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Beer 101 with Stone Brewery in Escondido

Posted at 2:24 PM, Nov 10, 2017
and last updated 2017-11-10 17:28:17-05

(KGTV) - Craft beer is as much a part of San Diego as apple pie is a part of America.

Bold statement? Sure. But there's no denying the impact the local industry has had on the region over the past decade.

RELATED: San Diego getting an official craft beer known as '72 and Hoppy'

At Stone Brewery, the craft of beer is taken seriously - much like at many other local breweries that now pepper San Diego County.

Padraic "Paddy" Lenehan, Stone Brewing's global beer curator, walked 10News through the different tastes that San Diegans crave when it comes to craft beers.

Beer 101

Lenehan walked us through a few of Stone's popular beers offered throughout the year and seasonally: Stone Ripper San Diego-style Pale Ale, Stone Vengeful Spirit IPA, Miguel Ceja Andrade/Brandon Berube Stone Merc Machine Double IPA, and Stone Xocoveza Mocha Stout.

Pale Ale

Pale Ales are considered a good balance of both malt and hops and can range to include fruity notes or varying degrees of floral tastes. American versions tend to be hoppier, while British version tend to be maltier.

IPA (India Pale Ale)

An Indian Pale Ale is generally a herbal, citric beer with a hoppy bitterness. These beers can range in color from golden brown to a reddish amber and can also range in flavors to include fruity notes or more floral hints.

Double IPA

The Double IPA is often referred to as an American IPA on steroids. Those tastes of an IPA are amplified and stronger than their single IPA relatives. The style, credited as West Coast-style IPAs, are generally very hoppy to the taste.

American stouts are inspired by traditional English-style stouts, with a balanced and generally heavy taste. Many U.S. brewers commonly add coffee and chocolate to compliment the roasted malt flavors and the trend of aging stouts in bourbon or whiskey barrels has also taken off.

For more about your favorite styles, beer website Beer Advocate has a lengthy list of styles and what makes them each unique.

At Stone in Escondido...

Stone Brewery has developed a reputation as one of the area's top breweries. Its Escondido brewery and bistro is evidence of that - sporting rotating taps of the brewery's latest creations and favorite brews.

RELATED: 10 days of events on tap for San Diego Beer Week

The brewery has taken those beers and crafted up a menu to compete with taste buds, with options available for the entire family.

As always, a designated driver or ride sharing is encouraged when visiting the brewery. Services like Lyft and Uber often give special pricing or codes for certain events and Stone offers a lower designated driver price.


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Best Educational Apps | The 15 Best Learning Apps of 2020 [Updated]

Best Educational Apps | The 15 Best Learning Apps of 2020

Best Educational Apps | The 15 Best Learning Apps of 2020

Nowadays, people are learning online via Apps. So, that’s why we have created a list of Best Educational Apps of 2020.

There is not a single aspect of human life that does not reap the benefits of tablets & Smartphones.

In a similar manner, learning has become much more convenient & accessible with the help of such advanced gadgets. There is a multitude of educational applications accessible in the current times featuring various grade levels & subjects.

Few educational apps cover only general topics while few are designed by keeping in mind the specialized study fields. Best Learning Apps & Best Educational Apps are several in the market.

If you want your learning app idea also to be one of the best, you can create one easily with the help of a mobile app development company.

It is best to go through the top picks for iOS & Android for understanding what kind of learning app you want to create.

Best 15 Educational Apps:

List of sought-after Learning Applications:

1. TED

Ted Education App

If you want to create the best eLearning apps for adults, then you can take ideas from apps like TED. Here people can engage in smart talks with reputable personalities according to their preferences & mood.

This excellent application has the affluence of practical information almost on every topic. This application consists of countless videos which are an extremely precious source for valid and authentic knowledge on numerous topics.

  1. Bookmarking feature for watching talks later
  2. Subtitles accessible in more than 100 languages
  3. Options available for syncing the TED application with various Smart devices
  4. Users can gain entry to TED app Radio hour podcast

Download Android & iOS

2. Duolingo

Duolingo Learning App

You will find yourself amidst a load of information when you think about what are some educational apps.

For instance, Duolingo is one of the best language learning apps that will help you in grasping a new language within minutes.

The app is designed in a way that will offer you information about some fundamental signs that can function as your savior in tourist places where the language is unknown.

You can get directions from the app for learning to start conversations and you can ask the directions in full 80 languages.

  1. Supports every language
  2. You can practice reading, listening and speaking with the app
  3. The application helps in enhancing vocabulary skills & grammar via entertaining QA sessions
  4. You can even learn various languages with the app

Download Android & iOS

3. StudyBlue

Students who are keen to learn & study sometimes feel overwhelmed especially before the final exams. StudyBlue comes under the category of top educational apps that helps students learn in an easier manner.

Utilizing digital learning materials and creating flashcards are some of the activities they can engage in once they sign up.

There is no need to take stress before any kind of examination as this is one of the Best Learning Apps for Android that comes with a robust knowledge library.

  1. Students can set as many study reminders as they want
  2. Fantastic customization of study materials is possible with desired audio & images
  3. Students can get hands-on study materials across numerous devices
  4. The application comes with numerous quizzes for monitoring the overall progress of a student

Download Android & iOS

4. Wikipedia

Several students of the current era like to study from eLearning apps. Wikipedia is also regarded as one of the Best Educational Apps that can work seamlessly on both iOS & Android.

Any kind of knowledge a student is seeking, the application can easily provide in an effortless manner.

This top educational app boasts about its 40 million articles in almost 300 languages on the Android platform

  1. Informative articles
  2. Offline support
  3. There are no advertisements
  4. The application offers users options to decode contents in their local language

Download Android & iOS

5. Nova Elements

Right from childhood did you have a problem in understanding the functioning of the periodic table? Did you always use to wonder what gave every element its own exclusive name & set of properties?

Well, general knowledge apps like Nova Elements are exactly what you need to clear these kinds of confusions. Nova Elements enables you to discover the full periodic table in a straightforward manner & with complete ease.

While you engage in playing an entertaining game, you can actually learn about the periodic table.

This is one of the Best Learning Apps you will get just for iOS.

  1.  High-resolution assets for contemporary retina devices
  2. 64-bit application architecture
  3. Modernized and restructured Periodic Elements table & much more
  4. The application is incorporated with a scalable adaptation

Download iOS

6. Khan Academy

Khan Education Academy

Considering how challenging and tough CAT, IIT-JEE & GMAT examinations are, students can largely benefit from advanced tools like Khan Academy.

Regarded as one of the finest and Best Educational Apps, a student can prepare excellently for his/her further studies with this application.

Learning the basics is always important to excel in any complex examination. This is what exactly this study app-enabled students to do.

Right from geographical landscapes to preliminary music notations, this application is used not just by students but by adults as well for gaining knowledge.

  1. Students can practice quizzes & assess their progress
  2. Students can grasp a robust conceptual understanding
  3. They can also scale their efforts with badges & energy points
  4. There are more than 40,000 convertible practice questions available in the app

Download Android & iOS

7. Goodreads

GoodReads lerning App

This is one of the most sought-after iOS applications found in the Apple education store. This education app for iPads consists of more than 1 billion books.

This whopping figure makes this app extremely noteworthy. When you are a book reader & keen on getting hands-on the Best Learning Apps, Goodreads is the one for you.

  1. Users can read as well as write several book reviews
  2. Engage in reading book challenges
  3. Users can not only share notes but also progress updates
  4. Users can get hands-on personalized recommendations for exploring new books

Download Android & iOS

8. Edmodo

Are you on the lookout for the best educational apps? If yes, then you have reached the right space. Edmodo is one of the best education apps that enable users to engage in free online classroom communication.

