text:
Bill Ritchie Work in
in the
Mina and Hide Horiuchi Collection
1982. Cyanotype Commemorative Poster. Six-color offset lithograph. Tones of blue, overprinted with transparent gloss yellow process PMS inks on white 165 lb Warren Patina pH Neutral paper. 40 X 24 3/4 in. Eleven hundred printed. 850 recycled as catalog covers. Signed.
"Though this poster was printed by offset lithography, we made the plates from hand-drawn masters. To create the blended colors I worked with the plate maker and printer plus I mixed the inks. Three sources make the image: A map of the Colorado River, a leaf-like diagram the artist uses for computer animation and the famous woodblock print by Hokusai titled "The Great Wave . . ." I was influenced by cartography, computer technology and Japanese culture and also my family and studio mates as I thought of names for my fantasy map. Hide Horiuchi was part of the Carl Youngman and Eleanor Mathews group and they had a hand in helping me realize the image of the map background. He acquired the print when it was newly published, and then replaced it (it was damaged some time later) in 2005."
"C-Squares Off the Coast of Washington"
1981. Relief print from woodblock plates. Blue, red, brown, ochre, black on white. Image 10 X 15 in. on 11 1/4 x 16 1/4 in. Japanese handmade paper.
Artist's Comment:
"Cutting the blocks for the Locus and the Sea Squares took many weeks, plus I needed to align the printed images from them with the copperplate etching for the full size print that was coming along. I used the famous Great Wave print by Hokusai, almost exactly copied but I slightly altered the curl of the wave wave (to conform with my own system of composition based on the the locus of beauty series). The C-Squares I substituted for the fishing boats and Mt. Fuji became Mt. St. Helens. The sky changed to become part of the map of the Lake Powell region where the spaceship was filmed, and blends into the upper part of the print (not visible in this working proof)."
Arborescence, Cross and Calculus
1997. Intaglio and surface monoprint from etched and engraved copper plates. Black, red and white with orange and blue monotype on white Lennox and folded Arches Cover paper. Image 12 in X 9 in with 1 1/4 in folded border.
"Around the shop during Daniel Smith's Open Studios there were pieces of paper that the monoprint artists cast off. I retrieved one of these and began printing my etchings and engravings on them. I lost count how many times I printed; at one point I emulated those monoprint artists-painters, really-and created the cross shape, then resumed my intaglio printing. In all the two plates traveled through the press eight times."
Above: Mariner Halfwood Press #2
Legacy Mini Halfwood Press #23
in purpleheart wood
Mina also owns the Mariner and Mini Halfwood Presses in her studio-the latter is the unique purple heart model.
See the Patron's List for more peoples' collections - click


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RFC Frame Relay over L2TPv3 July present in the ICRQ in order to identify the PVC (together with the identity of the LCCE itself, as defined in. Layer 2 Tunnelling Protocol Version 3 is an IETF standard related to L2TP that can be used as IETF L2TPEXT working group · RFC – Layer Two Tunneling Protocol – Version 3 (L2TPv3) · RFC – Layer Two Tunneling Protocol "L2TP. Abstract This document describes the transport of Ethernet frames over the Layer 2 Tunneling Protocol, Version 3 (L2TPv3). This includes the transport of.
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Table of Contents 1. The following is a summary: Beyond the considerations when carrying other data link types, there are no additional considerations specific to carrying HDLC.
Waiting until the interface rffc to ACTIVE may be preferred, as it delays allocation of resources until absolutely necessary. The exact method of how this value is configured, retrieved, discovered, or otherwise determined at each LCCE is outside the scope of this document.
Rfx Working Group C. For purposes of this discussion, the action of locally associating an interface running HDLC with a PW by local configuration or otherwise is referred to as "provisioning" the HDLC interface. Specification of Requirements In this document, several words are used to signify the requirements of the specification.
A non-exhaustive list of examples and considerations of this transparent nature include: These words are often capitalized.
Reserved bits MUST be set to 0 when sending, and ignored upon receipt. Pignataro Request for Comments: Maria Alice Dos Santos provided helpful review and comment. The reader is expected to be very familiar with the terminology and protocol constructs defined in [ RFC ].
This gives all sessions basic dead peer and path detection between PEs. Distribution of this memo is unlimited.
RFC: L2TPv3 interface
Please refer to the current edition of the "Internet Official Protocol Standards" STD 1 for the standardization state and status of this protocol.
The value of N depends on the following fields: The specific negotiations and signaling of the protocol being transported are performed l2tv3 Remote Systems rtc, and the LCCE does not participate in them. All sessions established by a given control connection utilize the L2TP Hello facility defined in Section 4.
Please address the information to the IETF at ietf-ipr ietf. The IETF invites any interested party to bring to its attention any copyrights, patents or patent applications, or other proprietary rights that may cover technology that may rrc required to implement this standard.
This document is subject to the rights, licenses and restrictions contained in BCP 78and except as set forth therein, the authors retain all their rights. If so, the period and maximum number of retries MUST be configurable.
RFC – Frame Relay over Layer 2 Tunneling Protocol Version 3 (L2TPv3)
The MTU and fragmentation implications resulting from this are discussed in Section 4. Errors or corruption introduced in the HDLCPW payload during encapsulation or transit across the packet-switched network may not be detected. Additional HDLC result codes are defined as follows: This lack of integrity-check transparency may not be of concern if it is known that the inner payloads or upper protocols transported perform their own error and integrity checking.
Intellectual Property The IETF takes no position regarding the validity or scope of any Intellectual Property Rights or other rights that might be claimed to pertain to the implementation or use of the technology described in this document or the extent to which any license under such rights might or might not be available; nor does it represent that it has made any independent effort to identify any such rights. Applicability Statement HDLC Pseudowires support a "port to port" or "interface to interface" deployment model operating in gfc point-to-point fashion.
The sequencing mechanisms described k2tpv3 Section 4. Copies of IPR disclosures made to the IETF Secretariat and any assurances of licenses to be made available, or the result of an attempt made to obtain a general license or permission for the use of such proprietary rights by implementers or users of this specification can be obtained from the IETF on-line IPR repository at http: Sequencing may be enabled in the HDLCPW for some or all packets to detect lost, duplicate, or out-of-order packets on a per-session basis see Section 4.
The ICCN is the final stage in the session establishment, confirming the receipt of the ICRP with acceptable parameters to allow bidirectional traffic. For reference, this AVP is shown below:

subset: commoncrawl


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You Have Reached A Full Access SectionGet full access
More Than A Feeling
In this tutorial, Mike Olekshy will teach "More Than A Feeling", as made famous by Boston. Mike will teach all 5 guitar layers in this tutorial. A 12 string acoustic kicks off the song with an iconic arpeggiated riff that appears in all the verse sections. A clean electric guitar adds some ringing harmonics and arpeggiated chords. A crunch guitar sets the chorus sections on fire, and two additional lead guitars add some melodic harmonized leads. All of these guitars appear throughout the tune creating a rich tapestry of sound that became an industry standard of how to multi-layer guitars in the studio.
Lesson Info
Instructor Mike Olekshy
- Styles:
- Difficulty:
- Files
- Videos / Score
- Published
- More Than A Feeling: Introduction
- More Than A Feeling: Gear & Tone
- Sun Was Gone: Guitar 1 Acoustic Intro
- Start My Day: Guitar 2 Verse Harmonics
- I Slipped Away: Guitar 2 Pre-Chorus
- Closed My Eyes: Guitar 3 Pre Chorus Lead
- Begin Dreaming: Guitar 4 Chorus Riff
- Walkin' Away: Guitar 2 Post Chorus
- Summer Sky: Guitar 5 Pre Chorus Harmony
- Forget the Day: Guitar 4 Under Solo
- Hide in My Music: Guitar Solo
- Dream of a Girl: Guitar 5 Harmony Solo
- That Old Song: Guitar 4 Last Verse
- More Than A Feeling: Full Performance
- More Than A Feeling: Single Guitar Performance


