra push.
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Oct 14, 2013 When it comes to personal finance, a military-esque dedication to discipline can work well.
7 lessons the U.S. government could learn from Marketplace Money
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Oct 4, 2013 Our listeners are a smart, helpful bunch when it comes to money. Congress seems like it could use some help...
So you don't understand that medical bill fee...
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Interview with
Sep 27, 2013 L.A. Times consumer columnist David Lazarus answers listener questions about health care cost-shifting, whether account monitoring services are worth their costs, and what to do when you don't trust the bank you've got a home loan through.


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Posted by Derek
Stuart Schreiber and Paul Clemons of the Broad Institute have a provocative paper out in JACS on natural products and their use in drug discovery. As many know, a good part of the current pharmacopeia is derived from natural product lead structures, and in many other cases a natural product was essential for identifying a target or pathway for a completely synthetic compound.
But are there as many of these cases as we think - or as there should be? This latest paper takes a large set of interaction data and tries to map natural product activities on to it. It's already know that there are genes all up and down the "interactome" spectrum, as you'd expect, with some that seem to be at the crossroads of dozens (or hundreds) of pathways, and others that are way out on the edges. And it's been found that disease targets tend to fall in the middle of this range, and not so much in the too-isolated or too-essential zones on either side.
That seems reasonable. But then comes the natural product activity overlay, and there the arguing can start. Natural products, the paper claims, tend to target the high-interaction essential targets at the expense of more specific disease targets. They're under-represented in the few-interaction group, and very much over-represented in the higher ones. Actually, that actually seems reasonable, too - most natural products are produced by organisms as essentially chemical warfare, and the harder they can hit, the better. Looking at subsets of the natural product list (only the most potent compounds, for example) did not make this effect vanish. Meanwhile, if you look at the list of approved drugs (minus the natural products on it), that group fits the middle-range interactivity group much more closely.
But what does that mean for natural products as drug leads? There would appear to be a mismatch here, with a higher likelihood of off-target effects and toxicity among a pure natural-product set. (The mismatch, to be more accurate, is between what we want exogenous chemicals to do versus what evolution has selected them to do). The paper ends up pointing out that additional sources of small molecules look to be needed outside of natural products themselves.
I'll agree with that. But I suspect that I don't agree with the implications. Schreiber has long been a proponent of "diversity-oriented synthesis" (DOS), and would seem to be making a case for it here without ever mentioning it by name. DOS is the idea of making large collections of very structurally diverse molecules, with an eye to covering as much chemical space as possible. My worries (expressed in that link above) are that the space it covers doesn't necessarily overlap very well with the space occupied by potential drugs, and that chemical space is too humungously roomy in any event to be attacked very well by brute force.
Schreiber made a pitch a few years ago for the technique, that time at the expense of small-molecule compound collections. He said that these were too simple to hit many useful targets, and now he's taking care of the natural product end of the spectrum by pointing out that they hit too many. DOS libraries, then, must be just in the right range? I wish he'd included data on some of them in this latest paper; it would be worthwhile to see where they fell in the interaction list.
Comments (58)
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1. bbooooooya on July 12, 2010 7:57 AM writes...
I've always felt that big pharma's foolish adherence to Lipinski's "rules" to be one of the reasons so few new drugs are discovered. Following after Lipinski, one seeks to discover new drugs by copying old drugs. This seems to me like Columbus seeking to discover India by sailing up the Rhine.
I don't entirely buy the "10^63" foolishiness that ws propagated a few years ago, but I think that looking at chemical spaces we've not been before is more likely to afford more interesting drugs than constantly reinventing the same heterocycles.
Of course, getting someone to pay for a dd program that would take a mimimum of 5 to 10 years to bear fruit could be an issue. I guess big pharma just prefers to play where it's been.
2. Mark on July 12, 2010 8:02 AM writes...
I would argue that natural products provide a cheap route to a lot of structure diversity. Who would want to be the chemist to have to synthesis morphine in order to discover the mu-opioid receptor?
Natural products themselves might not be the best drug, but they are a great tool to probe for useful structural elements that can be used to create more drugable candidates.
3. processchemist on July 12, 2010 8:04 AM writes...
"Genome biology is shining a bright light on the origins of human disease. Unfortunately, the biological targets emerging as ideal points for therapeutic intervention are often viewed as being extremely difficult, if not impossible, to modulate with small molecules "
Nature 457, 153-154 (8 January 2009)
IMHO some good modulations with small molecules have been achieved. Not so much maybe, but the kinome is probably the most drugged family of targets of ever, and some SM performed pretty well in the therapeutic use.
By the way, it will be great to see some translations from metachemistry to the real world, and to see how they perform.
4. newnickname on July 12, 2010 9:06 AM writes...
Also recently: Samuel Danishefsky, Nat. Prod. Rep., 2010, DOI: 10.1039/c003211p "On the potential of natural products in the discovery of pharma leads: A case for reassessment."
Basically, natural products are valuable leads and deliberately diverting synthetic intermediates (from a total synthesis) can produce greater quantities of superior candidates.
5. CMCguy on July 12, 2010 9:10 AM writes...
Are natural products really still a source of new drugs anymore? Once this was a prime area for leads and even drugs but has lost so much emphasis in academia and more so industry that sadly potential contribution is no longer every meaningful. Maybe ventures in Biologics have supplanted some of that utilization of nature in a that sense rather then small molecules from biologic chemical factories.
Conceptually DOS might hold promise to look in chemical places that are not normally explored which is worthwhile however translations to actual treatments may be more difficult as may also carry along new problems. There are practical aspects that must be considered, which largely comes from experiences medchemistry skills then continues through development. Although #1 can criticize Lipinki's "rules" which may indeed have inhibited some efforts due to over application if they are taken like the Pirate Codes as "Guidlines" and applied properly can help avoid certain pitfalls.
