text:
A medical license is required for a doctor to practice medicine in a particular state. Requirements vary by state but most require, at a minimum, post-graduate training in the doctor’s specific specialty. An NPI number is a national identifier unique to an individual health care provider and is managed by the Center for Medicare & Medicaid Services (CMS).
Learn more about Dr. Victor Santana:
View the full profile to get information on:
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The overall average patient rating of Dr. Victor Santana is Excellent.
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ADHD in Adults
Specialties & Research
Dr. Victor Santana, MD is board certified in Pediatric Hematology-Oncology.
- He has special expertise in 16 areas:
- Acute Myeloid Leukemia
- Adjuvant Chemotherapy
- Bone Cancer
- Bone Marrow Transplantation
- Brain Cancer
- Chronic Myeloid Leukemia
- Diffuse Large B-Cell Lymphoma
- Local Neoplasm Recurrence
- Low Platelet Count (Thrombocytopenia)
- Non-Hodgkin Lymphoma
- Second Primary Neoplasms
- Skeletal Muscle Cancer (Rhabdomyosarcoma)
- Soft Tissue Cancer (Sarcoma)
Education & Awards
Dr. Santana graduated from University of Puerto Rico, San Juan. He has 3 awards.
Dr. Santana has 5 hospital affiliations:
- Baptist Memorial Hospital - Memphis
- Nea Medical Center
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- Additional Information
- Dr. Victor M Santana MD is a male Pediatric Oncologist, has 34 years of experience and practices in Pediatric Hematology-Oncology.
- Where does Dr. Victor M. Santana practice?
- Dr. Victor Santana has 1 office location.
Dr. Victor Santana practices Pediatric Hematology-Oncology near Memphis, TN.
See Memphis Oncologists.

domain: medical


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Students Disagree Over the Purpose of Required English Reading
December 12, 2019
Opinions towards the required literature in English classes vary, as many students speculate the value of the books that their teachers select. Skyline High School’s English department consists of Jill Thackeray, Diona Giannopoulos, Lisa Thornbrue, David Moore, Kirsten Rector, Debra Wilson, Tim Erickson, Colby Ottley, Robin Bucaria, Taylor Williams, and Rachel Giddings.
Generally, these are the books that each grade level may have to read at Skyline High School:
- Ninth Grade: Romeo and Juliet, Cry the Beloved Country, To Kill a Mockingbird, The Count of Monte Cristo
- Tenth Grade: Lord of the Flies, Julius Caesar, The House on Mango Street, Night
- Eleventh Grade: The Crucible, The Scarlet Letter, Narrative of the Life of Frederick Douglass, The Great Gatsby, How to Read Literature Like a Professor
- AP Literature: Crime and Punishment, Heart of Darkness, Our Mutual Friend, Beloved, A Doll’s House
It seems that teachers use books that help prepare their students. The school district creates an approved book list with available assignment material for high school English classes. This list is fairly broad, so teachers are allowed quite a bit of liberty towards what literature they assign.
Subsequent to teaching in Oregon, Debra Wilson began her career at Skyline and has continued her teaching for the past six years. When interviewed, Wilson said that she chooses books based on improving her students’ reading, writing and speaking skills.
Students’ opinions towards the importance of annotations differ. Emma Barker, a Skyline sophomore, considers English her favorite subject. Barker enjoyed reading The Count of Monte Cristo and Julius Caesar. When asked about whether or not she felt annotations helped her personally, she said “A little bit, because it causes you to think… in between the lines” however, she added later that annotating often “causes you to record… pointless things you already knew. Just a waste of time.” Some students at Skyline High School dread the required reading in English classes. Annotations and reading based quizzes often make up more of English grades than written essays. This hatred partially breeds from the extra work it takes to do annotations, while other students just dislike the books in general. Skyline junior Phia Bridge said that “annotating takes away from the enjoyment of reading.” Grace Erskine, a senior, mentions that annotating distracts her from understanding the story.
Granite School District requires four English credits to graduate high school (compared to only three years of math and three of science). English is arguably the most important subject because the reading and writing skills developed are used in every other subject in addition to the ACT.
Each grade level aims their attention at expanding different English skills. Freshman and sophomore year are centered around developing proficiency in communication. Eleventh grade English classes usually focus on analyzing American literature. Twelfth grade students may choose to take AP Literature for an opportunity to gain college credit opposed to Core English for the twelfth grade which focuses on writing.
An additional complaint towards English reading sparks from Shakespeare. While it can often be time-consuming to read works from a few hundred years ago, Shakespeare is a necessary tool to use to understand the English language. Shakespeare provided a significant contribution to literature and culture. Many words in the dictionary originated from Shakespeare and students can learn many valuable themes and messages including one of the most important which occurs throughout his writing: what it means to be human.
Required reading in English classes often sparks disagreement between students. Teachers choose which books will best help their students improve their English skills.

