text:
Workshop: Writing High Quality IEPs: Collaboration and Common Core Alignment
November 6, 2015
NYC Charter School Center - Training Room
111 Broadway, Suite 604, New York, NY 10006
Presented by Megan Davis-Hitchens
The Individual Education Program (IEP) is designed to outline supports and services required for individual students to achieve success. The IEP is also used to provide teachers and school staff with information and strategies to guide their work with the student. The quality of an IEP is only as meaningful as the team's approach to its development and how it is implemented. Participants will explore a collaborative process for writing IEPs and how to align goals and strategies to the Common Core. The training will provide participants with strategies and resources for creating authentic IEPs. This session is designed for anyone who plays a role in writing or implementing an IEP.
Suggested Audience: Teachers, Support Staff, Special Education Coordinators/Leads


text:
Get an overview of this hotelHotel in Tahlequah with free breakfast and indoor pool
Popular property highlights
Located in the heart of Tahlequah, this hotel is within 3 mi (5 km) of Cherokee Heritage Center, Cherokee National Capitol, and George M. Murrell Home. Northeastern State University is 2.8 mi (4.5 km) away.
Hotel Features
This hotel features an indoor pool, a fitness center, and a spa tub. Free full breakfast, free wired Internet in public areas, and free self parking are also provided. Additionally, coffee/tea in a common area, a business center, and laundry facilities are onsite.
Room Amenities
All 43 rooms offer conveniences like refrigerators and microwaves, along with free WiFi, free wired Internet, and LCD TVs. Guests will also find coffee makers, free long-distance calls, and free local calls.Information missing or incorrect? Tell us!Opens in a new window
Rodeway Inn
Hotel Amenities
Hotel Amenities
In addition to an indoor pool, Rodeway Inn provides a spa tub and a fitness center. A computer station is located on site and wired Internet access is complimentary. This hotel offers access to a business center. Guests can enjoy a complimentary breakfast each morning. This Tahlequah hotel also offers a picnic area, coffee/tea in a common area, and laundry facilities. Complimentary self parking is available on site.
Rodeway Inn has designated areas for smoking.
- 24-hour front desk
- Business center
- Total number of rooms - 43
- Number of floors - 2
- Coffee/tea in common areas
- Free breakfast
- Elevator/lift
- Fitness facilities
- Designated smoking areas
- Billiards or pool table
- Free wired Internet
- Computer station
- Laundry facilities
- Picnic area
- Safe-deposit box at front desk
- Free RV, bus, truck parking
- Free self parking
- Spa tub
- Indoor pool
Family Friendly Amenities
- Family Hotel
- Indoor pool
- Free Wi-Fi
- Laundry facilities
- Refrigerator
- Microwave
- Cribs/infant beds (complimentary)
Available in all rooms: Free WiFi , Free wired Internet
Available in some public areas: Free wired Internet
Free self parking, Free RV, bus, truck parking
Room Amenities
- Air conditioning
- In-room climate control (air conditioning)
- Free long-distance calls
- Phone
- Free local calls
- Refrigerator
- Coffee/tea maker
- Microwave
- Daily housekeeping
- Private bathroom
- Hair dryer
- Desk
- Free WiFi
- Free wired Internet
- Free cribs/infant beds
- Rollaway/extra beds (surcharge)
Where to Eat
Guests are offered a complimentary full breakfast each morning.
Nearby Things to Do
An indoor pool and a spa tub are on site. Other recreational amenities include a fitness center.
If you have requests for specific accessibility needs, please note them at check-out when you book your room.
- In-room accessibility
Hotel Policies
Check-in time ends at 7 AM
Check-in time starts at 2 PM
Check-out time is 11 AM
Payment types
Children and extra beds
- Children are welcome.
- Kids stay free! Children 18 years old and younger stay free when using existing bedding.
- Rollaway/extra beds are available for USD 10.00 per day.
- Free cribs (infant beds)!
- Pets not allowed
You need to know
Extra-person charges may apply and vary depending on property policy.
Government-issued photo identification and a credit card or cash deposit are required at check-in for incidental charges.
Special requests are subject to availability upon check-in and may incur additional charges. Special requests cannot be guaranteed.
Optional extras
- Rollaway bed fee: USD 10.00 per day
Hotel Name
- Best Western Tahlequah
- Best Western Tahlequah Inn
- Quality Inn Tahlequah
- Quality Tahlequah
- Rodeway Inn Hotel Tahlequah
- Rodeway Inn Tahlequah
We should mention
Children 18 years old and younger stay free when occupying the parent or guardian's room, using existing bedding.

subset: commoncrawl


text:
September 14, 2012 - Message from Matthew's Mother Suzy
Expand Messages
- Hello, everyone!
In a one-time departure from sending you only Matthew's monthly messages, I am sharing this link to "I Know My Galactic Family is Here Do You?"
The commentary and film clips of space crafts in this 18-minute documentary are so extraordinary and persuasive that I want to give you the link now rather wait to put it in my note at the end of the October message.
LOVE and PEACE...
Your message has been successfully submitted and would be delivered to recipients shortly.


text:
tuberculosis by alleviating certain symptoms, re-
lieving certain complications that may be present,
and putting the diseased organs in that condition
which is most favorable for a cure. These, then,
are the lines upon which we should base a rational
therapy for tuberculosis. Not any one of them
should be employed to the exclusion of the others,
but all should be worked out into one harmonious
whole. Of those remedies and measures which have
been put forth as "cures" for tuberculosis in the
past, nearly all have some merit, although the merit
is not always where it is supposed to be. Cod-liver
oil certainlv increases nutrition when well borne,
although there are more palatable ways of accom-
plishing this end. Creosote will often improve nu-
trition by its action upon the digestive system.
When given in too large doses, however, even in
suitable cases it does harm. It also has a beneficial
effect upon the mucous membranes of the air pas-
sages, but to think that it will kill the bacilli by its
antiseptic action is positively absurd. The pneu-
matic cabinet is based upon the idea of exercise for
the lung ; nitrogen gas, upon rest for the lung. The
various culture products find their basis in the nat-
ural defenses of the organism. Perhaps none of
these measures is wholly bad, but none of them
should be put forth as a "cure ;" they are aids to a
cure. They, and many more remedies and measures,
find a rational basis for employment in the treat-
ment of certain cases of tuberculosis, but they are
not to be used in a routine manner. The treatment
of tuberculosis is a matter of careful individualiza-
Recognizing the importance of nutrition, it should
be one stromectol 3 mg of our chief aims to maintain this at the
highest point. Everything which interferes with it
must be eliminated. ' The" hygienic-dietetic-open-air
treatment, which is deservedly so popular through-
cut the world to-day, has for its basis the betterment
of nutrition. One of the most noticeable, and per- stromectol uk
haps the most important effect of the open-air treat-
ment of tuberculous patients, is its effect upon diges-
tion and assimilation. Coincident with the beginning
of this treatment stromectol for lice we note a marked improvement
in the appetite. When digestion has been previously
slow, and attended with more or less unpleasant
svmptoms, we not infrequently observe _ a
disappearance of all embarrassment. Assimilation
improves, and the patient takes on flesh. The effect
of the open air is to enable the stromectol purchase patient to digest and
assimilate more food and to furnish the appetite
which demands it.