6. JRnonchemist on July 12, 2010 9:36 AM writes...
Stupid question: Maybe he isn't selling his existing library. Couldn't he be trying to isolate the portion of chemical space people should focus on if they are trying to make libraries of synthetic chemicals useful for drug discovery?
7. Hap on July 12, 2010 9:42 AM writes...
I wonder if a problem with small molecule leads is their inherent selectivities for receptors rather than their ability to hit receptors with the appropriate connectivities for disease genes. [Are small molecule leads as selective for their receptors as natural product-derived leads, or is their no such relation?] For example, I thought that Lipitor couldn't just be hitting its designed target because of its antilipidemic effect - it has to be inhibiting/modulating something else. Particularly with protein-protein interactions, it may be difficult to inhibit them specifically with a small molecule (though maybe that's just reason to look more closely).
8. Hap on July 12, 2010 9:43 AM writes...
9. milkshake on July 12, 2010 9:43 AM writes...
I doubt big pharma will do much in house natural product research anymore though it might still license it in - if the product is good and some academic group does all the synthesis and biology research work for them...
10. MLBpitcher_and_MedicinalChemist on July 12, 2010 9:48 AM writes...
Most of the low hanging fruit has already been discovered and medicinal chemistry are in competition with their previous creations, whether it is purely artificial based on only the knowledge of its target, or something refined through evolutionary chemical warfare like many antibiotics and rapamycin derivatives that target mTOR. Most of those drugs are going to go off patent anyway, so medicinal chemists would have to be ingenious enough to construct efficacious and safe molecules so they would be included in the formularies of health insurance companies and governments with ready access to generic drugs.
If I remember correctly, TKIs are not based on natural products and imatinib was discovered through rational drug design, not through a natural product derivative. All TKIs have basically the same motif (quinazoline).
Are natural product based drugs already picked low-hanging fruit that is about to go rotten due to the expiration of patents?
PS... Derek.. you lost against the Mets on Sunday giving up two runs in 5 1/3 innings. That sucks... Johan was just pwnd joo!!
11. MLBpitcher_and_MedicinalChemist on July 12, 2010 9:51 AM writes...
12. MedChem on July 12, 2010 10:00 AM writes...
#4 "Also recently: Samuel Danishefsky, Nat. Prod. Rep., 2010, DOI: 10.1039/c003211p "On the potential of natural products in the discovery of pharma leads: A case for reassessment."
Funny. Did you see Danishefsky's praise of this paper in C&EN? I guess they'd say whatever that fits the theme of the paper they're trying to publish at the time.
13. molecular architect on July 12, 2010 10:12 AM writes...
@MedChem: You should reread Danishefsky's "praise" of this paper. It's quite a cleverly worded back-handed compliment.
"Alas, as would have been expected from professor Schreiber ..."
14. RM on July 12, 2010 10:26 AM writes...
My thoughts can be summarized by misquoting Churchill:
"Natural products are the least reliable source of pharmaceuticals, except for all the others that have been tried."
15. MedChem on July 12, 2010 10:30 AM writes...
That's a good one!
16. ronathan richardson on July 12, 2010 11:19 AM writes...
Seeing Schreiber talk recently, he bragged extensively about the DOS collection's ability to hit "untargetable" targets, by which he mainly meant transcription factors, based on small molecule microarray data. I had thought TF's were the main untargetable target that we would cure diseases (at least cancer) if we could hit the way we hit kinases, but that "network connectivity" view of things might change my mind--TF's are central network regulators usually.
17. Ed on July 12, 2010 11:55 AM writes...
Natural products are very much the first-choice go-to molecules when considering antibody drug conjugates.
To suggest that the field is dead based only on immediate personal experience seems somewhat arbitrary and disingenious.
18. milkshake on July 12, 2010 12:04 PM writes...
AML drug that is currently in the clinic (phase II) for a glutamate transporter boosting in MAL patients is actually working as a transcription factor - and it is a small molecule - a semisynthetic cefam analogue that is already approved as injectable antibiotics
19. MLBpitcher_and_MedicinalChemist on July 12, 2010 1:45 PM writes...
Why can't we just replace small molecules with monoclonals now?
20. road on July 12, 2010 1:48 PM writes...
Because there are still a few important things that go on *inside* the cell.
21. newnickname on July 12, 2010 2:22 PM writes...
22. ronathan richardson on July 12, 2010 2:37 PM writes...
milkshake, I tried to figure out what molecule/target you were talking about in your post--could you clarify? thanks
23. milshake on July 12, 2010 3:34 PM writes...
I spoke with a neurologist here few days ago and she mentioned a lactam IV-administered cephalosporine-derived antibiotics that is in clinical trial for ALS. This antibiotics is supposed to boost levels of glutamate transporter in the brain - the one which is defective in ALS and this drives the neuronal loss. She said the drug acted as a transcription factor. I was amazed when I heard this because 1) targeting transcription is hard (but apparently this compound was discovered by screening a collection of approved drugs) 2) the stuff has to get into brain and into the nucleus
24. Drug Discoverer on July 12, 2010 3:55 PM writes...
In today's world of drug discovery, we all need as many sources of chemical leads as possible, be they natural products, existing compund banks, targeted libraries, or compounds covering new compound space. For many target classes, finding suitable chemical leads is not the problem, nor is optimizing on potency or even selectivity. The problem is having good drug properties in vivo, efficacy, safety. SS's approach does nothing toward solving these problems for us.
When people try to be too clever in providing guielines of gross generalizations, the results can often be less than helpful when applied too rigorously without context, thought, suitable judgement. Thanks Stu, again, for one of your insightful prognoses that has limited true application.