domain: literature


Scotland's Peter Wright and John Henderson won the World Cup of Darts after defeating Austria's Mensur Suljovic and Rowby-John Rodriguez in Sunday's final in Germany.
Wright lifts the trophy for the second time in his illustrious having done so with Gary Anderson in 2019 but his incredibly popular team-mate John Henderson is celebrating a maiden PDC title of any kind at the age of 48.
It's no wonder Hendo was in tears as he walked up on stage at the Sparkassen-Arena in Jena after Snakebite's 4-3 victory over Suljovic sealed an unassailable 3-1 lead in the tie and also prevented him from facing the agony of a deciding singles rubber with Rodriguez.
That's not to say the Huntly thrower wouldn't have been able to handle the pressure considering he memorably sunk the winning double in both of their pairs deciders against the Netherlands and defending champions Wales earlier on a memorable day for the duo (scroll down for semi-final and quarter-final action).
The Scottish pairing were favourites against Austria, who survived three missed match darts from Northern Ireland's Brendan Dolan in a sudden-death leg of their quarter-final before defeating England's James Wade and Dave Chisnall 2-0 to reach their first-ever World Cup final, but an upset looked on the cards when Suljovic crushed Henderson 4-1 in the opening singles rubber with the help of a stunning 160 checkout.
Wright responded by brushing Rodriguez aside by the same scoreline to leave the tie evenly poised ahead of the doubles rubber, which looked to be going the way of Austria when they stormed into a 3-0 lead.
However, Suljovic and Rodriguez combined to miss five match darts across the next three legs as Scotland forced a decider that they won thanks to Henderson keeping his cool once more on double 10.
With the reverse singles to come, Scotland only needed one more point for glory and it was the former world champion and current World Matchplay king who did it as he defeated Suljovic 4-2, firing in a 156 checkout along the way.
"To go back home as World Cup champions, I'm speechless," admitted Henderson. "To win this means everything - it's my first PDC title and it's been an honour to play with Peter.
"How he kept his nerve in that last game I don't know. It's been a team effort but I think we've been the best side throughout the whole tournament.
"It's a team game but he's a legend. I've got to thank Peter for everything he's done this week and all the advice.
"He has mentored me and I can't thank him enough. He's captained me so well and looked after me this weekend, and I believe his captaincy won this for us."
The victory was the biggest of Henderson's career and also secures him a spot in November's Cazoo Grand Slam of Darts.
"It's fantastic for Scotland and I'm going to enjoy this," he said. "Hopefully I can kick-start my own career and this is the start of many things to come."
Former world champion Wright said: "It means so much to me. Every time I play I'm putting everything on the line.
"We had the hardest draw but John helped to carry me through. He stood up proud and hit the doubles to get us into the final.
"It was a privilege to play with him - John's going to take over the world now like Jonny Clayton did after winning it last year."
Suljovic was still delighted after an impressive return to the big stage after missing the World Matchplay through illness. "It's a brilliant feeling," said Suljovic. "I'm so happy I'm back. After three months out I said I would give my best but asked Rowby to help me. I'm so happy to be in the final with my best friend."
Rodriguez is hoping to use the success as a springboard for his career. He said: "Of course if you lose the final you're disappointed, but for me there's happiness to get to the final.
"We didn't expect anything - we were not seeded and we went to the final. If you're in the final you want to be the champion, but unfortunately we didn't.
"I played really good in the semi-final but I didn't play my game in the final. We shouldn't have lost the Doubles game when we were 3-0 up."
John Henderson and Peter Wright have taken Scotland into their fourth World Cup of Darts final as they came through a deciding doubles rubber to defeat defending champions Wales 2-1.
The popular Hendo, who was a late replacement for Gary Anderson before the tournament and is yet to win a PDC title of any kind throughout his career, shocked world number one Gerwyn Price in the opening singles match 4-2 only for Jonny Clayton to reverse the scoreline against Peter Wright.
A hard-fought doubles decider was then all level at 3-3 and although Wales had the advantage of throw, Price's opening visit of 41 handed the initiative to the Scots and it was eventually left to Henderson to take out 46 - with Clayton waiting to come back on 40 - to send his side through to face Austria.
Wright is now bidding to lift the trophy for the second time in his career having done so with Anderson two years ago.
Austria won through to their first World Cup final with a sensational 2-0 defeat of England in Sunday's opening semi-final as Mensur Suljovic and Rowby-John Rodriguez rose to the occasion in Jena.
Suljovic opened the tie in brilliant fashion by averaging 109 in a 4-1 victory over James Wade to give Austria the opening Singles point.
Dave Chisnall opened his tie with Rodriguez with a 12-darter, but the former World Youth Championship finalist took out 109, 128 and 86 amongst four straight legs to seal a brilliant victory.
The win moves Austria into their first World Cup final, having never previously won past the quarter-finals, while both players have put themselves in line for a Grand Slam of Darts place in November.
Scotland's John Henderson and Peter Wright edged out Netherlands' Michael van Gerwen and Dirk van Duijvenbode in a sudden-death shoot-out to move into the semi-finals.
Van Gerwen had put the four-time winners in front by taking the opening Singles tie 4-1 against Henderson - after Scotland, who had previously seen off China and Poland to reach the final day, opted to switch their order of throw.
Wright then set up the Doubles decider by defeating Van Duijvenbode 4-1, and the Scottish duo opened up a 3-1 lead to move to the brink of the semis.
The Dutch produced back-to-back 14-darters to take the tie to a one-leg decider, with Wright's 140 leaving 64 for Henderson, who landed tops to claim a memorable win.
Mensur Suljovic and Rowby-John Rodriguez secured a first Cazoo World Cup of Darts semi-final for Austria as Northern Ireland suffered heartbreak in a sensational opening to Sunday's action.
The Singles ties were shared as Brendan Dolan edged out Suljovic 4-3 before Rodriguez averaged almost 100 as he defeated Gurney 4-2.
The Doubles contest went all the way in a see-saw contest, before Rodriguez initially missed double 16 to claim victory for Austria in the deciding - and sudden-death - leg.
However, Dolan missed three darts at double 12 and six to claim victory for the Northern Irish, and Suljovic returned to land double 16 in a stunning finale.
England's James Wade and Dave Chisnall cruised into a semi-final tie with Austria by defeating Germany's Gabriel Clemens and Max Hopp 2-0.
Wade averaged 101 and hit four doubles from six attempts - including a 130 finish - as he came from a leg down to defeat Clemens 4-1 in their opening tie.
Chisnall then finished four doubles from seven attempts in his 4-0 whitewash of Hopp to keep England on track to claim a fifth World Cup title.
Wales continued their World Cup title defence with a 2-0 defeat of Australia - ending Simon Whitlock and Damon Heta's hopes of claiming glory in memory of Kyle Anderson.
Gerwyn Price set the reigning champions on their way with a 4-1 defeat of Whitlock in the opening Singles tie, sealing the win with a 123 checkout.
Heta battled bravely in his bid to force a Doubles decider as his Singles contest with Jonny Clayton went all the way to a seventh leg, but the Welshman finished a brilliant 144 to seal their place in the last four.
Sunday September 11
Afternoon Session (1pm local time, 12pm BST)
TV Coverage: Sky Sports
Quarter-Finals (Best of 3 points)
(2x best-of-7-leg singles matches & one best-of-7-leg doubles decider if required)
Evening Session (7pm local time, 6pm BST)
Semi-Finals (Best of 3 points)
(2x best-of-7-leg singles matches & one best-of-7-leg doubles decider if required)
Final (Best of 5 points)
(2x best-of-7-leg singles matches, one best-of-7-leg doubles, then reverse singles)


VIDEO: Panama Expansion Reaches Final Stretch
The first-ever Panama Canal Expansion is a vision that will soon become a reality.
With the project 91% completed, the Panama Canal Expansion has reached its final stretch.
The massive Expansion Program will create a new lane of traffic along the Canal through the construction of a new set of locks, increasing the waterway’s capacity.
The new locks will have three chambers, water-saving basins, lateral filling and emptying system & rolling gates.


Thin film fabrication and characterization of proton conducting lanthanum tungstate†
Thin films of the proton conducting lanthanum tungstate phase, La28−xW4+xO54+δv2−δ, were fabricated by atomic layer deposition (ALD) and characterized by impedance spectroscopy. The films were prepared by combining the processes of deposition of La2O3 and WO3 using [La(thd)3 + O3] and [(tBuN)2(Me2N)2W(VI) + H2O]. Deposition of WO3 by the above mentioned precursor combinations is investigated in the range of 250–375 °C proving ALD growth at temperatures 275–325 °C. WOCl4 + H2O was evaluated for WO3 deposition. The observed surface sensitive growth resulted in limited film growth on selected substrates. The process of lanthanum tungstate deposition was optimized with respect to control of stoichiometry and 0.9 and 1.2 μm thick films were deposited on MgO and Pd for cross-plane and in-plane impedance spectroscopy measurements, respectively. Due to short-circuiting of films on Pd after heat treatment, an alternative deposition procedure was devised which reduced short-circuiting significantly. The films show primarily ionic conductivity under wet conditions. Oxide ions are the dominating conductors above 650 °C, while protons become more dominant at lower temperatures. There is a significant contribution from n-type electronic conductivity in highly reducing atmospheres.


