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This question already has an answer here:
- What to do about rep inflation? 11 answers
I was wondering about this for a while now.
Since people really only gain reputation and don't really lose it over time (barring extreme cases), will the various reputation levels stay consistent or will they move? Will an upvote always be 10 points and a downvote 2?
Since there is no real 'sink' to take reputation away, everyone will eventually have tons of it and everyone will be a 10k+ moderator. What will be done to prevent this? Or is this the ideal?


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Post by Stefan Van Eycken, Tokyo
Read more about Chichibu Distillery here.
Great news for the new peated ! Really looking forward to trying it ! Thanks for the notice.
Thanks for your kind words, Adrien. It's a beautiful whisky and if you liked (or missed!) the first Peated, be sure to get a bottle of this. You won't regret it.

subset: commoncrawl


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First, sign in at Device Support and then select Register new device. After you've registered, you'll see the warranty status for your device. If it's within warranty, repairs are free. If your device is out of warranty, you'll be charged a repair fee.
After you've registered your devices, follow these steps:
After Device repair receives your submission, they'll send you a service order number and an order confirmation email that has shipping or drop-off instructions.
Send in your device as soon as possible. If you don't ship within 30 days, your service order is canceled and the shipping label will no longer be valid. In countries or regions that offer a drop-off exchange, you must go to the drop-off center within 7 days from the date you created the order.
If after 24 hours you haven't received a confirmation email, check your email program's junk folder or spam filter. If you don't find the email in junk or spam, contact Xbox Support.
If you receive a message that your phone number or email address is invalid, go to How to change the email address associated with your Microsoft account to update your Microsoft account information.
The email confirmation for your service order request contains packing and shipping instructions. For illustrated packing instructions, see How to pack your Xbox console or Kinect sensor for shipping.
Remove all accessories from the Xbox console or Kinect sensor, and remove any discs from the Xbox hard drive. If you send them, you probably won't get them back.
Note The Xbox One S All-Digital Edition doesn't include an optical disc drive.
After your device has been packed, print your shipping label. Tape it to your package and then follow the shipping instructions in the confirmation email.
After your console or sensor has been received at our service center, the average time of service is 14 to 21 days, including shipping time.
To check your order status at any time, click on Order status in the box at the top of this page.
For more information, see Help with your existing Xbox or Kinect service order.
If you purchased a Microsoft Xbox accessory within the last 30 days, you can return it to the retailer with your original proof of purchase. If you purchased the accessory more than 30 days ago but within the accessory warranty period, you can order a replacement accessory from Device Support (console registration is required). Make sure you click Replace an accessory instead of "Repair my device." Follow the onscreen prompts to place an order.
The advance exchange service option allows you to receive a replacement product before you send in your non-working product. To find out if you're eligible for advance exchange, contact Xbox Support.
There are a few important things to know about advance exchange:
Thanks for your feedback!
Provide feedback for this topic
Would you like to contact Support regarding the "Getting your Xbox console or Kinect sensor serviced" issue you were reading about or a different issue?


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The Best Chocolate Cake with Chocolate Ganache
Of the hundreds of dessert recipes I have on my blog, I realized that I didn't have a chocolate cake recipe so I changed that.
With the easiest, one-bowl, five minute, from-scratch chocolate cake you'll ever make.
If you're addicted to cake mix, you can break free. I've been there.
I made this cake without a mixer and it was ready to go from bowl to oven in less than five minutes with just a couple turns of the whisk.
I'm the first to admit that cake mixes can be great because they're convenient, the results are nearly guaranteed, and they produce moist and light cakes.
This scratch cake does the same.
Except it's darker, richer, and more intensely chocolaty than a cake mix chocolate cake, which is a good thing if you like a nice dark, deeply chocolaty, chocolate cake.
One way in which I kept the cake moist was by adding yogurt, which can be replaced with sour cream if that's what you have on hand. Just don't use light or diet yogurt or sour cream. Use thicker or Greek-style full-fat yogurt. You're making chocolate cake, not diet food, so forego the watery diet yogurt.
I also kept the use of baking powder to a bare minimum because I find it dries out cupcakes, muffins, and cakes. The recipe uses just enough to give the cake lightness and lift so that it isn't confused with the denser and flatter chocolate slab that we all know as a brownie.
Finally, I do love butter and will almost always choose butter over oil in baking; except when baking a cake. Oil produces a moister cake in my experience and since all that lovely buttery flavor is going to be masked anyway from the cocoa powder, you're not giving up anything in the flavor department and gaining worlds in the moisture category by using oil rather than butter. A win-win for oil.
Not sold on the cake yet? Allow me to sell you on the chocolate ganache.
Ganache is made by heating cream and pouring it over chocolate and I kept this ganache super simple by heating the cream in the microwave. You could heat it over the stove, but why bother.
The beauty of the ganache is that even after it sets up, it still has a juicy quality to it in comparison to say buttercream frosting, which can become a bit hardened around the edges after it's been exposed to air for a few hours. Crunchy frosting is never a good thing.
If frosting can taste elegant and classy, this ganache is how; as opposed to this frosting which is more along the lines of a finger-lickin' good frosting.
There's no sugar added to the ganache and it's only as sweet as the chocolate you select, which in my case was semi-sweet chocolate chips. Go as milky or dark as you enjoy. Feel free to spike your ganache with a couple tablespoons of bourbon, rum, or a fancy flavored liqueur.
Skylar requested this cake for her next birthday and Scott said, "Good idea, honey. This cake does taste like chocolate birthday cake tastes."
Yes, of course it does because most chocolate birthday cakes are cake mix cakes.
Now you can bypass the cake mix and make this in five minutes instead.
The Best Chocolate Cake With Chocolate Ganache
This is the best chocolate cake I've ever had or made, and it's the easiest. One bowl, no-mixer, no creaming ingredients, and nothing funny. This cake is fast, easy, and always delivers amazing results. You can bake it as cupcakes, too. The ganache is rich and velvety, and the perfect pairing with this deep, dark, not-too-sweet, and very moist cake. The cake is a reader favorite!
Chocolate Cake
1 large egg
1 cup granulated sugar
6 ounces plain, vanilla, or chocolate yogurt (thicker Greek-style preferred, do not use diet, fat-free or light yogurt; sour cream may be substituted)
1/4 cup canola or vegetable oil
1 1/2 teaspoons vanilla extract
1/2 cup brewed coffee, room temperature or warm
1/2 cup unsweetened natural cocoa powder
1 cup all-purpose flour
1 teaspoon baking soda
1/2 teaspoon baking powder
1/2 teaspoon salt, optional
Chocolate Ganache
9 ounces semi-sweet chocolate (about 1 1/2 cups semi-sweet chocolate chips)
3/4 cup heavy cream or half-and-half
1 teaspoon vanilla extract (or optionally use 1 to 2 tablespoons rum, bourbon, coffee-, orange-, raspberry-, chocolate-flavored liqueur)
Cake – Preheat oven to 350° F. Line a 9-by-9-inch square baking pan with aluminum foil and spray with cooking spray, or grease and flour the pan; set aside.
In a large mixing bowl combine egg, sugar, yogurt, oil, vanilla, and whisk until smooth and combined. Add coffee, cocoa powder (I used Hershey's), and whisk vigorously until batter is smooth and free from lumps.
Add the flour, baking soda, baking powder, salt, and whisk vigorously until batter has just combined, about 1 minute. Note about coffee: The coffee does not make the cake taste like a coffee-flavored cake. Rather, it brings out and enhances the flavor of the cocoa powder and adds depth of flavor; I highly recommend coffee but use water if you must. The coffee can be any temperature other than piping hot; you don't want to scramble the egg.
Pour batter, which is a loose and fairly runny batter, into prepared pan and bake for about 25 minutes, or until top has set and a toothpick or cake tester inserted in the center comes out clean. Allow cake to cool in pan completely, at least 30 minutes, before adding ganache or frosting the cake, or before slicing and serving. Unfrosted cake can be stored in an airtight container at room temperature for up to 5 days, or store frosted cake in the refrigerator for up to 5 days.
Chocolate Ganache – Place chocolate in a medium microwave-safe bowl and heat on high power for 1 minute to soften chocolate; set aside.
In a small microwave-safe bowl or measuring cup, heat the cream (I used half-and-half) on high power just until it begins to bubble and show signs of boiling, about 60 to 75 seconds.
Pour hot cream over chocolate and let it stand about 1 minute. Whisk vigorously until chocolate has melted and mixture is smooth and velvety.
Add vanilla or optional flavorings and stir to combine. Set bowl aside for about 10 minutes, allowing ganache to cool and thicken a bit. Whisk mixture briefly before pouring all of it over the cake. Lightly smooth and spread the ganache with a spatula or offset knife. Allow ganache to set up for at room temperature for at least 30 minutes before slicing and serving the cake; or speed this process up by placing pan in the refrigerator or freezer briefly.
All images and content are copyright protected. Please do not use my images without prior permission. If you want to republish this recipe, please re-write the recipe in your own words, or simply link back to this post for the recipe. Thank you.
Related Recipes
White and Dark Chocolate Cream Cheese Chocolate Cake Bars – these use cake mix but the preparation method isn't traditional
Mounds Bar Chocolate Coconut Cake Mix Cookies
Fudgy Nutella Brownies with Cream Cheese Frosting – my favorite brownie base recipe which is as easy as making brownies from a box, I promise; and it's the brownie base I use for all brownies before doctoring them up with other add-ins or tweaks
Frozen Chocolate Pudding and Wafer Cake (No-Bake, 3 ingredients)
Chocolate Cake Batter Milkshake
Do you have a favorite from scratch cake recipe?
Feel free to link it up; chocolate, yellow, vanilla, carrot, red velvet, whatever it is as long as it's amazing.
How often do you use cake mixes?
I did a 15 Recipes Using Cake Mix (But None of Them Actually Make a Cake) post and since then, I've really cut down on the amount of cake mix I use. They have their time and place, and I will always use them I'm sure.
However, I'd like to post more classic type recipes on my blog and an easy, but practical, tasty, and moist chocolate cake from scratch was a good place to start.