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Murray/Soares And Spaniards Vie For US Open Crown
Fourth seeds aim for second Grand Slam doubles title this season
A new team will be crowned US Open champion on Saturday when fourth seeds Jamie Murray and Bruno Soares square off against unseeded Pablo Carreno Busta and Guillermo Garcia-Lopez.
For the British-Brazilian pairing, it will be an attempt at a second Grand Slam doubles title of the season after winning the Australian Open. Murray/Soares saw off defending champions Nicolas Mahut and Pierre-Hugues Herbert in the semi-finals and should they triumph in the final, they would become the first team to win multiple Grand Slam titles in a season since Bob Bryan and Mike Bryan won three in 2013.
The Brit/Brazilian duo, who started playing together this season, won the first Grand Slam tournament they played, the 2016 Australian Open. But they lost in the third round at Roland Garros and fell in the quarter-finals at Wimbledon.
Both have contested finals in New York before, however. Murray finished runner-up at Flushing Meadows last year (w/Peers) while Soares fell in the 2013 final (w/Peya). The Brazilian had previously tasted US Open success with mixed doubles titles in 2012 and 2014.
Their opponents, Spaniards Carreno Busta and Garcia-Lopez, have never progressed past the third round in a Grand Slam tournament. Coming into the US Open, they were 0-2 as a team this season (10-10 lifetime), although both had carried form over from the US hard-court swing.
Carreno Busta won his first ATP World Tour singles title and Garcia-Lopez won the doubles trophy at Winston-Salem. It would cap a strong turnaround for Garcia-Lopez, who started the season 0-11 in doubles before reaching the semi-finals in Atlanta last month.
Carreno Busta/Garcia Lopez become the first unseeded duo to reach the US Open final since 2000 when Lleyton Hewitt and Max Mirnyi captured the title (d. E. Ferreira/R. Leach).


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Everyone has seen clips of customers flocking to Costco Wholesale Corp. to stock up on everything from food to toilet paper and other necessities.
Cowen analysts say that coronavirus-related surge in demand will continue for months.
"We believe Costco is well positioned to continue delivering double-digit earnings growth over the near to medium term driven by square footage growth, membership revenue growth, and industry leading physical store traffic growth," wrote Cowen analysts in a Tuesday note.
Among the reasons for the upbeat view, besides the recent jump in demand, are the long-term investments that Costco
Read:Walmart stock wins second upgrade of the week as shoppers flock to grocers amid coronavirus
Costco customers have average household income of about $74,000, Cowen said.
"[W]e do acknowledge many of these new members may cancel their memberships once the coronavirus passes, but nevertheless expect a lift in total members," analysts wrote.
Even as stores struggle to keep some items in stock, Costco is able to shift to alternatives, particularly in categories like fresh food and domestic goods.
Cowen rates Costco shares outperform and, in a rare move these days, raised its price target to $360 from $350.
On Tuesday, Cowen lowered a slew of retail price targets, including off-price retailer Burlington Stores Inc.
Analyst groups are optimistic about the mass merchant sector, with Instinet analysts moving up their estimates for retailers like Costco, Walmart Inc.
See:General Mills says its food supply chain is operating 'effectively' and guidance assumes that will continue
"The sales lifts are partially offset by lower merchandise margins on our model due to a mix shift towards basics," Instinet wrote.
"In addition, we give back some of the leverage associated with sales increases as we model higher payroll dollars due to the need to increase staffing. We have not changed our estimates for club memberships for BJ's, Sam's Club [Walmart's membership club business] or Costco at this point, although all three could see some incremental membership sign ups."
UBS analysts also think Costco will benefit from the recent $1 billion acquisition of Innovel Solutions, which is described as a "middle mile and final mile delivery and installation business."
Don't miss:There are 382,000 job openings and counting as Amazon, Walmart, Domino's and others hire to meet coronavirus demand
Analysts led by Michael Lasser think that Costco's control of Innovel's 11 distribution centers will help it to grow in the "big and bulky" categories like grills, mattresses and major appliances.
"Overall, we think this deal further enhances Costco's strong position in the critical long-run competitive frontiers in retail: data and delivery," UBS said.
"We suspect that it will also be able to use this infrastructure to ship parcel items to better serve its overall e-commerce business. Right now, in some cases Costco charges higher prices for big and bulky items online than it does in its stores to account for delivery expenses.
UBS rates Costco stock buy with a $355 price target.
Costco stock has gained 18.3% over the last year while the S&P 500 index


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Bitstarz 42 casino
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UWC Academic Awards 2017: Excellent staff and students honoured
"When we celebrate excellence and achievement we are making a firm statement about what we value as an institution, and we are saying we value excellence - because not to value excellence is to encourage mediocrity. We see a rise in the culture of mediocrity gripping our nation, and it is our role and our responsibility as an academic institution to fight against that rising tide of mediocrity."
So said Professor Tyrone Pretorius, Rector and Vice-Chancellor of the University of the Western Cape (UWC), speaking at the University's inaugural Academic Achievers Awards in November 2017 - an occasion to acknowledge and reward the outstanding work of staff and students towards teaching, learning and community engagement.
An initiative of Professor Vivienne Lawack, Deputy Vice-Chancellor: Academic, the ceremony saw the best first-year students, undergraduates, honours and master's students from each faculty, together with staff members, honoured for their sterling work.
Among those staff members who were rewarded were Dr Karen Collett from the Education Faculty (Institutional Excellence Lecturer Award), Prof Moenieba Isaacs from PLAAS (Institutional Individual Engagement Award) and Prof Angeni Bheekie and team from the School of Pharmacy (Institutional Team Engagement Award).
Staff were also recognised in different faculties in the categories of Excellent Lecturer, Emerging Lecturer, Community Engagement Individual and Community Engagement Team.
For students (all in the 2016 academic year), Emily Dawson was the Best Overall First-Year, Gemma Froon the Best Final-Year Student, Tina Volkmann the Best Honours student, with Samuel Longford the Best Master's by Coursework awardee, and Mbulelo Bali the Best Master's by Dissertation winner.
Prof Lawack noted that the functions of learning, teaching and community engagement are often not recognised to the same extent as the research function - and universities are more than just places where knowledge is produced; they are also places where knowledge is shared and discussed, and used to help communities and improve society.
"Therefore it is important that our academic and support staff that excel in any of these functions are publicly recognised and suitably rewarded," she said.
"Consequently, as part of UWC's commitment to enhance the status of learning, teaching and community engagement, as well as the quality of our learning experiences provided to our students, a range of prestigious awards are conferred to recognise excellence in learning, teaching and community engagement for both staff and students."
In this way, Prof Lawack explained, the UWC community could honour all the central academic functions that enable the actualisation of achieving the University's mission, vision and values.
Prof Pretorius thanked Prof Lawack and her team for adding the event to the University calendar, and said that while it is in human nature to be concerned for the marginalised and those who are struggling, that must never be at the expense of celebrating excellence and achievement.
"High tide raises all boats," he said. "If one of us achieves, all of us are motivated and inspired to do our best. So when we celebrate excellence tonight we are not only celebrate the individuals we are celebrating the fact that their excellence has given all of us a lift and/or inspiration."


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#2 Most Winning Boston BTCA Norway 2016
The most winning list from Norwegian Boston Terrier Club (NBTK) is in, and I am very proud to see that I have four dogs in the lists.
#2 ADULT Mollyville's Believe In Faith (Wendy). She has done so well this year, with 3x CAC in Norway, 1x CAC in Denmark, 2x Crufts Qualifications and 1x CACIB. She has a BOB and a BOS at NKK shows, wich made her #3 on NKK's most winning list, only passed by two champion males, one being her own father.
#8 ADULT Mollyville's Believe In Magic (Franklin). He performed very well, showed 8 times in Norway, with 3x CAC, 1x CAC in Denmark, 2x Crufts Qualifications. He was #3 male on the NBTK's speciality show.
#1 PUPPY NORDJV-16 Mollyville's Castle Of Midnight Sun (Sam). His debut has been unreal. He has multiple group placing, and started his show carreer with a BIS all breed. He has many BOB, and a BOS from NBTK specialty show. From September, he started showing in junior class, and got 2x CAC in his two first shows, then went to Denmark and was Nordic Junior Winner 2016.
#6 PUPPY Mollyville's Castle Of Rosy Sunset (Emma). She has also done well, and with 3 BOB and 2 BOS, made it up the list.
We are so thankful to all who have helped us along the way, breeders of our dog's parents, co-owners.