As the best study apps, this application functions like a focal point that urges you to learn something fresh every day. You can also interact with the respective classes easily.

  1. The application offers the option of sending messages directly to parents & students
  2. Teachers can also use this app as it functions as a home stream
  3. The application ensures enhanced communication among various users
  4. Users can engage in classes as well as get hands-on assignments right at one place

Download Android & iOS

9. Photomath

Photomath App

Do you find it hard keeping your child interested in studies than in turn worries you about your child’s future? With this in mind, you can come out of this issue with the best learning apps for kids like Photomath.

Teaching math to a child is extremely challenging. But this is one of the best educational apps that comes for free and can solve math problems like calculus & arithmetic.

You can easily sync the application with your Smartphone camera for solving math problems via animated video steps that again come with comprehensive instructions.

  1. Offline support
  2. An application can solve all textbook & handwritten problems
  3. Support for over more than 30 languages
  4. Application is equipped with a scientific calculator & includes a multitude of solving methods

Download Android & iOS

10. Tynker

Developing software tools requires coding & not everybody has a fair understanding of it.

If you want to be a certified and professional software developer whose demand is ever increasing in the current digital world, then you must back yourself with skills.

You can easily grasp programming skills along with intuitive & interest-based activities with the help of Best Educational apps like Tynker.

You might be a seasoned programmer or just a beginner; this is one of those learning apps that can benefit both. Even it is possible to learn complex languages like JavaScript & Python with this application.

  1. Offline working is possible
  2. Linked device support
  3. Availability of character creator tool
  4. Coding tutorials are interactive

Download Android & iOS

11. Blinkist

Blinkist Reading App

Blinkist is one of the finest eLearning apps for both iOS & Android where you can get hands-on countless non-fiction books.

Ways to become more mindful of ways to win a dispute and on many topics, you can find ample information. This is an application that will always keep your mind polished.

  1. Ability to switch between text & audio
  2. Availability of more than 2500 bestselling nonfiction books
  3. Users can develop custom audio playlists
  4. Access to the finest business books

Download Android & iOS

12. Skillshare

Skillshare App

One of the most sought-after best educational apps, with such education apps like Skillshare you can easily get hands-on effective digital online classes.

As you keep on learning numerous professional illustrations, you can automatically boost and strengthen your career.

This is a great course app as it covers topics of every interest starting from entrepreneurial tips, creative art courses, etc.

  1. Users can download classes & they can choose to watch those in offline mode
  2. Users can watch a multitude of free classes that also makes this the best free education app
  3. The app includes a trial period of full 30 days
  4. Users can get hands-on unlimited classes

Download Android & iOS

13. ActiveX

Marked as a very popular & one of the best learning apps, this application can help you be physically fit & healthy at all times.

With several fitness tricks available in the app, this is a very useful learning app for the entire community who can get hands-on active physique by fulfilling all the fitness goals.

You can develop & follow workouts depending on your fitness level. You will also gain access to training schedules & equipment that will direct you towards an active lifestyle.

  1. Manifold users’ compatibility
  2. The ability to track body composition
  3. Working sessions in a personalized manner
  4. The app helps to keep body mass & metabolism in control

Download Android & iOS

14. Amazon Kindle

Amazon Kindle App

Are you a complete bookworm? Then you will be happy to learn about this eLearning app called Amazon Kindle.

The application offers you the liberty of scrolling via a multitude of books, newspapers, magazines, and a lot more. To utilize this application, you do not need to possess a Kindle device.

  1. Users can use built-in dictionary i.e. Google & Wikipedia
  2. Offline support available
  3. Users can get hands-on free books
  4. E-book shopping is possible in the app that includes bestsellers & new releases

Download Android & iOS

15. Lumosity

Lumosity App

If you want to make your brain sharp, then Lumosity is the application for you.

One of the highly remarkable free educational applications, you have the option of playing brainstorming games, engaging in various kinds of quizzes, and playing various programs with the app.

You can actually train the brain with numerous new sessions.

  1. Incorporates numerous workout modes
  2. There are more than 40 brain games
  3. Users can analyze each game
  4. Application activities challenge the academic & core cognitive capability of users

Download Android & iOS

With so many ideas about Best Educational Apps & Best Learning Apps, you must by now feel the temptation to build your own learning app.

As you hire mobile app developers, you can get hands-on some of the most fantastic informative tools that you can offer to the world so that people can benefit from it.

With us, you can be rest assured that you are associating with a reputable company as our team of developers never compromises with quality.

Want to Develop Online Learning Education App?Popular FAQ:

What are the Best Language Learning Apps?

Duolingo, Goodreads, TED, Wikipedia are some of the Best Language Learning Applications.

What are the Best Learning Apps for Toddlers?

Moose Math, Metamorphabet, Bugs, and Button, Alien Buddies are some of the Best Learning Apps for Toddlers.

Which App is best for Online Study?

Duolingo, Goodreads, TED, Khan Academy are Best for Online Study.

What are Best Educational Apps?

Nova Elements, Wikipedia, StudyBlue, Skillshare are some of the Best Educational Apps.

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Lórí-Iró leadership and herdsmen nationalism

 Lórí-Iró (based on deliberate falsehood or lie) is a metaphoric expression that unpacks the relationship of falsehood between Nigerian politicians and the public.

Popularised recently by an Ibadan-based street evangelist, Gbadamosi Ismail, Lórí-Iró is useful in dissecting the failures of social institutions in Nigeria. It reveals how relationships are consummated based on lies and culminate in heartbreaks, broken relationships, and fragile national unity. Blessed with deceitful lips, an average Nigerian politician, whether holding an umbrella or broom, mesmerizes the vulnerable electorate with messianic posture as a harbinger of growth, development, peace, and prosperity. This is the social context that characterized the ascendancy of the repackaged candidate, Major General Muhammadu Buhari (retd.), who had been serially rejected thrice. His rejections then were anchored on the electorate’s fear of voting a religious fundamentalist and a clannish lord. Those in opposition then, particularly from western Nigeria campaigned against candidate Buhari for fear of violence, clannish rule, and alleged Islamisation agenda. By 2014, the opposites harmonized with an assemblage of strange bird fellows, and the foundation of what we experience today was laid by ambitious acclaimed leaders who failed to learn anything from history. They clothed candidate Buhari as a converted democrat. Their campaign was anchored on lori-iro and they presented a false outward identity and pretended that the inward identity of their candidate was no longer important. Today, that Lórí-Iró identity is hunting the national life as fear of victimization by bandits and terror herders envelopes the land.

The regret now is that President Muhammadu Buhari who promised to fight corruption, defeat terrorism, and fix the economy has not delivered on this tripod upon which his regime is mounted.  Many of his statements, one of which is ‘I belong to nobody’ have come to be appreciated as Lórí-Iró based on lived experiences of Nigerians since 2015. From 2010 through to 2016, Nigeria’s best ranking on the global Corruption Perceptions Index (CPI) has been 136 out of the 176 countries. By the end of 2019 when Buhari contested the second term, the CPI of Nigeria was 146 and nosedived further to 149 in the 2020 CPI ranking. Although the government is challenging the 2020 CPI report, the National Bureau of Statistics 2019 study affirmed the deepening corruption under Buhari and the upward mobility of insecurity as the major concern of Nigerians. Under this presidency, might is right and criminal herdsmen are unleashing terror on farming communities, raping, kidnapping, and grabbing ancestral lands. This is what I call, herdsmen nationalism.

