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The Telomere Effect – A Revolutionary Approach to Living Younger, Healthier, Longer
telomere_brochure (1) by Nobel Prize Winner, Elizabeth Blackburn, PhD and Elissa Epel, PhD
August-September 2017 Events: YOUTH Skin Care and PERFORMANCE Sport Nutrition
We are excited to share the science and the results of our brand new lines: YOUTH Anti-Aging Skin Care and PERFORMANCE Sport Nutrition!
Please join our team's events. We ask you to RSVP before coming. All times are in Central Time.
- YOUTH Skin Care. Demo Party. August 19th, Saturday. West Plano, TX. 1-2pm or 2-3pm or 3-4pm.
- SOCIAL DINNER. August 19th, Saturday. 6:30-9:30pm.
- YOUTH Skin Care. Online Zoom Presentation. August 20th, Sunday. 6-6:30pm
- ENERGY Performance Sport Nutrition. Online Zoom Presentation. August 22th, Tuesday. 7-7:30pm.
- YOUTH Skin Care. Demo Party. August 27th, Sunday. Murphy, TX. 2-3:30pm.
- YOUTH Skin Care. Wine Demo Party. September 8th, Friday. Murphy, TX. 6-8pm.
- YOUTH Skin Care. Demo Booth. September 30th, Saturday. Murphy Maize Days, Murphy, TX. 10am-6pm.
- 5×5 RESET. Online Zoom Presentation. Every Monday. 7-7:30pm.
- BUSINESS OPPORTUNITY. Online Zoom Presentation. Every Monday 8-8:30pm.
To RSVP, please e-mail at firstname.lastname@example.com or respond via Calendar Page.
If you are not able to join any of these meetings, you can review online information on YOUTH Skin care HERE or PERFORMANCE Sport Nutrition HERE.
For questions or schedule a personalized appointment, please call/text (972) 489-7449, email email@example.com. Nadya Tatsch
!! Referral Program: YOUTH Skin Care – refer 2 people who purchase YOUTH Advanced Anti-Aging Regiment, receive yours for $30; refer 3 people, receive yours FREE.
We are excited to share this amazing natural wellness possibility with you and look forward to your stories!
Help Me Support St. Jude's Children on My Birthday
June 11th is my birthday! To celebrate, during my birthday month I want to give a gift that is bigger than me and donate money to children who can't help themselves. Alone I can only donate so much but together we can donate so much more!
June 1 through 15th I am asking for your help to raise as much as we can for St. Jude's hospital. St. Jude Children's Research Hospital is a pediatric treatment and research facility focused on children's catastrophic diseases.
Two ways to contribute:
1. Buy some healthy products for yourself and help kids at the same time. I will donate 10% of sales.
Shaklee is #1 natural nutrition company in the U.S. (with 100 years of heritage) providing natural nutrition supplements, weight-management products, beauty products, and household products. http://thenaturalpower.myshaklee.com/us/en/shop
2. Donate directly (just let me know) https://www.stjude.org/give.html
I thank you for your heart and accepting my call for support St. Jude's children!
Women's Health Events (May, 2017)
Women's Health Chats via ZOOM to inspire Healthier Lives!!!
5/19 Fri noon-12:30 5/24 Wed noon-12:30 5/25 Thurs 7-7:30pm
Join in & INVITE:-) Know any women who take care of others and would benefit in talking better care of themselves??
We will address this and promise to inspire those who come!!!
Join from PC, Mac, Linux, iOS or Android: https://zoom.us/j/9188471767
Or join by phone: +1 646 568 7788 (US Toll) or +1 415 762 9988 (US Toll)
Meeting ID: 918 847 1767
RSVP: text 972-489-7449 or email firstname.lastname@example.com (Nadya)
My Story and Shaklee Sport Nutrition Testimonial (for runners)
My Run Story
In 2014 I could hardly run 5K. I was hurting and it was not pretty. It shaped my decision not to run longer distances. But I had 2 motivated people in my fitness life: one who asked to join for weekly runs in the park (so I did) and another one made a joke (and planted a seed of possibility in my head) to run 10K.
Soon enough I ran 5K formal run and finished 6th in my category. I was hurting. But I didn't stop running; I had regular runs and work outs. In 2016 I tired a formal 10K run ("I Am Second"); why not; just a few more miles. I finished 6th in my category.
In mid December of 2016 I created my first dream/goal board. I put "Half Marathon" in it as just for fun. Why not It is a dream board after all. On January 1st 2017 my family ran Commitment Day 5K at our local gym. As soon as I completed the run, a sign caught my eye: 'every day is leg day – Half Marathon 12-week Training." I registered. In 3 months, with a proper training, some minor body adjustments, support #teamnoexcuses, I moved up from 10K to 13.1 mile.
On March 19th 2017 I ran 13.29 mile Rock and Roll Half Marathon with a 10 min per mile and finished at 2:10:49. My coach said, 'your first half was faster than my first half! I think it's a testament to your overall healthy lifestyle, and you train to be much more than just a runner. I'm definitely looking forward to seeing you at the finish line of a full marathon in 2017."
My Shaklee Sport Nutrition Testimonial (for runners)
I was smart on how to treat and supplement my body. I knew Shaklee had been providing support for over 136 Olympic medalists. Shaklee created AstroAid for astronauts in 1993 and has powered 7 out of 25 world ventures. It's gotta work for me!
- Few months up to a week before the run. 7 Days Healthy Cleanse or 5×5 Reset diet. To help lose unnecessary weight, help digestion and natural energy production, cleanse your body from toxins. It's a great foundation to build your strength and training on.
- 2 days before the run until 2 days after the run, I took 2/day Join Pain Complex to help with joints, 2/day Omega Guard and 10/day Alfalfa to reduce possible inflammation. A day before I also used a carbohydrate diet.
- A morning of the run. Right after wake up, glass of lemon water. 5 min strength exercise and stretching. 8 ounces of Performance. Energy tea upon desire. Oatmeal and 180 Meal Bar.
- During the run. 9 ounces of Performance was enough to keep me hydrated (sipped on every half a mile) so I didn't need to slow down for water stations. I had 2 Energy Chews in my pocket and used one during the run.
- Right after the run. 18 ounces of water. One banana.
- An hour after the run. Big nutritious lunch.
- Upon arrival home (2 hours after the run). Cool tub to help reduce inflammation. Joint and Muscle Pain Cream. 6 ounces of Performance.
- And of course, Vitalizer was my regiment along the way!
I know I was able to find the EDGE because I treated and supplemented my body to the full potential. I know with Shaklee I can do it all in my lifetime!
Live Well with Shaklee (with Spanish Strategy Session)
You are invited to the following event:
Event to be held at the following time, date, and location:
Friday, February 17, 2017 from 7:00 PM to 9:30 PM (CST)
Hilton Garden Inn
1001 W President George Bush Turnpike
Richardson, TX 75080
Charlene Fike, Shaklee Presidencial Master Coordinator y Shaklee México Consejo Asesor, encabezará esta emocionante reunión de tres partes. / Shaklee Presidential Master Coordinator and Shaklee Mexico Advisory Board, will lead this exciting 3-part meeting.
6:30-7:00PM Inscripción (ahorra con tus entradas en línea) / Registration (Save by getting your tickets online)
7:00-7:40PM Shaklee Reunión de oportunidades en español / Shaklee Opportunity Meeting in Spanish
7:40-8:00PM Meet & Greet con comida y bebidas. Santo Guacamole! / Meet & Greet with food and beverages provided. Holy Guacamole!