25. MedChem on July 12, 2010 4:10 PM writes...
My reaction after reading the article was a lazy "so?". I really don't see the significance and brilliance that the reviewers obviously saw.
26. MoMo on July 12, 2010 4:38 PM writes...
SS always is full of good advice-NOT
How many drugs has his efforts afforded? I would think the answer is ZERO
I would like to know. In Boston we call people who dress, think and perform like him "Shreiberphiles"
Natural products will always be a good starting point for new drugs regardless of how many drugs SS and his followers produce- which I believe is near ZERO.
27. Eraser on July 12, 2010 4:54 PM writes...
I agree.
I think Schreiber has started to belive too much in his own brilliance. Trying to cover chemical space simply by casting a net in different directions with no clear guide except "diversity" ?
Good luck
28. Phil on July 12, 2010 4:58 PM writes...
"For many target classes, finding suitable chemical leads is not the problem, nor is optimizing on potency or even selectivity. The problem is having good drug properties in vivo, efficacy, safety."
This is the part that most academics just don't understand. Activity at the picomolar level and exquisite selectivity are just the beginnings of a good drug, and even these are often sacrificed for better pharmacological behavior. These are problems that can only be solved by rational design, which is why no one should be worried about being replaced by CombiChem, DOS, or any other snake oil for drug discovery someone like Schreiber is trying to sell.
29. barry on July 12, 2010 5:28 PM writes...
Tularik spent years and tens of millions screening 2x^6 cmpds for a small-molecule inhibitor of a mammalian transcription factor and found zero. While this is rarely the hardest part of the drug discovery process, it was the killer in transcription factors. If prof. Schreiber has solved this, that's far more interesting than this paper.
30. Phil on July 12, 2010 5:41 PM writes...
re #29
TFs are specific example of what I'd argue is a very different drug target than medicinal chemists have tried to hit before, which is why it wasn't until very recently any success was found. I don't think Schreiber's DOS is going to help with that either because as Derek points out, the chemical space is practically infinite.
Chemical biology seems to have made a breakthrough in TF inhibition. http://www.the-scientist.com/blog/display/56143/
31. anonymous on July 12, 2010 6:05 PM writes...
sanofi is laying off chemists/medicinal chemists tomorrow. mgmt finds out who early morning, then meets with the doomed. site meeting tomorrow afternoon. stay tuned.
32. Anonymous on July 12, 2010 6:09 PM writes...
I'm surprised no one has mentioned Infinity. Schreiber founded Infinity several years ago, based on the claim that they could use DOS to discover revolutionary compounds against undruggable targets. Infinity raised over $100 million in VC money.
So, how did that turn out? The "DOS" part was a total failure. They found absolutely nothing. Infinity's lead clinical candidate, IPI-504, differs from the natural product geldanamycin by -- get ready -- two hydrogen atoms. Apparently when you spend $100 million on "DOS", you can figure out how to convert the quinone to the hydroquinone.
Schreiber likes to write reviews about "chemical space" and druggable proteins, but the truth is that his lab has no track record of producing useful compounds against even the most simple targets, let alone transcription factors (at least for the past 15 years, post-trapoxin). I can't think of anyone who takes Schreiber seriously at this point. Derek, why do you still post about this stuff?
33. peturbagen on July 12, 2010 7:36 PM writes...
#28 nails it. I heard Schreiber give a talk about 6 years ago where he spent half the time singing the praises about DOS then the rest of the time talking up how natural products have superior properties as drugs with no acknowledgment of the contradiction.
Isn't the problem with DOS that, to easily achieve "diversity" you need to have syntheses that work robustly in aqueous conditions? This generates libraries of molecules that are easily hydrolyzed in physiological milieus and hence would never achieve the PK profile of "drugs."
34. adrien brody on July 12, 2010 8:25 PM writes...
I enjoy your analyses on such matters (i.e., the question of what chemical matter seems most promising). I don't agree with some of the posts here, which seem a little overzealous about discounting the academic approach to finding interesting molecules. I don't like the way the arguments are being built.
It seems that a recurring criterion is to ask "what drugs have you discovered"?
Isn't that the whole point? The current strategies don't work as well as they're supposed to, right? Don't we need complementary approaches that aren't necessarily limited by the conventional wisdom of drug companies? I'm confused.
How do we find new drugs? How to we hit undruggable targets? This entire topic -- DOS, natural products, "drug-like" compounds -- it's an open question to be sure. And it's not clear that anyone here has the solution.
Personally, I think Schreiber is off the mark. I have a special place in my heart for NPs. But that's another post.
Finally, a question I have for poster 32 is this: Is it fair to say DOS is a bad concept because Infinity didn't produce a new drug lead? If they had produced a drug lead, would you feel better? (I'm guessing probably not). It's fine if you don't like Schreiber. Great. But I'd feel better if that wasn't your M.O.
35. adrien brody on July 12, 2010 8:30 PM writes...
By posts I mean comments.
36. JB on July 12, 2010 8:44 PM writes...
"These are problems that can only be solved by rational design"
There's a team of 11 medicinal chemists working at the Broad screening center (and DOS library chemists are pulled in for medchem as well):
One of the design features of the DOS libraries is the ability for rapid analogging- not just at the diversity sites but within the backbone as well (see papers on the build-couple-pair strategy.)
37. Got_QSAR? on July 12, 2010 11:10 PM writes...
Natural products, DOS libraries, combichem... What ever happened to traditional medchem approaches? ANALYZE THE DATA YOU'VE ALREADY GENERATED - find trends between structure and data - make next compound. I think they use to call it rational drug design.
QSAR (2D and 3D) plus structure based design techniques is where I will put my money every time.
38. student on July 12, 2010 11:27 PM writes...
