If you are wondering about the status of your Family Tree Maker software, here is an email that I received today. Please note that FTM has been purchased by MacKiev software company and isn't going away! I'm still using it and plan on continuing to do so.
Thanks for signing up for the Family Tree Maker mailing list!
After six years as the developer of all the Mac editions of Family Tree Maker, we are so glad that Ancestry chose us to pick up where they left off as the publishers of this wonderful old brand. A new era for Family Tree Maker has begun, and we're looking forward to keeping you up to date.
• Users of FTM 2014 and Mac 3 – Free updates are coming soon. If your copy is working well, just hang in there and we'll send you an email to let you know as soon as they are available. If however you are experiencing crashes or the application has slowed to a crawl with really large trees, see "What About That Free Update" below to find out how to get an interim update sooner.
• Users of older FTM editions – No matter how old your copy of FTM is, or whether it's running on Windows or Mac, you can download an upgrade for $29.95 (vs. $69.95 regular price). Click here to take advantage of this limited-time upgrade offer today. You'll also be presented with an option to purchase a hard copy on CD ($10) or our new natural wood USB drive pictured above ($14).
• New users – If you have never owned a copy of Family Tree Maker before, you can download a full edition from our online store for $69.95 by going to www.familytreemaker.com and clicking the Store button. You can purchase a download with or without a hard copy on CD or USB drive. And on startup, you'll get an offer for a 14-Day free trial you can use to search the 16 billion records on Ancestry.com.
As it gets closer to the end of 2016, we're understandably hearing this question a lot. That's because Ancestry initially said they'd only support FTM through the end of December 2016. But that was last year back in December 2015 when they also announced the brand wouldn't continue at all. All that changed 7 weeks later on February 2nd — the day Ancestry announced that they'd decided after all to sell this wonderful old brand to us. And that together we would be building on what Ancestry had started, including building a new sync technology together.
So relax. TreeSync® is not ending at the stroke of midnight this December 31st. And though it will be retired at some point, before that happens, there will be new syncing technology available to replace it. It's already well into development and we will be starting outside beta testing before the end of the year. And that means syncing as we know it for FTM is going to live on into 2017 and beyond. So if you have been worried about what happens at the end of the year, well you can just stop worrying. Syncing, Ancestry search, and shaky leaf hints are all here to stay.
Software MacKiev is now happily supportIng all versions of Family Tree Maker for both Mac and Windows, though Ancestry will continue to assist us through the end of 2016 and beyond.
Support Requests. If you don't find what you need in the Knowledge Base articles (at support.familytreemaker.com) just click the link for "additional support" at the bottom of the page and you will see the Technical Support request form. Typically we get back to you in 2 days or less.
Live Chat. When you file a Support Request (see above) between the hours of 9am and 6pm EST, 7 days a week, you will have an option to have a live chat with an experienced support agent. This can be very helpful for urgent issues or those that require a discussion rather than a single email.
Facebook Group. There is an excellent unofficial but very active Facebook group called "Family Tree Maker® Users" which you might want to consider joining. They have many very experienced users who are very generous with sharing their time and wisdom to help other users solve issues.
Replacement Copies. We have set up an online Replacement Center which is always open. The Center can only provide replacements for those with FTM 2014 or Mac 3 and later. If that's you, then have a look at "Getting a Replacement Copy" below.
2. Click "for additional assistance" at the bottom of the page.
The Replacement Center checks that you have a copy of FTM 2014 or Mac 3 registered with Ancestry and then provides you with a free fresh link by email. You will also be given an option to purchase a backup disc for $10 or our new natural wood USB backup drive for $14. Note that what you get will be a full free-standing installer, so it won't be looking for your old copy, a disc, or anything else.
You will also notice that the replacement copy installer doesn't ask you for an activation code. That's because we don't use them. Why? Well, we don't like them ourselves, so we decided a long time ago we weren't going to torment our customers with them. Instead, we use this old-fashioned thing called the honor system. It's been working pretty well for us for more than two decades now, so don't expect us to be changing that any time soon.
WHAT ABOUT THAT FREE UPDATE?
When we happily rescued FTM earlier this year, we set out to create free updates that we could wholeheartedly recommend to all current users of FTM 2014 and Mac 3. That work is still in progress, but if you'd like to get your hands on a copy and you're OK with a near-final build, then you can have one any time. Even right now.
That's because a couple of months ago we started making the latest interim builds of FTM 2014.1 and Mac 3.1 available for free from our Replacement Center for any registered FTM 2014 or Mac 3 user. And since then, when anyone has come to us with a serious issue that's fixed in the new editions, we have sent them there to get a copy right away.
Why so cautious? Well, because this is a very complex product. And because we feel an awesome responsibility in dealing with what often enough is literally decades of a user's work. So we are taking the time to get it right – to ensure that when we release final builds of Family Tree Maker 2014 and Mac 3 they're as ready as they can be to meet that high standard.
So, should you get the latest build right now then? Well, it depends. The improvements we're made are mostly in stability and performance. So if FTM is crashing or has slowed to a crawl with large trees, then have at it. Same if the waiting is driving you crazy, or you usually download interim updates anyway.
But if, like most users of FTM 2014 and Mac 3, your copy is working just fine, and you like being conservative about installing updates, we still suggest waiting for the final build. This is, after all, not a new version. It's a patch. That's why it's free. And if you don't think you need it right away, then you probably don't.
2. Click "for further assistance" at the bottom of the page.
Most everything you will need to know can be found on our Family Tree Maker home page.
FAQ – Find answers to the most frequently asked questions.
Feedback – Let us know what we're doing right and what to improve.
Report a Bug – Tell us what you think needs to be fixed.
Suggest a Feature – What you would like to see in our next edition?
Beta Tester Signup – To help us test upcoming editions, sign up here.
If you have questions for us, please first read our FAQ as we've tried to answer the most common ones there. If you don't find the answer you are looking for there, please send your question through our Feedback Form which you'll find on our FTM Home Page (see above). Thanks!
© 2016 The Software MacKiev Company. Family Tree Maker is a registered trademark of The Software MacKiev Company. Ancestry.com and TreeSync are registered trademarks of Ancestry.com Operations, Inc.
To be removed from future Family Tree Maker emails, just reply to this email with 'unsubscribe' in the subject line.


text:
Story Uuid: e1e1d7c0-3fe2-4c21-a15e-e6b324cd40e6
Story Link: /#story/e1e1d7c0-3fe2-4c21-a15e-e6b324cd40e6
Ad Zone: news/auto-matters
Story Slug: 3-things-to-know-about-the-mazda-cx-30
3 things to know about the Mazda CX-30
By Jill Ciminillo, Automotive Editor 1562620484000
2020 Mazda CX-30 (Sinclair Broadcast Group / Jill Ciminillo)
It's now been a few months since Mazda launched the CX-30 at the Geneva International Motor Show, and we still don't know too much about this petite new crossover -- except that it is coming to the United States.
However, it wasn't shown at the New York International Auto Show in April, so we'll have to assume it'll make its North American debut at the LA Auto Show in the fall.
So, what do we know?
Why it's not called the CX-4
The CX-30 sits between the CX-3 and the CX-5 in terms of size and pricing, so using the CX-4 designation would have made sense. But -- there's already a CX-4 in China, and it's not this vehicle.
So, Mazda had to punt. We don't think this will hearken in a completely new nomenclature for the brand, and we're assuming this will be a one-off deviation from the single digit CX structure.
However, reality often deviates from expectations. So stay tuned.
What the engine lineup looks like
We know that globally, the CX-30 will be available with Skyactiv-G gasoline engine, Skyactiv-D diesel engine and the all-new Skyactiv-X gasoline engine that operates like a diesel. Additionally, there will also be a hybrid version of this vehicle available.
But what does that mean for the U.S. exactly? We don't know for sure.
We can make a good bet that the vehicle will launch in the states with an engine that's already here, which would be the 2.5-liter Skyactiv-G, 4-cylinder engine that also appears in the new Mazda3.
We have high hopes that the Skyactiv-X engine would soon follow – especially since we've had the chance to test this engine in a prototype vehicle and loved it.
But will the hybrid version or diesel engine make it here, too? No idea.
When it will be in the U.S.
At the Geneva show, exces said that the CX-30 will hit the European market sometime this summer and that it would come to the United States sometime after that – probably by the end of the year.
There was also no model year confirmation, but because of the timing, it makes sense for it to be a 2020 model.
We do have confirmation that the European model will be out imminently (this week or next) and that there will be some U.S. news coming in November.
Mazda is going to have a bit of an uphill battle to climb with the CX-30 in the United States. Not only has Mazda deviated from its normal nomenclature, but CX-30 also sounds a lot like QX30, which is another small SUV from a completely different automaker.
The CX-30 looks great, and if the new direction Mazda set with the Mazda3 is anything to go by, it'll have a distinctly upscale feel and it will be fun to drive.
So, maybe the name won't matter?

redpajama_set_name: RedPajamaCommonCrawl


Where the valley and industry come together. The New Mexico Rail Runner Express serves residents of Albuquerque's North Valley and commuters heading to businesses located in the ever-growing Journal Center business district.
There are approximately 142 free parking spaces located to the east of the platform and another 120 free parking spaces, just to the south of the station, both accessible from El Pueblo Road. The North Diversion Channel Trail runs right by this station, allowing you to ride your bike to the station and then either take it on board with you, or leave it parked at the bicycle lockers or racks provided.
View directions to the Los Ranchos / Journal Center Station.


text:
Javier Mota García (Motril, Granada, 28 de mayo de 1984) es un cantante, actor, bailarín y modelo español.

Biografía
En 1996, con solamente 15 años, participó en la programa de televisión "Menudo Show" y dos años más tarde en el programa "Veo Veo". En 1999, presentó el programa de radio "La Mañana", un programa de música juvenil.

Sus comienzos en el mundo musical vinieron con el nacimiento del grupo musical Gypsy Teens en el año 2000, con la discográfica Universal Music Spain. Llegaron a realizar una gira por Europa y lanzaron los singles "Club Tropicana" y "Bamboleo" "2001" compaginando con el programa de televisión club megatrix.

Su gran éxito musical comercial llegó en 2007 con la música y la danza, cuando integró el grupo Banghra con Lidia Guevara y, durante algún tiempo, con Victoria Gómez. Con la compañía discográfica Vale Music, el grupo Banghra intentó reintroducir la danza del vientre. En junio de 2007, lanzó su primer álbum, La Danza del Vientre con canciones interpretadas en español y en inglés. El álbum alcanzó la posición # 1 en las listas de ventas del pop en español, vendiendo más de 150.000 discos (disco de platino). El grupo continuó su trayectoria con el álbum ... a bailar! y se disolvió a finales de 2008.