Internal combustion engines are way, way better at propelling cars than any of the electrical whatnot we have come up with. Sadly, oil is terrible for the environment, fraught with political tensions, and getting more and more expensive. Mercedes has one (temporary) solution to this problem in the form of the new B200 Natural Gas Drive. While burning natural gasses still produces carbon emissions, it produces much less than burning oil does; this puts our reckoning at the cold hands of angry ice-caps further away, which is a good thing.
The B200 NGD offers 16% less emissions than the next most efficient B-class while still delivering a respectable 156hp.


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Our Shiga Prefecture produced black bean express a robust taste and charm while providing superior nutritional value. The black beans that have been procured from farms within the prefecture are used to make roasted beans and candied beans that refine the delicate flavor of our bean based confections. As our products are directly linked to the black bean harvest, you can enjoy high quality beans for a reasonable price.
|3-54-8 Hieidaira, Otsu City
About 10 min. from the Nishi-otsu Bypass/Ojiyama Ramp via the Kyoto-higashi Interchange/Meishin Expressway
Monday, Tuesday, Thursday, Friday
*We will also open regardless of the date or time’s written above if contacted.

domain: agronomy


Jointly Created Development Board Accelerates Design of Industrial Applications for Control and Automation MarketsSAN JOSE, Calif. -- Jan. 29, 2007
-- Designers of next-generation industrial control and automation systems challenged by requirements of the IEEE 1588 standard for precision clock synchronization can now accelerate their connectivity designs with the first 8-port switch development board. The board provides key features essential to end products by combining devices and intellectual property (IP) from Altera Corporation (Nasdaq: ALTR - News), National Semiconductor Corporation (NYSE: NSM - News) and Germany-based design and IP provider MorethanIP (MTIP).
The new reference board enables rapid implementation of the IEEE 1588 standard across a range of applications demanding sub-microsecond accuracy. This level of accuracy is critical for meeting strict communications latency and quality-of-service (QoS) requirements in the industrial connectivity market. Target applications are switches employing industrial standards like Ethernet/IP, ProfiNet, Ethernet Powerlink and other Ethernet protocols. According to the 2005 Industrial Ethernet Worldwide Outlook by ARC Advisory Group, the industrial Ethernet switch market is estimated at 325,000 units in 2006, growing at a compounded annual growth rate (CAGR) of 49 percent. This market is seeing a heavy adoption of IEEE 1588-based technology.
The reference board includes 10/100-Mbps Ethernet media access controllers (MACs) compliant with the IEEE 802.3 standard, as well as supporting IEEE 1588 versions 1 and 2 for timing control with transparent end-to-end (E2E) and peer-to-peer (P2P) clock sequencing. It offers high port density with low pin count, RMII interfaces and a programmable uplink. Since the board incorporates the recently announced IP core from MorethanIP for Altera® Stratix® II and Cyclone® II FPGAs ( http://www.altera.com/morethanipaltera
), designers can quickly update designs when the second revision of the IEEE 1588 standard is completed in early 2007.
"This reference board makes designing flexible switch products far easier," said Francois Balay, CEO of MorethanIP. "The boards fully conform to specifications and will provide designers with a fast start on their next products."
The current board features Altera's Stratix II device and uses four DP83849 dual-port physical layer transceivers from National Semiconductor. This high-speed industrial connectivity design features the low deterministic latency required for precise clock synchronization and offers National's patent-pending Flex-Port switching for fully integrated range extension, media conversion and hardware-based failover. National's low-dropout and buck regulators power the FPGAs and transceivers. Future models will use a device from Altera's low-cost Cyclone family of FPGAs.
"Ethernet switch manufacturers now have a fully integrated switch solution applying the inherent flexibility of programmable logic," said Michael Samuelian, director of Altera's industrial business unit. "We are demonstrating our commitment to the industrial market by offering a fully integrated 8-port switch with IEEE 1588 compliance, which can be easily integrated into Altera FPGAs. This board speeds development time and enables designs to adapt to changing market requirements."Price and Availability
The reference board is available now for $995 and includes an IP license from MorethanIP. For more information on this reference board, visit: http://www.morethanip.com/boards_ethernetswitch.htm
MorethanIP, founded in 2000, is an expert in design and IP for high-speed communications, serial backplane and embedded system technologies. This includes design, specification and implementation of standard products, system architectures and customer-specific solutions. Combining its methodology with proven technical expertise based on over ten years of industry experience in hardware and software design, MorethanIP generates rapid design cycles to meet time-to-market, functional and budgetary objectives.About National Semiconductor
National Semiconductor, the industry's premier analog company, creates high-value analog devices and subsystems. National's leading-edge products include power-management circuits, display drivers, audio and operational amplifiers, interface products and data conversion solutions. National's key analog markets include wireless handsets, displays and a variety of broad electronics markets, including medical, automotive, industrial, and test and measurement applications. Headquartered in Santa Clara, Calif., National reported sales of $2.16 billion for fiscal year 2006, which ended May 28, 2006. Additional company and product information is available at www.national.com
Altera's programmable solutions enable system and semiconductor companies to rapidly and cost-effectively innovate, differentiate and win in their markets. Find out more at www.altera.com


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Legendary Black Sabbath drummer Bill Ward has shared a brief video clip on social meida, expressing his love for the other founding members of the band: Tony Iommi, Geezer Butler, and Ozzy Osbourne. He claims he would be open to any chance to reunite and perform together again. Ward was excluded from the bands’ “The End” farewell tour after initially agreeing to participate in the dates. The band has retired from touring, mostly due to health concerns from Iommi and Osbourne, but have not ruled out one-off gigs and festivals in the future. The band has been featured at events recently for the 50th anniversary of the founding of the group, such as the Hall of Heavy Metal exhibition and the Black Sabbath Bridge and Bench unveiling in their hometown of Birmingham, UK. Even Ozzy has recently expressed a desire to play with Bill again, so hopefully, this moves it closer to reality.
A quick update. pic.twitter.com/qWMSTWeCs9
— Bill Ward (@billwarddrums) July 3, 2019

domain: news


text:
[Part 3 of 5] Aminah continues her quest to find the lair of the Queen Peony and Rose Princesses. There it is, a great vine of flesh eating Nepenthes plants surrounding the entire place. Aminah then remembered her village folk tales about the Enchanted Garden when she was little. ‘Find the Lily flowers, hold onto it as you venture through the Nepenthes, you will be invincible to them’. The smell of the Lilies is so intense that it has shielded Aminah from being detected by the Nepenthes.
Nepenthes is another name for the tropical pitcher plant. A unique type of plant that thrive in tropical weather. This carnivorous plant is found abundance in the land of Borneo. The unique features of Nepenthes has captivated the artisan to exhibit the beauty of it in this scarf. A digital hand drawing of Nepenthes luring the insects into it’s opening.