8:00-9:00PM Sesión de Estrategia: Cómo acercarse a la comunidad hispana local, utilizar los actuales incentivos de Shaklee y aprovechar el relanzamiento de Shaklee México.
8:00-9:00PM Strategy Session: How to approach the local Hispanic community, utilize the current Shaklee incentives and leverage the re-launch of Shaklee Mexico.
We hope you can make it!
Charlene Fike, Shaklee Presidencial Master Coordinator y Shaklee México Consejo Asesor, Jack Peskuski, The Shaklee Possibility Team and The North Texas Shaklee Association
Shoulder Pain Relief
There is nothing worse than shoulder pain. It hurts every time you try to lift your arm. Is there anything you can do to quickly relieve shoulder pain?
Julie Donnelly, LMT is a Deep Muscle Massage Therapist with 20 years of experience specializing in the treatment of chronic joint pain and sports injuries.
Shoulder Pain Relief
What Causes Shoulder Pain And How Do You Treat It?
Author: Julie Donnelly, LMT – The Pain Relief Expert
Editor: Dr. Stephen Chaney
Shoulder joint pain was preventing a father from throwing a baseball to his son and he was very distressed. He was complaining to a friend of his, who is a client of mine. Even though he had been recommended to go for surgery, his friend convinced him to give muscle therapy a chance. So yesterday "Frank" came in to see me.
He demonstrated throwing a ball, but he could barely lift his arm, and he definitely couldn't bring it back. He said that his time with his son is precious to him, and that their favorite pastime is throwing a baseball. If I could just help him do that he would be happy.
Why Muscles Cause Shoulder Joint Pain
Your shoulder has more muscle attachments than any other joint in your body. A muscle pulls in only one direction, muscles never push. When you consider all the movements you can make with your shoulder and arm, you can see why there are so many muscles involved.
The important fact is when a muscle is shortened from spasms, it will cause pain at its insertion point on the bone at the shoulder joint.
The reason is evident when you consider an analogy I frequently use to describe joint pain. If you pull your hair at the end, it hurts at your scalp. However, you don't need to massage your scalp, you don't need to take aspirin for the headache, and you definitely don't need brain surgery! You just need to let go of your hair!
The exact same thing is true to stop your shoulder joint pain. You just need to let go of the tight muscles that insert into your shoulder.
The Muscles That Cause Shoulder Joint Pain
Perhaps you've heard of the rotator cuff muscles: supraspinatus, infraspinatus, teres minor, and subscapularis. However, my experience has proven that there are a lot of other muscles that aren't considered shoulder muscles, but that will cause shoulder joint pain. Those muscles are your biceps and triceps, your levator scapulae, and your latissimus dorsi (among others).
While not rotator cuff muscles, your biceps and triceps both originate deep within your shoulder joint. The other two muscles will move your shoulder blade (scapula). When they are in spasm, which shortens the muscle fibers, it will cause a strain to be placed on the muscle tendon, which will then cause a strain, and pain, on your shoulder joint.
How To Release Shoulder Joint Pain
There are so many muscles involved in shoulder joint pain that I couldn't show all of them here, that's why I wrote Treat Yourself to Pain-Free Living.
However, I do want to show you how to do one treatment, for your infraspinatus muscle.
But first, back to "Frank." I treated each of the muscles mentioned, and then using Treat Yourself to Pain-Free Living, I showed him how to treat each of the muscles of his shoulder. He was thrilled! He could easily, and painlessly, throw a baseball. In fact, he went outside and tried it just to make sure.
The key is self-treatment. Muscles will again shorten up until you train them to be their normal, longer, length. You can't go to a therapist as often as necessary to make the muscles return to their proper length. However, you can treat yourself every day! That's how you really stay flexible and pain-free — frequent self-treatment.
An Easy Treatment For Shoulder Joint Pain
The following pictures are from Treat Yourself to Pain-Free Living
Step 1: To treat your left infraspinatus, put the Perfect Ball in your right hand and bring it under your arm, going back as far as you can so you are on top of your infraspinatus muscle.
Step 2: Lean into a wall. Find the "hot spot" (the spasm). You'll know you're on it because it will hurt.
Step 3: Stay still for 30-60 seconds, then move a little bit to roll the ball back and forth on the muscle.
Treat Yourself to Pain-Free Living will explain this further, and will give you pictures and descriptions of how to self-treat the other muscles that cause shoulder joint pain.
It just takes a little bit of direction and effort to learn how to self-treat. But, I've seen so many times that you CAN stop shoulder joint pain!
Wishing you well, Julie Donnelly
These statements have not been evaluated by the Food and Drug Administration. This information is not intended to diagnose, treat, cure or prevent any disease.
About The Author
Julie Donnelly is a Deep Muscle Massage Therapist with 20 years of experience specializing in the treatment of chronic joint pain and sports injuries. She has worked extensively with elite athletes and patients who have been unsuccessful at finding relief through the more conventional therapies.
She has been widely published, both on – and off – line, in magazines, newsletters, and newspapers around the country. She is also often chosen to speak at national conventions, medical schools, and health facilities nationwide.
Check It Out!
If you would like easy to follow instructions on how to relieve joint pain and muscle tightness from head to toe click here to check out Julie Donnelly's Pain Relief System today. Whenever, I have pain and stiffness I use her techniques. They work!
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Courtesy of 2014 Health Tips From The Professor.


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Michella and Eddy - Crete Wedding Photography
Dream Destination Wedding in Crete, Greece by award-winning wedding photographers Liam Collard Photography.
Crete Wedding Photography – On a stunning summers day on the island of Crete, couple Michella and Eddy from Abu Dhabi had the joyous moment of becoming man and wife in the village of Agios Nikolaos, in Plaka. The ocean front location provided a wonderful backdrop for their bride and groom portraits, with dramatic scenery all round.
Follow Michella and Eddy's incredible wedding day journey through the Greek islands of Santorini and Crete on our blog.

subset: commoncrawl


text:
Inside Larry and Sergey's Brain
Format: Hardcover
Language: English
Format: PDF / Kindle / ePub
Size: 9.00 MB
Downloadable formats: PDF
Pages: 256
Publisher: Portfolio; First Printing edition (September 17, 2009)
Karl Marx Collective: Economy, Society and Religion in a Siberian Collective Farm (Cambridge Studies in Social and Cultural Anthropology)
The big six: The selling out of America's top accounting firms
Telecommunication Services in Sub-Saharan Africa: An Analysis of Access and Use in the Southern Volta Region in Ghana (Development Economics and Policy)
Occupational Health Practice
Ron is serving as the Construction Quality Acceptance Manager for this project. The $80 million project includes upgrades to Loop 1604 from Bandera to Culebra, and is funded by the Texas Department of Transportation (TxDOT). There has also been a $40 million extension to the project that includes upgrades to SH 151 at Loop 1604. ELVIS (Electronic Laboratory Verification Information System) – An award-winning, web-based construction management tool developed and customized by RKI for each project to meet specific needs and to support our Quality Management Services The Russian Enterprise in Transition: Case Studies (Management and Industry in Russia Series). Unify and simplify snapshot management with a single console for all the top hardware storage vendors — meaning you no longer require a different toolset or low-level scripting expertise for each storage array. Our built-in reporting and alerting lets you perform more detailed utilization and capacity planning for your hardware snapshots Logistics Clusters: Delivering Value and Driving Growth (MIT Press). Mobile money transfer process (Adapted from [15]). money to their intended receivers irrespective of their actual location or receive through cash-out processes Summary: Clutter-Proof Your Business - Mike Nelson: How to De-Clutter Your Business and Why You Should Do It. Look at the categories identified above, and try to collect anything that fits into a category. Also do a quick assessment of the potential usability of the item. For example, in one company I looked at, they had an old project management intranet site. I was told "There is lots of good stuff there." When I was able to resurrect the site, most of the links were broken, and much of the documentation attached to the site no longer existed Improving Rural Mobility: Options for Developing Motorized and Nonmotorized Transport in Rural Areas (World Bank Technical Papers). We work at the regional and local scale in rural, suburban and urban environments. Read our new Services Brochure to learn how we can help you. Green infrastructure is made up of the interconnected network of waterways, wetlands, woodlands, wildlife habitats, and other natural areas; greenways, parks, and other conservation lands; working farms, ranches and forests; and wilderness and other open spaces that support native species, maintain natural ecological processes, sustain air and water resources and contribute to health and quality of life (McDonald, Benedict, and O'Conner, 2005) The Sweet Side of Little Rock: A History of Candy Making in Arkansas.