Teatro musical
Javi Mota también ha demostrado en teatro (especialmente en musicales) un talento innato y un saber hacer sobre el escenario increíble, como en el musical " A" DE NACHO CANO, GREASE TOUR o FLASH DANCE TOUR. Pero su verdadera vocación gira en torno a la música. Ha editado varios discos en España con la discográfica Universal Music-Spain, uno en su adolescencia con el grupo Gypsy Teens y dos álbumes con el grupo Banghra; formación que se alzó con el número 1 en ventas del país y que consiguió ser disco de platino.
En 2004 formó parte del grupo La Década Prodigiosa e interpretó el musical Flashdance con mencionado grupo.
Otra gran aventura musical fue Mecandance, un proyecto llevado de la mano de Nacho Cano (líder de Mecano) editado en España y México; que versionaba las canciones del mítico grupo español que triunfó en la década de los ochenta. Con esta formación visitó el famoso programa Mexicano "Décadas" de Televisa.

Solitario
En 2010, Javi Mota intentó participar en el concurso de preselección española en un intento por representar a España en el Festival de la Canción de Eurovisión 2010. Presentó la canción "Amarte Hoy", escrito por Roel García y producido por Iván Vázquez, pero no clasificó.

El 14 de mayo de 2011 Javi Mota lanzó un nuevo sencillo titulado "Llevaré" (con "Producciones Victorya").

El 8 de mayo de 2012 Javi Mota lanzó un álbum en solitario Inesperado IV+I con 12 canciones. La primera canción single del álbum fue "Y qué más da"

El 17 de octubre de 2012 es seleccionado para formar parte del programa "La Voz" de Telecinco, formando parte del equipo de Melendi; siendo este el último componente de todo su equipo. A pesar de su entrada en el programa fue expulsado en la tercera fase.

En diciembre de 2014 empezó a trabajar con la Orquesta Olympus de Galicia.

En 2018 empezó a trabajar con la Orquesta Taxxara de Granada.

Sus influencias musicales son Luís Fonsi, Alejandro Sanz, Reik, Ricky Martin… pero Mota tiene su propio sello musical y le pone a sus composiciones ese aire andaluz que le caracteriza, transmitiendo sentimiento en todas sus interpretaciones.

A partir de 2019 se vuelca en su trabajo en solitario, empieza una etapa mucho más introspectiva y para ello ha estado componiendo un repertorio de temas con un estilo más auténtico y personal.

El 3 de mayo de 2019 nos presenta su nuevo sencillo Iguales, un tema con sonido urbano y aires aflamencados que nace con la vocación de concienciar sobre el acoso escolar, en colaboración con el bailaor Rafael Amargo. Una canción con más de 150.000 reproducciones en Youtube.

El 13 de diciembre de 2019 sale a la luz su segundo sencillo Valientes, una canción intimista en la que habla de superación y en ella deja su huella personal; ese aire flamenco que envuelve sus temas.

En el mes de abril en pleno confinamiento publicó su tercer single OJOS NEGROS.

El 6 de noviembre  de 2020 nos presenta su cuarto sencillo  " El despertar "
 es un proceso de transformación interior en el
que empiezas a tomar conciencia de ti mismo; a mirar y a sentir la vida de otro modo; es abrir los ojos a una realidad que siempre estuvo ahí, pero
que nunca antes habías podido ver por las distorsiones de la mente. El despertar está siendo toda una revelación en las radios nacionales del País.

Actualmente Javi Mota continúa trabajando en más sencillos para poder presentarlos y que cada vez más personas puedan seguir disfrutando de ese arte que tiene al cantar. Compaginando su faceta de cantante bailarín y actor con la formación de nuevos talentos.

Álbumes
En Banghra

En solo

Sencillos
En Gypsy Teens
 2000: Club Tropicana
 2001: Bamboleo
En Banghra
 2007: My Own Way
 2008: Promised Land
 2008: Una especie en extinción
 2008: Unidos
Solo
 2010: Amarte Hoy
 2011: Llevaré
 2012: Y qué más da
 2013: Tú no me cortas las alas
 2014: Ready to Start
 2015: "Vivir asi" [7]
 2016: "Agua Bendita"
 2019: "Iguales"
 2019: "Valientes"
 2020: OJOS NEGROS Y "El Despertar"

Referencias

Enlaces externos
 [https://web.archive.org/web/20140601042203/http://www.javimotamusica.com/

Cantantes de pop de España
Cantantes de la provincia de Granada
Participantes de La voz
Músicos de Granada
Nacidos en Motril

redpajama_set_name: RedPajamaWikipedia


The front and rear wings based on aerodynamics from the Enviate, specialized floor, side skirts and defuser make enough downforce to at highway speeds to crush the average aftermarket coilover.
On our previous spring setup, Beastie was compressing onto the bump stops at highway speeds. Eibach partnered with us to supply an innovative solution using bump springs to provide critical low speed suspension travel, with resilient high spring rates at high downforce speeds.
Beastie is presently running a stock J3282 engine with a Garrett GTX3576 at 9 lbs of boost. It produces roughly 375 hp and 325 tq on 92 octane. Future plans include stiffer valve springs, 1 bar of boost and race gas to produce around 530 hp.
380 mm carbon rotors with full carbon pads from RPS with the complete rotor, including the hat, weighing just 9.5 lbs.
Pegasus Auto Racing Supplies: Fittings, connections and all misc lines & hoses.


text:
'To Infinity and Beyond!' - Buzz Lightyear
Writing: Varun Sivanandham (Year 8), Nathan John (Year 9)
'The Word': a poetry competition that two of Challoner's students will cherish. On the 28th of November, Ben Cameron (7P) and Sammy Guha (9P) were thrilled to discover that their poems were both shortlisted from thousands of entries of their category.
Buzz Lightyear would be thrilled with the theme of the competition: space, more specifically the 1969 moon-landings, to commemorate its 50th year anniversary.
Having to write a 100-word poem is tricky, but fuelled by the incentive of £100 worth of book vouchers, Ben won the competition's ages 12 to 16 category with his poem.
Both Ben, Sammy, and thousands of others submitted their poems in the Lichfield Cathedral (the venue of the competition) and were judged by none other than the poet Michael Symmons Roberts, well-known for his several collections of poetry.
Having won, the students said in reflection that
'you need to work hard, spend a lot of time on it and include as much descriptive vocabulary as possible'.
When asked, 'What would you change if you could?' Ben replied
'I wouldn't change a thing'.
This perfectly sums up the success that both Challoner's students had in this competition; well done to both Ben and Sammy!


text:
ACCEPTED

#### According to
International Plant Names Index

#### Published in
null

#### Original name
Euodia irifica Coode

### Remarks
null

redpajama_set_name: RedPajamaGithub


Acura\'s three-row gets the performance hybrid treatment.
If we ask you to name a current Acura model, your mind will probably go straight to NSX. That's to be expected. It is far and away Acura's most exciting model, with second place belonging to, well, maybe all of them and none of them at the same time, right?
It's not necessarily that people think little of Acura, it's that they simply devote little thought to Acura. And who can blame them? It has been a company lacking a coherent identity (and, let's face it, enthusiast credentials) for nearly a decade. Remember the ZDX? Well, you do now.
Progress has come in fits and starts over the past ten years, and it wasn't until the brand's 30th birthday that it seemed to finally turn a corner in a meaningful way--a fitting course correction for the millennial automaker.
Thirty somethingEasy; it's not what you're thinking. Acura has not declared itself the official (or unofficial) luxury automaker of millennials or anything like that. Rather, Acura sees itself as a millennial of sorts.
Think about it. Born in 1986. Showered with praise as a child. Still lives with its parents. Just getting over a bout of questionable style. Fancies itself deserving of more credit and recognition than it seems to receive. Wakes up every day to see its successful peers doing strange things with Sriracha on Instagram.
Yeah, we'd say that's spot-on.
All grown upLike many who find themselves entering their third decades, Acura has made yet another commitment to reinventing itself. This time, hopefully, a bit more permanently.
It started with the NSX--an iconic nameplate not just by Acura's standards, but by those of any bona fide automotive enthusiast. It was a project that Acura could not afford to mismanage. The result was nothing short of a home-run--a new everyday supercar in the true spirit of the original.
And that's all well and good, but two-seat, mid-engined exotics do not drive volume.
Did all that by the age of twenty-oneWhere to next? A new Integra? How about a Legend? These are both nameplates with heavy positive equity, and neither appears to be completely off the table. When will they return? When Acura is prepared build a car worthy of the name, we've been assured. But when will that be?
Sadly, at least for those of us who remember those cars fondly, this is not the era of the sedan; be it a sport compact like the former or an executive car like the latter, the market is simply stagnant--even hostile.
What does that leave, then? Well, when you find yourself in possession of the hottest entry in the three-row luxury game, you press the advantage, right?
Better broad, better automobileNow, If we ask you--without doing any Google research or referring back to our sales stories--to name the best-selling luxury three-row crossover in America, would you immediately spit out " Acura MDX"? Of course you would, because this is an article about the newest variant of precisely that car, and it would be contextually foolish of us to make that reference otherwise. Plus, you're clever. And attractive. Have you been working out?
We'd best end this conversation, lest we end up sparking something romantic. After all, romance can lead to love, and love leads to lovin', and enough lovin' can put you in a position where you need to purchase a large family vehicle. Perhaps a large family vehicle with three-row seating, premium appointments and a performance-oriented hybrid powertrain.
Where on earth would we find such a thing?
Got the right stockThe release of the 2017 MDX Sport Hybrid roughly coincides with the model's overall facelift. While the gasoline-powered 2017 MDX led the Sport Hybrid's launch by about six months, they're functionally part of the same roll-out. When compared to the 2016, the new MDX gets a few exterior upgrades (the new "Diamond Pentagon" grille chief among them), some new optional extras (including LED fog lights and Acura's Surround View camera system) and, in keeping with its image of family-car leadership, standard AcuraWatch (the company's suite of semi-autonomous driving and advanced safety features).
Not much sets the Sport Hybrid model apart from the regular MDX in the visual department. There's the badge, of course, and if you're particularly eagle-eyed, you may be able to spot the Sport Hybrid's slightly larger front brakes.
Under the metal, however, it's a completely different ballgame.
The right car to buyLet's get something out of the way: The 2017 Acura MDX Sport Hybrid is not your stereotypical hybrid buyer's hybrid. The Sport Hybrid is the faster, funner MDX.
It all starts with a 3.0L, naturally aspirated V6. By itself, the gasoline engine is good for 257 horsepower and 218lb-ft of torque. Up front, it's mated to a direct-drive motor which produces 47 horsepower and 109lb-ft of torque. In the rear differential (Super-Handling All-Wheel-Drive is standard), there are two more electric motors (one per side), each producing 36 horsepower and 54lb-ft of torque. Integrated with the front drive motor is the Sport Hybrid's seven-speed dual-clutch transmission.
In the grand hybrid power calculating tradition of "1+1 = Cheeto," the total system output for the Sport Hybrid is 321 horsepower and 289lb-ft of torque. That's a 31-horsepower and 22-foot-pound bump over the standard MDX. The battery and power regulation systems are located beneath the seats in the cabin to optimize the Sport Hybrid's center of gravity.
Acura didn't stop there, however. While the standard MDX is equipped with frequency-selective dampers, the Sport Hybrid gets a full-blown adaptive system which is integrated with its drive modes (Acura refers to this as the "Integrated Dynamics System."), so selecting "Comfort," "Normal," or "Sport" in the Sport Hybrid means not only changing up the powertrain's responsiveness, but softening or firming up the suspension as well. And thanks to that trick twin-motor rear differential, you get electronically controlled torque vectoring as well.
If this all sounds very NSX, that's no accident. In fact, many of the hybrid system components were lifted almost directly. You'll hear OEMs talk about "shared DNA" and such things, but this goes beyond that. By "trickling down" the NSX tech to its Sport Hybrid models (The RLX sedan is offered as one as well; that's the big one, since you probably forgot about it.), Acura is actually taking advantage of increased production scale.
In other words, buying a Sport Hybrid model makes it easier for Acura to build cool cars. You're not buying a hybrid minivan. No, you're doing your duty as a car enthusiast. And it won't even cost you that much extra; you're only spending another $1,500 to spring for the Sport Hybrid over the equivalent MDX SH-AWD.
Don't let the patent leather shoes fool youThe 2017 Acura MDX Sport Hybrid is not fast, even by hybrid standards. That word is reserved for the likes of the Mercedes-Benz GLE550e and the Volvo XC90 T8; the former boasts 436 horsepower and the latter 400 even. "Fast" in this segment also comes at a price; they'll both set you back another fifteen grand.
But 321 horsepower is more than you'll get in a Lexus RX450h or BMW X5 xDrive 40e. Let's not even talk about the QX60 Hybrid, though we're sure Acura would appreciate it if we did. Remember too that the hybrid SUV market is still somewhat young, and the segments not fully fleshed-out. The Lexus and BMW are both two-row SUVs (so is the Benz, for that matter), so not only are you getting more power with the Acura, you're actually getting more car.
This is not a crossover you purchase because it gets better fuel mileage (though it does) or because it's equipped with all sorts of newfangled engineering wizardry (which it is). You buy it in spite of those things, because they are not central to the driving experience.
Following in the grand tradition of the Accord V6 Hybrid (hello, 2006!) and Acura's own RLX Sport Hybrid (again, that's the big one), the MDX Sport Hybrid brings performance to the table first.
Take the engine note, for example. It's all V6, and it's there when you expect it. Like any luxury car, the MDX's cabin has been generously isolated from the powertrain, but not because of the unpleasant cacophony you tend to associate with HEV powertrains. It's the right amount of quiet blended with the right amount of aggression--each present when you want it and absent when you don't.
At no point does its hybrid-ness intrude upon the experience of driving the car. It's a footnote--a conversation piece or curiosity, not a feature. The only sign that anything out of the ordinary is afoot is the MDX's ability to pull away from a stoplight in EV mode. Just think of it as a really, really good auto stop/start system.
Thanks to the unholy deluges typical of March in the Seattle area, we weren't able to push the limits of the MDX Sport Hybrid's dry-weather grip, but we can confidently report that the SH-AWD system is relentlessly effective in the wet--and we mean really, really wet. Unfortunately, this also meant we weren't able to photograph the MDX for ourselves.
Leftlane's bottom lineIf you're already looking at a higher-trim MDX (and according to Acura's stats, the average buyer is), the Sport Hybrid is a no-brainer. It's more fast, more fun, and with a projected $450 in fuel savings per year, more than capable of paying for itself in short order. Don't think of it as a hybrid. Just think of it as the "big engine" option in Acura's already-solid family hauler.