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Persona 5 and Musou have come together, not like peanut butter and jelly but something else entirely. It's hard to know what to expect when you come into Persona 5 Strikers for the first time, as the two genres are so finely blended it can be hard to process at first.
But you'll eventually learn the intricacies here, and become an expert in the coolest MegaTen action game since Devil Summoner. I mean, yeah, it's the only one since then, but still. It's good.
As I played through Persona 5 Strikers on the way to writing our review, I took note of some of what felt like the most important points. Some of them came up in the review, but the rest are great material for a general "tips and tricks" style guide.
So here we are. We may go further in-depth if necessary, but for now if you haven't dived in yet, these pointers may be worth keeping in mind before you get started.
Persona 5 Strikers Tips and Tricks
Like a normal Shin Megami Tensei-adjacent game, SP is a precious resource. It's the same in Strikers, especially since it can be hard to even find useful SP restorative items. That said, you'll only be burning SP if you summon your Persona to use a skill directly.
If magic comes out as part of your combo-enders, it's free. However, even if you hit a weakness you won't get the same bonuses.
You're gonna have to grind; sorry. Persona 5 Strikers does have some level checks. They aren't intense, but in some cases (especially minor boss fights), if your numbers aren't high enough you'll see your margin of error dissolve pretty quickly. Sometimes you just have to run around and level up a bit.
Speaking of leveling up, you also want to swap your party members around as much as you can early on. This is because in addition to leveling up and getting stronger, characters also gain new abilities or passives for things like their gun attacks. These are all super useful, so filling that stuff out as early as possible will help you out big time.
Most of the time in Musou games you don't really have to pay attention to what enemies are doing. Every now and then there's an exception, but generally speaking you'll be fine just worrying about how you're issuing pain. Strikers is different, thanks to all the different consequences of eating damage.
And the different spells have very different physical properties, even within the same line. For example, when an enemy casts Bufu you'll see a little AoE indicator on the ground and have time to react. But if you see a demon cast Mabufu, you have about the time it takes to read that to get out of the way as a trail of ice barrels towards your face.
From Zio to Garu, there's almost always some variation of physicality, so it's important to pay enough attention to learn those variables and what you need to do.
You'll come to learn quickly that Strikers has replaced Social Links with something a bit simpler in the team's overall Bond level. This extra meter builds up passively as you play and advance the story, and it's pretty slow.
But if you can hold off a bit and just buy some rate ups, your Bond level will go up way faster, and you'll be able to snag super helpful stuff like post-combat HP/SP heals much earlier.
The best asset to your progress is the facet you can run away. Unlike the Persona games proper, Strikers lets you dip out of a Jail early without any repercussions. Combined with the checkpoint system, there's no reason not to dip out for a bit to heal up, check the shop for more items, manage your Personas or whatever.
If you don't want to blow items just leveling or exploring, there's nothing wrong with leaving outright even if you're gonna jump back in right away.
My biggest problem with Persona 5 Strikers is the camera. It's zoomed in a bit too much for what's actually happening in the game, making some of the chaos harder to digest compared to other games like this. But if you keep that in mind and prepare yourself to put a little extra effort into keeping tabs on the battlefield, you'll be fine.
This is mostly relevant for making sure you don't miss things like All-Out Attack prompts, which can pop up all around you depending on the circumstances.
In regular Persona games, keeping the protagonist's starting Persona around is more of a thing you have to want to do. But in Strikers, Arsene has quite a few more skills than usual, so he's definitely worth keeping around for a while to fill that up.
Arsene is also good fusion material though, but it can be worth the money to grab them right back from the compendium.
Persona Points seem like something you'll want to hang onto, since Personas are plentiful and leveling them up is slow going otherwise. But it's super easy to get these points, especially once you get certain Bond skills.
Don't hesitate to pump up your Personas as soon as you can, to make sure you're getting access to skills and not falling behind in strength. Smoke 'em if you got 'em.
Persona 5 Strikers is a super busy game that throws all kinds of stuff at you. Reacting to everything can seem overwhelming at first, but once you click with the systems you'll adjust just fine. This applies to fans of either side of the hybrid here, both Musou fans, Persona fans and anyone in-between.
If you're on the fence about whether or not you even want to try Strikers out, hopefully our coverage will help you decide. Afterwards, let us know if you enjoy the game or not over at the Prima Games Twitter and Facebook channels!


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Now that we have a
programmingLanguageType slot, we need to link it to our
Imagine if our utterances were hard-coded names of common guesses, such as:
- Is it Ruby
- Is it Python
- Is it JavaScript
- Is it Java
We want to replace these hard-coded utterances with the
language slot. We can use
{} to specify which portion of a user's utterance to capture as the slot.
All of the utterances above could be captured with the following utterance:
- Is it {language}
The steps in the instructions below will guide you through the process of adding sample utterances to your
The video on the right walks you through the steps to associate a slot with the LanguageIntent.
Create LanguageIntent
Since you have already created the custom
programmingLanguageType slot, you can add a few utterances to a new intent using the following steps:
- Create a new intent called
- Add
Is it {language}as a sample utterance to the
LanguageIntentand press enter
- On the right side of the screen, and under
Intent Slots, select
Choose a slot type...and select
- Add a few more utterances. See below for examples:
Could it be {language}
I think it's {language}
Build Model when you're done


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Smart Choice Communications offers custom tailored security
Smart Choice Communications (SCC) a leading technology provider, today announced that Kabbage, Inc. is staying protected and secure with the help of a customized security solution. Utilizing an access control security solution, SCC's unique platform hard and software components is compatible with any type of door.
"We wanted to allow people access to physical spaces without compromising security," said Basil Stepanov, CTO of Smart Choice Communications. "With our services a key card, RFID readers, or a simple-to-use phone app may grant the user access to a classified area."
Kabbage, Inc. was expanding to a New York City location and wanted better protection than their current legacy system in their Atlanta, Georgia office. Smart Choice Communications is defining the future of the security industry through groundbreaking, end-to-end solutions. Delivering the world's best technology, SCC provides access control and video analytics products that consistently outperform the competition. Any security solution they approved would have to be scalable and versatile.
Smart Choice Communications installed a security solution and the benefits of the implemented solution have been substantial. SCC's systems engineers designed and provided an infrastructure solution that was customized specifically for Kabbage, Inc. business needs, including low voltage cabling to each door. The new location is split between two floors, allowing for a stairwell access point on each floor, in addition to the main, back, and side doors. The card readers have a Bluetooth option and motion sensors were installed, which was a huge improvement. For further protection and security of the workplace, a camera was positioned at the entrance to see who comes and goes. Kabbage, Inc. was extremely pleased with the professionalism of SCC's service engineer's work and the access control system they were provided with, and wants to upgrade their office in Atlanta, Georgia.
About Smart Choice Communications
SCC acts as a single point of contact for all of your telecommunications needs. We pride ourselves on providing personalized, cost-effective solutions customized specifically for each of our clients. SCC provides a single source, end to end solution for your voice, data and security networks – from design, installation and implementation to management and 24×7 support. One Provider, One Bill, One Smart Cloud Solution.
For more information, visit www.smartchoiceus.com


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Discussion Starter · #1 ·
Contacted the 3X service department on Monday to find out how things were progressing with the warranty claim that was submitted at the beginning of July for my Tornado TRE. (The claim was for the loop back plug, clutch modification, both lower fairing panels due to peeling paint and an exhaust can that was blowing from both ends.) I was told they would speak to KJM and I would receive a call back later that day - no call back. Chased it again on Wednesday - same result - no call back. Contacted them again Friday with the response "I will come back to you in the next half hour" - no call back. Saturday I contacted the dealership manager who apologised for the lack of response but then went on to say things like "I think the warranty on bodywork is only for a year" - oh really! "There was no recall on the clutch problem" - then why did the factory issue a modification kit to "fix" the neutral problem and the real gem "By the time we get the parts sorted for your warranty claim we will probably no longer be Benelli dealers" - oh great! I think 3X are trying to wash their hands of Benelli and any owners with outstanding problems - not good....not good at all. >:


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Board meetings have prompted a lot of eye rolling | Notes on Nonprofits
A few weeks ago, someone good naturedly accused me of rolling my eyes during a meeting. I admit I was, but like a 14-year-old I thought I'd done it without moving my eyes. My friend informed me that like most moms she has the super power of being able to detect eye rolling when nothing is moving.
Suddenly I was worried. Not because of what I'd done in that meeting but because of the 10,000 times I've rolled my eyes during board meetings for the past 25 years thinking no one could tell. Not only am I now haunted by the memories of all the moms in those rooms who probably knew exactly what I was doing but I'm flooded with the memories of why I was rolling them in the first place.
I rolled at least one eye when board members ask the same question that was asked and answered 10 minutes earlier. Rolled both eyes when those board members didn't hear the original discussion because they were trying to read the board packet they didn't read before the meeting while pretending they weren't.
High performing board members read the packet before coming to the meeting and practice active listening during meetings.
I'm guilty of rolling my eyes in my mind when board members who never follow through are the first ones who volunteer to do things. Board members don't earn eye rolls when they already know they are overcommitted and say so or ask for others to help. And board members who always follow through are sent silent kisses and hugs.
Board members who overthink and over talk a $100 overage in the financial statements but are not concerned there is no money in reserves have been the beneficiaries of many silent eye rolls over the years. Board members should focus on the big picture and sustainability of the organization and not get into the weeds.
I confess I have rolled my eyes when board members repeatedly don't let anyone know they can't attend the meeting. Not making quorum at a board meeting is a lion's roar that something isn't working with the board and it can cripple the organization's ability to meet legal and fiduciary responsibilities. I'm not talking about board members who occasionally get stuck and can't let anyone know. I'm talking about the ones that no one ever knows if they will really be there.
It's not just board members. I have reacted to EDs who dominate discussion in board meetings. EDs have to practice servant leadership by facilitating the board's work without usurping it. I've been in meetings before when the EDs has cut into a discussion and told board members they can't do things or when they won't stop talking long enough to let the board members speak. Remember, it's the board's meeting not just a board meeting.
I have rolled my eyes so badly they could possibly stick in the up position when I have read colleague board members who aren't helping with our fundraiser postings on social media asking people to buy tickets to another nonprofit's fundraiser. I'd like to offer a better way to react, but I literally just rolled my eyes as I wrote this. Sometimes the eye rolls are truly deserved.
I've been tempted to gasp out loud when EDs report something they've done without board approval. Like agreeing to receive funding for a program that isn't part of the strategic plan and strays a little off mission. Or draw down from the emergency line of credit.
Any time the ED starts to believethey have the authority to do whatever they want I can guarantee that sooner or later a board member will challenge their perception about that. A savvy board will do it sooner rather than later.
My rolling eyes have become fixed and intense when a board member is being inappropriate. A board chair once introduced our highly regarded ED at a public event as "that short woman over there." I didn't roll my eyes but I did have a strong private conversation with the chair later. It's my humble opinion that my secret eye rolling would have been easier on him.
I've rolled my eyes inside my head when board members complain about the location of their table at an event that has already started. Feedback like that needs to be given later if it's really a problem and not an ego.
I love when board members are creative and come up with a gazillion ideas. But admittedly I get a little eye-rolling-irritated with board members who often have great ideas and expect the rest of us to implement them. Unless it's a board member who is working as hard as they possibly can, doing an incredible job and the rest of us really do need to get our act together.
Even though it doesn't sound like it here, I really have been very fortunate that in my consulting, leadership and service relationships with boards of directors and nonprofits most people have not earned what I now know is my poorly disguised, judgmental and inappropriate eye roll. And now that I know I may not have been as discrete as I intended I won't be doing it to anyone ever again.
Notes on Nonprofits is written collaboratively by Kelly Otte, MPA and Alyce Lee Stansbury, CFRE, President of Stansbury Consulting. We'd like to know, besides this column, what you roll your eyes at by writing to us at firstname.lastname@example.com.


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The Organic Farming Experience in Takahata
Final Report Spring 2019 By Hwee Cheng Yeo
Childhood Dreams
When I was a child, I used to wonder about what life would be like as a country farm girl. Having only ever known cities or suburban neighborhoods, I was naturally curious about it, and would often imagine highly idealized visions of a rural lifestyle for myself to enjoy. In these imaginations, farms were a green paradise where humans, plants, and animals happily coexisted together. I also developed a strong love of nature at this point in my life. Of course, I eventually learned the truth about modern commercialized farming and its questionable practices after I became older. Still, my love of nature never faded, and led me to pursue environmental studies in my education. Taking this course, Understanding the Environment Through Culture, was just one of the ways I had chosen to do so. Although I did enjoy the entire course, it was the fieldwork in Takahata that ended up being my favorite part of it. This is because our class's stay in Takahata, despite being brief, was a wonderful experience in which I managed to come closer to my childhood dream.
Takahata Day 1 – Friday, June 28
The first day of the trip was tiring, yet enjoyable. We took the shinkansen from Tokyo Station in the morning and arrived at Takahata Station in the afternoon. I was already excited at this point, because Takahata was so different from Tokyo! There were much fewer buildings and a lot more greenery, which was expected, but still pleasant to see. The atmosphere of the town was also very different. There was none of that busy city energy that is always present in Tokyo. Instead, I felt relaxed and at ease.
The main event of the day was the visit to a local elementary school. We were there to learn about how this school had implemented an organic farming program in order to pass down the area's agricultural traditions to its students, as well as to provide students and teachers alike with fresh, healthy food. Despite not understanding very much of what was being said, it was interesting to walk around and observe the kids either working or demonstrating some task to the class. They were knowledgeable, and after getting over their initial shyness, quite eager to teach us what they knew. It was nice to see their enthusiasm for the farm work. I was also delighted to find frogs hopping around the crop areas, a sign of nature and humans coexisting. Already, Takahata was living up to my childhood expectations of farm environments and farming life.
That night, we had dinner at Ryokan Ebisuya, where we would be staying. Our class was divided into the groups that we would be in for our fieldwork tomorrow. Each group ate together with the farmer who would host them. Our group's host farmer was Mr. Minoru. I was not able to converse at length with him because of the language barrier, so I just listened to the others' conversations around me.
After dinner, I went along with a small group of students to go firefly spotting in the rice fields. A local drove us out to a dark field, but weren't able to see any fireflies at first. However, we didn't give up and continued searching. Then, we finally saw them! They were hard to spot at first, but we soon got used to it and realized that there were many fireflies hiding around us. As it was the first time I had ever seen a firefly, I was very satisfied with the excursion, and was also happy to see another example of humans and nature living in harmony (fireflies living in human-made rice fields).
Takahata Day 2 – Saturday, June 29
On the second day, we woke up early and set off with Mr. Minoru to his farm. It was a pleasant drive, and I once again admired the Takahata countryside. At the farm, we rode in the back of a truck (Fun!) to get to the grape field. Mr. Minoru explained our task: to wrap the grapes with wax paper "hats" in order to protect them from rain. He explained which type of grapes needed wrapping and which ones didn't, which was interesting to me because I didn't even notice the difference in types until he pointed it out. Our group kept at this for the whole day, stopping twice for a break and then lunch. Despite the repetitive nature of this activity, I didn't become as frustrated with it as I thought I would. Rather, I was able to relax and let my mind wander around vaguely for a few hours. I didn't talk very much while working, but I wasn't bored.
A surprising thing to note about Mr. Minoru's farm was that it was much bigger than I thought! Aside from grapes, there were many other crops being grown in other areas, none of which we went to. Also, the field with the grape trees was full of frogs! We had to be careful not to step on them, but I thought it was really cool how everything in Takahata is just surrounded by nature.
I was very impressed with the idea of collective, community-supported agriculture that I learned about in Takahata. This system, also known as teikei , allows consumers to purchase locally grown organic food items directly from nearby farmers. Both sides benefit, with the customers receiving healthy, non-chemically infused foods that are in season, and the farmers obtaining a stable source of income. Mr. Minoru happened to be part of one such network of farmers and consumers, a fact I was happy to learn. Here was yet even more fuel for my happy childhood farm fantasies.
Takahata Day 3 – Sunday, June 30
On our third and last day, the main focus of our activities was learning about the history of Takahata. To start off, we went to the community library built by farmers. To be completely honest, I did not understand the lecture, but was still able to appreciate the dedication of the farmers in carrying out such a task. Next, we went to a historical building to for another lecture, this time about the entire history of Takahata, from the feudal era to the present. Finally, our third lecture was at the Hamada Hirosuke Memorial Hall. Here, we were introduced to his most famous story, "The Red Oni Who Wept". All three lectures taught us something about the character of Takahata. First, the story of the farmers building the library showed the powerful collaborative spirit of Takahata citizens, which can still be seen in the cooperative teikei system between consumers and farmers today. Second, the lecture regarding the historical progress and transformation of Takahata into its present-day form as an organic farming village shows how peoples' values have shifted over time, with environmental concerns now being at the forefront for both regular citizens and farmers. Thirdly, the story of the Red Oni demonstrates the importance of making tough decisions and sacrificing something personal for the good of the community. In Takahata, farmers choose to take the difficult path of organic agriculture, sacrificing the easy path of using chemicals and genetic modifications to make higher profits. In this way, they support both their community and their natural surroundings by providing healthy food to consumers with as little environmental damage as possible.
Final Thoughts
The Takahata organic farming community is inspirational in so many ways. In addition to the basic practice of organic farming, already admirable in and of itself, the people of Takahata go above and beyond in the way that they emphasize the importance of community values. This is shown by things like the collective farmers' library and the collaborative teikei system, which is especially something that should be implemented in more places around the world. By taking a stand and refusing to succumb to modern commercialized farming, the Takahata farmers are able to protect the delicate relationship between humans and nature. I am very thankful to have been able to experience Takahata for myself, as it is everything that my kid self had dreamed that farming would be.