The best effect of open air can be obtained only
by using it discreetly. While in itself harmless,
doubtless more lives have been wrecked while try-
ing to follow this mode of treatment than by anv
other measure. Open air is not a cure for tubercu-
losis: it is onlv a measure for the production of a
certain end. If used properly, it generic stromectol is one of the great-
est aids to nutrition that can be employed ; if used
improperly, it will defeat its own purpose.
An individual suft'ering from tuberculosis should
not be told that open air will cure him, but that
proper living in the open air will be one of his great-
est aids. Many an individual has eaten good food
and remained in the open air all the time, and yet
killed himself. The oft-repeated advice of well-
meaning eastern physicians to their patients to "go
\\ est, live in the open buy cheap ivermectin air or rough it, and keep
away from physicians," is responsible for the deaths
of hundreds of patients annually. Not open air,
but the proper use of open air, is one of the chief
aids in the cure of tuberculosis.
Open air should be supplemented by proper food
and carefully regulated rest and exercise to make it
most effective. While we stromectol buy recognize that rest is a
wonderful aid to nutrition, and that overexertion
decreases the resisting power of the patient, yet
there comes a time in the treatment of order stromectol online nearly all
cases of tuberculosis when exercise short of tiring
will increase nutrition and hasten recovery. The
physician must be the judge when this time comes.
Beside prescribing open air, a carefully selected
diet, and the proper amount of rest and exercise, the
physician must control and regulate the entire life of
the tuberculous patient. He must guide him even
to the minutest detail of his life. Nothing of im-
portance should be left to the patient's judgment
until he has proven himself competent.
Another measure of great value in improving
nutrition is hvdrotherapy. The careful and intelli-
gent application of water offers us one of our most
valuable and most flexible aids to nutrition, and
should never be om.itted.
Climatic conditions aft'ect the state of nutrition
very decidedly. While sunshine is not indispensable
to the treatment, as is shown by the results obtained
in many places where there is a larp'e percentage of
cloudy days, yet those of us who are fortunate
enough to be able to give our patients the benefit
of almost constant sunshine realize its value. Its
cheering and tonic effect is a very potent factor in
aiding nutrition. A climate which not only affords
an opportunity, but which invites the patient to be
out of doors a great portion of the time, and which
also affords a large amount of sunshine, is a great
aid in the treatment of tuberculosis. stromectol canada
Modern buy ivermectin research points to the possibility of the
laboratory giving us cures for all bacterial diseases.
N'accination of bacterial toxins is assuming an im-
portant and rational place in treatment. It is now
about fifteen years since the first efforts at specific
treatment in tuberculosis began. This first trial of
tuberculin marks one of the saddest pages in the
history of the treatment of this or any other dis-
ease. Never were hopes raised higher, and never
were they dashed lower. The misuse of tuberculin
in the early nineties not only resulted in the death
of many patients, but it so embittered the medical
jirofession against it that it will still take time before
the remedy can be assigned its proper place. Dur-
ing all these years those suffering from this disease
have been denied the help which could have been
rendered bv this immunizing treatment. The per-
sistence of a few men, however, such as Spengler,
Petreschky, Turban, Goetch, Trudeau. and von
Ruck, who were convinced of the value of tuber-
culin, has finally made the profession reconsider and
give a more favorable opinion.
Laboratorv experiment, as well as clinical evi-
dence, shows stromectol online that tuberculin will aid in the cure of
tuberculosis. Its effect on local lesions, such as stromectol for scabies can
be seen bv the eye, in the laryn.x, for example,
proves its value beyond question. The increase in
the agglutinating and the opsonic power of the blood
Nov. cheap stromectol 10, 1906]
of those patients who are treated by it, shows that
its action is that of a specific immunizer.
Tuberculin stimulates the cells of the stromectol price body so that
they throw out more specific antibodies into the
bloodstream, and should scabies stromectol be employed in the treat-
ment of this disease. So we can do more than nour-
ish our patient; we can artificially increase his re-
sisting power. We can make him more able to
destroy the tubercle bacilli and tiie toxins which
they form.
Since the important researches of Wright and
Douglas upon the opsonic power of the blood have
shown us that Buchner and Nuttall were right in
ascribing an antibacterial action to the serum of the
blood, we can see the wisdom of keeping areas
which are infected with tubercle bacilli well bathed
in serum. The action of the Finsen light is to cause
an irritation, with an increased How of blood to the
part. Poultices to certain lupus patches have
hastened their cure. Bier's method of treating tu-
berculous joints, as well as acute inflammations, by
passive congestion, can be explained in this same
way. In this way we can also e.xplain the action of
violet light upon pulmonary tuberculosis. By
causing an active hyperemia it is aiding in bathing
the parts with serum. Thus, all these measures
which tend to divert more blood to the part involved
are of value, and should be used in connection with
tuberculin, for by so doing we are bathing the dis-
eased areas with a blood which is rich in antibodies.
.\nother measure which is of value is the giving
of raw meat or muscle juice. Experiments of
Richet and Hericourt, also of Philip and Galbraith.
show definitely that the emnloyment of raw meat
and raw meat juice causes a much greater retention
of nitrogen than when the meat has been cooked.
It is also the belief of these writers that there is
something specific against the muscle waste, in the
ingestion of the raw muscle.
In order to be most successful in the general
therapy of tuberculosis, all distressing symptoms
and complications should be carefully managed. It
is rarely ivermectin stromectol necessary to give medicines for cough,
night sweats, shortness of breath, loss of appetite,
indigestion, or fever of the early or moderately early
cases. The careful management of buy cheap stromectol the patient, put-
ting him to rest in the open air, together with the
proper hydrotherapeutic measures, will usually
relieve all these symptoms very quickly. Organic
diseases of the stomach should receive most careful
attention, for a good stomach is indispensable. The
bowels should also be kept active. In more ad-
vanced cases, sometimes these distressing symptom?
will have to be relieved by appropriate drugs.
Among the most distressing complications are
dry pleurisy, which can be best relieved by strap-
ping, and pleurisy with effusion, which should be
removed if it causes embarrassment of the heart or
respiration : tuberculous laryngitis, which will yield
most readily to tuberculin, local cleanliness, rest, and
wet packs ; and tuberculosis of the bowel, which will
require careful regulation of the diet and such harm-
less astringents as bismuth in large quantities, or
lead and opium in intractable cases. The tubercu-
lous patient is also subject to all other "ills that flesh
is heir to." and when present they must be treated
Mixed infection is a very serious complication.
Tuberculosis does not long remain a simple process.
Germs, other than the tubercle bacilli, soon gain
entrance to the diseased areas, thus complicating the
condition. Just what part mixed infection plays in
the pathology- order stromectol of tuberculosis is as yet uncertain,
but the advent of other germs is generally looked
u]jun as being a buy stromectol online serious complication. Mixed infec-
tion unquestionably hastens destruction of tissue in
the local areas and causes the liberation of toxins
wliich are responsible for many grave constitutional
Mixed infection is doubtless present early in the
infection, long before we are wont to recognize it
by the symptoms which are usually ascribed to it,
and it is undoubtedly the part of wisdom always to
bear this in mind in treatment. When the symp-
toms have once become marked the patient should
be put to bed in the open air. The temperature
should be relieved by sponging, the patient should
be encouraged to eat plenty of good food, taking
solid food at that time of the day when the tem-
perature is low, and relying on milk, eggs, and
muscle juice mostly at other times. All distressing
symptoms should be relieved, and the patient kept
in as cheerful a condition as possible. Every effort
should be made to keep up the patient's nutrition.