text:
Pigment epithelium-derived factor protects retinal ganglion cells
Iok-Hou Pang1,
Hong Zeng1,
Debra L Fleenor1 &
Abbot F Clark1
Retinal ganglion cells (RGCs) are responsible for the transmission of visual signals to the brain. Progressive death of RGCs occurs in glaucoma and several other retinal diseases, which can lead to visual impairment and blindness. Pigment epithelium-derived factor (PEDF) is a potent antiangiogenic, neurotrophic and neuroprotective protein that can protect neurons from a variety of pathologic insults. We tested the effects of PEDF on the survival of cultured adult rat RGCs in the presence of glaucoma-like insults, including cytotoxicity induced by glutamate or withdrawal of trophic factors.
Cultured adult rat RGCs exposed to glutamate for 3 days showed signs of cytotoxicity and death. The toxic effect of glutamate was concentration-dependent (EC50 = 31 μM). In the presence of 100 μM glutamate, RGC number decreased to 55 ± 4% of control (mean ± SEM, n = 76; P < 0.001). The glutamate effect was completely eliminated by MK801, an NMDA receptor antagonist. Trophic factor withdrawal also caused a similar loss of RGCs (54 ± 4%, n = 60, P < 0.001). PEDF protected against both insults with EC50 values of 13.6 ng/mL (glutamate) and 3.4 ng/mL (trophic factor withdrawal), respectively. At 100 ng/mL, PEDF completely protected the cells from both insults. Inhibitors of the nuclear factor κB (NFκB) and extracellular signal-regulated kinases 1/2 (ERK1/2) significantly reduced the protective effects of PEDF.
We demonstrated that PEDF potently and efficaciously protected adult rat RGCs from glutamate- and trophic factor withdrawal-mediated cytotoxicity, via the activation of the NFκB and ERK1/2 pathways. The neuroprotective effect of PEDF represents a novel approach for potential treatment of retinopathies, such as glaucoma.
Glaucoma, one of the world's leading causes of visual impairment and blindness [1], is characterized by excavation of the optic nerve head and selective apoptotic loss of retinal ganglion cells (RGCs), resulting in a progressive decline in visual function. Elevated intraocular pressure is a major risk factor for the development and progression of glaucoma, although the loss of vision in glaucoma patients does not always correlate with intraocular pressure and lowering pressure sometimes does not completely impede the disease process [2–4]. Clearly, ocular hypertension is not the exclusive cause of glaucomatous retinopathy, and additional mechanisms likely play a role in the degeneration of RGCs. In the past years, several additional mechanisms for glaucomatous optic neuropathy and retinopathy have been proposed, including disrupted retrograde transport of neurotrophic factors, glutamate toxicity, retinal and/or optic nerve ischemia, and immune abnormality [5–7]. These molecular events can eventually lead to apoptosis of RGCs. Unfortunately, the exact contribution of any of these factors in the pathogenesis of glaucomatous damage has not been unequivocally determined. It is probable that more than one etiology and multiple mechanisms are responsible in different patients and in different stages of glaucoma.
Despite our incomplete understanding of the disease processes and causes of RGC death, pharmacological protection of RGCs is under active investigation in ophthalmology research. Many neuroprotective strategies designed to prevent or delay the degeneration of RGCs are being evaluated, including some that are mechanism-specific. For example, glutamate receptor antagonists selectively protect against glutamate-induced cytotoxicity and may not have significant beneficial effects on other insults potentially involved in glaucoma. In contrast, other agents can protect RGCs against several toxic insults. These compounds, with their broader protective spectrum, are likely more useful as therapeutic agents for glaucoma. Pigment epithelium-derived factor (PEDF) appears to be one of these agents.
PEDF is a 50-kDa protein initially isolated from fetal human retinal pigment epithelial cells [8] and was later found to be expressed in various ocular tissues and cells, including the limbal region of the cornea and non-pigmented ciliary epithelial cells [9–12]. PEDF is also found in the brain and spinal cord, as well as non-neuronal tissues, such as endothelial cells and osteoblasts [13–15]. PEDF is a member of the serpin super-family of serine protease inhibitors [16]. However, unlike many serpins, PEDF does not inhibit serine proteases [17]. Instead, it exhibits potent antiangiogenic, neurotrophic and neuroprotective activities [13–15, 18].
PEDF has broad neuroprotective effects in several neuronal cells and tissues. PEDF reduces glutamate-induced death of cerebellar granular cells, hippocampal neurons, and spinal cord motor neurons [19–21]. It decreases post-axotomy death of motor neurons and completely prevents atrophy of the surviving neurons [20]. In the retina, PEDF improves the survival of cultured mixed retinal cells under oxidative stress [22]. It also protects against light-induced damage to photoreceptor cells in vivo [23].
Intravitreal injection of recombinant PEDF or an adenoviral vector expressing PEDF was demonstrated to reduce retinal ischemia-induced RGC loss [24, 25]. Although this animal model may not be relevant to glaucoma per se, the diverse protective effects of PEDF are nonetheless intriguing. We therefore tested PEDF in cultured adult rat RGCs to further characterize its potential protective effects against glaucoma-like insults.
The adult rat retinal cell cultures using the method described herein contained RGC-enriched retinal neurons. More than 90% of the cells were positively labeled with neuron-specific enolase antibody, indicating that the majority of cells are neurons (data not shown). Approximately 20–30% of these cells expressed Thy-1, and all Thy-1-positive cells were also positive for neurofilament-L (Figure 1). Both Thy-1 and neurofilament-L are selective cellular markers for RGC [26]. In contrast, cells in culture did not express marker proteins for other retinal cell types: they are negative for arrestin (photoreceptor), glial fibrillary acidic protein (GFAP; astroglia and Müller cell), glutamine synthetase (Müller cell), or ED1 (microglia). Less than 10% of the cells were labeled with the protein kinase Cα antibody (rod bipolar cells) (data not shown).
Identification of cultured adult rat RGCs. Cultured cells were co-labeled with anti-Thy-1 antibody (A), anti-NF-L antibody (B), and DAPI (C). (D) A digitally merged image simultaneously represents all three fluorescent labels. (E) The corresponding phase-contrast image. The cells were cultured for 3 days under control conditions. Scale bar = 50 μm.
Morphologically, the Thy-1-positive cells had the characteristic appearance of neurons. After 2–3 days in culture, neurite outgrowth typically had 2–4 main branches of approximately 20–50 μm in length (Figure 2). As the culture period increased, the neurites lengthened and became more extensive, with most spanning greater than 100 μm in length after 7 or 11 days in culture (Figure 2).
Morphology of cultured adult rat RGCs. The cells, cultured for 3 (A & B), 7 (C & D), and 11 (E & F) days, were labeled with anti-Thy-1 antibody (red) and DAPI nuclear stain (blue). (B), (D), are (F) are the corresponding phase-contrast images. Scale bar = 50 μm.
The RGCs appeared normal and healthy after 11 days in culture. For the sake of convenience, however our cell survival assays were performed using 3-day cultures. Under these conditions, there were 151 ± 7 Thy-1-positive cells/well (mean ± SEM, n = 124). Treatment with glutamate, an excitatory amino acid, damaged the cells. Glutamate (100 μM) caused significant changes in the morphology of many RGCs, including the loss of neurites, increased number of vacuoles in the cytoplasm, and compromised integrity of the plasma membrane (Figures 3A and 3B). In addition, there was formation of a greenish autofluorescence in the dying/dead RGCs, which, combined with the red fluorescent second antibody for Thy-1 detection, appeared yellow or orange (Figure 3B). Glutamate significantly (P < 0.001) reduced the number of RGCs in culture to 84 ± 6 cells/well (n = 76), corresponding to a 42% loss of RGCs (35–55% loss among studies) compared to control samples (Figure 3C). Glutamate toxicity was concentration-dependent with a calculated EC50 of 30.8 μM (Figure 3D). MK801, an antagonist for the N-methyl-D-aspartate (NMDA) glutamate receptor subtype, blocked the glutamate toxicity in a dose-dependent manner (Figure 3E). At 100 nM, MK801 completely prevented cell loss induced by 100 μM of glutamate. Agonists for non-NMDA glutamate receptors, such as kainate (100 μM, selective for ionotropic AMPA/kainate receptors), quisqualate (100 μM, activates both AMPA/kainate and metabotropic receptors), S-4-carboxy-3-hydroxyphenyl-glycine (50 μM, Group I metabotropic receptor agonist), L-carboxycyclopropylglycine (10 μM, Group II metabotropic receptor agonist), and L-(1)-2-amino-4-phosphonobutyrate (10 μM, Group III metabotropic receptor agonist) did not significantly affect RGC survival (data not shown). Glutamate toxicity appeared to be specific to the RGCs. At 100 μM, glutamate did not significantly affect Thy-1-negative cells in culture (data not shown).