What's with all the hate for Schreiber? Does everyone want to stick with the traditional drug discovery approaches where drugs cost 1B$ to generate for all eternity? At least he's trying something new, goddamit, cut him some slack. Drug discovery is a clusterfuck of a problem, and there's no shame in not coming up with a drug in 15 years in an academic setting. Just ask Derek. Smart people are going to have to keep on trying new approaches that fail (combichem, DOS, etc), and put up with all the jeers of trying something new, if we're ever going to find something that revolutionizes the biz. Natural products are good starting points because they're usually drugs in the first place -- warfare agents, for instance, that can cross membranes and fuck shit up. But they're far from ideal, and it's not sustainable to keep on the same old path for many new druggable problems that are out there.
39. Got_QSAR on July 12, 2010 11:37 PM writes...
#38 "Does everyone want to stick with the traditional drug discovery approaches..."
IMHO that's the problem. We/they aren't sticking with the traditional approaches. In my medchem experience thus far (albeit anecdotal) I have seen more brute force approaches than rational ones being applied.
40. cliffintokyo on July 13, 2010 2:26 AM writes...
Whoah Guys:
Be certain that SS knows the patent game rules.
He needs *something* he is able to *talk* about and *some (other) thing* he is able to patent.
Academics have the *luxury* of being able to do both......
41. Anonymous on July 13, 2010 7:39 AM writes...
Adrien Brody: "Is it fair to say DOS is a bad concept because Infinity didn't produce a new drug lead? If they had produced a drug lead, would you feel better? "
You're saying: "If the experimental result had been the opposite, would you have a different opinion?"
Yes, that's how it works.
The idea that DOS can be used to target undruggable proteins has been put to the test -- in expensive experiments at Infinity, at Schreiber's huge lab at the Broad, in the labs of his many scientific progeny. The result has been a big silence.
Sure, it was worth a try, even though the logic behind DOS is somewhat dubious, as Derek and many others have pointed out. But to claim, in 2010, that Schreiber-type DOS is going to allow us to finally target undruggable proteins! -- that is just laugh-out-loud ridiculous. Just completely disconnected from reality, when everything points to the opposite conclusion.
42. alkaloid chemist on July 13, 2010 8:20 AM writes...
I don't think Schreiber, or anyone else, is seriously anticipating DOS to pop out the next lipitor. That's not the point. The point, as #33's name implies, is to discover perturbagens of biological systems which will give us new insight into cellular mechanisms that might not have ever been discovered otherwise (robotnikinin, for example). This information is critical, and something academia is very good at (as opposed to actually making drugs). I applaud Schreiber and others for developing a rational (yes, rational) approach for discovering new and unique biological probes. Schreiber is not suggesting we stop looking to natural products to study disease biology (undoubtedly they are the best source), only that our focus may be too narrow. I guess that makes me a Schreiberphile?
43. Anonymous on July 13, 2010 8:39 AM writes...
alkaloid chemist:
poster #33 was mocking Schreiber by calling himself "perturbagen".
44. alkaloid chemist on July 13, 2010 8:45 AM writes...
#43: Thanks, but I caught that. That's why I mentioned it (sarcastically) to make a counterpoint.
45. Anonymous on July 13, 2010 9:13 AM writes...
I am starting to think that Schreiber is starting to go over the end. One of his recent talks was very confusing in its message and I thought he was trying to claim credit for some of the recent major advances in cancer and made him self out to be some sort of crusader with a I hate cancer bandana tied to his forehead. I wanted to ask him if his molecule collection could cure baldness - but then I decided no to. But its funny to see chemist lap up what he dishes out. A group of sensible biologist would hve him running for the hills.
46. iridium on July 13, 2010 1:35 PM writes...
I do not see big conceptual difference between combichem and DOS.
Could somebody comment on that?
Thank you.
47. Anonymous on July 13, 2010 2:14 PM writes...
combichem is for the synthesis of small molecules.
DOS is for the synthesis of perturbagens.
48. Hap on July 13, 2010 2:17 PM writes...
I think that combichem generally takes a common skeleton with pendant functional groups and tries to append a variety of groups on it, so there is peripheral diversity but on a common skeleton. DOS is supposed to take building blocks that are functionalizable in various ways to get different skeletons (which, depending on the functionality that can be incorporated into the building blocks, can then be functionalized peripherally as well). Basically, I think DOS is combichem in which the cores are subject to the same generation of diversity as the periphery.
I would guess it's probably hard to generate diversifiable cores reliably, because the functional handles needed to put on peripheral diversity impede the DOS sequences - so although DOS should be able to generate a greater level of diversity, it probably can't because you can't functionalize the products as well. You should get greater diversity in chemical space from a DOS library because the cores are different, but I don't know.
49. Anonymous on July 13, 2010 3:21 PM writes...
I remember reading the original Schreiber paper on DOS numerous times, trying to see just what the difference between "CombiChem" and DOS was.
Basically, all I could understand was that they were the same thing except that "CombiChem" was done by stupid people and DOS was done by smart people.
50. cynical1 on July 13, 2010 3:53 PM writes...
ronathan and milkshake - I believe the drug you are talking about for ALS is Ceftriaxone. It does have good CNS penetration. I don't know about intracellular transport.
51. Phil on July 13, 2010 3:55 PM writes...
#34 "I don't agree with some of the posts here, which seem a little overzealous about discounting the academic approach to finding interesting molecules."
I never said academics don't find interesting molecules. The point has already been made that NPs have played a critical role in elucidating protein function, and many of the molecules discovered by DOS could serve that purpose as well.
Most of us in the chemical industry just cringe when we read a paper by someone like Schreiber that seems to suggest the next breakthrough small molecule drug is going to come from their revolutionary approach. There is a world of difference between "interesting molecule" and "drug candidate" and traversing that divide is the part that few academics understand.
52. adrien brody on July 13, 2010 4:40 PM writes...