It is not at all uncommon to find patients who are
thus carefully treated run a course of fever for
weeks, and yet gain in weight.
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text:
System Status: Password not working? See the Status Page for more information.
Select the first letter of the word to jump to the appropriate section of the glossary.
Add to my list: The conference you are visiting is not on your Conference List. Click this link to add the conference to your Conference List.
Archived Topic: A topic that has been archived by the conference host. To see a list of such topics, select Retired in the Toolbar.
Browse Bar: The graphic bar above a topic list that determines which topics are displayed.
Conference: A virtual discussion area organized around a general subject or theme.
Conference banner: The graphic title of a conference. Clicking the conference banner displays a conference information page.
Conferencing window: The main browser window in Well Engaged.
Create topic: Start a new topic in a conference.
Edit My List: A utility for creating or editing your personal conference list.
Filter: A utility for removing the responses of specific participants from your view. Also known as a "killfile" or "bozofilter."
Forget: The command to remove a specific topic from your view of a topic list.
Forget elsewhere: Click this link to remove a topic from view in each conference to which it is linked, but not in the conference you are in.
Forget everywhere: Click this link to remove a topic from all conferences to which it is linked.
Forget here: Click this link if you only want to remove a topic from the conference you are reading.
Forgotten: A selection in the Browse Bar that lists topics you have removed from the default topic list.
Frozen topic: A topic designated "read-only" by a conference host. Frozen topics are preceded by an ice-cube icon.
Hide: To suppress a response from view. Only the author of a response or the conference host may hide it. Unhide reverses the hide command.
Hidden response: A response which cannot be read in the conferencing window. To see a hidden response, click its hypertext link.
History: A listing of items you have recently read.
Host: The online "innkeeper" of a conference. Hosts help support conference participants and keep conversations lively.
Hypertext transfer protocol: A format for displaying pages on the Web.
Keep new: A command to reset a topic so that responses that have been seen in a session will be flagged New as if they had not been read when you return to the conference.
Keyboard shortcut: A single letter keyboard command that moves you through your conference list.
Kill: To permanently remove a topic from a conference. Only a conference host may kill a topic.
Log off: To exit Well Engaged. Unless you have checked "Remember me on this computer", logging off erases the browser cookie with your username and password, requiring that you log in before returning to a conference.
Mark all as if seen: Remove the "New" tags on a topic list in a conference as if you have already read all the posts in in the conference.
My conference list: A participant's list of frequently visited conferences.
My list: A button on the Toolbar that returns you to your personal conference list.
"New" flag: A clickable graphic that appears next to the names of conferences or topics which contain responses that you have not yet read.
Participant: An individual who has registered a username for access to The WELL.
Personal conference list: A participant's list of frequently visited conferences.
Placemark: A marker indicating that an item can be retrieved at any time. To placemark an item, check the placemark box. Also, a button on the Toolbar used to access your list of placemarked topics and responses.
Post: To publish a response to a topic.
Post and Go: To post a response and move on without seeing the posted response. See Settings.
Profile: An information screen maintained by each Well Engaged participant. To modify your profile, click Settings in the Toolbar. Some profiles also show UNIX Information, from a file called .plan that is kept in their UNIX home directory. If you want assistance changing your UNIX Plan Information, please contact Helpdesk.
Pseudonym: A participant's chosen nickname, listed before the username in each response header.
Recent: A selection on the Browse Bar that places topics with new responses at the top of the Topic List.
Remember: To reinstate a forgotten topic to the default topic list.
Remember everywhere: Reinstates a forgotten topic to the topic list of each conference to which it is linked.
Remove from My List: Remove this conference from My Conference List.
Response: A comment added to a discussion topic.
Response header: The information preceding each posted response, including response number, pseudonym, username, date and time.
Retired topic: A topic that has been archived by the conference host. To see a list of such topics, select Retired in the Toolbar.
Scribble: To remove the text of a response from a topic. Only the author of a response or the conference host may scribble a response.
See New: A command to display discussion items posted since your last visit.
Settings: Participant configurable features including display options, password, profile, filters and the Personal Conference List.
Shortcut: A typed command issued in the shortcut box. Also see Keyboard shortcut.
Slipping in: To post a response while another participant is composing a response. Also referred to as "slippage."
Spellcheck: Highlights misspelled words and shows a draft response as it will appear when posted.
Thaw: Opens a frozen (read-only) topic for participant response. Only a host may thaw a frozen topic.
This topic is linked: A click on this link just below the title of a topic will show the conferences and topic numbers to which a topic is linked.
Toolbar: A graphic bar at the bottom of your conferencing window which provides access to conferencing features.
Topic: A specific discussion inside a conference. A topic is comprised of individual participant responses.
Topic list: A list of discussions in a conference. To read a topic, click on its name. To create one, click Create Topic at the top of the topic page.
Unhide: Reinstates a hidden response.


text:
It seems there's a new leader in the dash to become the best video game racing simulation. While players await the arrival of a new Gran Turismo for PlayStation 3 in 2010, its biggest rival on the Xbox 360 has zoomed to the front of the pack.
Developers Turn 10 have finely tuned the racing experience for Forza Motorsport 3, delivering astounding depth and greater accessibility.
Longtime Xbox owners shouldn't be surprised. They've likely been enamored with the critically-acclaimed series since its debut on the original Xbox in 2005.
For the third installment, there's a greater level of openness to the game when compared to its predecessors. Difficulty settings have been tailored in such a way as to invite players of any skill level to sit behind the wheel of Forza 3's 400+ cars.
A series of assists allow players to customize the difficulty for each race, such as equipping autobraking, traction control and stability control. Players can also add driving lines to advise them on how best to approach difficult turns. However, Forza veterans can rest easy in knowing that once those assists are shut off, racing becomes much more challenging. It's also more rewarding, as the game allows players to earn more credits on the tougher difficulties.
Also making its debut is the Rewind feature, a welcome addition for players seeking to drive the perfect race. When a player makes a mistake, they press a button to rewind the race a few seconds to the spot of their choosing. The feature can be used as many times as a player wants. Rewind is an effective way for players to correct errors during an event without having to quit and restart a race.
Another sign of Forza 3's openness is in its overall structure. Players can opt to tackle events individually or through Season Play, which is meant to mimic a standard racing season. Most events are open to race in at any time, as long as you have the appropriate car.
After each race, players notch experience points to boost their overall driver level as well as experience levels for each car. As players move up a level, they're rewarded with a new car for their garage. Advancing through car levels snags discounts players can use on vehicle upgrades. Experience points can be earned in any game mode, even online multiplayer racing. Players also earn credits they can use to purchase new vehicles or upgrades.
During my time with Forza 3, I found myself bouncing around between Season Play and the Event List, for those times when I wanted to use a specific car or try out a particular event, such as drag racing. Most of the major car manufacturers are represented, ranging from Ford and Toyota to Ferrari and Lamborghini. Cars are broken down into performance classes. For example, the lowest group features vehicles such as the Toyota Yaris and Scion xD, while the A class showcases the Audi R8 and Lamborghini Murcielago.
Most impressive is studio Turn 10's ability to make the experience inside each car feel unique beyond just the model and paint color. Differences in speed, acceleration and handling are easy to pick out, while each engine roars with distinct sounds when revved up.