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The following commentary does not necessarily reflect the views of AgWeb or Farm Journal Media. The opinions expressed below are the author's own.
Here's your chance to share a photo of your favorite tractor.
Written by Larry Gay
In late October 1938, Harry Ferguson of England brought a Ferguson-Brown tractor with a hydraulically-controlled hitch to the U.S. and demonstrated his tractor and attached implements to Henry Ford. Ford was very impressed with how Ferguson's tractor outperformed the Allis-Chalmers B and Fordson tractors that Ford used for comparison. As a result, Ford and Ferguson sat at a table in the field and worked out an agreement that Ford would manufacture a tractor with Ferguson's patented hitching system and Ferguson would market the tractor and implements. The discussion ended with a handshake and was never put in writing.
Ten Ford engineers, led by Harold Brock, started designing the new tractor in January 1939. Two of Ferguson's assistants helped adopt the hydraulic-hitching system into the tractor. To simplify the design process, the Ford engineers used many production automobile and truck parts and the 4-cylinder, 120-cubic-inch engine was derived from the Mercury V-8 automobile engine.
On June 29, 1939, the Ford-Ferguson 9N tractor was introduced to the press and the public. The 9N was a small, low-profile tractor with the operator's seat positioned immediately above the transmission case, requiring the operator to straddle the transmission. Although the tractor had four wheels with one on each corner, it was not a standard-tread tractor because the wheels could be adjusted to match the spacing of row crops and the front axle had 21 inches of clearance. The 9N was the first example of what we now identify as a utility tractor.
One of the biggest problems encountered during the development process was what name to put on the tractor. Eventually it was decided to put the Ford name on one plate and Ferguson System on another plate. The tractor weighed about 2,140 pounds and the initial retail price was $585. About the first 750 were built with a cast aluminum hood until the stamping dies for the sheet metal hood were built.
The trade magazines were impressed by the unique hitching system on the rear of the tractor for attaching a series of wheel-less implements. Demonstrations during the introduction meeting emphasized the ease of attaching the implements, backing into corners, and the weight transfer to the tractor's rear wheels. This hitching system soon became known as a 3-point hitch.
The 9N model became the 2N during World War II with the material changes required due to the war, but the serial number retained the 9N prefix. From 1939 through 1947, Ford Motor Company built about 99,000 of the 9N and 207,000 of the 2N for a total of about 306,000 tractors.
Harold Brock continued to lead the Ford tractor engineers until 1959. By 1963, he was the leader of the John Deere tractor engineers when the John Deere 4020 tractor was introduced. Two classic tractors in one engineer's lifetime is an outstanding achievement. Harold Brock passed away on January 2, 2011 at the age of 96.
Larry Gay is the author of four tractor books published by the American Society of Agricultural and Biological Engineers, including A Guide to Ford, Fordson, and New Holland Tractors. This book may be obtained from ASABE at 800-695-2723 or asabe.org, click publications and then click history books.
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Clean for Sustainability
Rochester Midland Corporation (RMC) is a leading manufacturer of specialty chemicals for food sanitation, water treatment, legionella control, facility maintenance , restroom odor control, feminine bin services, and industrial cleaning.
Our HACCP-based BrandGuard® Program offers solutions to food manufacturers across all aspects of food safety including brand protection and sustainable solutions.
Rochester Midland is the leader in Green Housekeeping and manufactures Enviro Care®, an extensive line of environmentally preferable products for all markets, as well as many other bio-based products.
RMC Water Energy programs for cooling towers, boilers and other closed loop programs save energy through improved heat transfer efficiency by removing existing deposits and preventing future deposits. The wastewater treatment programs increase water reuse, decrease solid waste and ensure compliance with wastewater discharge requirements.
Long involved with green initiatives and other sustainable efforts, RMC began formalization of its Sustainability efforts in 2010, with the publication of its first Sustainability Report. Rochester Midland is committed to developing sustainable solutions for health, productivity and the environment.


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Riding Overseas: Get Your International Driving Permit
Because I wasn't exactly clear on the function of the International Driving Permit, I was unsure of whether or not I needed to have one when we head to Italy.
What is an International Driving Permit/License?
It is a booklet that translates the type of American license you hold (ie. motorcycle, car, bus etc. ) into 10 different languages. It is to be carried along with your American license. Inside, it contains your name and birth date information, a passport-sized photo of you and your signature. Your IDP is valid for 1 year.
An IDP does not give you "permission" to drive abroad. Your own United States license does this. It simply helps whomever needs to see your US license understand just what it is they are looking at and the type of vehicle you are permitted to operate.
Many European car or motorcycle rental outfits will require that you have an IDP in order to use their services.
Where do you get an International Driving Permit?
There are 2 associations to get an IDP from: American Automobile Association and The National Automobile Club.
I was able to walk in to my local AAA office and get an IDP on the spot. It was $15 plus a nominal fee for them to take 2 passport photos. The whole process took less than 15 minutes. If you do not have a local AAA office, you can order your IDP via mail, as well.
The Verdict
Do you "need" an International Driving Permit? You might be able to get by without it, but for less than $20 why take the risk and open yourself up to unnecessary hassle? Get one.
More Information


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Hi guys,
I've been working on a practice problem the last couple hours but for some reason can't decide how best to solve it. The problem is as follows:
"you are given the following two portfolios:
Portfolio A consists of a 1000 par-value 4 year bond with 7% annual coupons and a 5 year zero coupon bond with a par value of X. Both bonds redeem at par."
Portfolio B consists of a single 4 year zero coupon bond with maturity value of 10000
All bonds yield an annual effective rate of 7%. The portfolios both have the same volatility. Find X."
Currently, I've done
(10,000/1.07^4)-1000 = 6628.95
But I'm not even sure I'm headed in the right direction.
Any help is appreciated. Thanks!