Effect of glutamate on RGC morphology and survival. Cells were treated with glutamate or vehicle for 3 days. (A and B) Morphology of RGCs with glutamate (100 μM) treatment. (A) The cells were labeled with anti-Thy-1 antibody (red) and DAPI nuclear stain (blue). (B) The corresponding phase-contrast image. (C) Effect of glutamate (100 μM) on RGC survival (n = 76). *** represents P < 0.001 vs. the control group by Student's t-test. (D) Concentration-dependent toxicity of glutamate on cultured RGCs (n = 6). * represents P < 0.05 vs. the control group by One-way ANOVA then Dunnett's test. (E) Effect of MK801 on glutamate-induced RGC toxicity. Cells were treated with the indicated concentrations of MK801 in the presence of 100 μM of glutamate (n = 6). * represents P < 0.05 vs. the glutamate alone group by One-way ANOVA then Dunnett's test. Cell survival in (C), (D), and (E) was assessed by manually counting the Thy-1-positive cells. Data are presented as mean ± SEM.
Incubation of the RGCs with PEDF dose-dependently (EC50 = 13.6 ng/mL) protected against glutamate-induced toxicity. Complete protection was achieved by 100 ng/mL PEDF (Figure 4A). The same concentration of PEDF alone did not affect RGC survival or normal cell morphology. Although the PEDF receptor has not been well characterized, the biological effects of PEDF in other tissues and cell types are known to be mediated by the nuclear factor κB (NFκB) and/or extracellular signal-regulated kinases 1 and 2 (ERK1/2) cell signal transduction pathways [13–15]. Therefore, we evaluated the effects of inhibitors for these pathways on the protective action of PEDF in our RGC culture system. As shown in Figure 4B, the PEDF-mediated RGC protection against glutamate toxicity was abolished by either NFκB-SN50, a cell-permeable NFκB inhibitor peptide, or ERK1/2 inhibitors, PD98059, SL327 and U0126. The effects of NFκB-SN50 and PD98059 were concentration-dependent (Figures 4C and 4D). At the highest concentrations tested, these two compounds alone did not affect RGC survival (data not shown).
Protective effect of PEDF against glutamate-induced RGC toxicity. (A) Cells were treated with the indicated concentrations of PEDF in the presence or absence of 100 μM of glutamate (n = 6). (B) Effects of various compounds on PEDF protection against excitotoxicity. Numbers on the bars represent sample sizes. (C and D) Concentration-dependent reversal of the PEDF protection by NFκB inhibitor NFκB-SN50 and ERK1/2 inhibitor PD98059, respectively. * represents P < 0.05 vs. the respective control group by One-way ANOVA then Dunnett's test. Glu = glutamate.
In addition to glutamate, the survival of RGCs in culture was also sensitive to trophic factor withdrawal. Removal of brain-derived neurotrophic factor (BDNF), basic fibroblast growth factor (bFGF), ciliary neurotrophic factor (CNTF), and forskolin from the culture media for three days caused a significant (P < 0.001) loss of RGCs, such that only 82 ± 6 cells/well (n = 60) remained, which corresponded to an average 47% RGC loss compared to controls. PEDF effectively protected the RGC against this insult in a concentration-dependent manner with a calculated EC50 of 3.4 ng/mL (Figure 5A). The PEDF protective effect on trophic factor withdrawal was also fully blocked by NFκB-SN50 and ERK1/2 inhibitors (Figures 5B, 5C, and 5D), similar to its effect against glutamate toxicity.
Protective effect of PEDF against trophic factor withdrawal-induced RGC toxicity. (A) Cells were treated with the indicated concentrations of PEDF in the presence or absence of trophic factors (n = 6). (B) Effects of various compounds on the PEDF protection against trophic factor withdrawal-induced cytotoxicity. Numbers on the bars represent sample sizes. TFW = trophic factor withdrawal. (C and D) Concentration-dependent reversal of the PEDF protection by NFκB inhibitor NFκB-SN50 and ERK1/2 inhibitor PD98059, respectively. Three trophic factors, bFGF, BDNF, and CNTF were removed from the culture medium in the trophic factor withdrawal group. * represents P < 0.05 vs. the respective control group by One-way ANOVA then Dunnett's test.
We have shown that glutamate was toxic to adult rat RGCs in culture, resulting in increased numbers of cells with aberrant morphology and decreased total numbers of surviving cells. This finding is similar to reports of glutamate toxicity in many other neurons. Glutamate is known to activate the NMDA, AMPA/kainite, and metabotropic glutamate receptors. Although RGCs express all of these receptor subtypes, the glutamate toxicity in our cultured RGC model is primarily mediated by NMDA receptors, because the NMDA receptor-specific antagonist MK801 blocked the response Agonists for the other glutamate receptors did not seem to be lethal to the cells. These results corroborate previous findings that the NMDA receptor is important for excitotoxicity in RGCs [27, 28]. Nevertheless, because of controversies regarding glutamate-induced RGC toxicity, these data contradict other published findings. For example, some reported that both NMDA and kainite receptors contribute to RGC death (e.g., reference [29]), while others showed that only the kainite and not the NMDA receptor is responsible for RGC toxicity (e.g., reference [30]). Yet another group of investigators demonstrated that RGCs are resistant to glutamate or NMDA toxicity (e.g., reference [31]). The exact reasons for these disparities are not fully understood, but could be due to the different study conditions, which include the age and species of animals used, the presence or absence of other retinal cells in culture, or the duration and concentration of drug treatment. For example, in studies where excitotoxicity was not obvious, the incubation time was typically shorter (usually less than 24 h)[31] than that when excitotoxicity was observed (3 days in the current study)[27].
We also found that neurotrophic factors were essential for the survival of cultured RGCs. Numerous previous studies indicated that BDNF [32, 33], CNTF [32, 33], and bFGF [34] are essential survival factors. However, other trophic factors, such as nerve growth factor, glial cell line-derived neurotrophic factor, neurotrophins-3 and -4, have also been shown to be beneficial (reviewed in [35]). In the current cell culture, removal of BDNF, CNTF, and bFGF significantly reduced the survival of RGCs. Preliminary studies suggest that among these three trophic factors BDNF, in the presence of forskolin, was the most important for the health of the RGCs (unpublished observation).
Interestingly, not all RGCs were damaged by either type of insult in our culture system. Only about half of the RGCs were lost after either glutamate treatment or trophic factor withdrawal. Even with higher concentrations of glutamate or longer incubation times, we still did not observe a complete loss of the cells. Similar partial loss has been reported previously [27, 29, 36–40]. It is not clear if the neurons remaining after these insults differed biologically and functionally from those that perished. Dreyer and co-workers suggested that larger RGCs are more sensitive to glutamate toxicity [36]. However, we did not detect any size preferences of RGCs in susceptibility to either of the insults (unpublished observation).
PEDF protected cultured RGCs against both excitotoxicity and trophic factor withdrawal-induced cytotoxicity. Complete protection was observed at 100 ng/mL, a concentration shown to be neurotrophic and neuroprotective in other neurons [22, 41, 42]. This neuroprotective concentration of PEDF appears relevant because PEDF concentration in human vitreous and aqueous humor was determined to be approximately 0.5 to 3 μg/mL [43–49]. If RGCs in the retina are also exposed to similar levels of PEDF, PEDF may serve as one of the trophic factors that help sustain the health of RGCs. Interestingly, PEDF levels in aqueous humor of patients with advanced glaucoma are only about half of that of control eyes [48]. If PEDF levels in the vitreous and retina are also reduced in glaucomatous patients, the RGCs may be more susceptible to glaucomatous insults. The major sources of PEDF expression are in the retinal pigment epithelium, ciliary epithelium, and cornea [13–15]. In addition, RGCs themselves also make PEDF [10–12]. This locally produced PEDF may act as an autocrine effector and provide neurotrophic support for the RGCs.
Similar to other trophic factors, PEDF is expected to exert its biological effects by specifically binding and activating one or more receptors. However, PEDF receptors have not yet been fully characterized. Human retinoblastoma Y-79 cells, rat cerebellar granule neurons, cells in the ganglion cell layer, and inner segments of photoreceptor cells of bovine eyes have high affinity PEDF binding sites (Kd = 3 nM) [50]. Most recently, a PEDF-binding protein, named PEDF-R, was identified from the pigment epithelium of human retina [51]. PEDF binds to this protein specifically and with high affinity. PEDF binding activates the protein and stimulates its phospholipase A2 enzymatic activity [51]. Currently, it is unclear whether PEDF-R is the only PEDF receptor subtype in the retina. Furthermore, its relationship to the cell signaling pathways responsible for the biological activity of PEDF is yet to be determined. Despite our incomplete knowledge of the PEDF receptor, the NFκB and ERK1/2 pathways appear to be involved in PEDF's activities [13–15]. Our studies with cultured RGCs also indicate that both pathways are essential for the neuroprotective effects of PEDF. Inhibition of either pathway was sufficient to abolish the protective effects of PEDF. Activation of the transcription factor NFκB induces expression of other neurotrophic factors, such as BDNF and nerve growth factor, as well as antiapoptotic genes, including Bcl2, Bcl-x, and superoxide dismutase [52, 53]. ERK1/2 activation leads to modulation of other kinases, phosphatases, transcription factors, and regulators of apoptosis [54, 55]. The identification of the down-stream effectors involved in the PEDF protection of RGCs awaits further studies.