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A federal judge ruled Tuesday that a suburban Cincinnati man is competent to stand trial on charges that he plotted to attack the U.S. Capitol in support of the Islamic State group.
"The court finds that a preponderance of the evidence supports that conclusion," U.S. District Judge Sandra Beckwith wrote.
She noted in her order that a psychologist for the defense testified in a Monday hearing that Christopher Lee Cornell, 22, is currently able to participate in his defense. The psychologist had filed an evaluation last year concluding Cornell couldn't properly assist his defense, but has modified his opinion, Beckwith wrote.
Psychologist Scot Bresler, of the University of Cincinnati, who has met repeatedly with Cornell, said for the first time Sunday he asked to be called "Chris" instead of Raheel Mahrus Ubaydah, which he had adopted as his Muslim name. The long hair and beard Cornell had when arrested in January 2015 have been cut off.
The psychologist testified Cornell has anxiety and personality disorders and can be deeply depressed, and urged he be re-evaluated before trial because his competency could change.
Prosecutors filed a report by another psychologist concluding Cornell is competent, and also filed exhibits including letters from Cornell the government said show he understands the charges against him and can help his attorneys.
Cornell, held without bond, has pleaded not guilty to four charges, including attempted murder of U.S. officials and employees. His father has said he was misled and coerced by "a snitch."
His attorneys could still pursue an insanity defense.


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Nestled 35 miles south of Atlanta in the secluded Chattahoochee Hills is a playhouse like no other, and this Spring and Summer are great times to head out to the rustic community to experience theater in a new way. Serenbe's director, Brian Clowdus, creates a theater environment like no other. Immersing visitors into the middle of the scenery is one thing that keeps bringing guests back for more each year.
Playing now through April 10, Carousel has a fabulous theater environment including a working Ferris Wheel. No carnival would be complete without an assortment of booths and interesting characters like a bearded lady and Siamese twins. And yes, there is even a carousel!
"In a more innocent time, Americans sought entertainment in the form of carnivals and fairs, where delights of all kinds were just a ticket away. This spring, we invite you to step right up and experience Carousel, the second installment within the Rodgers & Hammerstein canon featuring the reunited all-star cast of Serenbe Playhouse's beloved 2014 production of Oklahoma! The principles of this adored cast return to tell the tale of Billy Bigelow, his lovely Julie Jordan and their daughter, Louise, in a rendition that highlights the dark undertones of a cruel world juxtaposed with the enduring power of love. Along with the reimagined telling, you'll find the rolling hills of Serenbe transformed into a turn of the century carnival, complete with cotton candy, games galore, wonders on display and, of course, a carousel. Come and take a whirl!"
8pm, Wednesday – Saturday
2pm & 8pm Sundays
Be sure to visit Serenbe April 2 and April 9 from noon to 5pm to experience a turn of the century carnival. Admission is free!
$1.00 per Ticket
$20.00 for 25 Tickets
Ferris wheel – 5 tickets
Carousel – 4 tickets
High striker – 1 ticket per swing
Games – 1 turn (3 tries) for 3 tickets or 2 turns (6 tries) for 5 tickets
Want more information on Serenbe Playhouse?
Visit their social media outlets below.
Images from Serenbe Playhouse website.


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Aqua Mech Water Treatment
Aqua Mech Water Treatment
Aqua Mech believes that quality water is your right. They are central New Jersey's leader in quality water treatment. Consider the humble water filter. It keeps impurities out of your water, giving you fresh, clean, healthy water to drink at any time of the day. But when you care about quality water, you want a water filter that can handle even the toughest jobs.
Digital Blueprint:


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"Considered a classic and most sought after re-issues on the vinyl format, the CD was originally released in 1997.
Give It Back! is the sixth studio album and notably, is the only album that features Peter Hayes, who went on to found the Black Rebel Motorcycle Club.
The Brian Jonestown Massacre is a psychedelic rock band originally from San Francisco, California, led by guitarist/singer Anton Newcombe. Originally Newcombe was heavily influenced by The Rolling Stones' psychedelic phase - the name comes from Stones guitarist Brian Jones combined with a reference to cult leader Jim Jones, but his work in the 2000s has expanded into aesthetic dimensions approximating the UK Shoegazing genre of the 1990s and incorporating influences from world music, especially Middle Eastern and Brazilian music."
- Cargo Records