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Several new features in Microsoft Office SharePoint Server 2007 allow you to share, control, and reuse business information. This article provides an overview of the new features, describes how the features relate to each other, and helps you find resources for more information.
In this article
Overview of Business Intelligence features
Traditionally, the tools for accessing large amounts of unstructured data for the purpose of analysis were available only to people with years of experience in data warehousing or data mining. Publishing to the Web by using data from multiple sources is something historically restricted to developers and consultants. By using the new features available in Office SharePoint Server 2007, information workers can assemble data from multiple sources and publish that data on the Web.
Office SharePoint Server 2007 can link to business applications, such as SAP, Siebel, and Microsoft SQL Server 2005, allowing you to easily publish reports, lists, and key performance indicators (KPIs).
When you publish reports from the data in one of these systems, you provide strategic or operational data for decision-makers. Examples of reports include Microsoft Office Excel workbooks, a SQL Server Reporting Services report, or a Microsoft Office Access report. Executives and line managers rely on timely and accurate reports to make informed decisions.
At the center of the new Office SharePoint Server 2007 Business Intelligence features is the Report Center. The Report Center is a site that provides a central location for storing reports that are common to a group, whether it is as small as a one team or as large as an entire organization.
The Report Center
The Report Center site provides a central location for business-intelligence-related information. It contains special document libraries for storing reports, lists, and connections to external data sources. It also provides access to page templates and Web Parts to help you create pages and lists that contain business information. Within the Report Center, users can search for items by using categories, view a calendar of upcoming reports, and subscribe to reports that are relevant.
By default, one Report Center site is created under the top-level portal site. However, with the appropriate permissions, anyone can create a Report Center site within a team, department, or organization site.
All of the features described in this article are available in the Report Center site. However, each of the features can be accessed and used in any site and from any page within Office SharePoint Server 2007. This allows you to decide how you want to take advantage of the business intelligence features within your own Office SharePoint Server 2007 environment.
Excel Services
Excel Services enables you to store an Excel workbook on a server and then publish any part of that workbook on a Web page. Users need only a browser to view and interact with the live data. The workbook is published on the Web page by using the Excel Web Access (EWA) Web Part.
One advantage of publishing workbooks in a Web Part is that all of the calculation occurs on the server. As a result, the business logic in the workbook is never exposed. Another advantage is that there is only one copy of the workbook, and it is stored in a central, secure place.
From the Web page, you can give users "view only" rights to limit access to the workbook. For example, you can prevent users from opening a workbook by using Excel or control what they are allowed to view.
You can also create a snapshot of a workbook, rather than publishing it in interactive mode.
Connections to external data sources
In addition to using external data sources in Excel workbooks, you can use data from other business applications, such as SAP and Siebel, in SharePoint lists, pages, and Web Parts.
Administrators usually create the system connections and can store them in a Data Connection Library in the Report Center. That way, the central pool of connections can easily be accessed and reused by anyone with permissions. However, you can create and store data connections anywhere in the Office SharePoint Server 2007 system.
By using connections to external data sources, you can build Web Pages and SharePoint lists that allow users to interact with the data in the external source without ever leaving the SharePoint page.
Key Performance Indicators (KPIs)
A Key Performance Indicator (KPI) is a visual cue that communicates the amount of progress made toward a goal. KPIs are valuable for teams, managers, and businesses to evaluate quickly the progress made against measurable goals. By using SharePoint KPIs, you can easily visualize answers to the following questions:
What am I ahead or behind on?
How far ahead or behind am I?
What is the minimum I have completed?
Each area of a business may choose to track different types of KPIs, depending on the business goals they are trying to achieve. For example, to increase customer satisfaction, a call center might set a goal to answer a specific number of calls within a shorter period of time. Or the sales department might use KPIs to set performance goals, such as the number of new sales calls made per month.
KPIs are created by using KPI lists and then are displayed by using special KPI Web Parts. You can store KPI lists in the Report Center or in any other site in Office SharePoint Server 2007, where they can be reused by anyone with permissions to access them.
Filter Web Parts
Filters allow you to display only the subset of data that you are interested in viewing. For example, a data set can contain five years' history of multiple products for the entire country/region. By using filters, you can display something more meaningful, such as only one sales region, only one product, or only the current year.
Office SharePoint Server 2007 has 10 Filter Web Parts that enable you to enter or choose one or more values to change the contents of one or more Web Parts on a page to display exactly the information you need.
For example, the Current User Filter Web Part automatically filters information based on who is logged on to the computer. This is useful when you want to display only information, such as customer accounts or tasks, that is currently assigned to that user.
Another way to use filters is to display a workbook in an Excel Web Access Web Part and link that workbook to a filter that allows people to choose a product for which they want to view information. In addition, you can link the Filter Web Part to more than one Web Part on the page. As a result, when a different product is selected in the Filter Web Part, all other Web Parts on the page are updated to reflect the currently selected product.
Dashboards are tools that are used to communicate status and to drive action. An Office SharePoint Server 2007 dashboard is a Web page template that allows you to assemble and display information from disparate sources such as reports, charts, metrics, and key performance indicators.
You can create your own dashboard page by using various Web Parts, or you can add Web Parts to pages that already exist in your site. However, if you are creating a dashboard on a new page, starting with the template may be faster. It is just a starting point — you can add or delete items and change the appearance of the page after you create it.
The following Web Parts are included with the dashboard page template.
Web Part
Provides the ability to
Excel Web Access
Add an Excel workbook, worksheet, or worksheet range.
KPI List
Display a KPI List (optional).
Apply Filters (button)
Display the Apply Filters button.
Related Information
Have links related to other page items.
Describe information about plans and status.
Contact Details
List the name of the person to contact about the page.


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A facility in Lenoir County that has been around for nearly five years is still barely known by many in the area.
There is a 5-year-old facility in Lenoir County that to many people is still unknown.
Almost every Friday night, motorists or pedestrians passing by The Gate at 201 E. Gordon St. can hear music pumping from the walls, the laughter of children playing or the sound of teenagers sitting around chatting.
The Gate of Lenoir County opened in 2008. Because of the increase of violence among youth in Lenoir County, it was developed as a place where youth could retreat from the street in a safe, yet fun environment. The mission is to offer �hope for a future to the youth of Lenoir County through Christian values and principles.�
The Gate�s goal is to provide exceptional facilities, faith-based counseling and educational opportunities that will counter cultures of violence, hopelessness, neglect, poverty and abuse with the hope that is found in Jesus Christ. It is open every Friday night for youth in grades six through 12 and is equipped with two PlayStation 3s, a Wii, air hockey, two Fooseball tables and a ping pong table.
Services are provided throughout the week for youth and their families. On Tuesdays, The Gate offers Bible Study for teenaged girls from 5:15 to 7 p.m., free beginning and intermediate guitar classes from 4 to 5 p.m., and free Zumba classes from 6 to 7 p.m. The Gate is working on a mentoring/tutorial program that will match youth with mentors who have specific social and educational skills that meet their needs.
The Gate�s annual fundraiser, The Gatekeeper�s Dinner, is planned for 6:30 p.m. Oct. 25. This year�s Gatekeeper of the Year is Alice Tingle.
Tingle is well known in Lenoir County and has been an advocate for The Gate since its inception. She serves on numerous community agencies, including the Kinston-Lenoir County Chamber of Commerce Board of Directors, the Lenoir Memorial Hospital Foundation Board and the Salvation Army Ladies Auxiliary. She also has been a member of the City Council.
Kent Henderson of Grace Fellowship Church will be honored as Volunteer of the Year. He has taught guitar classes at The Gate for the past three years and has been the praise and worship leader for several events. He is staff pastor at Grace Fellowship, working with congregational care and youth and children�s music ministries. This year, The Gate will also honor three churches that have been instrumental in supporting its mission and vision.
A silent auction will be held during the Gatekeeper�s Dinner. Items available for auction, donated by local businesses, include: oil paintings by youth who attend The Gate; SAKS Fifth Avenue perfumes; UNC tickets; gift certificates to several local restaurants, including Chef and the Farmer; jewelry from J.R. Michaels Jewelers; a basket from The Fresh Market in Greenville; and jewelry from Bailey�s Jewelers of Greenville.
The public is invited to the celebration. Requested donations are $30 per person, available by calling Wanda Hall, executive director, at 252-939-3223.


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This week, two long-awaited movies -- "Taken 2" and "Frankenweenie" -- hit the cinema. Plus, "Princess Bride" gets a 25th anniversary Blu-ray, and an all African-American cast stars in a remake of "Steel Magnolias."
TUESDAY: 'Princess Bride'
"Inconceivable!" "You keep using that word. I do not think it means what you think it means." "Anybody want a peanut?" The wonderfully quotable "Princess Bride" turns 25 this month, and a 25th anniversary Blu-ray offers a fun batch of extras, including an all-new featurette called "True Love: The Princess Bride Phenomenon." Other goodies include interviews with the cast and crew, a video diary from star Cary Elwes and commentaries by director Rob Reiner and screenwriter William Goldman (who also wrote the novel upon which the film is based). Have fun storming the castle! (On sale Oct. 2.)
FRIDAY: 'Taken 2' and 'Frankenweenie'
In 2008's "Taken," Liam Neeson turned into a killing machine after his daughter was kidnapped. So how to reboot that scenario for "Taken 2"? This time around, it's his ex-wife who's taken by the same evil group from the first film. What are the odds? Also opening this week is the full-length version of "Frankenweenie," famous as the short film that got Tim Burton fired from Disney in the 1980s. Now that Burton's a big-name director, the studio gave him big money and resources to turn the idea into a big-screen, full-length 3-D release. The plot hasn't changed over the decade: Kid scientist Victor Frankenstein brings his dog Sparky back from the dead, and to no one's shock but his, that wasn't a great idea. (Both movies open Oct. 5.)
SUNDAY: 'Steel Magnolias'
The original "Steel Magnolias" came out way back in 1989, but if you've ever seen an armadillo groom's cake at a wedding, you know its influence still lingers. Now Lifetime has remade the classic Southern tearjerker with an all African-American cast. The new film features Condola Rashad (Phylicia and Ahmad's daughter) in the Julia Roberts' role of Shelby, with Queen Latifah in the Sally Field role as Shelby's mother. Also starring are Phylicia Rashad herself, Alfre Woodard and Jill Scott. (Oct. 7, 9 p.m., Lifetime.)
Related content:


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Please Mr Postman: snail mail doomed to disappear
Snail mail is crawling to a standstill for Australia Post.
Under the ''education'' tab of the Australia Post website, there is a page that opens with a quaint lesson for young students. The enthusiastic explainer reads: ''Communication has not always been about wall posts, status updates, texts, tweets or emails.''
It is the beginning of a basic but meandering online lesson covering everything from hieroglyphics to rock paintings, feather quills to the printing press, carrier pigeons to pack mules. For those of us who grew up on postcards and love letters and printed bank statements, the subtext is plain: your beloved snail mail will soon become part of this history lesson. The letter is doomed.
Physical mail volume peaked in Australia in 2008 and has declined ever since. In the past five years, the amount of mail sent has dropped from 5.3 billion (2009) to 4.5 billion (2013).
The number of actual letters sent in that time dropped by 30 per cent, and some Australia Post estimates suggest the decline is about to assume exponential speed. At this moment in the 205-year history of the organisation, uncertainty is the only constant - except for one.
The one constant is the ever-present niggling need (or civic duty) for Australia Post to meet its Community Service Obligations - to provide a quick and reliable letter service at a single domestic rate, to all Australians, while maintaining 10,000 mail boxes and 4000 post offices.
This is a gargantuan and expensive task, which has become harder with an expanding population. A root and branch review of the company was needed and conducted. Changes have been made and more are forecast - everything from Saturday package delivery to extended hours at post offices.
The most recent and controversial adjustment was the shedding of 900 head office jobs this week, although the losses would not have come as a surprise. The US Postal Service has shed more than 170,000 jobs since 2006. The Royal Mail in Britain has similarly trimmed more than 50,000 jobs since 2003.
These cuts dwarf the 900 positions eliminated at Australia Post, but as Communication Workers Union secretary Joan Doyle points out, 500 more positions were lost to attrition last year and more than 1000 other positions have been made temporary. The full-time equivalent losses over a four-year period could be closer to 2500. And this is the beginning - not the end.
Company chief executive Ahmed Fahour has confirmed he is lobbying the federal government to reduce the community service obligation that demands delivery five days a week, leading to fears of more job losses.
With very little fanfare this month, ''two speed'' service was rolled out, with businesses in Australia able to choose the speed of their delivery based on price - an arrangement similar to the ''second class stamps'' system used by the Royal Mail in Britain.
That there has been little outcry over implementation is a big win for Australia Post, given that 95 per cent of all letter mail is sent by businesses, corporations and government.
The same system will be rolled out to the public next year.
Professor Stephen King, an economist at Monash University, points out that different price points for different services is nothing new to the company. And yet it is also equally clear that changes to the core business of sending letters - delivery on fewer days, or in a less timely fashion - would be widely felt. King, a former member of the Australian Competition and Consumer Commission, explains that the more Australia Post tries to increase revenue without offering anything new, the more individuals and companies will turn online.
''The more Australia Post squeezes, the more it kills the letter,'' he said.
Which brings us to the man assisting the euthanisation, Fahour. Change agents - even successful ones - make an easy target for upset stakeholders.
Fahour is also fond of emotive language, whether forecasting the potential ''extinction'' of the organisation or lamenting the regulated letter business ''bleeding money''.
His frankness may be necessary, but it does not endear him to all.
''Without change and reform to letter services, we do not have the ability to absorb this loss and could, for the first time since corporatisation, become a cost to the government and ultimately the taxpayer,'' he has said.
Hidden in that statement is a fact lost on many. Despite mail use having peaked and letters making a regular loss, Australia Post is still profitable - including $312 million last financial year. Revenue has increased over the past five years by $1 billion.
The image of a sinking behemoth is easily sold to the public, but the organisation returned a 2013 dividend to the government of $244 million, and paid taxes of $447 million.
Thanks are due in large part to the packages and courier company StarTrack - the parcel delivery arm of the business, which is now wholly owned by Australia Post. Last year, the $218 million loss made in the regulated mail side of the business (mostly letters), was easily cushioned by a $648 million profit on the non-regulated side (mostly parcels).
Indeed, for the first time in two centuries, Australia Post is now predominantly a parcel delivery business.
The simple question, of course, is why can't this increase in package profits offset the losses in letters? Inexpensive city mailing subsidises costly country mailing - why can't parcels subsidise the post? The issue is that parcel post is an increasingly competitive sector and reinvesting in technology is paramount. While other logistics companies such as Toll and TNT can return a profit to investors and still sink cash into development, Australia Post must return a dividend to the government while also compensating for significant losses in its core business - a business it is bound to by law.
With this in mind, and with one eye on the rollout of the National Broadband Network, Australia Post is instead repositioning itself for a digital future, namely with the MyPost Digital Mailbox.
The ambitious dream for this potentially late-to-the-party initiative is that it will become a one-stop shop for email, banking, paying bills and receiving government documents. This push into digital is part of a broader long-term strategic goal to widen the spectrum of services offered not only online, but also in post offices.
Of course, all of this development is costly. At the end of this financial year, the company could come close to breaking even or posting an overall loss for only the second time in its history.
Yet the letter trade will not be the sole factor.
Partial and full privatisation of postal services is not new. Examples include Germany, Holland, Austria and, more recently, Britain. But most believe the time is not right to sell Australia Post.
And yet privatisation may be the only manoeuvre left in the (distant) future.
When the national broadband network is complete, it will have its own set of community service obligations, which could render obsolete the obligations of Australia Post. Once that occurs, experts say it would make little sense for the government to maintain control of what would in essence be nothing more than a good parcel company.
The real question is how this country will deal with the death of the standard letter, and the only answer can be ''gradually'' - and with special assistance to those who require a careful weaning.
Konrad Marshall is a senior writer


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"The Forgetting: A Portrait of Alzheimer's" premiered January 2004.
About the Show
"The Forgetting: A Portrait of Alzheimer's" is a Primetime Emmy award-winning documentary produced by Twin Cities PBS that takes a dramatic, compassionate, all-encompassing look at the growing epidemic of Alzheimer's disease. The 90-minute documentary is based on the best-selling book by David Shenk.
In the film, three individuals and their families bring viewers into the intense, real-world experience of Alzheimer's disease. Gladys Fuget, still in Alzheimer's early stage, jokingly denies her memory problems even as we witness her struggling to recognize her own image in a photograph. Fran Noonan wrestles the disease's middle stage, tormented by outbursts of anger, sadness and confusion. In Alzheimer's final stage, Isabelle McKenna loses everything but the ability to sense human touch and the steadfast devotion of her family. During each stage of the illness, we witness these families' tenacity, frustration, grief and humor.
At the time of filming "The Forgetting," Gladys and Harry Fuget were a retired couple in their 70s. For several years, Gladys had been slipping into the early stages of Alzheimer's, which slowly progressed. Initially, words, dates and people's names escaped her memory. Amidst these struggles, her husband Harry moved into the role of caregiver. He rarely left her side and took over most of her household tasks. Harry was in a position that many caregivers experience: coping with the double stress of added responsibility and losing the wife he's always known. Harry and Gladys have both died since "The Forgetting" was filmed.
The Noonan family carries an extremely rare genetic mutation that — if inherited — guarantees early onset Alzheimer's. The incidence of this gene mutation that causes early onset Alzheimer's is believed to occur in just two to five percent of all Alzheimer's cases. The Noonans have lost their mother and a sister to the disease. In the documentary, they band together to comfort their brother, Butch, — diagnosed with Alzheimer's just before the filming — and care for their sister, Fran, who, at age 55, already had mid-stage Alzheimer's and lived in a nursing home. The remaining Noonan siblings live every day knowing they have a 50 percent chance of getting the disease, which, if inherited, could also be passed along to their children.
At the time of filming, Isabel McKenna was nearing the end of her journey with Alzheimer's disease. Her experience with the disease was a difficult, yet typical, progression into late stage Alzheimer's. She was no longer able to talk and had limited movement. Her husband and daughters had spent 13 years watching the slow progression of her decline. Having experienced everything from home care to nursing home care, they recalled their frustrations, love, fears and realizations as they prepared for the end of a long goodbye. Mr. McKenna died before Isabel, shortly after the documentary aired.
"The Forgetting" also offers a window into the world of Alzheimer's research. World-renown scientists share groundbreaking discoveries on the disease, and explain how and why Alzheimer's dismantles the day-to-day lives of people like Gladys, Fran, Isabelle and their families. As the number of Alzheimer's cases skyrockets and the research forges ahead, "The Forgetting"portrays the personal and social impact of the disease, and gives viewers reason for hope.
Major funding for "The Forgetting: A Portrait of Alzheimer's" was provided by MetLife Foundation, Public Television Viewers and PBS. "The Forgetting" was produced by Twin Cities Public Television. The producer and director of "The Forgetting" is Elizabeth Arledge. The documentary is based on the book, "The Forgetting: Alzheimer's: Portrait of An Epidemic" by David Shenk.


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Jul 1, 2012 8:39 PM
Posts: 311
Leshan deception
Went to Leshan recently and got taken in by a slick trick. Thought I would warn others who might be going in the near future.
I was traveling solo by intercity bus from Emeishan. Boarded at Baoguosi Station 报国寺旅游汽车站 and got off at the end of the run, Xiaoba Station 肖坝站 on the outskirts of Leshan. The bus was met by the usual touts, but I had read to just take the #13 city bus to avoid having to deal with them.
I found the #13 city bus nearby, but on the way towards it a young woman asked (in Chinese) "Are you folks going to the Big Buddha?" I and a dozen or so Chinese tourists all said yes and followed her onto the #13 city bus. Remember thinking at the time that it was unusual to have someone guide you onto an ordinary city bus. I confirmed with the driver that the fare was only 1 Yuan, and felt somewhat reassured to find that it was.
We wound through town, making the usual city bus stops, but it was clear that most of us were tourists heading to see the Big Buddha. Few people got on or off. After 20 minutes or so, two young women stood up at the front and one began telling us facts about the Big Buddha while the other one passed out free Buddha pendants on a red string.
Recognizing this as another definite warning sign that things were not quite kosher, I got up and looked at the route map posted near the exit door. Located a stop labeled 大佛战 (Big Buddha Station) and started counting down to it, so I would not be fooled.
But the bus didn't stop there. I guess the driver was in cahoots with the scammers. It continued beyond that stop to an unmarked point and let us out near a cluster of souvenir stands and small restaurants. Hawkers swarmed as we got out, trying to get us to come shop or eat. I broke away and walked out front in search of a ride back to the entrance.
Several "helpful locals" approached and volunteered that the entrance was only a little bit farther down the road, an easy walk. As I got near, other "helpful locals" were saying things like "Big Buddha right this way; Big Buddha step right up and buy your ticket here." This isn't customary at major tourist sites. Major tourist sites don't need hawkers.
Turned out this was the entrance to the "Oriental Buddhist Theme Park" 东方佛院, built in 1994. One could actually reach the Big Buddha from here, but it would involve a two and a half hour hike to get to the back of it, from which point you needed another couple hours to climb down the cliff along Buddha's head to his feet and up again on the other side. So round trip from here would take seven hours on foot and would include some secondary destinations that might not be of interest.
I eventually caught a bus back towards town and found the proper entrance, much closer to the Big Buddha. The boat dock was also walking distance from there, providing another option. But all in all this was a pretty slick game, and it would not be difficult to get fooled by it if you are just following the flow of the crowd.
Source: http://www.lonelyplanet.com/thorntree/t ... ID=2220261