Phil, Thanks for keeping the discussion going. Please call me Adrein.
Two things:
1. Correct me if I'm wrong: Has SLS started making claims at using DOS to discover new drugs? I thought he was going after "probes" or perturbogens. This is why I said 'interesting molecules', instead of drugs. I'm sure most would agree academia is not the place to do drug discovery, at least on purpose.
2. You're the rationale design guy, right? I love rationale design. Our lab does some. But you should take yourself down a notch. Cuz there are just a few instances where a design model doesn't behave the way it's supposed to. And it sucks when it's in the later stages of drug discovery. Our beloved blogger, Derek, writes about this now and again. Combichem, DOS, or whatever you want to call it, is supposed to fill in gaps in rationale design when little to nothing is known about a target. And, sometimes, this makes for good, fun, satisfying research! So relax, pleeez.
P.S. Did you see my abs in the latest Predators movie?
53. Phil on July 13, 2010 6:36 PM writes...
From Schreiber's 2009 JACS paper (doi: 10.1021/ja900414s)
"Small molecules are widely used for studying biology or
treating diseases. Their discovery increasingly relies on small molecule screening, although these studies have revealed the
inadequacy of screening collections based on natural products
and commercial vendor libraries. We have been exploring the
build/couple/pair strategy for the synthesis of transformative
small-molecule screening collections. These have properties that increase the probability of success in all facets of probe- and drug-discovery pipelines in which synthesis plays a role,
including discovery of initial leads, optimization of them, and
manufacturing of the optimized variant."
Sounds like a claim for DOS's transformative effect on drug discovery.
His fallacious argument is that commercial vendor libraries and NPs have failed (are inadequate). They produce hits on a regular basis. Biological activity comes cheap. Pharmacological suitability has to be worked out over several iterations.
As for your second remark, you should find a less snarky way to tell me something I already know, or I won't be keeping the discussion going for long.
54. adrien brody on July 13, 2010 8:31 PM writes...
haha, okay.
55. noname on July 16, 2010 10:32 AM writes...
I always equated DOS with "natural product-like", as did a lot of the Schreiber groupies at the latest CombiChem GRC, oops I mean High Throughput Chemical Biology GRC. So my first reaction to this paper was he was shooting himself in the foot, which I admire. But Derek's point about the Schreiberites arguing DOS occupyies the magic middle is disturbingly persuasive.
The real point is, all these theoretical arguments are attempts to address the fundamental shortcoming of our ability to explore the bioactivity of chemical space. If we could interrogate ten times the number of species for one tenth the cost, we wouldn't be making a lot of these arguments. Hmmm, I wonder if there is a technology that could do that...
56. JB on July 16, 2010 8:17 PM writes...
Are you are possibly at GSK formerly Praecis, noname?
57. ret on July 18, 2010 7:47 PM writes...
A comment which is a little late to the party but I don't think has been mentioned.
Over the last hundred years most natural products have been tested for antibiotic activity and general cytotoxicity. Our main problem is a general lack of good information on how these compounds perform in broad screens. I am sure as we increase the number of quality assays we will find natural products with broader activity.
58. Jeff on July 2, 2012 10:46 AM writes...
This company (usahealthresource.com) provides over 12,000 non-commercially available compounds (library) prepared from chemically untapped natural products by collection of HPLC column isolated compound peaks for your new drug lead discovery.
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text:
A darling of the international custom-sneaker world, Mark Ong sits at the desk of his Singaporean design studio. He's designing in his head while taking care of logistics: packing, weighing, and sticking stamps on a box of shoes created for a customer in the U.S.
"We do everything—all this real stuff, not just the design work. It's the punk, it's the aesthetic, it's the energy," he grins. "It's all part of what we do. I love it."
Ong is definitely a hands-on kind of guy. He takes sneakers from the likes of Nike and DC and paints, chops, and studs them in his own unique way—to the delight of collectors from Mexico City to Milwaukee, from his friend Jeffrey Koh at the local food court to Kobe Bryant—at anything from $250–$800 a pop.
"It's a bit weird, really. We can go anywhere in Singapore and not be recognized, but when we went to Mexico City for a DC launch there, the publicity people had done this massive Fly logo three stories high on the front of a warehouse for us, there were TV stations waiting to interview Mark, and we were driving around in a limo. It was crazy." - Sue-Anne Lim, Ong's wife
Crazy, maybe—but Ong admits he's never really been one for the ordinary life. He started his love affair with shoes when he was just a kid, a renegade 9-year-old skateboarder back in the late 80s. Ong and his friends—many of whom he still hangs out and skates with—would hit the street, make their own ramps, learn tricks, run away from the cops when they were spotted some place they shouldn't have been, and generally disappoint their parents.
"I was fascinated by the '80s American culture," Ong remembers. "I thought I was living in the U.S.!" Of course, he wasn't. His family was in Singapore, in the days when it wasn't yet a glossy city-state. "My dad was really keen for me to be a success. He wanted me to be a lawyer or a doctor," Ong says, "but I just wanted to do the things he didn't want me to."
He carried on with his skating, getting through shoes (Airwalks, Chuck Taylors) pretty fast on the boards. Unable to afford new pairs, he started patching them up with leather, rubber, bicycle tires, whatever he could get his hands on.
"What we were doing then was what we had to," Ong explains. "Skating brought us a discipline, and we just fixed up what we didn't have," he explains.
This creativity, and his ability to craft style out of minimal resources, led Ong to study at nearby Temasek Polytechnic for a degree in visual communications. Like life with his father, it wasn't all roses.
"We had one lecturer, Iskandar Jalil, a potter, a very hard man. If he didn't like what you had done, he would just kick it to pieces," Ong remembers. "That taught me not to take offense, but to look even more critically at what I'd done and be an optimist about the next time. That influence is still with me."