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Why Business Showers are a No
I have rather mixed feelings about this "Business shower" thing everyone keeps sharing posts about, and quoting Elon Musk on.
I am highly suspicious that he ever said it though. In a recently clubhouse session he said the following.
There is this incident that Shekhar Kirani narrates, where they were evaluating a company for investment and there was some concerns as to whether there was really an opportunity gap big enough for a venture funded company to make a play. While the team was solid, and the fund would have easily made an exit, Shekhar's concern was as to whether funding the company would send the wrong signal to the founders where they chase the wrong market (with speed of capital now) rather than exploring the opportunity that is right for them. The most expensive cost would be the time and energy of the founders - ESPECIALLY of a team that's brilliant.
That's the incident that comes to mind when there is so much talk about business showers. If a business gets pity traction early on from friends and family, it isn't just a false positive (that can be very hard to isolate), but it also skews all the metrics that a business needs early on to actually achieve product market fit (or pivot).
You might be inadvertently causing harm by sending off a founder on a wild goose chase for a market that doesn't exist.
Listen to the market. Build something it will pay for.
In my opinion, anyone who stands in the way of the conversation between the entrepreneur and the market creating noise, is not a friend.
Several entrepreneurs make the same mistake when they do things like launch their product on Product Hunt and then go around asking people to upvote them - whether they think the person is a potential customer or not, and if the solution actually solves any problem for them.
What you end up with is 1000+ upvotes, and a really really noisy funnel that leaks like a submarine blown up by a torpedo and just extremely hard to identify who your real customers are, and to fine tune the solution for them. Stop doing that to yourself, trying to make it into a popularity contest. The best launches I've seen have moderate upvotes, but high quality leads that help them refine the product. Please ditch that vanity.
To be an entrepreneur, the first thing we need to stop fooling, is ourselves.
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Listen to my interview (Kiki Says it All) with Harmony Slater on the Harmony Slater podcast AND my interview with Adam Keen on the Keen on Yoga Podcast. I share stories, discuss my Yoga journey and much more! Listen for FREE.
PLUS: I was so happy to be invited to the MeatRx podcast as a Yoga Expert: Watch the full podcast here.
See below for more Insider content on KikiTV
January 4 – Monday
Meditation (15 min)
There are A Thousand Ways to Kneel and Kiss the Ground. A Thousand Ways to Go Home Again. Support your hope, faith and vision. Rumi's beautiful poetry guides us to vision beyond what we see. Stream on KikiTV.Life!
January 4 – Monday, 11AM EST (check below for your time zone)
Sutra Chapter 1 – Live on Zoom (45 min)
Imagine your consciousness as a perfect jewel. Without the continuous expression of habitual thought (vrttis) our mind is as a clear crystal illuminating all as it is. This is Yoga mind.
January 9 – Saturday
I am preparing for Saturday's New Year Your Gift-Led Life workshop!
Saturday 9th January, 2pm UK / 9am EST (2 hours)
Your Gift Led Life: 2021 Live Your Life of Meaning:
Let's look to the ancient Yoga traditions to support our modern Yoga lives. Are you ready to live your life as you often dream it could be?
This in depth workshop will cover 4 aspects to chart your course for the New Year – with a full heart, wise mind and respect for your precious gifts and your precious time!
Cost £20 Book Now
What to Stream
1. Kiki Thrive Event: Sankalpah (45 mins)
New Year's Resolutions in light of Yoga knowledge. How can we turn to the life we desire and meet our goals? Let's look at the concept of "auspicious visualization" known as Sankalpah. Watch here.
2. Meditation (15 min)
Mindfulness Lights My Path
Mindfulness Lights My Path. I See a Clear Solution For Each and Every Concern and Hope. My Life is My Own. Residing in the mindful moment, each moment, lights our path and clears the way to see the best course forward for each and every opportunity and goal. Join me in this meditation.
3. Chant! Sutra 2 (30 min)
Our consciousness is filled with obstacles that prevent change. A front of mind desire, longing, discipline or directive is not enough to uncover and remove the conflicts. Let's look at this more closely. Chant with me!
4. Weekly Podcast featuring Tim Shieff (1 hour)
Movement As a Path to Truth and Human Potential with Tim Shieff
In the early days of YouTube the most thrilling content was being shared by extreme movement artists and athletes especially in Parkour / Free Running and extreme sports and this is when I first became aware of Tim Shieff and his incredible boundary pushing and seemingly effortless movement.
Tim Shieff was break dancing and walking in handstands when he became inspired to try Parkour. He became a dedicated practitioner and it opened up a world where he was a sponsored athlete and had opportunities to compete as well as work in film and television (and he may be especially known for his standout abilities in the Ninja Warrior series). Tim continues to explore movement and learn from great mentors, pioneers, and from nature. He is also committed to unlocking human truth and the potential for expanded consciousness through body / mind seeking.
Tim is sharing Way of the Rope inspired by David Weck of The Weck Method.
Find Tim's ropes and trainings here and get a DISCOUNT with a special code: http://wayoftherope.co.uk/
Code: KIKI20
Find out more about Tim and follow him here:
Instagram: https://www.instagram.com/humantimothy
Way of the Rope: https://www.instagram.com/wayoftherope
5. I was so happy to be invited to the MeatRx podcast as a Yoga Expert:
Watch the full podcast (for free) here.


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Don't overcommit yourself this fall
September 21, 2018
As UT's newest class of freshmen settle into their dorms and classes, they are also beginning to get involved on campus. Many fill out applications for Student Government or spirit groups while simultaneously attending informational sessions for organizations they might find a home in. With an array of organization fairs such as Party on the Plaza, UT does a great job introducing freshmen to student organizations, internship opportunities and other extracurricular activities. These events give new students the opportunity to thrive but also leave room for new and unassuming students to ovecommit themselves.
Overcommitment is a side effect of the UT freshman experience — a result of freshmen trying to fit in by whatever means necessary. Roberto Soto III, a theatre and dance freshman, has already been cast in an Alpha Phi Omega play. Soto said the play requires 16 hours of rehearsal per week. Soto joined APO because he wanted to be more involved and "to put it on (an) acting résumé."
Soto is right, involvement on UT's campus can lead to social and professional opportunities in the long run. But before freshmen begin filling their Google Calendars with meetings or, in Roberto's case, rehearsals, it's important for them to listen to the wise words of our upperclassmen and avoid overcrowding their schedules.
Angela Kang, a biology junior, joined nine organizations during her first semester at UT. These organizations included Texas THON, Undergraduate Mentorship Agency, Camp Texas and Senate of College Councils. Kang said she would have six to seven meetings per week. At first Kang believed she was balancing academics and extracurriculars, but soon found herself becoming irritated and distracted. "I felt like I couldn't prioritize my academics and often found myself using my outside commitments as distractions from doing my academic work," Kang said. "I didn't really know how to handle my mental health."
Similarly, Alyssa Ashcraft, a Humanities and government junior, joined six organizations her first freshman year and interned at the Texas State Capitol. As a result of her hectic first year, she urges freshmen to focus on themselves and the few things they really love. "As a student commit yourself to a few organizations and build your community and your passions through them," Ashcraft said.
By their sophomore year, both Ashcraft and Kang left several organizations to focus on a handful they truly enjoyed. Meanwhile, Soto firmly believes "reminders and planners" will help him balance his membership with Alpha Phi Omega and a 15-hour course load. "I'm just constantly checking on myself to be productive and proactive," Soto said. The plague of overcommitment does not only extend to freshmen. Many students at UT commit to more extracurriculars and organizations than they have time for. If you feel yourself becoming overwhelmed there is no shame in withdrawing from an organization. Campus involvement is a great way to establish and better yourself but always remember that you are your first and foremost priority.
Torres is a Plan II, English & creative writing junior from San Antonio.


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Adel Najdowski, Ph.D., BCBA-D
Adel Najdowski, Ph.D., BCBA-D is an Associate Professor and Director of the M.S. in Applied Behavior Analysis program at Pepperdine University. She also serves on the board of directors for the California Association for Behavior Analysis (CalABA). Dr. Najdowski has over 40 publications including her books, Flexible and Focused! Teaching Executive Function Skills to Individuals with Autism and Attention Disorders and A Workbook of Ethical Case Scenarios in Applied Behavior Analysis. She currently serves on the editorial board of the Journal of Applied Behavior Analysis and has previously served for Behavior Analysis in Practice and as a Guest Editor for a special issue in Research in Autism Spectrum Disorders. Her research interests include evaluating methods for teaching higher order perspective-taking and executive function skills to individuals with autism. She is a frequent speaker at conferences and on radio and web-based shows.
- PhD, University of Nevada, Reno
- MA, University of Nevada, Reno
- BA, University of Nevada, Reno