Of course, the cars look absolutely gorgeous, as do the landscapes that house the game's 100 tracks. The game provides players with plenty of different environments to view while speeding down the raceway. Drivers can go from racing inside Germany's legendary Nürburgring to Italy's breathtaking Amalfi Coast or down the streets of New York City.
Events within the single-player experience are focused solely on straightforward racing, ranging manufacturer-specific races to super-lap events and endurance runs lasting dozens of miles. Unfortunately, I didn't notice many other challenges among the single-player options, such as drift events or time trials. However, they are present through online multiplayer.
Turn 10 has also incorporated Forza's devoted community further by adding a new Storefront feature. The series has made a reputation off players who create amazing paint jobs like these using the game's editor. Players can now take those liveries and make them available for purchase using Forza's credit system. A player's storefront also holds in-race photos and specially designed vehicles available for sale.
For now, Forza Motorsport 3 sits atop the list of video game racing simulations, thanks to hours upon hours of content and a willingness to extend the experience to drivers of every skill level.
Publisher: Microsoft
Developer: Turn 10
Platform: Xbox 360
Release Date: Oct. 27
Price: $59.99
Score: 4 stars (out of 4)
By Brett Molina
Mike Snider began covering the video game industry during the Super Nintendo-Sega Genesis clash in 1992. An original pinball wizard, he eventually was seduced by Robotron: 2084 and Tempest. These days he is a fan of action/shooters and lives out his Keith Moon fantasies playing a mean drum kit on music games. More about Mike.
Brett Molina has been writing about video games for USA TODAY since 2005. He is well-versed in Madden NFL, the fighting genre and first-person shooters. The first video game he played was Asteroids at a local arcade. He has been hooked ever since. More about Brett.


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010 Editor contains a number of methods for opening files. Clicking the 'File > Open File...' menu option, or pressing Ctrl+O opens a file dialog box. After selecting a file and clicking the Open button, the file will be displayed as either a Text Editor Window or a Hex Editor Window in the main display. See Using the Text Editor or Using the Hex Editor for information on editing the file. When opening a file, if the Open as read-only toggle is selected in the dialog, the file will be opened in read-only mode. To control which directory is used when the Open File dialog is shown see the Directory Options dialog.
The editor stores a list of files that have been recently opened. This list can be accessed from the 'File > Open Recent' menu option, from the Workspace (see Using the Workspace), or from the Startup Page (see the Using the Startup Page). Click a file from the Open Recent menu to load it into memory. The number of files in the list can be controlled from the General Options dialog.
Another way of opening files is to use the standard Windows Explorer program. When 010 Editor was installed, enabling the 'Add 010 Editor to explorer right-click menu' toggle in the install program will allow files to be opened from the Explorer. Right click on a file and select the '010 Editor' option. Another method of opening files is to drag-and-drop a file from the Windows Explorer onto a running 010 Editor program. If dragging and dropping an Intel Hex or Motorola S-Record file, the file will automatically be imported (this functionality can be turned off using the Importing Options dialog). Files can also be associated with 010 Editor, meaning that double-clicking a file in the Windows Explorer will open the file in 010 Editor.
Intel Hex files or Motorola S-Record files can be automatically associated with 010 Editor by selecting the 'Associate Intel Hex files with 010 Editor' or 'Associate Motorola S-Records with 010 Editor' toggle in the install program. For more information on Intel Hex or Motorola S-Record files, see Importing/Exporting Files.
The Workspace also contains a simplified browser that can be used to open files. Files can also be loaded from the Favorite Files list or the Bookmarked Files list in the Workspace.
Files can be opened when starting 010 Editor from the command line. See Command Line Parameters for more information.
010 Editor can also be used to edit hard drives and processes. See the Editing Drives or Editing Processes help topics for more information.
010 Editor v8.0 Manual - Windows EditionCopyright © 2003-2017 SweetScape Software - www.sweetscape.com
This is the manual for 010 Editor, a professional
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text: Classification: People: By occupation: Clergy: Cardinals: By nationality: Monegasque also: Monaco: People: By occupation: Clergy: Cardinals no:Kategori:Monegaskiske kardinaler "Antonio Riberi (June 15, 1897—December 16, 1967) was a Monacan Cardinal of the Roman Catholic... Antonio Riberi Pages in category "Monegasque cardinals" This category contains only the following page. R Antonio Riberi Retrieved from "http://religion.wikia.com/wiki/Category:Monegasque_cardinals?oldid=60979" Ad blocker interference detected! Wikia is a free-to-use site that makes money from advertising. We have a modified experience for viewers using ad blockers Wikia is not accessible if you've made further modifications. Remove the custom ad blocker rule(s) and the page will load as expected. Categories: Monegasque Clergy Cardinals by nationality Monegasque Roman Catholics European cardinals


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Cupid Clues is an alluring, beige tussar silk dupatta decorated with colourful "nakshi" kantha-embroidered floral designs. The plain canvas of the dupatta is enlivened by bright red roses and green leaves adorning it. The combination of colours and intricacy of patterns defines the charm of this dupatta. Drape this over a plain, green or red silk kurta or kurti to create a vibrant ensemble.


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Dean Fisher bio
Dean Fisher attended the American Academy of Art in Chicago (1978-82) and studied independently in Europe (1984-88). He currently lives and works in Connecticut. Fisher's work has been in featured in numerous solo shows, most recently J. Cacciola Gallery in New York (2012) and Bachelier Cardonsky Galley in Kent, Connecticut (2008). His work is included in many corporate and private collections.


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Ethylene dichloride "Asia, Europe & US" prices, markets & analysis
ICIS publishes pricing information which you can use in settlements and contracts in order to optimise your deals and negotiations.
Use the independent price assessments and market coverage in our price reports to track the regional Ethylene dichloride market.
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Ethylene dichloride news and market information products from ICIS
We offer the following regional Ethylene dichloride coverage to keep you informed of factors and developments affecting prices in the "Asia, Europe & US" Ethylene dichloride marketplace.
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Updated to Q1 2017
Ethylene dichloride (EDC) prices were on an uptrend in Asia throughout the first quarter. Higher upstream feedstock ethylene prices contributed to the EDC price increases. Overall availability of cargoes in Asia were tight which also pushed up the prices of the spot cargoes. Producers of EDC also firmed up their offers on the back of better downstream polyvinyl chloride (PVC) demand.
However there was a wide buy-sell gap in the region. Buyers in northeast Asia, particularly Chinese buyers, were not willing to increase their bids. Only limited deals were heard concluded throughout the period. Buyers in the region argued that with the current offers of EDC , itwould make more economic sense for them to buy ethylene and produce EDC by themselves. Sellers however are unlikely to lower prices on the back of overall tight availability of spot cargoes and better downstream PVC demand in the spring season.
Updated to Q2 2017
European ethylene dichloride (EDC) spot prices were stable in Q2 although some downward pressure is expected in the market due to lower global EDC and polyvinyl chloride (PVC) prices.
Sources said that there was a downward tendency in sentiment during the quarter because of generally lower PVC prices, as well as a decrease in feedstock ethylene prices for June.
However, few new spot deals were agreed despite some PVC production issues in Europe later in the quarter, so any price reductions could not be confirmed.