domain: biology


Retrieving the trouble codes on your OBD I Toyota Corolla isn't difficult. In this tutorial I'll explain how you can do it in a step-by-step way.
Checking to see what trouble code is lighting up the check engine light (malfunction indicator light -MIL) is done by jumpering together the TE1 and E1 terminals of the Data Link Connector (DLC) with a jumper wire (with the Key On Engine Off).
Once the jumper wire is installed, the malfunction indicator light (MIL) will start flashing the trouble codes stored in the fuel injection computer's memory.
Contents of this tutorial:
You can find this tutorial in Spanish here: Cómo Leer Los Códigos OBD I (1990-1995 1.6L Toyota Corolla) (at: autotecnico-online.com).
Reading The ON/OFF Flashes Of The Check Engine Light
As mentioned at the beginning, your OBD I Toyota Corolla flashes the malfunction indicator light (MIL -also known as the check engine light CEL) once you have jumpered terminals TE1 and E1 in the diagnostic link connector (DLC).
The DLC is located on the left strut tower in the engine compartment. To see a photo of the DLC, go to:
These are the steps to retrieve the trouble codes:
- Make sure your battery is fully charged before starting (its customary to place a charger on the battery while retrieving trouble codes to keep the battery from discharging).
- Turn the key to the On position but don't start the vehicle.
- Jumper terminals TE1 and E1 of the diagnostic link connector in the engine compartment.
- Count the number of flashes of the malfunction indicator light (MIL).
- If no trouble codes are present:
- The MIL will flash continuously and evenly (see illustration below).
- If trouble codes are present:
- The MIL will flash the trouble codes in a specific pattern.
- The digits of the trouble code will be flashed at about 1/2 (.5) second intervals. A 1 1/2 (1.5) second pause will separate first and second digits of the code (see illustration above).
- If more than one trouble code is stored, a 2 1/2 (2.5) second pause will separate the next flashed trouble code.
- Once all trouble codes are flashed. a 4 1/2 (4.5) second pause will occur. After this 4.5 second pause, the trouble codes will be repeated.
- Trouble codes are flashed in order of smallest to largest number.
Once you've confirmed and written down the trouble codes, remove the jumper wire from the diagnostic link connector (DLC) and turn the key to the Off position.
Location Of The Diagnostic Link Connector (DLC)
The diagnostic link connector (DLC) on your Toyota Corolla is located in the engine compartment. More specifically, it's attached to the left-side strut tower (see image above).


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Blockchain analysts estimate that Nakamoto had mined about one million bitcoins before disappearing in 2010, when he handed the network alert key and control of the code repository over to Gavin Andresen. Andresen later became lead developer at the Bitcoin Foundation. Andresen then sought to decentralize control. This left opportunity for controversy to develop over the future development path of bitcoin, in contrast to the perceived authority of Nakamoto's contributions.
The price of bitcoins has gone through cycles of appreciation and depreciation referred to by some as bubbles and busts. In 2011, the value of one bitcoin rapidly rose from about US$0.30 to US$32 before returning to US$2. In the latter half of 2012 and during the 2012–13 Cypriot financial crisis, the bitcoin price began to rise, reaching a high of US$266 on 10 April 2013, before crashing to around US$50. On 29 November 2013, the cost of one bitcoin rose to a peak of US$1,242. In 2014, the price fell sharply, and as of April remained depressed at little more than half 2013 prices. As of August 2014 it was under US$600. During their time as bitcoin developers, Gavin Andresen and Mike Hearn warned that bubbles may occur.
Cryptocurrencies are systems that allow for the secure payments of online transactions that are denominated in terms of a virtual "token," representing ledger entries internal to the system itself. "Crypto" refers to the fact that various encryption algorithms and cryptographic techniques, such as elliptical curve encryption, public-private key pairs, and hashing functions, are employed.
Every transaction is a file that consists of the sender’s and recipient’s public keys (wallet addresses) and the amount of coins transferred. The transaction also needs to be signed off by the sender with their private key. All of this is just basic cryptography. Eventually, the transaction is broadcasted in the network, but it needs to be confirmed first.
The domain name "bitcoin.org" was registered on 18 August 2008. On 31 October 2008, a link to a paper authored by Satoshi Nakamoto titled Bitcoin: A Peer-to-Peer Electronic Cash System was posted to a cryptography mailing list. Nakamoto implemented the bitcoin software as open-source code and released it in January 2009. Nakamoto's identity remains unknown.

domain: finance


- 1/2 HP continuous-duty motor.
- 115, 230*, 460* VAC. (*230 and 460 volt units use a step-down power transformer to achieve 115 volt operating voltage.)
- 40:1 gear-box running in a continuous oil bath.
- Arm rotates 90 degrees in approximately 1.5 seconds.
- Class II, III and IV applications.
- Compliant with UL 325 and 991. ETL Listed. (Note: To be compliant with UL 325 and industry safety guidelines, additional secondary entrapment prevention devices may need to be installed with this gate operator.)
- Dimensions (operator only): 15.25”W x 39.5”H x 14.75”D.
Options available are:
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For more information, contact your local locksmith distributor or DoorKing, telephone 800-826-7493, web site www.doorking.com.
Make sure the site is prepped and the gate itself is operating well, then carefully select the right equipment. In this case the DoorKing 9100 and BEA remote filled the bill.
Securitron has several gate locking solutions which can be used to design the locking solution for your next gate security application.