Fulani herdsmen nationalism is the notion that the cultures of the Fulani and its herding community and their interests are superior to any other cultures in Nigeria. Emboldened by this ethnocentrism and the desire to actualize it, criminal herdsmen are strengthened with the current political capital in Aso Rock. They are energized and empowered by the consciousness that their patron is in power and the pendulum of power tilts to their side. Mouthing the narrative of having the right to live anywhere as ‘Nigerians’, criminal herdsmen trample on the livelihoods of farmers, rape their women, displace them and acquire their lands. The consequences of these intended actions are food insecurity as farmers can no longer access their farms owing to fear of being attacked by terror herders and public resistance to herdsmen atrocities in southern Nigeria.

The negligence of governments and perceived pampering of criminal herders by the security agencies underlie ongoing sustained resistance and outcry against criminal herders in southern Nigeria. This is happening because our Lórí-Iró leaderships are negating the lyrical counsel preached in our national anthem that ‘living just and true’ enables a country to attain lofty heights of nationhood to build a country where peace and JUSTICE reign. Nigeria’s Lórí-Iró leaders only sing the national anthem but do not act the lyrics. While leadership at the national and sub-national levels is preaching peaceful living, little is being said about JUSTICE. Justice is the pillar upon which PEACE stands. Justice is needed for those killed, kidnapped, raped, and displaced in farming communities by criminal herders. We are often reminded (based on lies/lori-iro) that we are one indivisible country even though there are obvious diversities. For instance, southern Nigeria operates Criminal Code while northern Nigeria operates Penal Code. Some states in northern Nigeria operate Sharia law with Sharia court and their enforcement agents. Whoever is found within that space irrespective of whether you believe in it or not must comply. Child Rights Act is implemented in most southern states while northern states have been lukewarm. Show me how many southerners have violated cultural and religious norms in northern Nigeria and have been spared without sanction. What then gives a criminal herder the right to migrate down south to cause acrimony and challenge local norms, values, and laws governing human conduct?

Self-help is activated when government fails to live up to the constitutional roles of assuring the safety of lives and property. When nobody is sure of tomorrow or who the next victim of criminality will be, a defensible space approach becomes inevitable and this is manifested in territorial protection against perceived enemies. The mindset of criminal herders is better appreciated through the lens of the Governor of Bauchi State, Bala Muhammed, who postulated the theory of AK-47 defense. This governor who is a Fulani from his maternal side had hitherto asked Nigerians in a television interview to continue to live with the realities of herders. This is why a sympathetic Fulani-headed regime cannot shut borders on criminal herders migrating into Nigeria to wreak havoc at the expense of law-abiding indigenous Fulani herders. Muhammed informs us that the AK-47 assault rifle brandished by criminal Fulani herders is for self-defense and protection against their endangered lives and livelihoods in the forests.

If the Fulani are being profiled, Sheik Gumi’s motivated trip into the den of Fulani bandits in Zamfara affirmed that framing. Gumi revealed meeting with over one battalion (1,000) of armed Fulani bandits in three locations inside Zamfara forest. He claims that the bandits are angry with their governor but refused to reveal the reasons for their anger. His advocacy is now how to use state resources to placate bandits created by the system they run. Down South and within the same regime, harmless #ENDSARS protesters are hounded and dehumanized by security forces. This is the tragedy of the inequality in securing Nigeria— the State negotiates with terrorists and bandits but clamps down on genuine and harmless protesters. What the government is saying is that the kingdom of Nigeria suffereth violence and only the violent sit with the high and mighty in government and gets the best treatment. This is a path to destruction as criminals in other zones will adopt a similar approach and demand to be appeased.

False denial of the causes of this tension will escalate the raging tribal solidarity. The government should allow security agencies to perform their work professionally. Since the culture of pastoral nomadism aligns with the cultures in the north, northern governors should embrace the Kano State approach of establishing ranch while those herding in southern Nigeria should do so in compliance with state laws. Systems nurturing the growth of Fulani bandits in the North must be reviewed and blocked. The government must check the inflow of people from the Sahel region and control the flow of small arms and light weapons. The present centralized policing system cannot sustain the demands of modern security in Nigeria. Many believe in Nigeria but not at the expense of their lives as only the living has a country. Oral plea to Nigerians to embrace peace will not work without ensuring that justice is served. Otherwise, there will be the rise of more insurgent citizens.

Dr Tade, a sociologist, sent this piece via Dotad2003@yahoo.com.

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You can find numerous articles on the web comparing Linux and Windows. Often the debate focuses on which operating system provides the best device support. What would be some reasonable criteria for assessing OS device support? Using those criteria, which OS do you believe provides the best support? Write a short paper answering these questions.

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Better OS Driver Support – the difficulties in developing criteria

The first issue of enumerating “reasonable” criteria for assessing OS device support is not as straightforward as it may seem – consider, for example, how complexity burgeons the instant one asks the following questions: For whom are these criteria applicable – which users, what expertise-level of users, and are we talking about groups for whom a device is pertinent or we referring to individuals? And, perhaps even more critically, what are the devices and for what uses are these operating systems—Windows and Linux—supposed to be providing support? Notice, thus, how the determination of “reasonableness” is inextricably complicated even at this base level of the issue. Further complicating matters is the relevant issue of what we mean by, for example, “Linux” in this context? Are we talking about the Linux distributions even casual Linux users are...

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MEDIA BROADCAST Launches DVB-S2 Transmission Platform On Astra 23.5° East

MEDIA BROADCAST, Europe's leading full service provider for the broadcast and media sector, launched a DVB-S2 transmission platform on Astra 23.5° East (Astra 3B).
The platform enables the efficient use of available transponder capacities for the transmission of HDTV programmes. MEDIA BROADCAST is targeting markets in Central and Eastern Europe, with a focus on the Czech Republic and Slovakia, via the satellite's Europe Wide Beam. The first programmes on the new DVB-S2 platform will include the Czech TV HD channel as well as media services from the Federal Parliament. The signal will enable the feed-in of Czech TV HD into regional cable networks as well as supplying DTH broadcasting to 1.5 million Czech households.
"The launch of DVB-S2 services on Astra 23.5° East is an important step for MEDIA BROADCAST, providing emerging TV markets in Eastern Europe with efficient transmission services for SD-HD migration that best use the bandwidths available on the transponder," explained Dr. Ute Haimerl, Head of Broadcast Satellite Services. "In doing this, we are creating an additional technical foundation for the sustainable promotion of our international activities in these important European markets." MEDIA BROADCAST is currently leading concrete negotiations with additional programme providers regarding the use of the new DVB-S2 transmission platform.
MEDIA BROADCAST is Europe's largest full-service provider in the media and broadcast industry. Its core business comprises the planning, installation and operation of multimedia transmission platforms both in Germany and internationally for television and radio, based on modern transmitter, cable and satellite networks. As a member of the TDF Group, MEDIA BROADCAST supports around 750 national and international customers, including both public and private broadcasters, TV and radio production companies, international broadcasters and network operators, media companies and the film industry. Its service portfolio virtually encompasses the entire process chain of broadcasting from production and content management to transmission. To find out more about MEDIA BROADCAST, please go to
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‘UFC 223: Khabib vs. Iaquinta’ Live Results

Written by 5thRound.com Staff
April 7th, 2018

“UFC 223: Khabib vs. Iaquinta” goes down Saturday night inside Barclays Center in Brooklyn, New York.