The European EDC market is structurally quiet because the majority of production is integrated into PVC production systems. Spot deals are therefore rare except in the event of production issues at a producer. The ramping up of KEM ONE's EDC plant at Lavera, France has improved potential availability in Europe compared to the previous quarter, but no impact has been detected on prices so far.
Updated to Q1 2017
US ethylene dichloride (EDC) prices moved up $50/tonne FOB US Gulf during the first quarter.
Even so, US producers fought tightening margins as feedstock ethylene costs moved up sharply in January to peak in early February.
The EDC price increase roughly followed its raw material cost factor derivative polyvinyl chloride (PVC). EDC accounts for about 45% of PVC raw material costs. PVC rose about $100/tonne during the quarter and contract prices rose 4 cents/lb, or $88/tonne.
US EDC exports fell during the last four months of 2016 compared with the same period in 2015, but started 2017 with the highest January export volumes of the past four years. Still, US exports were up 10% for 2016 compared with 2015.
US EDC prices are expected to continue to follow the values for PVC during the second quarter.
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ICIS price assessments are based on information gathered from a wide cross-section of the market, comprising consumers, producers, traders and distributors from more than 250 reporters world-wide. Confirmed deals, verified by both buyer and seller, provide the foundation of our price assessments.
Our in-depth market knowledge drives our specialist focus, as we recognise the importance of individual market dynamics and not a one-size-fits-all approach.
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Brian Mahoney reluctantly walked away from St. John's University yesterday. He was asked to leave the job he once coveted for years, the one for which he waited patiently if anxiously in the spring of 1992 while a slow-moving search process eliminated more-established candidates.
Less than one year later, Mahoney was the Big East coach of the year. Today he is unemployed.
Five days before, at the somber conclusion of a third consecutive nonwinning season, Mahoney had stood in an emptying dressing room in Madison Square Garden and repeated that he had no intention of resigning as head basketball coach.
"He was asked to step down," said Ed Manetta, the St. John's athletic director, who delivered his decision to Mahoney during a meeting yesterday. The resignation, after an 11-16 season completed Mahoney's four-year record of 56-58, including 31-47 in Big East play, leads St. John's to a situation the university has not faced for decades, if ever.
St. John's must now respond to the forced departure of a coach without anything close to an obvious replacement, as pressure builds to produce a high-powered successor. When Frank Mulzoff left in 1973 after three post-season appearances in three years, Lou Carnesecca was ready to return from the New York Nets of the defunct American Basketball Association. When Dusty DeStefano, an assistant under Frank McGuire, was removed as head coach in 1956 after an experience similar to that of Mahoney, Joe Lapchick was eager to return from the Knicks.
Now, as other metropolitan area teams work to raise their profiles, St. John's must start over.
"There will be no search committee," Manetta said. "I will interview the candidates. I will select the finalists."Continue reading the main story
At that point, Manetta said, he will make his recommendation to the Rev. Donald J. Harrington, the school president, who declined to discuss the decision yesterday. The president's office released a two-paragraph statement that said in part: "At St. John's, our priority has always been the total development of our student athletes -- both as competitors and as people. That is our commitment to them. Ed's decision has been made in keeping with that commitment, and he has my support."
Manetta said he did not have a timetable in mind. Although the process may be more direct than it was in 1992, the marketplace has grown four years more complex and costly. The search will soon establish whether St. John's can break from the pattern established by past Big East hires by meeting the demands of high-profile candidates seeking minimum packages of $500,000 a year.
The second- and third-generation coaches hired by Big East schools, like Jim Calhoun of Connecticut and Steve Lappas of Villanova, established their coaching credentials at a level beneath the elite leagues. A move within that economic framework could lead Manetta to conversations with Fran Fraschilla of Manhattan, Mike Jarvis of George Washington, Herb Sendek of Miami of Ohio and Bob McKillop of Davidson.
Fraschilla, when reached at his office yesterday afternoon, said his only concern was preparing the Jaspers for their National Invitation Tournament game against Wisconsin. "That is really all I am going to allow myself to think about," he said. "I owe it to them."
The choice of a coach with a higher profile, such as P. J. Carlesimo of the Portland Trail Blazers or Tom Penders of Texas, would require an unprecedented economic commitment, enough to possibly require the school to establish an endowed position. Penders has seven years remaining on his contract.
"I'm not expecting anyone to call me," Penders said last night. "I'm not looking for a job. I don't need an offer to improve my situation. I don't think it would be fair to Texas or the kids I have in my program."
Attempts to reach Mahoney were unsuccessful. A 16-year assistant under Carnesecca, he was rewarded with a seven-year extension after his first season ended with a second-round National Collegiate Athletic Association tournament appearance in 1993. Manetta did not discuss details, except to say: "We have an existing contract with Brian. We'll fulfill what needs to be done."
Mahoney had insisted in recent weeks that his contract was guaranteed to the year 2000. A person familiar with the contract, speaking on the condition of anonymity, said that a provision calls for the university to cover the difference if Mahoney's future salary should be less than than his base pay at St. John's.
Felipe Lopez, whose decision to enroll at St. John's as the national high school player of the year intensified the program's expectations two years ago, said the players had been told they would meet with administrators today to have the decision explained to them.
"It was a struggle all year for the coaches and the players," Lopez said. "It's kind of surprising because coming in, we had a great recruiting class. We never knew that it would come to this."Continue reading the main story


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text: Politics 19 March 2007 Time for a new "ism"? The death of a great thinker also marks the end of a movement Sign up for our weekly email * With the passing of Jean Baudrillard, should we be asking if postmodernism has gone the same way? The argument that postmodernism is over has already been made by academics, yet it is a grave mistake to restrict the debate to the practices and suppositions of philosophers and critics. Many academics will simply decide that, finally, they would rather stay with Baudrillard than go over to anything new. Again, there have been writers (such as the New Puritans, if you remember them) and artists (such as the Stuckists) who have declared the end of postmodernism, but it won't be replaced by some manifesto signed at a café by bullish young aesthetes. And yet, a compelling case can be made that postmodernism is dead, just by looking at the cultural production of our times. I have in front of me a module description, downloaded from the website of a British university's English department. It includes details of assignments and a week-by-week reading list for the optional module Postmodern Fictions. Most of this year's undergraduates will have been born in 1985 or after, and all but one of the primary texts for the module were written before their lifetime. Far from being "contemporary", these works were published in another world: The French Lieutenant's Woman, Nights at the Circus, If On a Winter's Night a Traveller, Do Androids Dream of Electric Sheep (and Blade Runner), White Noise. This is Mum and Dad's culture. It's all about as "contemporary" as the Smiths, as hip as shoulder pads, as happening as a Betamax VCR. These are texts just coming to grips with the existence of TV and rock music; they do not dream of the possibility of any of the technologies - mobile phones, email, in every house a computer powerful enough to put a man on the moon - that today's undergraduates take for granted. Look out at the cultural landscape and you will catch hardly a glimpse of postmodernism. Its hallmarks - self-conscious reflection on the process of representation and manipulation of inherited artistic expectations; irony; the asserted impossibility of knowing "reality"; the interplay of high and low culture; the constructed nature of selfhood, and so on - are absent from almost all the dominant texts and cultural forms of our century. The only place where the postmodern is vibrantly extant is in cartoons such as Shrek and The Incredibles, as a sop to parents obliged to sit through them with their toddlers. And this has happened so quickly. The word itself has become dreadfully unhip; the cultural modes associated with it are nowhere to be seen. What has superseded it? Good question, but one for another day. For now, weary English lecturers might care to note that they are going to have to prepare another module for next year's undergraduates: the one on "postmodern fictions", supplemented by a new one on "contemporary literature". It keeps them off the streets. Subscribe from just £1 per issue This article first appeared in the 19 March 2007 issue of the New Statesman, Trident: Why Brown went to war with Labour More


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UK Dating
I met a man on here in feb and we had been seeing each other but things got too serious too quickly so we seperated... more..