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Elf on the Shelf 3. All of these pages feature a boy elf.
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domain: hobby


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4-5 May 2017 / 2nd International Conference on Tourism and Cultural Heritage in Mediterranean Faro, PORTUGAL23 November 2017
14-15 Octobre 2017 / Symposium UNESCO- ICOMOS Expert group on the Oasis and Traditional Settlements Florence ITALY8 December 2017
Within the framework of the World Heritage Regional Programme for the Arab States, the World Heritage Centre will organize, from 15 to 19 May next, in Tangier (Morocco), an international expert meeting on the role of the historic urban landscape approach in the conservation of cultural landscapes. In its first part, this meeting will deal with several cases of cultural landscapes, from different regions of the world, inscribed on the World Heritage List. It will then address the issue of identification and protection of this category of cultural properties in the Arab region and, finally, discuss the project of nomination of the heritage of the city of Chefchaouen (Morocco), for inscription on the World Heritage List. The meeting will be held in a special context marked by the adoption, in September 2015, of the 2030 Sustainable Development Agenda and notably Sustainable Development Goal 11 on "Sustainable cities and communities". It will also integrate the adoption, in October 2016, of the New Urban Agenda by the Third United Nations Conference on Housing and Sustainable Urban Development (Habitat III). This new context calls for the reinforcement of the role of culture, including the protection and conservation of cultural heritage, in development strategies. The objectives of the meeting are to explore how the historic urban landscape approach can be used for the conservation and management of cultural landscapes that hold urban attributes, with a focus on the Arab region, and to deal with the case of the city of Chefchaouen.

domain: geography


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Vincent Van Gogh: A Stroke of Genius
Take a comprehensive look at a life of passion and genius. Explore Vincent Van Gogh's remarkable life, including his complicated relationships with women and his long partnership with his brother Theo, and get the real story of why he cut off his own ear. Cliff Edwards, author of Van Gogh & God, offers insight into the powerful obsessions that tormented Van Gogh, and how his struggles as an artist affected his personal life.
Rent DVDs for only $4.99 a month.
- Vincent Van Gogh
- John Griffin
- This movie is
NRNot rated. This movie has not been rated by the MPAA.
Full Screen 1.33:1Subtitles
NoLanguage and sound
English: Dolby Digital 2.0 StereoOther features
Color; interactive menus; scene access.
Vincent Van Gogh: A Stroke of GeniusClose
Common Sense Note
- Age appropriate
- Not an issue
- Depends on your kid and your family
- Not appropriate for kids of the age most likely to want to see it

domain: entertainment


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Here’s our fantasy premier league GW8 wildcard article where we pretend we are using our wildcard. It gives player suggestions with more longevity than just for the up coming gameweek.
fantasy premier league GW8 wildcard – the FFGeek imaginary wildcard
See also Rob Reid’s actual wildcard article
This article brings together the various earlier articles in the week.
It’s a short article where I’m pretending I’m using my wildcard to give you player picks with more longevity than the next game. It’s short as there are few stats.
I’ve given links to articles below with all the detailed stats you’ll need if you want to investigate a player in more detail.
In this article there’s some brief narrative on the selection below. There’s stats in the player ranking articles which can be found here using the links below
The FFGeek imaginary wildcard team
My value at the moment is a fairly modest £102m and the teams fit within that. Remember I only wildcarded a couple of weeks ago so I hoped there weren’t major changes
The structure is flexible with Hojbjerg the only player you wouldn’t start the team with. It could be either 3-4-3, 4-3-3 or 4-4-2 depending on fixtures. Kane is in for the Cardiff fixture with an immediate switch to Aguero afterwards
Goalkeeper and defence
I was tempted to go double Wolves defence with Patricio but stuck with Foster with Watford as the next best £4.5m defence beside Wolves. I’m keeping the non playing GK as I think it avoids missing the odd 11 pointer when you get an unexpected clean sheet.
In defence I still think the 3 top defences are City, Liverpool and Chelsea and that’s where I’ve landed. It’s possible you could put Trippier in for the Cardiff game which could see him with alot of attacking potential through set pieces as an alternative.
So from those 3 defences I’ve gone for the value of Alexander Arnold, the attack of Alonso and what seems to be the selection favouritism of Laporte. However 1 way of using the cash generated from going from Aguero to Kane would be an upgrade to Mendy.
Wolves are the best £4.5m by some distance for me with also a very strong attacking option in Doherty. Wan Bissaka is great value and looks to be a magnet for bonus points when the clean sheets are handed out.
I’m still a believer in Salah given the ridiculous underlying stats even with how tentative he looked v Chelsea. With Huddersfield, Cardiff and Fulham in GW9, GW10 and GW12 I would keep him even if he was moved to left back!
Fraser I think really is looking great value with a few good fixtures left.
Hazard fits the 7 of the 10 test for the top 10 managers I follow. That plus the fact I’ve ranked him highly means he’s in
Lastly there’s Maddison who I picked over Walcott. I wanted Vardy in my forwards but couldn’t afford him so hopefully Maddison picks up some of the crumbs
Kane in for the week then on to a hopefully rested over the international break Aguero over his foot problem and ready to play 90 mins again.
Mitrovic is great value even with the fixtures being slightly less than optimal.
Lastly Ings due to budget restrictions but he does give me a strong first sub and options to rotate. I would have liked to get Vardy in there but that wasn’t financially viable.
That’s it. Hope you found it useful
See also the Rob Reid’s wildcard article, first contributors teams article the bandwagons and sinking ships article early ffgeek team thoughts, 10 top FPL manager analysis article, fixture ease article, underlying stats for players up to GW7 and a review of GW7 in isolation
Geek League links and details
Enter PIN: 8367679
League PIN is SGDKX9Y3

domain: sports


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A new strategic affiliation will link a second Southern Tier hospital system together with a Pennsylvania hospital.
The Lake Erie Regional Health System signed a five-year agreement with UPMC Hamot, a 412-bed hospital in Erie, Pa., an affiliate of the University of Pittsburgh Medical Center.
While stopping short of a merger or acquisition, the agreement is the first step in exploring how the two systems can work together collaboratively to create efficiencies and provide better care for patients.
The Lake Erie Regional Health System serves the northern Chautauqua County region. With more than 1,000 employees, the system includes Brooks Memorial Hospital, Lake Shore Health Care Center and the outpatient sites of TLC Health Network. The system has been working over the past year to examines its options for a strategic affiliation with a larger health care organization.
The Erie hospital, formerly known as Hamot Medical Center, came together with UPMC in January 2011, making it its tertiary hub for Northwestern Pennsylvania. With total revenue of $486 million, the hospital system includes 433 physicians and a total staff of 3,159.
It is the second cross-state hospital affiliation for the region: Olean General Hospital came together with Bradford Regional Medical Center in 2009 under the Upper Allegheny Health System.
According to a statement released May 24 by Lake Erie Regional, the system says an affiliation with UPMC Hamot allows it to preserve local governance and control, supports physician development and recruitment efforts, assist in a strategic/master facility planning process and provide expertise for clinical and operational areas.
“If, over time, a closer type of affiliation or relationship is deemed to have potential benefits, the board will evaluate and consider the merits of such a change at that point,” they wrote. “We are confident that the anticipated relationship with UPMC Hamot will avail our community and our organization to resources and expertise that will serve as a stabilizing force in our efforts to ensure a bright, sustainable future for LERHSNY and for the delivery of high quality health care throughout this region.”
Lake Erie Regional pointed to Hamot’s recent ranking as a Top 100 Hospital by Thompson Reuters as a factor in the agreement, saying it will work closely with Hamot to make sure its own patients receive the highest levels of quality and service.
Over time, Lake Erie Regional said it expects to provide greater access to its patients to more primary care physicians and specialists through the relationship, which will reduce waiting times for appointments and reduce the need to travel outside the area for care, it said.