Fox Sports 1 airs the preliminary bouts live starting at 8PM ET/5PM PT. The pay-per-view broadcast begins immediately after at 10PM ET/7PM PT.

Tonight wraps up arguably the most chaotic week in MMA history. Between interim lightweight champion Tony Ferguson abruptly pulling out of the main event against Khabib Nurmagomedov, featherweight champ Max Holloway agreeing to step in on just six days’ notice, then exiting one day before showtime due to weight cutting issues, and of course the whole Conor McGregor fiasco which resulted in three bouts in the lineup being nixed.

The UFC certainly took the scenic route, but at least we are finally here. Nurmagomedov now fights Al Iaquinta for the vacant lightweight title in the main attraction.

Rose Namajunas defends her strawweight belt against Joanna Jedrzejczyk in the co-main event.

Here are the official results from tonight’s fights:

Preliminary Card:

(Fox Sports 1 8PM ET/5PM PT)

Devin Clark Defeats Mike Rodriguez via unanimous decision (29-28, 30-27, 30-27)

Ashlee Evans-Smith Defeats Bec Rawlings via unanimous decision (30-27, 30-27, 30-27)

Olivier Aubin-Mercier Defeats Evan Dunham via TKO (strikes) at 0:53 in the 1stRound

Karolina Kowalkiewicz Defeats Felice Herrig via split decision (29-28, 28-29, 29-28)

Main Card:

(Pay-Per-View 10PM ET/7PM PT)

Chris Gruetzemacher Defeats Joe Lauzon via TKO (Corner stoppage) at 5:00 in the 2ndRound

Zabit Magomedsharipov Defeats Kyle Bochniak via unanimous decision (29-28, 30-27, 30-27)

Renato Moicano Defeats Calvin Kattar via unanimous decision (29-28, 30-27, 30-27)

Rose Namajunas Defeats Joanna Jedrzejczyk via unanimous decision (49-46, 49-46, 49-46) (Namajunas retains UFC women’s strawweight title)

Khabib Nurmagomedov Defeats Al Iaquinta via unanimous decision (50-44, 50-43, 50-43) (Nurmagomedov captures UFC lightweight title)

Don’t forget to follow @5thRound on Twitter, Facebook and Google+!


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Epidermal growth factor receptor (EGFR)

Epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase receptor that plays a central role in regulating cell division and death. It belongs to the HER family of receptors, which includes EGFR (HER1/ErbB1), ERBB2 (HER2/neu), ERBB3 (HER3), and ERBB4 (HER4). These receptors are characterized by an extracellular ligand-binding domain, a transmembrane domain, and a cytoplasmic domain containing the tyrosine kinase region followed by a carboxy-terminal tail with tyrosine autophosphorylation sites. Several growth factors, including EGF, transforming growth factor-α (TGF-α), amphiregulin (AR), epiregulin (EREG), heparin-binding EGF (HB-EGF), betacellulin (BTC), and epigen (EPG) bind to the ErbB receptors.

Mutations in the gene encoding EGFR that lead to overexpression of the protein have been associated with a number of different cancers. Furthermore, this upregulation appears to be frequently associated with adverse prognosis. These discoveries have stimulated researchers to identify novel biomarkers that can be used to determine which patients have the mutations so that they can receive therapeutics targeted to their cancer.

Here I present an overview of the EGFR signaling pathway, as well as testing and therapeutic strategies for patients who test positive for various mutations in the signaling pathway.

EGFR Signaling Pathway

Following ligand binding at the extracellular domain, EGFR forms functionally active homo- or hetero-dimers. Dimerization induces the activation of the tyrosine kinase domain, leading to autophosphorylation of the receptor on multiple tyrosine residues. This phosphorylation triggers recruitment of a range of adaptor proteins, such as Src homology 2 domain containing (SHC) protein and growth factor receptor-bound protein 2 (GRB2), followed by activation of a series of intracellular signaling cascades that affect cell proliferation, apoptosis, invasion, metastasis, and angiogenesis.

Downstream effects of EGFR activation include modulation of three major pathways that have been well characterized (Figure 1). Induction of the RAS-RAF-MAPK pathway occurs when phosphorylated EGFR recruits the guanine-nucleotide exchange factor via the GRB2 and SHC adapter proteins, which activates RAS. This step subsequently stimulates RAF and the MAP kinase pathway, ultimately affecting cell proliferation, tumor invasion, and metastasis.

Figure 1
EGFR Signaling Pathway
Figure 1: EGFR Signaling Pathway
EGFR is activated either as a homo- or heterodimer resulting in regulation of multiple pathways. In particular the RAS/RAF/MAPK, AKT, and JAK/STAT pathways downstream of EGFR play integral roles in cell migration, proliferation, and survival, respectively. Anti-EGFR antibodies are targeted to the external ligand binding domains while the small molecule inhibitors or tyrosine kinase inhibitors (TKIs) target its cytoplasmic kinase domains.

Following activation of the EGFR pathway, the phosphatidylinositol 3-kinase (PI3K/AKT) pathway induces the major cellular survival and anti-apoptosis signals by stimulating nuclear transcription factors such as NFKB. Involvement of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway also is implicated in activating transcription of genes associated with cell survival.

EGFR activation affects other not so commonly known pathways as well. These include phosphorylation of phospholipase C gamma 1(PLCG) and subsequent hydrolysis of phosphatidylinositol 4,5 biphosphate (PIP2) into inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DAG), which results in activation of protein kinase C (PRKC). Activation of this kinase turns on the MAPK and c-Jun kinase pathways.

Today we know that EGFR signaling plays an essential role in cell proliferation, survival, and migration. Activating mutations of the EGFR gene are found predominantly in females, individuals who have never smoked, and individuals with Asian ethnicity. Though its altered activity has been studied primarily in development and growth of non-small cell lung cancer (NSCLC), many other tumors, including head and neck, ovary, cervix, bladder, esophagus, stomach, brain, endometrium, colon, breast, and liver are also known to exhibit deregulation of EGFR.

Therapeutic Strategies Targeting EGFR

Gene amplification and over-expression of the Erb family of receptors (EGFR and ErbB2) has been observed in breast, lung, and colorectal cancers, while the deregulated activation of intracellular mitogenic signaling has been implicated in many other cancers. These two pathways make protein target-based therapies very promising tools for treatment.

In fact, pharmaceutical companies have developed several potential therapies that use anti-EGFR monoclonal antibodies (mAbs) and small-molecule tyrosine kinase inhibitors (TKIs) that target distinct domains of EGFR. Anti-EGFR monoclonal antibodies, such as cetuximab, panitumumab, and nimotuzumab, bind to the extracellular domain of the EGFR monomer and compete for receptor binding by the endogenous ligands, triggering receptor internalization and blocking ligand-induced receptor activation. Cetuximab, which binds to the L2 domain of EGFR, is a chimeric protein antibody composed of variable and constant regions from mouse and human sources, respectively, while panitumumab and nimotuzumab are fully humanized EGFR antibodies. To date, the Food and Drug Administration has approved EGFR-targeted mAbs for use in advanced colorectal cancer, gliomas, and head and neck tumors. Patients receive the drugs intravenously.

On the other hand, EGFR-specific small molecule inhibitors such as erlotinib (Tarceva) and gefitinib (Iressa), which are taken orally, translocate across the plasma membrane and interact with the cytoplasmic domain of EGFR. Small molecule inhibitors belong to a class of therapeutics called tyrosine kinase inhibitors or TKIs. In the cell, TKIs compete with ATP to bind the catalytic domain of the kinase, which in turn inhibits EGFR autophosphorylation and downstream signaling, including cell proliferation and survival. TKIs have been approved for treatment of advanced NSCLC and pancreatic carcinoma.