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Booster Shot: A Vaccine Primer and Update
The field of HIV prevention has its share of raging controversies, but there's one thing almost everyone agrees on -- an effective HIV vaccine is desperately needed. After an embarrassing burst of optimism for a failed first-generation product in the early 1990s, vaccine research has been widely perceived as stagnant. But in the past year or so, promising new research is starting to rekindle hopes that an HIV vaccine is possible.
The way the next generation vaccines may work, however, is still considered less than perfect by some researchers. An ideal vaccine would be one that prevents HIV from ever establishing itself in the body. Known as "sterilizing immunity," such a vaccine would leave an individual free from HIV after an exposure. With our current technology, that may be very difficult to achieve. This has led researchers to concentrate on developing vaccines that, if unable to prevent infection, may at least prevent the virus from subsequently causing illness. Several vaccine candidates attempting this approach are now entering human trials, and the scientists involved are cautiously optimistic that their studies may prove successful. But questions remain about what counts as "success." If a vaccine allows HIV to enter the body but then controls it, is there a chance that the virus could be reactivated later in life and cause disease? Might regular booster vaccinations be required to maintain control? Only long-term studies can provide answers, and with infection rates in some countries poised to explode, there is the compelling argument that, for those at risk, some protection against AIDS is better than none at all.
To grasp the science behind these issues, it's necessary to delve into the complex workings of the immune system. Over the past decade, AIDS research has helped revolutionize our understanding of how the immune system fights infection and has opened new windows onto how vaccines really work.
Remembrance of Things Past
The key concept behind vaccination is immune system memory. The famous experiments of Edward Jenner uncovered this aspect of immunity in the late 1700s. Jenner noticed that women and girls who milked cows regularly seemed resistant to the scourge of smallpox, and he guessed the reason might be connected with their exposure to cowpox, a very similar disease that struck cattle. In an experiment that would be considered far from ethical today, Jenner made a preparation from cowpox lesions and gave it to a young boy to inhale. Despite subsequent exposures to smallpox, the boy avoided disease.
Remarkably, it has taken over two centuries to begin to understand exactly why Jenner's guesswork paid off. The technical challenges involved in studying the immune system have, until recently, obscured many details of how the body "remembers" past infections in order to protect against future exposures. Even more relevant to HIV/AIDS, the way the body controls infectious agents that stay in the body for life -- like hepatitis B or TB, for example -- has also been a mystery.
Unraveling Immunity: T-cells, B-cells, and Antibodies
The immune system is like a complex army of cells that perform many different functions in the battle to maintain health. The first line of defense against infection is called innate immunity. This refers to cells such as neutrophils and natural killer (NK) cells that respond to infections in a general way without specifically recognizing or "remembering" the infectious agent responsible. The more important aspect of immune function when it comes to vaccines and most serious illnesses is called adaptive immunity. Members of the adaptive immune system -- T-cells and B-cells -- actually target specific infectious agents and then afterwards provide the body with a "memory" of these particular bugs.
T-cells and B-cells both belong to a class of cells called lymphocytes. The job of B-cells is to make antibodies. Antibodies are like flags that stick to infectious agents as they float freely in the bloodstream, thus marking them for destruction and elimination from the body. The production of antibodies is key for protection against certain kinds of infections, such as those caused by bacteria. However, for viruses like herpes and HIV, which actually insert themselves into the body's cells (the technical term for these nasties is "intracellular pathogens"), antibodies don't work as well. To control this type of inside-the-cell infection, it appears that the body depends on its T-cells.
Our understanding of the role of T-cells in immunity has progressed by leaps and bounds over the past few years. For this we must thank the involuntary altruism of thousands of mice, which have been specifically bred for the study of the T-cell immune system. Technological approaches to analyzing T-cell function have also improved. New insights into how T-cells work have provided the basis for many of the latest HIV vaccines and proposed immune-based treatments for HIV infection. The next section of this article attempts to summarize our new understanding of T-cells and their functions.
Down to a T: Helpers and Killers
There are two important families of T-cells in the body, and markers on the cell's surface can identify them. T-cells with a marker called CD4 belong to a family known as T-helper cells. T-helper cells fulfill the commander's role in the immune response, delivering signals to other immune system cells that allow them to carry out their functions. CD8 markers are found on another important family of T-cells called cytotoxic T-lymphocytes or CTLs for short. "Cytotoxic" means that they can kill cells in the body that have been infected with a virus or another pathogen -- for this reason CTLs are also known as killer T-cells.
T-cells start life in the cell-making factories buried within our bones. From there the immature or "progenitor" T-cells travel to a small organ located just behind the breastbone called the thymus. The thymus acts a boot camp for T-cells, and only cells that graduate are allowed to enter the body's circulation as new recruits to the immune system army.
Several important events occur in the thymus. It's there that a T-cell acquires the CD4 or CD8 marker that signals the cell's function. Both CD4 and CD8 T-cells also develop a structure called a T-cell receptor (TCR). The TCR is a docking bay for pieces of infectious agents, like viruses and bacteria that have been picked up by one of the body's scavenger cells. The TCR has to recognize not only the infectious agent, but also a protein called MHC that identifies the scavenger cell as trustworthy. The MHC is like a secret handshake the T-cell needs to receive before it can act. If the T-cell's TCR locks snugly onto a piece of an infectious agent combined with an MHC protein, an immune response can be triggered. Any piece of infectious agent that can fit into a TCR and trigger an immune response is called an antigen. It is the TCR that allows an immune response to be directed against a specific pathogen. New TCRs are produced and individualized in the thymus by an essentially random shuffling of the T-cell's genetic code, or DNA. Billions of T-cells with many differently shaped TCR docking bays are made in this way. This seems to be the body's method of making sure that for any potential pathogen, there will be at least some T-cells able to recognize its antigens.
There's a downside to this process. T-cells are also made with TCRs able to dock with pieces of one's own body tissues, or self-antigen. If these anti-self cells leave the thymus and enter the circulation, there can be an immune response against the very body that the T-cells are supposed to protect. This problem is called autoimmunity. So the final task for the thymus is to eliminate T-cells with TCRs that might cause autoimmune responses. In fact, 95 percent of newly made T-cells are destroyed in the thymus for this very reason. Members of the remaining 5 percent graduate from T-cell boot camp, enter the circulation and start patrolling for antigen to fit their TCR and trigger a T-cell response.
These fresh T-cells are called naive, because they have not yet responded to an infection. They can be thought of as the rookie T-cells of the immune system. If a new infection (or fake infection in the form of a vaccine) shows up, naive T-cells with TCRs that can dock with pieces of the infectious agent will be the ones recruited to respond. This first encounter of naive T-cells with a new infection is called the primary immune response.
An average adult is estimated to have one to two trillion naive T-cells on patrol at any given time. New naive T-cells are made and graduate from the thymus every day, replacing an equivalent number of naive cells that never found an infection to respond to. Scientists estimate that the body makes about one to four billion new naive T-cells a day during adulthood, though this number declines dramatically as individuals age.
From Naïve to Memory, or Jenner Explained
The events set into motion when a naïve T-cell docks with antigen fitting its TCR are key to understanding immunity. To walk through what scientists think occurs, it's helpful to look at the immune response to a viral infection most everyone has experienced: Chickenpox.
Chickenpox is caused by an easily transmitted virus called herpes zoster virus (HZV). Most people become infected with HZV during childhood. When the virus first arrives in the body, immune sentries chop it up and its pieces are transported to the lymph nodes by immune system foot soldiers called dendritic cells. The lymph nodes are immune system command centers and T-cells visit them regularly, eager to mix it up with infectious agents. When a dendritic cell carrying HZV fragments arrives at the lymph node, it displays pieces of the virus for passing T-cells to inspect. This is called antigen presentation. Any naïve T-cell with a TCR that docks snugly to HZV antigen will be embraced by the dendritic cell. This removes the T-cell from patrol and starts the immune response process against HZV.
The T-cell/dendritic cell embrace lasts several days, during which time signals are exchanged that cause the T-cell to prepare for battle. Eventually, the T-cell becomes activated, which means that it starts to make copies of itself. And each copy made starts to make copies of itself, also. Since a single naïve T-cell can make twenty or more copies of itself, this multiplication process generates a cascade of millions of T-cell clones that all have the same kind of TCR, in this case TCRs that specifically dock with HZV antigen.
This army of activated, HZV-specific T-cells leaves the lymph nodes on a search-and-destroy mission. Their task is to find and eliminate HZV-infected cells and limit the ability of the virus to reproduce. To perform this mission, activated T-cells also develop enhanced infection-fighting skills. They release chemicals called cytokines and chemokines that can communicate with other cells and, in some cases, directly block viral replication. CD8 killer T-cells release chemical weapons such as "perforin" that punch holes in virus-infected cells.
Most people can remember what it felt like when the war between the immune system and HZV was raging. Fever, swollen lymph nodes and blistering skin are the unforgettable hallmarks of chickenpox. As you might guess, many of these symptoms stem from the activity of the HZV-fighting T-cells themselves. Swollen lymph nodes result from the proliferation of naïve T-cells when they become activated. Fever is partly a result of the cytokines and chemokines that the T-cells release (one of the best known cytokines is called IL-2, and when used as a treatment, IL-2 is notorious for causing fever and flu-like symptoms).
Fortunately, after a week or so of this misery, the T-cells have usually gained the upper hand. HZV replication is controlled, and most of the newly made, activated T-cells automatically die off. The symptoms of chickenpox subside. What has been long suspected, but only recently proven, is that some of the HZV-specific T-cells survive. Out of the twenty or so duplicates made by each naïve T-cell activated by the virus, it seems that two to five cells become memory T-cells. These memory T-cells can be thought of as a SWAT team the body retains to deal with HZV should it ever try to cause trouble again. HZV, like hepatitis B and tuberculosis, is an example of an infectious agent that remains in the body for life.
Recent studies have helped show how memory T-cells prevent infections from recurring. Remember the lingering embrace between the antigen-presenting dendritic cell and the naïve T-cell? A memory T-cell can become activated and get into battle after a much shorter embrace -- the immune system equivalent of a hug, perhaps. Memory T-cells also seem to be able to copy themselves more rapidly, and they start releasing cytokines, chemokines, and other infection-fighting chemicals almost instantly (See Genes Are Go below).
As you may have already realized, it's the difference between naïve and memory T-cell response rates that were responsible for the success of Edward Jenner's experiment and all the vaccines that came after. The dried cowpox used by Jenner to vaccinate the young boy was presented to naïve T-cells, and those cells with TCRs fitting the cowpox antigens responded and left a legacy of cowpox-specific memory T-cells. The similarities between cowpox and smallpox antigens meant that this SWAT team of T-cells was able to respond rapidly when the boy was later exposed to smallpox. And most importantly, thanks to this rapid response, deadly disease was averted.
In addition to two trillion or so naïve T-cells, an adult usually has a pool of around three trillion memory T-cells. This pool contains memory T-cells produced in response to past infections, and in some ways can be thought of as a library containing a body's history with infectious disease. AIDS is a horrific illustration of the importance of these memory T-cells -- the opportunistic infections that are the hallmark of AIDS are all caused by pathogens that stay in our bodies for life. When the memory T-cell squads that control these infections are diminished in number by HIV infection, pathogens such as pneumocystis, candida, cytomegalovirus, and toxoplasma can become active and cause disease.
Vaccine Memories: The Importance of T-cell Subsets
It is here in the T-cell story that we must climb to another level of complexity. For the sake of clarity -- never easy to achieve when discussing the immune system -- the above discussion of chickenpox talked about T-cells in a general way. But as already mentioned, the CD4 and CD8 markers identify two important groups of T-cells -- helpers and killers -- with very different functions. Although the process (described above) that leads to the creation of memory T-cells is similar for both CD4 and CD8 T-cells, the ways antigens are presented to CD4 and CD8 cells are somewhat different. This is important since researchers would like a vaccine that creates a squad of both CD4 and CD8 memory T-cells.
CD4 helper T-cells seem to divide into two major groups. Type 1 (called Th1) CD4 T-cells provide important help to CD8 killer T-cells. Type 2 (called Th2) CD4 T-cells help B-cells make antibodies. Again, these distinctions become critical when designing vaccines. Researchers are now trying to work out what type of memory T-cell squad is more important for protecting against a particular infection. If antibodies are important, then a vaccine had better trigger the development of Th2 CD4 memory T-cells that will respond rapidly to provide help for B-cells. If a pathogen manages to penetrate cells in the body and CD8 killer T-cells are needed to eliminate or control it, then a squad of Th1 CD4 memory T-cells has to be created to help get those killer cells going. For some infections -- including HIV -- it may be best to trigger both Th1 CD4 and CD8 killer memory T-cells. That way, the whole team will be ready to roll.
It's important to stress that one type of T-cell response does not mean the other type can't respond simultaneously. However, the relative strength of the different types of T-cell response appears to be important for determining whether an infection is successfully battled. Looking back at the example of HZV, it's likely that all of these different T-cell players get involved in the battle -- both Th1 and Th2 CD4 T-cells, CD8 killer T-cells, B-cells, and antibodies.
Based on experience with other viruses, many researchers suspect that it's the teamwork between Th1 CD4 and CD8 killer T-cells that plays the most important role in controlling HZV over the long haul. These suspicions are supported by research in animals with similar viruses that stay in the body for life but remain controlled by memory T-cells. Conversely, with other infections the strength of the Th2 CD4 T-cell response and the production of effective antibodies by B-cells seems key.