After so many teasers, Realme Q smartphone has been finally launched in China. It a new series of the smartphone but actually its the rebranded version of the Realme 5 Pro smartphone. The biggest highlight of the smartphone is its quad-camera setup at the back and the Qualcomm Snapdragon 712 processor. It is launched in China in three different variants. Check all the details here.
Realme Q Price
As said above, Realme Q has three different variants. Realme Q price starts at CNY 998 which is roughly Rs 10000. It comes with 4GB RAM+64GB storage. The second variant comes with the 6GB RAM+64GB storage and price is CNY 1198 which is roughly equal to Rs 12000. The third variant of the phone has the 8GB RAM+128GB storage and price is CNY 1298 (roughly Rs 15000). There are two colors of the phone i.e the Light Green and Light Blue. It will be available in China from 9th September.
Realme Q smartphone has a 6.3-inches display with a screen resolution of 1080×2340 pixels. There is a Corning Gorilla Glass 3+ protection available on the display. It has an Octa-Core Snapdragon 712 processor. There is 4GB/6GB/8GB RAM on the phone with an internal storage of 64GB/128GB. The storage of the phone is expandable via microSD card up to 256GB.
Moving to the camera specifications of the phone, Realme Q has quad camera setup. The rear camera has 48MP primary sensor, 8MP wide-angle camera lens, 2MP macro lens and a 2 MP portrait lens. On the front, there is a 16MP camera. It has a battery of 4035mAh.The phone runs on the Android Pie operating system.