Small molecule inhibitors are thought to be less specific than mAbs since they can potentially target any tyrosine kinase, diluting the therapeutic effect on the target of interest. To increase the specificity and improve clinical effectiveness of TKIs, researchers have also developed bi-specific inhibitors such as lapatinib that target EGFR/ErbB2. However, the overall clinical effectiveness of these therapies and their correlation to EGFR expression is not clear. EGFR inhibitors are effective in only a small subset of patients, despite high levels of EGFR expression. Some cancers appear to acquire resistance to EGFR inhibitors, and multiple mechanisms seem to underlie the lack of sensitivity to the targeted therapies, including mutations in the EGFR gene itself, as well as in down-stream effectors such as RAS, RAF, and AKT that appear to be associated with differential clinical outcomes.

Impact of Mutations in EGFR and Downstream Signaling Pathways

The EGFR gene is present on chromosome 7p11.2 and has 28 exons coding for a transmembrane receptor protein of 464 amino acids. Within EGFR, exons 5–7 and 13–16 code for the ligand binding domain while exons 18–24 code for the TK domain. Autophosphorylation occurs in the region encoded by exons 25–28.

Although mutations can occur anywhere within the TK domain, a significant set of EGFR mutations in lung cancer that are associated with objective response to single agent TKI therapy are observed in exons 18–21. The most frequent of these are in-frame deletions in exon 19 that occur in approximately 45% of cases, followed by point mutations in exon 21, in 40–45% of cases. While more than 20 different deletions are observed in exon 19, L858R in exon 21 is the most common point mutation detected (Figure 2). Greater response to TKIs also correlates with EGFR amplification that frequently coexists with EGFR mutations and is more common in gefitinib-sensitive NSCLC with increased expression of ErbB3.

Figure 2
Spectrum of EGFR Mutations
Figure 2: Spectrum of EGFR Mutations

Researchers have also observed resistance to anti-EGFR therapies in a significant number of cancers, altering the clinical impact of anti-EGFR treatments. De novo mutations are known to occur within EGFR that constitutively turn on the receptor, allowing the tyrosine kinase to work much better than normal and overcoming the effects of the TKI. While the most important of these is T790M, a point mutation in exon 20 that accounts for about 50% of cases, insertional mutations in exon 20, which occur in about 5% of cases, have also been associated with TKI resistance.

Primary resistance to EGFR TKIs is mostly due to the presence of wild-type EGFR, since these tumors harbor mutations in other genes downstream of EGFR such as KRAS and BRAF that may play a role in predicting clinical response to anti-EGFR therapies. Mutations in KRAS at codons 12 and 13 occur in about 15–50% of NSCLC patients, while BRAF mutations are detected in 1–2% of lung cancer patients. KRAS and EGFR mutations appear to be mutually exclusive in NSCLC, with EGFR mutations occurring in non-smokers and KRAS mutations in smokers. Exclusivity is also observed in the case of BRAF and EGFR mutations. This makes it difficult to evaluate whether the observed resistance to EGFR-targeted TKIs is due to the presence of mutated KRAS or BRAF or the absence of mutated EGFR.

Inactivation of PTEN is observed in several cancers, including colon, breast, brain, gastric, and lung, which results in activation of the PI3K/AKT pathway and subsequent degradation of EGFR that generates insensitivity to anti-EGFR therapies. EML4-ALK fusions are a rarer abnormality only detected in 3–13% of lung adenocarcinomas, mutually exclusive of EGFR status. Lung cancers positive for these fusions are resistant to EGFR-targeted TKIs but sensitive to ALK TKIs such as crizotinib (also known as Xalkori).

Acquired or secondary resistance to EGFR-targeted TKI therapies also includes secondary mutations in EGFR, particularly the T790M that is observed post gefitinib treatment and is thought to occur due to selection pressure. Similarly, mutations in PIK3CA and MET are also believed to be associated with acquired resistance. PIK3CA mutations occur in approximately 5% of EGFR mutant lung cancers, while amplification of MET is detected in up to 20% of lung cancer specimens that developed acquired resistance to gefitinib or erlotinib. The data suggests that EGFR TKI treatment may select for preexisting cells with MET amplification during the acquisition of EGFR TKI resistance.

Testing for Mutations in the EGFR Pathway

Clearly, the therapeutic implications of EGFR pathway mutations are substantial. Laboratory studies to identify the mutations are therefore integral to evaluating the efficacy of anti-EGFR therapies designed to manage and treat patients with positive test results.

Traditional methods for detecting EGFR mutations involved screening by direct DNA sequencing of the tumor tissue. Sanger sequencing technology is available in most molecular diagnostic laboratories, and it has the singular advantage of detecting alterations across a gene, including novel variants. However, the sensitivity of this method is low. In a heterogeneous tumor, there must be at least 10–30% mutant DNA in the background of normal DNA. Mutation screening by sequencing is also time- and labor-intensive, making the test costly.

Recent methodologies have therefore focused on targeted screening of mutations to achieve more rapid, robust, and sensitive tests. Molecular diagnostic laboratories currently use a variety of methods, including amplification refractory mutation system, pyrosequencing, smart amplification process, high-resolution melting analysis, and restriction fragment length polymorphism, to name a few. These methods all distinguish between mutant and wild-type DNA within the region of interest. In contrast to direct sequencing, the limit of detection for targeted analysis is ~1–5% mutant DNA in the background of normal DNA. The disadvantage, of course, is that the assay will only detect those specific mutations targeted by the assay.

Laboratories would be well advised to choose a method after considering a number of factors, including availability of instrumentation, reagents required, and other preferences and practices in the lab. However, by far the most important consideration in choice of methodology is the amount of sample available for testing. More often than not, a very small amount of tumor is available. Furthermore, clinicians need the test results quickly to evaluate drug sensitivity or resistance, so the turnaround time must be as short as possible. In many cases, depending upon the technology and platform used, establishing a viable cost-benefit ratio also becomes a challenge. In sum, these considerations generally point to targeted screening of EGFR mutations.

Today, most laboratories use formalin-fixed, paraffin-embedded (FFPE) tissue to test for EGFR mutations. A few also use frozen tumor tissue. However, screening FFPE samples poses significant challenges, including successfully extracting the DNA, interferences from the fixatives used for embedding tissue, and most importantly, obtaining shorter amplicons for effective analysis, particularly if a PCR-based methodology is used.

Alternate sample types such as fine needle aspirates and pleural effusions are currently being evaluated as viable options to enable quicker, easier diagnosis of malignancy. Micro-dissection of the tumor prior to testing is also helpful as it effectively enriches the sample, thereby increasing sensitivity.

Strategies for Therapy

Understanding the efficacy of anti-EGFR treatments, as well as how efficacy correlates to mutations within the EGFR, RAS, BRAF, and other pathways, as well as with crosstalk to the EGFR pathway, has proven to be challenging. In a majority of cancers, single therapies are either short-lived or completely ineffective. Some of the factors that may contribute to these observations are the presence of mutations in multiple pathways and the induction of mutations in non-targeted pathways that have a domino effect, impacting efficacy of the targeted therapy by feedback inhibition (acquired resistance).