You may be wondering what types of immune responses were created by your childhood vaccinations. Philip Kourilsky, a researcher from the Pasteur Institute in France, has recently highlighted the fact that for almost all commercially available vaccines (such as hepatitis B, measles, polio, etc.) what makes them effective -- and which T-cell responses they create -- is not known. "We've had many successful vaccines over the past decades but we've missed a chance to see how these vaccines work," Kourilsky said at a recent HIV vaccine meeting. Up until recently the assumption had been that antibodies were responsible for the success of vaccines, but it is now thought that this isn't the case, a point stressed at the same meeting by Neal Nathanson, former director of the U.S. Office of AIDS Research. "Hepatitis B vaccine is a good example. It's amazingly effective but no one knows how it works. And what's really interesting is that it does work, even though hepatitis B is a persistent infection -- like HIV." Supporting Nathanson's interest is a study that compared people who controlled hepatitis B infection naturally with those who had been vaccinated. In that study, natural immunity seemed to rely on Th1 CD4 T-cell responses, not the Th2 responses that are associated with antibody production.
Killer T-cells, Dude
While scientists may never get around to analyzing how older vaccines do their job, HIV researchers are benefiting greatly from the latest advances in T-cell research. Several vaccine candidates that are specifically designed to create Th1 CD4 and CD8 killer memory T-cell responses against HIV are now entering clinical trials for the first time.
Attempts to create CD8 killer T-cell responses have been assisted by the development of a vaccine technology called "naked DNA." This strategy uses sections of DNA that contain genes for making fake HIV proteins that can act as antigens to trigger an immune response. Because these fake antigens have the same structure as real HIV antigens, naïve T-cells are embraced and memory T-cells specific for HIV antigen are created. One downside is that the dendritic cells needed to present these antigens to T-cells are not very impressed by the fakery involved. As a result, the memory T-cell response to naked DNA vaccination alone is rather weak.
Researchers have addressed this problem by following naked DNA vaccination with a booster shot. The booster shot uses harmless bird viruses that have also been tinkered with so that they too produce fake HIV antigens. The booster bird virus does a better job of fooling the antigen-presenting cells than plain DNA, thus causing a massively enhanced T-cell response.
One of the first inklings of the potential success of this strategy came in an article published in 1998 by a group of Australian researchers led by Dr. Stephen Kent. Kent's team tried a naked DNA shot followed by a bird virus (called fowlpox) booster in macaque monkeys. Strong Th1 CD4 memory T-cell and CD8 memory T-cell responses were created by the vaccine regimen. They later injected real HIV into the monkeys and found that, after a short burst of viral replication, the memory T-cells kicked in and reduced HIV activity to undetectable levels. However, the type of monkey used in that experiment doesn't progress to AIDS or develop high levels of HIV replication -- even without vaccination. While it was a good first step, more studies were needed.
A year later Dr. Harriet Robinson, a former colleague of Kent's, published similarly promising results obtained with her own version of what's being called the "prime-boost strategy." Robinson actually feels she may have bested Kent's efforts by using a method for delivering the naked DNA under the skin (intradermally). Robinson also challenged her vaccinated monkeys with a potentially lethal form of monkey HIV called SHIV. After publishing her results Robinson pointed out that "protection did not prevent infection -- what we saw were contained infections." Although SHIV took root, virus could not be detected using viral load tests, showing that the memory T-cell response had squelched SHIV replication very effectively.
In both the Kent and Robinson studies, it was notable that antibody responses to the vaccines were variable and often not detectable. The researchers concluded that the Th1 CD4 and CD8 killer T-cell response generated by these vaccines was able to control virus activity in the absence of antibody. This observation truly heralds a new era for vaccine research, which for so long has been hamstrung by the notion that antibodies are central to all types of protective immunity.
Meet the Candidates
Equipped with a better understanding of the immune responses required to control HIV, several companies and research teams are moving their vaccine candidates into human trials.
Stephen Kent's vaccine has now been named Co-X-Gene. The manufacturer is a small Australian company called Virax with limited resources, leading to some concerns about their ability to move the product forward. As this article went to press, Virax announced they have entered into partnership with Aventis Pasteur, a huge French vaccine manufacturer that produces a billion doses of commercial vaccines a year. Flush with this injection of support, Virax plans clinical trials of Co-X-Gene during 2001, with larger trials possible within three years.
Merck & Co., the pharmaceutical giant, has also been quietly working away on a T-cell based HIV vaccine. Merck is also using a naked DNA and fowlpox booster strategy, although researchers there claim to have modified the DNA so that it generates HIV antigens more efficiently. Merck surprised everyone by announcing the first human safety study of this product last year. The government's assistant director of AIDS vaccine research, Margaret Johnston, waxed enthusiastic in the Wall Street Journal: "It's good to see Merck involved, and testing an approach that is right now thought to be on the cutting edge." The trial is already under way, with one of the participating sites being the State University of New York at Stony Brook. Potential volunteers can call Michael Thorn, RN, at (516) 444-1659 for more information.
Another DNA vaccine made by Apollon, Inc. is also in human trials. Currently, the product does not feature a bird virus booster but could potentially be modified if studies support such a move. Temporarily laboring under the rather forgettable name of APL-400-03, the vaccine is under study at the National Institutes of Health [contact: Grace Kelly, 1-800-772-5464, extension 57744, and the University of Pennsylvania, contact: Kim Lacy at (215) 662-6434].
Further afield, a collaboration between English and Kenyan researchers plans safety testing of a DNA vaccine with a booster made from a type of virus called vaccinia (the full name is modified vaccinia Ankara, or MVA). The initial studies will be in the UK with further work scheduled in Nairobi, Kenya.
In Uganda, plans are under way to test the first-ever oral HIV vaccine candidate. The brainchild of researchers at Robert Gallo's Institute of Human Virology in Baltimore, this novel approach uses genetically modified salmonella bacteria to produce HIV antigens in the gut. Because most HIV transmission occurs through vaginal or anal mucosal surfaces, stimulating a strong T-cell response in these kinds of tissues could be particularly useful. The always cautious Dr. Tony Fauci, head of the U.S. National Institute of Allergies and Infectious Diseases (NIAID), recently relayed a cheekily guarded optimism about the product to the journal Nature: "We have been burned before in trying to predict how a candidate will fare before the trial even starts. Having said that, I like this approach."
While this is a sampling of the newer vaccines furthest along in development, the scent of potential success may soon prompt more products into the field. In anticipation, NIAID recently announced a revamping of their HIV Vaccine Trials Network (HVTN), expanding it to include sites in sub-Saharan Africa, Asia, Latin America, and the Caribbean. Significantly, the effort is being led by veteran T-cell immunologist Lawrence Corey, M.D., from the Fred Hutchinson Cancer Research Center (FHCRC) in Seattle. Hopefully, the HVTN will be able to conduct the type of follow-up necessary to answer questions about the long-term efficacy of T-cell based vaccines and the ultimate outcome of an HIV infection that is controlled rather than evicted from the body.
Having crossed the cusp of a new millennium, there is a sense that HIV vaccine research has also reached a turning point. Not only is there optimism that the immune system can be prepared to do battle with this wily virus, but several promising new strategies may eventually prove able to block HIV's ability to create a home for itself in the human body. One thing is certain: The clouds of despair that dimmed the vaccine horizon are beginning to clear.
Revenge of the Antibodies
Although vaccine approaches focusing on T-cells have come to the fore, researchers have not entirely given up on antibodies. The difficulty has been triggering the body to produce antibodies that actually block HIV replication. HIV's outer envelope is notorious for mutating rapidly to avoid the antibody attack, and some scientists speculate that this is part of the virus's defense against the immune system. With some smart thinking, two teams of researchers believe they may be starting to surmount this problem.
Jack Nunberg from the University of Montana has worked out a way to generate antibodies that block HIV as it prepares to gain entry into T-cells. This first step of the entry process is called fusion, and Nunberg has dubbed his souped-up antibodies "fusion-competent." The clever idea that led to creation of these antibodies was to literally freeze HIV just as it was changing shape to fuse with a T-cell. The immune systems of mice were then used to make antibodies to these previously hidden parts of the virus. Isolated in the test tube, these antibodies were able to block replication of a wide variety of HIV strains collected from around the world. There is much more work to be done before this strategy can be tried in humans, but Nunberg remains cautiously optimistic that his research will eventually bear fruit.
At the National Cancer Institute in Maryland, Dr. John Schiller is trying another cleverly designed antibody-based approach. It was discovered several years ago that HIV uses two T-cell surface molecules when latching onto and invading a cell. One latch has long been known to be the CD4 molecule itself, which is vital to helper T-cell function. Early attempts to block the CD4 latch failed spectacularly. The second latch HIV needs is a receptor called CCR5, the function of which -- if any -- is not known. What is known is that some people naturally lack CCR5 receptors on their T-cells due to a genetic mutation. Not only are these people highly resistant to HIV infection, but as far as anyone can tell they are perfectly healthy. These observations have prompted several drug companies to design drugs that block CCR5, betting that they might become effective treatments for HIV.
Dr. Schiller had another idea -- why not try to get the body to make antibodies that block CCR5? This approach has a number of advantages: a vaccine that created antibodies against CCR5 just might offer the kind of long-term protection against HIV infection seen in people naturally lacking the CCR5 receptor. And as a treatment, a shot or two of a vaccine would be immensely preferable to the daily ingestion of a drug. Schiller has reported success with the approach in mice and is moving on to macaque monkeys. "If we can do it in macaques, then the chances that it won't work in humans are small," says Schiller. If either Nunberg or Schiller hit the jackpot, antibodies will be back in the HIV business.
Out with the Old?
Lest we forget, there are HIV vaccines further along in human trials than those discussed in the body of this article. Unfortunately, they were developed prior to the recent significant insights into T-cell immunity. AIDSVAX is a vaccine that uses a fake copy of HIV's outer envelope to try to stimulate antibodies against the virus. Many researchers now feel that this product may have a limited protective effect, if any. This dour outlook emerged as several breakthrough HIV infections occurred during early AIDSVAX trials. Pasteur Merieux Connaught's ALVAC vaccine attempts to induce both antibodies and T-cell responses by combining pieces of HIV's envelope with a bird virus booster. The results so far have been disappointing, with killer T-cells being detected in only one-third of study participants. UK killer T-cell expert Dr. Andrew McMichael, when asked his opinion by the journal Science, was underwhelmed: "Two-thirds of the people (had) no killer T-cell response, and, if killer T-cells are important, they wouldn't be protected."
Pick Your Antigens and Adjuvants
Two additional details are critical to the design of an effective HIV vaccine. Naked DNA, bird viruses, and a variety of other strategies can be used to deliver fake HIV antigens (pieces of HIV that can trigger an immune response) into the body. But which pieces of HIV should be used? Early vaccine research focused on HIV's outer envelope, but it has become apparent that the rapid mutation of this viral cloak may be part of its defense against the immune system. It also seems that HIV's envelope proteins create antibody responses, not the Th1 CD4 and CD8 killer T-cell activity now thought to be vital for a successful vaccine. Researchers are now targeting certain inner proteins of HIV called core proteins that are revealed only after the virus has infected a T-cell. The genes that make these core proteins have catchy names like gag, pol, nef, and tat. In some cases single proteins may be able to induce T-cell immune responses. Italian researcher Barbara Ensoli has tried a vaccine that uses HIV's tat protein, and this approach was sufficient to protect two thirds of her vaccinated cynomolgus monkeys from active HIV replication. Ensoli acknowledges, however, that single protein approaches can probably be improved upon if combined with other vaccines. The most important lesson from recent vaccine studies is that HIV's core proteins create much stronger Th1 CD4 and CD8 killer T-cell responses than the ever-changing viral envelope. Whether particular core proteins have unique advantages when it comes to vaccination is not yet known. Because a T-cell with a TCR that fits an HIV gag protein won't respond to tat, it may be better to include as many core proteins as possible, thereby maximizing the number of T-cells that respond to the vaccine.
Adjuvants are special vaccine ingredients designed to boost what researchers call "immunogenicity." Simply shooting a fake HIV protein into the body does not necessarily ensure that dendritic cells will be inclined to pick it up, take it to the lymph nodes, and present it to T-cells the way they would with a real virus. An adjuvant is designed to help fool the antigen-presenting dendritic cells into treating the vaccine like the real thing. Many older vaccines use adjuvants made up of bits of dead bacteria suspended in an emulsion of oil and soap that helps mobilize a larger immune response. Naked DNA vaccines can contain bits of bacteria-like DNA called CpG motifs, and these also appear to have adjuvant effects (although, there are some yet-to-be researched questions about the safety of these CpG adjuvants). Bird virus boosters seem to trigger the body to produce cytokines that help spark antigen presentation, which is another reason they have become favorites in HIV vaccine studies. Research into adjuvants continues, with a recent study actually using a patient's own dendritic cells to carry vaccine antigens into the lymph nodes. A single shot of dendritic cells generated a huge T-cell response. Unfortunately, harvesting, then re-infusing dendritic cells is costly and it's unclear whether this approach can be made affordable enough for widespread use.
Genes Are Go: Giving Memory T-cells a Head Start
The reason memory T-cells outperform naive T-cells when responding to infections is related to the activity of genes within the cell. Genes are short stretches of DNA that contain code for making certain proteins. The proteins then perform specific functions in the body. Most of us are familiar with the idea that we inherit genes from our parents for things like eye color. It's often less appreciated that our genes are at work every second that we are alive. Every cell in our body (apart from red blood cells) contains a complete copy of our DNA blueprint (called the genome) and all our genes are contained within it. However, cells only use the genes they need to function. A T-cell uses certain genes to make the proteins it needs to fight infection. A kidney cell will use different genes to perform the waste-eliminating functions of the kidney. One way to think about this is that each cell carries a complete library containing the thousands of instruction manuals needed for making an entire body. But each cell checks out only those volumes needed to carry out its specific functions.
For more information . . .
An illustrated pamphlet, Understanding the Immune System, is available from the National Institutes of Health (NIH) Web site: http://www.niaid.nih.gov/publications.
For more on vaccines, Understanding Vaccines http://www.niaid.nih.gov/publications/vaccine/undvacc.htm
Back to the GMHC Treatment Issues November/December 2000 contents page.