The in vitro protective effects of PEDF suggest that PEDF may also protect RGCs in vivo. Indeed, intravitreal injection of PEDF significantly, albeit partially, protected against RGC loss and thinning of the inner retinal layers due to transient retinal ischemia in the rat [24]. Similar protection against the same insult and a reduction in apoptosis of the RGC were observed when adenoviral vector encoding PEDF was injected intravitreally [25]. Our results, together with these in vivo studies, suggest that PEDF is a potent and efficacious protectant for RGCs. PEDF should be a novel and effective therapeutic agent for glaucoma and other neuroretinopathies associated with RGC damage, provided obstacles to its delivery and metabolism can be overcome.
Pigment epithelium-derived factor potently and efficaciously protects cultured adult rat RGC against glutamate- or trophic factor withdrawal-induced cytotoxicity. The protective effects of PEDF were mediated by activation of NFκB and ERK1/2 pathways. This neuroprotective effect of PEDF may lead to a novel approach for the treatment of retinopathies, such as glaucoma.
Retinal cell culture
Handling of animals in this study was conducted in accordance with the policies for use of animals in neuroscience research established by the Society for Neuroscience and by the Animal Care and Use Committee in Alcon. Isolation of retinal cells was modified from a previously reported procedure [27]. Briefly, adult Sprague-Dawley rats were euthanized by CO2 asphyxiation and their eyes enucleated. The retina from each eye was dissected and incubated in a papain solution, containing 2 mg/mL papain (Sigma, St. Louis, MO), 0.4 mg/mL DL-cysteine (Sigma), and 0.4 mg/mL bovine serum albumin (Sigma) in Neurobasal medium (Gibco/Invitrogen, Carlsbad, CA), for 25 min at 37°C, then washed 3 times with RGC culture medium [56] (Neurobasal/B27 medium containing 100 units/mL penicillin (Sigma), 100 μg/mL streptomycin (Sigma), 1 mM pyruvate (Gibco/Invitrogen), 2 mM glutamine (Gibco/Invitrogen), 5 μg/mL insulin (Sigma), 100 μg/mL transferrin (Sigma), 100 μg/mL bovine serum albumin (Sigma), 60 ng/mL progesterone (Sigma), 16 μg/mL putrescine (Sigma), 40 ng/mL sodium selenite (Sigma), 40 ng/mL thyroxine (Sigma), 40 ng/mL tri-iodothyronine (Sigma), 50 ng/mL BDNF (Biosource, Camarillo, CA), 10 ng/mL CNTF (Biosource), 10 ng/mL bFGF (Biosource), 5 μM forskolin (Sigma), and 1% fetal calf serum (Atlas Biologicals, Fort Collins, CO)). Retinal pieces were triturated by passing through a fire-polished disposable glass pipette until cells were dispersed. Cell density in the suspension was assessed with a Coulter counter (Beckman Coulter, Fullerton, CA). 1 × 106 to 3 × 106 cells/well were placed onto poly-D-lysine- and laminin-coated 8-well chambered culture slides (surface area = 0.69 cm2/well; Becton Dickinson, Franklin Lakes, NJ) and cultured in 95% air/5% CO2 at 37°C.
Cells were fixed with 3.7% formaldehyde in phosphate buffered saline (PBS)(EMD Chemicals, Gibbstown, NJ) at room temperature for 30 min, rinsed in PBS (Gibco) three times, and incubated for 1 h with PBS containing 0.02% saponin (Sigma) and the appropriate primary antibodies: Thy-1 (1:500; Chemicon, Temecula, CA), neurofilament-L (NF-L; 1:200; Serotec, Raleigh, NC), neuron-specific enolase (1:200; Chemicon), arrestin (1:200; Abcam, Cambridge, MA), protein kinase Cα (1:250; Oxford Biomedical Research, Oxford, MI), GFAP (1:500; Chemicon), glutamine synthase (1:500; Sigma), or ED1 (1:100; Santa Cruz Biotechnology). The primary antibody was then removed, cells rinsed again, and incubated for 30 min with fluorescence-labeled secondary antibodies (1:300), Alexa fluor 594-labeled goat anti-mouse IgG (Invitrogen/Molecular Probes, Carlsbad, CA), Oregon green-labeled goat anti-rabbit IgG (Invitrogen/Molecular Probes), or Alexa fluor 488-labeled rabbit anti-goat IgG (Invitrogen/Molecular Probes). The cells were subsequently incubated with DAPI solution (100 ng/mL; Sigma) for 5 min to stain their nuclei. The slides were rinsed with distilled water, covered with Fluoromount G (Southern Biotech, Birmingham, AL) and a cover glass (VWR, Westchester, PA). The retinal cells was examined by fluorescence microscopy and digital images obtained.
Cytotoxic insults
For glutamate-induced toxicity studies, cells were pre-treated with vehicle or the indicated compounds for 30 min, followed by L-glutamate (0–1000 μM) (Sigma) for 3 days. For trophic factor withdrawal studies, three trophic factors, bFGF, BDNF, and CNTF, together with forskolin, were removed from the culture medium. Cells were cultured in this medium for 3 days.
Quantification of cell survival
At the end of the incubation period, the cells were fixed then labeled for Thy-1 and DAPI. RGC survival was quantified by manually counting Thy-1-positive healthy cells in each well.
Cell counts are expressed as mean ± SEM. Two-tailed Student's t-test was used to compare between two groups. One-way ANOVA followed by Dunnett's test was used to compare among three or more study groups. P < 0.05 is regarded as statistically significant.
Quigley HA, Broman AT: The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006, 90 (3): 262-267. 10.1136/bjo.2005.081224.
Van Buskirk EM, Cioffi GA: Glaucomatous optic neuropathy. Am J Ophthalmol. 1992, 113 (4): 447-452.
Schumer RA, Podos SM: The nerve of glaucoma!. Arch Ophthalmol. 1994, 112 (1): 37-44.
Weih LM, Nanjan M, McCarty CA, Taylor HR: Prevalence and predictors of open-angle glaucoma: results from the visual impairment project. Ophthalmology. 2001, 108 (11): 1966-1972. 10.1016/S0161-6420(01)00799-0.
Clark AF, Pang IH: Advances in glaucoma therapeutics. Exp Opin Emerging Drugs. 2002, 7 (1): 141-163. 10.1517/14728214.7.1.141.
Kuehn MH, Fingert JH, Kwon YH: Retinal ganglion cell death in glaucoma: mechanisms and neuroprotective strategies. Ophthalmol Clin North Am. 2005, 18 (3): 383-95, vi. 10.1016/j.ohc.2005.04.002.
Pang IH, Li B, Clark AF: The pathogenesis of retinal ganglia cell apoptosis induced by glaucoma. Chin J Ophthalmol. 2004, 40 (7): 495-499.
Tombran-Tink J, Chader GG, Johnson LV: PEDF: a pigment epithelium-derived factor with potent neuronal differentiative activity. Exp Eye Res. 1991, 53 (3): 411-414. 10.1016/0014-4835(91)90248-D.
Ortego J, Escribano J, Becerra SP, Coca Prados M: Gene expression of the neurotrophic pigment epithelium-derived factor in the human ciliary epithelium. Synthesis and secretion into the aqueous humor. Invest Ophthalmol Vis Sci. 1996, 37 (13): 2759-2767.
Karakousis PC, John SK, Behling KC, Surace EM, Smith JE, Hendrickson A, Tang WX, Bennett J, Milam AH: Localization of pigment epithelium derived factor (PEDF) in developing and adult human ocular tissues. Mol Vis. 2001, 7: 154-163.
Behling KC, Surace EM, Bennett J: Pigment epithelium-derived factor expression in the developing mouse eye. Mol Vis. 2002, 8: 449-454.
Ogata N, Wada M, Otsuji T, Jo N, Tombran-Tink J, Matsumura M: Expression of pigment epithelium-derived factor in normal adult rat eye and experimental choroidal neovascularization. Invest Ophthalmol Vis Sci. 2002, 43 (4): 1168-1175.
Tombran-Tink J, Barnstable CJ: Therapeutic prospects for PEDF: more than a promising angiogenesis inhibitor. Trends Mol Med. 2003, 9 (6): 244-250. 10.1016/S1471-4914(03)00074-1.
Barnstable CJ, Tombran-Tink J: Neuroprotective and antiangiogenic actions of PEDF in the eye: molecular targets and therapeutic potential. Prog Retin Eye Res. 2004, 23 (5): 561-577. 10.1016/j.preteyeres.2004.05.002.
Tombran-Tink J: The neuroprotective and angiogenesis inhibitory serpin, PEDF: new insights into phylogeny, function, and signaling. Front Biosci. 2005, 10: 2131-2149.
Steele FR, Chader GJ, Johnson LV, Tombran-Tink J: Pigment epithelium-derived factor: neurotrophic activity and identification as a member of the serine protease inhibitor gene family. Proc Natl Acad Sci U S A. 1993, 90 (4): 1526-1530. 10.1073/pnas.90.4.1526.
Becerra SP, Sagasti A, Spinella P, Notario V: Pigment epithelium-derived factor behaves like a noninhibitory serpin. Neurotrophic activity does not require the serpin reactive loop. J Biol Chem. 1995, 270 (43): 25992-25999. 10.1074/jbc.270.43.25992.
Patricia Becerra S: Focus on Molecules: Pigment epithelium-derived factor (PEDF). Exp Eye Res. 2006, 82 (5): 739-740. 10.1016/j.exer.2005.10.016.
Taniwaki T, Becerra SP, Chader GJ, Schwartz JP: Pigment epithelium-derived factor is a survival factor for cerebellar granule cells in culture. J Neurochem. 1995, 64 (6): 2509-2517.