Given these shortcomings in targeted therapies, researchers are also evaluating combinatorial therapies, such as sorafenib (targets RAF) with erlotinib, for EGFR mutations and the downstream signaling pathways in NSCLC and glioblastoma. Similarly in patients with both EGFR and PIK3CA mutations, clinicians might consider combination therapy with an EGFR TKI and a PI3K inhibitor. Solving this problem will require algorithms that facilitate testing for mutations, not just in EGFR, but also in molecules downstream (RAS, RAF, AKT, and PIK3CA, etc.). This information might allow clinicians to predict patients' clinical response to standard therapies, particularly for combinatorial approaches that in theory appear to be the most effective.

Many questions need to be answered in order to effectively treat patients with defects in the EGFR family of pathways. Should patients be tested for de novo mutations sequentially or simultaneously in EGFR/RAS/RAF? Assuming they present with the same mutation profile, should patients' metastatic tumors be treated similarly to their primary tumor, or should the metastatic tumor be tested prior to treatment? Should patients receive personalized treatment based on the mutation profile that involves combinatorial therapies not evaluated before? Should pharmaceutical companies actively evaluate multi-arm combinatorial therapy clinical trials targeting EGFR pathways similar to those in triple-negative/triple-positive breast cancer?

To determine the most appropriate treatment for an individual, the American Society for Clinical Oncology recommends that patients with advanced NSCLC who have not previously had chemotherapy or an EGFR TKI drug have their tumors tested for EGFR mutations before therapy is administered. Given the acquired resistance to anti-EGFR therapies observed in tumors, ideally laboratories would test the primary, as well as recurrent metastatic tumors to ensure effective clinical response.

Clinicians and molecular testing laboratories will need to keep up-to-date with the growing body of literature on the mechanisms involved in modulation of signaling pathways such as EGFR in cancer, as well as its sensitivity and resistance to currently available treatments. Currently, there is no right or wrong strategy, only an appropriate one that can be personalized to benefit the patient.

Cheng L, Alexander RE, Maclennan GT, et al. Molecular pathology of lung cancer: Key to personalized medicine. Mod Pathol 2012;25:347–69.

Ellison G, Zhu G, Moulis A, et al. EGFR mutation testing in lung cancer: A review of available methods and their use for analysis of tumour tissue and cytology samples. J Clin Pathol 2013;66:79–89.

Lin L, Bivona TG. Mechanisms of resistance to epidermal growth factor receptor inhibitors and novel therapeutic strategies to overcome resistance in NSCLC patients. Chemother Res Pract 2012;2012:817297.

Scaltriti M, Baselga J. The epidermal growth factor receptor pathway: A model for targeted therapy. Clin Cancer Res 2006;12:5268–72.

Sharma SV, Bell DW, Settleman J, et al. Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer 2007;7:169–81.

Honey V. Reddi
Honey V. Reddi, PhD, is laboratory director of molecular genetics at Prevention Genetics, Marshfield, Wisc.
Email: [email protected]

Disclosure: The author has nothing to disclose.


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Bronze Flatware Cleaning

Copper, zinc and tin include the bulk of authentic bronze flatware, causing a dusky gold finish that’s occasionally enriched with a chemical or lacquer. Improper cleaning or a lack of cleaning can scratch the delicate surface and alter the appearance of the metal. Regular dusting, light polishing with a fabric to enhance shine, and washing with a mild dish detergent is generally sufficient when caring for bronze. Lacquered bronze, including fresh flatware, rarely requires polishing; however, unlacquered bronze, including several antiques, will develop a green patina that you are going to have to remove.

Caring for Display Items

Although you wo not have to wash lasagna debris off ornamental bronze flatware, allowing dirt and dust to build up does just as much harm as leaving behind specks of marinara. Wipe down bronze utensils with a soft flannel cloth to remove dust, and regularly dust the screen area, preferably once a week. Take a little extra time every month when dusting and utilize a flannel cloth to gently polish the metal. Don’t use a lot of elbow grease or see to the flatware like silver; only buff gently in circular motions as though you were applying lotion to your baby’s skin. If the dirt accumulation is extensive due to lack of dusting, place the utensils in around 12 cups of warm water mixed with 1 tbsp of salt. Don’t allow the flatware soak; rather, utilize the saltwater alongside a soft sponge to wash each piece. The salt dislodges dirt and gently buffs away sticky dirt. Rinse each piece thoroughly once you are completed, and dry them gently with a lint-free fabric.

Cleaning Functional Flatware

Wash flatware used for dishes after every use with mild, phosphate-free dish soap, warm water and a soft sponge or rag. Always hand-wash bronze flatware; the heat from the dishwasher and abrasiveness of this water and detergents will ruin the pure color of this metallic and mar the surface. Stay away from water stains by rinsing the flatware and drying with a soft fabric. When desired, gently buff the metal with a flannel cloth before storing to polish the surface.

Polishing Bronze

Decorative and functional non-lacquered bronze flatware require polishing on occasion, but regular dusting and proper cleaning minimizes how frequently it wants a fantastic buffing. When polishing becomes necessary, due to an extra darkening of the bronze or the development of a green patina, a mixture of whiting and distilled water works as a cheap yet powerful DIY polish. Create a thin paste with the two components; scoop some up with a flannel cloth and buff the glue into the bronze till it shines. Wash the wax off thoroughly; dry the utensil having a fabric and finish up by dry polishing with a clean flannel fabric. If the patina is particularly excessive, then you might want to resort to your store-bought bronze wax; even in case you are cleaning flatware which you eat with, make sure anything you buy is food safe. Tip: In case polishing doesn’t eliminate the patina, the bronze is likely lacquered.

Keep in Mind

Bronze has a high percent of copper, which is very soft. Avoid abrasive polishes and cloths, as they can scratch the surface. If lacquered bronze develops a green patina, take the flatware to your professional for polishing. Don’t attempt to strip the lacquer by yourself. Extra exposure to moisture damages the metal; for this reason, store bronze flatware at a climate-controlled area and avoid soaking the flatware in water, also when brushing. Store the pieces safely by wrapping them in a soft flannel fabric.

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Speaker Profile

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Mohammad Al-Duaij, CEO, Alea Global Group, a multi award winning conglomerate single family business. Al Duaij family, carries a legacy that holds great significance in Kuwait in particular, and the GCC in general settled there since the 17th Century. Al Duaij is a dynasty so established that part of the city’s old Souq carries the family name, as does the first charity and water foundations.


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Understanding and living with diabetes

Diabetes is a lifelong condition which causes the individual’s blood sugar levels to become too high. There are two main types of diabetes, with a range of symptoms.

Types of diabetes

There are two types of diabetes:

  • type 1 diabetes – where the body's immune system attacks and destroys the cells that produce insulin
  • type 2 diabetes – where the body doesn't produce enough insulin or the body's cells don't react to insulin

What causes diabetes?

Diabetes occurs when your body is unable to break down glucose into energy, due to there not being enough insulin to move the glucose into the cells, or the insulin produced by the pancreas doesn’t work properly. The risk of type 1 diabetes cannot be lowered by lifestyle changes, but type 2 diabetes is often linked to being overweight.

Living with diabetes

Individuals with diabetes may need to eat healthily, exercise regularly and carry out regular blood tests to ensure that glucose levels stay balanced. If you have type 1 diabetes, you may also require regular insulin injections for the rest of your life, whilst tablets may be required for type 2 diabetes, which is a progressive condition.

Treatment for diabetes

Although diabetes has no cure, symptoms can be controlled by keeping glucose levels as normal as possible. For individuals with type 1 diabetes, insulin injections are required regularly, either in the form of a needle or an under-skin pump. Monitoring your blood glucose levels regularly will ensure that your blood is as normal and as stable as possible.