But now Ong has come full circle, doing the influencing himself. Wannabe interns write and Facebook him from all over Asia, and as far away as New Zealand, the U.K., and the U.S., begging to come and learn the art of sneakerpimping. International stars drop by too.
"In our last office on Haji Lane, we heard a knock on the door, and when we opened it, there were the guys from Linkin Park," laughs Sue-Anne. "Mike Shinoda invited us to their concert. It was great."
Kobe Bryant bought a pair of Nike Black Mamba customs from Ong; now Q-Tip, Don Johnson, and DJ Clark Kent proudly wear his sneakers—not bad for someone who used to dodge the cops in patched-up shoes.
After graduating from school, Ong continued skating, created a graffiti tag (Sabotage, or SBTG, which he now uses as his label) and worked in a sneaker shop. He developed into a real sneakerhead, buying at least two pairs a month.
"By the time I was 22 or so, I had 80 pairs," he grins. Then, in 2003, he entered a competition to customize sneakers on Niketalk.com. He won, and his world changed overnight. The resulting publicity scored him an immediate order for 72 pairs from a Tokyo retailer. "It was, like — boom! I didn't know what to do as I'd only done a few for friends before that, so I hired my friend Andy to help me," he says.
After that it was up, up, and up for SBTG. Since that first bull's-eye, he's worked with Nike, DC, adFunture, DJ Unkle; exhibited worldwide in the Finish Line gallery show; and established the highly successful SBTG business selling sneakers and the Royalefam clothing line.
When it comes to packaging and plastering on stamps, there's plenty of work for him and Sue-Anne. His wife says there's more to come. "Mark has enough creative ideas to last a lifetime," she says, smiling. "He doesn't like doing the same thing twice." The goal of her husband's design is twofold, she says: to create something both organic and empowering.
Ong agrees: "Royalefam stands for empowerment; I want people to share that when they wear my shoes."
Download The Red Bulletin iPad app now at http://www.redbulletin.com/ipad to read the full article.
Check out Ong's designs at www.royalefam.com and also catch the special Canon-SBTG feature video by No Average Joe at http://vimeo.com/channels/noaveragejoe#21735753


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It's the long lines, stupid
I went Christmas shopping this weekend, arriving at Macy's around 10AM. Even at this early hour, the cashiers were already overwhelmed with lines of customers six to eight deep. Nor was this phenomena entirely peculiar to Macy's the lines were everywhere.
Newsflash to retailers: long lines mean lost sales. The prospect of standing in line at shop after shop was discouraging enough for me that I abandoned the attempt, as I'm sure did many others.
In this dire moment for the economy, I suggest that retailers think outside the box. Temporary staffing agencies are ready and waiting to provide retail cashiers on a moment's notice.
Too expensive, you say? Not if you think in terms of what those lost sales are worth. Given the typical retail markup, it would take no more than one or two otherwise lost sales per hour to pay the entire cost of that extra salesperson.
Temps won't be sufficiently well-trained or sufficiently presentable, you say? You underestimate staffing agencies. The good ones and, yes, you do need to develop a relationship with a good one, not just call one at random when you are desperate the good ones do plenty of screening.
You say it will upset your regular workers to have temps come in? Tough. In the current environment, we're talking about survival. The first 80% or so of your sales just covers your costs. It's that last part you need to justify the existence of your business, and to grow and prosper. If your company culture is antagonistic to temporary workers, put the word out that your company culture has just changed. You need those sales that are walking out the door in frustration.
Out of curiosity, I tried googling for temporary staffing agencies specializing in cashiers. Near the top of google's sort was Cashiers Unlimited, an Orange County CA staffing firm. But you need not find a specialist by our estimate about a third of all staffing firms provide salespeople, so a few calls should get you the help you need.
The end of year is a time for reflection, redemption and self-correction. Scrooge became a better man this time of year. So did George Bailey. Retailers, I beseech you, as the voice of recession present, or as an observant angel if you prefer, add some temporary cashiers immediately. The hour is not too late. You may yet turn the tide of declining sales. You may yet save your business, even perhaps boost the economy. Just get some more damn cashiers.


text: A short one today, just to share with you this video by London Session Productions introducing Senhor Prundêncio's SS15 collection, "Homonima". It is filled with dreamy slow-mo and double exposures but fear not, this isn't another fashion film cliché. When I first received the link to the video, I watched it five times just to listen to the music (Casino Lisboa by Dirty Beaches). The following ten screenings mainly involved me staring at the model's silky hair. Serious competition for Jon Kortajarena there.


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There's a high-value Carseat Canopy coupon code that's valid for $49.95 off any Carseat Canopy or $50 off other purchases. Since all Carseat Canopies are priced $49.95, you'll get one FREE after coupon and just pay shipping.
This would make a great (and frugal) gift if you know anyone with a new baby or having a one soon!
- Visit Carseat Canopy
- Add any Carseat Canopy valued at $49.95 to your cart
- Enter the Carseat Canopy coupon code ABABY912 upon checkout
- Pay $12.90 shipping and handling
This Carseat Canopy coupon code will also take $50 off any The Whole Caboodle purchase. Starting as low as $79.95, you can get the following for as low as $29.95 plus shipping and handling:
- Minky Slip Cover
- Minky Head Support Pillow
- Baby ap Blanket with Minky Lining
- Replacement Umbrella with Minky Lining
- Carseat Canopy with Mink Interior and 100% Cotton Outer
Not sure when this coupon expires, so if you're interested don't wait. There are many easy ways to get free stuff online if you know where to look!
(Thanks Free Sample Freak!)


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Being the only doctor in my family, I am constantly quizzed by relatives both close at home and by the distant ones, about how one can stay healthy given their busy lives. Now, we all know what an understatement "busy lives" is, when the people that I am talking about happen to be residents of San Diego, a county with over 1.6 million overweight or obese people! With a fast paced life, it simply becomes almost impossible to maintain a healthy diet, which in my opinion is the most important key to a healthy body and lifestyle.