Download Inside Larry and Sergey's Brain pdf
The Aircraft Designers: A Grumman Historical Perspective (Library of Flight)
Water, Electricity, and the Poor: Who Benefits from Utility Subsidies? (Directions in Development)
Building IBM: Shaping an Industry and Its Technology (History of Computing)
Public Expenditure Review of Armenia (Country Studies)
Near Miss Reporting as a Safety Tool
Skunk Works: A Personal Memoir of My Years of Lockheed
Infrastructure Finance in Europe: Insights into the History of Water, Transport, and Telecommunications
Implementing Energy Subsidy Reforms: Evidence from Developing Countries (Directions in Development)
Chemistry of Change: Problems, Phases and Strategy
Future of Audio and Video Markets As Presented to Congress (Media and Communications - Technologies, Policies and Challenges)
Institutions and the Evolution of Modern Business
Climate Variability and Water Resources Degradation in Kenya: Improving Water Resources Development and Management (World Bank Working Papers)
Kaizen Strategies for Successful Organizational Change: Evolution and Revolution in the Organization
A Place to Live and Work: The Henry Disston Saw Works and the Tacony Community of Philadelphia
Lebenthal On Munis: Straight Talk About Tax-Free Municipal Bonds for the Troubled Investor Deciding "Yes...or No!"
Developing Headquarters Guidance for Army Installation Sustainability Plans in 2007
The Depths of Russia: Oil, Power, and Culture after Socialism
Rocket Fuel: The One Essential Combination That Will Get You More of What You Want from Your Business
Mitigating Vulnerability to High and Volatile Oil Prices: Power Sector Experience in Latin America and the Caribbean (Directions in Development)
The Nokia Revolution : The Story of an Extraordinary Company That Transformed an Industry
German Aircraft Industry and Production: 1933-1945
Marcus's economics: The value and grown up double theory


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BlueHost Coupon
Bluehost is one of the renowned webhosting companies in the world. Bluehost is internationally known because of the quality services it provides to its clients. Some of these services are free and unlimited. One of the unlimited packages that Bluehost offer to its clients is the IMAP/Secure IMAP E-mail Support.
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Order by: most recent most popular relevance
Massive automotive recalls continue to grab headlines and raise concerns industry-wide. Recalls of light vehicles topped 50 million units in 2016
The recent decisions of the USPTO Patent Trial and Appeal Board (PTAB) granting Celgene's requests for rehearing in parallel Inter Partes Review
The introduction of near autonomous vehicles to public roadways is set to completely revolutionize the way humans and goods navigate cityscapes in the
Certain job advertisements have drawn media scrutiny in recent weeks, including dozens of postings seeking applicants with a "neutral" accent for
We have previously discussed how the Department of Labor (DOL) often issues guidance to assist employers in applying and complying with the DOL's
Congress is now back in session and, once again, focus has turned to health care. With all eyes on returning health care reform to the forefront, a
China is already the largest automotive market in the world, and by some estimates, will have more than 30 million annual vehicle sales by 2020. Thi
It's been over a year since the Consumer Financial Protection Bureau (CFPB) turned the real estate settlement services industry on its head by
In Southwire Co. v. Cerro Wire LLC, the Federal Circuit upheld the USPTO decision rendered in an inter partes reexamination proceeding that found
This year, India celebrates Diwali on October 19, 2017. "The Festival of Lights," as Diwali (or Deepavli) is commonly called, is celebrated across


text:
a nuclear reactor using water as coolant and moderator, steam being produced in the reactor itself: enriched uranium oxide cased in zirconium is the fuel BWR
Tagged: b
Read Also:
- Bokeh
noun Examples
- Boke
verb to retch or vomit noun a retch; vomiting fit Historical Examples The Art or Crafte of Rhetoryke Leonard Cox Shakespeare Jest-Books; Unknown Two Dyaloges (c. 1549) Desiderius Erasmus The Earliest Arithmetics in English Anonymous The Boke of Noblesse Unknown The Path-Way to Knowledg Robert Record The Mathematicall Praeface to Elements of Geometrie of Euclid […]
- Bokhara-clover
white melilot.
- Bokhara
Bukhara. Historical Examples Famous Men and Great Events of the Nineteenth Century Charles Morris Stories by English Authors: Orient Various Clovers and How to Grow Them Thomas Shaw Historical Sketches, Volume I (of 3) John Henry Newman The Diary of a Hunter from the Punjab to the Karakorum Mountains Augustus Henry Irby Genghis Khan, Makers […]


text:
Bike Ride
938 ft
- Begins in:
- Franklin Lakes, NJ, United States
- Created By:
- sleeeepguy Best Time: 1:22:00
- Description:
- This is a 25.68 mi Bike Ride in Franklin Lakes, NJ, United States. The Bike Ride has a total ascent of 938.1 ft and has a maximum elevation of 526.12 ft. This route was created by sleeeepguy on 09/06/2007. View other Bike Rides that sleeeepguy has done or find similar maps in Oakland.
- Type:
- Bike Ride


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text:
|Publication number
|Publication type
|Application number
|Publication date
|Oct 25, 1977
|Filing date
|Sep 2, 1975
|Priority date
|Sep 2, 1975
|Publication number
|Sie-Yearl Chai, John P. Yardley
|Original Assignee
|American Home Products Corporation
|Export Citation
|BiBTeX, EndNote, RefMan
|Patent Citations (2), Referenced by (1), Classifications (11)
|External Links: USPTO, USPTO Assignment, Espacenet
The structure of the growth hormone release inhibiting factor, somatostatin, has been determined by Brazeau et al., Science, 179, 77(1973). Several techniques for synthesizing somatostatin have been reported in the literature, including the solid phase method of Rivier, J.A.C.S. 96, 2986(1974) and the solution methods of Sarantakis et al., Biochemical Biophysical Research Communications 54, 234(1973) and Immer et al., Helv. Chim. Acta, 57, 730(1974).
In accordance with this invention, there is provided a growth hormone release inhibiting compound of the formula; (Gly3 --Ala)1 -Somatostatin, and simple amides thereof as well as the non-cyclic form of the heptadecapeptide, the protamine zinc and protamine aluminum adducts, non-toxic acid addition salts thereof, and protected intermediates useful for the synthesis of the heptadecapeptide. The heptadecapeptides of this invention are useful in the treatment of conditions characterized by excessive growth hormone production, such as diabetes mellitus and acromegaly.