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Two parts of the brain 'decide who we are attracted to'Posted on: November 8, 2012 16:33:52
Scientists have discovered the part of the brain that decides who we are attracted to.
Researchers at Trinity College Dublin recruited 151 volunteers for a speed dating study to find out how people make romantic decisions.
Prior to the event, 39 volunteers had MRI scans while being shown images of potential dates who would be at the session later in the day.
They were then asked to rate them on a scale of one to four, based on how much they would like to date them.
Like a typical speed dating event, the students were later introduced to others in the study and had the opportunity to speak to them for five minutes.
The findings identified two regions in the brain which assess whether or not someone is a compatible match and make an instant decision on a person's attractiveness.
Predictions beforehand made from the photographs alone proved to be accurate, with people sticking to their initial thoughts about a person 63 per cent of the time.
Got in mind the kind of person you want to date? Try online dating!
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Hong Kong Phil boss "dreams of working with Jackie Chan"Posted on: April 17, 2014 16:26:26
The musical director of one of Asia rsquo s most well-known orchestras dreams of bringing in some unorthodox talent to perform with his musicians Speaking to the South China Morning...
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Lee Ryan and Casey Batchelor steam up the CBB housePosted on: January 6, 2014 17:25:01
They may have been shackled together when they entered the house but Lee Ryan and Casey Batchelor have done anything but drift apart since they were set free In fact...
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The online dating racePosted on: January 6, 2014 16:22:05
New research has revealed how likely single people are to get a message from an online dating site throughout According to MailOnline age matters more to men than women as...
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Sweethearts get engaged after failures on reality TVPosted on: January 3, 2014 19:02:42
When Danielle Cornwall-Nash appeared on ITV s prime time dating show Take Me Out last year she hoped that she would find a new partner and maybe even a new...
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Pancreatic beta cell senescence contributes to the pathogenesis of type 2 diabetes in high-fat diet-induced diabetic mice
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During the pathogenesis of type 2 diabetes insulin resistance causes compensatory proliferation of beta cells. As beta cells have a limited replication potential, this compensatory proliferation might accelerate cellular senescence and lead to diabetes. We examined the cellular senescence of beta cells after proliferation during lipoglucotoxicity.
Senescence-associated markers in beta cells were examined in nutrient-induced diabetic C57BL/6J mice that were fed a high-fat diet. After 4 and 12 months of the high-fat diet, intraperitoneal glucose tolerance tests (IPGTTs) and histochemical analyses of Ki-67, p38, senescence-associated beta-galactosidase, and beta cell mass were performed.
At 4 months, the AUC for plasma insulin levels during the IPGTT (AUCinsulin) was higher, beta cell mass was 3.1-fold greater, and the proliferation of beta cells was 2.2-fold higher than in the control group. However, at 12 months, AUCinsulin declined, the frequency of Ki-67-positive beta cells decreased to one-third that of the control group, and the senescence-associated, beta-galactosidase-positive area increased to 4.7-fold that of the control group. Moreover, small amounts of p38, which is induced by oxidative stress and mediates cellular senescence, were found in beta cells from the high-fat diet group, but not in beta cells from the control group. Furthermore, the senescence-associated, beta-galactosidase-positive area in the high-fat diet group had a highly significant negative correlation with AUCinsulin (r=−0.852, p<0.01).
Beta cell senescence occurred in diet-induced type 2 diabetes and led to insufficient insulin release. These findings suggest that cellular senescence contributes to the pathogenesis of diet-induced diabetes.
KeywordsCellular proliferation Cellular senescence High-fat diet Pancreatic beta cell Type 2 diabetes
- AUCglucose
AUC for plasma glucose levels during IPGTT
- AUCinsulin
AUC for plasma insulin levels during IPGTT
extracellular signal-regulated kinase
intraperitoneal glucose tolerance test
c-Jun N-terminal kinase
mitogen-activated protein kinase
reactive oxygen species
- SA beta-gal
senescence-associated beta-galactosidase
terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling
Defective insulin secretion in type 2 diabetes mellitus is caused by beta cell dysfunction and reduced beta cell mass. Beta cell dysfunction is caused by chronic hyperglycaemia and/or hyperlipidaemia respectively referred to as glucotoxicity and lipotoxicity, which have been previously reviewed in detail [1, 2, 3].
Long-term regulation of beta cell mass is determined by the balance of beta cell growth, including replication and neogenesis, and beta cell loss through apoptosis, necrosis and senescence [4, 5, 6, 7]. Decreased beta cell mass occurs in humans with type 2 diabetes and animal models of type 2 diabetes [6, 7, 8, 9, 10, 11, 12]. Chronic hyperglycaemia leads to progressive loss of beta cell mass with a prolonged increase in the rate of beta cell apoptosis without a compensatory increase in beta cell growth. In addition to necrosis, markedly increased beta cell apoptosis is regarded as one of the major factors in the pathogenesis of diabetes. The cellular mechanisms of increased beta cell apoptosis, which include hyperglycaemia-induced oxidative stress [8, 12], are being intensively studied [13, 14, 15, 16, 17, 18].
Beta cell senescence also affects beta cell mass, but has not been studied in diabetes. Mammalian cells, with the exceptions of germ line cells and stem cells, have a limited replication potential in vivo, defined as replicative senescence, which amounts to irreversible growth arrest after a limited number of cell divisions [19]. Cellular senescence is also associated with reactive oxygen species (ROS), the incessant damaging products generated from aerobic metabolism such as oxidative stress [20, 21, 22, 23]. During the pathogenesis of type 2 diabetes, beta cell proliferation increases to compensate for the increased insulin demand caused by insulin resistance, and the generation of ROS is induced by hyperglycaemia [6, 7, 8, 12, 24]. It would seem that beta cell proliferation and/or ROS generation accelerate cellular senescence and lead to diabetes. Type 2 diabetes in C57BL/6J mice is provoked by a high-fat diet and is associated with obesity, hyperglycaemia and hyperinsulinaemia [25, 26], which induce beta cell proliferation and ROS production in beta cells. To test the hypothesis that cellular senescence occurs in beta cells and contributes to the pathogenesis of type 2 diabetes, we fed C57BL/6J mice a high-fat diet for 12 months and examined cellular proliferation and ageing markers in the beta cells.
Materials and methods
Six-week-old C57BL/6J male mice were purchased from Clea Japan (Tokyo, Japan). The control group was fed a normal diet (AIN-93; 14% protein, 72% carbohydrates, 4% fat) [27], with free access to water. The high-fat diet group was given free access to a high-fat diet, in which beef tallow replaced 36% of the carbohydrates in the normal diet (high-fat diet: 14% protein, 36% carbohydrates, 40% fat). The mice were housed in a temperature-controlled room with a 12 h light–dark cycle. All experiments were approved by the Animal Ethics Committee of Kagawa Nutrition University and complied with the "Principles of laboratory animal care" (NIH publication no. 85-23, revised 1985).