Bistro MD coupon codes –>
So every morning you are either stuffing yourself with a burger and a milkshake or juice bought from a drive-through while driving your car, OR stuffing yourself with whatever you could find in the refrigerator at your home. In both scenarios, a commonality exists—that of an unplanned, unhealthy diet. There is simply no time or motivation left to prepare well-balanced and healthy food, if you are going to have to juggle readying your kids, giving them a ride to school, driving yourself to work and then after a long day at work, come home dead tired.
Considering all of these complexities, the responsibility of me as a doctor to prescribe methods to maintain a healthy lifestyle to my family and clients, increases manifold.
Is there a way then, to escape this daily grind and emerge healthy every day?
As a doctor, nothing gives me more pleasure than informing my clients (I do not like to call them my patients) that the answer is a solid YES! There is a healthy diet, that promises to fulfill every dietary need of your body and one which does not require any special effort (other than following the diet strictly, of course) from your side! And it is called San Diego diet food delivery plan by BistroMD.
Like actress Camille Guaty, I love BistroMD.
What is a San Diego diet first of all?
It is a diet developed by Bistro MD, that makes losing weight easy without having to give up on your favorite dishes! Bistro MD is a diet food delivery service operating in San Diego (and some other states as well), where registered dietitians and award-winning chefs work together to develop some of the most healthy and amazing gourmet dishes. These people have a passion for good food.
And let me tell you, this is not your typical diet food. The food is comparable to that you could find in good restaurants in San Diego. Only the freshest ingredients sourced from local farmers, fishermen and ranchers are used in preparation of the food at Bistro MD following strict nutritional guidelines. Under the Bistro MD diet food delivery service, you can avail diet food programs that are especially developed for men and women separately. The best thing about the BistroMD diet food service? It is 100% healthy, requires minimum cooking by you and is extremely affordable!
Is it Worth the Cost?
It is for me! Consider for a moment the time it takes you to go grocery shopping, cook, wash dishes, and count calories. And even if you have time to do all this, you also need to know how to cook healthy. BistroMD does all this for you.
Special Inside Tip: To get a discount on the diet food programs by Bistro MD, you can avail some very useful Bistro MD discount coupons and Bistro MD discount codes, found easily on the Internet!
Imagine getting up in the morning or coming home late at night from work, and not having to worry about what to eat for breakfast or where to go for dinner! Under the San Diego diet food delivery plan from Bistro MD, you get pre-packaged meals delivered right at your doorsteps with a variety of gourmet dishes to choose from. So even as you chomp on that Beef Stroganoff, you can just forget about how much calories you must be taking in your meal. This is because each of the food - whether sea food, meat or vegetarian dishes, all of them are prepared under strict medical supervision and count less than 500 calories. While the menu has the best California meats, the Bistro MD diet also offers modified vegetarian diets for people who are averse to meat, so you do not have to worry if you cannot find a vegetarian dish on the menu.
Worried that this "gourmet" food delivery system might be pricey? Well, it is NOT.
Enrolling in a 5-day program with the Bistro MD standard plan costs $149.95 for the first week (i.e. about $30 a day for 3 gourmet meals), and $169.90 (i.e $30 + an additional $4 per day for 3 gourmet meals) in the following weeks.
Enrolling in a 7-day program with the Bistro MD standard plan is the more economical option of the two, and costs $179.95 for the first week (i.e. about $25 a day for 3 gourmet meals), and $199.90 (i.e. about $28.50 per day for 3 gourmet meals).
Still think it is too costly? Well you can always use one of those precious Bistro MD coupons and Bistro MD discount codes, that are easily available on the Internet, to get a further discount on these plans.
The San Diego diet food by Bistro MD is all I need to stay fit and energetic, a viewpoint that is now shared by half my relatives as well as my clients. There now exist two things that I love most about San Diego—its ever pleasant climate and my favorite San Diego diet food by Bistro MD.


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Today is a rather busy day for this Muse.�� How's your day been so far?�� This morning I was trying to quick dab and go makeup and was looking through some of my older, mixed up makeup draws and I happened upon some of my Mirenesse collection.� Whoa totally a break down moment as I forgot how much I enjoyed the brand back in the day.
In honor of my dash and go look I created today using Mirenesse I thought I'd do a little Product Musing about it.
Gather round kids let's Muse Mirenesse.


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We make perfect sense
Sixth Sense Communications & PR Consultancy is a boutique Public Relations agency that specialises in providing PR Consultancy and Marketing Communications Consultancy services for clients in the Food & Beverage, Consumer Lifestyle, Hospitality and Arts industries.
Established since 2001, Sixth Sense aims to boost clients' businesses through executing strategic PR campaigns and developing effective marketing communications tools. Clients can expect a high standard of professionalism, swift and creative execution, prompt delivery and above all, a dedication to personalised client servicing. Don't just take our word for it – read what our clients have to say under our testimonials.
Sixth Sense also possesses a proven track record of garnering excellent results through customising successful communication strategies for many satisfied clients.


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Rescue Teams Search For Missing 12-year-old British Boy On Porquerolles Island
French gendarmes and policemen prepare on October 29, 2012 to search... News PhotoAdolescence,Adult,Boys,British Culture,Child,Cycling,Drowning,Elevated View,France,French Culture,Gendarme,Gendarmerie,Horizontal,Law,Police Force,Porquerolles,Preparation,Searching,Var,Young Adult,Young MenPhotographer GERARD JULIENCollection: AFP 2012 AFPFrench gendarmes and policemen prepare on October 29, 2012 to search for a 12-year-old British boy, who disappeared on October 27, on Porquerolles island, southeastern France. Sixty soldiers and three civil security dog-handlers from Brignoles are paricipating in the search. AFP PHOTO GERARD JULIEN (Photo credit should read GERARD JULIEN/AFP/Getty Images)


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Get 12 iPad & iPhone editions for just £12
Only £1 an Issue!