Houenou LJ, D'Costa AP, Li L, Turgeon VL, Enyadike C, Alberdi E, Becerra SP: Pigment epithelium-derived factor promotes the survival and differentiation of developing spinal motor neurons. J Comp Neurol. 1999, 412 (3): 506-514. 10.1002/(SICI)1096-9861(19990927)412:3<506::AID-CNE9>3.0.CO;2-E.
Bilak MM, Corse AM, Bilak SR, Lehar M, Tombran-Tink J, Kuncl RW: Pigment epithelium-derived factor (PEDF) protects motor neurons from chronic glutamate-mediated neurodegeneration. J Neuropathol Exp Neurol. 1999, 58 (7): 719-728.
Cao W, Tombran-Tink J, Chen W, Mrazek D, Elias R, McGinnis JF: Pigment epithelium-derived factor protects cultured retinal neurons against hydrogen peroxide-induced cell death. J Neurosci Res. 1999, 57 (6): 789-800. 10.1002/(SICI)1097-4547(19990915)57:6<789::AID-JNR4>3.0.CO;2-M.
Cao W, Tombran-Tink J, Elias R, Sezate S, Mrazek D, McGinnis JF: In vivo protection of photoreceptors from light damage by pigment epithelium-derived factor. Invest Ophthalmol Vis Sci. 2001, 42 (7): 1646-1652.
Ogata N, Wang L, Jo N, Tombran-Tink J, Takahashi K, Mrazek D, Matsumura M: Pigment epithelium derived factor as a neuroprotective agent against ischemic retinal injury. Curr Eye Res. 2001, 22 (4): 245-252. 10.1076/ceyr.22.4.245.5506.
Takita H, Yoneya S, Gehlbach PL, Duh EJ, Wei LL, Mori K: Retinal neuroprotection against ischemic injury mediated by intraocular gene transfer of pigment epithelium-derived factor. Invest Ophthalmol Vis Sci. 2003, 44 (10): 4497-4504. 10.1167/iovs.03-0052.
Chidlow G, Casson R, Sobrado Calvo P, Vidal Sanz M, Osborne NN: Measurement of retinal injury in the rat after optic nerve transection: an RT-PCR study. Mol Vis. 2005, 11: 387-396.
Pang IH, Wexler EM, Nawy S, DeSantis L, Kapin MA: Protection by eliprodil against excitotoxicity in cultured rat retinal ganglion cells. Invest Ophthalmol Vis Sci. 1999, 40 (6): 1170-1176.
Sucher NJ, Lipton SA, Dreyer EB: Molecular basis of glutamate toxicity in retinal ganglion cells. Vision Res. 1997, 37 (24): 3483-3493. 10.1016/S0042-6989(97)00047-3.
Luo X, Heidinger V, Picaud S, Lambrou G, Dreyfus H, Sahel J, Hicks D: Selective excitotoxic degeneration of adult pig retinal ganglion cells in vitro. Invest Ophthalmol Vis Sci. 2001, 42 (5): 1096-1106.
Otori Y, Wei JY, Barnstable CJ: Neurotoxic effects of low doses of glutamate on purified rat retinal ganglion cells. Invest Ophthalmol Vis Sci. 1998, 39 (6): 972-981.
Ullian EM, Barkis WB, Chen S, Diamond JS, Barres BA: Invulnerability of retinal ganglion cells to NMDA excitotoxicity. Mol Cell Neurosci. 2004, 26 (4): 544-557. 10.1016/j.mcn.2004.05.002.
Mey J, Thanos S: Intravitreal injections of neurotrophic factors support the survival of axotomized retinal ganglion cells in adult rats in vivo. Brain Res. 1993, 602 (2): 304-317. 10.1016/0006-8993(93)90695-J.
Meyer Franke A, Kaplan MR, Pfrieger FW, Barres BA: Characterization of the signaling interactions that promote the survival and growth of developing retinal ganglion cells in culture. Neuron. 1995, 15 (4): 805-819. 10.1016/0896-6273(95)90172-8.
Bahr M, Vanselow J, Thanos S: Ability of adult rat ganglion cells to regrow axons in vitro can be influenced by fibroblast growth factor and gangliosides. Neurosci Lett. 1989, 96 (2): 197-201. 10.1016/0304-3940(89)90057-8.
Yip HK, So KF: Axonal regeneration of retinal ganglion cells: effect of trophic factors. Prog Retin Eye Res. 2000, 19 (5): 559-575. 10.1016/S1350-9462(00)00009-4.
Dreyer EB, Pan ZH, Storm S, Lipton SA: Greater sensitivity of larger retinal ganglion cells to NMDA-mediated cell death. Neuroreport. 1994, 5 (5): 629-631. 10.1097/00001756-199401000-00024.
Kitano S, Morgan J, Caprioli J: Hypoxic and excitotoxic damage to cultured rat retinal ganglion cells. Exp Eye Res. 1996, 63 (1): 105-112. 10.1006/exer.1996.0096.
Morgan J, Caprioli J, Koseki Y: Nitric oxide mediates excitotoxic and anoxic damage in rat retinal ganglion cells cocultured with astroglia. Arch Ophthalmol. 1999, 117 (11): 1524-1529.
Kawasaki A, Otori Y, Barnstable CJ: Muller cell protection of rat retinal ganglion cells from glutamate and nitric oxide neurotoxicity. Invest Ophthalmol Vis Sci. 2000, 41 (11): 3444-3450.
Yamasaki M, Mishima HK, Yamashita H, Kashiwagi K, Murata K, Minamoto A, Inaba T: Neuroprotective effects of erythropoietin on glutamate and nitric oxide toxicity in primary cultured retinal ganglion cells. Brain Res. 2005, 1050 (1-2): 15-26. 10.1016/j.brainres.2005.05.037.
Taniwaki T, Hirashima N, Becerra SP, Chader GJ, Etcheberrigaray R, Schwartz JP: Pigment epithelium-derived factor protects cultured cerebellar granule cells against glutamate-induced neurotoxicity. J Neurochem. 1997, 68 (1): 26-32.
DeCoster MA, Schabelman E, Tombran-Tink J, Bazan NG: Neuroprotection by pigment epithelial-derived factor against glutamate toxicity in developing primary hippocampal neurons. J Neurosci Res. 1999, 56 (6): 604-610. 10.1002/(SICI)1097-4547(19990615)56:6<604::AID-JNR6>3.0.CO;2-B.
Patel JI, Tombran-Tink J, Hykin PG, Gregor ZJ, Cree IA: Vitreous and aqueous concentrations of proangiogenic, antiangiogenic factors and other cytokines in diabetic retinopathy patients with macular edema: Implications for structural differences in macular profiles. Exp Eye Res. 2006, 82 (5): 798-806. 10.1016/j.exer.2005.10.002.
Funatsu H, Yamashita H, Nakamura S, Mimura T, Eguchi S, Noma H, Hori S: Vitreous levels of pigment epithelium-derived factor and vascular endothelial growth factor are related to diabetic macular edema. Ophthalmology. 2006, 113 (2): 294-301. 10.1016/j.ophtha.2005.10.030.
Duh EJ, Yang HS, Haller JA, De Juan E, Humayun MS, Gehlbach P, Melia M, Pieramici D, Harlan JB, Campochiaro PA, Zack DJ: Vitreous levels of pigment epithelium-derived factor and vascular endothelial growth factor: implications for ocular angiogenesis. Am J Ophthalmol. 2004, 137 (4): 668-674. 10.1016/S0002-9394(03)01422-3.
Ogata N, Nishikawa M, Nishimura T, Mitsuma Y, Matsumura M: Unbalanced vitreous levels of pigment epithelium-derived factor and vascular endothelial growth factor in diabetic retinopathy. Am J Ophthalmol. 2002, 134 (3): 348-353. 10.1016/S0002-9394(02)01568-4.
Spranger J, Osterhoff M, Reimann M, Mohlig M, Ristow M, Francis MK, Cristofalo V, Hammes HP, Smith G, Boulton M, Pfeiffer AF: Loss of the antiangiogenic pigment epithelium-derived factor in patients with angiogenic eye disease. Diabetes. 2001, 50 (12): 2641-2645.
Ogata N, Matsuoka M, Imaizumi M, Arichi M, Matsumura M: Decreased levels of pigment epithelium-derived factor in eyes with neuroretinal dystrophic diseases. Am J Ophthalmol. 2004, 137 (6): 1129-1130. 10.1016/j.ajo.2003.11.080.
Boehm BO, Lang G, Volpert O, Jehle PM, Kurkhaus A, Rosinger S, Lang GK, Bouck N: Low content of the natural ocular anti-angiogenic agent pigment epithelium-derived factor (PEDF) in aqueous humor predicts progression of diabetic retinopathy. Diabetologia. 2003, 46 (3): 394-400.
Alberdi E, Aymerich MS, Becerra SP: Binding of pigment epithelium-derived factor (PEDF) to retinoblastoma cells and cerebellar granule neurons. Evidence for a PEDF receptor. J Biol Chem. 1999, 274 (44): 31605-31612. 10.1074/jbc.274.44.31605.
Notari L, Baladron V, Aroca Aguilar JD, Balko N, Heredia R, Meyer C, Notario PM, Saravanamuthu S, Nueda ML, Sanchez Sanchez F, Escribano J, Laborda J, Becerra SP: Identification of a lipase-linked cell membrane receptor for pigment epithelium-derived factor. J Biol Chem. 2006, 281 (49): 38022-38037. 10.1074/jbc.M600353200.
Courtois G: The NF-kappaB signaling pathway in human genetic diseases. Cell Mol Life Sci. 2005, 62 (15): 1682-1691. 10.1007/s00018-005-5031-5.
Wu JT, Kral JG: The NF-kappaB/IkappaB signaling system: a molecular target in breast cancer therapy. J Surg Res. 2005, 123 (1): 158-169. 10.1016/j.jss.2004.06.006.
Yoon S, Seger R: The extracellular signal-regulated kinase: multiple substrates regulate diverse cellular functions. Growth Factors. 2006, 24 (1): 21-44.
Rubinfeld H, Seger R: The ERK cascade: a prototype of MAPK signaling. Mol Biotechnol. 2005, 31 (2): 151-174. 10.1385/MB:31:2:151.
Barres BA, Silverstein BE, Corey DP, Chun LL: Immunological, morphological, and electrophysiological variation among retinal ganglion cells purified by panning. Neuron. 1988, 1 (9): 791-803. 10.1016/0896-6273(88)90127-4.
This study was supported by Alcon Research, Ltd.
Alcon Research, Ltd., 6201 South Freeway, R3-24, Fort Worth, TX, 76134, USA
Iok-Hou Pang, Hong Zeng, Debra L Fleenor & Abbot F Clark
Iok-Hou Pang
Hong Zeng
Debra L Fleenor
Abbot F Clark
Correspondence to Iok-Hou Pang.
IHP contributed to the conception and design of the study, performed statistical analyses, and drafted the manuscript. HZ participated in the design of the study and carried out the cell assays. DLF participated in the design of the study, identified appropriate test agents, assisted in the interpretation of data, and helped to draft the manuscript. AFC participated in the conception and design of the study, assisted in the interpretation of data, and helped to draft the manuscript. All authors read and approved the final manuscript.
Pang, IH., Zeng, H., Fleenor, D.L. et al. Pigment epithelium-derived factor protects retinal ganglion cells. BMC Neurosci 8, 11 (2007). https://0-doi-org.brum.beds.ac.uk/10.1186/1471-2202-8-11
Received: 06 November 2006
Retinal Ganglion Cell
Trophic Factor
Glutamate Toxicity