Blood analysis and glucose tolerance tests
For the intraperitoneal glucose tolerance test (IPGTT), mice fasted for 12 h and blood was drawn from the tail vein at 0, 30, 60 and 120 min after i.p. injection of glucose (2 g/kg of body weight). To measure plasma lipids, blood was collected from the tail vein before the i.p. injection of glucose. Plasma glucose, NEFA, triglycerides and total cholesterol were measured by commercial kits (Wako Pure Chemical Industries, Osaka, Japan). Plasma insulin was measured using a rat insulin enzyme immunoassay system (Amersham Biosciences, Piscataway, NJ, USA). At each time point, blood samples (approximately 70 μl) were taken in one capillary tube, with the exception of the blood samples taken at the 0 time point (approximately 100 μl in 1.5 capillary tubes). Because of the small body weight of the mice, the blood volume needed for microanalyses was only 2 μl, with the exception of the insulin analyses (20 μl). The trapezoid rule was used to determine the AUC for glucose and insulin concentrations in each animal. The insulinogenic index was calculated by dividing the AUC for plasma insulin levels during IPGTT (AUCinsulin) by the AUC for plasma glucose levels during IPGTT (AUCglucose) (0–30 min).
Isolation of islets and islet study
Islets were isolated from the pancreas by collagenase digestion and collected under a microscope after 4 and 12 months of the high-fat diet. Islets were cultured for 12 h in RPMI 1640 medium containing 11.1 mmol/l glucose, 10% heat-inactivated fetal bovine serum, 100 IU/ml penicillin and 100 μg/ml streptomycin, as previously described [28, 29]. Then, size-matched islets were pre-incubated for 60 min at 37 °C with KRB containing 0.2% BSA and 2.8 mmol/l glucose. After pre-incubation, 10 islets were stimulated with KRB at the indicated concentration of glucose for 1 h at 37 °C. Immediately thereafter, the supernatant was collected and stored at −80 °C until the insulin assay. Then, islets were washed with PBS three times and homogenised with acid ethanol (0.18 mol/l HCl in 95% ethanol) to determine the insulin content.
Immunohistochemical analysis
For double-immunohistochemical staining of insulin and glucagon, Ki-67, or phospho-p38 (Thr180/Tyr182), pancreases from mice after 4 and 12 months of the experimental period were weighed, fixed overnight in 4% paraformaldehyde at 4 °C, embedded in paraffin, and sectioned. Three sections (3 μm) separated by 200 μm were incubated with rabbit anti-human glucagon polyclonal antibody (DakoCytomation, Carpinteria, CA, USA) diluted to 1:100, rat anti-mouse Ki-67 monoclonal antibody (TEC-3; DakoCytomation) diluted to 1:50, or mouse anti-human phospho-p38 monoclonal antibody (28B10; New England BioLabs, Beverly, MA, USA) diluted to 1:50. As secondary antibodies, swine anti-rabbit IgG (DakoCytomation) diluted to 1:1,000, rabbit anti-rat IgG antibody (DakoCytomation) diluted to 1:200, or rabbit anti-mouse IgG antibody (Rockland, Gilbertsville, PA, USA) diluted to 1:1,000 were used. We used 3,3′-diaminobenzidine tetrahydrochloride (DAB; Dojin, Tokyo, Japan) as substrate chromogen. Next sections were washed with 0.1 mol/l glycine–HCl buffer (pH 2.2) following incubation with guinea pig anti-porcine insulin antibody (DakoCytomation) diluted to 1:200. As a secondary antibody, rabbit anti-guinea pig IgG coupled to peroxidase (Rockland) diluted to 1:1,000 was used. Sections were stained with 3-amino-9-ethylcarbazole (Sigma-Aldrich, St. Louis, MO, USA) as substrate chromogen and counterstained in haematoxylin.
Pancreatic islet morphology
For morphometric analysis of beta cell mass, three sections of each pancreas were covered systematically by capturing images from non-overlapping fields with a digital camera (Nikon 950; Nikon, Tokyo, Japan). The islet area and the section area were analysed using NIH Image 1.63 software, as previously described [30]. The percentage of beta cell area in the islet area was calculated by dividing the area of all insulin-positive cells by the islet area and by multiplying by 100. The islet mass was calculated by multiplying the pancreas weight by the percentage of islets per pancreas. The beta cell mass was calculated by multiplying islet mass by the percentage of beta cells per islet. To assess the relative rate of beta cell neogenesis from exocrine duct cells, we quantified the percentage of exocrine duct cells that were immunoreactive for insulin, as previously described [31]. The resulting data were expressed as the percentage of duct cells that were positive for insulin in each pancreas, and the mean was calculated for each group.
Beta cell proliferation
Beta cell replication per islet was calculated by comparing the insulin and Ki-67 stains and averaging the number of Ki-67-positive beta cells from approximately 80 islets per mouse.
Detection of cellular senescence
Cellular senescence was evaluated by immunohistochemistry with cellular senescence marker phospho-p38 and by senescence-associated beta-galactosidase (SA beta-gal) staining. The frequency of beta cell senescence determined by immunohistochemistry was calculated using the method described for cell replication. The detection of SA beta-gal was performed as previously described [32] with minor modifications. After 12 months of the experimental period, pancreases were fixed for 3 h in 4% paraformaldehyde at 4 °C, placed overnight in PBS (pH 7.2) containing 30% sucrose at 4 °C, embedded in Tissue-Tek OCT compound (Miles, Elkhart, IN, USA), frozen, and sectioned into 8 μm thick slices by a refrigerated microtome. SA beta-gal was detected by a senescence detection kit (BioVision, Mountain View, CA, USA) and counterstained with Kernechtrot. For each pancreas, the images of islets in two sections separated by 200 μm were captured with a digital camera (Nikon). The SA beta-gal-positive area in the islets and the islet area were analysed using NIH Image 1.63 software, as previously described [30]. The percentage of SA beta-gal-positive area was calculated by dividing the SA beta-gal-positive area in the islets by the islet area and multiplying by 100.
Detection of apoptosis
To detect apoptosis, three sections (3 μm) separated by 200 μm were stained by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) method using an in situ apoptosis detection kit (Wako Pure Chemical Industries, Japan). DAB was used as substrate chromogen. Frequency of pancreatic islet cell apoptosis, which was expressed as events per islet, was calculated by averaging the number of TUNEL-positive beta cells in approximately 60 islets from each pancreas.
Statistical analysis
All data analyses were conducted using StatView 5.0 (SAS Institute, Cary, NC, USA). Data are shown as the mean ± SEM. Correlation analysis was performed between cellular senescence and cellular proliferation, AUCglucose, AUCinsulin, insulinogenic index or p38 mitogen-activated protein kinase (MAPK). The significance of correlation coefficients was analysed by Fisher's z-transformation. Statistical analysis of the other data was performed with the Mann–Whitney U-test. We considered p values of less than 0.05 to be statistically significant.