By GQ magazine Photos by Dan Matthews 09 November 11
Bi-metal was once a byword for the go-go Eighties, but guess what - it's back. And how. These two-tone designs in classic silver, rose red and burnished gold make any wrist worth a second glance.
Imperiale Bi-Colour by Chopard, £6,670. chopard.com


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So it's time, I suppose, to make a simple declarative statement. There's no such thing. This is not a craze. This is not a fad. There are some exceptions, but overall, this isn't a get rich quick scheme for us. It's probably not a get rich at all scheme for most of us.
It's a small part of a growing contingent of artisans. Talented and hardworking people who want to show you something new, or maybe something old. These are people you should take seriously. Good food should not be treated as a fad. Fads come and go. I want good food to stay.
It is an exciting time to live in Columbus. Food is getting better, amazing even, and it's not just a rash of cupcake shops because cupcakes are in. It's people blazing new trails or doing old comfortable things in new and exciting ways.
I had a donut today. A donut in solid contention for the best donut I've ever had, and I've had a few in my day. The concept seems so simple and it is, in a way. This is an item you can find within one or two miles of where you sit right now. This donut, however, towers well above all others and not because it has maple and sausage in it, but because it is crafted in a way that makes it better. It's not overproofed, so it isn't just a wisp of sweet, airy regret. It has some chew, an appropriate density. The oil temperature was obviously closely monitored, because it wasn't greasy or heavy. The sweetness wasn't over the top, leaving room for you to enjoy the other flavors. Someone loved that donut (before me), and wanted to share it with you. This is what the food culture is becoming, and it's a great thing. This is an idea we should get behind. Maybe there will be a donut craze...
I'm pretty sure that Dan, on That Food truck, is insane. He isn't just bringing you a wonderful product, but he's so concerned about the quality of his product that he is cutting and curing his own meat. Your meat, really.
It's not a second thought to most people, as they are loading up on scalding hot hodduk and dduk boki from Laura at Ajumama, how much time and effort is involved in crafting that product from the ground up. Kimchee(s) and (eese), sauces, marinades... sourcing ingredients alone has to occupy hours.
As far as we're concerned... there isn't much to say beyond tater tots. So. Many. Tater Tots. Then, we have the rest of the menu to prepare, also from scratch, down to the bacon.
It's control. We can all tell you, where pretty much every ingredient on the truck came from specifically down to the ingredient. We're accountable, because we made it, or we know who did.
There is a clear picture of where this goes. Portland, LA, Manhattan, DC... trucks are now an integral part of the restaurant culture of those cities. The food coming off of these trucks deserves to be taken seriously and held to the same standards; judged at the same level as any brick and mortar.
If you ask most of us, I'm sure you'll find that we're up to the challenge.
Check out our offerings and schedule www.swoopfood.com
Try a little Seoul food at it's best www.ajumama.com
See what's happening with the fellas on the other Big Red, www.thatfoodtruck.com
Find out when and how to get the best damned donut you've ever had in your life www.destinationdonuts.com


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Country Life
Make puppets from shadows, find hidden clues, give a guided tour or design your own house. These are just some of the things you can do at YOUR museum.
Clubs run over four Saturdays for two hours each day. For details on our latest club check the Calendar of Events.
Make a Booking
Family Activities and Resources in other museums:
Decorative Arts & History
Natural History
Tuesday - Saturday: 10am - 5pm
Sunday: 2pm - 5pm
Closed Mondays, Christmas Day and Good Friday
+353 1 6777444
Get directions to all four sites


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Results: You Made It Quotable!
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- Cat enthusiastically sets up a trip line for the family dog. — fuzzles
- Fluffy fell for the ole "toy on a hidden string" practical joke once again. — lostinsomniac
- Fluffy didn't know that unraveling his owner's robe meant never being the same again. — CaterpillarGirl


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|Rio to spend $1.8b on Yandi
|Friday, 23 November 2012 14:01
Rio Tinto's biggest iron ore mine just got bigger. Under a deal with the WA Government, Rio will splurge $1.8 billion on an upgrade of its Yandicoogina mine in the East Pilbara.
Part of the mining giant's push to produce 353 million tonnes of ore in WA by the first half of 2015, the Yandi expansion will increase production at the mine from about 53mt a year to a peak of 60mtpa and extend the asset's operating life "well into the 2020s".
Yandi is so big that it is one of the few mines with iron ore marketed under its own name, a contrast to the industry-wide practice of blending different ore types and qualities from smaller operations.
The expansion, which will replace depleted pockets of the site, also ensures Rio retains bragging rights over its Hope Downs joint venture partner Gina Rinehart, who is rushing to build her own 55mtpa mine at Roy Hill.
Premier Colin Barnett said the investment demonstrated the resilience of WA's mining industry.
"The iron ore industry will remain a major driver of investment and employment in WA into the future," the Premier said in a statement.
"As well as creating hundreds of construction jobs, this proposal will add eight years to the life of the Yandicoogina project, providing continued employment for about 1000 people. It will also . . . add to the state's royalty income."
The royalty boost will more than offset some of the hit the State's coffers took on Monday when Mr Barnett announced he would back a royalty exemption for WA's magnetite producers.
The move was partly designed to calm aggrieved Chinese mining companies that are angry their expensive WA investments are yet to show a return while being hit by the carbon tax and slow infrastructure developments, including Oakajee port.
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Michelin Pilot Sport SC Scooter Tires
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