The heptadecapeptides of this invention present the amino acid sequence: ##STR2## in the [6-17] cyclic form and are devoid of the disulfide linkage in the linear form, the group R representing hydroxyl, dimethylamino alkylamino of 1-5 carbon atoms or phenethylamino. The protamine zinc and protamine aluminum derivatives of the heptadecapeptide represent derivatives conventionally derived from polypeptides for characterization and administrative purposes. The acid addition salts of the heptadecapeptide are derived from both inorganic and organic acids known to afford pharmaceutically acceptable non-toxic addition products, such as hydrochloric, hydrobromic, sulfuric, phosphoric, maleic, acetic, citric, benzoic, succinic, malic, ascorbic acid and the like.
The heptadecapeptides of this invention are prepared by solid phase methodology, employing as the initial reactant the fully protected peptidoresin R1 -Ala-Gly-Cys (R2)-Lys (R3)-Asn-Phe-Phe-Trp-Lys (R4)-Thr(R5)-Phe-Thr (R6)-Ser (R7)-Cys (R8)-O-Resin, in which each of the protective R groups are defined, infra. Deprotection of the α-amino protecting group (R1) of the alanyl moiety followed by the sequential coupling and deprotection of two glycyl moieties followed by the introduction of the terminal glycyl group affords the fully protected intermediate R1 -Gly-Gly-Gly-Ala-Gly-Cys (R2)-Lys (R3)-Asn-Phe-Phe-Trp-Lys (R4)-Thr (R5)-Phe-Thr (R6)-Ser (R7)-Cys (R8)-O-Resin, which is totally deprotected and removed from the Resin support by treatment with liquid hydrofluoric acid in the presence of anisole to yield the linear heptadecapeptide H-Gly-Gly-Gly-L-Ala-Gly-L-Cys-L-Lys-L-Asn-L-Phe-L-Phe-L-Trp-L-Lys-L-Thr-L-Phe-L-Thr-L-Ser-L-Cys-OH. If desired, the fully protected heptadecapeptide may be removed from the Resin support by aminolysis employing dimethylamine, methylamine, ethylamine, n-propylamine, i-propylamine, butylamine, iso-butylamine, pentylamine, or phenethylamine, to yield the 17-Cysteine amide of the fully protected linear heptadecapeptide. The protecting groups may then be removed by treatment with liquid HF in the presence of anisole or by catalytic (e.g. Pd on BaSO4) hydrogenation under conditions avoiding attack of the tryptophan moiety.
The deprotected linear heptadecapeptide and the corresponding amides are readily converted to the [6-17] cyclic disulfide (H-Gly-Gly-Gly-Ala)1 -Somatostatin derivative by mild oxidation (e.g. air), preferably through exposure of a solution of the linear compound to atmospheric oxygen. The protamine zinc and protamine aluminum complexes and non-toxic acid addition salts are produced by methods conventional in the polypeptide art.
Thus the intermediates which constitute part of this invention may be represented as:
R1 -Gly-Gly-Gly-Ala-Gly-Cys (R2)-Lys (R3)-Asn-Phe-Phe-Trp-Lys- (R4)-Thr (R5)-Phe-Thr (R6)-Ser (R7)-Cys (R8)-X, in which X represents --OH, dimethylamine, alkylamino of 1 to 5 carbon atoms, phenethylamine or O--CH2 -[polystyrene resin support]; in which:
R1 represents hydrogen or an α-amino protecting group;
R2 and R8 are protecting groups for the sulfhydryl group of the two cysteinyl moieties, independently selected from the group consisting of 3,4-dimethylbenzyl and p-methoxy-benzyl;
R3 and R4 are protecting groups for the epsilon amino group of the two lysyl moieties selected from benzyloxycarbonyl, 2-chloro benzyloxycarbonyl and 4-nitrobenzyloxycarbonyl;
R5, r6 and R7 are benzyl.
The αamino protecting group represented by R1 may be any group known in the art to be useful in the stepwise synthesis of polypeptides. The preferred α-amino protecting group defined by R1 is of the urethane type and in particular tert-butyloxycarbonyl.
The criterion for selecting protecting groups for R2-8 are (a) the protecting group must be stable to the reagent and under the reaction conditions selected for removing the α-amino protecting group at each step of the synthesis, (b) the protecting group must retain its protecting properties (i.e. not be split off under coupling condition), and (c) the side chain protecting group must be removable upon the completion of the synthesis of the desired amino acid sequence, under reaction conditions that will not alter the peptide chain.
The group --O--CH2 -[polystyrene resin support] defining X in the intermediates of this invention described supra, represents the ester moiety of one of the many functional groups of the polystyrene resin support.
The solid phase method of preparing the heptadecapeptides of this invention is generally known in the art and is described by Merrifield, J.A.C.S., 85, 2149(1963). The resin support employed may be any suitable resin conventionally employed in the art for the solid phase preparation of polypeptides, preferably polystyrene which has been cross-linked with from 0.5 to about 3 percent divinyl benzene, which has been either chloromethylated or hydroxymethylated to provide sites for ester formation with the initially introduced α-amino protected amino acid.
The α-amino and sulfhydryl protected cysteine is coupled to the chloromethylated resin according to the procedure of Gisin, Helv. Chim. Acta., 56, 1476 (1973). Following the coupling of the α-amino and sulfhydryl protected cysteine to the resin support, the α-amino protecting group is removed by standard methods employing trifluoroacetic acid in methylene chloride, trifluoroacetic acid alone or HCl in dioxane. The deprotection is carried out at a temperature between about 0� C. and room temperature. After removal of the α-amino protecting group the remaining α-amino protected amino acids are coupled, seriatim, in the desired order to obtain the product. Alternatively, multiple amino acid groups may be coupled by the solution method prior to coupling with the resin supported amino acid sequence. The selection of an appropriate coupling reagent is within the skill of the art. A particularly suitable coupling reagent is N,N1 -diisopropyl carbodiimide. Another suitable coupling reagent is N,N1 -dicyclohexycarbodiimide.
Each protected amino acid or amino acid sequence is introduced into the solid phase reactor in about a four-fold excess and the coupling is carried out in a medium of dimethylformamide: methylene chloride (1:1) or in dimethylformamide or methylene chloride alone. In cases where incomplete coupling occurred the coupling procedure is repeated before removal of the α-amino protecting group, prior to introduction of the next amino acid to the solid phase reactor. The success of the coupling reaction at each stage of the synthesis is monitored by the ninhydrin reaction as described by E. Kaiser et al., Analyt. Biochem, 34, 595 (1970).