Body weight, blood analyses, and glucose tolerance tests
Body weight, plasma triglycerides, NEFA, total cholesterol, glucose, and insulin levels of C57BL/6J mice before and after 4 and 12 months of a high-fat diet
Body weight (g)
NEFA (mEq/l)
Triglycerides (mmol/l)
Total cholesterol (mmol/l)
Glucose (mmol/l)
Insulin (ng/ml)
0 months
High fat
4 months
High fat
12 months
High fat
AUCglucose, AUCinsulin, and insulinogenic index during IPGTT in C57BL/6J mice after 4 and 12 months of a high-fat diet
4 months
12 months
AUCglucose(mmol l−12 h−1)
High fat
AUCinsulin(ng ml−12 h−1)
High fat
Insulinogenic index (ng/mmol)
High fat
Islet studies
Beta cell mass and proliferation
Morphometric analysis of pancreas of C57BL/6J mice after 4 and 12 months of a high-fat diet
High fat diet
4 months
% Beta cell/islet
% Islet area/pancreas area
Pancreas weight (g)
Islet mass (mg)
Beta cell mass (mg)
12 months
% Beta cell/islet
% Islet area/pancreas area
Pancreas weight (g)
Islet mass (mg)
Beta cell mass (mg)
Beta cell senescence and apoptosis
Correlation between cellular senescence and proliferation, AUCglucose, AUCinsulin, insulinogenic index and p38 MAPK
The markers of cellular senescence in beta cells were increased in mice fed a high-fat diet. Preceding senescence of the beta cells, increased proliferation was observed under hyperglycaemic conditions. There was a highly negative correlation between cellular proliferation and senescence. These findings indicate that cellular senescence occurs after rapid proliferation of beta cells and causes decreased cellular proliferation and beta cell mass.
Reduced pancreatic beta cell mass is a major factor in the pathogenesis of type 2 diabetes, as well as beta cell dysfunction. The long-term regulation of beta cell mass depends on the balance of beta cell supply from replication and neogenesis and beta cell death mainly from apoptosis [4, 5, 6, 7]. To adapt to hyperglycaemia during the pathogenesis of type 2 diabetes, augmented beta cell proliferation causes a compensatory increase in beta cell mass. The disruption of an adequate increase in beta cell mass leads to type 2 diabetes [6, 7, 8, 9, 10, 11, 12]. After a long-term, high-fat diet, the beta cell proliferation markedly decreased and islet cellular senescence was observed. We were unable to perform beta-galactosidase staining on the islets from 4-month-old mice. However, if senescence stops proliferation, then the necrosis and apoptosis that follow will reduce islet mass. Cell division and cell death are independent events as in the case of neurons, but beta cells are vulnerable to lipoglucotoxicity, and islet mass may be decreased by apoptosis. Reduced hypertrophy may also contribute to the reduction of islet mass. To judge from these findings, beta cell senescence causes decreased beta cell mass and may lead to type 2 diabetes.
Cellular senescence and decreased cellular proliferation occur in chronic diseases with high cellular turnover. For example, liver cirrhosis, in which chronic hepatocyte death and renewal is the major predisposing factor, is caused by hepatocyte senescence with concomitant telomere shortening that limits the number of cell divisions in humans [33]. Recent in vitro studies [34] have found that senescence of human primary pancreatic beta cells is responsible for limiting the number of cell divisions. It seems likely that repeated replication during differentiation, such as high cellular turnover during the pathogenesis of liver cirrhosis, could cause islet cells to become senescent. Many studies indicate that the high cellular turnover of beta cells that is caused by beta cell replication and apoptosis is observed in the pathogenesis of type 2 diabetes. However, no previous reports discuss whether beta cell senescence occurs in type 2 diabetes. The current theory is that insufficient beta cell proliferation occurs at an early stage of type 2 diabetes pathogenesis and that the markedly increased beta cell apoptosis is the main factor of reduced beta cell mass in the pathogenesis of type 2 diabetes. Actually, we observed markedly increased cellular apoptosis after a long-term, high-fat diet. However, in our study (for 4 months) and another [14] longitudinal study in rodents, proliferation of beta cells was found even after a long-term prediabetic stage, suggesting that compensatory beta cell proliferation is maintained until the loss of the remaining beta cell divisions.
In addition to high cellular turnover, there may be another pathway of beta cell senescence in diabetes. Senescence of human primary pancreatic beta cells is caused by a telomere-independent pathway because senescence is not prevented by the expression of telomerase, which extends telomere length [34]. Additionally, telomere length in mice is much longer than in humans, suggesting that telomeres are not related to cellular senescence in mice [35, 36]. Many studies demonstrate that cellular senescence is caused by ROS and is mediated by enhancing the activity of MAPK, which consists of at least three enzymes, including extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAPK. For example, in rat kidney cells the ageing process parallels increases in ROS that strongly enhance the activities of ERK, JNK, and p38 MAPK [21]. Isawa et al. reported that p38 MAPK is an important causative molecule in both telomere-dependent and telomere-independent cellular senescence, including ROS-induced senescence in both human and mouse fibroblasts [37]. Oxidative stress occurs in the diabetic state [8, 38], and ROS are produced in islets through the non-enzymatic glycosylation reaction and the electron transport chain in mitochondria [12, 39]. It was recently reported that p38 MAPK in isolated rat islets is activated by oxidative stress [40]. In our study, the active form of phospho-p38 was observed in the islets of diet-induced diabetic mice at the late stage of the high-fat diet, but the frequency of phospho-p38 was small compared with the percentage of SA beta-gal staining in the islets. Moreover, there was a significant positive correlation between the frequency of phospho-p38-positive beta cells and the percentage of SA beta-gal-positive area in islets of the high-fat diet group. The cyclin-dependent kinase inhibitors p16 and p21 are increased in p38-activated senescence [37]. Furthermore, oxidative stress induces p21 (WAF1/CIP1/Sdi1) expression in isolated rat islet cells by treatment with H2O2 and pancreatic rat islet cells of hyperglycaemic Zucker diabetic fatty rats [41]. Our results and the previous findings suggest that beta cell senescence is caused by oxidative stress and may be mediated by the p38 MAPK pathway, resulting in the elevation of p21.
In conclusion, decreased beta cell proliferation and cellular senescence are found in diet-induced type 2 diabetic mice. Cellular senescence may be caused by the compensatory rapid proliferation of beta cells needed to maintain adequate beta cell mass and/or the accumulation of ROS in beta cells. Beta cell senescence leads to insufficient insulin release as a consequence of decreased beta cell mass and contributes to the pathogenesis of diet-induced diabetes.
This study was supported by the High-Technology Research Centre Project of Kagawa Nutrition University from the Ministry of Education, Japan. We thank Dr Yasunori Kanazawa (Jichi Medical School Tochigi, Japan) for helpful discussions.


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Drying Up: What to Do About Droughts in the People's Republic of China
Climate change is one of a few major factors that ensure the country will continue to struggle to supply its cities and industries and fields with enough water, particularly in the North, as well as face more frequent and longer droughts.
The country has shown a stunningly agile disaster response system, but its system for disaster prevention and management is far less developed. The road to greater drought management and sustainable water supplies is demand management. How to achieve this in a historically hydraulic-engineering society is explored through the case study of Guiyang Municipality in Guizhou Province.
- Foreword
- Executive Summary
- Drought and Shortage - A New Normal or a Wake-Up Call?
- Track 1: Drought Risk Management
- Track 2: Optimal Infrastructure
- Track 3: Ecosystem-Based Management
- Conclusion
- Appendix: Nonstructural Demand Management / Risk Management Measures