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Blood relationship is always found to be stronger and more valuable than mere friendship formed through acquaintance. Blood ties are lasting. They have a firmer bond of affection than all other relationships. Friends may be sincere and willing to help. But they have got their limits. They often stop when they find themselves to be in troubled waters. But blood relatives such as father, mother, brother or sister will stand by our side risking even their necks. They in fact are our true allies. There might be exceptions to this rule. But true and sincere friends are often hard to get. Even if they are true and sincere, we cannot expect the greatest sacrifice from them. They give more importance to their own kith and kin. So even if true and sincere friendship is to be given due credit, we should value blood ties more. The most unselfish service is often got from our kith and kin than from friendship formed through acquaintance. They last longer and are often found to be stronger than the latter.


text:
Q: how to interpret 8 neighbors as follows i would like to find 8 neighbors. In an algorithm it is written as
int Nx[] = {-1, 1, 0, 0, -1, -1, 1,  1}; //8-neighbors
int Ny[] = {0, 0, -1, 1,  1, -1, 1, -1};

how 3*3 matrix is interpreted like this?

A: These are relative x- and y- coordinates. It becomes clearer if you convert this to coordinate pairs:
 x  y     neighbour
----------------------
-1  0     left
 1  0     right
 0 -1     bottom
 0  1     top
-1  1     left-top
-1 -1     left-bottom
 1  1     right-top
 1 -1     right-bottom

redpajama_set_name: RedPajamaStackExchange


text:
Q: Forced Updated Display view controller from .xib I am attempting to display a view controller from .xib that indicates to a user that an update to the app is available. For some reason, the following code seems to do nothing:
if ([serverObject[@"newServerBuilt"] isEqualToString:@"YES"])    {

                //we want to display the text from the server to user
                NSString * displayText=serverObject[@"displayText"];

                ForceUpdate * forceUpdateViewController = [[ForceUpdate alloc] initWithNibName:@"ForceUpdate" bundle:nil];

                forceUpdateViewController.textToShow=displayText;

                [self presentViewController:forceUpdateViewController    animated:NO completion:nil];
}

Does anyone know why? As you can see, I'm allowing myself to display an update view controller based upon a customizable message on the server.
Also, when I click on a textlabel in the .xib, it says the textlabel connects to the "File's ownder" but should it connect to "Forced Update"?
and the forced update.h looks like so:
#import <UIKit/UIKit.h>

@interface ForceUpdate : UIView

@property (nonatomic, strong) NSString * textToShow;

@end

A: I guess you would be doing it in AppDelegate.m file. if YES then you need to presentViewController from [[[UIApplication sharedApplication] keyWindow] rootViewController] insetead self.
[[[[UIApplication sharedApplication] keyWindow] rootViewController] presentViewController:forceUpdateViewController    animated:NO completion:nil];


text:
by Crea Hickson
As the current academic year comes to an end it is a great time to reflect on the last 12 months. It has been a challenging year, but we are taking this moment to look back on some of the achievements of our lab members during this time. All of us have been working from home, and indeed many of us have taken to remote parts of Ireland to do so! As we are now dotted around the country we have included some photos from our current workspaces to bring a smile to your face during these difficulties times – but also to encourage you to visit our lab here in beautiful Ireland at some stage! Below is a taste of the interesting and inspiring work carried out at SASHLab every year.
New Graduate Alert!
In December 2020, Grace successfully defended her PhD Thesis entitled 'The Role of Attachment and Social Support for the Psychological and Physiological Health of Adolescents and Young Adults' which was supervised by Prof. Stephen Gallagher and Dr Ann-Marie Creaven. Her Viva Voca was chaired by our own Dr Eric Igou, from the Department of Psychology in UL, and her Thesis was examined by two external examiners Prof. Anna Whittaker (Stirling) and Dr. Samantha Dockray (UCC). At the time of her Viva, her first two thesis studies were already published in Stress and Health and Psychophysiology (which you can find here and here) and shortly after her Viva, the third and final study was published in the International Journal of Psychophysiology which can be found here.
New Pastures!
Siobhán G and Grace moved from their teaching posts in the Department, and took up new positions in the Department in February of this year. They are now working as part of a European Research Council (ERC) Advanced Grant awarded to Prof Orla Muldoon, examining social identity, trauma, and health. However, they will thankfully be staying on as part of SASHLab!
Funding Success!
Ann-Marie was awarded an Irish Research Council New Foundations grant for ELSIE - Exploring Loneliness and Social Isolation in Emerging adulthood - a collaboration with SpunOut.ie. Follow our ELSIE project page for more! (Link to this page here)
Siobhán G applied for a Marie Skłodowska-Curie Global Individual Fellowship to travel to Baylor University in the USA to work with our collaborator Dr Annie Ginty, and has scored highly - she is now on the waitlist for this prestigious award and will be given a Marie Curie Seal of Excellence for her application. Fingers crossed!
Teaching Success!
Grace McMahon was awarded a Teaching Hero Award which was announced at the Student Achievement Awards Ireland event in April 2021. The Teaching Hero Awards are Ireland's only national, student-led awards for all those who teach in higher education and was organised by the National Teaching Forum and the Union of Students in Ireland.
March 2021 saw one example of the international impact of SASHLab research; a study published in American Psychological Association's Health Psychology journal arising directly from "a call to research" published by SASHLab member, Dr Siobhán Howard, along with colleagues in NUI Galway and Shaanxi Normal University, China. Manigault et al.'s (2021) paper in Health Psychology arose directly from a previous review by Hughes, Lü, and Howard (2018) outlining the importance of examining how people adapt to stress and its implications for disease processes; examination of cardiovascular stress-response adaptation. Dr Howard and colleagues have been investigating the importance of cardiovascular stress-response adaptation as an important mechanism that ultimately predicts disease development. In the review, Dr Howard and colleagues called on researchers to examine previously collected data that allowed scrutiny of how individuals habituated to recurrent stress to add to the growing evidence that patterns of cardiovascular stress-response adaptation are particularly revealing in detailing psychosocial moderators of disease processes. Manigault et al. (2021) answered this call and published a secondary analysis of data they had collected previously. Their results showed that a stress reduction intervention that increased perceived control over thoughts led to greater stress-response habituation to the stressor. More details can be found on both papers here and here.
In December, Ann-Marie gave a talk at the BPS Psychobiology Section annual meeting titled "For Better or for Worse: The Impact of Social Connections on Physiology".
In April, Siobhán G gave a virtual talk about her research on emotion regulation and cardiovascular responses to stress at the Self-Regulation, Emotion, and Attention Lab, in Reading University (UK) and in June, she gave a talk about her research to members of CoRPS (the Center of Research on Psychological and Somatic disorders) at Tilburg University (Netherlands), pictured right. These were great opportunities to connect with other emotion regulation and psychophysiology researchers!
We were also delighted to welcome Dr Stefanie Duijndam (virtually) to SASHLab to talk about her work to date on social inhibition and physiological responses to stress (pictured below). It proved to be a fruitful discussion that we hope to continue one day face-to-face!
Contribution to the Field
Ann-Marie, Páraic, and Stephen were part of the scientific committee for this year's Psychology, Health and Medicine Conference #PHM2021.
Siobhán and Aisling were judges at this year's 42nd All-Ireland Student Congress held virtually by UCC. This event is a great way for Psychology students (undergraduate and postgraduate) to showcase their research! Well done to a fabulous organising committee and presenters for an engaging conference!
Ann-Marie also hosted a National Forum for the Enhancement of Teaching and Learning in Higher Education Seminar on team approaches to undergraduate project supervision. Our own Adam O'Riordan was one of the speakers. Watch the seminar recording: here and find the seminar preprint here: here
Ann-Marie spoke regularly about stress and coping over the past year on RTE Radio 1 show, Today with Claire Byrne. Listen back to Ann-Marie share her expertise on social support here: here, or to the discussion about trauma in frontline workers: here. This discussion was informed by the research conducted by our colleagues Professor Donal Fortune, Dr Elaine Kinsella, and Dr Rachel Sumner
Tracey had the opportunity to peer review, which she found to be very beneficial.
Dr Stephen Gallagher published studies on caring during the Covid-19 pandemic. He summarised his work in a blog which can be found on our SASH Lab website here.
A special thanks to Kevin Casey who spent his co-op with us over the last six months, and to all the research interns who worked with Grace and Siobhán G since last October as part of the Dept of Psychology VIP-R programme: Ailbhe Dempsey, Amy Lennon, Chloe Looney, Crea Hickson, Hannah Knittle, Jade Daly, Megan Carroll, Michelle McLaughlin, Saoirse Warren, & Steven O'Brien. Thank you for all your hard work over the year – we hope to see you back with us some day!
Some views from our work-from-home locations. While some of us are living and working in Limerick remotely, others are spread out around Ireland, for example Clare, Kerry, Kilkenny, Mayo, & Tipperary!
Selected Conference Presentations
18th Annual Psychology, Health and Medicine Conference (PHM), online via UCC (May, 2021).
The 18th Annual Psychology Health and Medicine Conference was jointly hosted by the Schools of Public Health and Applied Psychology in University College Cork. This year's theme was "Perspectives and pathways to improving the research and application of health psychology". We had excellent representation from SASHLab again this year, with oral and poster presentations….It was an excellent conference, with some inspiring keynotes and presentation!
Emma Kirwan presented a poster on her PhD research "Loneliness in young adulthood: a protocol for a scoping review of the quantitative and qualitative literature. (Online Poster: https://osf.io/jfcmp/). Collaborators: O'Súilleabháin, P., Burns, A., McMahon, J., Summerville, S., Creaven, A-M.
Ciara Price presented on her systematic review "A Systematic review of religiosity, spirituality, and cardiovascular reactions to acute psychological stress".
Aisling Costello presented on her systematic review "Defining cardiovascular recovery from acute psychological stress: A systematic review".
Adam O'Riordan gave an oral presentation on his latest study, a systematic review of blunted reactivity: "Blunted cardiovascular reactivity to acute psychological stress: A systematic review".
Tracy Keogh presented on one of her laboratory studies "Depression and blunted cardiovascular reactivity to acute psychological stress: early life adversity as a moderator". This paper has been published, for a quick synopsis see this blog post.
Grace McMahon gave an oral presentation on her PhD research "Cardiovascular reactivity to acute stress: attachment styles and invisible stranger support".
Siobhán Griffin gave an oral presentation about her latest study, and first study of her postdoc, about "Affiliation with new group memberships formed after an Acquired Brain Injury predicts post-traumatic growth prospectively" (co-authors: Elaine Kinsella, Daragh Bradshaw, Grace McMahon, Ali Nightingale, Donal Fortune, and Orla Muldoon).
13th Annual Health Preconference at the 22nd Annual Convention of the Society for Personality and Social Psychology (SPS), Online Conference (February 2021).
Siobhán G presented a poster on a laboratory study where she manipulated reappraisal: "Reappraisal as a strategy to cope with recurrent stress: Implications for performance and cardiovascular responding to stress". This paper has been published open-access, for a quick synopsis see this blog post.
60th Annual Meeting of the Society for Psychophysiological Research, Vancouver, Canada (moved online; October, 2020)
Siobhán G presented a poster about an online study she conducted examining perceived stress and emotion regulation "Emotion regulation, perceived stress, and health" at the 60th Annual Meeting of the Society for Psychophysiological Research.
Since January 2021
Gallagher, S., Creaven, A-M., Howard, S., Ginty, A. T., & Whittaker, A. C. (in press). Gratitude, social support and cardiovascular reactivity to acute psychological stress. Biological Psychology. [Q2, IF: 2.627].
Griffin, S. M., & Howard, S. (2021). Instructed reappraisal and cardiovascular adaption to recurrent stress. Psychophysiology, doi: 10.1111/psyp.13783. [Q1, IF: 3.378].
Keogh, T. M., Howard, S., O'Riordan, A., & Gallagher, S. (2021). Motivational orientation mediates the association between depression and cardiovascular reactivity to acute psychological stress. Psychophysiology, 58(2), e13732.
McMahon, G., Creaven, A. M., & Gallagher, S. (2021). Cardiovascular reactivity to acute stress: Attachment styles and invisible stranger support. International Journal of Psychophysiology, 164, 121-129.
Tyra, A. T., Griffin, S. M., Fergus, T. A., & Ginty, A. T. (2021). Individual differences in emotion regulation prospectively predict COVID-19 posttraumatic stress symptoms. Journal of Anxiety Disorders, 81. doi: 10.1016/j.janxdis.2021.102411.
Coyle, D. K. T., Howard, S., Bibbey, A., Gallagher, S. Whittaker, A. C., Creaven, A-M. (2020). Personality and physiological reactions to acute psychological stress in the Midlife in the United States (MIDUS) study. International Journal of Psychophysiology, 148, 67-74. [Q2, IF: = 2.407].
Creaven, A. M., Higgins, N. M., Ginty, A. T., & Gallagher, S. (2020). Social support, social participation, and cardiovascular reactivity to stress in the Midlife in the United States (MIDUS) study. Biological Psychology, 155, 107921.
Gallagher, S., O'Sullivan, L., Hughes, Z., & O'Connell, B. H. (2020). Building Resources in Caregivers: Feasibility of a Brief Writing Intervention to Increase Benefit Finding in Caregivers. Applied Psychology: Health and Well‐Being, 12(2), 513-531.
Gallagher, S., Solano, A. C., & Liporace, M. F. (2020). State, but not trait gratitude is associated with cardiovascular responses to acute psychological stress. Physiology & behavior, 221, 112896.
Gallagher, S., Bennett, K. M., & Roper, L. (2020). Loneliness and depression in patients with cancer during COVID-19. Journal of psychosocial oncology, 1-7.
Gallagher, S., & Wetherell, M. A. (2020). Risk of depression in family caregivers: unintended consequence of COVID-19. BJPsych open, 6(6).
Ginty, A. T., Tyra, A. T., Young, D. A., John-Henderson, N. A., Gallagher, S., & Tsang, J. A. C. (2020). State gratitude is associated with lower cardiovascular responses to acute psychological stress: A replication and extension. International Journal of Psychophysiology, 158, 238-247.
Griffin, S. M., & Howard, S. (2020). Establishing the validity of a novel passive stress task. Psychophysiology, e13555. [Q1, IF: 3.378].
Howard, S., Fitzgerald, G., & Gallagher, S. (2020). Cardiovascular stress reactions in recent- and long-retired rugby players when watching a game. Physiology & Behavior, 219, 112832.. [Q2, IF: 2.635].
McMahon, G., Creaven, A. M., & Gallagher, S. (2020). Stressful life events and adolescent well‐being: The role of parent and peer relationships. Stress and Health, 36(3), 299-310.
McMahon, G., Creaven, A. M., & Gallagher, S. (2020). Perceived social support mediates the association between attachment and cardiovascular reactivity in young adults. Psychophysiology, 57(3), e13496.
O'Riordan, A., Howard, S., Brown, E., & Gallagher, S. (2020). Type D personality and cardiovascular reactivity to acute stress: The mediating effects of social support and negative social relationships. Psychophysiology, 57, e13660. [Q1, IF: 3.378].
O'Riordan, A., Howard, S., & Gallagher, S. (2020). Type D personality and life event stress: The mediating effects of social support and negative social relationships. Anxiety, Stress, and Coping, 33, 452-465. [Q2, IF: 1.981].
O'Reilly, P., Kennedy, C., Meskell, P., Coffey, A., Dore, L., Howard, S., Scanlon, C., Wilson, D., Whelan, B., & Ryan, S. (2020). The psychological impact of Stevens Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) on patients' lives: A critically appraised topic. British Journal of Dermatology, 183, 452-461. [Q1, IF: 6.714]
Sumner, R. C., Bennett, R., Creaven, A. M., & Gallagher, S. (2020). Unemployment, employment precarity, and inflammation. Brain, behavior, and immunity, 83, 303-308.