The in vivo activity of the compounds of this invention was established by subjecting (Gly3 -Ala)1 -Somatostatin, as a representative compound of this invention, to the following standard test procedure: three groups of nine albino male rats were arranged to provide a control group, a group for observation of Somatostatin activity as the standard and a group for the study of the test compound (Gly3 -Ala)1 -Somatostatin. Nembutal (50 mg/kg) was injected intraperitoneally into each rat. Fifteen minutes later a subcutaneous injection of the test compound, somatostatin (200 μg/kg) and physiological saline was administered separately to each of the three groups of rats. Ten minutes later 0.5 milliliters of arginine (300 mg/ml, pH 7.2) was injected into the rats heart. The rats were decapitated five minutes later and their blood was collected in Trasylol.sup.� -EDTA. Aliquot samples were assayed for growth hormone, glucagon and/or insulin. The compound of this invention, selected as representative of the group of compounds disclosed for test pruposes, was employed in two distinct test procedures at the 100 μg/kg and 300 μg/kg dose levels. The results of these test are as follows:
______________________________________ Glucagon (pico- Insulin GH grams/ml) μ units/ml (ng/ml)______________________________________(Gly3 Ala)1 -Somatostatin 0.5 � 0.1 130 � 14(100 μg/kg)Somatostatin 1.5 � 0.8 202 � 29Saline 6.4 � 1.5 199 � 15(Gly3 -Ala)1 -Somatostatin 1.4 � 0.7 104 � 10 27 � 7(300 μg/kg)Somatostatin 1.6 � 0.9 115 � 11 12 � 2Saline 4.2 � 0.6 165 � 13 133 � 15______________________________________
Thus, the compounds of this invention (Gly3 -Ala)1 -Somatostatin and the amides thereof are comparable in activity at the 100 and 300 μg/kg dose levels to somatostatin itself and are effective substitutes for somatostatin in the treatment of diabetes mellitus and acromegaly, even though the heptadecapeptides of this invention contain more amino acid residues than somatostatin.
Administration of the heptadecapeptides of this invention may be by conventional routes common to somatostatin and related polypeptides, under the guidance of a physician, orally or parenterally, in an amount dictated by the extent of the dysfunction as determined by the physician. The compound may be administered alone or in conjuction with conventional pharmaceutically acceptable carriers and adjuvants, in unit dosage form containing from about 2 to about 100 milligrams per kilogram host body weight. Furthermore, the protamine zinc or protamine aluminum adducts present desireable administrable forms of the heptadecapeptide as is conventional in therapy involving the use of polypeptides.
The resin (58 g.) is substituted to the extent of 0.46 mmoles of t-butyloxycarbonyl-S-p-methoxybenzyl-L-cysteine per gram of resin.
The t-butyloxycarbonyl-S-p-methoxybenzyl-L-cysteine resin (29 g.) of Example 1 is placed in a Merrifield vessel of 300 ml. capacity, washed with methanol (200 ml.) twice and methylene chloride (200 ml.) twice, allowing a contact time of at least 3 minutes each. The peptide resin is then subjected to a ninhydrin test following the procedure of E. Kaiser et al., Analytical Biochemistry 34, 595 (1970). It should be negative at this stage.
The deprotection of the α-amino group from t-butyloxycarbonyl-S-p-methoxybenzyl-L-cysteine is carried out as follows: The peptide-resin is treated with a 1:1 solution of trifluoroacetic acid-methylene chloride which contains 5% 1,2-ethanedithiol (three times for 15 minutes each), and put through the following wash cycle:
(a) methylene chloride: (b) dimethylformamide; (c) triethylamine 12.5% in dimethylformamide (three times for 10 minutes each); (d) methanol (two times); (e) methylene chloride (two times). Again, a sample of the peptide resin is subjected to a ninhydrin test. The sample is now strongly positive indicating removal of the α-amino protecting group from the cysteine molecule attached to the resin.
The resin so prepared is then gently shaken with t-butyloxycarbonyl-O-benzyloxy-L-serine (8.4 g., 28.5 moles) in dimethylformamide. 22 ml. of 1 M dicyclohexyl-carbodiimide in dimethylformamide is added in two portions over a period of 30 minutes. Shaking is contined at ambient temperature for a total of 18 hours. The peptide resin is then washed successively with methanol (twice) and methylene chloride (twice). To test for completeness of reaction, the peptide resin is subjected to a ninhydrin agent. It should be negative at this stage.
The removal of the α-amino protecting group at each step is performed as described for the deprotection of the t-butyloxycarbonyl-S-p-methoxybenzyl-L-cysteine resin.
The following amino acid residues are then introduced consecutively (BOC means butyloxycarbonyl): t-BOC-O-benzyl-L-threonine (28.5 mmoles, 28.5 moles DCC), t-BOC-L-phenylalanine (28.5 moles, 28.5 mole DCC), t-BOC-O-benzyl-L-threonine (28.5 moles, 28.5 moles DCC), t-BOC-ε-benzyloxycarbonyl-L-lysine (28.5 moles, 28.5 moles DCC), t-BOC-L-tryptophan (28.5 moles, 28.5 moles DCC), t-BOC-L-phenylalanine (28.5 moles, 28.5 moles DCC), t-BOC-L-phenylalanine (28.5 moles, 28.5 moles DCC), t-BOC-L-asparagine-p-nitrophenyl ester (28.5 moles, 1% acetic acid in DMF (200 ml.)), t-BOC-ε-benzyloxycarbonyl-L-lysine (28.5 moles, 28.5 moles DCC), t-BOC-S-p-methoxy-benzyl-L-cysteine (28.5 moles, 28.5 moles DCC), and t-BOC-L-alanylglycine (28.5 moles, 28.5 moles DCC). Each coupling step is carried out in a medium of dimethylformamide with the exception of asparagine which is used as 1% acetic acid in dimethylformamide.
At this point in the synthesis, the resin which is linked to the polypeptides--t-BOC-L-alanyl-glycyl-S-p-methoxybenzyl-L-cysteinyl-benzyloxycarbonyl-L-lysyl-L-asparaginyl-L-phenylalanyl-L-phenylalanyl-L-tryptophyl-benzyloxycarbonyl-L-lysyl-O-benzyl-ε-threonyl-L-phenylalanyl-O-benzyl-L-threonyl-O-benzyl-L-seryl-S-p-methoxybenzyl-L-cysteine--is removed from the reactor before the deblocking step, dried and weighed. The weight of the resin bearing the tetradecapeptide is now 47 g. 8.0 g. of this intermediate is coupled with t-BOC-glycine (11.4 mmoles, 6 ml. DCC), the pentadecapeptide bound resin is again removed before the deblocking step. The resin is washed, dried in vacuo, and yields 8.1 g. of the protected resin. Again, the synthesis is continued on a 4.0 g. scale and the following amino acid residues are added: t-BOC-glycine(5.7 mmoles, 3.0 ml. DCC), t-BOC-glycine (5.7 mmoles, 3.0 ml. DCC). At this stage the heptadecapeptide bound resin is washed, dried in vacuo, and yields 4.0 g. of the above titled compound.
The above described peptide (4.0 g) in Example 2 is treated in vacuo with liquid hydrogen fluoride (40 ml.) and (12 ml.) at ice bath temperature for 1 hour. The hydrogen fluoride and the anisole are removed as quickly as possible under reduced pressure and the residue washed with ether. The peptide is dissolved in 10% acetic acid (degassed) and separated from the resin by filtration. Lyophilization yields the above titled product as white powder (860 mg.).
Alternatively, the peptide resin product of Example 2 is removed from the resin support by treatment with an amine of the formula ##STR3## in which R10 and R12 are methyl or R10 is hydrogen and R12 is methyl, ethyl, propyl, isopropyl, butyl, secondary butyl, pentyl, or phenethyl followed by removal of any excess of the amine to yield the intermediate ##STR4## in which the groups R1 --R12 are defined, supra.