For individuals with type 2 diabetes, medication may be required regularly, usually in the form of tablets. A medicine called metformin is usually prescribed initially, with another stronger medicine being recommended if your blood sugar levels don’t stabilise within three months.

More information

Diabetes UK:
My Diabetes My Way:
Diabetes Research & Wellness Foundation:


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So many little pimples coming out of this big one........ from looking at this picture I just want to pop them all and poor alcohol in them, but I know that would make my scaring worse.

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I hated the initial breakout accutane caused. I experienced the same thing! You might consider using Klaron lotion (should help with the redness).

I would definitely keep your hands away from your face.

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hey man, i feel for you.

my acne is as bad as that in a different way.

like its not clumped together, but more spread out i have some cysts around my jaw from the initial break out and my forehead too where before there was nothing, kinda wishing i hadnt started with this drug.

im 2 months in to accutane and so far it has just made my skin worse. to the point where i dont want to go out much.

i got my hopes up that accutane would work in 2 month or atleast start to.

but im staying optomistic that it will get better because from what people say it takes at least 3months to see improvement.

so we just gotta stick it out i guess.

ill get some pics up soon so you can see what i mean

how old are you?

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My man

From looking at your photos it looks like you're squeezing your spots. Please don't do that.

Really, I think if you ride out the storm it'll all be good on the other side.

I had acne from when I was about 15 until 22. My mistake was that I insisted on popping every single spot that came along and now I have pockmarks. I'm convinced that if I had let them be I wouldn't have any scrarring now. It sucks ass having a big custard pie spot BUT remember, it'll be gone in a week. A squeezed spot leaves a scar that lasts a lifetime. Squeeze in haste, repent at leisure. Believe me.

BTW you look like you have some Irish in you. Slainte!

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Hi Sweetie,

Just wanted to say, like some others here have already said, hang in there. I had severe cystic acne in my teens/early twenties. I went on roaccutane (accutane) and it was like a miracle. My skin cleared up completely. Initially it broke out (on the tane) but after two courses my skin was completely acne free. And it stayed that way for about 3 years. After that I got an occasional pimple but NOTHING like the ugly, big cysts that I'd had before.

Stick with it because at some point soon you WILL see positive results!!! Please keep us posted on your progress.

Best of luck...big hug to you too!

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Hey there is nothing wrong with popping the white heads takes all that puss out it's not good for your skin if you leave that puss in your skin.

I did sure i got some scars but most people with sever acne will scar sorry to say.

But you could take care of the scars when you're acne free no worries man!

One step at a time!!

Be patient DuDE !!!

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Hong Kong International Airport Pre-school

The Hong Kong International Airport Preschool is a new facility that caters to the day care needs of airport employees. Besides serving the employees’ children, the preschool also hopes to inspire other corporates to offer similar service. The preschool is adjacent to Terminal 2 and enjoys a view to the Lantau mountains through the 7m high curtain wall. The design takes full advantage of the height and daylight and provides as much room as possible to the children. All the utility spaces line the back wall and they are given the form of a series of pitch roofs to decrease the massiveness. The roof pitches transform into a wooden diagrid which wraps the back wall and the ceiling, which helps to conceal the building systems, and accentuate the gradient of soft colours in the space. Every effort is made to minimize voc in this space, from certified furniture suppliers, to flushing the space with fresh air per leed standards.


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Saturday, January 10, 2009

Two Book Reviews

Among the books I've been reading lately two stand out in my mind right now, and I've been wanting to write little "reviews" of them - perhaps some of my readers will want to read these books, too. I read a riveting novel over the summer, and a fascinating book on maternity care in the fall, and only now am I getting around to posting about those good reads! Here goes...

1) Quo Vadis by Henryk Sienkiewicz:

I had no idea how much I would enjoy this book, and I could not have predicted that I would be so drawn into the storyline that I would stay up far too late, night after night, reading. The title is Latin for "Where are you going?", drawn from when Peter met Jesus on his way to be crucified. Quo Vadis is set in the very earliest days of Christianity, and tells of a love story between a pagan Roman military officer, Vinitius, and a young Christian girl, Ligia. Once I was a little way into the book and the plot got moving, I was swept up in the story, which culminates in depictions of famous events: the burning of Rome, and the subsequent feeding of Christians to the lions. The book is inspiring without being preachy - something that can't be said of much historical fiction involving Christianity! The characters really come alive, and I found myself sickened by Nero's cruelty, deceit, and wickedness, drawn to Ligia and other Christians like her, and eagerly awaiting each appearance of Peter or Paul (although they are not very developed characters) in the pages of the book.

I found myself thinking of Diotima's ladder as I progressed through Quo Vadis. Diotima's ladder, or "the ascent passage" from Plato's Symposium, describes how love ascends from a base love (love of a particular body) to the highest love, love of Beauty (as a Form; inseparable from Truth and Goodness). While the connection between the two books is not a precise one, the one certainly reminded me of the other. Vinitius, a pagan entrenched in the ways of Nero's corrupt court, initially lusts after Ligia. So that he might possess her, Romans remove the girl from her home by force, and she is essentially to be a concubine to Vinitius. Through the events of the book, his heart is changed, and he grows to love Ligia's soul, and through her eternal soul, to see and love the beauty of Christ.

Through Christ both Ligia and eventually Vinitius learn to live a life free of fear, a life dramatically different from the typical Roman lifestyle in every way. Vinitius's conversion and subsequent growing faith is powerfully and beautifully told.
"His faith had become so strong that eternity seemed to him something incomparably more real and true than the fleeting existence that he had lived up to that time."

The book describes in vivid detail the persecution of the Christians. Even the wicked, godless Romans who come to the arena to see the sights are sickened by the events that follow - and how much more so was I! At this point in the book, I admit that my vision of the page was occasionally blurred... it is a very sad story, indeed - saddest because it is true.

At the moment when Ligia is in the arena with wild animals, Vinitius's only words are, "I believe! I believe! Grant a miracle, O Christ!"

As to what follows, I recommend you read the book!

Peace to the martyrs.

2) Pushed: The Painful Truth About Childbirth and Modern Maternity Care by Jennifer Block:

My friend Story (who is in the final stages of becoming a certified nurse midwife) lent me this book, and I highly recommend it to anyone and everyone. The scientific and medical aspects of the book are made easy to understand, and the statistics on modern American birth are fascinating. The stories in the book - tales of one unnecessary intervention after another, C-sections of convenience, and agenda-oriented hospitals - certainly ring true with the experiences many of my family members and friends have had in their birth experiences. Suffice it to say that when it comes to low-risk pregnancies, I'm a home birth advocate!

One of the things that struck me as most tragically ironic as I read this book was the concept of "reproductive rights." We hear a lot about women's reproductive rights, don't we? As it turns out, the only right that is getting easier and easier for women to obtain is the right not to reproduce! When women want to reproduce, it's increasingly difficult for them to do so in the way they deem safest, healthiest, and best for mother and baby. The book even describes situations in which lawyers were appointed to unborn fetuses in order to assure the baby a "safe" hospital birth. In a time when fetuses are generally granted few if any rights when a mother wishes to terminate a pregnancy, is it only me who finds this a very sad irony? Most "women's rights" groups are interested only in women's rights to abortion, not real reproductive rights.

Whether you're male or female, young or old, expecting or not, you should read this book. In the interest of true women's rights and reproductive rights, all women should have the intellectual power to know what kind of birth experience they want, and to what kind of procedures and interventions they will or will not consent.

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An Official Website Of The United States Government

47.303-4 F.o.b. origin, freight prepaid.

My Favorites

47.303-4 F.o.b. origin, freight prepaid.