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Perspective Free access | 10.1172/JCI6491
Howard Hughes Medical Institute L-474, Vollum Institute, Oregon Health Sciences University, Portland, Oregon 97201-3098, USA
Address correspondence to: John D. Scott, Howard Hughes Medical Institute L-474, Vollum Institute, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97201-3098, USA. Phone: (503) 494-4652; Fax: (503) 494-0519; E-mail: firstname.lastname@example.com
Find articles by Schillace, R. in: JCI | PubMed | Google Scholar
Howard Hughes Medical Institute L-474, Vollum Institute, Oregon Health Sciences University, Portland, Oregon 97201-3098, USA
Address correspondence to: John D. Scott, Howard Hughes Medical Institute L-474, Vollum Institute, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97201-3098, USA. Phone: (503) 494-4652; Fax: (503) 494-0519; E-mail: email@example.com
Find articles by Scott, J. in: JCI | PubMed | Google Scholar
Published March 15, 1999 - More info
The issue of specificity in cellular signaling has attracted the interest of many researchers for four decades. At its heart lies a rather simple question: How do the protein kinases and phosphatases that govern changes in the phosphorylation state of cellular proteins modify the correct substrate? This is a complex problem when one considers that over 2,000 protein kinases and 1,000 protein phosphatases are estimated to be present in the human genome (1). Although many effector-mediated signaling pathways employ a similar repertoire of protein kinases and phosphatases to implement their intracellular effects, somehow fidelity is retained to ensure that the appropriate intracellular responses occur. One hypothesis that has gained acceptance over the past decade is the idea that targeting of kinases and phosphatases close to their substrates is crucial to ensure tight regulation of the phosphorylation events. The basis for this postulate has developed from evidence that a molecular framework of adapter, anchoring, and scaffold proteins exists to maintain kinases and phosphatases in defined subcellular compartments (2). Evidence is now also accumulating in support of the clustering and organization of receptors and channels with intracellular signaling cascades. This Perspective will highlight the importance of protein domains in the compartmentalization of signaling enzymes close to their activators and targets, with a focus on kinase-mediated signal transduction.
A classic example of kinase anchoring is the organization of components involved in the mitogen-activated protein (MAP) kinase cascades (Fig. 1a). For example, in the budding yeast Saccharomyces cerevisiae, the pheromone mating response is initiated through G protein–linked activation of the kinase Ste20. This leads to stimulation of a MAP kinase cascade in which Ste11 phosphorylates and activates Ste7, which in turn phosphorylates and activates the MAP kinase homologs Fus 3 or Kss1 (3). This signaling pathway can be tightly controlled because each of the component enzymes is physically associated with a scaffold protein called Ste5. Through this type of organization, many of the early components in the pheromone mating pathway are localized together. This probably facilitates the rapid transduction of signals through the complex and also may ensure that there is a segregation of this MAP kinase module from related signaling cascades in yeast. This view is supported by the identification of a second yeast scaffold protein called Pbs2 that coordinates components of the osmoregulatory pathway. The transmembrane osmosensor Sho1 is coupled to a MAP kinase cascade containing Ste11, Pbs2, and the MAP kinase Hog1. Pbs2 serves a dual function in this pathway as a component of the MAP kinase cascade and as the scaffold protein that maintains the signaling complex (4). The importance of Pbs2 and Ste5 in segregating signaling specificity is emphasized by the observation that although the pheromone mating and osmosensory pathways share a common kinase component, Ste11, they show no crosstalk.
MAP kinase scaffolding. A schematic representation of proteins involved in scaffolding yeast and mammalian MAP kinases. (a) The yeast pheromone mating response is initiated through G protein–linked activation of the kinase Ste20. This leads to stimulation of a MAP kinase cascade composed of Ste11, Ste7, and Fus3, all of which are bound to the scaffold Ste5. Osmotic regulation results from activation of the receptor SHO1, which initiates a phosphorylation cascade of Ste11, Pbs2, and HOG1. The signaling molecules are targeted to SHO1 through interactions with Pbs2. This cascade prompts the cell to increase cellular osmolarity in response to external conditions. (b) Localization of adapter proteins, such as GRB2, with signaling molecules mediates growth factor stimulation of the RAF/MEK/ERK kinase cascade, which is scaffolded through interactions with the adapter protein MP1. Additionally, JIP-1 sequesters MLK3/DLK, MKK7, and JNK for response to cytokine or stress signaling. MAP, mitogen-activated protein.
Recently, parallel levels of organization have been proposed for mammalian MAP kinase cascades (Fig. 1b). The identification of JIP-1, a scaffold protein that binds the kinases MKK7, MLK1, and JNK in vitro, suggests that mammalian kinase cascades are scaffolded in a manner similar to those in yeast. Each kinase binds to a distinct region of JIP-1, and overexpression of the scaffold protein specifically enhances the transduction of signals through the pathway (5). Mammalian MAP kinase pathways may also be ordered by the adapter protein MP1. MP1 enhances activation of the classical MAP kinase cascade by bringing together MEK1 and ERK1. Overexpression of MP1 favors the formation of MEK1/ERK1 complexes with a concomitant increase in ELK1 transcription, a commonly used index of MAP kinase activation (6). MP1 seems to represent a novel class of MAP kinase adapter protein, as it only binds two members of the kinase cascade, whereas JIP-1, Pbs2, and Ste5 organize and segregate complete MAP kinase pathways. As yet, it is unclear what the functional role of MP1 may be, but it has been proposed to facilitate interactions specifically involving MEK1. It will be of interest to establish whether MP1 has other binding partners.
The spatial organization of the cAMP-dependent protein kinase (PKA) is another well-known example of kinase anchoring. Upon binding of cAMP to the tetrameric PKA holoenzyme, the active catalytic (C) subunits are released from the regulatory (R) subunit dimer and are free to phosphorylate substrates in their vicinity. One of the regulatory mechanisms in place to restrict the movement of C subunits and prevent nonspecific phosphorylation events is the subcellular localization of the PKA holoenzyme through association with A-kinase anchoring proteins (AKAPs) (7). The AKAPs are a functionally related family of 30 or so proteins that are classified on the basis of their ability to bind the R subunits of PKA. Although there is little sequence similarity between individual anchoring proteins, each AKAP contains a region of approximately 24 residues responsible for binding the R-subunit dimer. Structural studies suggest that AKAP sequences adopt an amphipathic helical conformation that inserts into a hydrophobic pocket formed by the R-subunit dimer (8). Numerous side-chains participate in the tight packing of the AKAP and R-binding surfaces and may explain why AKAP peptides constitutively bind PKA with nanomolar affinities. Accordingly, AKAP peptides are ideal antagonists of PKA anchoring inside cells and have been used to demonstrate that compartmentalized pools of PKA modulate cAMP-responsive events. For example, cardiac and skeletal muscle L-type calcium channel activity is enhanced by PKA (9). These effects are inhibited by an anchoring inhibitor peptide that is patterned after the conserved AKAP sequence and uncouples PKA localization. Similar experiments have implicated a role for anchored pools of PKA in the modulation of smooth muscle calcium-activated potassium channels, kidney ROMK channels, and neuronal AMPA/kainate glutamate receptors (9, 10).
Targeting of the PKA holoenzyme to discrete intracellular environments is the defining feature of each AKAP. This is achieved through specialized targeting signals that maintain protein–lipid and protein–protein interactions with ligands at defined intracellular sites. The intracellular locations of some well-characterized AKAPs are presented in Fig. 2. For example, membrane attachment of a small-molecular-weight anchoring protein, called AKAP15/18, is mediated through myristoylation and dual palmitoylation signals (11). Members of the AKAP-KL family are attached to the actin cytoskeleton at the apical membrane in epithelial cells, whereas sAKAP84/DAKAP1 contains a mitochondrial targeting sequence (12, 13). Recently, a protein called yotiao, which binds to the cytoplasmic tail of NMDA receptors containing the NR1/1A subunit, has also been identified as an AKAP. Interestingly, yotiao binds the type I protein phosphatase (PP1), thereby maintaining a signaling complex of two enzymes with opposing actions that are physically associated with their substrate. Functional experiments indicate that anchored PP1 is active and limits channel activity. PKA activation overcomes the phosphatase to confer rapid cAMP- enhancement of NMDA receptor currents. Thus, a recurring theme in PKA-mediated signal transduction is the colocalization of kinases and phosphatases in signaling complexes. This is further exemplified by AKAP79, which coordinates the location of PKA, PKC, and protein phosphatase 2B (calcineurin) at the postsynaptic densities of neurons, and by AKAP220, a vesicle-associated anchoring protein that binds PKA and PP1 (14). The clustering of kinases and phosphatases furnishes an additional level of control to the coordination of signaling events by positioning the enzymes close to selected substrates, where they can respond to signals generated by activators. There is no doubt that additional AKAP signaling complexes remain to be identified.
A schematic representation of the subcellular localization of AKAPs. The localization of PKA to different cellular compartments is mediated through interactions with AKAPs. A selection of AKAPs, the signaling molecules that they bind, and their subcellular location are depicted here. The targeting of mAKAP to the perinuclear membrane is a recent observation from our lab. See text and ref. 1 for details on targeting of the remaining AKAPs pictured here. AKAPs, A-kinase anchoring proteins.