The fully protected intermediate amide is then deprotected with liquid HF in the presence of anisole to yield ##STR5##
Thus, the protected peptide resin product of Example 2 (4.0 g.) in anhydrous ethylamine (143 ml.) is stirred at room temperature for 18 hours in a glass pressure bottle. The product is filtered, washed with dimethylformamide (three times) and the combined filtrate and washings is concentrated in vacuo to yield the fully protected derivative of (Gly-Ala)1 -somatostatin-HHC2 H5, which is treated with liquid HF (40 ml.) and anisole (9.3 ml.) in vacuo at ice bath temperature for one hour. The HF is removed so quickly as possible. Degassed water (300 ml. � 2) is added to the residue and extracted with diethyl ether. The combined aqueous layer is lyophilized to yield fully deprotected (Gly3 -Ala)1 -somatostatin-NHC2 H5.
The linear peptide acid (860 mg.) of Example 3 is dissolved in 860 ml. of a degassed ammonium acetate solution which contains 8.6 g. of ammonium acetate and adjusted to pH 7.5 with ammonium hydroxide.
The solution is flushed with nitrogen, and the solution is allowed to stand in air for 96 hours at room temperature. After lyophilization, a white powder (850 mg.) is obtained
The amides of Example 3 are readily cyclized under the same conditions.
The crude peptide acid (850 mg.) of Example 4 is dissolved in a minimum volume of 2.0 N acetic acid and applied to a Sephadex G-25 (fine) gel filtration column (200 cm. � 2.5 cm.) and eluted with same solvent. Fractions of 9 ml. each are collected. The fractions (72-95) containing the desired peptide are located by ninhydrin spot test and UV analysis (280 mu). After pooling and lyophilization, a white fluffy powder (236 mg.) is obtained.
A partition column of Sephadex G-25 (100 cm. � 2.5 cm.) is prepared by equilibration with low phase and then upper phase of BAW solvent system (n-butanol:acetic acid:water, 4:1:5).
The lyophilized peptide (236 mg.) from above is applied in a minimum volume (10 ml.), of upper phase. Elution with upper phase (4 ml. fractions) affords the desired product which is located by ninhydrin sport test and UV analysis (280 mu). After pooling and lyophilization, a white powder (68 mg.) of the above titled peptide is obtained.
The optical rotation is measured on a Carl Zeiss LEP A-2 photoelectric precision polarimeter, [α]D = -41.04 (c=1.0, 1% acetic acid); amino acid analysis gives the following ratios: Asn (1.1), Thr (2.0); Ser (0.9); Cys (2.2); Ala (1.0); Gly (4.0); Phe (2.9); Lys (2.0); Trp (0.7); Rf (on silica); 0.26 (n-butanol: acetic acid:water, 4:1:5).
Essentially the same purification technique is employed with the amide as is used for the free acid, to obtain the purified amide.
|Cited Patent
|Filing date
|Publication date
|Jun 12, 1974
|Sep 9, 1975
|Salk Inst For Biological Studi
|Somatostatin and acylated des-(ala' 1', gly' 2') derivatives thereof
|Jan 27, 1975
|Jan 6, 1976
|American Home Products Corporation
|(H-gly-gly-tyr-ala)1 -somatostatin
|Citing Patent
|Filing date
|Publication date
|Jun 14, 1980
|Feb 23, 1982
|The Salk Institute For Biological Studies
|Extended N-terminal somatostatin
|U.S. Classification
|International Classification
|Cooperative Classification
|European Classification


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In this instructors led lab, IBM business partners will learn how to integrate a product with the IBM Cloud partner marketplace using the development platform and tooling.
You will have hands-on experience working with the following lab exercises:
- Ex. 1: Setup your marketplace service
- Ex. 2: Implement and deploy end points for a mock service
- Ex. 3: Integrate with a SaaS type service
- Ex. 4: Demo. Deploy a SoftLayer image from marketplace
This lab does not require elaborate technical skills, a basic knowledge of Linux and Eclipse for Java web application development would be helpful to do lab exercises.
If you are attending the InterConnect 2015 conference, sign up for this lab session early before the seat is gone. Meet us at the conference Solution Center in the IBM Cloud Marketplace pedestal to learn more about the partner marketplace and how to integrate your products and services with the marketplace.
How do Business Partners participate in IBM Cloud marketplace?
- Apply to Become a Business Partner
Complete and submit the nomination form https://www.marketplace.ibmcloud.com/joinnow/ to be considered for partnership in the IBM Cloud marketplace.
- Qualify for the IBM Cloud marketplace
We will review your form and reply as quickly as possible to discuss your service and next steps. Some replies take up to two weeks, depending on your service. To qualify for premium programs (e.g. Bluemix), services must meet additional criteria.
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Once you are invited to include your service, you will need to a) register for marketplace and b) accept the IBM Cloud Marketplace Business Partner terms:
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Within 90 days of signing the IBM Cloud Marketplace Business Partner agreement, you must integrate your service to the IBM Cloud marketplace APIs. Services designed for Bluemix must support an additional call.
Details in the Business Partner Guide here:
Service orchestration documentation package (password provided upon commercial agreement signing):
- Qualify for integration to premium options (e.g. Bluemix) – Can be in parallel with above
Prospective Bluemix, PureApplication Service on SoftLayer, or HPC Analytics services must meet certain additional criteria.
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This is really part 3 of our AreYou Called to Preach series.
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Closure to "Forests and Stream Flow by W. G. Hoyt and H. C. Troxell"
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Serial Information: Transactions of the American Society of Civil Engineers, 1934, Vol. 99, Issue 1, Pg. 94-111
Document Type: Discussion & Closure
Subject Headings: Streamflow | Forests
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Felixstowe: Car fire on A14 between Dock Spur and Trimley St Mary roundabout
PUBLISHED: 13:37 12 March 2014 | UPDATED: 15:01 12 March 2014
A car fire in Felixstowe has now been cleared.
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Handmade by Birdie
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Shiny Appy Children
- By admin
- 15 December, 2014
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With Christmas holidays round the corner, a lot of mothers and fathers are considering the pros and cons of digital books. Storyapps are a hybrid of books, short movies and digital video games. In the Nosy Crow Cinderella app for illustration, children do not just hear and read through the story. They can dress Cinderella's stepsisters in their ball clothing, aid Cinderella tidy up plates in the kitchen and even insert their "selfie" in one of the magic mirrors.
Many storybook apps claim to help children's budding literacy. The Nosy Crow app acquired rave evaluations and a number of prestigious awards. Yet ongoing study warns that the extremely interactive features that make apps so interesting could truly disrupt children's ability to learn from them.
Two current research at Royal Holloway University present that with conventional print picture books, studying is facilitated by straightforward, non-manipulatable stories with realistic illustrations. When books have functions that can be manipulated, young children are less able to comply with the storyline and focus instead on the a variety of characteristics they can play with. Flaps, for instance, such as opening a window in a print book, can create a form of interaction that is great for capturing children's consideration.
Nevertheless, to obtain a deeper comprehending, kids need to have to value the flow of a narrative and progressively learn that there is a sequence to occasions, sentences, phrases and certainly letters that afford that means and coherence. High-high quality children's books are characterised by wealthy vocabulary and grammatically complicated sentences. If we get children's attention away from this kind of rich language stimulations and replace them with a fancy game rather, kids are unlikely to advantage from repeated exposure to high-degree text and basically invest that time playing the game.
Parental or peer support is also vital when kids are learning to go through from print books and this may be much less accessible when youngsters interact with storyapps. In 2012, researchers explored the differences between reading designs when mothers and fathers and children study a print book as compared to a story presented on a children's touch-delicate electronic console guide. The more electronic features there were in the guide, the significantly less mothers and fathers engaged in supportive reading through designs and the decrease the children's all round story comprehension.