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Your doctor may prescribe medicine to help get and keep your blood glucose in your target range.
There are different types of diabetes medicines that work in different ways to lower blood glucose.
Your doctor may prescribe more than one to help you get to your target range.
Some people with type 2 diabetes take both pills and insulin or insulin by itself.
Starting New Medicines
If you are starting new medicines, ask your doctor, pharmacist or diabetes educator the following questions:
- How many pills do I take?
- How often should I take them, and when?
- Should I take my medicine on an empty stomach or with food?
- What if I forget to take my medicine and remember later?
- What side effects could I have?
- What should I do if I have side effects?
- Will my diabetes medicine cause a problem with any of my other medicines?
If you think you are having side effects from your medicine, or have questions, call your doctor or pharmacist. Don't stop taking it unless the doctor tells you to.
Remember, your medicine will work best if you also make healthy changes to how you eat and if you are active.
Next: Checking Blood Glucose


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1) What is a Bezel?
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I hated the Bespin Guards as a kid... They were boring, and I still think they're just sorta "meh" to me. The vintage figures don't even cost much, so that's a nice thing I guess.
The alien version does nothing for me as well because of the ill-fitting hat
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2 results for tag: Team Nalu 26:2
Mahalo Team Nalu 26:2!
Would you run and marathon or half marathon for something you believed in? A group of high schoolers and one adult from High Desert, California literally went 'the extra mile' (or 12 or 26 !) and ran either a half or full marathon to raise awareness and funds for STN. We are impressed, inspired, and humbled to have such amazing people investing their time and talent to supporting the cause of STN. (more…)