Often the targeting of kinases and phosphatases is mediated by specialized domains or sequences that interact with other proteins. Perhaps the best understood example is the Src homology 2 domain (SH2), which is found in many protein tyrosine kinases and signaling components of growth factor–mediated transduction cascades. The SH2 is a module of approximately 100 amino acids that binds to specific phosphotyrosine sequences on its partner proteins, often providing a physical link to the activated growth factor receptor (15). Other domains that facilitate protein–protein interactions of signaling molecules include PTB domains, which also bind phosphotyrosine sequences, and src homology 3 (SH3) and WW domains, which bind proline-rich sequences. Often, signaling proteins contain more than one of these protein modules; for example, the adapter protein Grb2 contains two SH3 domains and an SH2 domain. Simultaneous association of Grb2 or its relatives with multiple binding partners permits the formation of oligomeric signaling complexes containing both protein tyrosine kinases and protein tyrosine phosphatases (Fig. 1b). The involvement of these complexes in insulin signaling and diabetes is the focus of another Perspective in this series and therefore will not be discussed further here.
Coupling receptor activation to signaling cascades is essential for the transmission of intracellular signals. Ample research has now demonstrated that another protein module, the PDZ domain, coordinates the location of transmembrane proteins with cytoskeletal elements and signaling enzymes (16). The PDZ domain takes its name from the three proteins in which it was originally identified: PSD-95, at the postsynaptic density, Discs Large, of Drosophila imaginal discs; and ZO-1, of epithelial tight junctions. PDZ proteins often contain multiple PDZ domains that permit simultaneous association with several proteins via recognition of the COOH-terminal motif E(S/T)DV. The role of PDZ domains in epithelial cells will be the focus of another essay in this series. It is appropriate, however, for this Perspective to discuss briefly the contribution of PDZ interactions to the localization of certain second messenger–regulated kinases and phosphatases and the function of PDZ domains in neuronal receptor clustering and targeting.
In neurons, the AMPA-type glutamate receptor ion channel is in part regulated by the type 1 protein phosphatase (PP1). This phenomenon has recently been associated with a PDZ protein called spinophilin, which binds PP1 and is proposed to colocalize with the AMPA receptor in the postsynaptic membranes of neostriatal neurons (17). EBP50/NHERF is a PDZ protein involved in regulation of sodium–hydrogen transport in the apical membrane of epithelial cells. Two studies demonstrate that EBP50/NHERF binds to the cystic fibrosis transmembrane conductance regulator (CFTR) and ezrin, a cytoskeletal component that has been proposed to anchor PKA (18, 19). Because PKA phosphorylation has been implicated in regulation of CFTR, these data indicate a potential role for anchored PKA via an ezrin/EBP50 complex. These studies suggest that CFTR may be compartmentalized in a complex with its intracellular effector, PKA.
An elegant series of neurobiological experiments have demonstrated that glutamate receptors and other ion channels also are organized through PDZ interactions at the postsynaptic membranes of neurons (20). A main player in this system is PSD-95, a member of the MAGUK family of PDZ proteins. PSD-95 contains three PDZ domains, a SH3 domain, and a guanylate kinase–like sequence. The first and second PDZ domains of PSD-95 bind the NMDA receptor subunit NR2B and the potassium channel Kv 4.1. Ion channel clustering occurs through homomeric PSD-95 interactions. It has been further proposed that stabilization of these clusters may be mediated through an adapter protein called CRIPT, which binds the third PDZ domain of PSD-95 and may tether the complex to the neuronal cytoskeleton. PSD-95 also organizes signaling molecules such as neuronal nitric oxide synthase (nNOS), an enzyme that catalyzes the formation of the second messenger nitric oxide in response to Ca2+ entry across the postsynaptic membrane. Simultaneous binding of PSD-95 to NMDA receptors and nNOS may provide a scaffold to bring the enzyme close to its calcium source. Furthermore, PSD-95 may participate in the regulation of Ras-controlled signaling pathways through binding to a Ras–GTPase activating protein called SynGAP (21).
In addition to being regulated by spinophilin and PP1, the AMPA-sensitive glutamate receptors (GluR2 and GluR3) are clustered at postsynaptic sites through association with other PDZ domain–containing proteins (Fig. 3a). For example, GRIP is an adapter protein with seven PDZ domains, the fourth and fifth of which interact with the AMPA receptor subunits, leaving the remaining domains free to interact with signaling molecules or cytoskeletal components (22). Likewise, the G protein–linked metabotropic glutamate receptors, mGluR1 and mGluR5, bind Homer, a scaffold protein with a PDZ-like domain. Homer also binds phospholipase C (PLC) and may regulate phosphoinositide signaling at excitatory synapses (23).
Localization of signaling complexes with channels and clustered receptors. (a) A cartoon representation of neuronal receptor clustering and regulation. PDZ domain–containing proteins are responsible for clustering several types of glutamate receptors (see text for details). Evidence is now also accumulating in support of the regulation of receptor activity through targeted kinases and phosphatases, as illustrated by the interaction of the AKAP yotiao with PKA, PP1, and the NR1 subunit of the NMDA receptor. (b) The targeting and clustering of receptors and channels with intracellular signaling molecules responsible for phototransduction in Drosophila eye. The PDZ domains of InaD target PLC-β, PKC, and calmodulin to the membrane and cluster the TRP channels with these signaling molecules. Homomeric and heteromeric InaD interactions facilitate the formation of this transducisome complex.
A particularly sophisticated example of the involvement of PDZ domains in signaling complexes is the InaD transducisome in Drosophila eye phototransduction (Fig. 3b). The InaD (inactivation no-afterpotential) protein contains five PDZ domains that interact with various signaling partners, including calmodulin, PLC-β, the eye isoform of protein kinase C, and the transient receptor potential protein (TRP) store–operated calcium channel. Light-stimulated rhodopsin activates PLC-β through Gαq, which induces channel activity via IP3. The channel is then inactivated by PKC phosphorylation. Thus, InaD functions to rapidly activate phototransduction through stimulation of the TRP channel by sequestering signaling enzymes with their activators and substrates. Importantly, the reverse process is also favored, as InaD maintains PKC close to TRP. It appears that the interactions in this complex are not simple, but are multivalent, forming a web of signaling molecules and receptors that functions to regulate phototransduction through the speed of activation and feedback regulation (24, 25).
Now that many adapter, anchoring, and scaffolding proteins are known, the challenge facing researchers is to define how these interactions are regulated and what functional advantages are provided by multienzyme signaling complexes. Thus far, the formation and breakdown of these complexes appear to be regulated by a variety of mechanisms, but phosphorylation is implicated in several cases. For example, SH2 domains and most PTB domains bind after tyrosine phosphorylation of their binding partners, illustrating how extracellular signals can promote the assembly of multiprotein complexes when and where they are required. Second messengers, however, can promote the disassembly of such complexes, as illustrated by the uncoupling of the inwardly rectifying potassium channel Kir 2.3 from PSD-95 by PKA phosphorylation of a serine within the PDZ recognition motif (26). SH2, PTB, and PDZ domains recognize short sequences of only four to six amino acids; therefore, signaling events that modify these acceptor sequences may have profound effects upon complex formation. It is likely that the development of small molecules that perturb these interactions will have some therapeutic potential, in addition to advancing knowledge about the regulation of receptor and signal cascade targeting. Finally, we envision that many future advances in our understanding of the functional implications of signaling complexes and receptor targeting will arise from genetic manipulations. This view is supported by recent analysis of mice strains engineered to produce a mutant PSD-95 protein. NMDA receptor clustering is normal, but the mutant PSD-95 is unable to interact with the neuronal cytoskeleton or engage downstream signaling pathways. Electrophysiological and behavioral studies show that certain cognitive processes of the mutant mice, such as increased long- term potentiation (LTP) and aberrant spatial learning, are altered (27). We therefore anticipate that transgenic and targeted gene disruption experiments will have an increasingly important role in developing our understanding of the functional importance of multiprotein scaffolding in the process of signal transduction.
The authors wish to thank our colleagues in the Scott lab for insightful comments and discussion during the preparation of this manuscript. R.V. Schillacewas supported by DK 44239. The authors acknowledge that due to the shortened length constraints of the Perspective format, they were unable to cite all primary reports on certain findings.
Organization of kinases, phosphatases, and receptor signaling complexesRobynn V. Schillace et al.
PDZ domains: fundamental building blocks in the organization of protein complexes at the plasma membraneAlan S. Fanning et al.
Recent developments in lymphocyte activation: linking kinases to downstream signaling eventsJames L. Clements et al.
Protein–protein interaction in insulin signaling and the molecular mechanisms of insulin resistanceAntti Virkamäki et al.


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