This body of investigation appears to contradict the claims made by numerous storyapp producers. But we need to request whether or not we want storyapps to educate or entertain or indeed the two, ie edutain children. Just as print books fulfil purposes past education, so do storybook apps. To fully comprehend their worth, we need to have to evaluate storyapps not only in terms of their possible to educate language and literacy skills, but also in terms of their likely to appeal to younger readers to stories and to nurture readers' identities.
We know from observational studies that dad and mom and young children have a fantastic time when interacting with storyapps, with a whole lot of fun and bonding as a loved ones. Many storyapps supply scaffolding for the emerging reader (eg highlighting the text when every word is read aloud) or let the little one decide on independently how to advance the story (eg by choosing substitute story endings). This is fantastic for cultivating children's independent studying capability and can assistance understanding.
Investigation with print books shows that for specific groups of young children, for instance for youngsters with language impairments, books that can be manipulated to perform better for finding out than the ones with no interactive characteristics. Some basic customisation attributes (this kind of as enlarging the text or changing the background colour) make reading through less complicated for these who are not assured. Similarly, for children with consideration difficulties, feedback embedded in apps aids capture their consideration and enhance attitudes about studying.
A especially accomplished feature in many storyapps is the capability to customise and personalise the story to tailor the reading to the child's demands and interests. Personalising digital stories signifies that storybooks can enrich relationships that presently exist. Family members members can be numerous story characters, Daddy can be Superman, children and mothers and fathers can compose and illustrate stories together.
Personalisation is specially useful for youngsters with particular requirements. For illustration, for young children with severe learning issues, the ability to personalise the digital story can offer a distinctive opportunity to share their feelings with others in the classroom. Digital interactive books can also be modified for diverse markets much more simply than print books and as a result may possibly greater handle the problem of diversity in children's books than print media.
For each and every child, mothers and fathers and teachers require to choose the appropriateness of any story, the context of use and the platform it is delivered on. They also want to bear in thoughts that no matter how well-created and interactive the storyapp is, young children nonetheless need adults and other peers to share the story experience with. This old truth applies to children's interaction with Tv, digital video games or storybooks. Their hybridisation in storyapps has intensified its relevance for the new generation.


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- Merce (mɜːs). 1919–2009 US dancer and choreographer. His experimental ballets include Suit for Five (1956) and Travelogue (1977)
WordReference Random House Unabridged Dictionary of American English © 2017
Cun•ning•ham (kun′ing ham′),USA pronunciation n.
(mûrs),USA pronunciation born 1919?, U.S. dancer and choreographer.
- BiographicalGlenn ("Kansas Ironman''), born 1909, U.S. track-and-field athlete.
Collins Concise English Dictionary © HarperCollins Publishers::
Cunningham /ˈkʌnɪŋəm/ n
'Cunningham' also found in these entries:


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Home » celebrating occasions
Moments in life that never comes back needs to be celebrated in all pomp and glory. Heyday Balloons makes every moment of an occasion most spectacular. The range of colors and the high quality HD pin sharp printing process of Heyday make each occasion a memorable one.


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DaiichiSankyo Co.
DaiichiSankyo Co.
Suzuki Y.,DaiichiSankyo Co. |
Kato T.,DaiichiSankyo Co. |
Kikkawa Y.,DaiichiSankyo Co. |
Suzuki T.,DaiichiSankyo Co. |
And 2 more authors.
Powder Technology | Year: 2015
In the pharmaceutical lubricant mixing process, lubricity of granules after mixing was evaluated by measuring the contact angle with water and tablet hardness. The granules were prepared using three different types of popular tumble mixers; V-blender (effective volumetric capacity: 70. L), Container blender (36. L) and Bin blender (20. L) with different powder loading rates (10-88%), blender rotation speeds (18-37. rpm) and mixing times (5-120. min) for model placebo formulation. Contact angle measurement and tablet hardness are useful as alternative characteristics for evaluation of granule lubricity. Based on the experimental data, mixing performance index (MPI), which is an empirical equation including blender type, powder loading ratio, mixing rotation speed and batch size as functional parameters, was developed. Mixing ability (MA) was defined by the combination of MPI and mixing time. Calculated MA exhibited good correlation with tablet hardness (correlation coefficient is 0.89) in all datasets. MA was verified by nine different drug product data with different manufacturing scales, to enable the MA model to support the formulation researcher to set mixing process parameters when the batch size or blender type changes. © 2015.
Morishima Y.,DaiichiSankyo Co. |
Kamisato C.,DaiichiSankyo Co. |
Honda Y.,DaiichiSankyo Co.
European Journal of Pharmacology | Year: 2014
Edoxaban is an oral and direct activated factor X inhibitor. In this study, the acute treatment effect of edoxaban on venous thrombosis is investigated in rats by single and multiple administrations, and compared to the conventional parenteral anticoagulants, enoxaparin and fondaparinux. Venous thrombus was induced in the inferior vena cava by partial stenosis plus topical application of 10% ferric chloride for 5 min. After 1-h thrombus maturation, oral edoxaban and subcutaneous enoxaparin and fondaparinux were given. In the single administration experiment, thrombus weight was measured 1 or 4 h after thrombus induction. In the multiple administration experiments, edoxaban was orally administered once daily (QD) and twice daily (BID) for 3 days. In the single administration experiment, oral administration of edoxaban (3.0 and 10 mg/kg) 1 h after thrombus formation significantly regressed the venous thrombus compared to the thrombus at 1 h after thrombus formation. Similarly the significant venous thrombus regression was observed with enoxaparin (10 mg/kg) and fondaparinux (0.30-3.0 mg/kg). In the multiple administration experiment, both QD and BID administration of edoxaban at daily doses of 5 and 10 mg/kg exerted significant treatment effects. QD administration of edoxaban including lower doses (1-10 mg/kg) significantly reduced thrombus weight. Edoxaban administered QD and BID was effective in the treatment of venous thrombosis, and the treatment effect of edoxaban was comparable to the conventional parenteral anticoagulants. These data demonstrate the potential of edoxaban as an oral anticoagulant in the acute treatment of venous thromboembolism. © 2014 Elsevier B.V. All rights reserved.
Nishimiya D.,Biologics |
Mano T.,Chiyoda Corporation |
Miyadai K.,Chiyoda Corporation |
Yoshida H.,DAIICHISANKYO CO. |
Takahashi T.,Biologics
Applied Microbiology and Biotechnology | Year: 2013
Secretory capacities including folding and assembly are believed to be limiting factors in the establishment of mammalian cell lines producing high levels of recombinant therapeutic proteins. To achieve industrial success, it is also important to improve protein folding, assembly, and secretory processes in combination with increasing transcription and translation. Here, we identified the expression of CHOP/Gadd153 and GRP78, which are unfolded protein response (UPR)-related genes, correlated with recombinant antibody production in stable CHO cells. Subsequently, CHOP overexpression resulted in increasing recombinant antibody production in some mammalian cell lines, and in addition a threefold further enhancement was obtained by combining expression with UPR-related genes or ER chaperones in transient assays. Overexpression of CHOP had no effect on the biochemical characteristics of the product. These results suggest overexpression of CHOP and its combinations may be an effective method to efficiently select a single cell line with a high level of antibody production in the development of cell lines for manufacturing. © 2012 Springer-Verlag.