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One patient of a French family with Gerstmann-Sträussler-Scheinker syndrome with the mutation in codon 117 of the prion protein (PrP) gene displayed unexpected neuritic degeneration around PrP plaques and numerous diffuse neurofibrillary tangles, whereas other members did not. The tau profile in this patient’s brain was analysed and compared with one from another member of the Gerstmann-Sträussler-Scheinker family as well as with the Alzheimer’s tau profile. A panel of well characterised antibodies against both normal tau protein and paired helical filaments-tau protein was used on immunoblots of brain proteins resolved by mono and two dimensional gels. The tau profile in the patient with Gerstmann-Sträussler-Scheinker syndrome without neurofibrillary tangles was normal. The tau profile from the patient with Gerstmann-Sträussler-Scheinker syndrome and neurofibrillary tangles was characterised by a hyperaggregation state of tau protein. This case illustrates the phenotypic heterogeneity of the GSS117 mutation not only from one family to another, but also between members of the same family. In this family, the presence of neurofibrillary tangles is still unexplained, but could be correlated with either the protracted duration of the disease or the old age of the patient.
- prion diseases
- neurofibrillary tangles
- tau proteins
Statistics from Altmetric.com
Gerstmann-Sträussler-Scheinker disease is an inherited human progressive neurodegenerative disease which has been associated with various mutations in the prion gene.1 The clinical picture may associate dementia, ataxia, extrapyramidal, and pyramidal signs or pseudobulbar syndrome. Neuropathological findings in the brain include neuronal loss, spongiform change, and gliosis as well as unicentric or more often multicentric amyloid plaques. Neurofibrillary tangles are consistently present in patients with mutation at codon 1982 or 2173 of the prion protein (PrP) gene, each found in a single family, and in a Japanese patient with a stop mutation at codon 145.4
Neurofibrillary tangles correspond to intraneuronal changes, of which the most important components are phosphorylated tau proteins.5 They were first described in Alzheimer’s disease, in which immunoblot labelling in brain homogenates using the highly specific and sensitive monoclonal antibody AD2, which binds to a phosphorylation site located at the carboxy terminal of the tau protein molecule,6 showed the presence of a typical tau triplet (55, 64, 69 kDa).7
We report here the unpublished case of one patient from the previously described French Alsatian Gerstmann-Sträussler-Scheinker syndrome family with the codon 117 mutation,8-9 who, on neuropathological examination, showed unexpected and numerous neurofibrillary tangles. A biochemical study of tau proteins was performed in this patient and in another case of the Gerstmann-Sträussler-Scheinker syndrome family with the same PrP mutation but devoid of neurofibrillary tangles. In parallel, biochemical results were compared with those obtained in typical cases of Alzheimer’s disease.
Material and methods
The two patients were from two generations of an Alsatian family in which 13 members had already developed the disease (fig1).
Patient 1 (IV.4) was healthy until the age of 64. At this time, she was admitted to hospital because of gait impairment and tremor. Neurological examination disclosed parkinsonian signs with rest tremor, hypertonia, and akinesia in her right upper and lower limbs. Neuropsychological tests showed difficulties in memory as well as constructive apraxia and agraphia. The patient was dysarthric and had a bilateral grasping reflex. Despite treatment with levodopa, her neurological state worsened progressively. The patient was not seen again until she was 70, at which time she had become bedridden because of extrapyramidal and pyramidal signs (right hemiplegia). She had developed epileptic fits. Her speech was extremely reduced. Pseudobulbar signs and global dementia appeared later and she died at the age of 73.
Patient 2 (V.15) developed, at the age of 33, fatiguability of his right lower limb which progressively worsened. His voice became hoarser and a few months later, he had to leave his job because of difficulties in concentration and lack of attention. At the age of 34, neurological examination showed pyramidal signs in all four limbs, axial akinesia, and cerebellar signs which increased the gait difficulties. Facial diplegia, dysphagia, and dysarthria were present and the patient became extremely emotional. At 35, he was bedridden with pyramidal, extrapyramidal, and cerebellar symptoms. Pseudobulbar syndrome was significant. Cognitive dysfunction increased slowly and the patient died at the age of 39.
The genetic study performed by Tateishi et al has been previously reported.8-9 All the patients had the same mutation in the PrP gene: they carried a silent A to G transition at the third position of the alanine codon at 117, a C to T transition at the second position of the same codon leading to an alanine to valine (val) change (val 117), and an A to G transition at the first position of codon 129 that results in a methionine (met) to valine (val) substitution (val 129). In these two patients, the A to G transition at the first position of codon 129 was absent in the normal allele, and both were heterozygous met-val at codon 129. Apolipoprotein E genotype was E3/E3 in patient 1.
Antiglial fibrillary acidic protein (GFAP) antibody (Dako), antineurofilament antibody reacting with 70 kDa, 60 kDa, and 200 kDa polypeptide subunits (Dako), antiubiquitin antibody (Dako), anti-tau antibody reacting with phosphorylated and non-phosphorylated forms of the protein (Dako), antipaired helical filaments antibody (ICN), anti-Aβ antibody (Dako), and anti-PrP antibody (kindly provided by Dr S Prusiner) were used for immunohistochemical staining.
The antibody AD2 was used for the specific immunoblot staining of pathological tau protein.6 AD2 is a monoclonal antibody raised against a paired helical filament preparation isolated from Alzheimer tissue. It has a high specificity and sensitivity for phosphorylated tau proteins6 10 and it recognises an epitope located at the carboxy terminal part of the tau molecule including phosphorylated serines 396 and 404. Indeed, AD2 is able to directly detect pathological tau proteins in crude sodium dodecyl sulphate brain tissue homogenates.6 M19G is a polyclonal antibody directed against the synthetic peptide corresponding to the amino terminal part of the tau molecule6 11 and labels both normal and pathological tau proteins. Other antibodies against tau proteins were also used: a polyclonal antibody 13312 which is raised against the first 16 amino acids of all tau proteins, and two other polyclonal antibodies 304 and 189 which recognise the 29 or 58 amino terminal inserts respectively, and therefore specifically detect the adult variants of tau proteins.5 Adult tau proteins are composed of six isoforms, and antiserum 304 recognises four isoforms and antiserum 189 recognises only the two longest isoforms. neuropathology At the time of necropsy, which was limited to
At the time of necropsy, which was limited to the brain and spinal cord, one cerebral hemisphere from each of the two patients was frozen at −80°C for neurochemical, molecular genetic, and transmission studies. The remaining parts of the CNS were fixed in 10% formalin. Multiple brain tissue blocks were
embedded in paraffin and sections were stained with haematoxylin and eosin, cresyl violet, Congo red, Luxol fast blue/cresyl violet, and Bodian’s silver method. Immunohistochemical staining was performed on selected sections. A standard peroxidase-antiperoxidase technique was used. Spinal cord sections were stained with haematoxylin and eosin, cresyl violet, and Luxol fast blue/cresyl violet.
An electron microscopic study was performed in cases 1 and 2. Samples of frontal cortex and cerebellar cortex were fixed in 3% buffered glutaraldehyde at the time of necropsy, then postfixed in 1% osmium tetroxide and embedded in Epoxy resin. Ultrathin sections were stained with uranyl acetate and lead citrate. They were examined with an EM 300 Philips electron microscope.
Several brain area samples from patients 1 and 2 were studied, using a previously described semiquantitative western blot approach.7 Brain tissue samples were heat treated in Laemmli sample buffer at a ratio of 1 g/10 ml. Homogenates (10 μl) were then loaded on SDS-PAGE (10–20% slab gel). Proteins were transferred on to nitrocellulose membranes (0.45 μm pore size, Schleicher and Schuell) for 90 minutes. (current: 0.8 mA /cm2) using an LKB Multiphor II Nova Blot (Pharmacia) according to the manufacturer’s instructions. Blocking was carried out with tris buffered saline containing 5% (w/v) dry milk and 0.05% (w/v) Tween 20. The blotted proteins were incubated with monoclonal antibody AD2 at a final concentration of 0.3 μg/ml for two hours at room temperature. They were then revealed with horseradish peroxidase labelled sheep antimouse or antirabbit immunoglobulins (Diagnostics Pasteur) and detected with the ECL western blotting system (Amersham).
Two dimensional gel analysis
A more detailed analysis of the tau profile from patient 1 was performed using two dimensional gel electrophoresis. Its pattern was compared with the one from a patient with Alzheimer’s disease. Two dimensional gels were obtained according to a modified O’Farell’s method,13 as described by Sergeant et al.14 The first dimension gel contained 9.5M urea, 2% Triton X100, 5% (vol/vol) (Pharmacia) with 4% pH 3 to 10 and 1% pH 4 to 6.5. Brain homogenates (15 μl) in Laemmli sample buffer were heat treated for five minutes at 100°C and centrifuged at 10 000 g for 10 minutes at 4°C. Thirty five microlitres of a solution containing 8 M urea and 4% Triton X-100 were added to the supernatant. Samples were run for 20 hours at 500 V and at 700 V for 30 minutes on 10 cm long, 3 mm diameter capillary tubes. The first dimensional gels were then equilibrated for five minutes in 5 ml equilibrium buffer containing 10% glycerol, 0.5% dithio treitol, 3% SDS, and 0.25 M tris at pH 6.8. The second SDS-PAGE dimension and western blot analysis were performed as described for immunoblotting.