47.303-4 F.o.b. origin, freight prepaid.

      (a) Explanation of delivery term."F.o.b. origin, freight prepaid" means-

           (1) Free of expense to the Government delivered-

                (i) On board the indicated type of conveyance of the carrier (or of the Government, if specified) at a designated point in the city, county, and State from which the shipments will be made and from which line-haul transportation service (as distinguished from switching, local drayage, or other terminal service) will begin;

                (ii) To, and placed on, the carrier’s wharf (at shipside, within reach of the ship’s loading tackle, when the shipping point is within a port area having water transportation service) or the carrier’s freight station;

                (iii) To a U.S. Postal Service facility; or

                (iv) If stated in the solicitation, to any Government-designated point located within the same city or commercial zone as the f.o.b. origin point specified in the contract (the Federal Motor Carrier Safety Administration prescribes commercial zones at Subpart B of 49 CFR part 372); and

           (2) The cost of transportation, ultimately the Government’s obligation, is prepaid by the contractor to the point specified in the contract.

      (b) Contractor responsibilities. The contractor’s responsibilities are the same as those listed in 47.303-1(b), except that the contractor shall prepare commercial bills of lading or other transportation receipts and shall prepay all freight charges to the extent specified in the contract.

      (c) Contract clause. The contracting officer shall insert in solicitations and contracts the clause at 52.247-32, F.o.b. Origin, Freight Prepaid, when the delivery term is f.o.b. origin, freight prepaid.


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Greyhounds dumped on A43 believed to have been found

Authorities believe two greyhounds reportedly thrown from a van onto a busy Northamptonshire road have been reunited with their owner.

Northamptonshire Police Update

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AfG Cinema Awareness Campaign 2
“The Race For Life”

Please like on YouTube and share

AfG Cinema Awareness Campaign 3
“Greyhounds – Dying to Entertain You”

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Our two main Campaign Events for 2020 are:

  • “REMEMBER RUSTY” WEEKEND May - Sat. 2nd and Sun. 3rd ( Remember Rusty Day May 2nd)
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Please see the our ‘How you can help’ section for more details and contact AFG if you would like some of our awareness leaflets for distribution or display.


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Next government must do more to help people with M.E.

June 09, 2017

In the lead up to the general election, Action for M.E. ran a pledge campaign asking you to contact your parliamentary candidates, and joined 80 other charities in calling for an end to disability benefit cuts.

With nearly all votes counted, no party attained a majority in parliament and as yet no coalition or minority government has been confirmed.

As negotiations begin that will determine who forms the next government, we call on all parties to prevent further cuts to disability benefits, and engage with us, people with M.E. and other vulnerable groups to ensure that their needs are met.

All parties will be aware of the urgent need for funding for and reform of health and social care, and ought to consider the impact their eventual policies will have on large numbers of people in the UK, particularly those with long-term conditions such as M.E.

Action for M.E. will continue to actively engage with parliamentarians and policy-makers to raise the issues that matter to people with M.E. throughout this parliament, and ask what they can do to meet the needs of the 250,000 children and adults in the UK affected by the condition.


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Gem #107: Preventing Deallocation for Reference-counted Types

by Ada Magica —C.K.W. Grein

In Gem #97, a reference-counting pointer was presented, where a Get function returns an access to the data. This could be dangerous, since the caller might want to free the data (which should remain under control of the reference type). In this Gem, we present a method to prevent the misuse of the result of Get.

Let's repeat the relevant declarations:

  type Refcounted is abstract tagged private;
  type Refcounted_Access is access Refcounted'Class;

  type Ref is tagged private;  -- our smart pointer

  procedure Set (Self: in out Ref; Data: Refcounted'Class);
  function  Get (Self: Ref) return Refcounted_Access;

  type Ref is new Ada.Finalization.Controlled with record
    Data: Refcounted_Access;
  end record;

The function Get lets us retrieve and modify the accessed object. The problem with this function is that it compromises the safety of the pointer type Ref, in that a caller might copy the result access object and deallocate the accessed object:

  Copy: Refcounted_Access := Get (P);
  Free (Copy);

where Free is an appropriate instantiation of Unchecked_Deallocation.

To cure the situation, we no longer return a direct access to the data. Instead we define an accessor, a limited type with such an access as a discriminant, and let Get return an object of such a type:

  type Accessor (Data: access Refcounted'Class) is limited null record;
  function Get (Self: Ref) return Accessor;

Making the type limited prevents copying, and access discriminants are unchangeable. The discriminant also cannot be copied to a variable of type Refcounted_Access. The result is that the discriminant can be used only for reading and writing the object, but not for deallocation. Thus we have achieved our goal of making accesses safe.

A user might now declare some type derived from Refcounted and change the value of the accessed object like so:

    type My_Refcount is new Refcounted with record
      I: Integer;
    end record;

    P: Ref;

    Set (P, My_Refcount'(Refcounted with I => -10));
    My_Refcount (Get (P).Data.all).I := 42;

This view conversion to My_Refcount will incur a tag check that will succeed in this example. In general, you have to know the type with which to view-convert in order to access the relevant components. An alternative is to declare a generic package like the following:

    type T is private;
  package Generic_Pointers is
    type Accessor (Data: access T) is limited private;
    type Smart_Pointer is private;
    procedure Set (Self: in out Smart_Pointer; Data: in T);
    function  Get (Self: Smart_Pointer) return Accessor;
    ... implementation not shown
  end Generic_Pointers;

Instantiate with type Integer and the last line becomes instead:

  Get (P).Data.all := 42;

So how do we implement the function Get? This is quite straightforward in Ada 2005, using a function returning a limited aggregate. (Note that in Ada 95, limited objects were returned by reference, whereas in Ada 2005 limited function results are built in place.)

  function Get (Self: Ref) return Accessor is
     return Accessor'(Data => Self.Data);
  end Get;

Alas, we are not yet completely safe. To see this, we have to consider in detail the lifetime of the Accessor objects. In the example above, the lifetime of Get (P) ends with the statement and the accessor is finalized. That is, it ceases to exist (in Ada vernacular, the master of the object is the statement). So, tasking issues aside, nothing can happen to the accessed object (the integer in our example) as long as the accessor exists.

Now consider a variant of the above. Imagine we have a pointer P whose reference count is 1, and let's extend the accessor's lifetime:

     A: Accessor renames Get (P);
     Set (P, ...);  -- allocate a new object
     My_Refcount (A.Data.all).I := 42;  -- ?
  end;  -- A's lifetime ends here

In this example, the master of the accessor is the block (and there are other ways to make the lifetime as long as one wishes). Now in the block, the pointer P is given a new object to access. Since we said that P was the only pointer to the old object, it's finalized with disastrous effect: A.Data is now a dangling pointer granting access to a nonexistent object until the end of the declare block.

(Note that this issue also existed in the original GNATCOLL.Refcount implementation.)

To cure the situation, we have to prevent the deallocation. That suggests increasing the reference count with the construction of an accessor and decreasing the count when the accessor is finalized again. The easiest way to accomplish this is to piggyback upon the properties of the smart pointer type:

  type Accessor (Data: access Refcounted'Class) is limited record
    Hold: Ref;
  end record;

  function Get (Self: Ref) return Accessor is
    return Accessor'(Data => Self.Data, Hold => Self);
  end Get;

Incidentally, as a final note, the type Accessor should probably be declared as limited private, to avoid the possibility of clients constructing aggregates (which, by the way, would be quite useless).

Last Updated: 10/13/2017
Posted on: 6/6/2011


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