text:
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A panel of experts discusses arts, culture and entrepreneurship to inspire participation in the President's Innovation Challenge.
Poets discuss the intersection of personal and political for a pre-election reading at Harvard Art Museums.
Live silent film accompanist and organist Peter Krasinski helps films find a voice.
Artists put the art in ARTS FIRST. Jason Luke '94 makes their performances work as a festival.
How I created "What a Loving and Beautiful World" with the touch of my hand.
Two novelists, both prolific, talk about the craft and the stenography of their lives.


How long does it take to get to know a place? The answer depends on the place and is contingent on how one defines the word 'know'. There is also a difference between feeling connected to something and having intimate knowledge of it. One may come to the realization that you might never really know a place, no matter how much you want to.
This was how I felt leaving Olympic National Park on Washington's Olympic Peninsula. Looking back, I wish I had stayed longer, but hindsight is 20/20 and we aren't blessed with knowledge of the future. Even if I had extended my visit, it wouldn't have changed my conclusion that I will never really know this incredible and diverse landscape.
There were no bad memories of my time in Western Washington, with the exception of an inordinate number of delays due to roadwork. When not stopped in traffic my time was spent rushing to and fro. Thankfully the summer sun sets late at these latitudes, giving me a chance to fit a little more into the day.
Case in point was a hike up the Sunrise Ridge trail from the Hurricane Deck Visitor area. The day began with me on a ferry leaving Seattle, then visiting a couple of lighthouses.
In the afternoon, I stopped at the Olympic National Park Visitor Center in Port Angeles to obtain a backpacking permit for the following day. After securing the permit there was just enough time to drive like a Californian up the mountain, visit the Hurricane Deck Visitor Center, and proceed to the trailhead.
Leaving this scene behind, I started north towards Mount Angeles. It didn't take long to leave most of the people behind. Probably due to the lateness of the day, I didn't see anyone past the half-mile point. What followed was miles of pleasant hiking with grand vistas of the glaciated summits of the Olympic Mountains. Returning to my car I witnessed the high peaks bathed in the last light of the day.
The following day couldn't have been more different. Instead of hiking along a ridge above 5000' with expansive views of the top of the Olympics, I was sauntering through the Hoh Rain Forest, heading up the Hoh River Valley. Yesterday there were clear skies, today I walked under heavy overcast with rain in the forecast. A hurried pace wasn't required, which was welcome due to carrying a backpack instead of a light rucksack, though I didn't have to carry much water with me since the river was never far away.
After a couple of hours of walking, all the while admiring the lush rainforest and breathing in the abundant oxygen, I arrived at Five Mile Island camp. The tent was quickly pitched, for although it hadn't rained yet, the odds are it would before nightfall. Aside from preparing dinner, the rest of the day unscheduled. This is one of the joys of backpacking, once you are situated, you can, if you so choose, rest and relax. Sure you can explore the area, write in your journal, perhaps bag a peak, but you can also prepare a cup of tea, read a book, or take a nap. Today was a day to relish in doing nothing; the Italians have a saying for this: "dolce far niente".
Few, far too few, are the times where I sit back and just let the day go by. Sad, really, since there is much to be obtained by just being still. Here, on the bank of the Hoh River, I was content just to be. Surrounded by wildness I felt a deep calm come over me as the daylight slowly waned.
Light precipitation fell during the night, no real surprise when camping in a rain forest, and it had been in the forecast. My tent provided comfortable shelter and by morning there was only a light drizzle. The sun never made an appearance during my time in the Hoh Valley; drying my gear would have to wait.
The walk back to the trailhead was peaceful and there was almost no one on the trail. The few people I did encounter were other backpackers until I was close to the Visitor Center. At my car, instead of being elated, I was felt melancholy.
The visit to Olympic National Park had been all too brief. A much longer stay was required. Yet I understood, no matter how many trips I made here, I would never really 'know' the park, and probably never achieve anywhere close to the level of comfort I have with my favorite haunts. The park was too large, too diverse, and too dense for me to ever fully explore, especially given the logistical challenges to get here from my home in Southern California. Normally this is where I would quote Robert Service and be glad for a 'Land of Beyond', but today the poet's words provided no solace. I found Olympic National Park too late in life, and with it, the awareness there are other places just as spectacular which I've still yet to behold.
Thankfully, there is still time to push back the veil on some of these locales while choosing a select few to become intimate with. After all, that's the most anyone can realistically do with just one life.


Florida's largest LGBTQ Pride event has announced an historic event happening at this year's Pride. For the first time in the state's history the St. Pete Pride parade will kick off by the TransPride March consisting of all members of the transgender, gender-non-conforming, queer communities, their families, friends, allies & supporters on Saturday June 24th. Eric Skains, Executive Director of St Pete Pride stated, "Somewhere along the way, in the fight for acceptance & equality, our movement allowed the rights of trans individuals to be pushed to be back of the line. Pride celebrations all over the nation accepted & often embraced, the term 'Gay Pride' even though it was those within the Trans community who helped begin the Pride movement. We could very well not be celebrating Pride today if it weren't for the Trans community. Pride month began with Trans people & the issues facing the Trans community & the progress made, need to be recognized at every Pride." Gina Duncan, Director of Transgender Equality, Equality Florida concluded, "TransAction Florida is so proud to sponsor this historic march recognizing the entire spectrum of the transgender community. It is time that all identities feel safe to step forward out of the shadows and demand that the world see us as we see ourselves. We call on all Floridians to join us at this historic event." The TransPride March is proudly sponsored by Equality Florida & its transgender inclusion initiative, TransAction Florida. The first 500 people to register will be given a TransPride T-shirt & transgender pride flag. All marchers are encouraged to bring transgender pride flags.


text:
Promenade (2020)
A single or multiple projections
(3d animation, a perfect loop, infinitely playback)
F_Station (2020)
A trigger which inspired this minute, and a kind of an opposite situation of inactivity and silence, was my accidental visit to a train station named "Factory" situated in my hometown in Banat, Serbia during the pandemic and restrictions on movement in spring 2020.
The station is bleak and empty for decades, where trains are quite rare and on that spot, nothing has changed.
The Player (2019)
Yamb is a social game with dices, as a rule, played with an unlimited number of players, but with no less than two.
This short video form is inspired by the player who plays this game with himself and by this dialogue that follows;
"You were busy last night, is that so?"
"Yes, I played yamb".
"With whom?"
"With myself."
"How...well, are you winning?"
"Sometimes I win, more often lose. I found the way how to cheat lately. Although in the end, the only game matters".
Stretching of Daily life
This video is a product of contemplation on simple human actions in public space, whether it concerns people in movement or not. Through the process, I have established the connection and simultaneity among any of these actions, as well as unity within each individual action. This specific kind of collage needs to provide a new sight on our reality and daily life, and the triptych form seems to be quite a logical solution in this case.
A loop playback installation
A/V interpretation of William Shakespeare's sonnet
Forgotten faces
This video is part of Forgotten faces cycle, and reflects a kind of contemplation about all those faces from past, deformed by memory faults but many other factors as well.
Installation, (according to the Angelus of J.F.Millet)
Violence against women in 30 seconds
Dogville interaction, video projection for theatrical art performance
A projection mapping draft


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