Isoelectric points were determined using the CarbamylyteTMcalibration kit (Pharmacia). Five microlitres of carbamylated creatine phosphokinase was added to the brain homogenate, as recommended by Pharmacia. GFAP immunostaining was also used for calibration, after AD2 staining. M19G was used either as the first antibody, the blot being then stripped in accordance with the Amersham ECL western blotting system, and lastly stained with AD2, or vice versa (AD2 staining first, stripping followed by M19G staining).
Patient 1 (No 40743-IPS) (fig 2)
The left cerebral hemisphere was severely atrophic. Microscopy disclosed PrP amyloid plaques that were numerous in the cerebral cortex, basal ganglia, thalamus, and the cerebellar cortex where they also affected the granular layer. They were often unicentric and large. Most of them were accompanied by many neuritic degenerations which were immunolabelled with anti-tau antibodies, including AD2, and which ultrastructurally consisted of dense bodies and paired helical filaments. Numerous PrP amyloid deposits were scattered throughout the cerebral and cerebellar white matter. In the cerebral grey matter swollen neurons were seen and astrocytic reactions were pronounced. Spongiform change varied in intensity and was often associated with PrP amyloid deposits. Numerous neurofibrillary tangles, immunolabelled with anti-tau and antipaired helical filament antibodies, were found in the cerebral cortex, amygdala, and thalamus. Ultrastructurally, they consisted of paired helical filaments. Senile plaques were absent. However, rare Aβ protein deposits, always associated with PrP deposits, were found in the cerebral cortex and lower striatum. The spinal cord was histologically normal.
Patient 2 (No 40683-IPS)
Microscopy disclosed, as in patient 1, numerous PrP amyloid plaques in the cerebral cortex, basal ganglia, and thalamus. Neuritic reactions were absent or mild. Spongiform change varied in intensity but on the whole was moderate. Neuronal loss was suspected in the frontal cortex and confirmed in the globus pallidus and thalamus. Neurofibrillary tangles and Aβ protein deposits were absent.
Monodimensional western blot analyses (fig 3)
For patient 2, AD2 immunoreactivity was absent whereas it was positive for a patient with Alzheimer’s disease who displayed a characteristic pathological tau triplet. On the same immunoblot, AD2 immunostaining for patient 1 was extremely strong, with smears all along the electrophoretic migration tracks. Pathological tau proteins were not dectectable because they were masked by the smears.
M19G immunostaining—Using M19G, the group of normal tau proteins with molecular weight ranging from 45 to 64 kDa was detected for patient 2. Bands with a low molecular weight corresponding to tau catabolic products were also detected. For patient 1, tau proteins had a molecular weight in the range of Alzheimer’s disease pathological tau proteins. However, tau proteins as well as their catabolic products were only present in small amounts.
Two dimensional western blot analysis (fig 4)
In the resolved Alzheimer’s disease brain extract, AD2 immunodetected the triplet of pathological tau proteins, with an isoelectric point between 6.9 and 5.8. A higher component with a molecular weight of 74 kDa as already described,14 was also present. For patient 1, huge amounts of smears were found. Smears were in the isoelectric point range of 7.1 to 6.2. Low molecular weight components corresponding to catabolic products were absent, with the exception of three characteristic low molecular weight components detected at 26, 27, and 29 kDa and with an isoelectric point ranging from 7.2 to 6.6. All brain areas studied were affected, and especially the limbic structures.
M19G staining—In the Alzheimer’s disease brain extract, the triplet of pathological tau proteins and a 74 kDa component were immunodetected. A very acidic isoelectric variant at isoelectric point 5.8 corresponding to the 74 kDa component was detected with M19G, antibodies 133, 304, and 189 (data not shown), but not with AD2. These results show that the 74 kDa band corresponds to an adult tau protein isoform with exon 2 and 3. Numerous catabolic products were found.They were widely distributed all over the pH gradient. In brain extract from patient 1, the triplet of 55, 64, and 69 kDa tau proteins, and a 74 kDa component were detected, whereas the smears were faintly immunolabelled. However, a stronger band with a higher molecular weight of 78 kDa was also present. A very acidic component of the 74–78 double band was present at isoelectric point 5.8. Catabolic products were almost undetectable.
Gerstmann-Sträussler-Scheinker syndrome has been associated with six mutations of the PrP gene. The presence of neurofibrillary tangles, in addition to PrP immunoreactive amyloid deposits, is one of the neuropathological distinctive features of Gerstmann-Sträussler-Scheinker syndrome families with mutations at codon 198, 217, or 145 (table). In the codon 217 mutation,15 carried by two patients from a Swedish family, pathological studies showed numerous Aβ deposits besides PrP immunoreactive deposits. Some of them were found around PrP plaques but true senile plaques as well as Aβ blood vessel deposits were also detected, so that the association of Gerstmann-Sträussler-Scheinker syndrome and Alzheimer’s disease could not be ruled out.3The codon 145 mutation was found in one Japanese patient4in whom amyloid deposits were immunolabelled with antibodies to PrP but not with antibodies to Aβ protein. Finally, codon 198 mutation has been described in a large American Indiana family;16-17pathological studies showed numerous neurofibrillary tangles and, around PrP amyloid deposits, abnormal neurites which were immunostained by tau protein and ubiquitin antibodies, and which were composed as in Alzheimer’s disease of paired helical filaments. Tagliavini et al 18 showed that A68, an abnormally phosphorylated form of tau proteins and a major component of paired helical filaments in Alzheimer’s disease, is present in the paired helical filaments of GSS198. No Aβ deposits were found except in the older patients, in whom Aβ immunoreactivity was seen only around some PrP deposits.19
As in mutations at codon 102 and 105, neurofibrillary tangles are usually absent in the mutation at codon 117. Mutation 117 has been described in three families. The lack of cerebellar involvement in the first reported American family20 led to the definition of the 117 genotype as the “telencephalic form” of Gerstmann-Sträussler-Scheinker syndrome. However, the neuropathological findings in these French cases, with numerous PrP plaques in the cerebellum and presence of neurofibrillary tangles illustrate the phenotypical heterogeneity of mutation 117. In this Alsatian family, neurofibrillary tangles and neuritic degeneration have been found only in patient 1 (among three who were necropsied, and another one with cerebral biopsy). Using immunochemical analyses, pathological tau proteins were not detected in brain homogenates from patient 2 but were found in huge amounts in almost all cortical areas for patient 1, in good agreement with the neuropathological findings. The tau protein pattern was characterised by the presence of smears all along the migrating track as visualised by AD2 immunostaining. Smears have already been reported in Alzheimer’s disease but this phenomenon is by far more important for patient 1 ; they correspond to the carboxy terminal part of the tau protein21 or, as they were also detected in the range of low molecular weight, to small fragments of the tau protein which are still aggregated, even after SDS solubilisation. Low amounts of variants with a molecular weight similar to the pathological Alzheimer’s disease tau proteins (55,64, and 69 kDa) and a 74 kDa band which was more intense than in Alzheimer’s disease extracts were found with M19G. Another higher band of 78 kDa was detected as well. Together, the analysis of tau proteins shows a hyperaggregation state of tau proteins in patient 1 compared with Alzheimer’s disease.
The inconstant presence of neurofibrillary tangles in GSS 117 led us to ask why some patients develop neurofibrillary tangles whereas others do not. From a clinical point of view, as proposed in Alzheimer’s disease,22 neurofibrillary tangles could be correlated with severity of the dementia. Indeed, cognitive impairment usually occurs only in the latest stage of the disease in patients with mutation at codon 10223 or 105,24 but is one of the first signs in patients with mutation at codons 145, 198, or 217 where neurofibrillary tangles are constant. However, in patients with mutation at codon 117, dementia is a cardinal feature of the disease in the French family and in one of the two American families,20 25 but neurofibrillary tangles were found in only one patient.
Although the codon 129 genotype has been shown to influence phenotypic expression of some prion diseases,26 it cannot be linked to neurofibrillary tangle formation in Gerstmann-Sträussler-Scheinker syndrome. A val genotype in codon 129 was present in the mutant allele of all patients with the codon 117 mutation (either with neurofibrillary tangles or not) and the table confirms the absence of correlation between the presence of neurofibrillary tangles and codon 129 genotype in various PrP gene mutations. Because Aβ protein increases the phosphorylation of tau proteins in vitro,27coexistence of Aβ deposits in patient 1 could have contributed to paired helical filament formation. However, Aβ deposits are inconsistent in other PrP mutations with the presence of neurofibrillary tangles (table). In patient 1, coexistence of Gerstmann-Sträussler-Scheinker syndrome and Alzheimer’s disease, as proposed in the codon 217 mutation, seems also to be excluded as Aβ deposits were too rare and always located around PrP deposits. Finally, at least in this mutation, neurofibrillary tangles could be correlated with either the old age of the patient (the oldest in this family), or the protracted duration of the disease, as the clinical course of our patient was the longest in the Alsatian family (nine years).
In conclusion, this case, with cerebellar involvement and neurofibrillary tangles, illustrates the phenotypical heterogeneity of GSS 117 not only from one family to another, but also between cases from the same family. Factors other than PrP genotype, still unknown, should be implicated in the phenotypic expression of the disease.
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