Kobayashi N.,DaiichiSankyo Co.
Bioanalysis | Year: 2014
At the 5th Japan Bioanalysis Forum symposium, distinguished bioanalytical scientists from government and industry commentated on the bioanalytical method validation guidelines/guidance issued by their own regions, including the draft bioanalytical method validation guideline for ligand binding assay by the Japanese Ministry of Health, Labour and Welfare, which was finalized in April 2014. Additionally, the Japan Bioanalysis Forum Discussion Group, in which daily bioanalytical issues/interests were scientifically discussed, picked up five topics, and more than 200 conference attendees openly exchanged their views on a wide range of bioanalytical issues with discussion group members. This manuscript provides an overview of the highlights out of the symposium. © 2014 Future Science Ltd.
Namba E.,DaiichiSankyo Co. |
Okumura R.,DaiichiSankyo Co. |
Chiba M.,Daiichi Sankyo |
Hoshino K.,Daiichi Sankyo |
Tateda K.,Toho University
Japanese Journal of Antibiotics | Year: 2013
We evaluated the in vitro activity of sitafloxacin against Japanese clinical isolates of Streptococcus pyogenes by broth microdilution susceptibility testing and time-kill studies to elucidate its eradication potential against S. pyogenes. One hundred and nineteen clinical isolates of S. pyogenes isolated from pharynx were tested to sitafloxacin and seven other agents in the susceptibility testing. The time-kill studies were conducted with five strains, one of which was resistant to clarithromycin, one resistant to levofloxacin and one type strain of S. pyogenes. In the time-kill studies, sitafloxacin, garenoxacin, amoxicillin and clarithromycin were assessed at static concentrations of their respective peak concentrations in plasma (C max) when administered as oral single doses for adult patients with S. pyogenes infections. We found the rank order of antimicrobial activity against S. pyogenes isolates was: cefcapene (MIC90, 0.015 μg/mL) > amoxicillin (0.03 μg/mL) > sitafloxacin (0.12 μg/mL) > garenoxacin (0.25 μg/mL) > levofloxacin (4 μg/mL) > minocycline (16 μg/mL). Macrolide-resistant isolates accounted for 72 (60.5%), resulting in clarithromycin and azithromycin MIC90s of >32 and >128//g/mL, respectively. Sitafloxacin exhibited the most rapid bactericidal activity (≥3 log reduction from the initial inoculum) within 2 h against all tested strains, including even one levofloxacin-resistant strain. For garenoxacin, bactericidal activity was achieved between 2 and 6 h. Amoxicillin revealed no significant bactericidal activity up to 6 h. Clarithromycin showed no bactericidal activity and did not inhibit growth of a clarithromycin-resistant strain. These data indicate the potential usefulness of sitafloxacin for the treatment of S. pyogenes eradication.
PubMed | DaiichiSankyo Co.
Type: Journal Article | Journal: Cell biology international | Year: 2010
We have demonstrated that a unique megakaryocytic cell line UT-7/TPO could respond to one of the primary platelet signals through GP (glycoprotein) VI and a secondary signal of the AA (arachidonic acid) cascade. Unlike other megakaryocytic cell lines, UT-7/TPO was found to express GPVI and its associate signal molecule of FcRgamma (Fc receptor gamma chain). When UT-7/TPO was stimulated with the GPVI agonist convulxin, the [Ca2+]i (intracellular Ca2+) was elevated in a convulxin concentration-dependent manner, and [Ca2+]i elevation was blocked by pretreatment with the Src family kinase inhibitor PP2 and the phospholipase inhibitor U73122. These results strongly indicate that endogenously expressed GPVI signal molecules are functional in UT-7/TPO. Concerning the AA cascade, the expression of COX (cyclooxygenase)-1 and TX (thromboxane) synthase was observed, and this cell line was able to produce TX by exogenous AA, followed by [Ca2+]i elevation mediated through the TX receptor. It is worth noting that convulxin stimulation did not cause TX generation, even through the GPVI pathway and the AA cascade are functional in this cell line. As there are many reports that convulxin-stimulated platelets failed to produce TX, it is suggested that UT-7/TPO has the same property as the platelets in regards to convulxin stimulation. Thus, UT-7/TPO is useful for the observation of both the GPVI pathway and AA cascade without requiring either the induction of differentiation or GPVI transfection. Furthermore, this cell line provides a new tool for research on platelet activation signals.


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Pho 75
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Reviews & Posts
Hanoi beef noodle soup (Phở #1)
"It comes with everything: tripe, tendon, fatty brisket and meatballs. It's my favorite dish in the world. If I don't get this dish once a week, I get the shakes."
Phở w/ soft tendon & fatty brisket
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No. 6 phở
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This time, we got "Develop in the womb" crossword puzzle clue. Next we will look for a few extra hints for Develop in the womb, 7 letters answer". Finally, using all gathered information, we will solve Develop in the womb crossword definition and get the correct entry. We hope that our website has all the answers you are looking for, and it will help you solve your crossword.
Similar crossword puzzle definitions:
Be pregnant;
Develop over time, as an idea;
Develop an idea;
Try this 7 letters answer: GESTATE
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The University of Richmond veterinary technology
Think about what career is best suited for you, and where you want to study. Request more information now.
Think about what career is best suited for you, and where you want to study. Request more information now.
Think about what career is best suited for you, and where you want to study. Request more information now.
Information about The University of Richmond veterinary technology, and registering for elective discussion sections and seminars. Which college degrees give you the best chances of finding employment after graduation? Nursing is one of the fastest-growing job areas, and for good reason. As the population ages, medical care will continue to expand rapidly. Concentrating on The University of Richmond veterinary technology, for example, you may gain an advantage in job recruiting on-campus. Check with the vet tech department for course registration deadlines, and veterinary program requirements. Please use the form above to request admissions info for The University of Richmond.
Veterinary assistants and laboratory animal caretakers look after animals in laboratories, animal hospitals, and clinics. Veterinary technologists and technicians perform medical tests under the supervision of a licensed veterinarian to assist in diagnosing the injuries and illnesses of animals. Veterinary technicians must complete an associates program in veterinary technology, while veterinary technologists require a 4-year bachelors degree. The median annual wage for veterinary technologists and technicians was $32,800 in May 2017. Employment opportunities are projected to grow 20% over the coming decade, much faster than the average for all medical occupations.
In 2017, there were 231 veterinary technology programs accredited by the American Veterinary Medical Association (AVMA). Most states require veterinary technicians to pass the Veterinary Technician National Examination (VTNE), offered by the American Association of Veterinary State Boards. For technologists seeking work in a research facility, the American Association for Laboratory Animal Science (AALAS) offers the following certifications: Laboratory Animal Technician (LAT) and Laboratory Animal Technologist (LATG). To become certified, candidates must have work experience in a laboratory animal facility and pass the AALAS examination. Beyond major requirements within the vet tech department, you may consider Norfolk State University medical assistant program as a complementary elective to your primary course of study.
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As the largest Passive House Certified project that will consume 92% less energy than buildings of similar size, this is one of the most innovative and sustainable housing developments in the making.
My objective was to develop a true-to-scale, fully immersive VR experience that would engage a not-too-tech-savvy target audience and efficiently boost pre-sales.
Currently used in Second & Delaware Sales Center, it has proven to be a very efficient sales channel, as the vast majority of people who try the VR experience end up signing a lease.