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The first pinch-me moment came early this week for Virginia alum Denny McCarthy in the players' parking lot at Chambers Bay Golf Course in University Place, Wash.
Rolling into the lot Sunday with his brother and caddie, Ryan, in an off-white Lexus SUV — a courtesy perk for players competing in this week's U.S. Open — was an awesome way for McCarthy to start the week. Then, it just got ridiculous.
Before he even opened his door, McCarthy looked to his right to see a near-duplicate SUV parking next to him. Out stepped none other than 14-time major winner Tiger Woods.
"We were literally unloading my clubs from the trunk as Tiger was," McCarthy said. "We...


text: ISPC 18.104.22.168 Why do I have to set the customer number via the API? If I leave it empty i get this error: SOAP Error: customer_no_error_unique If I want to add a client in ISPC this field is marked with a *, so it is optional. Where is the sense of the customer number? Regards


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Celebrating illustration, design, cartoon and comic art of the mid-20th century.
Thursday, January 17, 2008
Rejecting the Pigeon Hole
"We set up some meetings with Cooper Studios and some others," says Tom. "We flew to New York and they all said, 'Yeah, you could probably work here... but your gonna start at the bottom.' And we said, 'What's it cost to live in New York?'
'Oh, you won't live here... you'll take the train in from the suburbs.'
Anyway, I thought about it, we both did - we both had young families - and I didn't think I wanted to do that. Jerry was the same."
"What I learned from the experience is I'm really glad I decided to stay in Toronto. Canada might be a smaller pond, but a visual artist in Canada can have a longer career. In New York, you might make a lot of money for ten years, grinding out the same solution every day, with the same handing and the same concept and design... you get tired. And they just chuck you. And if you can't move on, prove that you can jump onto something new..."
"Some did, but the vast majority would just make money... and burn out.
In Canada, because of the small market, there was never any time when you would have so much work from any one client that you were that bored. It still could happen but not nearly as bad. They wanted to pigeon-hole you [in New York] because it made more money for everybody."
"That guy is really good at line drawing... well, they wouldn't bother him with anything but line drawing. And that was an efficient way to merchandise the talent."
"That's what I sensed New York was like."
This coming weekend will see the launch of "Tom McNeely, 50 Years of Visual Arts", a book showcasing work from every period in Tom's career. If you would like to order the book, you can contact the artist at fmcneely(at)rogers(dot)com
My Tom McNeely Flickr set.
4 comments:
These pieces are just beautiful line work meshed it seems effortlessly with perfect color choices. The python piece I found striking and if I were the writer of the accompanying fiction, I'd have been in seventh heaven having such a striking visual accompany my story.ReplyDelete
Oh wow, that's funny - Jerry Sevier as an instructor of mine in my first year at OCA. For colour class if I recall.ReplyDelete
Thank you Leif for showing Tom McNeely's work. He is amazingly versatile, a quality that seems to by shared by other Canadian illustrators whose work you've featured. I too, like his line work very much. he can be fairly tight when it's needed as in the car ad but also wonderfully loose, as in my favorite piece, the Navy. His line work reminds me of that of Ken Dallison, a Canadian whose work I have admired for donkey's years. I like his comments about it having been for the best that he remained in Canada instead of starting in again in New York. Cooper's was a great place to start but but, as Tom points out, he probably wouldn't have become the versatile artist he is had he moved to NY. Thanks to you both!ReplyDelete
Way to go showcasing one of our own.ReplyDelete
But On a Completely Different Tack...
I was suddenly reminded of those How and Why Wonder Books..remember them? Have you done any research on those or the illustrators...something to work on sometime.


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Aged thirteen, Theo Decker, son of a devoted mother and a reckless, largely absent father, survives an accident that otherwise tears his life apart. Alone and rudderless in New York, he is taken in by the family of a wealthy friend. He is tormented by an unbearable longing for his mother, and down the years, clings to the thing that most reminds him of her: a small, strangely captivating painting that ultimately draws him into the criminal underworld. As he grows up, Theo learns to glide between the drawing rooms of the rich and the dusty antique store where he works. He is alienated and in love- and his talisman, the painting places him at the centre of a narrowing and ever more dangerous circle.This book was amazing. Donna Tartt's first book, The Secret History is one of my favourites but I didn't even finish her second, The Little Friend. However, she is an author that will always interest me and I know that The Goldfinch will stay with me forever.
At just under 800 pages, The Goldfinch is rather a challenging prospect. But at no point was I bored or waiting for something to happen. Donna Tartt fills every page with beautiful prose and mesmerising detail.
The story feels almost Dickensian, the characters are so well formed and intriguing. The story spans many years, with characters disappearing and popping up when you least expect them to.
I'm not going to say anymore as I don't want to give the plot away. Just read it, The Goldfinch is one of the most remarkable books that I have ever read.


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The Victoria Cross, instituted 1856 by Queen Victoria, is the Commonwealth's premier military decoration for gallantry. It is awarded in recognition of the most exceptional bravery displayed in the presence of the enemy, although in rare instances the decoration has been given to mark other courageous acts. The first recipients saw action in the Crimean War. Among them a Canadian lieutenant, Alexander Roberts Dunn, was awarded the VC for heroism during the charge of the Light Brigade at the Battle of Balaklava.
Over the years, Canada's recipients (living and posthumous) have totalled 94, including Canadians who were attached to the forces of other Commonwealth countries and some non-Canadians serving in Canadian units. The decoration is in the form of a bronze cross patée bearing the royal crest and the words "For Valour." The ribbon is dark crimson. The awarding of the medal was dropped in 1972 when the Canadian bravery awards were created; however, in April 1987 Brian Mulroney's Conservative government asked the deputy director of the Chancellory of Canadian Orders and Decorations to consider its reinstatement.
As a result, on 2 February 1993 Queen Elizabeth II approved the creation of a Canadian VC. The award has the same criteria as the original British decoration. The Canadian VC resembles the original VC except that the Latin inscription Pro Valore replaces the equivalent English inscription "For Valour." No Canadian VCs have yet been awarded.
See also honours.